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UTX (gene)

2017-11-23T09:45:41Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{Infobox_gene}}

'''Lysine-specific demethylase 6A''' also known as '''Ubiquitously transcribed tetratricopeptide repeat, X chromosome''' ('''UTX'''), is a [[protein]] which in humans is encoded by the ''KDM6A'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: KDM6A lysine demethylase 6A | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7403| accessdate = }}</ref><ref name="pmid9381176">{{cite journal |vauthors=Lahn BT, Page DC | title = Functional coherence of the human Y chromosome | journal = Science | volume = 278 | issue = 5338 | pages = 675–80 |date=October 1997 | pmid = 9381176 | doi = 10.1126/science.278.5338.675 | url = }}</ref><ref name="pmid9499428">{{cite journal |vauthors=Greenfield A, Carrel L, Pennisi D, Philippe C, Quaderi N, Siggers P, Steiner K, Tam PP, Monaco AP, Willard HF, Koopman P | title = The UTX gene escapes X inactivation in mice and humans | journal = Hum. Mol. Genet. | volume = 7 | issue = 4 | pages = 737–42 |date=April 1998 | pmid = 9499428 | doi = 10.1093/hmg/7.4.737 | url = }}</ref> It belongs to the [[2-oxoglutarate (2OG)-dependent dioxygenases | 2-oxoglutarate (2OG)-dependent dioxygenase]] superfamily.

== Function ==

UTX has been linked with [[demethylation]] of lysine residues on [[histone]], in particular H3K27, resulting in a gene de-repression, a potential means of regulating cellular metabolism.<ref name="pmid17761849">{{cite journal |vauthors=Lee MG, Villa R, Trojer P, Norman J, Yan KP, Reinberg D, Di Croce L, Shiekhattar R | title = Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination | journal = Science | volume = 318 | issue = 5849 | pages = 447–50 |date=October 2007 | pmid = 17761849 | doi = 10.1126/science.1149042 | url = }}</ref>

==References==
{{reflist}}

==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal |vauthors=Lahn BT, Page DC |title=Functional coherence of the human Y chromosome. |journal=Science |volume=278 |issue= 5338 |pages= 675–80 |year= 1997 |pmid= 9381176 |doi=10.1126/science.278.5338.675 }}
*{{cite journal |vauthors=Greenfield A, Carrel L, Pennisi D, etal |title=The UTX gene escapes X inactivation in mice and humans. |journal=Hum. Mol. Genet. |volume=7 |issue= 4 |pages= 737–42 |year= 1998 |pmid= 9499428 |doi=10.1093/hmg/7.4.737 }}
*{{cite journal |vauthors=Grbavec D, Lo R, Liu Y, etal |title=Groucho/transducin-like enhancer of split (TLE) family members interact with the yeast transcriptional co-repressor SSN6 and mammalian SSN6-related proteins: implications for evolutionary conservation of transcription repression mechanisms |journal=Biochem. J. |volume=337 ( Pt 1) |issue= Pt 1|pages= 13–7 |year= 1999 |pmid= 9854018 |doi=10.1042/0264-6021:3370013 | pmc=1219929 }}
*{{cite journal |vauthors=Foresta C, Ferlin A, Moro E |title=Deletion and expression analysis of AZFa genes on the human Y chromosome revealed a major role for DBY in male infertility |journal=Hum. Mol. Genet. |volume=9 |issue= 8 |pages= 1161–9 |year= 2000 |pmid= 10767340 |doi=10.1093/hmg/9.8.1161 }}
*{{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 }}
*{{cite journal |vauthors=Agate RJ, Choe M, Arnold AP |title=Sex differences in structure and expression of the sex chromosome genes CHD1Z and CHD1W in zebra finches |journal=Mol. Biol. Evol. |volume=21 |issue= 2 |pages= 384–96 |year= 2004 |pmid= 14660691 |doi= 10.1093/molbev/msh027 }}
*{{cite journal |vauthors=Colland F, Jacq X, Trouplin V, etal |title=Functional Proteomics Mapping of a Human Signaling Pathway |journal=Genome Res. |volume=14 |issue= 7 |pages= 1324–32 |year= 2004 |pmid= 15231748 |doi= 10.1101/gr.2334104 | pmc=442148 }}
*{{cite journal |vauthors=Beausoleil SA, Jedrychowski M, Schwartz D, etal |title=Large-scale characterization of HeLa cell nuclear phosphoproteins |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130–5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101 | pmc=514446 }}
*{{cite journal |vauthors=Ballif BA, Villén J, Beausoleil SA, etal |title=Phosphoproteomic analysis of the developing mouse brain |journal=Mol. Cell. Proteomics |volume=3 |issue= 11 |pages= 1093–101 |year= 2005 |pmid= 15345747 |doi= 10.1074/mcp.M400085-MCP200 }}
*{{cite journal |vauthors=Gerrard DT, Filatov DA |title=Positive and negative selection on mammalian Y chromosomes |journal=Mol. Biol. Evol. |volume=22 |issue= 6 |pages= 1423–32 |year= 2005 |pmid= 15758204 |doi= 10.1093/molbev/msi128 }}
*{{cite journal |vauthors=Cho YW, Hong T, Hong S, etal |title=PTIP Associates with MLL3- and MLL4-containing Histone H3 Lysine 4 Methyltransferase Complex |journal=J. Biol. Chem. |volume=282 |issue= 28 |pages= 20395–406 |year= 2007 |pmid= 17500065 |doi= 10.1074/jbc.M701574200 | pmc=2729684 }}
*{{cite journal |vauthors=Agger K, Cloos PA, Christensen J, etal |title=UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development |journal=Nature |volume=449 |issue= 7163 |pages= 731–4 |year= 2007 |pmid= 17713478 |doi= 10.1038/nature06145 }}
*{{cite journal |vauthors=Lee MG, Villa R, Trojer P, etal |title=Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination |journal=Science |volume=318 |issue= 5849 |pages= 447–50 |year= 2007 |pmid= 17761849 |doi= 10.1126/science.1149042 }}
*{{cite journal |vauthors=Lan F, Bayliss PE, Rinn JL, etal |title=A histone H3 lysine 27 demethylase regulates animal posterior development |journal=Nature |volume=449 |issue= 7163 |pages= 689–94 |year= 2007 |pmid= 17851529 |doi= 10.1038/nature06192 }}
*{{cite journal |vauthors=Hong S, Cho YW, Yu LR, etal |title=Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=104 |issue= 47 |pages= 18439–44 |year= 2008 |pmid= 18003914 |doi= 10.1073/pnas.0707292104 | pmc=2141795 }}
}}
{{refend}}

{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}


{{PBB_Controls
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = no
| update_citations = yes
}}

[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]

{{gene-X-stub}}

PHF8

2017-11-23T09:42:30Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{Infobox_gene}}
'''PHD finger protein 8''' is a [[protein]] that in humans is encoded by the ''PHF8'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PHF8 PHD finger protein 8| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23133| accessdate = }}</ref>

== Function ==

PHF8 belongs to the family of ferrous iron and [[2-oxoglutarate (2OG)-dependent dioxygenases | 2-oxoglutarate (2OG)-dependent dioxygenase]] superfamily.,<ref>{{cite journal | vauthors = Loenarz C, Schofield CJ | title = Expanding chemical biology of 2-oxoglutarate oxygenases | journal = Nature Chemical Biology | volume = 4 | issue = 3 | pages = 152–6 | date = Mar 2008 | pmid = 18277970 | doi = 10.1038/nchembio0308-152 }}</ref> and is active as a [[histone]] lysine demethylase with selectivity for the di-and monomethyl states.<ref name= "PMID19843542">{{cite journal | vauthors = Loenarz C, Ge W, Coleman ML, Rose NR, Cooper CD, Klose RJ, Ratcliffe PJ, Schofield CJ | title = PHF8, a gene associated with cleft lip/palate and mental retardation, encodes for an Nepsilon-dimethyl lysine demethylase | journal = Human Molecular Genetics | volume = 19 | issue = 2 | pages = 217–22 | date = Jan 2010 | pmid = 19843542 | doi = 10.1093/hmg/ddp480 }}</ref>

== Clinical significance ==

Mutations in PHF8 cause Siderius type [[X-Linked mental retardation|X-linked mental retardation]] (XLMR) ({{OMIM6|300263}}).<ref>{{cite journal | vauthors = Siderius LE, Hamel BC, van Bokhoven H, de Jager F, van den Helm B, Kremer H, Heineman-de Boer JA, Ropers HH, Mariman EC | title = X-linked mental retardation associated with cleft lip/palate maps to Xp11.3-q21.3 | journal = American Journal of Medical Genetics | volume = 85 | issue = 3 | pages = 216–20 | date = Jul 1999 | pmid = 10398231 | doi = 10.1002/(SICI)1096-8628(19990730)85:3<216::AID-AJMG6>3.0.CO;2-X }}</ref><ref name="OMIM300263">{{cite web|url=https://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300263|title=OMIM: Siderius X-linked mental retardation syndrome|accessdate=2009-10-21}}</ref><ref name="OMIM300560">{{cite web|url=https://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300560|title=OMIM: PHD finger protein 8; PHF8|accessdate=2009-10-21}}</ref>
In addition to moderate [[intellectual disability]], features of the Siderius-Hamel syndrome include facial dysmorphism, [[cleft lip]] and/or cleft palate, and in some cases [[microcephaly]].<ref>{{cite journal | vauthors = Abidi F, Miano M, Murray J, Schwartz C | title = A novel mutation in the PHF8 gene is associated with X-linked mental retardation with cleft lip/cleft palate | journal = Clinical Genetics | volume = 72 | issue = 1 | pages = 19–22 | date = Jul 2007 | pmid = 17594395 | pmc = 2570350 | doi = 10.1111/j.1399-0004.2007.00817.x }}</ref><ref>{{cite journal | vauthors = Laumonnier F, Holbert S, Ronce N, Faravelli F, Lenzner S, Schwartz CE, Lespinasse J, Van Esch H, Lacombe D, Goizet C, Phan-Dinh Tuy F, van Bokhoven H, Fryns JP, Chelly J, Ropers HH, Moraine C, Hamel BC, Briault S | title = Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate | journal = Journal of Medical Genetics | volume = 42 | issue = 10 | pages = 780–6 | date = Oct 2005 | pmid = 16199551 | pmc = 1735927 | doi = 10.1136/jmg.2004.029439 }}</ref><ref name="PMID17661819">{{cite journal | vauthors = Koivisto AM, Ala-Mello S, Lemmelä S, Komu HA, Rautio J, Järvelä I | title = Screening of mutations in the PHF8 gene and identification of a novel mutation in a Finnish family with XLMR and cleft lip/cleft palate | journal = Clinical Genetics | volume = 72 | issue = 2 | pages = 145–9 | date = Aug 2007 | pmid = 17661819 | doi = 10.1111/j.1399-0004.2007.00836.x }}</ref> A chromosomal [[microdeletion]] on Xp11.22 encompassing all of the ''PHF8'' and ''FAM120C'' genes and a part of the ''WNK3'' gene was reported in two brothers with [[autism spectrum disorder]] in addition to Siderius-type XLMR and [[cleft lip and palate]].<ref>{{cite journal | vauthors = Qiao Y, Liu X, Harvard C, Hildebrand MJ, Rajcan-Separovic E, Holden JJ, Lewis ME | title = Autism-associated familial microdeletion of Xp11.22 | journal = Clinical Genetics | volume = 74 | issue = 2 | pages = 134–44 | date = Aug 2008 | pmid = 18498374 | doi = 10.1111/j.1399-0004.2008.01028.x }}</ref>

This catalytic activity is disrupted by clinically known mutations to ''PHF8'', which were found to cluster in its catalytic JmjC domain. The F279S mutation of PHF8, found in 2 Finnish brothers with mild [[intellectual disability]], facial [[dysmorphism]] and [[cleft lip/palate]],<ref name="PMID17661819"/> was found to additionally prevent [[nuclear localisation]] of PHF8 overexpressed in human cells.<ref name= "PMID19843542" />

The catalytic activity of PHF8 depends on molecular [[oxygen]],<ref name= "PMID19843542" /> a fact considered important with respect to reports on increased incidence of [[cleft lip/palate]] in mice that have been exposed to [[Hypoxia (medical)|hypoxia]] during [[pregnancy]].<ref>{{cite journal | vauthors = Millicovsky G, Johnston MC | title = Hyperoxia and hypoxia in pregnancy: simple experimental manipulation alters the incidence of cleft lip and palate in CL/Fr mice | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 78 | issue = 9 | pages = 5722–3 | date = Sep 1981 | pmid = 6946511 | pmc = 348841 | doi = 10.1073/pnas.78.9.5722 }}</ref> In humans, [[fetal]] cleft lip and other [[congenital abnormalities]] have also been linked to maternal hypoxia, as caused by e.g. [[Smoking and pregnancy|maternal smoking]],<ref>{{cite journal | vauthors = Shi M, Wehby GL, Murray JC | title = Review on genetic variants and maternal smoking in the etiology of oral clefts and other birth defects | journal = Birth Defects Research. Part C, Embryo Today | volume = 84 | issue = 1 | pages = 16–29 | date = Mar 2008 | pmid = 18383123 | pmc = 2570345 | doi = 10.1002/bdrc.20117 }}</ref> maternal [[alcohol abuse]] or maternal [[hypertension]] treatment.<ref>{{cite journal | vauthors = Hurst JA, Houlston RS, Roberts A, Gould SJ, Tingey WG | title = Transverse limb deficiency, facial clefting and hypoxic renal damage: an association with treatment of maternal hypertension? | journal = Clinical Dysmorphology | volume = 4 | issue = 4 | pages = 359–63 | date = Oct 1995 | pmid = 8574428 | doi = 10.1097/00019605-199510000-00013 }}</ref>
{{Clear}}

== References ==
{{reflist|33em}}

== External links ==
* {{MeshName|PHF8+protein,+human}}

{{NLM content}}
{{Transcription factors|g3}}
{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:Transcription factors]]
[[Category:Genes on human chromosome X]]
[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]

Lysyl hydroxylase

2017-11-23T09:41:10Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{infobox protein
| Name = procollagen-lysine 1, 2-oxoglutarate 5-dioxygenase 1
| caption =
| image =
| width =
| HGNCid = 9081
| Symbol = PLOD1
| AltSymbols = LLH, PLOD
| EntrezGene = 5351
| OMIM = 153454
| RefSeq = NM_000302
| UniProt = Q02809
| PDB =
| ECnumber = 1.14.11.4
| Chromosome = 1
| Arm = p
| Band = 36.3
| LocusSupplementaryData = -36.2
}}
{{infobox protein
| Name = procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2
| caption =
| image =
| width =
| HGNCid = 9082
| Symbol = PLOD2
| AltSymbols =
| EntrezGene = 5352
| OMIM = 601865
| RefSeq = NM_000935
| UniProt = O00469
| PDB =
| ECnumber =
| Chromosome = 3
| Arm = q
| Band = 24
| LocusSupplementaryData =
}}
'''Lysyl hydroxylases''' (or '''procollagen-lysine 5-dioxygenases''') are [[2-oxoglutarate (2OG)-dependent dioxygenases | 2-oxoglutarate (2OG)-dependent dioxygenase]] [[enzyme]]<nowiki/>s that catalyze the [[hydroxylation]] of [[lysine]] to [[hydroxylysine]].<ref>{{cite journal | vauthors = Hausmann E | title = Cofactor requirements for the enzymatic hydroxylation of lysine in a polypeptide precursor of collagen | journal = Biochimica et Biophysica Acta | volume = 133 | issue = 3 | pages = 591–3 | date = Apr 1967 | pmid = 6033801 | doi = 10.1016/0005-2795(67)90566-1 }}</ref><ref>{{cite journal | vauthors = Rhoads RE, Udenfriend S | title = Decarboxylation of alpha-ketoglutarate coupled to collagen proline hydroxylase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 60 | issue = 4 | pages = 1473–8 | date = Aug 1968 | pmid = 5244754 | pmc = 224943 | doi = 10.1073/pnas.60.4.1473 }}</ref> Lysyl hydroxylases require [[iron]] and [[vitamin C]] as [[cofactor (biochemistry)|cofactors]] for their oxidation activity. It takes place (as a [[post-translational modification]]) following collagen synthesis in the cisternae (lumen) of the [[rough endoplasmic reticulum|rough endoplasmic reticulum (ER)]]. There are three lysyl hydroxylases (LH1-3) encoded in the human genome, namely: ''PLOD1'', ''PLOD2'' and ''PLOD3''. From ''PLOD2'' two splice variant can be expressed (LH2a and LH2b), where LH2b differs from LH2a by incorporating the small exon 13A. LH1 and LH3 hydroxylate lysyl residues in the collagen triple helix, whereas LH2b hydroxylates lysyl residues in the telopeptides of collagen. In addition to its hydroxylation activity, LH3 has glycosylation activity that produces either monosaccharide (Gal) or disaccharide (Glc-Gal) attached to collagen hydroxylysines.

Collagen lysyl hydroxylation is the first step in collagen [[pyridinoline]] cross-linking, that is necessary for the stabilization of [[collagen]].

==Pathology==
Mutations in the ''PLOD2'' gene have been linked to [[Bruck syndrome]] in humans.

A deficiency in its cofactor, vitamin C, is associated with [[scurvy]].

== References ==
{{reflist}}

== External links ==
* {{MeshName|Lysyl+Hydroxylase}}

{{Amino acid metabolism enzymes}}
{{Fibrous proteins}}
{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]
[[Category:Extracellular matrix remodeling enzymes]]

{{oxidoreductase-stub}}

KDM5D

2017-11-23T09:40:24Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{Infobox_gene}}
'''Lysine-specific demethylase 5D''' is an [[enzyme]] that in humans is encoded by the ''KDM5D'' [[gene]].<ref name="pmid795123">{{cite journal | vauthors = Froggatt P | title = The foundation of the "Inst" medical department and its association with the Belfast Fever Hospital | journal = The Ulster Medical Journal | volume = 45 | issue = 2 | pages = 107–45 | date = Feb 1977 | pmid = 795123 | pmc = 2385577 | doi = }}</ref><ref name="pmid8841177">{{cite journal | vauthors = Kent-First MG, Maffitt M, Muallem A, Brisco P, Shultz J, Ekenberg S, Agulnik AI, Agulnik I, Shramm D, Bavister B, Abdul-Mawgood A, VandeBerg J | title = Gene sequence and evolutionary conservation of human SMCY | journal = Nature Genetics | volume = 14 | issue = 2 | pages = 128–9 | date = October 1996 | pmid = 8841177 | pmc = | doi = 10.1038/ng1096-128 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: JARID1D jumonji, AT rich interactive domain 1D| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8284| accessdate = }}</ref> KDM5D belongs to the [[2-oxoglutarate (2OG)-dependent dioxygenases | 2-oxoglutarate (2OG)-dependent dioxygenase]] superfamily.

This gene encodes a [[protein]] containing [[zinc finger]] domains. A short peptide derived from this protein is a [[minor histocompatibility antigen]] which can lead to graft rejection of male donor cells in a female recipient.<ref name="entrez"/>

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Simpson E, Scott D, Chandler P | title = The male-specific histocompatibility antigen, H-Y: a history of transplantation, immune response genes, sex determination and expression cloning | journal = Annual Review of Immunology | volume = 15 | issue = | pages = 39–61 | year = 1997 | pmid = 9143681 | doi = 10.1146/annurev.immunol.15.1.39 }}
* {{cite journal | vauthors = Wolf U | title = The serologically detected H-Y antigen revisited | journal = Cytogenetics and Cell Genetics | volume = 80 | issue = 1-4 | pages = 232–5 | year = 1998 | pmid = 9678364 | doi = 10.1159/000014986 }}
* {{cite journal | vauthors = Agulnik AI, Mitchell MJ, Lerner JL, Woods DR, Bishop CE | title = A mouse Y chromosome gene encoded by a region essential for spermatogenesis and expression of male-specific minor histocompatibility antigens | journal = Human Molecular Genetics | volume = 3 | issue = 6 | pages = 873–8 | date = June 1994 | pmid = 7524912 | doi = 10.1093/hmg/3.6.873 }}
* {{cite journal | vauthors = Wang W, Meadows LR, den Haan JM, Sherman NE, Chen Y, Blokland E, Shabanowitz J, Agulnik AI, Hendrickson RC, Bishop CE | title = Human H-Y: a male-specific histocompatibility antigen derived from the SMCY protein | journal = Science | volume = 269 | issue = 5230 | pages = 1588–90 | date = September 1995 | pmid = 7667640 | doi = 10.1126/science.7667640 }}
* {{cite journal | vauthors = Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N | title = Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain | journal = DNA Research | volume = 3 | issue = 5 | pages = 321–9, 341-54 | date = October 1996 | pmid = 9039502 | doi = 10.1093/dnares/3.5.321 }}
* {{cite journal | vauthors = Agulnik AI, Bishop CE, Lerner JL, Agulnik SI, Solovyev VV | title = Analysis of mutation rates in the SMCY/SMCX genes shows that mammalian evolution is male driven | journal = Mammalian Genome | volume = 8 | issue = 2 | pages = 134–8 | date = February 1997 | pmid = 9060413 | doi = 10.1007/s003359900372 }}
* {{cite journal | vauthors = Rufer N, Wolpert E, Helg C, Tiercy JM, Gratwohl A, Chapuis B, Jeannet M, Goulmy E, Roosnek E | title = HA-1 and the SMCY-derived peptide FIDSYICQV (H-Y) are immunodominant minor histocompatibility antigens after bone marrow transplantation | journal = Transplantation | volume = 66 | issue = 7 | pages = 910–6 | date = October 1998 | pmid = 9798702 | doi = 10.1097/00007890-199810150-00016 }}
* {{cite journal | vauthors = Lau YF, Zhang J | title = Expression analysis of thirty one Y chromosome genes in human prostate cancer | journal = Molecular Carcinogenesis | volume = 27 | issue = 4 | pages = 308–21 | date = April 2000 | pmid = 10747295 | doi = 10.1002/(SICI)1098-2744(200004)27:4<308::AID-MC9>3.0.CO;2-R }}
* {{cite journal | vauthors = Shen P, Wang F, Underhill PA, Franco C, Yang WH, Roxas A, Sung R, Lin AA, Hyman RW, Vollrath D, Davis RW, Cavalli-Sforza LL, Oefner PJ | title = Population genetic implications from sequence variation in four Y chromosome genes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 13 | pages = 7354–9 | date = June 2000 | pmid = 10861003 | pmc = 16549 | doi = 10.1073/pnas.97.13.7354 }}
* {{cite journal | vauthors = Skaletsky H, Kuroda-Kawaguchi T, Minx PJ, Cordum HS, Hillier L, Brown LG, Repping S, Pyntikova T, Ali J, Bieri T, Chinwalla A, Delehaunty A, Delehaunty K, Du H, Fewell G, Fulton L, Fulton R, Graves T, Hou SF, Latrielle P, Leonard S, Mardis E, Maupin R, McPherson J, Miner T, Nash W, Nguyen C, Ozersky P, Pepin K, Rock S, Rohlfing T, Scott K, Schultz B, Strong C, Tin-Wollam A, Yang SP, Waterston RH, Wilson RK, Rozen S, Page DC | title = The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes | journal = Nature | volume = 423 | issue = 6942 | pages = 825–37 | date = June 2003 | pmid = 12815422 | doi = 10.1038/nature01722 }}
* {{cite journal | vauthors = Agate RJ, Choe M, Arnold AP | title = Sex differences in structure and expression of the sex chromosome genes CHD1Z and CHD1W in zebra finches | journal = Molecular Biology and Evolution | volume = 21 | issue = 2 | pages = 384–96 | date = February 2004 | pmid = 14660691 | doi = 10.1093/molbev/msh027 }}
* {{cite journal | vauthors = Miklos DB, Kim HT, Miller KH, Guo L, Zorn E, Lee SJ, Hochberg EP, Wu CJ, Alyea EP, Cutler C, Ho V, Soiffer RJ, Antin JH, Ritz J | title = Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission | journal = Blood | volume = 105 | issue = 7 | pages = 2973–8 | date = April 2005 | pmid = 15613541 | pmc = 1350982 | doi = 10.1182/blood-2004-09-3660 }}
* {{cite journal | vauthors = Piper KP, McLarnon A, Arrazi J, Horlock C, Ainsworth J, Kilby MD, Martin WL, Moss PA | title = Functional HY-specific CD8+ T cells are found in a high proportion of women following pregnancy with a male fetus | journal = Biology of Reproduction | volume = 76 | issue = 1 | pages = 96–101 | date = January 2007 | pmid = 16988213 | doi = 10.1095/biolreprod.106.055426 }}
* {{cite journal | vauthors = Iwase S, Lan F, Bayliss P, de la Torre-Ubieta L, Huarte M, Qi HH, Whetstine JR, Bonni A, Roberts TM, Shi Y | title = The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases | journal = Cell | volume = 128 | issue = 6 | pages = 1077–88 | date = March 2007 | pmid = 17320160 | doi = 10.1016/j.cell.2007.02.017 }}
* {{cite journal | vauthors = Lee MG, Norman J, Shilatifard A, Shiekhattar R | title = Physical and functional association of a trimethyl H3K4 demethylase and Ring6a/MBLR, a polycomb-like protein | journal = Cell | volume = 128 | issue = 5 | pages = 877–87 | date = March 2007 | pmid = 17320162 | doi = 10.1016/j.cell.2007.02.004 }}
{{refend}}

== External links ==
* {{MeshName|JARID1D+protein,+human}}

{{NLM content}}
{{Transcription factors|g2}}
{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:Transcription factors]]
[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]

{{protein-stub}}

KDM5C

2017-11-23T09:39:59Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{Infobox_gene}}
'''Lysine-specific demethylase 5C''' is an [[enzyme]] that in humans is encoded by the ''KDM5C'' [[gene]].<ref name="pmid7951230">{{cite journal | vauthors = Agulnik AI, Mitchell MJ, Mattei MG, Borsani G, Avner PA, Lerner JL, Bishop CE | title = A novel X gene with a widely transcribed Y-linked homologue escapes X-inactivation in mouse and human | journal = Human Molecular Genetics | volume = 3 | issue = 6 | pages = 879–84 | date = Jun 1994 | pmid = 7951230 | pmc = | doi = 10.1093/hmg/3.6.879 }}</ref><ref name="pmid8162017">{{cite journal | vauthors = Wu J, Ellison J, Salido E, Yen P, Mohandas T, Shapiro LJ | title = Isolation and characterization of XE169, a novel human gene that escapes X-inactivation | journal = Human Molecular Genetics | volume = 3 | issue = 1 | pages = 153–60 | date = Jan 1994 | pmid = 8162017 | pmc = | doi = 10.1093/hmg/3.1.153 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: JARID1C jumonji, AT rich interactive domain 1C| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8242| accessdate = }}</ref> KDM5C belongs to the [[2-oxoglutarate (2OG)-dependent dioxygenases | 2-oxoglutarate (2OG)-dependent dioxygenase]] superfamily.

== Function ==

This gene is a member of the SMCY homolog family and encodes a protein with one [[ARID domain]], one JmjC domain, one JmjN domain and two PHD-type zinc fingers. The DNA-binding motifs suggest this protein is involved in the regulation of transcription and chromatin remodeling. Mutations in this gene have been associated with X-linked mental retardation. Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only one has been determined.<ref name="entrez" />

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Agate RJ, Choe M, Arnold AP | title = Sex differences in structure and expression of the sex chromosome genes CHD1Z and CHD1W in zebra finches | journal = Molecular Biology and Evolution | volume = 21 | issue = 2 | pages = 384–96 | date = Feb 2004 | pmid = 14660691 | doi = 10.1093/molbev/msh027 }}
* {{cite journal | vauthors = Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP | title = Large-scale characterization of HeLa cell nuclear phosphoproteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 33 | pages = 12130–5 | date = Aug 2004 | pmid = 15302935 | pmc = 514446 | doi = 10.1073/pnas.0404720101 }}
* {{cite journal | vauthors = Jensen LR, Amende M, Gurok U, Moser B, Gimmel V, Tzschach A, Janecke AR, Tariverdian G, Chelly J, Fryns JP, Van Esch H, Kleefstra T, Hamel B, Moraine C, Gecz J, Turner G, Reinhardt R, Kalscheuer VM, Ropers HH, Lenzner S | title = Mutations in the JARID1C gene, which is involved in transcriptional regulation and chromatin remodeling, cause X-linked mental retardation | journal = American Journal of Human Genetics | volume = 76 | issue = 2 | pages = 227–36 | date = Feb 2005 | pmid = 15586325 | pmc = 1196368 | doi = 10.1086/427563 }}
* {{cite journal | vauthors = Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S | title = Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes | journal = Genome Research | volume = 16 | issue = 1 | pages = 55–65 | date = Jan 2006 | pmid = 16344560 | pmc = 1356129 | doi = 10.1101/gr.4039406 }}
* {{cite journal | vauthors = Santos C, Rodriguez-Revenga L, Madrigal I, Badenas C, Pineda M, Milà M | title = A novel mutation in JARID1C gene associated with mental retardation | journal = European Journal of Human Genetics | volume = 14 | issue = 5 | pages = 583–6 | date = May 2006 | pmid = 16538222 | doi = 10.1038/sj.ejhg.5201608 }}
* {{cite journal | vauthors = Tzschach A, Lenzner S, Moser B, Reinhardt R, Chelly J, Fryns JP, Kleefstra T, Raynaud M, Turner G, Ropers HH, Kuss A, Jensen LR | title = Novel JARID1C/SMCX mutations in patients with X-linked mental retardation | journal = Human Mutation | volume = 27 | issue = 4 | pages = 389 | date = Apr 2006 | pmid = 16541399 | doi = 10.1002/humu.9420 }}
* {{cite journal | vauthors = Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP | title = A probability-based approach for high-throughput protein phosphorylation analysis and site localization | journal = Nature Biotechnology | volume = 24 | issue = 10 | pages = 1285–92 | date = Oct 2006 | pmid = 16964243 | doi = 10.1038/nbt1240 }}
* {{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | date = Nov 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 }}
* {{cite journal | vauthors = Iwase S, Lan F, Bayliss P, de la Torre-Ubieta L, Huarte M, Qi HH, Whetstine JR, Bonni A, Roberts TM, Shi Y | title = The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases | journal = Cell | volume = 128 | issue = 6 | pages = 1077–88 | date = Mar 2007 | pmid = 17320160 | doi = 10.1016/j.cell.2007.02.017 }}
* {{cite journal | vauthors = Tahiliani M, Mei P, Fang R, Leonor T, Rutenberg M, Shimizu F, Li J, Rao A, Shi Y | title = The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation | journal = Nature | volume = 447 | issue = 7144 | pages = 601–5 | date = May 2007 | pmid = 17468742 | doi = 10.1038/nature05823 }}
{{refend}}

== External links ==
* {{MeshName|JARID1C+protein,+human}}

{{NLM content}}
{{Transcription factors|g2}}
{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

{{gene-X-stub}}

[[Category:Transcription factors]]
[[Category:Genes on human chromosome X]]
[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]

KDM5A

2017-11-23T09:39:31Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{Infobox_gene}}
'''Lysine-specific demethylase 5A''' is an [[enzyme]] that in humans is encoded by the ''KDM5A'' [[gene]].<ref name="pmid1857421">{{cite journal | vauthors = Defeo-Jones D, Huang PS, Jones RE, Haskell KM, Vuocolo GA, Hanobik MG, Huber HE, Oliff A | title = Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product | journal = Nature | volume = 352 | issue = 6332 | pages = 251–4 | date = Jul 1991 | pmid = 1857421 | pmc = | doi = 10.1038/352251a0 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: JARID1A jumonji, AT rich interactive domain 1A| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5927| accessdate = }}</ref>

== Function ==

The protein encoded by this gene is a ubiquitously expressed nuclear protein. It binds directly, with several other proteins, to retinoblastoma protein which regulates cell proliferation. It was formerly known as Retinoblastoma Binding Protein 2 (RBP2). This protein also interacts with rhombotin-2 which functions distinctly in erythropoiesis and in T-cell leukemogenesis. Rhombotin-2 is thought to either directly affect the activity of the encoded protein or may indirectly modulate the functions of the retinoblastoma protein by binding to this protein. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.<ref name="entrez"/>

The ''Drosophila'' homolog, LID, was found to be an H3K4 histone [[demethylase]] that binds to [[Myc|c-Myc]].<ref>{{cite journal | vauthors = Secombe J, Li L, Carlos L, Eisenman RN | title = The Trithorax group protein Lid is a trimethyl histone H3K4 demethylase required for dMyc-induced cell growth | journal = Genes & Development | volume = 21 | issue = 5 | pages = 537–51 | date = Mar 2007 | pmid = 17311883 | pmc = 1820896 | doi = 10.1101/gad.1523007 }}</ref> It was recently renamed to Lysine Demethylase 5A (KDM5A).

Enzymatically can be designated as a [[trimethyllysine dioxygenase]], which is a member of the [[2-oxoglutarate (2OG)-dependent dioxygenases | 2-oxoglutarate (2OG)-dependent dioxygenase]] superfamily ({{EC number|1.14.11.8}}).

== Interactions ==

JARID1A has been shown to [[Protein-protein interaction|interact]] with [[Estrogen receptor alpha]],<ref name=pmid11358960>{{cite journal | vauthors = Chan SW, Hong W | title = Retinoblastoma-binding protein 2 (Rbp2) potentiates nuclear hormone receptor-mediated transcription | journal = The Journal of Biological Chemistry | volume = 276 | issue = 30 | pages = 28402–12 | date = Jul 2001 | pmid = 11358960 | doi = 10.1074/jbc.M100313200 }}</ref> [[LMO2]]<ref name=pmid9129143>{{cite journal | vauthors = Mao S, Neale GA, Goorha RM | title = T-cell oncogene rhombotin-2 interacts with retinoblastoma-binding protein 2 | journal = Oncogene | volume = 14 | issue = 13 | pages = 1531–9 | date = Apr 1997 | pmid = 9129143 | doi = 10.1038/sj.onc.1200988 }}</ref> and [[Retinoblastoma protein]].<ref name=pmid11358960/><ref name=pmid7935440>{{cite journal | vauthors = Kim YW, Otterson GA, Kratzke RA, Coxon AB, Kaye FJ | title = Differential specificity for binding of retinoblastoma binding protein 2 to RB, p107, and TATA-binding protein | journal = Molecular and Cellular Biology | volume = 14 | issue = 11 | pages = 7256–64 | date = Nov 1994 | pmid = 7935440 | pmc = 359260 | doi=10.1128/mcb.14.11.7256}}</ref>

JARID1A is a major component of the circadian clock, the upregulation of which at the end of the sleep phase blocks HDAC1 activity. Blocking HDAC1 activity results in an upregulation of CLOCK and BMAL1 and consequent upregulation of PER proteins. The PSF (polypyrimidine tract-binding protein-associated splicing factor) within the PER complex recruits SIN3A, a scaffold for assembly of transcriptional inhibitory complexes and rhythmically delivers histone deacetylases to the Per1 promoter, which repress Per1 transcription.<ref name="pmid21960634">{{cite journal | vauthors = DiTacchio L, Le HD, Vollmers C, Hatori M, Witcher M, Secombe J, Panda S | title = Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences the circadian clock | journal = Science | volume = 333 | issue = 6051 | pages = 1881–5 | year = 2011 | pmid = 21960634 | pmc = 3204309 | doi = 10.1126/science.1206022 }}</ref><ref name="pmid21680841">{{cite journal | vauthors = Duong HA, Robles MS, Knutti D, Weitz CJ | title = A molecular mechanism for circadian clock negative feedback | journal = Science | volume = 332 | issue = 6036 | pages = 1436–9 | year = 2011 | pmid = 21680841 | pmc = 3859310 | doi = 10.1126/science.1196766 }}</ref>

Knockdown of JARID1A promoted osteogenic differentiation of human adipose-derived stromal cells in vitro and in vivo and resulted in marked increases of mRNA expression of osteogenesis-associated genes such as alkaline phosphatase (ALP), osteocalcin (OC), and osterix (OSX). RBP2 was shown to occupy the promoters of OSX and OC to maintain the level of the [[H3K4me3]] mark by chromatin immunoprecipitation assays. RBP2 was also physically and functionally associated with RUNX2, an essential transcription factor that governed osteoblastic differentiation. RUNX2 knockdown impaired the repressive activity of RBP2 in osteogenic differentiation of human adipose-derived stromal cells.<ref name="pmid21604327">{{cite journal | vauthors = Ge W, Shi L, Zhou Y, Liu Y, Ma GE, Jiang Y, Xu Y, Zhang X, Feng H | title = Inhibition of osteogenic differentiation of human adipose-derived stromal cells by retinoblastoma binding protein 2 repression of RUNX2-activated transcription | journal = Stem Cells (Dayton, Ohio) | volume = 29 | issue = 7 | pages = 1112–25 | year = 2011 | pmid = 21604327 | doi = 10.1002/stem.663 }}</ref>

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Kim YW, Otterson GA, Kratzke RA, Coxon AB, Kaye FJ | title = Differential specificity for binding of retinoblastoma binding protein 2 to RB, p107, and TATA-binding protein | journal = Molecular and Cellular Biology | volume = 14 | issue = 11 | pages = 7256–64 | date = Nov 1994 | pmid = 7935440 | pmc = 359260 | doi = 10.1128/mcb.14.11.7256}}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Fattaey AR, Helin K, Dembski MS, Dyson N, Harlow E, Vuocolo GA, Hanobik MG, Haskell KM, Oliff A, Defeo-Jones D | title = Characterization of the retinoblastoma binding proteins RBP1 and RBP2 | journal = Oncogene | volume = 8 | issue = 11 | pages = 3149–56 | date = Nov 1993 | pmid = 8414517 | doi = }}
* {{cite journal | vauthors = Baens M, Aerssens J, van Zand K, Van den Berghe H, Marynen P | title = Isolation and regional assignment of human chromosome 12p cDNAs | journal = Genomics | volume = 29 | issue = 1 | pages = 44–52 | date = Sep 1995 | pmid = 8530100 | doi = 10.1006/geno.1995.1213 }}
* {{cite journal | vauthors = Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA | title = A "double adaptor" method for improved shotgun library construction | journal = Analytical Biochemistry | volume = 236 | issue = 1 | pages = 107–13 | date = Apr 1996 | pmid = 8619474 | doi = 10.1006/abio.1996.0138 }}
* {{cite journal | vauthors = Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, Dietrich N, DuBuque T, Favello A, Gish W, Hawkins M, Hultman M, Kucaba T, Lacy M, Le M, Le N, Mardis E, Moore B, Morris M, Parsons J, Prange C, Rifkin L, Rohlfing T, Schellenberg K, Bento Soares M, Tan F, Thierry-Meg J, Trevaskis E, Underwood K, Wohldman P, Waterston R, Wilson R, Marra M | title = Generation and analysis of 280,000 human expressed sequence tags | journal = Genome Research | volume = 6 | issue = 9 | pages = 807–28 | date = Sep 1996 | pmid = 8889549 | doi = 10.1101/gr.6.9.807 }}
* {{cite journal | vauthors = Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA | title = Large-scale concatenation cDNA sequencing | journal = Genome Research | volume = 7 | issue = 4 | pages = 353–8 | date = Apr 1997 | pmid = 9110174 | pmc = 139146 | doi = 10.1101/gr.7.4.353 }}
* {{cite journal | vauthors = Mao S, Neale GA, Goorha RM | title = T-cell oncogene rhombotin-2 interacts with retinoblastoma-binding protein 2 | journal = Oncogene | volume = 14 | issue = 13 | pages = 1531–9 | date = Apr 1997 | pmid = 9129143 | doi = 10.1038/sj.onc.1200988 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1-2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
* {{cite journal | vauthors = Chan SW, Hong W | title = Retinoblastoma-binding protein 2 (Rbp2) potentiates nuclear hormone receptor-mediated transcription | journal = The Journal of Biological Chemistry | volume = 276 | issue = 30 | pages = 28402–12 | date = Jul 2001 | pmid = 11358960 | doi = 10.1074/jbc.M100313200 }}
* {{cite journal | vauthors = Sandrock B, Egly JM | title = A yeast four-hybrid system identifies Cdk-activating kinase as a regulator of the XPD helicase, a subunit of transcription factor IIH | journal = The Journal of Biological Chemistry | volume = 276 | issue = 38 | pages = 35328–33 | date = Sep 2001 | pmid = 11445587 | doi = 10.1074/jbc.M105570200 }}
* {{cite journal | vauthors = Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP | title = Large-scale characterization of HeLa cell nuclear phosphoproteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 33 | pages = 12130–5 | date = Aug 2004 | pmid = 15302935 | pmc = 514446 | doi = 10.1073/pnas.0404720101 }}
* {{cite journal | vauthors = Benevolenskaya EV, Murray HL, Branton P, Young RA, Kaelin WG | title = Binding of pRB to the PHD protein RBP2 promotes cellular differentiation | journal = Molecular Cell | volume = 18 | issue = 6 | pages = 623–35 | date = Jun 2005 | pmid = 15949438 | doi = 10.1016/j.molcel.2005.05.012 }}
* {{cite journal | vauthors = Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S | title = Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes | journal = Genome Research | volume = 16 | issue = 1 | pages = 55–65 | date = Jan 2006 | pmid = 16344560 | pmc = 1356129 | doi = 10.1101/gr.4039406 }}
* {{cite journal | vauthors = Tzschach A, Lenzner S, Moser B, Reinhardt R, Chelly J, Fryns JP, Kleefstra T, Raynaud M, Turner G, Ropers HH, Kuss A, Jensen LR | title = Novel JARID1C/SMCX mutations in patients with X-linked mental retardation | journal = Human Mutation | volume = 27 | issue = 4 | pages = 389 | date = Apr 2006 | pmid = 16541399 | doi = 10.1002/humu.9420 }}
* {{cite journal | vauthors = Roesch A, Becker B, Schneider-Brachert W, Hagen I, Landthaler M, Vogt T | title = Re-expression of the retinoblastoma-binding protein 2-homolog 1 reveals tumor-suppressive functions in highly metastatic melanoma cells | journal = The Journal of Investigative Dermatology | volume = 126 | issue = 8 | pages = 1850–9 | date = Aug 2006 | pmid = 16645588 | doi = 10.1038/sj.jid.5700324 }}
* {{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | date = Nov 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 }}
{{refend}}

== External links ==
* {{MeshName|JARID1A+protein,+human}}

{{NLM content}}
{{Transcription factors|g2}}
{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:Transcription factors]]
[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]

KDM4D

2017-11-23T09:38:45Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{Infobox_gene}}
'''Lysine-specific demethylase 4D''' is an [[enzyme]] that in humans is encoded by the ''KDM4D'' [[gene]].<ref name="pmid15138608">{{cite journal |vauthors=Katoh M, Katoh M | title = Identification and characterization of JMJD2 family genes in silico | journal = Int J Oncol | volume = 24 | issue = 6 | pages = 1623–8 |date=May 2004 | pmid = 15138608 | pmc = | doi = 10.3892/ijo.25.3.759}}</ref><ref name="entrez">{{cite web | title = Entrez Gene: JMJD2D jumonji domain containing 2D| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55693| accessdate = }}</ref> KDM4D belongs to the [[2-oxoglutarate (2OG)-dependent dioxygenases | 2-oxoglutarate (2OG)-dependent dioxygenase]] superfamily.


{{PBB_Summary
| section_title =
| summary_text =
}}

==References==
{{reflist}}

==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal |vauthors=Shin S, Janknecht R |title=Activation of androgen receptor by histone demethylases JMJD2A and JMJD2D. |journal=Biochem. Biophys. Res. Commun. |volume=359 |issue= 3 |pages= 742–6 |year= 2007 |pmid= 17555712 |doi= 10.1016/j.bbrc.2007.05.179 }}
*{{cite journal |vauthors=Whetstine JR, Nottke A, Lan F, etal |title=Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. |journal=Cell |volume=125 |issue= 3 |pages= 467–81 |year= 2006 |pmid= 16603238 |doi= 10.1016/j.cell.2006.03.028 }}
*{{cite journal |vauthors=Taylor TD, Noguchi H, Totoki Y, etal |title=Human chromosome 11 DNA sequence and analysis including novel gene identification. |journal=Nature |volume=440 |issue= 7083 |pages= 497–500 |year= 2006 |pmid= 16554811 |doi= 10.1038/nature04632 }}
*{{cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}
*{{cite journal |vauthors=Ota T, Suzuki Y, Nishikawa T, etal |title=Complete sequencing and characterization of 21,243 full-length human cDNAs |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 }}
*{{cite journal |vauthors=Bonaldo MF, Lennon G, Soares MB |title=Normalization and subtraction: two approaches to facilitate gene discovery |journal=Genome Res. |volume=6 |issue= 9 |pages= 791–806 |year= 1997 |pmid= 8889548 |doi=10.1101/gr.6.9.791 }}
}}
{{refend}}

{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}


{{PBB_Controls
| update_page = yes
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[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]

{{gene-11-stub}}

KDM4C

2017-11-23T09:38:28Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{Infobox_gene}}
'''Lysine-specific demethylase 4C''' is an [[enzyme]] that in humans is encoded by the ''KDM4C'' [[gene]].<ref name="pmid9872452">{{cite journal | vauthors = Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O | title = Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro | journal = DNA Research | volume = 5 | issue = 5 | pages = 277–86 | date = Oct 1998 | pmid = 9872452 | pmc = | doi = 10.1093/dnares/5.5.277 }}</ref><ref name="pmid15138608">{{cite journal | vauthors = Katoh M, Katoh M | title = Identification and characterization of JMJD2 family genes in silico | journal = International Journal of Oncology | volume = 24 | issue = 6 | pages = 1623–8 | date = Jun 2004 | pmid = 15138608 | pmc = | doi = 10.3892/ijo.25.3.759 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: JMJD2C jumonji domain containing 2C| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23081| accessdate = }}</ref>

== Function ==

This gene is a member of the Jumonji domain 2 (JMJD2) family and encodes a protein with one JmjC domain, one JmjN domain, two PHD-type zinc fingers, and two [[Tudor domain]]s. This nuclear protein belongs to the [[2-oxoglutarate (2OG)-dependent dioxygenases | 2-oxoglutarate (2OG)-dependent dioxygenase]] superfamily. It functions as a trimethylation-specific demethylase, converting specific trimethylated histone residues to the dimethylated form. Chromosomal aberrations and increased transcriptional expression of this gene are associated with esophageal squamous cell carcinoma.<ref name="entrez" />

== Model organisms ==
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: right;" |
|+ ''Kdm4c'' knockout mouse phenotype
|-
! Characteristic!! Phenotype
|-
| [[Homozygote]] viability || bgcolor="#488ED3"|Normal
|-
| Fertility || bgcolor="#488ED3"|Normal
|-
| Body weight || bgcolor="#488ED3"|Normal
|-
| [[Open Field (animal test)|Anxiety]] || bgcolor="#488ED3"|Normal
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
|-
| Grip strength || bgcolor="#488ED3"|Normal
|-
| [[Hot plate test|Hot plate]] || bgcolor="#488ED3"|Normal
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
|-
| Body temperature || bgcolor="#488ED3"|Normal
|-
| Eye morphology || bgcolor="#488ED3"|Normal
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
|-
| [[Blood plasma|Plasma]] [[immunoglobulin]]s || bgcolor="#488ED3"|Normal
|-
| [[Haematology]] || bgcolor="#C40000"|Abnormal<ref name="Haematology">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBXV/haematology-cbc/ |title=Haematology data for Kdm4c |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Peripheral blood lymphocyte]]s || bgcolor="#488ED3"|Normal
|-
| [[Micronucleus test]] || bgcolor="#488ED3"|Normal
|-
| Heart weight || bgcolor="#488ED3"|Normal
|-
| Skin Histopathology || bgcolor="#C40000"|Abnormal
|-
| Eye Histopathology || bgcolor="#488ED3"|Normal
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Salmonella'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBXV/salmonella-challenge/ |title=''Salmonella'' infection data for Kdm4c |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| ''[[Citrobacter]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Citrobacter'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBXV/citrobacter-challenge/ |title=''Citrobacter'' infection data for Kdm4c |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| colspan=2; style="text-align: center;" | All tests and analysis from<ref name="mgp_reference">{{cite journal | doi = 10.1111/j.1755-3768.2010.4142.x | title = The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice | year = 2010 | author = Gerdin AK | journal = Acta Ophthalmologica | volume = 88 | pages = 925–7 }}</ref><ref>[http://www.sanger.ac.uk/mouseportal/ Mouse Resources Portal], Wellcome Trust Sanger Institute.</ref>
|}
[[Model organism]]s have been used in the study of KDM4C function. A conditional [[knockout mouse]] line, called ''Kdm4ctm1a(KOMP)Wtsi''<ref name="allele_ref">{{cite web |url=http://www.knockoutmouse.org/martsearch/search?query=Kdm4c |title=International Knockout Mouse Consortium}}</ref><ref name="mgi_allele_ref">{{cite web |url=http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4362199 |title=Mouse Genome Informatics}}</ref> was generated as part of the [[International Knockout Mouse Consortium]] program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.<ref name="pmid21677750">{{cite journal | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = Jun 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = Jun 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = Jan 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref>

Male and female animals underwent a standardized [[phenotypic screen]] to determine the effects of deletion.<ref name="mgp_reference" /><ref name="pmid21722353">{{cite journal | vauthors = van der Weyden L, White JK, Adams DJ, Logan DW | title = The mouse genetics toolkit: revealing function and mechanism | journal = Genome Biology | volume = 12 | issue = 6 | pages = 224 | year = 2011 | pmid = 21722353 | pmc = 3218837 | doi = 10.1186/gb-2011-12-6-224 }}</ref> Twenty five tests were carried out on [[mutant]] mice and two significant abnormalities were observed.<ref name="mgp_reference" /> [[Homozygous]] mutant males had decreased [[haematocrit]] and [[haemoglobin]] levels, while animals of both sex displayed an increase in [[sebaceous gland]] size.<ref name="mgp_reference" />

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Yang ZQ, Imoto I, Fukuda Y, Pimkhaokham A, Shimada Y, Imamura M, Sugano S, Nakamura Y, Inazawa J | title = Identification of a novel gene, GASC1, within an amplicon at 9p23-24 frequently detected in esophageal cancer cell lines | journal = Cancer Research | volume = 60 | issue = 17 | pages = 4735–9 | date = Sep 2000 | pmid = 10987278 | doi = }}
* {{cite journal | vauthors = Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S | title = Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes | journal = Genome Research | volume = 16 | issue = 1 | pages = 55–65 | date = Jan 2006 | pmid = 16344560 | pmc = 1356129 | doi = 10.1101/gr.4039406 }}
* {{cite journal | vauthors = Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y | title = Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases | journal = Cell | volume = 125 | issue = 3 | pages = 467–81 | date = May 2006 | pmid = 16603238 | doi = 10.1016/j.cell.2006.03.028 }}
* {{cite journal | vauthors = Cloos PA, Christensen J, Agger K, Maiolica A, Rappsilber J, Antal T, Hansen KH, Helin K | title = The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3 | journal = Nature | volume = 442 | issue = 7100 | pages = 307–11 | date = Jul 2006 | pmid = 16732293 | doi = 10.1038/nature04837 }}
* {{cite journal | vauthors = Wissmann M, Yin N, Müller JM, Greschik H, Fodor BD, Jenuwein T, Vogler C, Schneider R, Günther T, Buettner R, Metzger E, Schüle R | title = Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression | journal = Nature Cell Biology | volume = 9 | issue = 3 | pages = 347–53 | date = Mar 2007 | pmid = 17277772 | doi = 10.1038/ncb1546 }}
* {{cite journal | vauthors = Katoh Y, Katoh M | title = Comparative integromics on JMJD2A, JMJD2B and JMJD2C: preferential expression of JMJD2C in undifferentiated ES cells | journal = International Journal of Molecular Medicine | volume = 20 | issue = 2 | pages = 269–73 | date = Aug 2007 | pmid = 17611647 | doi = 10.3892/ijmm.20.2.269 }}
* {{cite journal | authors = Erhu Zhao, Jane Ding,.....Hongjuan Cui, Han-Fei Ding| title = KDM4C and ATF4 Cooperate in Transcriptional Control of Amino Acid Metabolism | journal = Cell Reports | volume = 14| issue = | pages = 506–519| date = 2016 | pmid = 26774480| doi = 10.1016/j.celrep.2015.12.053 | pmc=4731315}}

{{refend}}

{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]
[[Category:Genes mutated in mice]]

{{gene-9-stub}}

KDM4B

2017-11-23T09:37:54Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{Infobox_gene}}
'''Lysine-specific demethylase 4B''' is an [[enzyme]] that in humans is encoded by the ''KDM4B'' [[gene]].<ref name="pmid10048485">{{cite journal |vauthors=Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O | title = Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro | journal = DNA Res | volume = 5 | issue = 6 | pages = 355–64 |date=May 1999 | pmid = 10048485 | pmc = | doi =10.1093/dnares/5.6.355 }}</ref><ref name="pmid15138608">{{cite journal |vauthors=Katoh M, Katoh M | title = Identification and characterization of JMJD2 family genes in silico | journal = Int J Oncol | volume = 24 | issue = 6 | pages = 1623–8 |date=May 2004 | pmid = 15138608 | pmc = | doi = 10.3892/ijo.25.3.759}}</ref><ref name="entrez">{{cite web | title = Entrez Gene: JMJD2B jumonji domain containing 2B| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23030| accessdate = }}</ref> KDM4B belongs to the [[2-oxoglutarate (2OG)-dependent dioxygenases | 2-oxoglutarate (2OG)-dependent dioxygenase]] superfamily.


{{PBB_Summary
| section_title =
| summary_text =
}}

==References==
{{reflist}}

==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal |vauthors=Nakajima D, Okazaki N, Yamakawa H, etal |title=Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones. |journal=DNA Res. |volume=9 |issue= 3 |pages= 99–106 |year= 2003 |pmid= 12168954 |doi=10.1093/dnares/9.3.99 }}
*{{cite journal |vauthors=Andersson B, Wentland MA, Ricafrente JY, etal |title=A "double adaptor" method for improved shotgun library construction. |journal=Anal. Biochem. |volume=236 |issue= 1 |pages= 107–13 |year= 1996 |pmid= 8619474 |doi= 10.1006/abio.1996.0138 }}
*{{cite journal |vauthors=Yu W, Andersson B, Worley KC, etal |title=Large-scale concatenation cDNA sequencing. |journal=Genome Res. |volume=7 |issue= 4 |pages= 353–8 |year= 1997 |pmid= 9110174 |doi= 10.1101/gr.7.4.353| pmc=139146 }}
*{{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 }}
*{{cite journal |vauthors=Grimwood J, Gordon LA, Olsen A, etal |title=The DNA sequence and biology of human chromosome 19. |journal=Nature |volume=428 |issue= 6982 |pages= 529–35 |year= 2004 |pmid= 15057824 |doi= 10.1038/nature02399 }}
*{{cite journal |vauthors=Beausoleil SA, Jedrychowski M, Schwartz D, etal |title=Large-scale characterization of HeLa cell nuclear phosphoproteins. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130–5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101 | pmc=514446 }}
*{{cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}
*{{cite journal |vauthors=Gray SG, Iglesias AH, Lizcano F, etal |title=Functional characterization of JMJD2A, a histone deacetylase- and retinoblastoma-binding protein. |journal=J. Biol. Chem. |volume=280 |issue= 31 |pages= 28507–18 |year= 2005 |pmid= 15927959 |doi= 10.1074/jbc.M413687200 }}
*{{cite journal |vauthors=Whetstine JR, Nottke A, Lan F, etal |title=Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. |journal=Cell |volume=125 |issue= 3 |pages= 467–81 |year= 2006 |pmid= 16603238 |doi= 10.1016/j.cell.2006.03.028 }}
*{{cite journal |vauthors=Katoh Y, Katoh M |title=Comparative integromics on JMJD2A, JMJD2B and JMJD2C: preferential expression of JMJD2C in undifferentiated ES cells. |journal=Int. J. Mol. Med. |volume=20 |issue= 2 |pages= 269–73 |year= 2007 |pmid= 17611647 |doi= 10.3892/ijmm.20.2.269}}
}}
{{refend}}

{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}


{{PBB_Controls
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}

[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]

{{gene-19-stub}}

KDM4A

2017-11-23T09:37:29Z

2407:7000:81AD:4400:D497:974B:2344:E1F6: /* Function */

{{Infobox_gene}}
'''Lysine-specific demethylase 4A''' is an [[enzyme]] that in humans is encoded by the ''KDM4A'' [[gene]].<ref name="pmid9734811">{{cite journal | vauthors = Ishikawa K, Nagase T, Suyama M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O | title = Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro | journal = DNA Research | volume = 5 | issue = 3 | pages = 169–76 | date = June 1998 | pmid = 9734811 | pmc = | doi = 10.1093/dnares/5.3.169 }}</ref><ref name="pmid15138608">{{cite journal | vauthors = Katoh M, Katoh M | title = Identification and characterization of JMJD2 family genes in silico | journal = International Journal of Oncology | volume = 24 | issue = 6 | pages = 1623–8 | date = June 2004 | pmid = 15138608 | pmc = | doi = 10.3892/ijo.25.3.759 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: JMJD2A jumonji domain containing 2A| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9682| accessdate = }}</ref>

== Function ==

This gene is a member of the Jumonji domain 2 (JMJD2) family and encodes a protein with a JmjN domain, a JmjC domain, a JD2H domain, two [[TUDOR domain]]s, and two PHD-type zinc fingers. This nuclear protein belongs to the [[2-oxoglutarate (2OG)-dependent dioxygenases | 2-oxoglutarate (2OG)-dependent dioxygenase]] superfamily. It functions as a trimethylation-specific demethylase, converting specific trimethylated histone on histone H3 lysine 9 and 36 residues to the dimethylated form and lysine 9 dimethylated residues to monomethyl, and as a transcriptional repressor.<ref name="entrez" />

Alterations in this gene have been found associated with chromosomal instability that leads to cancer.({{PMID|23871696}})

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = September 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 }}
* {{cite journal | vauthors = Yoon HG, Chan DW, Reynolds AB, Qin J, Wong J | title = N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso | journal = Molecular Cell | volume = 12 | issue = 3 | pages = 723–34 | date = September 2003 | pmid = 14527417 | doi = 10.1016/j.molcel.2003.08.008 }}
* {{cite journal | vauthors = Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW | title = Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation | journal = Nature Biotechnology | volume = 22 | issue = 6 | pages = 707–16 | date = June 2004 | pmid = 15146197 | doi = 10.1038/nbt971 }}
* {{cite journal | vauthors = Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S | title = Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions | journal = Genome Research | volume = 14 | issue = 9 | pages = 1711–8 | date = September 2004 | pmid = 15342556 | pmc = 515316 | doi = 10.1101/gr.2435604 }}
* {{cite journal | vauthors = Gray SG, Iglesias AH, Lizcano F, Villanueva R, Camelo S, Jingu H, Teh BT, Koibuchi N, Chin WW, Kokkotou E, Dangond F | title = Functional characterization of JMJD2A, a histone deacetylase- and retinoblastoma-binding protein | journal = The Journal of Biological Chemistry | volume = 280 | issue = 31 | pages = 28507–18 | date = August 2005 | pmid = 15927959 | doi = 10.1074/jbc.M413687200 }}
* {{cite journal | vauthors = Zhang D, Yoon HG, Wong J | title = JMJD2A is a novel N-CoR-interacting protein and is involved in repression of the human transcription factor achaete scute-like homologue 2 (ASCL2/Hash2) | journal = Molecular and Cellular Biology | volume = 25 | issue = 15 | pages = 6404–14 | date = August 2005 | pmid = 16024779 | pmc = 1190321 | doi = 10.1128/MCB.25.15.6404-6414.2005 }}
* {{cite journal | vauthors = Tao WA, Wollscheid B, O'Brien R, Eng JK, Li XJ, Bodenmiller B, Watts JD, Hood L, Aebersold R | title = Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry | journal = Nature Methods | volume = 2 | issue = 8 | pages = 591–8 | date = August 2005 | pmid = 16094384 | doi = 10.1038/nmeth776 }}
* {{cite journal | vauthors = Kim J, Daniel J, Espejo A, Lake A, Krishna M, Xia L, Zhang Y, Bedford MT | title = Tudor, MBT and chromo domains gauge the degree of lysine methylation | journal = EMBO Reports | volume = 7 | issue = 4 | pages = 397–403 | date = April 2006 | pmid = 16415788 | pmc = 1456902 | doi = 10.1038/sj.embor.7400625 }}
* {{cite journal | vauthors = Huang Y, Fang J, Bedford MT, Zhang Y, Xu RM | title = Recognition of histone H3 lysine-4 methylation by the double tudor domain of JMJD2A | journal = Science | volume = 312 | issue = 5774 | pages = 748–51 | date = May 2006 | pmid = 16601153 | doi = 10.1126/science.1125162 }}
* {{cite journal | vauthors = Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y | title = Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases | journal = Cell | volume = 125 | issue = 3 | pages = 467–81 | date = May 2006 | pmid = 16603238 | doi = 10.1016/j.cell.2006.03.028 }}
* {{cite journal | vauthors = Chen Z, Zang J, Whetstine J, Hong X, Davrazou F, Kutateladze TG, Simpson M, Mao Q, Pan CH, Dai S, Hagman J, Hansen K, Shi Y, Zhang G | title = Structural insights into histone demethylation by JMJD2 family members | journal = Cell | volume = 125 | issue = 4 | pages = 691–702 | date = May 2006 | pmid = 16677698 | doi = 10.1016/j.cell.2006.04.024 }}
* {{cite journal | vauthors = Klose RJ, Yamane K, Bae Y, Zhang D, Erdjument-Bromage H, Tempst P, Wong J, Zhang Y | title = The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36 | journal = Nature | volume = 442 | issue = 7100 | pages = 312–6 | date = July 2006 | pmid = 16732292 | doi = 10.1038/nature04853 }}
* {{cite journal | vauthors = Shin S, Janknecht R | title = Activation of androgen receptor by histone demethylases JMJD2A and JMJD2D | journal = Biochemical and Biophysical Research Communications | volume = 359 | issue = 3 | pages = 742–6 | date = August 2007 | pmid = 17555712 | doi = 10.1016/j.bbrc.2007.05.179 }}
* {{cite journal | vauthors = Chen Z, Zang J, Kappler J, Hong X, Crawford F, Wang Q, Lan F, Jiang C, Whetstine J, Dai S, Hansen K, Shi Y, Zhang G | title = Structural basis of the recognition of a methylated histone tail by JMJD2A | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 26 | pages = 10818–23 | date = June 2007 | pmid = 17567753 | pmc = 1891149 | doi = 10.1073/pnas.0704525104 }}
* {{cite journal | vauthors = Ng SS, Kavanagh KL, McDonough MA, Butler D, Pilka ES, Lienard BM, Bray JE, Savitsky P, Gileadi O, von Delft F, Rose NR, Offer J, Scheinost JC, Borowski T, Sundstrom M, Schofield CJ, Oppermann U | title = Crystal structures of histone demethylase JMJD2A reveal basis for substrate specificity | journal = Nature | volume = 448 | issue = 7149 | pages = 87–91 | date = July 2007 | pmid = 17589501 | doi = 10.1038/nature05971 }}
* {{cite journal | vauthors = Lee J, Thompson JR, Botuyan MV, Mer G | title = Distinct binding modes specify the recognition of methylated histones H3K4 and H4K20 by JMJD2A-tudor | journal = Nature Structural & Molecular Biology | volume = 15 | issue = 1 | pages = 109–11 | date = January 2008 | pmid = 18084306 | pmc = 2211384 | doi = 10.1038/nsmb1326 }}
{{refend}}

{{PDB Gallery|geneid=9682}}
{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]

{{gene-1-stub}}

KDM3B

2017-11-23T09:36:45Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{Infobox_gene}}
'''Lysine-specific demethylase 3B''' is an [[enzyme]] that in humans is encoded by the ''KDM3B'' [[gene]].<ref name="pmid15138608">{{cite journal | vauthors = Katoh M, Katoh M | title = Identification and characterization of JMJD2 family genes in silico | journal = International Journal of Oncology | volume = 24 | issue = 6 | pages = 1623–8 | date = Jun 2004 | pmid = 15138608 | pmc = | doi = 10.3892/ijo.25.3.759 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: JMJD1B jumonji domain containing 1B| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51780| accessdate = }}</ref> KDM3B belongs to the [[2-oxoglutarate (2OG)-dependent dioxygenases | 2-oxoglutarate (2OG)-dependent dioxygenase]] superfamily.

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T | title = Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones | journal = DNA Research | volume = 9 | issue = 3 | pages = 99–106 | date = Jun 2002 | pmid = 12168954 | doi = 10.1093/dnares/9.3.99 }}
* {{cite journal | vauthors = Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ | title = Shotgun sequencing of the human transcriptome with ORF expressed sequence tags | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 7 | pages = 3491–6 | date = Mar 2000 | pmid = 10737800 | pmc = 16267 | doi = 10.1073/pnas.97.7.3491 }}
* {{cite journal | vauthors = Lai F, Godley LA, Fernald AA, Orelli BJ, Pamintuan L, Zhao N, Le Beau MM | title = cDNA cloning and genomic structure of three genes localized to human chromosome band 5q31 encoding potential nuclear proteins | journal = Genomics | volume = 70 | issue = 1 | pages = 123–30 | date = Nov 2000 | pmid = 11087669 | doi = 10.1006/geno.2000.6345 }}
* {{cite journal | vauthors = Lai F, Godley LA, Joslin J, Fernald AA, Liu J, Espinosa R, Zhao N, Pamintuan L, Till BG, Larson RA, Qian Z, Le Beau MM | title = Transcript map and comparative analysis of the 1.5-Mb commonly deleted segment of human 5q31 in malignant myeloid diseases with a del(5q) | journal = Genomics | volume = 71 | issue = 2 | pages = 235–45 | date = Jan 2001 | pmid = 11161817 | doi = 10.1006/geno.2000.6414 }}
* {{cite journal | vauthors = Hu Z, Gomes I, Horrigan SK, Kravarusic J, Mar B, Arbieva Z, Chyna B, Fulton N, Edassery S, Raza A, Westbrook CA | title = A novel nuclear protein, 5qNCA (LOC51780) is a candidate for the myeloid leukemia tumor suppressor gene on chromosome 5 band q31 | journal = Oncogene | volume = 20 | issue = 47 | pages = 6946–54 | date = Oct 2001 | pmid = 11687974 | doi = 10.1038/sj.onc.1204850 }}
* {{cite journal | vauthors = Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP | title = Large-scale characterization of HeLa cell nuclear phosphoproteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 33 | pages = 12130–5 | date = Aug 2004 | pmid = 15302935 | pmc = 514446 | doi = 10.1073/pnas.0404720101 }}
* {{cite journal | vauthors = Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M | title = Nucleolar proteome dynamics | journal = Nature | volume = 433 | issue = 7021 | pages = 77–83 | date = Jan 2005 | pmid = 15635413 | doi = 10.1038/nature03207 }}
* {{cite journal | vauthors = Yamane K, Toumazou C, Tsukada Y, Erdjument-Bromage H, Tempst P, Wong J, Zhang Y | title = JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor | journal = Cell | volume = 125 | issue = 3 | pages = 483–95 | date = May 2006 | pmid = 16603237 | doi = 10.1016/j.cell.2006.03.027 }}
* {{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | date = Nov 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 }}
{{refend}}

== External links ==
* {{MeshName|JMJD1B+protein,+human}}

{{NLM content}}
{{Transcription factors|g2}}
{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:Transcription factors]]
[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]

{{gene-5-stub}}

JMJD6

2017-11-23T09:36:10Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{Infobox_gene}}
'''Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6''' is an [[enzyme]] that in humans is encoded by the ''JMJD6'' [[gene]].<ref name="pmid11877474">{{cite journal | vauthors = Vandivier RW, Fadok VA, Hoffmann PR, Bratton DL, Penvari C, Brown KK, Brain JD, Accurso FJ, Henson PM | title = Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis | journal = The Journal of Clinical Investigation | volume = 109 | issue = 5 | pages = 661–70 | date = March 2002 | pmid = 11877474 | pmc = 150889 | doi = 10.1172/JCI13572 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: JMJD6 jumonji domain containing 6| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23210| accessdate = }}</ref>

== Function ==

This gene encodes a nuclear protein with a [[JmjC domain]]. JmjC domain-containing proteins belong to the [[2-oxoglutarate (2OG)-dependent dioxygenases | 2-oxoglutarate (2OG)-dependent dioxygenase]] superfamily. They are predicted to function as protein [[hydroxylase]]s or histone demethylases. This protein was first identified as a putative [[phosphatidylserine]] receptor involved in [[phagocytosis]] of [[Apoptosis|apoptotic cells]]; however, subsequent studies have suggested that the protein may cross-react with a monoclonal antibody that recognizes the phosphatidylserine receptor and does not directly function in the clearance of apoptotic cells. Multiple transcript variants encoding different isoforms have been found for this gene.<ref name="entrez" /> JMJD6 has been implicated in mammary tumorigenesis, and it increases breast cancer aggressiveness and metastasis in mice.<ref name="aprelikova">{{cite journal | vauthors = Aprelikova O, Chen K, El Touny LH, Brignatz-Guittard C, Han J, Qiu T, Yang HH, Lee MP, Zhu M, Green JE | title = The epigenetic modifier JMJD6 is amplified in mammary tumors and cooperates with c-Myc to enhance cellular transformation, tumor progression, and metastasis | journal = Clin Epigenetics | volume = 8 | issue = 38 | date = 14 Apr 2016 | doi = 10.1186/s13148-016-0205-6 | url = http://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-016-0205-6 | accessdate = }}</ref>

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Boeckel JN, Guarani V, Koyanagi M, Roexe T, Lengeling A, Schermuly RT, Gellert P, Braun T, Zeiher A, Dimmeler S | title = Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 8 | pages = 3276–81 | date = February 2011 | pmid = 21300889 | doi = 10.1073/pnas.1008098108 | pmc=3044381}}
* {{cite journal | vauthors = Webby CJ, Wolf A, Gromak N, Dreger M, Kramer H, Kessler B, Nielsen ML, Schmitz C, Butler DS, Yates JR, Delahunty CM, Hahn P, Lengeling A, Mann M, Proudfoot NJ, Schofield CJ, Böttger A | title = Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA splicing | journal = Science | volume = 325 | issue = 5936 | pages = 90–3 | date = July 2009 | pmid = 19574390 | doi = 10.1126/science.1175865 }}
* {{cite journal | vauthors = Zakharova L, Dadsetan S, Fomina AF | title = Endogenous Jmjd6 gene product is expressed at the cell surface and regulates phagocytosis in immature monocyte-like activated THP-1 cells | journal = Journal of Cellular Physiology | volume = 221 | issue = 1 | pages = 84–91 | date = October 2009 | pmid = 19492415 | doi = 10.1002/jcp.21829 }}
* {{cite journal | vauthors = Hahn P, Böse J, Edler S, Lengeling A | title = Genomic structure and expression of Jmjd6 and evolutionary analysis in the context of related JmjC domain containing proteins | journal = BMC Genomics | volume = 9 | pages = 293 | year = 2008 | pmid = 18564434 | pmc = 2453528 | doi = 10.1186/1471-2164-9-293 }}
* {{cite journal | vauthors = Chang B, Chen Y, Zhao Y, Bruick RK | title = JMJD6 is a histone arginine demethylase | journal = Science | volume = 318 | issue = 5849 | pages = 444–7 | date = October 2007 | pmid = 17947579 | doi = 10.1126/science.1145801 }}
* {{cite journal | vauthors = Klose RJ, Kallin EM, Zhang Y | title = JmjC-domain-containing proteins and histone demethylation | journal = Nature Reviews Genetics | volume = 7 | issue = 9 | pages = 715–27 | date = September 2006 | pmid = 16983801 | doi = 10.1038/nrg1945 }}
* {{cite journal | vauthors = Williamson P, Schlegel RA | title = Hide and seek: the secret identity of the phosphatidylserine receptor | journal = Journal of Biology | volume = 3 | issue = 4 | pages = 14 | year = 2005 | pmid = 15453906 | pmc = 549716 | doi = 10.1186/jbiol14 }}
* {{cite journal | vauthors = Böse J, Gruber AD, Helming L, Schiebe S, Wegener I, Hafner M, Beales M, Köntgen F, Lengeling A | title = The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal | journal = Journal of Biology | volume = 3 | issue = 4 | pages = 15 | year = 2005 | pmid = 15345036 | pmc = 549712 | doi = 10.1186/jbiol10 }}
* {{cite journal | vauthors = Nagase T, Ishikawa K, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O | title = Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro | journal = DNA Research | volume = 5 | issue = 1 | pages = 31–9 | date = February 1998 | pmid = 9628581 | doi = 10.1093/dnares/5.1.31 }}
* {{cite journal | vauthors = Fadok VA, Bratton DL, Rose DM, Pearson A, Ezekewitz RA, Henson PM | title = A receptor for phosphatidylserine-specific clearance of apoptotic cells | journal = Nature | volume = 405 | issue = 6782 | pages = 85–90 | date = May 2000 | pmid = 10811223 | doi = 10.1038/35011084 }}
* {{cite journal | vauthors = Ajmone-Cat MA, De Simone R, Nicolini A, Minghetti L | title = Effects of phosphatidylserine on p38 mitogen activated protein kinase, cyclic AMP responding element binding protein and nuclear factor-kappaB activation in resting and activated microglial cells | journal = Journal of Neurochemistry | volume = 84 | issue = 2 | pages = 413–6 | date = January 2003 | pmid = 12559004 | doi = 10.1046/j.1471-4159.2003.01562.x }}
* {{cite journal | vauthors = Chan A, Seguin R, Magnus T, Papadimitriou C, Toyka KV, Antel JP, Gold R | title = Phagocytosis of apoptotic inflammatory cells by microglia and its therapeutic implications: termination of CNS autoimmune inflammation and modulation by interferon-beta | journal = Glia | volume = 43 | issue = 3 | pages = 231–42 | date = September 2003 | pmid = 12898702 | doi = 10.1002/glia.10258 }}
* {{cite journal | vauthors = Wang X, Wu YC, Fadok VA, Lee MC, Gengyo-Ando K, Cheng LC, Ledwich D, Hsu PK, Chen JY, Chou BK, Henson P, Mitani S, Xue D | title = Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12 | journal = Science | volume = 302 | issue = 5650 | pages = 1563–6 | date = November 2003 | pmid = 14645848 | doi = 10.1126/science.1087641 }}
* {{cite journal | vauthors = Cui P, Qin B, Liu N, Pan G, Pei D | title = Nuclear localization of the phosphatidylserine receptor protein via multiple nuclear localization signals | journal = Experimental Cell Research | volume = 293 | issue = 1 | pages = 154–63 | date = February 2004 | pmid = 14729065 | doi = 10.1016/j.yexcr.2003.09.023 }}
* {{cite journal | vauthors = Cao WM, Murao K, Imachi H, Hiramine C, Abe H, Yu X, Dobashi H, Wong NC, Takahara J, Ishida T | title = Phosphatidylserine receptor cooperates with high-density lipoprotein receptor in recognition of apoptotic cells by thymic nurse cells | journal = Journal of Molecular Endocrinology | volume = 32 | issue = 2 | pages = 497–505 | date = April 2004 | pmid = 15072554 | doi = 10.1677/jme.0.0320497 }}
* {{cite journal | vauthors = Cikala M, Alexandrova O, David CN, Pröschel M, Stiening B, Cramer P, Böttger A | title = The phosphatidylserine receptor from Hydra is a nuclear protein with potential Fe(II) dependent oxygenase activity | journal = BMC Cell Biology | volume = 5 | pages = 26 | date = June 2004 | pmid = 15193161 | pmc = 442123 | doi = 10.1186/1471-2121-5-26 }}
* {{cite journal | vauthors = Hong JR, Lin GH, Lin CJ, Wang WP, Lee CC, Lin TL, Wu JL | title = Phosphatidylserine receptor is required for the engulfment of dead apoptotic cells and for normal embryonic development in zebrafish | journal = Development | volume = 131 | issue = 21 | pages = 5417–27 | date = November 2004 | pmid = 15469976 | doi = 10.1242/dev.01409 }}
* {{cite journal | vauthors = Köninger J, Balaz P, Wagner M, Shi X, Cima I, Zimmermann A, di Sebastiano P, Büchler MW, Friess H | title = Phosphatidylserine receptor in chronic pancreatitis: evidence for a macrophage independent role | journal = Annals of Surgery | volume = 241 | issue = 1 | pages = 144–51 | date = January 2005 | pmid = 15622002 | pmc = 1356857 | doi = }}
{{refend}}

{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]

{{gene-17-stub}}

JARID2

2017-11-23T09:35:24Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{Infobox_gene}}

'''Protein Jumonji''' is a [[protein]] that in humans is encoded by the ''JARID2'' [[gene]].<ref name="pmid8894700">{{cite journal |vauthors=Berge-Lefranc JL, Jay P, Massacrier A, Cau P, Mattei MG, Bauer S, Marsollier C, Berta P, Fontes M | title = Characterization of the human jumonji gene | journal = Hum Mol Genet | volume = 5 | issue = 10 | pages = 1637–41 |date=Feb 1997 | pmid = 8894700 | pmc = | doi =10.1093/hmg/5.10.1637 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: JARID2 jumonji, AT rich interactive domain 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3720| accessdate = }}</ref> JARID2 is a member of the [[2-oxoglutarate (2OG)-dependent dioxygenases | 2-oxoglutarate (2OG)-dependent dioxygenase]] superfamily.

Jarid2 (jumonji, AT rich interactive domain 2) is a protein coding gene that functions as a putative transcription factor. Distinguished as a nuclear protein necessary for mouse embryogenesis, Jarid2 is a member of the jumonji family that contains a DNA binding domain known as the AT-rich interaction domain (ARID).<ref name="Kim">{{cite journal |vauthors=Kim TG, Kraus JC, Chen J, Lee Y |title=Jumonji, a critical factor for cardiac development, functions as a transcriptional repressor |journal=J. Biol. Chem. |volume=278 |issue= 43 |pages= 42247–55 |year= 2004 |pmid= 12890668 |doi= 10.1074/jbc.M307386200 }}</ref><ref name="Mysliwiec2">{{cite journal |vauthors=Mysliwiec MR, Kim TG, Lee Y |title=Characterization of zinc finger protein 496 that interacts with jumonji/jarid2. |journal=FEBS Letters |volume=581 |issue= 14 |pages= 2633–40 |year= 2007}}</ref><ref name="Takahashi">{{cite journal |vauthors=Takahashi M, Kojima M, Nakajima K, Suzuki-Migishima R, Motegi Y, Yokoyama M, Takeuchi, T|title=Cardiac abnormalities cause early lethality of jumonji mutant mice |journal=Biochemical and Biophysical Research Communications |volume=324 |issue= 4 |pages= 1319–23 |year= 2004}}</ref><ref name="Toyota">{{cite journal |vauthors=Toyoda M, Kojima M, Takeuchi T |title=Jumonji is a nuclear protein that participates in the negative regulation of cell growth|journal=Biochemical and Biophysical Research Communications |volume=274 |issue= 2 |pages= 332–6 |year= 2000}}</ref> In vitro studies of Jarid2 reveal that ARID along with other functional domains are involved in DNA binding, nuclear localization, transcriptional repression,<ref name="Klassen">{{cite journal |vauthors=Klassen SS, Rabkin SW |title=Nitric oxide induces gene expression of jumonji and retinoblastoma 2 protein while reducing expression of atrial natriuretic peptide precursor type B in cardiomyocytes |journal=Folia Biologica |volume=54 |issue=2 |pages=65–70 |year=2008 }}</ref> and recruitment of Polycomb-repressive complex 2 (PRC2).<ref name="Pasini">{{cite journal |vauthors=Pasini D, Cloos PA, Walfridsson J, Olsson L, Bukowski JP, Johansen JV, Helin K|title=JARID2 regulates binding of the polycomb repressive complex 2 to target genes in ES cells. |journal=Nature |volume=464 |issue= 7286 |pages= 306–10 |year= 2010}}</ref><ref name="Son">{{cite journal |vauthors=Son J, Shen SS, Margueron R, Reinberg D |title=Nucleosome-binding activities within JARID2 and EZH1 regulate the function of PRC2 on chromatin |journal=Genes & Development |volume=27 |issue= 24 |pages= 2663–77 |year= 2013}}</ref> Intracellular mechanisms underlying these interactions remain largely unknown.

In search of developmentally important genes, Jarid2 has previously been identified by gene trap technology as an important factor necessary for organ development.<ref name="Kim"/><ref name="Klassen"/><ref name="Jung">{{cite journal |vauthors=Jung J, Mysliwiec MR, Lee Y |title=Roles of Jumonji in mouse embryonic development |journal=Developmental Dynamics |volume=232 |issue=1 |pages=21–32 |year= 2005 }}</ref> During mouse organogenesis, Jarid2 is involved in the formation of the neural tube and development of the liver, spleen, thymus and cardiovascular system.<ref name="Motoyama">{{cite journal |vauthors=Motoyama J, Kitajima K, Kojima M, Kondo S, Takeuchi T|title=Organogenesis of the liver, thymus and spleen is affected in jumonji mutant mice. |journal=Mechanisms of Development |volume=66 |issue= 1-2 |pages= 27–37 |year= 1997}}</ref><ref name="Takeuchi">{{cite journal |vauthors=Takeuchi T, Yamazaki Y, Katoh-Fukui Y, Tsuchiya R, Kondo S, Motoyama J, Higashinakagawa T |title=Gene trap capture of a novel mouse gene, jumonji, required for neural tube formation|journal=Genes & Development |volume=9 |issue= 10 |pages= 1211–22 |year= 1995}}</ref> Continuous Jarid2 expression in the tissues of the heart, highlight its presiding role in the development of both the embryonic and the adult heart.<ref name="Kim"/> Mutant models of Jarid2 embryos show severe heart malformations, ventricular septal defects, noncompaction of the ventricular wall, and dilated atria.<ref name="Kim"/> Homozygous mutants of Jarid2 are found to die soon after birth.<ref name="Kim"/> Overexpression of the mouse Jarid2 gene has been reported to repress cardiomyocyte proliferation through it close interaction with retinoblastoma protein (Rb), a master cell cycle regulator.<ref name="Klassen" /><ref name="Jung" /><ref name="Mysliwiec">{{cite journal |vauthors=Mysliwiec MR, Chen J, Powers PA, Bartley CR, Schneider MD, Lee Y|title=Generation of a conditional null allele of jumonji. |journal=Genesis |volume=44 |issue= 9 |pages= 407–11 |year= 2000}}</ref> Retinoblastoma-binding protein-2 and the human SMCX protein share regions of homology between mice and humans.<ref name="pmid8894700" />

==Model organisms==
{| class="wikitable sortable" border="1" cellpadding="2" style="float: right;" |
|+ ''Jarid2'' knockout mouse phenotype
|-
! Characteristic!! Phenotype
|-
| [[Homozygote]] viability || bgcolor="#C40000"|Abnormal
|-
| [[Recessive]] lethal study || bgcolor="#C40000"|Abnormal
|-
| Fertility || bgcolor="#488ED3"|Normal
|-
| Body weight || bgcolor="#488ED3"|Normal
|-
| [[Open Field (animal test)|Anxiety]] || bgcolor="#488ED3"|Normal
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
|-
| Grip strength || bgcolor="#488ED3"|Normal
|-
| [[Hot plate test|Hot plate]] || bgcolor="#488ED3"|Normal
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
|-
| Body temperature || bgcolor="#488ED3"|Normal
|-
| Eye morphology || bgcolor="#488ED3"|Normal
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
|-
| [[Blood plasma|Plasma]] [[immunoglobulin]]s || bgcolor="#488ED3"|Normal
|-
| [[Haematology]] || bgcolor="#488ED3"|Normal
|-
| [[Peripheral blood lymphocyte]]s || bgcolor="#488ED3"|Normal
|-
| [[Micronucleus test]] || bgcolor="#488ED3"|Normal
|-
| Heart weight || bgcolor="#488ED3"|Normal
|-
| Skin Histopathology || bgcolor="#488ED3"|Normal
|-
| Brain histopathology || bgcolor="#488ED3"|Normal
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Salmonella'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAEF/salmonella-challenge/ |title=''Salmonella'' infection data for Jarid2 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| ''[[Citrobacter]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Citrobacter'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAEF/citrobacter-challenge/ |title=''Citrobacter'' infection data for Jarid2 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| colspan=2; style="text-align: center;" | All tests and analysis from<ref name="mgp_reference">{{cite journal| doi = 10.1111/j.1755-3768.2010.4142.x| title = The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice| year = 2010| author = Gerdin AK| journal = Acta Ophthalmologica| volume = 88| issue = S248 }}</ref><ref>[http://www.sanger.ac.uk/mouseportal/ Mouse Resources Portal], Wellcome Trust Sanger Institute.</ref>
|}

[[Model organism]]s have been used in the study of JARID2 function. A conditional [[knockout mouse]] line, called ''Jarid2tm1a(KOMP)Wtsi''<ref name="allele_ref">{{cite web |url=http://www.knockoutmouse.org/martsearch/search?query=Jarid2 |title=International Knockout Mouse Consortium}}</ref><ref name="mgi_allele_ref">{{cite web |url=http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4362782 |title=Mouse Genome Informatics}}</ref> was generated as part of the [[International Knockout Mouse Consortium]] program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the [[Wellcome Trust Sanger Institute]].<ref name="pmid21677750">{{Cite journal
| last1 = Skarnes |first1 =W. C.
| doi = 10.1038/nature10163
| last2 = Rosen | first2 = B.
| last3 = West | first3 = A. P.
| last4 = Koutsourakis | first4 = M.
| last5 = Bushell | first5 = W.
| last6 = Iyer | first6 = V.
| last7 = Mujica | first7 = A. O.
| last8 = Thomas | first8 = M.
| last9 = Harrow | first9 = J.
| last10 = Cox | first10 = T.
| last11 = Jackson | first11 = D.
| last12 = Severin | first12 = J.
| last13 = Biggs | first13 = P.
| last14 = Fu | first14 = J.
| last15 = Nefedov | first15 = M.
| last16 = De Jong | first16 = P. J.
| last17 = Stewart | first17 = A. F.
| last18 = Bradley | first18 = A.
| title = A conditional knockout resource for the genome-wide study of mouse gene function
| journal = Nature
| volume = 474
| issue = 7351
| pages = 337–342
| year = 2011
| pmid = 21677750
| pmc =3572410
}}</ref><ref name="mouse_library">{{cite journal |author=Dolgin E |title=Mouse library set to be knockout |journal=Nature |volume=474 |issue=7351 |pages=262–3 |date=June 2011 |pmid=21677718 |doi=10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal |vauthors=Collins FS, Rossant J, Wurst W |title=A mouse for all reasons |journal=Cell |volume=128 |issue=1 |pages=9–13 |date=January 2007 |pmid=17218247 |doi=10.1016/j.cell.2006.12.018 }}</ref>

Male and female animals underwent a standardized [[phenotypic screen]] to determine the effects of deletion.<ref name="mgp_reference" /><ref name="pmid21722353">{{cite journal|vauthors=van der Weyden L, White JK, Adams DJ, Logan DW | title=The mouse genetics toolkit: revealing function and mechanism. | journal=Genome Biol | year= 2011 | volume= 12 | issue= 6 | pages= 224 | pmid=21722353 | doi=10.1186/gb-2011-12-6-224 | pmc=3218837}}</ref> Twenty six tests were carried out and two [[phenotypes]] were reported. [[Homozygous]] [[mutant]] embryos were identified during gestation but almost half showed signs of [[oedema]], and in a separate study, only 1% survived until [[weaning]] (significantly less than the [[Mendelian ratio]]). The remaining tests were carried out on [[heterozygous]] mutant adult mice; no significant abnormalities were observed in these animals.<ref name="mgp_reference" />

==References==
{{reflist}}

==Further reading==
{{refbegin | 2}}

*{{cite journal |vauthors=Lee Y, Song AJ, Baker R, etal |title=Jumonji, a nuclear protein that is necessary for normal heart development. |journal=Circ. Res. |volume=86 |issue= 9 |pages= 932–8 |year= 2000 |pmid= 10807864 |doi= 10.1161/01.res.86.9.932}}
*{{cite journal |vauthors=Toyoda M, Kojima M, Takeuchi T |title=Jumonji is a nuclear protein that participates in the negative regulation of cell growth. |journal=Biochem. Biophys. Res. Commun. |volume=274 |issue= 2 |pages= 332–6 |year= 2000 |pmid= 10913339 |doi= 10.1006/bbrc.2000.3138 }}
*{{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 }}
*{{cite journal |vauthors=Mungall AJ, Palmer SA, Sims SK, etal |title=The DNA sequence and analysis of human chromosome 6. |journal=Nature |volume=425 |issue= 6960 |pages= 805–11 |year= 2003 |pmid= 14574404 |doi= 10.1038/nature02055 }}
*{{cite journal |vauthors=Volcik KA, Zhu H, Finnell RH, etal |title=Evaluation of the jumonji gene and risk for spina bifida and congenital heart defects. |journal=Am. J. Med. Genet. A |volume=126 |issue= 2 |pages= 215–7 |year= 2004 |pmid= 15057990 |doi= 10.1002/ajmg.a.20574 }}
*{{cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}
*{{cite journal |vauthors=Kim TG, Chen J, Sadoshima J, Lee Y |title=Jumonji represses atrial natriuretic factor gene expression by inhibiting transcriptional activities of cardiac transcription factors. |journal=Mol. Cell. Biol. |volume=24 |issue= 23 |pages= 10151–60 |year= 2005 |pmid= 15542826 |doi= 10.1128/MCB.24.23.10151-10160.2004 | pmc=529025 }}
*{{cite journal |vauthors=Pedrosa E, Ye K, Nolan KA, etal |title=Positive association of schizophrenia to JARID2 gene. |journal=Am. J. Med. Genet. B Neuropsychiatr. Genet. |volume=144 |issue= 1 |pages= 45–51 |year= 2007 |pmid= 16967465 |doi= 10.1002/ajmg.b.30386 }}
{{refend}}

== External links ==
* {{MeshName|JARID2+protein,+human}}

{{NLM content}}
{{Transcription factors|g2}}
{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]
[[Category:Transcription factors]]
[[Category:Genes mutated in mice]]

JARID1B

2017-11-23T09:34:41Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{Infobox_gene}}
'''Lysine-specific demethylase 5B''' also known as '''histone demethylase JARID1B''' is a [[demethylase]] [[enzyme]] that in humans is encoded by the ''KDM5B'' [[gene]].<ref name="pmid11483573">{{cite journal | vauthors = Lahoud MH, Ristevski S, Venter DJ, Jermiin LS, Bertoncello I, Zavarsek S, Hasthorpe S, Drago J, de Kretser D, Hertzog PJ, Kola I | title = Gene targeting of Desrt, a novel ARID class DNA-binding protein, causes growth retardation and abnormal development of reproductive organs | journal = Genome Research | volume = 11 | issue = 8 | pages = 1327–34 | date = August 2001 | pmid = 11483573 | pmc = | doi = 10.1101/gr.168801 }}</ref><ref name="pmid11478881">{{cite journal | vauthors = Zhu L, Hu J, Lin D, Whitson R, Itakura K, Chen Y | title = Dynamics of the Mrf-2 DNA-binding domain free and in complex with DNA | journal = Biochemistry | volume = 40 | issue = 31 | pages = 9142–50 | date = August 2001 | pmid = 11478881 | pmc = | doi = 10.1021/bi010476a }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: JARID1B jumonji, AT rich interactive domain 1B| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10765| accessdate = }}</ref> JARID1B belongs to the [[2-oxoglutarate (2OG)-dependent dioxygenases | 2-oxoglutarate (2OG)-dependent dioxygenase]] superfamily.

== Function ==

Jarid1B (also known as KDM5B or PLU1) is in the family of JHDM genes. These are responsible for demethylation of tri- and di-methylated lysines in the 4 position of histone 3 ([[H3K4me3]] and H3K4me2). Jarid1B is a multidomain enzyme that is part of the subfamily KDM5. The whole Jarid1 family is a protein family that possesses H3K4 histone demethylase activity.<ref name="pmid22420752">{{cite journal | vauthors = Kristensen LH, Nielsen AL, Helgstrand C, Lees M, Cloos P, Kastrup JS, Helin K, Olsen L, Gajhede M | title = Studies of H3K4me3 demethylation by KDM5B/Jarid1B/PLU1 reveals strong substrate recognition in vitro and identifies 2,4-pyridine-dicarboxylic acid as an in vitro and in cell inhibitor | journal = The FEBS Journal | volume = 279 | issue = 11 | pages = 1905–14 | date = June 2012 | pmid = 22420752 | doi = 10.1111/j.1742-4658.2012.08567.x }}</ref>

Jarid1B has been implicated in the development of prostate, breast, and skin cancer and also has been associated with melanoma maintenance. Knockout mice (Jarid1b−/−) produced are viable in neonatal life. These mice do exhibit the phenotype of premature mortality, decreased fertility in female mice, reduction in body weight and impairment in mammary gland development. It also acted to decrease serum estrogen levels and caused reduced mammary epithelial cell proliferation in the early stages of puberty. These Jarid1b−/− mice seem to be greatly affected in many regulators of the development of mammy development such as FOXA1 and estrogen receptor α.<ref name="pmid24802759">{{cite journal | vauthors = Zou MR, Cao J, Liu Z, Huh SJ, Polyak K, Yan Q | title = Histone demethylase jumonji AT-rich interactive domain 1B (JARID1B) controls mammary gland development by regulating key developmental and lineage specification genes | journal = The Journal of Biological Chemistry | volume = 289 | issue = 25 | pages = 17620–33 | date = June 2014 | pmid = 24802759 | pmc = 4067197 | doi = 10.1074/jbc.M114.570853 }}</ref> However, others have shown that a Jarid1B knockout embryos usually have neonatal lethality due to the failure of their respiratory system. Knockout embryos have also been seen to have several different neural defects including: disorganized cranial nerves, increased incidences of exencephaly, and defects in eye development.<ref name="pmid23637629">{{cite journal | vauthors = Albert M, Schmitz SU, Kooistra SM, Malatesta M, Morales Torres C, Rekling JC, Johansen JV, Abarrategui I, Helin K | title = The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3 | journal = PLoS Genetics | volume = 9 | issue = 4 | pages = e1003461 | date = April 2013 | pmid = 23637629 | pmc = 3630093 | doi = 10.1371/journal.pgen.1003461 }}</ref>

== Interactions ==

JARID1B has been shown to [[Protein-protein interaction|interact]] with [[FOXG1]]<ref name=pmid12657635>{{cite journal | vauthors = Tan K, Shaw AL, Madsen B, Jensen K, Taylor-Papadimitriou J, Freemont PS | title = Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9 | journal = The Journal of Biological Chemistry | volume = 278 | issue = 23 | pages = 20507–13 | date = June 2003 | pmid = 12657635 | doi = 10.1074/jbc.M301994200 }}</ref> and [[PAX9]].<ref name=pmid12657635/>

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Lu PJ, Sundquist K, Baeckstrom D, Poulsom R, Hanby A, Meier-Ewert S, Jones T, Mitchell M, Pitha-Rowe P, Freemont P, Taylor-Papadimitriou J | title = A novel gene (PLU-1) containing highly conserved putative DNA/chromatin binding motifs is specifically up-regulated in breast cancer | journal = The Journal of Biological Chemistry | volume = 274 | issue = 22 | pages = 15633–45 | date = May 1999 | pmid = 10336460 | doi = 10.1074/jbc.274.22.15633 }}
* {{cite journal | vauthors = Kashuba V, Protopopov A, Podowski R, Gizatullin R, Li J, Klein G, Wahlestedt C, Zabarovsky E | title = Isolation and chromosomal localization of a new human retinoblastoma binding protein 2 homologue 1a (RBBP2H1A) | journal = European Journal of Human Genetics | volume = 8 | issue = 6 | pages = 407–13 | date = June 2000 | pmid = 10878660 | doi = 10.1038/sj.ejhg.5200474 }}
* {{cite journal | vauthors = Barrett A, Madsen B, Copier J, Lu PJ, Cooper L, Scibetta AG, Burchell J, Taylor-Papadimitriou J | title = PLU-1 nuclear protein, which is upregulated in breast cancer, shows restricted expression in normal human adult tissues: a new cancer/testis antigen? | journal = International Journal of Cancer | volume = 101 | issue = 6 | pages = 581–8 | date = October 2002 | pmid = 12237901 | doi = 10.1002/ijc.10644 }}
* {{cite journal | vauthors = Tan K, Shaw AL, Madsen B, Jensen K, Taylor-Papadimitriou J, Freemont PS | title = Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9 | journal = The Journal of Biological Chemistry | volume = 278 | issue = 23 | pages = 20507–13 | date = June 2003 | pmid = 12657635 | doi = 10.1074/jbc.M301994200 }}
* {{cite journal | vauthors = Patsialou A, Wilsker D, Moran E | title = DNA-binding properties of ARID family proteins | journal = Nucleic Acids Research | volume = 33 | issue = 1 | pages = 66–80 | year = 2005 | pmid = 15640446 | pmc = 546134 | doi = 10.1093/nar/gki145 }}
* {{cite journal | vauthors = Tzschach A, Lenzner S, Moser B, Reinhardt R, Chelly J, Fryns JP, Kleefstra T, Raynaud M, Turner G, Ropers HH, Kuss A, Jensen LR | title = Novel JARID1C/SMCX mutations in patients with X-linked mental retardation | journal = Human Mutation | volume = 27 | issue = 4 | pages = 389 | date = April 2006 | pmid = 16541399 | doi = 10.1002/humu.9420 }}
* {{cite journal | vauthors = Yamane K, Tateishi K, Klose RJ, Fang J, Fabrizio LA, Erdjument-Bromage H, Taylor-Papadimitriou J, Tempst P, Zhang Y | title = PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation | journal = Molecular Cell | volume = 25 | issue = 6 | pages = 801–12 | date = March 2007 | pmid = 17363312 | doi = 10.1016/j.molcel.2007.03.001 }}
* {{cite journal | vauthors = Barrett A, Santangelo S, Tan K, Catchpole S, Roberts K, Spencer-Dene B, Hall D, Scibetta A, Burchell J, Verdin E, Freemont P, Taylor-Papadimitriou J | title = Breast cancer associated transcriptional repressor PLU-1/JARID1B interacts directly with histone deacetylases | journal = International Journal of Cancer | volume = 121 | issue = 2 | pages = 265–75 | date = July 2007 | pmid = 17373667 | doi = 10.1002/ijc.22673 }}
{{refend}}

== External links ==
* {{MeshName|JARID1B+protein,+human}}

{{NLM content}}
{{Transcription factors}}
{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:Transcription factors|g2]]
[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]

{{gene-1-stub}}

FTO gene

2017-11-23T09:33:42Z

2407:7000:81AD:4400:D497:974B:2344:E1F6: /* Function */

{{Infobox_gene}}
'''Fat mass and obesity-associated protein''' also known as '''alpha-ketoglutarate-dependent dioxygenase FTO''' is an [[enzyme]] that in humans is encoded by the ''FTO'' [[gene]] located on [[Chromosome 16 (human)|chromosome 16]]. As one homolog in the [[AlkB]] family proteins, it is the first mRNA demethylase that has been identified.<ref name="Jia_2011"/> Certain variants of the FTO gene appear to be [[correlated]] with [[obesity]] in [[human]]s.<ref name="Loos_2014"/>

== Function ==

The [[amino acid]] [[sequence (biology)|sequence]] of the [[transcription (genetics)|transcribed]] FTO protein shows high similarity with the enzyme [[AlkB]] which oxidatively [[demethylation|demethylates]] [[DNA]].<ref name="Gerken_2007"/><ref name="Sanchez-Pulido_2007"/> FTO is a member of the superfamily of non-haem Fe(II) and [[2-oxoglutarate (2OG)-dependent dioxygenases]]. Recombinant FTO protein was first discovered to catalyze demethylation of 3-methylthymine in single-stranded DNA, and 3-methyluridine in single-stranded RNA, with low efficiency.<ref name="Gerken_2007"/> The [[nucleoside]] [[N6-methyladenosine]], an abundant modification in [[RNA]], was then found to be a major substrate of FTO.<ref name="Jia_2011" /><ref name="Meyer_2012"/> The FTO gene expression was also found to be significantly upregulated in the [[hypothalamus]] of rats after food deprivation and strongly negatively correlated with the expression of orexigenic [[galanin-like peptide]] which is involved in the stimulation of food intake.<ref name="Fredriksson_2008"/>

Increases in hypothalamic expression of FTO are associated with the regulation of energy intake but not feeding reward.<ref name="Olszewski_2009"/>

People with two copies of the risk allele for the rs9939609 single nucleotide polymorphism ([[Single-nucleotide polymorphism|SNP]]) showed differing neural responses to food images via [[fMRI]].<ref name="pmid26340902">{{cite journal | vauthors = Wiemerslage L, Nilsson EK, Solstrand Dahlberg L, Ence-Eriksson F, Castillo S, Larsen AL, Bylund SB, Hogenkamp PS, Olivo G, Bandstein M, Titova OE, Larsson EM, Benedict C, Brooks SJ, Schiöth HB | title = An obesity-associated risk allele within the FTO gene affects brain activity for areas important for emotion, impulse control, and reward in response to food images. | journal = Eur J Neurosci | year = 2016 | pmid = 26797854 | doi = 10.1111/ejn.13177 | volume=43 | pages=1173–80}}</ref> However, rs9939609's association with ''FTO'' is controversial, and may actually affect another gene, called iroquious homeobox protein 3 (''[[IRX3]]'').<ref name="pmid26797854">{{cite journal | vauthors = Rask-Andersen M, Almén MS, Schiöth HB | title = Scrutinizing the FTO locus: compelling evidence for a complex, long-range regulatory context. | journal = Hum Genet | year = 2015 | pmid = 26340902 | doi = 10.1007/s00439-015-1599-5 | volume=134 | pages=1183–93}}</ref>

== FTO demethylates m6A in mRNA ==

[[N6-methyladenosine|'''''N'''''6-methyladenosine''']] (m6A) is an abundant modification in [[mRNA]] and is found within some viruses,<ref name="Aloni_1979"/><ref name="Beemon_1977"/> and most eukaryotes including mammals,<ref name="Desrosiers_1974"/><ref name="Adams_1975"/><ref name="Wei_1976"/><ref name="Perry_1975"/> insects,<ref name="Levis_1978"/> plants,<ref name="Nichols_1979"/><ref name="Kennedy_1979"/><ref name="Zhong_2008"/> and yeast.<ref name="Clancy_2002"/><ref name="Bodi_2010"/> It is also found in [[tRNA]], [[rRNA]], and [[small nuclear RNA]] (snRNA) as well as several [[long non-coding RNA]], such as ''[[Xist]]''.<ref name="Meyer_2012"/><ref name="Dominissini_2012"/> Adenosine methylation is directed by a large m6A methyltransferase complex containing [[METTL3]] as the [[S-Adenosyl methionine|SAM]]-binding sub-unit.<ref name="Bokar_1997"/> ''In vitro'', this methyltransferase complex preferentially methylates RNA oligonucleotides containing GGACU<ref name="Harper_1990"/> and a similar preference was identified ''in vivo'' in mapped m6A sites in Rous sarcoma virus genomic RNA<ref name="Kane_1985"/> and in bovine prolactin mRNA.<ref name="Horowitz_1984"/> In plants, the majority of the m6A is found within 150 nucleotides before the start of the [[poly(A) tail]].<ref name="Bodi_2012"/>

Mapping of m6A in human and mouse RNA has identified over 18,000 m6A sites in the transcripts of more than 7,000 human genes with a [[consensus sequence]] of [G/A/U][G>A]m6AC[U>A/C]<ref name="Meyer_2012"/><ref name="Dominissini_2012"/> consistent with the previously identified motif.<ref name="Harper_1990"/> Sites preferentially appear in two distinct landmarks—around [[stop codons]] and within long internal [[exons]]—and are highly conserved between [[human]] and [[mouse]].<ref name="Meyer_2012"/><ref name = "Dominissini_2012"/> A subset of stimulus-dependent, dynamically modulated sites has been identified. Silencing the m6A [[methyltransferase]] significantly affects gene expression and alternative [[RNA splicing]] patterns, resulting in modulation of the [[p53]] (also known as [[TP53]]) signalling pathway and [[apoptosis]].

FTO demethylates m6A containing RNA efficiently in vitro.<ref name="Jia_2011"/> FTO [[Gene knockdown|knockdown]] with [[siRNA]] led to increased amounts of m6A in polyA-RNA, whereas [[overexpression]] of FTO resulted in decreased amounts of m6A in human cells.<ref name="Meyer_2012"/> FTO partially co-localizes with [[nuclear speckles]], which supports the notion that m6A in nuclear RNA is a major physiological [[substrate (biochemistry)|substrate]] of FTO. Function of FTO likely affects the processing of [[pre-mRNA]], other nuclear RNAs, or both. The discovery of the FTO-mediated oxidative [[demethylation]] of m6A in nuclear RNA may initiate further investigations on biological regulation based on reversible chemical modification of RNA.<ref name="Jia_2011"/><ref name="Meyer_2012"/>

== Tissue distribution ==
The FTO gene is widely expressed in both fetal and adult tissues.<ref name="Frayling_2007"/>

== Clinical significance ==

=== Association with obesity ===
[[File:3LFM FAT Mass and Obesity Associated (Fto) Protein.png|thumb|Fat Mass and Obesity-Associated (FTO) Protein]]

A study of 38,759 Europeans for variants of FTO identified an obesity risk [[allele]].<ref name="Frayling_2007"/> In particular, [[Zygosity|carriers of one copy]] of the allele weighed on average {{convert|1.2|kg|lb}} more than people with no copies. [[Zygosity|Carriers of two copies]] (16% of the subjects) weighed {{convert|3|kg|lb}} more and had a 1.67-fold higher [[Rate (mathematics)|rate]] of obesity than those with no copies. The association was observed in ages 7 and upwards. This gene is not directly associated with diabetes; however, increased body-fat also increases the risk of developing [[type 2 diabetes]].<ref name="Sandholt_2012"/>

Simultaneously, a study in 2,900 affected individuals and 5,100 controls of French descent, together with 500 trios (confirming an association independent of population stratification) found association of [[Single-nucleotide polymorphism|SNP]]s in the very same region of FTO ([[rs1421085]]).<ref name=" Dina_2007 "/> The authors found that this variation, or a variation in strong [[Linkage disequilibrium|LD]] with this variation explains 1% of the population BMI variance and 22% of the population attributable risk of obesity. The authors of this study claim that while obesity was already known to have a genetic component (from [[twin studies]]), no [[repeatability|replicated]] previous study has ever identified an obesity risk allele that was so common in the human population. The risk allele is a cluster of 10 [[single nucleotide polymorphism]] in the first [[intron]] of FTO called rs9939609. According to [[HapMap]], it has population frequencies of 45% in the West/Central Europeans, 52% in [[Yoruba people|Yorubans]] (West African natives) and 14% in Chinese/Japanese. Furthermore, [[morbid obesity]] is associated with a combination of FTO and [[INSIG2]] [[single nucleotide polymorphism]]s.<ref name="Chu_2008"/>

In 2009, variants in the FTO gene were further confirmed to associate with [[obesity]] in two very large genome wide association studies of [[body mass index]] (BMI).<ref name="Thorleifsson_2009"/><ref name="Willer_2009"/>

In adult humans, it was shown that adults bearing the at risk AT and AA alleles at rs9939609 consumed between 500 and 1250 kJ more each day than those carrying the protective TT genotype (equivalent to between 125 and 280 kcal per day more intake).<ref name="Speakman_2008"/> The same study showed that there was no impact of the polymorphism on energy expenditure. This finding of an effect of the rs9939609 polymorphism on food intake or satiety has been independently replicated in five subsequent studies (in order of publication).<ref name="Wardle_2008"/><ref name="Timpson_2008"/><ref name="Haupt_2009"/><ref name="Wardle_2009"/><ref name="Cecil_2008"/> Three of these subsequent studies also measured resting energy expenditure and confirmed the original finding that there is no impact of the polymorphic variation at the rs9939609 locus on energy expenditure. A different study explored the effects of variation in two different SNPs in the FTO gene (rs17817449 and rs1421085) and suggested there might be an effect on circulating leptin levels and energy expenditure, but this latter effect disappeared when the expenditure was normalised for differences in body composition.<ref name="Do_2008"/> The accumulated data across seven independent studies therefore clearly implicates the FTO gene in humans as having a direct impact on food intake but no effect on energy expenditure.

The obesity-associated noncoding region within the FTO gene interacts directly with the promoter of [[IRX3]], a homeobox gene, and [[IRX5]], another homeobox gene. The noncoding region of FTO interacts with the promoters of IRX3 and FTO in human, mouse and zebrafish, and with IRX5. Results suggest that IRX3 and IRX5 are linked with obesity and determine body mass and composition. This is further supported by the fact that obesity-associated [[single nucleotide polymorphisms]], in which cytosine is substituted for thymine, are involved in the expression of IRX3 and IRX5 (not FTO) in human brains. The enhanced expression of IRX3 and IRX5 resulting from this single nucleotide alteration promoted a shift from energy-dissipating beige adipocytes to energy-storing white adipocytes and a subsequent reduction in [[Mitochondrion#Heat production|mitochondrial thermogenesis]] by a factor of 5.<ref name="Smemo_2014"/><ref>http://www.medscape.com/viewarticle/849799</ref> Another study found indications that the FTO allele associated with obesity represses mitochondrial thermogenesis in adipocyte precursor cells in a tissue-autonomous manner, and that there is a pathway for adipocyte thermoregulation which involves the proteine [[ARID5B]], the single-nucleotide variant rs1421085, and the IRX3 and IRX5 genes.<ref name="pmid26287746">{{cite journal |vauthors=Claussnitzer M, Dankel SN, Kim KH, Quon G, Meuleman W, Haugen C, Glunk V, Sousa IS, Beaudry JL, Puviindran V, Abdennur NA, Liu J, Svensson PA, Hsu YH, Drucker DJ, Mellgren G, Hui CC, Hauner H, Kellis M |title=FTO Obesity Variant Circuitry and Adipocyte Browning in Humans |journal=The New England Journal of Medicine |volume= 373|issue= |pages= 895–907|year=2015 |pmid=26287746 |doi=10.1056/NEJMoa1502214 |pmc=4959911}}</ref>

=== Association with Alzheimer's disease ===

Recent studies revealed that carriers of common FTO gene polymorphisms show both a reduction in frontal lobe volume of the brain<ref name="Ho_2010"/> and an impaired verbal fluency performance.<ref name="Benedict_2011"/> Fittingly, a population-based study from Sweden found that carriers of the FTO rs9939609 A allele have an increased risk for incident Alzheimer disease.<ref name="Keller_2011"/>

=== Association with other diseases ===

The presence of the FTO rs9939609 A allele was also found to be positively correlated with other symptoms of the [[metabolic syndrome]], including higher fasting insulin, glucose, and triglycerides, and lower [[HDL cholesterol]]. However all these effects appear to be secondary to weight increase since no association was found after correcting for increases in [[body mass index]].<ref name="Freathy_2008"/> Similarly, the association of rs11076008 G allele with the increased risk for [[degenerative disc disease]] was reported.<ref name="Lao_2014"/>

== Model organisms ==

[[Model organism]]s have been used in the study of FTO function. In contrast to the findings in humans deletion, analysis of the ''Fto'' gene in mice showed loss of function is associated with no differences in energy intake but greater energy expenditure and this results in a reduction of body weight and fatness.<ref name="Fischer_2009"/>
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: right;" |
|+ ''Ftotm1a(EUCOMM)Wtsi'' phenotype
|-
! Characteristic!! Phenotype

|-
| [[Homozygote]] viability || bgcolor="#488ED3"|Normal
|-
| Fertility || bgcolor="#488ED3"|Normal
|-
| Body weight || bgcolor="#488ED3"|Normal
|-
| [[Open Field (animal test)|Anxiety]] || bgcolor="#488ED3"|Normal
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
|-
| Grip strength || bgcolor="#488ED3"|Normal
|-
| [[Hot plate test|Hot plate]] || bgcolor="#488ED3"|Normal
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
|-
| [[Radiography]] || bgcolor="#C40000"|Abnormal<ref name="Radiography"/>
|-
| Body temperature || bgcolor="#488ED3"|Normal
|-
| Eye morphology || bgcolor="#488ED3"|Normal
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
|-
| [[Blood plasma|Plasma]] [[immunoglobulin]]s || bgcolor="#488ED3"|Normal
|-
| [[Haematology]] || bgcolor="#488ED3"|Normal
|-
| [[Micronucleus test]] || bgcolor="#488ED3"|Normal
|-
| Heart weight || bgcolor="#488ED3"|Normal
|-
| Skin Histopathology || bgcolor="#488ED3"|Normal
|-
| Brain histopathology || bgcolor="#488ED3"|Normal
|-
| Eye Histopathology || bgcolor="#488ED3"|Normal
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Salmonella'' infection"/>
|-
| ''[[Citrobacter]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Citrobacter'' infection"/>
|-
| colspan=2; style="text-align: center;" | All tests and analysis from<ref name="mgp_reference"/><ref name="mouseportal"/>
|}
Another conditional [[knockout mouse]] line, called ''Ftotm1a(EUCOMM)Wtsi''<ref name="allele_ref"/><ref name="mgi_allele_ref"/> was generated as part of the [[International Knockout Mouse Consortium]] program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.<ref name="Skarnes_2011"/><ref name="mouse_library"/><ref name="mouse_for_all_reasons"/> Male and female animals from this line underwent a standardized [[phenotypic screen]] to determine the effects of deletion.<ref name="mgp_reference" /><ref name="van_der_Weyden_2011"/> Twenty five tests were carried out on [[mutant]] mice and only significant skeletal abnormalities were observed, including [[kyphosis]] and abnormal vertebral [[transverse processes]], and only in female [[homozygous]] mutant animals.<ref name="mgp_reference" />

The reasons for the differences in FTO [[phenotype]] between humans and different lines of mice is presently uncertain. However, many other genes involved in regulation of energy balance exert effects on both intake and expenditure.

== Origin of name ==

By [[exon]] trapping, Peters et al. (1999) cloned a novel gene from a region of several hundred kb deleted by the mouse 'fused toes' (FT) mutation. They named the gene 'fatso' (Fto) due to its large size.<ref name="Peters_1999"/><ref name="Kim_2011"/>

==References==
{{Reflist|colwidth=35em|refs =

<ref name="''Citrobacter'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBLR/citrobacter-challenge/ |title=''Citrobacter'' infection data for Fto |publisher=Wellcome Trust Sanger Institute}}</ref>

<ref name="''Salmonella'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBLR/salmonella-challenge/ |title=''Salmonella'' infection data for Fto |publisher=Wellcome Trust Sanger Institute}}</ref>

<ref name="Adams_1975">{{cite journal | vauthors = Adams JM, Cory S | title = Modified nucleosides and bizarre 5'-termini in mouse myeloma mRNA | journal = Nature | volume = 255 | issue = 5503 | pages = 28–33 | date = May 1975 | pmid = 1128665 | doi = 10.1038/255028a0 | bibcode = 1975Natur.255...28A }}</ref>

<ref name="allele_ref">{{cite web |url=http://www.knockoutmouse.org/martsearch/search?query=Fto |title=International Knockout Mouse Consortium}}</ref>

<ref name="Aloni_1979">{{cite journal | vauthors = Aloni Y, Dhar R, Khoury G | title = Methylation of nuclear simian virus 40 RNAs | journal = J. Virol. | volume = 32 | issue = 1 | pages = 52–60 | date = October 1979 | pmid = 232187 | pmc = 353526 | doi = | url = }}</ref>

<ref name="Beemon_1977">{{cite journal | vauthors = Beemon K, Keith J | title = Localization of N6-methyladenosine in the Rous sarcoma virus genome | journal = J. Mol. Biol. | volume = 113 | issue = 1 | pages = 165–79 | date = June 1977 | pmid = 196091 | doi = 10.1016/0022-2836(77)90047-X }}</ref>

<ref name="Benedict_2011">{{cite journal | vauthors = Benedict C, Jacobsson JA, Rönnemaa E, Sällman-Almén M, Brooks S, Schultes B, Fredriksson R, Lannfelt L, Kilander L, Schiöth HB | title = The fat mass and obesity gene is linked to reduced verbal fluency in overweight and obese elderly men | journal = Neurobiol. Aging | volume = 32 | issue = 6 | pages = 1159.e1–5 | date = June 2011 | pmid = 21458110 | doi = 10.1016/j.neurobiolaging.2011.02.006 }}</ref>

<ref name="Bodi_2010">{{cite journal | vauthors = Bodi Z, Button JD, Grierson D, Fray RG | title = Yeast targets for mRNA methylation | journal = Nucleic Acids Res. | volume = 38 | issue = 16 | pages = 5327–35 | date = September 2010 | pmid = 20421205 | pmc = 2938207 | doi = 10.1093/nar/gkq266 }}</ref>

<ref name="Bodi_2012">{{cite journal | vauthors = Bodi Z, Zhong S, Mehra S, Song J, Graham N, Li H, May S, Fray RG | title = Adenosine Methylation in Arabidopsis mRNA is Associated with the 3' End and Reduced Levels Cause Developmental Defects | journal = Front Plant Sci | volume = 3 | issue = | pages = 48 | year = 2012 | pmid = 22639649 | pmc = 3355605 | doi = 10.3389/fpls.2012.00048 }}</ref>

<ref name="Bokar_1997">{{cite journal | vauthors = Bokar JA, Shambaugh ME, Polayes D, Matera AG, Rottman FM | title = Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase | journal = RNA | volume = 3 | issue = 11 | pages = 1233–47 | date = November 1997 | pmid = 9409616 | pmc = 1369564 | doi = }}</ref>

<ref name="Cecil_2008">{{cite journal | vauthors = Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CN | title = An obesity-associated FTO gene variant and increased energy intake in children | journal = N. Engl. J. Med. | volume = 359 | issue = 24 | pages = 2558–66 | date = December 2008 | pmid = 19073975 | doi = 10.1056/NEJMoa0803839 }}</ref>

<ref name="Chu_2008">{{cite journal | vauthors = Chu X, Erdman R, Susek M, Gerst H, Derr K, Al-Agha M, Wood GC, Hartman C, Yeager S, Blosky MA, Krum W, Stewart WF, Carey D, Benotti P, Still CD, Gerhard GS | title = Association of morbid obesity with FTO and INSIG2 allelic variants | journal = Arch Surg | volume = 143 | issue = 3 | pages = 235–40; discussion 241 | year = 2008 | pmid = 18347269 | doi = 10.1001/archsurg.2007.77 }}</ref>

<ref name="Clancy_2002">{{cite journal | vauthors = Clancy MJ, Shambaugh ME, Timpte CS, Bokar JA | title = Induction of sporulation in Saccharomyces cerevisiae leads to the formation of N6-methyladenosine in mRNA: a potential mechanism for the activity of the IME4 gene | journal = Nucleic Acids Res. | volume = 30 | issue = 20 | pages = 4509–18 | date = October 2002 | pmid = 12384598 | pmc = 137137 | doi = 10.1093/nar/gkf573 }}</ref>

<ref name="Desrosiers_1974">{{cite journal | vauthors = Desrosiers R, Friderici K, Rottman F | title = Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 71 | issue = 10 | pages = 3971–5 | date = October 1974 | pmid = 4372599 | pmc = 434308 | doi = 10.1073/pnas.71.10.3971 | url = | bibcode = 1974PNAS...71.3971D }}</ref>

<ref name="Dina_2007 ">{{cite journal | vauthors = Dina C, Meyre D, Gallina S, Durand E, Körner A, Jacobson P, Carlsson LM, Kiess W, Vatin V, Lecoeur C, Delplanque J, Vaillant E, Pattou F, Ruiz J, Weill J, Levy-Marchal C, Horber F, Potoczna N, Hercberg S, Le Stunff C, Bougnères P, Kovacs P, Marre M, Balkau B, Cauchi S, Chèvre JC, Froguel P | title = Variation in FTO contributes to childhood obesity and severe adult obesity | journal = Nature Genetics | volume = 39 | issue = 6 | pages = 724–6 | year = 2007 | pmid = 17496892 | doi = 10.1038/ng2048 }}</ref>

<ref name="Do_2008">{{cite journal | vauthors = Do R, Bailey SD, Desbiens K, Belisle A, Montpetit A, Bouchard C, Pérusse L, Vohl MC, Engert JC | title = Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec Family Study | journal = Diabetes | volume = 57 | issue = 4 | pages = 1147–50 | date = April 2008 | pmid = 18316358 | doi = 10.2337/db07-1267 }}</ref>

<ref name="Dominissini_2012">{{cite journal | vauthors = Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L, Osenberg S, Cesarkas K, Jacob-Hirsch J, Amariglio N, Kupiec M, Sorek R, Rechavi G | title = Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq | journal = Nature | volume = 485 | issue = 7397 | pages = 201–6 | date = May 2012 | pmid = 22575960 | doi = 10.1038/nature11112 | bibcode = 2012Natur.485..201D }}</ref>

<ref name="Fischer_2009">{{cite journal | vauthors = Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Brüning JC, Rüther U | title = Inactivation of the Fto gene protects from obesity | journal = Nature | volume = 458 | issue = 7240 | pages = 894–8 | date = April 2009 | pmid = 19234441 | doi = 10.1038/nature07848 | bibcode = 2009Natur.458..894F }}</ref>

<ref name="Frayling_2007">{{cite journal | vauthors = Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI | author-link4 = Eleftheria Zeggini | title = A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity | journal = Science | volume = 316 | issue = 5826 | pages = 889–94 | year = 2007 | pmid = 17434869 | pmc = 2646098 | doi = 10.1126/science.1141634 | bibcode = 2007Sci...316..889F }}</ref>

<ref name="Freathy_2008">{{cite journal | vauthors = Freathy RM, Timpson NJ, Lawlor DA, Pouta A, Ben-Shlomo Y, Ruokonen A, Ebrahim S, Shields B, Zeggini E, Weedon MN, Lindgren CM, Lango H, Melzer D, Ferrucci L, Paolisso G, Neville MJ, Karpe F, Palmer CN, Morris AD, Elliott P, Jarvelin MR, Smith GD, McCarthy MI, Hattersley AT, Frayling TM | author-link9 = Eleftheria Zeggini | title = Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected, given its effect on BMI | journal = Diabetes | volume = 57 | issue = 5 | pages = 1419–26 | year = 2008 | pmid = 18346983 | pmc = 3073395 | doi = 10.2337/db07-1466 }}</ref>

<ref name="Fredriksson_2008">{{cite journal | vauthors = Fredriksson R, Hägglund M, Olszewski PK, Stephansson O, Jacobsson JA, Olszewska AM, Levine AS, Lindblom J, Schiöth HB | title = The obesity gene, FTO, is of ancient origin, upregulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain | journal = Endocrinology | volume = 149 | issue = 5 | pages = 2062–71 | year = 2008 | pmid = 18218688 | doi = 10.1210/en.2007-1457 }}</ref>

<ref name="Gerken_2007">{{cite journal | vauthors = Gerken T, Girard CA, Tung YC, Webby CJ, Saudek V, Hewitson KS, Yeo GS, McDonough MA, Cunliffe S, McNeill LA, Galvanovskis J, Rorsman P, Robins P, Prieur X, Coll AP, Ma M, Jovanovic Z, Farooqi IS, Sedgwick B, Barroso I, Lindahl T, Ponting CP, Ashcroft FM, O'Rahilly S, Schofield CJ | author-link12 = Patrik Rorsman | author-link21 = Tomas Lindahl | author-link22 = Chris Ponting | author-link23 = Frances Ashcroft | author-link24 = Stephen O'Rahilly | title = The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase | journal = Science | volume = 318 | issue = 5855 | pages = 1469–72 | year = 2007 | pmid = 17991826 | pmc = 2668859 | doi = 10.1126/science.1151710 |bibcode = 2007Sci...318.1469G }}</ref>

<ref name="Harper_1990">{{cite journal | vauthors = Harper JE, Miceli SM, Roberts RJ, Manley JL | title = Sequence specificity of the human mRNA N6-adenosine methylase in vitro | journal = Nucleic Acids Res. | volume = 18 | issue = 19 | pages = 5735–41 | date = October 1990 | pmid = 2216767 | pmc = 332308 | doi = 10.1093/nar/18.19.5735 }}</ref>

<ref name="Haupt_2009">{{cite journal | vauthors = Haupt A, Thamer C, Staiger H, Tschritter O, Kirchhoff K, Machicao F, Häring HU, Stefan N, Fritsche A | title = Variation in the FTO gene influences food intake but not energy expenditure | journal = Exp. Clin. Endocrinol. Diabetes | volume = 117 | issue = 4 | pages = 194–7 | date = April 2009 | pmid = 19053021 | doi = 10.1055/s-0028-1087176 }}</ref>

<ref name="Ho_2010">{{cite journal | vauthors = Ho AJ, Stein JL, Hua X, Lee S, Hibar DP, Leow AD, Dinov ID, Toga AW, Saykin AJ, Shen L, Foroud T, Pankratz N, Huentelman MJ, Craig DW, Gerber JD, Allen AN, Corneveaux JJ, Stephan DA, DeCarli CS, DeChairo BM, Potkin SG, Jack CR, Weiner MW, Raji CA, Lopez OL, Becker JT, Carmichael OT, Thompson PM | title = A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 107 | issue = 18 | pages = 8404–9 | date = May 2010 | pmid = 20404173 | pmc = 2889537 | doi = 10.1073/pnas.0910878107 | bibcode = 2010PNAS..107.8404H }}</ref>

<ref name="Horowitz_1984">{{cite journal | vauthors = Horowitz S, Horowitz A, Nilsen TW, Munns TW, Rottman FM | title = Mapping of N6-methyladenosine residues in bovine prolactin mRNA | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 81 | issue = 18 | pages = 5667–71 | date = September 1984 | pmid = 6592581 | pmc = 391771 | doi = 10.1073/pnas.81.18.5667 | bibcode = 1984PNAS...81.5667H }}</ref>

<ref name="Jia_2011">{{cite journal | vauthors = Jia G, Fu Y, Zhao X, Dai Q, Zheng G, Yang Y, Yi C, Lindahl T, Pan T, Yang YG, He C | title = N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO | journal = Nat. Chem. Biol. | volume = 7 | issue = 12 | pages = 885–7 | date = December 2011 | pmid = 22002720 | pmc = 3218240 | doi = 10.1038/nchembio.687 }}</ref>

<ref name="Kane_1985">{{cite journal | vauthors = Kane SE, Beemon K | title = Precise localization of m6A in Rous sarcoma virus RNA reveals clustering of methylation sites: implications for RNA processing | journal = Mol. Cell. Biol. | volume = 5 | issue = 9 | pages = 2298–306 | date = September 1985 | pmid = 3016525 | pmc = 366956 | doi = 10.1128/mcb.5.9.2298}}</ref>

<ref name="Keller_2011">{{cite journal | vauthors = Keller L, Xu W, Wang HX, Winblad B, Fratiglioni L, Graff C | title = The obesity related gene, FTO, interacts with APOE, and is associated with Alzheimer's disease risk: a prospective cohort study | journal = J. Alzheimers Dis. | volume = 23 | issue = 3 | pages = 461–9 | year = 2011 | pmid = 21098976 | doi = 10.3233/JAD-2010-101068 }}</ref>

<ref name="Kennedy_1979">{{cite journal | vauthors = Kennedy TD, Lane BG | title = Wheat embryo ribonucleates. XIII. Methyl-substituted nucleoside constituents and 5'-terminal dinucleotide sequences in bulk poly(AR)-rich RNA from imbibing wheat embryos | journal = Can. J. Biochem. | volume = 57 | issue = 6 | pages = 927–31 | date = June 1979 | pmid = 476526 | doi = 10.1139/o79-112 }}</ref>

<ref name="Kim_2011">{{cite journal | vauthors = Kim B, Kim Y, Cooke PS, Rüther U, Jorgensen JS | title = The fused toes locus is essential for somatic-germ cell interactions that foster germ cell maturation in developing gonads in mice | journal = Biol Reprod | volume = 84 | issue = 5 | pages = 1024–32 | year = 2011 | pmid = 21293032 | doi = 10.1095/biolreprod.110.088559 }}</ref>

<ref name="Lao_2014">{{cite journal | vauthors = Lao L, Zhong G, Li X, Liu Z | title = A preliminary association study of fat mass and obesity associated gene polymorphisms and degenerative disc disease in a Chinese Han population. | journal = J Int Med Res | volume = 42 | issue = 1 | pages = 205–12 | date = Feb 2014 | pmid = 24304927 | doi = 10.1177/0300060513503761 | url = http://imr.sagepub.com/content/42/1/205.long }}</ref>

<ref name="Levis_1978">{{cite journal | vauthors = Levis R, Penman S | title = 5'-terminal structures of poly(A)+ cytoplasmic messenger RNA and of poly(A)+ and poly(A)- heterogeneous nuclear RNA of cells of the dipteran Drosophila melanogaster | journal = J. Mol. Biol. | volume = 120 | issue = 4 | pages = 487–515 | date = April 1978 | pmid = 418182 | doi = 10.1016/0022-2836(78)90350-9 | url = }}</ref>

<ref name="Loos_2014">{{cite journal | vauthors = Loos RJ, Yeo GS | title = The bigger picture of FTO: the first GWAS-identified obesity gene | journal = Nat Rev Endocrinol | volume = 10 | issue = 1 | pages = 51–61 | year = 2014 | pmid = 24247219 | pmc = 4188449 | doi = 10.1038/nrendo.2013.227 }}</ref>

<ref name="Meyer_2012">{{cite journal | vauthors = Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR | title = Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3' UTRs and near Stop Codons | journal = Cell | volume = 149 | issue = 7 | pages = 1635–46 | date = May 2012 | pmid = 22608085 | pmc = 3383396 | doi = 10.1016/j.cell.2012.05.003 }}</ref>

<ref name="Meyer_2012">{{cite journal | vauthors = Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR | title = Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3' UTRs and near Stop Codons | journal = Cell | volume = 149 | issue = 7 | pages = 1635–46 | date = May 2012 | pmid = 22608085 | pmc = 3383396 | doi = 10.1016/j.cell.2012.05.003 }}</ref>

<ref name="mgi_allele_ref">{{cite web |url=http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4432397 |title=Mouse Genome Informatics}}</ref>

<ref name="mgp_reference">{{cite journal | doi = 10.1111/j.1755-3768.2010.4142.x | title = The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice | year = 2010 | author = Gerdin AK | journal = Acta Ophthalmologica | volume = 88 | pages = 925–7 }}</ref>

<ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A Mouse for All Reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | year = 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref>

<ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | year = 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref>

<ref name="mouseportal">[http://www.sanger.ac.uk/mouseportal/ Mouse Resources Portal], Wellcome Trust Sanger Institute.</ref>

<ref name="Nichols_1979">{{cite journal | vauthors = Nichols JL | title = N6-methyladenosine in maize poly(A)-containing RNA | journal = Plant Science Letters |date=August 1979 | volume = 15 | issue = 4 | pages = 357–361 | doi = 10.1016/0304-4211(79)90141-X}}</ref>

<ref name="Olszewski_2009">{{cite journal | vauthors = Olszewski PK, Fredriksson R, Olszewska AM, Stephansson O, Alsiö J, Radomska KJ, Levine AS, Schiöth HB | title = Hypothalamic FTO is associated with the regulation of energy intake not feeding reward | journal = BMC Neurosci | volume = 10 | pages = 129 | date = October 2009 | pmid = 19860904 | pmc = 2774323 | doi = 10.1186/1471-2202-10-129 }}</ref>

<ref name="Perry_1975">{{cite journal | vauthors = Perry RP, Kelley DE, Friderici K, Rottman F | title = The methylated constituents of L cell messenger RNA: evidence for an unusual cluster at the 5' terminus | journal = Cell | volume = 4 | issue = 4 | pages = 387–94 | date = April 1975 | pmid = 1168101 | doi = 10.1016/0092-8674(75)90159-2 }}</ref>

<ref name="Peters_1999">{{cite journal | vauthors = Peters T, Ausmeier K, Rüther U | title = Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse mutation | journal = Mamm. Genome | volume = 10 | issue = 10 | pages = 983–6 | date = October 1999 | pmid = 10501967 | doi = 10.1007/s003359901144 }}</ref>

<ref name="Radiography">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBLR/x-ray-imaging/ |title=Radiography data for Fto |publisher=Wellcome Trust Sanger Institute}}</ref>

<ref name="Sanchez-Pulido_2007">{{cite journal | vauthors = Sanchez-Pulido L, Andrade-Navarro MA | title = The FTO (fat mass and obesity associated) gene codes for a novel member of the non-heme dioxygenase superfamily | journal = BMC Biochem. | volume = 8 | pages = 23 | year = 2007 | pmid = 17996046 | pmc = 2241624 | doi = 10.1186/1471-2091-8-23 }}</ref>

<ref name="Sandholt_2012">{{cite journal | vauthors = Sandholt CH, Hansen T, Pedersen O | title = Beyond the fourth wave of genome-wide obesity association studies | journal = Nutr Diabetes | volume = 2 | issue = | pages = e37 | year = 2012 | pmid = 23168490 | pmc = 3408643 | doi = 10.1038/nutd.2012.9 | url = http://www.nature.com/nutd/journal/v2/n7/fig_tab/nutd20129t1.html#figure-title }}</ref>

<ref name="Skarnes_2011">{{cite journal | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–342 | year = 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref>

<ref name="Smemo_2014">{{cite journal | vauthors = Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gómez-Marín C, Aneas I, Credidio FL, Sobreira DR, Wasserman NF, Lee JH, Puviindran V, Tam D, Shen M, Son JE, Vakili NA, Sung HK, Naranjo S, Acemel RD, Manzanares M, Nagy A, Cox NJ, Hui CC, Gomez-Skarmeta JL, Nóbrega MA | title = Obesity-associated variants within FTO form long-range functional connections with IRX3 | journal = Nature | volume = 507 | issue = 7492 | pages = 371–375 | date = 12 March 2014 | pmid = 24646999 | doi = 10.1038/nature13138 |bibcode = 2014Natur.507..371S | pmc=4113484}}</ref>

<ref name="Speakman_2008">{{cite journal | vauthors = Speakman JR, Rance KA, Johnstone AM | title = Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure | journal = Obesity (Silver Spring) | volume = 16 | issue = 8 | pages = 1961–5 | date = August 2008 | pmid = 18551109 | doi = 10.1038/oby.2008.318 }}</ref>

<ref name="Thorleifsson_2009">{{cite journal | vauthors = Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, Styrkarsdottir U, Gretarsdottir S, Thorlacius S, Jonsdottir I, Jonsdottir T, Olafsdottir EJ, Olafsdottir GH, Jonsson T, Jonsson F, Borch-Johnsen K, Hansen T, Andersen G, Jorgensen T, Lauritzen T, Aben KK, Verbeek AL, Roeleveld N, Kampman E, Yanek LR, Becker LC, Tryggvadottir L, Rafnar T, Becker DM, Gulcher J, Kiemeney LA, Pedersen O, Kong A, Thorsteinsdottir U, Stefansson K | title = Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity | journal = Nat. Genet. | volume = 41 | issue = 1 | pages = 18–24 | date = January 2009 | pmid = 19079260 | doi = 10.1038/ng.274 }}</ref>

<ref name="Timpson_2008">{{cite journal | vauthors = Timpson NJ, Emmett PM, Frayling TM, Rogers I, Hattersley AT, McCarthy MI, Davey Smith G | title = The fat mass- and obesity-associated locus and dietary intake in children | journal = Am. J. Clin. Nutr. | volume = 88 | issue = 4 | pages = 971–8 | date = October 2008 | pmid = 18842783 | doi = }}</ref>

<ref name="van_der_Weyden_2011">{{cite journal | vauthors = van der Weyden L, White JK, Adams DJ, Logan DW | title = The mouse genetics toolkit: revealing function and mechanism | journal = Genome Biol. | volume = 12 | issue = 6 | pages = 224 | year = 2011 | pmid = 21722353 | pmc = 3218837 | doi = 10.1186/gb-2011-12-6-224 }}</ref>

<ref name="Wardle_2008">{{cite journal | vauthors = Wardle J, Carnell S, Haworth CM, Farooqi IS, O'Rahilly S, Plomin R | title = Obesity associated genetic variation in FTO is associated with diminished satiety | journal = J. Clin. Endocrinol. Metab. | volume = 93 | issue = 9 | pages = 3640–3 | date = September 2008 | pmid = 18583465 | doi = 10.1210/jc.2008-0472 }}</ref>

<ref name="Wardle_2009">{{cite journal | vauthors = Wardle J, Llewellyn C, Sanderson S, Plomin R | title = The FTO gene and measured food intake in children | journal = Int J Obes (Lond) | volume = 33 | issue = 1 | pages = 42–5 | date = January 2009 | pmid = 18838977 | doi = 10.1038/ijo.2008.174 }}</ref>

<ref name="Wei_1976">{{cite journal | vauthors = Wei CM, Gershowitz A, Moss B | title = 5'-Terminal and internal methylated nucleotide sequences in HeLa cell mRNA | journal = Biochemistry | volume = 15 | issue = 2 | pages = 397–401 | date = January 1976 | pmid = 174715 | doi = 10.1021/bi00647a024 }}</ref>

<ref name="Willer_2009">{{cite journal | vauthors = Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM, Berndt SI, Elliott AL | title = Six new loci associated with body mass index highlight a neuronal influence on body weight regulation | journal = Nat. Genet. | volume = 41 | issue = 1 | pages = 25–34 | date = January 2009 | pmid = 19079261 | pmc = 2695662 | doi = 10.1038/ng.287 }}</ref>

<ref name="Zhong_2008">{{cite journal | vauthors = Zhong S, Li H, Bodi Z, Button J, Vespa L, Herzog M, Fray RG | title = MTA is an Arabidopsis messenger RNA adenosine methylase and interacts with a homolog of a sex-specific splicing factor | journal = Plant Cell | volume = 20 | issue = 5 | pages = 1278–88 | date = May 2008 | pmid = 18505803 | pmc = 2438467 | doi = 10.1105/tpc.108.058883 }}</ref>

}}

==External links==
* {{MeshName|FTO+protein,+human|3=FTO protein, human}}
* {{cite web | url = http://www.medicalnewstoday.com/articles/67666.php | title = Obesity Gene Discovered | accessdate = 2008-03-22 | author = Catharine Paddock | authorlink = | coauthors = | date = 2007-04-13 | format = | work = | publisher = Medical News Today | pages = | language = | archiveurl = | archivedate = | quote = }}

{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:Genes on human chromosome 16]]
[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]
[[Category:Genes mutated in mice]]

KDM2A

2017-11-23T09:32:52Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{Infobox_gene}}
'''Lysine-specific demethylase 2A''' (KDM2A) also known as '''F-box and leucine-rich repeat protein 11''' (FBXL11) is an [[enzyme]] that in humans is encoded by the ''KDM2A'' [[gene]].<ref name="pmid10231032">{{cite journal |vauthors=Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O | title = Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro | journal = DNA Res | volume = 6 | issue = 1 | pages = 63–70 | date = Jul 1999 | pmid = 10231032 | pmc = | doi = 10.1093/dnares/6.1.63 }}</ref><ref name="pmid10531037">{{cite journal |vauthors=Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW | title = A family of mammalian F-box proteins | journal = Curr Biol | volume = 9 | issue = 20 | pages = 1180–2 | date = Dec 1999 | pmid = 10531037 | pmc = | doi = 10.1016/S0960-9822(00)80021-4 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: FBXL11 F-box and leucine-rich repeat protein 11| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=22992| accessdate = }}</ref> KDM2A is a member of the superfamily of non-haem Fe(II) and [[2-oxoglutarate (2OG)-dependent dioxygenases]].

== Function ==

This gene encodes a member of the [[F-box protein]] family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of [[ubiquitin ligase|ubiquitin protein ligase]] complex called [[SCF complex|SCF]]s (SKP1-cullin-F-box), which function in [[phosphorylation]]-dependent [[ubiquitination]]. The F-box proteins are divided into 3 classes: Fbws containing [[WD40 repeat|WD-40]] domains, Fbls containing [[leucine-rich repeats]], and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class and, in addition to an F-box, contains at least 6 highly degenerated leucine-rich repeats.<ref name="entrez"/>

FBXL11/KDM2A is a [[histone H3]] lysine 36 [[demethylase]] enzyme. The enzymatic activity of FBXL11/KDM2A relies on a conserved JmjC domain in the [[N-terminus]] of the protein that co-ordinates iron and [[alpha-Ketoglutaric acid|alphaketoglutarate]] to catalyze [[demethylation]] via a hydroxylation based mechanism.<ref name="pmid16362057">{{cite journal |vauthors=Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y | title = Histone demethylation by a family of JmjC domain-containing proteins | journal = Nature | volume = 439 | issue = 7078 | pages = 811–6 | date = February 2006 | pmid = 16362057 | doi = 10.1038/nature04433 }}</ref> It has recently been demonstrated that a ZF-CxxC DNA binding domain within FBXL11/KDM2A has the capacity to interact with non-methylated DNA and this domain targets FBXL11/KDM2A to CpG island regions of the genome where it specifically removes histone H3 lysine 36 methylation.<ref name="pmid20417597">{{cite journal |vauthors=Blackledge NP, Zhou JC, Tolstorukov MY, Farcas AM, Park PJ, Klose RJ | title = CpG islands recruit a histone H3 lysine 36 demethylase | journal = Molecular Cell | volume = 38 | issue = 2 | pages = 179–90 | date = Apr 2010 | pmid = 20417597 | doi = 10.1016/j.molcel.2010.04.009 | pmc=3098377}}</ref> This mechanism acts to create a [[chromatin]] environment at CpG islands that highlights these regulatory elements and differentiates them from non-regulatory regions in large complex mammalian genomes. In a study in mouse hepatocytes, this gene was shown to regulate hepatic gluconeogenesis.<ref name="doi.10.1371/journal.pgen.1002761">{{cite journal |vauthors=Pan D, Mao C, Zou T, Yao AY, Cooper MP, Boyartchuk V, Wang YX | title = The Histone Demethylase Jhdm1a Regulates Hepatic Gluconeogenesis | journal = PLoS Genetics | volume = 8 | issue = 6 | pages = e1002761 | pmid = 22719268 | doi = 10.1371/journal.pgen.1002761 | pmc=3375226 | year=2012}}</ref>

==References==
{{Reflist}}

==Further reading==
{{Refbegin | 2}}
*{{cite journal |vauthors=Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T | title = Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones. | journal = DNA Res. | volume = 9 | issue = 3 | pages = 99–106 | year = 2003 | pmid = 12168954 | doi = 10.1093/dnares/9.3.99 }}
*{{cite journal |vauthors=Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M, Pagano M | title = Identification of a family of human F-box proteins. | journal = Curr. Biol. | volume = 9 | issue = 20 | pages = 1177–9 | year = 1999 | pmid = 10531035 | doi = 10.1016/S0960-9822(00)80020-2 }}
*{{cite journal |vauthors=Ilyin GP, Rialland M, Pigeon C, Guguen-Guillouzo C | title = cDNA cloning and expression analysis of new members of the mammalian F-box protein family. | journal = Genomics | volume = 67 | issue = 1 | pages = 40–7 | year = 2001 | pmid = 10945468 | doi = 10.1006/geno.2000.6211 }}
*{{cite journal |vauthors=Hattori A, Okumura K, Nagase T, Kikuno R, Hirosawa M, Ohara O | title = Characterization of long cDNA clones from human adult spleen. | journal = DNA Res. | volume = 7 | issue = 6 | pages = 357–66 | year = 2001 | pmid = 11214971 | doi = 10.1093/dnares/7.6.357 }}
*{{cite journal |vauthors=Watanabe N, Arai H, Nishihara Y, Taniguchi M, Watanabe N, Hunter T, Osada H | title = M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP. | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 101 | issue = 13 | pages = 4419–24 | year = 2004 | pmid = 15070733 | pmc = 384762 | doi = 10.1073/pnas.0307700101 }}
*{{cite journal |vauthors=Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM | title = Functional proteomics mapping of a human signaling pathway. | journal = Genome Res. | volume = 14 | issue = 7 | pages = 1324–32 | year = 2004 | pmid = 15231748 | pmc = 442148 | doi = 10.1101/gr.2334104 }}
*{{cite journal |vauthors=Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M | title = Nucleolar proteome dynamics. | journal = Nature | volume = 433 | issue = 7021 | pages = 77–83 | year = 2005 | pmid = 15635413 | doi = 10.1038/nature03207 }}
*{{cite journal |vauthors=Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y | title = Histone demethylation by a family of JmjC domain-containing proteins. | journal = Nature | volume = 439 | issue = 7078 | pages = 811–6 | year = 2006 | pmid = 16362057 | doi = 10.1038/nature04433 }}
*{{cite journal |vauthors=Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | year = 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 }}
{{Refend}}

{{PDB Gallery|geneid=22992}}
{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

{{DEFAULTSORT:Fbxl11}}
[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]

{{gene-11-stub}}

EGLN3

2017-11-23T09:32:27Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{Infobox_gene}}
'''Egl nine homolog 3''' is a [[protein]] that in humans is encoded by the ''EGLN3'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: EGLN3 egl nine homolog 3 (C. elegans)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=112399| accessdate = }}</ref> ELGN3 is a member of the superfamily of non-haem Fe(II) and [[2-oxoglutarate (2OG)-dependent dioxygenases]].

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Semenza GL | title = HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus | journal = Cell | volume = 107 | issue = 1 | pages = 1–3 | date = October 2001 | pmid = 11595178 | doi = 10.1016/S0092-8674(01)00518-9 }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1-2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
* {{cite journal | vauthors = Taylor MS | title = Characterization and comparative analysis of the EGLN gene family | journal = Gene | volume = 275 | issue = 1 | pages = 125–32 | date = September 2001 | pmid = 11574160 | doi = 10.1016/S0378-1119(01)00633-3 }}
* {{cite journal | vauthors = Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O'Rourke J, Mole DR, Mukherji M, Metzen E, Wilson MI, Dhanda A, Tian YM, Masson N, Hamilton DL, Jaakkola P, Barstead R, Hodgkin J, Maxwell PH, Pugh CW, Schofield CJ, Ratcliffe PJ | title = C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation | journal = Cell | volume = 107 | issue = 1 | pages = 43–54 | date = October 2001 | pmid = 11595184 | doi = 10.1016/S0092-8674(01)00507-4 }}
* {{cite journal | vauthors = Bruick RK, McKnight SL | title = A conserved family of prolyl-4-hydroxylases that modify HIF | journal = Science | volume = 294 | issue = 5545 | pages = 1337–40 | date = November 2001 | pmid = 11598268 | doi = 10.1126/science.1066373 }}
* {{cite journal | vauthors = Oehme F, Ellinghaus P, Kolkhof P, Smith TJ, Ramakrishnan S, Hütter J, Schramm M, Flamme I | title = Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors | journal = Biochemical and Biophysical Research Communications | volume = 296 | issue = 2 | pages = 343–9 | date = August 2002 | pmid = 12163023 | doi = 10.1016/S0006-291X(02)00862-8 }}
* {{cite journal | vauthors = Metzen E, Berchner-Pfannschmidt U, Stengel P, Marxsen JH, Stolze I, Klinger M, Huang WQ, Wotzlaw C, Hellwig-Bürgel T, Jelkmann W, Acker H, Fandrey J | title = Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing | journal = Journal of Cell Science | volume = 116 | issue = Pt 7 | pages = 1319–26 | date = April 2003 | pmid = 12615973 | doi = 10.1242/jcs.00318 }}
* {{cite journal | vauthors = Cioffi CL, Liu XQ, Kosinski PA, Garay M, Bowen BR | title = Differential regulation of HIF-1 alpha prolyl-4-hydroxylase genes by hypoxia in human cardiovascular cells | journal = Biochemical and Biophysical Research Communications | volume = 303 | issue = 3 | pages = 947–53 | date = April 2003 | pmid = 12670503 | doi = 10.1016/S0006-291X(03)00453-4 }}
* {{cite journal | vauthors = Aprelikova O, Chandramouli GV, Wood M, Vasselli JR, Riss J, Maranchie JK, Linehan WM, Barrett JC | title = Regulation of HIF prolyl hydroxylases by hypoxia-inducible factors | journal = Journal of Cellular Biochemistry | volume = 92 | issue = 3 | pages = 491–501 | date = June 2004 | pmid = 15156561 | doi = 10.1002/jcb.20067 }}
* {{cite journal | vauthors = Appelhoff RJ, Tian YM, Raval RR, Turley H, Harris AL, Pugh CW, Ratcliffe PJ, Gleadle JM | title = Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor | journal = The Journal of Biological Chemistry | volume = 279 | issue = 37 | pages = 38458–65 | date = September 2004 | pmid = 15247232 | doi = 10.1074/jbc.M406026200 }}
* {{cite journal | vauthors = Masson N, Appelhoff RJ, Tuckerman JR, Tian YM, Demol H, Puype M, Vandekerckhove J, Ratcliffe PJ, Pugh CW | title = The HIF prolyl hydroxylase PHD3 is a potential substrate of the TRiC chaperonin | journal = FEBS Letters | volume = 570 | issue = 1-3 | pages = 166–70 | date = July 2004 | pmid = 15251459 | doi = 10.1016/j.febslet.2004.06.040 }}
* {{cite journal | vauthors = Baek JH, Mahon PC, Oh J, Kelly B, Krishnamachary B, Pearson M, Chan DA, Giaccia AJ, Semenza GL | title = OS-9 interacts with hypoxia-inducible factor 1alpha and prolyl hydroxylases to promote oxygen-dependent degradation of HIF-1alpha | journal = Molecular Cell | volume = 17 | issue = 4 | pages = 503–12 | date = February 2005 | pmid = 15721254 | doi = 10.1016/j.molcel.2005.01.011 }}
* {{cite journal | vauthors = Lee S, Nakamura E, Yang H, Wei W, Linggi MS, Sajan MP, Farese RV, Freeman RS, Carter BD, Kaelin WG, Schlisio S | title = Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: developmental culling and cancer | journal = Cancer Cell | volume = 8 | issue = 2 | pages = 155–67 | date = August 2005 | pmid = 16098468 | doi = 10.1016/j.ccr.2005.06.015 }}
* {{cite journal | vauthors = Hopfer U, Hopfer H, Jablonski K, Stahl RA, Wolf G | title = The novel WD-repeat protein Morg1 acts as a molecular scaffold for hypoxia-inducible factor prolyl hydroxylase 3 (PHD3) | journal = The Journal of Biological Chemistry | volume = 281 | issue = 13 | pages = 8645–55 | date = March 2006 | pmid = 16407229 | doi = 10.1074/jbc.M513751200 }}
* {{cite journal | vauthors = Nakayama K, Gazdoiu S, Abraham R, Pan ZQ, Ronai Z | title = Hypoxia-induced assembly of prolyl hydroxylase PHD3 into complexes: implications for its activity and susceptibility for degradation by the E3 ligase Siah2 | journal = The Biochemical Journal | volume = 401 | issue = 1 | pages = 217–26 | date = January 2007 | pmid = 16958618 | pmc = 1698661 | doi = 10.1042/BJ20061135 }}
{{refend}}

{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]

{{gene-14-stub}}

EGLN2

2017-11-23T09:31:49Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{Infobox_gene}}
'''Egl nine homolog 2''' is a [[protein]] that in humans is encoded by the ''EGLN2'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: EGLN2 egl nine homolog 2 (C. elegans)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=112398| accessdate = }}</ref> ELGN2 is a member of the non-haem Fe(II) and [[2-oxoglutarate (2OG)-dependent dioxygenases]].


{{PBB_Summary
| section_title =
| summary_text = The [[hypoxia inducible factor]] (HIF) is a transcriptional complex which is involved in [[oxygen homeostasis]]. At normal oxygen levels, the alpha subunit of HIF is targeted for degradation by [[prolyl hydroxylase|prolyl hydroxylation]].
This gene encodes an enzyme responsible for this posttranslational modification. Multiple alternatively spliced variants, encoding the same protein, have been identified.<ref name="entrez" />
}}

==References==
{{reflist}}

==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal | author=Semenza GL |title=HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus |journal=Cell |volume=107 |issue= 1 |pages= 1–3 |year= 2001 |pmid= 11595178 |doi=10.1016/S0092-8674(01)00518-9 }}
*{{cite journal | vauthors=Hartley JL, Temple GF, Brasch MA |title=DNA Cloning Using In Vitro Site-Specific Recombination |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788–95 |year= 2001 |pmid= 11076863 |doi=10.1101/gr.143000 | pmc=310948 }}
*{{cite journal | vauthors=Wiemann S, Weil B, Wellenreuther R |title=Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs |journal=Genome Res. |volume=11 |issue= 3 |pages= 422–35 |year= 2001 |pmid= 11230166 |doi= 10.1101/gr.GR1547R | pmc=311072 |display-authors=etal}}
*{{cite journal | vauthors=Jaakkola P, Mole DR, Tian YM |title=Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation |journal=Science |volume=292 |issue= 5516 |pages= 468–72 |year= 2001 |pmid= 11292861 |doi= 10.1126/science.1059796 |display-authors=etal}}
*{{cite journal | vauthors=Ivan M, Kondo K, Yang H |title=HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing |journal=Science |volume=292 |issue= 5516 |pages= 464–8 |year= 2001 |pmid= 11292862 |doi= 10.1126/science.1059817 |display-authors=etal}}
*{{cite journal | author=Taylor MS |title=Characterization and comparative analysis of the EGLN gene family |journal=Gene |volume=275 |issue= 1 |pages= 125–32 |year= 2001 |pmid= 11574160 |doi=10.1016/S0378-1119(01)00633-3 }}
*{{cite journal | vauthors=Epstein AC, Gleadle JM, McNeill LA |title=C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation |journal=Cell |volume=107 |issue= 1 |pages= 43–54 |year= 2001 |pmid= 11595184 |doi=10.1016/S0092-8674(01)00507-4 |display-authors=etal}}
*{{cite journal | vauthors=Bruick RK, McKnight SL |title=A conserved family of prolyl-4-hydroxylases that modify HIF |journal=Science |volume=294 |issue= 5545 |pages= 1337–40 |year= 2001 |pmid= 11598268 |doi= 10.1126/science.1066373 }}
*{{cite journal | vauthors=Seth P, Krop I, Porter D, Polyak K |title=Novel estrogen and tamoxifen induced genes identified by SAGE (Serial Analysis of Gene Expression) |journal=Oncogene |volume=21 |issue= 5 |pages= 836–43 |year= 2002 |pmid= 11850811 |doi= 10.1038/sj.onc.1205113 }}
*{{cite journal | vauthors=Min JH, Yang H, Ivan M |title=Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling |journal=Science |volume=296 |issue= 5574 |pages= 1886–9 |year= 2002 |pmid= 12004076 |doi= 10.1126/science.1073440 |display-authors=etal}}
*{{cite journal | vauthors=McNeill LA, Hewitson KS, Gleadle JM |title=The use of dioxygen by HIF prolyl hydroxylase (PHD1) |journal=Bioorg. Med. Chem. Lett. |volume=12 |issue= 12 |pages= 1547–50 |year= 2002 |pmid= 12039559 |doi=10.1016/S0960-894X(02)00219-6 |display-authors=etal}}
*{{cite journal | vauthors=Oehme F, Ellinghaus P, Kolkhof P |title=Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors |journal=Biochem. Biophys. Res. Commun. |volume=296 |issue= 2 |pages= 343–9 |year= 2002 |pmid= 12163023 |doi=10.1016/S0006-291X(02)00862-8 |display-authors=etal}}
*{{cite journal | vauthors=Ivan M, Haberberger T, Gervasi DC |title=Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 21 |pages= 13459–64 |year= 2002 |pmid= 12351678 |doi= 10.1073/pnas.192342099 | pmc=129695 |display-authors=etal}}
*{{cite journal | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |display-authors=etal}}
*{{cite journal | vauthors=Metzen E, Berchner-Pfannschmidt U, Stengel P |title=Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing |journal=J. Cell Sci. |volume=116 |issue= Pt 7 |pages= 1319–26 |year= 2003 |pmid= 12615973 |doi=10.1242/jcs.00318 |display-authors=etal}}
*{{cite journal | vauthors=Cioffi CL, Liu XQ, Kosinski PA |title=Differential regulation of HIF-1 alpha prolyl-4-hydroxylase genes by hypoxia in human cardiovascular cells |journal=Biochem. Biophys. Res. Commun. |volume=303 |issue= 3 |pages= 947–53 |year= 2003 |pmid= 12670503 |doi=10.1016/S0006-291X(03)00453-4 |display-authors=etal}}
*{{cite journal | vauthors=Ota T, Suzuki Y, Nishikawa T |title=Complete sequencing and characterization of 21,243 full-length human cDNAs |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 |display-authors=etal}}
*{{cite journal | vauthors=Aprelikova O, Chandramouli GV, Wood M |title=Regulation of HIF prolyl hydroxylases by hypoxia-inducible factors |journal=J. Cell. Biochem. |volume=92 |issue= 3 |pages= 491–501 |year= 2004 |pmid= 15156561 |doi= 10.1002/jcb.20067 |display-authors=etal}}
*{{cite journal | vauthors=Colland F, Jacq X, Trouplin V |title=Functional Proteomics Mapping of a Human Signaling Pathway |journal=Genome Res. |volume=14 |issue= 7 |pages= 1324–32 |year= 2004 |pmid= 15231748 |doi= 10.1101/gr.2334104 | pmc=442148 |display-authors=etal}}
}}
{{refend}}

{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}


{{PBB_Controls
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}

[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]

{{gene-19-stub}}

ASPH

2017-11-23T09:31:12Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{For|camera lenses|Aspheric lens#Camera lenses}}
{{Infobox_gene}}
'''Aspartyl/asparaginyl beta-hydroxylase''' (''HAAH'') is an [[enzyme]] that in humans is encoded by the ''ASPH'' [[gene]].<ref name="pmid7821814">{{cite journal |vauthors=Korioth F, Gieffers C, Frey J | title = Cloning and characterization of the human gene encoding aspartyl beta-hydroxylase | journal = Gene | volume = 150 | issue = 2 | pages = 395–9 |date=Feb 1995 | pmid = 7821814 | pmc = | doi =10.1016/0378-1119(94)90460-X }}</ref><ref name="pmid10974562">{{cite journal |vauthors=Lim KY, Hong CS, Kim DH | title = cDNA cloning and characterization of human cardiac junctin | journal = Gene | volume = 255 | issue = 1 | pages = 35–42 |date=Nov 2000 | pmid = 10974562 | pmc = | doi =10.1016/S0378-1119(00)00299-7 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: ASPH aspartate beta-hydroxylase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=444| accessdate = }}</ref> ASPH is a member of the non-haem Fe(II) and [[2-oxoglutarate (2OG)-dependent dioxygenases]].

== Function ==

This gene is thought to play an important role in [[calcium]] [[homeostasis]]. Alternative splicing of this gene results in five transcript variants which vary in protein translation, the coding of catalytic domains, and tissue expression. Variation among these transcripts impacts their functions which involve roles in the calcium storage and release process in the endoplasmic and sarcoplasmic reticulum as well as hydroxylation of aspartic acid and asparagine in epidermal growth factor-like domains of various proteins.<ref name="entrez" />

== Clinical significance ==

As early as 1996, the over-expression of ''HAAH'' was recognized as an indicator of carcinoma in humans. Further research has correlated elevated ''HAAH'' levels (variously in affected tissue or [[blood serum]]) with hepatocellular ([[liver]]) [[carcinoma]]<ref name="Ince_2000">{{cite journal |vauthors=Ince N, de la Monte SM, Wands JR | title = Overexpression of human aspartyl (asparaginyl) beta-hydroxylase is associated with malignant transformation | journal = Cancer Res. | volume = 60 | issue = 5 | pages = 1261–6 |date=March 2000 | pmid = 10728685 | doi = }}</ref><ref name="Xue_2009">{{cite journal |vauthors=Xue T, Xue XP, Huang QS, Wei L, Sun K, Xue T | title = Monoclonal antibodies against human aspartyl (asparaginyl) beta-hydroxylase developed by DNA immunization | journal = Hybridoma (Larchmt) | volume = 28 | issue = 4 | pages = 251–7 |date=August 2009 | pmid = 19663697 | doi = 10.1089/hyb.2009.0017 }}</ref> [[adenocarcinoma]] ([[pancreatic cancer]]),<ref name="Palumbo_2002">{{cite journal |vauthors=Palumbo KS, Wands JR, Safran H, King T, Carlson RI, de la Monte SM | title = Human aspartyl (asparaginyl) beta-hydroxylase monoclonal antibodies: potential biomarkers for pancreatic carcinoma | journal = Pancreas | volume = 25 | issue = 1 | pages = 39–44 |date=July 2002 | pmid = 12131769 | doi = 10.1097/00006676-200207000-00010}}</ref> [[colorectal cancer]],<ref name="urlCC Detect - Serum-Based Diagnostic Test For Colon Cancer Available">{{cite web | url = http://www.emaxhealth.com/100/18177.html | title = CC Detect - Serum-Based Diagnostic Test For Colon Cancer Available | date = | work = | publisher = | quote = | accessdate = }}</ref> [[prostate cancer]].<ref name="Xue_2009" /> and [[lung cancer]].<ref name="pmid17986689">{{cite journal | author = Hampton T | title = New screening techniques show potential for early detection of lung cancer | journal = JAMA | volume = 298 | issue = 17 | pages = 1997 |date=November 2007 | pmid = 17986689 | doi = 10.1001/jama.298.17.1997 | url = }}</ref> The pancreatic study<ref name="Palumbo_2002" /> showed elevated ''HAAH'' only in diseased tissue, but not in adjacent normal and inflamed tissue.

Mutations in ASPH cause {{SWL|type=mutation_results_in|target=Traboulsi syndrome|label=Traboulsi syndrome}}.{{Cite journal
| pmid = 24768550
| year = 2014
| author1 = Patel
| first1 = N
| title = Mutations in ASPH Cause Facial Dysmorphism, Lens Dislocation, Anterior-Segment Abnormalities, and Spontaneous Filtering Blebs, or Traboulsi Syndrome
| journal = The American Journal of Human Genetics
| last2 = Khan
| first2 = A. O.
| last3 = Mansour
| first3 = A
| last4 = Mohamed
| first4 = J. Y.
| last5 = Al-Assiri
| first5 = A
| last6 = Haddad
| first6 = R
| last7 = Jia
| first7 = X
| last8 = Xiong
| first8 = Y
| last9 = Mégarbané
| first9 = A
| last10 = Traboulsi
| first10 = E. I.
| last11 = Alkuraya
| first11 = F. S.
| doi = 10.1016/j.ajhg.2014.04.002
| volume=94
| issue=5
| pages=755–9
}}

==References==
{{reflist}}
{{Clear}}

==External links==
* {{UCSC gene info|ASPH}}

==Further reading==
{{refbegin | 2}}
*{{cite journal |vauthors=Hirota K, Semenza GL |title=Regulation of hypoxia-inducible factor 1 by prolyl and asparaginyl hydroxylases |journal=Biochem. Biophys. Res. Commun. |volume=338 |issue= 1 |pages= 610–6 |year= 2005 |pmid= 16154531 |doi= 10.1016/j.bbrc.2005.08.193 }}
*{{cite journal |vauthors=Lavaissiere L, Jia S, Nishiyama M |title=Overexpression of human aspartyl(asparaginyl)beta-hydroxylase in hepatocellular carcinoma and cholangiocarcinoma |journal=J. Clin. Invest. |volume=98 |issue= 6 |pages= 1313–23 |year= 1996 |pmid= 8823296 |doi=10.1172/JCI118918 | pmc=507557 |display-authors=etal}}
*{{cite journal |vauthors=Zhang L, Kelley J, Schmeisser G |title=Complex formation between junctin, triadin, calsequestrin, and the ryanodine receptor. Proteins of the cardiac junctional sarcoplasmic reticulum membrane |journal=J. Biol. Chem. |volume=272 |issue= 37 |pages= 23389–97 |year= 1997 |pmid= 9287354 |doi=10.1074/jbc.272.37.23389 |display-authors=etal}}
*{{cite journal |vauthors=Wetzel GT, Ding S, Chen F |title=Molecular cloning of junctin from human and developing rabbit heart |journal=Mol. Genet. Metab. |volume=69 |issue= 3 |pages= 252–8 |year= 2000 |pmid= 10767180 |doi= 10.1006/mgme.2000.2966 }}
*{{cite journal |vauthors=Dinchuk JE, Henderson NL, Burn TC |title=Aspartyl beta -hydroxylase (Asph) and an evolutionarily conserved isoform of Asph missing the catalytic domain share exons with junctin |journal=J. Biol. Chem. |volume=275 |issue= 50 |pages= 39543–54 |year= 2001 |pmid= 10956665 |doi= 10.1074/jbc.M006753200 |display-authors=etal}}
*{{cite journal |vauthors=Treves S, Feriotto G, Moccagatta L |title=Molecular cloning, expression, functional characterization, chromosomal localization, and gene structure of junctate, a novel integral calcium binding protein of sarco(endo)plasmic reticulum membrane |journal=J. Biol. Chem. |volume=275 |issue= 50 |pages= 39555–68 |year= 2001 |pmid= 11007777 |doi= 10.1074/jbc.M005473200 |display-authors=etal}}
*{{cite journal |vauthors=Kirchhefer U, Neumann J, Baba HA |title=Cardiac hypertrophy and impaired relaxation in transgenic mice overexpressing triadin 1 |journal=J. Biol. Chem. |volume=276 |issue= 6 |pages= 4142–9 |year= 2001 |pmid= 11069905 |doi= 10.1074/jbc.M006443200 |display-authors=etal}}
*{{cite journal |vauthors=Sepe PS, Lahousse SA, Gemelli B |title=Role of the aspartyl-asparaginyl-beta-hydroxylase gene in neuroblastoma cell motility |journal=Lab. Invest. |volume=82 |issue= 7 |pages= 881–91 |year= 2002 |pmid= 12118090 |doi= 10.1097/01.lab.0000020406.91689.7f|display-authors=etal}}
*{{cite journal |vauthors=Ho SP, Scully MS, Krauthauser CM |title=Antisense oligonucleotides selectively regulate aspartyl beta-hydroxylase and its truncated protein isoform in vitro but distribute poorly into A549 tumors in vivo |journal=J. Pharmacol. Exp. Ther. |volume=302 |issue= 2 |pages= 795–803 |year= 2002 |pmid= 12130746 |doi=10.1124/jpet.302.2.795 |display-authors=etal}}
*{{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |display-authors=etal}}
*{{cite journal |vauthors=Maeda T, Sepe P, Lahousse S |title=Antisense oligodeoxynucleotides directed against aspartyl (asparaginyl) beta-hydroxylase suppress migration of cholangiocarcinoma cells |journal=J. Hepatol. |volume=38 |issue= 5 |pages= 615–22 |year= 2004 |pmid= 12713872 |doi=10.1016/S0168-8278(03)00052-7 |display-authors=etal}}
*{{cite journal |vauthors=Treves S, Franzini-Armstrong C, Moccagatta L |title=Junctate is a key element in calcium entry induced by activation of InsP3 receptors and/or calcium store depletion |journal=J. Cell Biol. |volume=166 |issue= 4 |pages= 537–48 |year= 2004 |pmid= 15302852 |doi= 10.1083/jcb.200404079 | pmc=1868564 |display-authors=etal}}
*{{cite journal |vauthors=Beausoleil SA, Jedrychowski M, Schwartz D |title=Large-scale characterization of HeLa cell nuclear phosphoproteins |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130–5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101 | pmc=514446 |display-authors=etal}}
*{{cite journal |vauthors=Xian ZH, Zhang SH, Cong WM |title=Expression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma |journal=Mod. Pathol. |volume=19 |issue= 2 |pages= 280–6 |year= 2006 |pmid= 16341145 |doi= 10.1038/modpathol.3800530 |display-authors=etal}}
*{{cite journal |vauthors=de la Monte SM, Tamaki S, Cantarini MC |title=Aspartyl-(asparaginyl)-beta-hydroxylase regulates hepatocellular carcinoma invasiveness |journal=J. Hepatol. |volume=44 |issue= 5 |pages= 971–83 |year= 2006 |pmid= 16564107 |doi= 10.1016/j.jhep.2006.01.038 |display-authors=etal}}
*{{cite journal |vauthors=Feldmann G, Nattermann J, Nischalke HD |title=Detection of human aspartyl (asparaginyl) beta-hydroxylase and homeobox B7 mRNA in brush cytology specimens from patients with bile duct cancer |journal=Endoscopy |volume=38 |issue= 6 |pages= 604–9 |year= 2006 |pmid= 16673309 |doi= 10.1055/s-2006-925065 |display-authors=etal}}
*{{cite journal |vauthors=Gundogan F, Elwood G, Greco D |title=Role of aspartyl-(asparaginyl) beta-hydroxylase in placental implantation: Relevance to early pregnancy loss |journal=Hum. Pathol. |volume=38 |issue= 1 |pages= 50–9 |year= 2007 |pmid= 16949909 |doi= 10.1016/j.humpath.2006.06.005 |display-authors=etal}}
{{refend}}

{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]

{{gene-8-stub}}

EGLN1

2017-11-23T09:29:04Z

2407:7000:81AD:4400:D497:974B:2344:E1F6:

{{Infobox_gene}}
'''Hypoxia-inducible factor prolyl hydroxylase 2''' (HIF-PH2), or '''prolyl hydroxylase domain-containing protein 2''' (PHD2), is an enzyme encoded by the ''EGLN1'' [[gene]]. It is also known as '''Egl nine homolog 1'''.<ref name="pmid11056053">{{cite journal |vauthors=Dupuy D, Aubert I, Duperat VG, Petit J, Taine L, Stef M, Bloch B, Arveiler B | title = Mapping, characterization, and expression analysis of the SM-20 human homologue, c1orf12, and identification of a novel related gene, SCAND2 | journal = Genomics | volume = 69 | issue = 3 | pages = 348–54 |date=Nov 2000 | pmid = 11056053 | pmc = | doi = 10.1006/geno.2000.6343 }}</ref><ref name="pmid11574160">{{cite journal | author=Taylor MS |title=Characterization and comparative analysis of the EGLN gene family |journal=Gene |volume=275 |issue= 1 |pages= 125–32 |year= 2001 |pmid= 11574160 |doi=10.1016/S0378-1119(01)00633-3 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: EGLN1 egl nine homolog 1 (C. elegans)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=54583| accessdate = }}</ref><ref name="pmid12912907">{{cite journal |vauthors=Berra E, Benizri E, Ginouvès A, Volmat V, Roux D, Pouysségur J | title = HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1α in normoxia | journal = The EMBO Journal | volume = 22 | issue = 16 | pages = 4082–4090 |date=Aug 2003 | pmid = 12912907 | pmc = 175782 | doi = 10.1093/emboj/cdg392 }}</ref> PHD2 is a member of the non-haem Fe(II) and [[2-oxoglutarate (2OG)-dependent dioxygenases]].

==The hypoxia response==
[[HIF1A|HIF-1α]] is a ubiquitous, constitutively synthesized [[transcription factor]] responsible for upregulating the expression of genes involved in the cellular response to [[hypoxia (medical)|hypoxia]]. These gene products may include proteins such as [[glycolytic]] enzymes and [[angiogenic]] growth factors.<ref name="pmid15581484">{{cite journal |vauthors=William C, Nicholls L, Ratcliffe P, Pugh C, Maxwell P | title = The prolyl hydroxylase enzymes that act as oxygen sensors regulating destruction of hypoxia-inducible factor α | journal = Advan. Enzyme Regul. | volume = 44 | issue = | pages = 75–92 | year = 2004 | month = | pmid = 15581484 | pmc = | doi = 10.1016/j.advenzreg.2003.11.017 }}</ref> In normoxia, HIF alpha subunits are marked for the [[proteasome#Ubiquitination and targeting|ubiquitin-proteasome]] degradation pathway through [[hydroxylation]] of [[proline]]-564 and proline-402 by PHD2. Prolyl hydroxylation is critical for promoting [[Von Hippel–Lindau tumor suppressor|pVHL]] binding to HIF, which targets HIF for polyubiquitylation.<ref name="pmid12912907" />

==Structure==
[[File:PHD2 iron binding site.png|thumb|left|The iron binding site of PHD2.]]
PHD2 is a 46-kDa enzyme that consists of an [[N-terminal]] domain homologous to [[MYND zinc finger]] domains, and a [[C-terminal]] domain homologous to the 2-oxoglutarate [[dioxygenases]]. The catalytic domain consists of a double-stranded [[Beta helix|β-helix]] core that is stabilized by three [[alpha helix|α-helices]] packed along the major β-sheet.<ref name="pmid16782814">{{cite journal | vauthors = McDonough M, Li V, Flashman E, Chowdhury R, Mohr C, Liénard ZJ, Oldham N, Clifton I, Lewis J, McNeill L, Kurzeja R, Hewitson K, Yang E, Jordan S, Syed R, Schofield C | title = Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2) | journal = Proc Natl Acad Sci USA | volume = 103 | issue = 26 | pages = 9814–9 |date=Jun 2006 | pmid = 16782814 | pmc = 1502536| doi = 10.1073/pnas.0601283103 }}</ref> The active site, which is contained in the pocket between the β-sheets, chelates iron(II) through histidine and aspartate coordination. 2-oxoglutarate displaces a water molecule to bind iron as well.<ref name="pmid19604478">{{cite journal |vauthors=Chowdhury R, McDonough M, Mecinović J, Loenarz C, Flashman E, Hewitson K, Domene C, Schofield C | title = Structural basis for binding of hypoxia-inducible factor to the oxygen-sensing prolyl hydroxylases | journal = Structure | volume = 17 | issue = 7 | pages = 981–9 |date=Jul 2009 | pmid = 19604478 | pmc = | doi = 10.1016/j.str.2009.06.002 }}</ref> The active site is lined by [[hydrophobic]] residues, possibly because such residues are less susceptible to potential oxidative damage by reactive species leaking from the iron center.<ref name="pmid16782814"/>

The enzyme has a high affinity for iron(II) and 2-oxoglutarate, and forms a long-lived complex with these factors.<ref name="pmid16880998">{{cite journal |vauthors=McNeill L, Flashman E, Buck M, Hewitson K, Clifton I, Jeschke G, Claridge T, Ehrismann D, Oldham N, Schofield C | title = Hypoxia-inducible factor prolyl hydroxylase 2 has a high affinity for ferrous iron and 2-oxoglutarate | journal = Mol. Biosys. | volume = 1 | issue = 4 | pages = 321–4 |date=Oct 2005 | pmid = 16880998 | pmc = | doi = 10.1039/b511249b }}</ref> It has been proposed that cosubstrate and iron concentrations poise the HIF hydroxylases to respond to an appropriate "hypoxic window" for a particular cell type or tissue.<ref name="pmid16952279">{{cite journal |vauthors=Ehrismann D, Flashman E, Genn DN, Mathioudakis N, Hewitson KS, Ratcliffe PJ, Schofield CJ | title = Studies on the activity of the hypoxia-inducible-factor hydroxylases using an oxygen consumption assay | journal = Biochem. J. | volume = 401 | issue = 1 | pages = 227–34 |date=Jan 2007 | pmid = 16952279 | pmc = 1698668 | doi = 10.1042/BJ20061151 }}</ref> Studies have revealed that PHD2 has a [[Michaelis-Menten kinetics|KM]] for [[dioxygen]] slightly above its atmospheric concentration, and PHD2 is thought to be the most important sensor of the cell's oxygen status.<ref name="pmid12788921">{{cite journal |vauthors=Hirsilä M, Koivunen P, Günzler V, Kivirikko KI, Myllyharju J | title = Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor | journal = J. Biol. Chem. | volume = 278 | issue = 33 | pages = 30772–80 |date=Aug 2003 | pmid = 12788921 | pmc = | doi = 10.1074/jbc.M304982200 }}</ref>

==Mechanism==
The enzyme incorporates one oxygen atom from dioxygen into the hydroxylated product, and one oxygen atom into the [[succinate]] coproduct.<ref name="pmid12039559">{{cite journal |vauthors=McNeill LA, Hewitson KS, Gleadle JM, Horsfall LE, Oldham NJ, Maxwell PH, Pugh CW, Ratcliffe PJ, Schofield CJ | title = The use of dioxygen by HIF prolyl hydroxylase (PHD1) | journal = Bioorg. Med. Chem. | volume = 12 | issue = 12 | pages = 1547–50 |date=Jun 2002 | pmid = 12039559 | pmc = | doi = 10.1016/S0960-894X(02)00219-6}}</ref> Its interactions with HIF-1α rely on a mobile loop region that helps to enclose the hydroxylation site and helps to stabilize binding of both iron and 2-oxyglutarate.<ref name="pmid19604478"/>
[[File:Prolyl hydroxylase 2 (PHD2) reaction scheme.png|thumb|center|500px|PHD2 acts as a dioxygenase to hydroxylate proline and convert 2-oxoglutarate to succinate.]]

==Biological role and disease relevance==
PHD2 is the primary regulator of HIF-1α [[steady state]] levels in the cell. A PHD2 [[Gene knockdown|knockdown]] showed increased levels of HIF-1α under normoxia, and an increase in HIF-1α nuclear accumulation and HIF-dependent transcription. HIF-1α steady state accumulation was dependent on the amount of PHD silencing effected by [[siRNA]] in [[HeLa]] cells and a variety of other human cell lines.<ref name="pmid12912907" />

However, although it would seem that PHD2 downregulates HIF-1α and thus also tumorigenesis, there have been suggestions of paradoxical roles of PHD2 in [[tumor]] proliferation. For example, one animal study showed tumor reduction in PHD2-deficient mice through activation of antiproliferative [[TGF beta signaling pathway|TGF-β signaling]].<ref name="pmid21436457">{{cite journal |vauthors=Ameln AK, Muschter A, Mamlouk S, Kalucka J, Prade I, Franke K, Rezaei M, Poitz DM, Breier G, Wielockx B | title = Inhibition of HIF prolyl hydroxylase-2 blocks tumor growth in mice through the antiproliferative activity of TGFβ | journal = Cancer Res. | volume = 71 | issue = 9 | pages = 3306–16 |date=May 2011 | pmid = 21436457 | pmc = | doi = 10.1158/0008-5472.CAN-10-3838}}</ref> Other in vivo models showed tumor-suppressing activity for PHD2 in [[pancreatic cancer]] as well as [[liver cancer]].<ref name="pmid21792862">{{cite journal |vauthors=Su Y, Loos M, Giese N, Metzen E, Büchler MW, Friess H, Kornberg A, Büchler P | title = Prolyl hydroxylase-2 (PHD2) exerts tumor-suppressive activity in pancreatic cancer | journal = Cancer | volume = 118 | issue = 4 | pages = 960–72 |date=Feb 2012 | pmid = 21792862 | pmc = | doi = 10.1002/cncr.26344 }}</ref><ref name="pmid22420978">{{cite journal |vauthors=Heindryckx F, Kuchnio A, Casteleyn C, Coulon S, Olievier K, Colle I, Geerts A, Libbrecht L, Carmeliet P, Van Vlierberghe H | title = Effect of prolyl hydroxylase domain-2 haplodeficiency on the hepatocarcinogenesis in mice | journal = J. Hepatol. | volume = 57 | issue = 1 | pages = 61–8 |date=Jul 2012 | pmid = 22420978 | pmc = | doi = 10.1016/j.jhep.2012.02.021 }}</ref> A study of 121 human patients revealed PHD2 as a strong prognostic marker in [[gastric cancer]], with PHD2-negative patients having shortened survival compared to PHD2-positive patients.<ref name="pmid22236543">{{cite journal |vauthors=Kamphues C, Wittschieber D, Klauschen F, Kasajima A, Dietel M, Schmidt SC, Glanemann M, Bahra M, Neuhaus P, Weichert W, Stenzinger A | title = Prolyl hydroxylase domain 2 protein is a strong prognostic marker in human gastric cancer | journal = Pathobiology | volume = 79 | issue = 1 | pages = 11–17 |date=Jan 2012 | pmid = 22236543 | pmc = | doi = 10.1159/000330170 }}</ref>

As an additional point of interest, recent [[genome-wide association studies]] have suggested that EGLN1 may be involved in the low [[hematocrit]] phenotype exhibited by the Tibetan population and hence that EGLN1 may play a role in the heritable adaptation of this population to live at high altitude.<ref name="pmid20466884">{{cite journal |vauthors=Simonson TS, Yang Y, Huff CD, Yun H, Qin G, Witherspoon DJ, Bai Z, Lorenzo FR, Xing J, Jorde LB, Prchal JT, Ge R | title = Genetic evidence for high-altitude adaptation in Tibet. | journal = Science | volume = 329 | issue = 5987 | pages = 72–5 |date=Jul 2010 | pmid = 20466884 | pmc = | doi = 10.1126/science.1189406 }}</ref>

==As a therapeutic target==
HIF's important role as a [[homeostatic]] mediator implicates PHD2 as a therapeutic target for a range of disorders regarding angiogenesis, [[erythropoeisis]], and cellular proliferation. There has been interest both in potentiating and inhibiting the activity of PHD2.<ref name="pmid15581484"/> For example, [[methylselenocysteine]] (MSC) inhibition of HIF-1α led to tumor growth inhibition in [[renal cell carcinoma]] in a PHD-dependent manner. It is thought that this phenomenon relies on PHD-stabilization, but mechanistic details of this process have not yet been investigated.<ref name="bmc-chintala">{{cite journal |vauthors=Chintala S, Najrana T, Toth K, Cao S, Durrani F, Pili R, Rustum Y | title = Prolyl hydroxylase 2 dependent and Von-Hippel-Lindau independent degradation of hypoxia-inducible factor 1 and 2 alpha by selenium in clear cell renal cell carcinoma leads to tumor growth inhibition | journal = BMC Cancer | volume = 12 | issue = | pages = 293 | year = 2012 | month = | pmid = 22804960| pmc = 3466155| doi = 10.1186/1471-2407-12-293 }}</ref> On the other hand, screens of small-molecule chelators have revealed hydroxypyrones and hydroxypyridones as potential inhibitors for PHD2.<ref name="pmid22687491">{{cite journal |vauthors=Flagg SC, Martin CB, Taabazuing CY, Holmes BE, Knapp MJ | title = Screening chelating inhibitors of HIF-prolyl hydroxylase domain 2 (PHD2) and factor inhibiting HIF (FIH) | journal = J. Inorg. Biochem. | volume = 113 | issue = | pages = 25–30 |date=Aug 2012 | pmid = 22687491 | pmc = 3525482 | doi = 10.1016/j.jinorgbio.2012.03.002 }}</ref> Substrate analog peptides have also been developed to exhibit inhibitory selectivity for PHD2 over factor inhibiting HIF (FIH), for which some other PHD-inhibitors show overlapping specificity.<ref name="pmid21665470">{{cite journal |vauthors=Kwon HS, Choi YK, Kim JW, Park YK, Yang EG, Ahn DR | title = Inhibition of a prolyl hydroxylase domain (PHD) by substrate analog peptides | journal = Bioorg. Med. Chem. Lett. | volume = 21 | issue = 14 | pages = 4325–8 |date=Jul 2011 | pmid = 21665470 | pmc = | doi = 10.1016/j.bmcl.2011.05.050 }}</ref>

==References==
{{reflist}}

==Further reading==
{{refbegin | 2}}
*{{cite journal | author=Semenza GL |title=HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus |journal=Cell |volume=107 |issue= 1 |pages= 1–3 |year= 2001 |pmid= 11595178 |doi=10.1016/S0092-8674(01)00518-9 }}
*{{cite journal |vauthors=Wax SD, Tsao L, Lieb ME |title=SM-20 is a novel 40-kd protein whose expression in the arterial wall is restricted to smooth muscle |journal=Lab. Invest. |volume=74 |issue= 4 |pages= 797–808 |year= 1996 |pmid= 8606489 |doi= |display-authors=etal}}
*{{cite journal | author=Taylor MS |title=Characterization and comparative analysis of the EGLN gene family |journal=Gene |volume=275 |issue= 1 |pages= 125–32 |year= 2001 |pmid= 11574160 |doi=10.1016/S0378-1119(01)00633-3 }}
*{{cite journal |vauthors=Epstein AC, Gleadle JM, McNeill LA |title=C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation |journal=Cell |volume=107 |issue= 1 |pages= 43–54 |year= 2001 |pmid= 11595184 |doi=10.1016/S0092-8674(01)00507-4 |display-authors=etal}}
*{{cite journal |vauthors=Oehme F, Ellinghaus P, Kolkhof P |title=Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors |journal=Biochem. Biophys. Res. Commun. |volume=296 |issue= 2 |pages= 343–9 |year= 2002 |pmid= 12163023 |doi=10.1016/S0006-291X(02)00862-8 |display-authors=etal}}
*{{cite journal |vauthors=Ivan M, Haberberger T, Gervasi DC |title=Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 21 |pages= 13459–64 |year= 2002 |pmid= 12351678 |doi= 10.1073/pnas.192342099 | pmc=129695 |display-authors=etal}}
*{{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |display-authors=etal}}
*{{cite journal |vauthors=Metzen E, Berchner-Pfannschmidt U, Stengel P |title=Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing |journal=J. Cell Sci. |volume=116 |issue= Pt 7 |pages= 1319–26 |year= 2003 |pmid= 12615973 |doi=10.1242/jcs.00318 |display-authors=etal}}
*{{cite journal |vauthors=Cioffi CL, Liu XQ, Kosinski PA |title=Differential regulation of HIF-1 alpha prolyl-4-hydroxylase genes by hypoxia in human cardiovascular cells |journal=Biochem. Biophys. Res. Commun. |volume=303 |issue= 3 |pages= 947–53 |year= 2003 |pmid= 12670503 |doi=10.1016/S0006-291X(03)00453-4 |display-authors=etal}}
*{{cite journal |vauthors=Aprelikova O, Chandramouli GV, Wood M |title=Regulation of HIF prolyl hydroxylases by hypoxia-inducible factors |journal=J. Cell. Biochem. |volume=92 |issue= 3 |pages= 491–501 |year= 2004 |pmid= 15156561 |doi= 10.1002/jcb.20067 |display-authors=etal}}
*{{cite journal |vauthors=Appelhoff RJ, Tian YM, Raval RR |title=Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor |journal=J. Biol. Chem. |volume=279 |issue= 37 |pages= 38458–65 |year= 2004 |pmid= 15247232 |doi= 10.1074/jbc.M406026200 |display-authors=etal}}
*{{cite journal |vauthors=Metzen E, Stiehl DP, Doege K |title=Regulation of the prolyl hydroxylase domain protein 2 (phd2/egln-1) gene: identification of a functional hypoxia-responsive element |journal=Biochem. J. |volume=387 |issue= Pt 3 |pages= 711–7 |year= 2006 |pmid= 15563275 |doi= 10.1042/BJ20041736 | pmc=1135001 |display-authors=etal}}
*{{cite journal |vauthors=Baek JH, Mahon PC, Oh J |title=OS-9 interacts with hypoxia-inducible factor 1alpha and prolyl hydroxylases to promote oxygen-dependent degradation of HIF-1alpha |journal=Mol. Cell |volume=17 |issue= 4 |pages= 503–12 |year= 2005 |pmid= 15721254 |doi= 10.1016/j.molcel.2005.01.011 |display-authors=etal}}
*{{cite journal |vauthors=Ozer A, Wu LC, Bruick RK |title=The candidate tumor suppressor ING4 represses activation of the hypoxia inducible factor (HIF) |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=102 |issue= 21 |pages= 7481–6 |year= 2005 |pmid= 15897452 |doi= 10.1073/pnas.0502716102 | pmc=1140452 }}
*{{cite journal |vauthors=Choi KO, Lee T, Lee N |title=Inhibition of the catalytic activity of hypoxia-inducible factor-1alpha-prolyl-hydroxylase 2 by a MYND-type zinc finger |journal=Mol. Pharmacol. |volume=68 |issue= 6 |pages= 1803–9 |year= 2006 |pmid= 16155211 |doi= 10.1124/mol.105.015271 |display-authors=etal}}
*{{cite journal |vauthors=To KK, Huang LE |title=SUPPRESSION OF HIF-1α TRANSCRIPTIONAL ACTIVITY BY THE HIF PROLYL HYDROXYLASE EGLN1 |journal=J. Biol. Chem. |volume=280 |issue= 45 |pages= 38102–7 |year= 2006 |pmid= 16157596 |doi= 10.1074/jbc.M504342200 | pmc=1307502 }}
*{{cite journal |vauthors=Kato H, Inoue T, Asanoma K |title=Induction of human endometrial cancer cell senescence through modulation of HIF-1alpha activity by EGLN1 |journal=Int. J. Cancer |volume=118 |issue= 5 |pages= 1144–53 |year= 2006 |pmid= 16161047 |doi= 10.1002/ijc.21488 |display-authors=etal}}
{{refend}}

{{PDB Gallery|geneid=54583}}
{{Dioxygenases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}

[[Category:Human 2OG oxygenases]]
[[Category:EC 1.14.11]]