Granulin: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Robot: Automated text replacement (-{{WikiDoc Cardiology Network Infobox}} +, -<references /> +{{reflist|2}}, -{{reflist}} +{{reflist|2}}))
 
(consistent citation formatting)
Line 1: Line 1:
<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
{{Infobox protein family
| update_page = yes
| Symbol = Granulin
| require_manual_inspection = no
| Name = Granulin
| update_protein_box = yes
| image = PDB 1g26 EBI.jpg
| update_summary = yes
| width =
| update_citations = yes
| caption = the solution structure of a well-folded peptide based on the 31-residue amino-terminal subdomain of human granulin a
| Pfam = PF00396
| Pfam_clan = 
| InterPro = IPR000118
| SMART =
| PROSITE = PDOC00634
| MEROPS =
| SCOP = 1pcn
| TCDB =  
| OPM family =  
| OPM protein =  
| CAZy =  
| CDD =  
}}
}}
'''Granulin''' is a [[protein]] that in humans is encoded by the ''GRN'' [[gene]].<ref name="pmid1417868">{{cite journal | vauthors = Bhandari V, Bateman A | title = Structure and chromosomal location of the human granulin gene | journal = Biochemical and Biophysical Research Communications | volume = 188 | issue = 1 | pages = 57–63 | date = October 1992 | pmid = 1417868 | pmc =  | doi = 10.1016/0006-291X(92)92349-3 }}</ref><ref name="pmid9826678">{{cite journal | vauthors = Zhang H, Serrero G | title = Inhibition of tumorigenicity of the teratoma PC cell line by transfection with antisense cDNA for PC cell-derived growth factor (PCDGF, epithelin/granulin precursor) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 24 | pages = 14202–7 | date = November 1998 | pmid = 9826678 | pmc = 24351 | doi = 10.1073/pnas.95.24.14202 | bibcode = 1998PNAS...9514202Z }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: GRN granulin| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2896| accessdate = }}</ref>


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
== Structure ==
{{GNF_Protein_box
 
| image = PBB_Protein_GRN_image.jpg
Granulins are a family of secreted, [[glycosylation|glycosylated]] peptides that are cleaved from a single precursor protein with 7.5 repeats of a highly conserved 12-[[cysteine]] granulin/epithelin motif. The 88 kDa precursor protein, progranulin, is also called proepithelin and [[prostate cancer]] (PC) cell-derived growth factor. Cleavage of the [[signal peptide]] produces mature granulin which can be further cleaved into a variety of active, 6 kDa peptides. These smaller cleavage products are named granulin A, granulin B, granulin C, etc. Epithelins 1 and 2 are synonymous with granulins A and B, respectively.
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1g26.
 
| PDB = {{PDB2|1g26}}
== Function ==
| Name = Granulin
 
| HGNCid = 4601
Both the peptides and intact granulin protein regulate cell growth. However, different members of the granulin protein family may act as inhibitors, stimulators, or have dual actions on [[cell growth]]. Granulin family members are important in normal development, [[wound healing]], and [[carcinogenesis|tumorigenesis]].<ref name="entrez"/>
| Symbol = GRN
 
| AltSymbols =; GEP; GP88; PCDGF; PEPI; PGRN
== Clinical significance ==
| OMIM = 138945
 
| ECnumber =
The human liver fluke (''[[Opisthorchis viverrini]]'') contributes to the development of [[cholangiocarcinoma|bile duct]] (liver) cancer by secreting a granulin-like growth hormone.<ref name="pmid19816559">{{cite journal | vauthors = Smout MJ, Laha T, Mulvenna J, Sripa B, Suttiprapa S, Jones A, Brindley PJ, Loukas A | title = A granulin-like growth factor secreted by the carcinogenic liver fluke, Opisthorchis viverrini, promotes proliferation of host cells | journal = PLoS Pathogens | volume = 5 | issue = 10 | pages = e1000611 | date = October 2009 | pmid = 19816559 | pmc = 2749447 | doi = 10.1371/journal.ppat.1000611 }}</ref>
| Homologene = 1577
 
| MGIid = 95832
Mutations in the ''GRN'' gene have been implicated in up to 25% of [[frontotemporal lobar degeneration]], inherited in an autosomal dominant fashion with high [[penetrance]].<ref name="Mackenzie2007">{{cite journal | vauthors = Mackenzie IR | title = The neuropathology and clinical phenotype of FTD with progranulin mutations | journal = Acta Neuropathologica | volume = 114 | issue = 1 | pages = 49–54 | date = July 2007 | pmid = 17458552 | pmc = | doi = 10.1007/s00401-007-0223-8 }}</ref> Several loss-of-function mutations disease-causing mutations in ''GRN'' have been identified.<ref name="Baker2006">{{cite journal | vauthors = Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R, Lindholm C, Snowden J, Adamson J, Sadovnick AD, Rollinson S, Cannon A, Dwosh E, Neary D, Melquist S, Richardson A, Dickson D, Berger Z, Eriksen J, Robinson T, Zehr C, Dickey CA, Crook R, McGowan E, Mann D, Boeve B, Feldman H, Hutton M | title = Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17 | journal = Nature | volume = 442 | issue = 7105 | pages = 916–9 | date = August 2006 | pmid = 16862116 | pmc = | doi = 10.1038/nature05016 | bibcode = 2006Natur.442..916B }}</ref><ref name="Cruts2006">{{cite journal | vauthors = Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H, Pirici D, Rademakers R, Vandenberghe R, Dermaut B, Martin JJ, van Duijn C, Peeters K, Sciot R, Santens P, De Pooter T, Mattheijssens M, Van den Broeck M, Cuijt I, Vennekens K, De Deyn PP, Kumar-Singh S, Van Broeckhoven C | title = Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21 | journal = Nature | volume = 442 | issue = 7105 | pages = 920–4 | date = August 2006 | pmid = 16862115 | pmc = | doi = 10.1038/nature05017 | bibcode = 2006Natur.442..920C }}</ref>
| GeneAtlas_image1 = PBB_GE_GRN_211284_s_at_tn.png
 
| GeneAtlas_image2 = PBB_GE_GRN_200678_x_at_tn.png
Granulin release by [[macrophages]] has been associated with [[fibrotic]] hepatic [[metastasis]] in [[pancreatic cancer]].<ref>{{cite journal | vauthors = Nielsen SR, Quaranta V, Linford A, Emeagi P, Rainer C, Santos A, Ireland L, Sakai T, Sakai K, Kim YS, Engle D, Campbell F, Palmer D, Ko JH, Tuveson DA, Hirsch E, Mielgo A, Schmid MC | title = Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis | journal = Nature Cell Biology | volume = 18 | issue = 5 | pages = 549–60 | date = May 2016 | pmid = 27088855 | doi = 10.1038/ncb3340 }}</ref>
| GeneAtlas_image3 = PBB_GE_GRN_216041_x_at_tn.png
 
| Function = {{GNF_GO|id=GO:0005125 |text = cytokine activity}} {{GNF_GO|id=GO:0008083 |text = growth factor activity}}
Mutations in this gene have been associated with [[hereditary spastic paraplegia]].<ref name=Faber2017>{{cite journal | vauthors = Faber I, Prota JR, Martinez AR, Lopes-Cendes I, França MC | title = A new phenotype associated with homozygous GRN mutations: complicated spastic paraplegia | journal = European Journal of Neurology | volume = 24 | issue = 1 | pages = e3-e4 | date = January 2017 | pmid = 28000352 | doi = 10.1111/ene.13194 }}</ref>
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005615 |text = extracellular space}} {{GNF_GO|id=GO:0005739 |text = mitochondrion}}  
 
  | Process = {{GNF_GO|id=GO:0001835 |text = blastocyst hatching}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007267 |text = cell-cell signaling}} {{GNF_GO|id=GO:0007566 |text = embryo implantation}} {{GNF_GO|id=GO:0008283 |text = cell proliferation}} {{GNF_GO|id=GO:0050679 |text = positive regulation of epithelial cell proliferation}}
== Interactions ==
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 2896
    | Hs_Ensembl = ENSG00000030582
    | Hs_RefseqProtein = NP_001012497
    | Hs_RefseqmRNA = NM_001012479
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 17
    | Hs_GenLoc_start = 39778017
    | Hs_GenLoc_end = 39785996
    | Hs_Uniprot = P28799
    | Mm_EntrezGene = 14824
    | Mm_Ensembl = ENSMUSG00000034708
    | Mm_RefseqmRNA = XM_984981
    | Mm_RefseqProtein = XP_990075
    | Mm_GenLoc_db =
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 102246571
    | Mm_GenLoc_end = 102252895
    | Mm_Uniprot = Q3TVQ3
  }}
}}
'''Granulin''', also known as '''GRN''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: GRN granulin| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2896| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
Granulin has been shown to [[Protein-protein interaction|interact]] with [[Cyclin T1]]<ref name="pmid12588988">{{cite journal | vauthors = Hoque M, Young TM, Lee CG, Serrero G, Mathews MB, Pe'ery T | title = The growth factor granulin interacts with cyclin T1 and modulates P-TEFb-dependent transcription | journal = Molecular and Cellular Biology | volume = 23 | issue = 5 | pages = 1688–702 | date = March 2003 | pmid = 12588988 | pmc = 151712 | doi = 10.1128/MCB.23.5.1688-1702.2003 }}</ref> and [[TRIB3]].<ref name="pmid18276110">{{cite journal | vauthors = Zhou Y, Li L, Liu Q, Xing G, Kuai X, Sun J, Yin X, Wang J, Zhang L, He F | title = E3 ubiquitin ligase SIAH1 mediates ubiquitination and degradation of TRB3 | journal = Cellular Signalling | volume = 20 | issue = 5 | pages = 942–8 | date = May 2008 | pmid = 18276110 | doi = 10.1016/j.cellsig.2008.01.010 }}</ref>
{{PBB_Summary
| section_title =  
| summary_text = Granulins are a family of secreted, glycosylated peptides that are cleaved from a single precursor protein with 7.5 repeats of a highly conserved 12-cysteine granulin/epithelin motif. The 88 kDa precursor protein, progranulin, is also called proepithelin and PC cell-derived growth factor. Cleavage of the signal peptide produces mature granulin which can be further cleaved into a variety of active, 6 kDa peptides. These smaller cleavage products are named granulin A, granulin B, granulin C, etc. Epithelins 1 and 2 are synonymous with granulins A and B, respectively. Both the peptides and intact granulin protein regulate cell growth. However, different members of the granulin protein family may act as inhibitors, stimulators, or have dual actions on cell growth. Granulin family members are important in normal development, wound healing, and tumorigenesis.<ref name="entrez">{{cite web | title = Entrez Gene: GRN granulin| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2896| accessdate = }}</ref>
}}


==References==
== References ==
{{reflist|2}}
{{reflist|2}}
==Further reading==
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
*{{cite journal | author=Eriksen J, Mackenzie IR |title=Progranulin: normal function and role in neurodegeneration. |journal=J Neurochem |volume=104 |issue=2 |pages= 287-297 |year= 2008 |pmid= 117953663 |doi= 10.1111/j.14714159.2007.04968.x }}
* {{cite journal | vauthors = Eriksen JL, Mackenzie IR | title = Progranulin: normal function and role in neurodegeneration | journal = Journal of Neurochemistry | volume = 104 | issue = 2 | pages = 287–97 | date = January 2008 | pmid = 17953663 | doi = 10.1111/J.1471-4159.2007.04968.X }}
{{PBB_Further_reading
* {{cite journal | vauthors = Serrero G | title = Autocrine growth factor revisited: PC-cell-derived growth factor (progranulin), a critical player in breast cancer tumorigenesis | journal = Biochemical and Biophysical Research Communications | volume = 308 | issue = 3 | pages = 409–13 | date = August 2003 | pmid = 12914763 | doi = 10.1016/S0006-291X(03)01452-9 }}
| citations =
* {{cite journal | vauthors = Ahmed Z, Mackenzie IR, Hutton ML, Dickson DW | title = Progranulin in frontotemporal lobar degeneration and neuroinflammation | journal = Journal of Neuroinflammation | volume = 4 | issue =  | pages = 7 | date = February 2007 | pmid = 17291356 | pmc = 1805428 | doi = 10.1186/1742-2094-4-7 }}
*{{cite journal | author=Serrero G |title=Autocrine growth factor revisited: PC-cell-derived growth factor (progranulin), a critical player in breast cancer tumorigenesis. |journal=Biochem. Biophys. Res. Commun. |volume=308 |issue= 3 |pages= 409-13 |year= 2003 |pmid= 12914763 |doi= }}
* {{cite journal | vauthors = Mackenzie IR | title = The neuropathology and clinical phenotype of FTD with progranulin mutations | journal = Acta Neuropathologica | volume = 114 | issue = 1 | pages = 49–54 | date = July 2007 | pmid = 17458552 | doi = 10.1007/s00401-007-0223-8 }}
*{{cite journal | author=Ahmed Z, Mackenzie IR, Hutton ML, Dickson DW |title=Progranulin in frontotemporal lobar degeneration and neuroinflammation. |journal=Journal of neuroinflammation |volume=4 |issue=  |pages= 7 |year= 2007 |pmid= 17291356 |doi= 10.1186/1742-2094-4-7 }}
* {{cite journal | vauthors = Pickering-Brown SM | title = Progranulin and frontotemporal lobar degeneration | journal = Acta Neuropathologica | volume = 114 | issue = 1 | pages = 39–47 | date = July 2007 | pmid = 17572900 | doi = 10.1007/s00401-007-0241-6 }}
*{{cite journal | author=Mackenzie IR |title=The neuropathology and clinical phenotype of FTD with progranulin mutations. |journal=Acta Neuropathol. |volume=114 |issue= 1 |pages= 49-54 |year= 2007 |pmid= 17458552 |doi= 10.1007/s00401-007-0223-8 }}
* {{cite journal | vauthors = Bhandari V, Palfree RG, Bateman A | title = Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 5 | pages = 1715–9 | date = March 1992 | pmid = 1542665 | pmc = 48523 | doi = 10.1073/pnas.89.5.1715 | bibcode = 1992PNAS...89.1715B }}
*{{cite journal | author=Pickering-Brown SM |title=Progranulin and frontotemporal lobar degeneration. |journal=Acta Neuropathol. |volume=114 |issue= 1 |pages= 39-47 |year= 2007 |pmid= 17572900 |doi= 10.1007/s00401-007-0241-6 }}
* {{cite journal | vauthors = Plowman GD, Green JM, Neubauer MG, Buckley SD, McDonald VL, Todaro GJ, Shoyab M | title = The epithelin precursor encodes two proteins with opposing activities on epithelial cell growth | journal = The Journal of Biological Chemistry | volume = 267 | issue = 18 | pages = 13073–8 | date = June 1992 | pmid = 1618805 | doi =  }}
*{{cite journal | author=Bhandari V, Bateman A |title=Structure and chromosomal location of the human granulin gene. |journal=Biochem. Biophys. Res. Commun. |volume=188 |issue= 1 |pages= 57-63 |year= 1992 |pmid= 1417868 |doi= }}
* {{cite journal | vauthors = Bateman A, Belcourt D, Bennett H, Lazure C, Solomon S | title = Granulins, a novel class of peptide from leukocytes | journal = Biochemical and Biophysical Research Communications | volume = 173 | issue = 3 | pages = 1161–8 | date = December 1990 | pmid = 2268320 | doi = 10.1016/S0006-291X(05)80908-8 }}
*{{cite journal | author=Bhandari V, Palfree RG, Bateman A |title=Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue= 5 |pages= 1715-9 |year= 1992 |pmid= 1542665 |doi=  }}
* {{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 | author=Plowman GD, Green JM, Neubauer MG, ''et al.'' |title=The epithelin precursor encodes two proteins with opposing activities on epithelial cell growth. |journal=J. Biol. Chem. |volume=267 |issue= 18 |pages= 13073-8 |year= 1992 |pmid= 1618805 |doi= }}
* {{cite journal | vauthors = Baba T, Hoff HB, Nemoto H, Lee H, Orth J, Arai Y, Gerton GL | title = Acrogranin, an acrosomal cysteine-rich glycoprotein, is the precursor of the growth-modulating peptides, granulins, and epithelins, and is expressed in somatic as well as male germ cells | journal = Molecular Reproduction and Development | volume = 34 | issue = 3 | pages = 233–43 | date = March 1993 | pmid = 8471244 | doi = 10.1002/mrd.1080340302 }}
*{{cite journal | author=Bateman A, Belcourt D, Bennett H, ''et al.'' |title=Granulins, a novel class of peptide from leukocytes. |journal=Biochem. Biophys. Res. Commun. |volume=173 |issue= 3 |pages= 1161-8 |year= 1991 |pmid= 2268320 |doi= }}
* {{cite journal | vauthors = Kardana A, Bagshawe KD, Coles B, Read D, Taylor M | title = Characterisation of UGP and its relationship with beta-core fragment | journal = British Journal of Cancer | volume = 67 | issue = 4 | pages = 686–92 | date = April 1993 | pmid = 8471426 | pmc = 1968365 | doi = 10.1038/bjc.1993.127 }}
*{{cite journal | author=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 |year= 1994 |pmid= 8125298 |doi= }}
* {{cite journal | vauthors = Zhou J, Gao G, Crabb JW, Serrero G | title = Purification of an autocrine growth factor homologous with mouse epithelin precursor from a highly tumorigenic cell line | journal = The Journal of Biological Chemistry | volume = 268 | issue = 15 | pages = 10863–9 | date = May 1993 | pmid = 8496151 | doi =  }}
*{{cite journal | author=Baba T, Hoff HB, Nemoto H, ''et al.'' |title=Acrogranin, an acrosomal cysteine-rich glycoprotein, is the precursor of the growth-modulating peptides, granulins, and epithelins, and is expressed in somatic as well as male germ cells. |journal=Mol. Reprod. Dev. |volume=34 |issue= 3 |pages= 233-43 |year= 1993 |pmid= 8471244 |doi= 10.1002/mrd.1080340302 }}
* {{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 = April 1996 | pmid = 8619474 | doi = 10.1006/abio.1996.0138 }}
*{{cite journal | author=Kardana A, Bagshawe KD, Coles B, ''et al.'' |title=Characterisation of UGP and its relationship with beta-core fragment. |journal=Br. J. Cancer |volume=67 |issue= 4 |pages= 686-92 |year= 1993 |pmid= 8471426 |doi=  }}
* {{cite journal | vauthors = Bhandari V, Daniel R, Lim PS, Bateman A | title = Structural and functional analysis of a promoter of the human granulin/epithelin gene | journal = The Biochemical Journal | volume = 319 ( Pt 2) | issue = 2 | pages = 441–7 | date = October 1996 | pmid = 8912679 | pmc = 1217788 | doi = }}
*{{cite journal | author=Zhou J, Gao G, Crabb JW, Serrero G |title=Purification of an autocrine growth factor homologous with mouse epithelin precursor from a highly tumorigenic cell line. |journal=J. Biol. Chem. |volume=268 |issue= 15 |pages= 10863-9 |year= 1993 |pmid= 8496151 |doi= }}
* {{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 = April 1997 | pmid = 9110174 | pmc = 139146 | doi = 10.1101/gr.7.4.353 }}
*{{cite journal | author=Andersson B, Wentland MA, Ricafrente JY, ''et al.'' |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 = 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 | author=Bhandari V, Daniel R, Lim PS, Bateman A |title=Structural and functional analysis of a promoter of the human granulin/epithelin gene. |journal=Biochem. J. |volume=319 ( Pt 2) |issue= |pages= 441-7 |year= 1996 |pmid= 8912679 |doi= }}
* {{cite journal | vauthors = Trinh DP, Brown KM, Jeang KT | title = Epithelin/granulin growth factors: extracellular cofactors for HIV-1 and HIV-2 Tat proteins | journal = Biochemical and Biophysical Research Communications | volume = 256 | issue = 2 | pages = 299–306 | date = March 1999 | pmid = 10079180 | doi = 10.1006/bbrc.1999.0317 }}
*{{cite journal | author=Yu W, Andersson B, Worley KC, ''et al.'' |title=Large-scale concatenation cDNA sequencing. |journal=Genome Res. |volume=7 |issue= 4 |pages= 353-8 |year= 1997 |pmid= 9110174 |doi= }}
* {{cite journal | vauthors = He Z, Bateman A | title = Progranulin gene expression regulates epithelial cell growth and promotes tumor growth in vivo | journal = Cancer Research | volume = 59 | issue = 13 | pages = 3222–9 | date = July 1999 | pmid = 10397269 | doi =  }}
*{{cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |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 |year= 1997 |pmid= 9373149 |doi= }}
* {{cite journal | vauthors = Thornton MA, Poncz M, Korostishevsky M, Yakobson E, Usher S, Seligsohn U, Peretz H | title = The human platelet alphaIIb gene is not closely linked to its integrin partner beta3 | journal = Blood | volume = 94 | issue = 6 | pages = 2039–47 | date = September 1999 | pmid = 10477733 | doi =  }}
*{{cite journal | author=Zhang H, Serrero G |title=Inhibition of tumorigenicity of the teratoma PC cell line by transfection with antisense cDNA for PC cell-derived growth factor (PCDGF, epithelin/granulin precursor). |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 24 |pages= 14202-7 |year= 1998 |pmid= 9826678 |doi=  }}
*{{cite journal | author=Trinh DP, Brown KM, Jeang KT |title=Epithelin/granulin growth factors: extracellular cofactors for HIV-1 and HIV-2 Tat proteins. |journal=Biochem. Biophys. Res. Commun. |volume=256 |issue= 2 |pages= 299-306 |year= 1999 |pmid= 10079180 |doi= 10.1006/bbrc.1999.0317 }}
*{{cite journal  | author=He Z, Bateman A |title=Progranulin gene expression regulates epithelial cell growth and promotes tumor growth in vivo. |journal=Cancer Res. |volume=59 |issue= 13 |pages= 3222-9 |year= 1999 |pmid= 10397269 |doi=  }}
*{{cite journal  | author=Thornton MA, Poncz M, Korostishevsky M, ''et al.'' |title=The human platelet alphaIIb gene is not closely linked to its integrin partner beta3. |journal=Blood |volume=94 |issue= 6 |pages= 2039-47 |year= 1999 |pmid= 10477733 |doi=  }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
== External links ==
{{WikiDoc Sources}}
*[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ftd-grn  GeneReviews/NCBI/NIH/UW entry on GRN-Related Frontotemporal Dementia]
 
{{PDB Gallery|geneid=2896}}
 
[[Category:Protein families]]
[[Category:Precursor proteins]]

Revision as of 21:46, 11 November 2017

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human
Granulin
File:PDB 1g26 EBI.jpg
the solution structure of a well-folded peptide based on the 31-residue amino-terminal subdomain of human granulin a
Identifiers
SymbolGranulin
PfamPF00396
InterProIPR000118
PROSITEPDOC00634
SCOP1pcn
SUPERFAMILY1pcn

Granulin is a protein that in humans is encoded by the GRN gene.[1][2][3]

Structure

Granulins are a family of secreted, glycosylated peptides that are cleaved from a single precursor protein with 7.5 repeats of a highly conserved 12-cysteine granulin/epithelin motif. The 88 kDa precursor protein, progranulin, is also called proepithelin and prostate cancer (PC) cell-derived growth factor. Cleavage of the signal peptide produces mature granulin which can be further cleaved into a variety of active, 6 kDa peptides. These smaller cleavage products are named granulin A, granulin B, granulin C, etc. Epithelins 1 and 2 are synonymous with granulins A and B, respectively.

Function

Both the peptides and intact granulin protein regulate cell growth. However, different members of the granulin protein family may act as inhibitors, stimulators, or have dual actions on cell growth. Granulin family members are important in normal development, wound healing, and tumorigenesis.[3]

Clinical significance

The human liver fluke (Opisthorchis viverrini) contributes to the development of bile duct (liver) cancer by secreting a granulin-like growth hormone.[4]

Mutations in the GRN gene have been implicated in up to 25% of frontotemporal lobar degeneration, inherited in an autosomal dominant fashion with high penetrance.[5] Several loss-of-function mutations disease-causing mutations in GRN have been identified.[6][7]

Granulin release by macrophages has been associated with fibrotic hepatic metastasis in pancreatic cancer.[8]

Mutations in this gene have been associated with hereditary spastic paraplegia.[9]

Interactions

Granulin has been shown to interact with Cyclin T1[10] and TRIB3.[11]

References

  1. ↑ Bhandari V, Bateman A (October 1992). "Structure and chromosomal location of the human granulin gene". Biochemical and Biophysical Research Communications. 188 (1): 57–63. doi:10.1016/0006-291X(92)92349-3. PMID 1417868.
  2. ↑ Zhang H, Serrero G (November 1998). "Inhibition of tumorigenicity of the teratoma PC cell line by transfection with antisense cDNA for PC cell-derived growth factor (PCDGF, epithelin/granulin precursor)". Proceedings of the National Academy of Sciences of the United States of America. 95 (24): 14202–7. Bibcode:1998PNAS...9514202Z. doi:10.1073/pnas.95.24.14202. PMC 24351. PMID 9826678.
  3. ↑ 3.0 3.1 "Entrez Gene: GRN granulin".
  4. ↑ Smout MJ, Laha T, Mulvenna J, Sripa B, Suttiprapa S, Jones A, Brindley PJ, Loukas A (October 2009). "A granulin-like growth factor secreted by the carcinogenic liver fluke, Opisthorchis viverrini, promotes proliferation of host cells". PLoS Pathogens. 5 (10): e1000611. doi:10.1371/journal.ppat.1000611. PMC 2749447. PMID 19816559.
  5. ↑ Mackenzie IR (July 2007). "The neuropathology and clinical phenotype of FTD with progranulin mutations". Acta Neuropathologica. 114 (1): 49–54. doi:10.1007/s00401-007-0223-8. PMID 17458552.
  6. ↑ Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R, Lindholm C, Snowden J, Adamson J, Sadovnick AD, Rollinson S, Cannon A, Dwosh E, Neary D, Melquist S, Richardson A, Dickson D, Berger Z, Eriksen J, Robinson T, Zehr C, Dickey CA, Crook R, McGowan E, Mann D, Boeve B, Feldman H, Hutton M (August 2006). "Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17". Nature. 442 (7105): 916–9. Bibcode:2006Natur.442..916B. doi:10.1038/nature05016. PMID 16862116.
  7. ↑ Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H, Pirici D, Rademakers R, Vandenberghe R, Dermaut B, Martin JJ, van Duijn C, Peeters K, Sciot R, Santens P, De Pooter T, Mattheijssens M, Van den Broeck M, Cuijt I, Vennekens K, De Deyn PP, Kumar-Singh S, Van Broeckhoven C (August 2006). "Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21". Nature. 442 (7105): 920–4. Bibcode:2006Natur.442..920C. doi:10.1038/nature05017. PMID 16862115.
  8. ↑ Nielsen SR, Quaranta V, Linford A, Emeagi P, Rainer C, Santos A, Ireland L, Sakai T, Sakai K, Kim YS, Engle D, Campbell F, Palmer D, Ko JH, Tuveson DA, Hirsch E, Mielgo A, Schmid MC (May 2016). "Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis". Nature Cell Biology. 18 (5): 549–60. doi:10.1038/ncb3340. PMID 27088855.
  9. ↑ Faber I, Prota JR, Martinez AR, Lopes-Cendes I, França MC (January 2017). "A new phenotype associated with homozygous GRN mutations: complicated spastic paraplegia". European Journal of Neurology. 24 (1): e3–e4. doi:10.1111/ene.13194. PMID 28000352.
  10. ↑ Hoque M, Young TM, Lee CG, Serrero G, Mathews MB, Pe'ery T (March 2003). "The growth factor granulin interacts with cyclin T1 and modulates P-TEFb-dependent transcription". Molecular and Cellular Biology. 23 (5): 1688–702. doi:10.1128/MCB.23.5.1688-1702.2003. PMC 151712. PMID 12588988.
  11. ↑ Zhou Y, Li L, Liu Q, Xing G, Kuai X, Sun J, Yin X, Wang J, Zhang L, He F (May 2008). "E3 ubiquitin ligase SIAH1 mediates ubiquitination and degradation of TRB3". Cellular Signalling. 20 (5): 942–8. doi:10.1016/j.cellsig.2008.01.010. PMID 18276110.

Further reading

External links

Retrieved from "https://www.wikidoc.org/index.php?title=Granulin&oldid=1417912"