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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox gene}}
{{PBB_Controls
'''Centromere protein J''' is a [[protein]] that in humans is encoded by the ''CENPJ'' [[gene]].<ref name="pmid11003675">{{cite journal | vauthors = Hung LY, Tang CJ, Tang TK | title = Protein 4.1 R-135 interacts with a novel centrosomal protein (CPAP) which is associated with the gamma-tubulin complex | journal = Molecular and Cellular Biology | volume = 20 | issue = 20 | pages = 7813–25 | date = Oct 2000 | pmid = 11003675 | pmc = 86375 | doi = 10.1128/MCB.20.20.7813-7825.2000 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CENPJ centromere protein J| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55835| accessdate = }}</ref> It is also known as [[centrosome|centrosomal]] [[EPB41|P4.1]]-associated protein (CPAP).
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During [[cell division]], this protein plays a structural role in the maintenance of [[centrosome]] integrity and normal [[Spindle apparatus|spindle]] morphology, and it is involved in [[microtubule]] disassembly at the centrosome. This protein can function as a transcriptional coactivator in the [[Stat5]] signaling pathway, and also as a coactivator of [[NF-kappaB]]-mediated transcription, likely via its interaction with the coactivator p300/[[CREB-binding protein]]. Mutations in this gene are associated with [[Seckel syndrome]] and primary autosomal recessive [[microcephaly]], a disorder characterized by severely reduced [[brain]] size and [[mental retardation]].<ref name="entrez" /><ref name="pmid20522431">{{cite journal | vauthors = Al-Dosari MS, Shaheen R, Colak D, Alkuraya FS | title = Novel CENPJ mutation causes Seckel syndrome | journal = Journal of Medical Genetics | volume = 47 | issue = 6 | pages = 411–4 | date = Jun 2010 | pmid = 20522431 | pmc =  | doi = 10.1136/jmg.2009.076646 | url =  }}</ref><ref>{{cite journal | vauthors = Gul A, Hassan MJ, Hussain S, Raza SI, Chishti MS, Ahmad W | title = A novel deletion mutation in CENPJ gene in a Pakistani family with autosomal recessive primary microcephaly | journal = Journal of Human Genetics | volume = 51 | issue = 9 | pages = 760–4 | year = 2006 | pmid = 16900296 | doi = 10.1007/s10038-006-0017-1 }}</ref>
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| update_summary = yes
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}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The ''[[Drosophila]]'' ortholog, '''sas-4''', has been shown to be a scaffold for a [[cytoplasm]]ic complex of [[CDK5RAP2|Cnn]], [[CEP152|Asl]], CP-190, [[tubulin]] and D-PLP (similar to the human proteins [[PCNT]] and [[AKAP9]]). These complexes are then anchored at the [[centriole]] to begin formation of the centrosome.<ref name="pmid21694707">{{cite journal | vauthors = Gopalakrishnan J, Mennella V, Blachon S, Zhai B, Smith AH, Megraw TL, Nicastro D, Gygi SP, Agard DA, Avidor-Reiss T | title = Sas-4 provides a scaffold for cytoplasmic complexes and tethers them in a centrosome | journal = Nature Communications | volume = 2 | issue =  | pages = 359 | year = 2011 | pmid = 21694707 | pmc = 3677532 | doi = 10.1038/ncomms1367 | bibcode = 2011NatCo...2E.359G }}</ref>
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Centromere protein J
| HGNCid = 17272
| Symbol = CENPJ
| AltSymbols =; LAP; LIP1; BM032; CPAP; MCPH6; MGC131581; MGC131582; MGC142222; MGC142224
| OMIM = 609279
| ECnumber = 
| Homologene = 10204
| MGIid = 2684927
| GeneAtlas_image1 = PBB_GE_CENPJ_220885_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_CENPJ_gnf1h01806_at_tn.png
| GeneAtlas_image3 = PBB_GE_CENPJ_gnf1h02733_at_tn.png
| Function = {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0015631 |text = tubulin binding}}
| Component = {{GNF_GO|id=GO:0005856 |text = cytoskeleton}} {{GNF_GO|id=GO:0005874 |text = microtubule}} {{GNF_GO|id=GO:0008275 |text = gamma-tubulin small complex}}
| Process = {{GNF_GO|id=GO:0007020 |text = microtubule nucleation}} {{GNF_GO|id=GO:0046785 |text = microtubule polymerization}} {{GNF_GO|id=GO:0051301 |text = cell division}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 55835
    | Hs_Ensembl = ENSG00000151849
    | Hs_RefseqProtein = NP_060921
    | Hs_RefseqmRNA = NM_018451
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 13
    | Hs_GenLoc_start = 24355171
    | Hs_GenLoc_end = 24395018
    | Hs_Uniprot = Q9HC77
    | Mm_EntrezGene = 219103
    | Mm_Ensembl = ENSMUSG00000064128
    | Mm_RefseqmRNA = NM_001014996
    | Mm_RefseqProtein = NP_001014996
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 14
    | Mm_GenLoc_start = 55480871
    | Mm_GenLoc_end = 55525942
    | Mm_Uniprot = 
  }}
}}
'''Centromere protein J''', also known as '''CENPJ''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: CENPJ centromere protein J| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55835| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
==Model organisms==
{{PBB_Summary
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: right;" |
| section_title =  
|+ ''Cenpj'' knockout mouse phenotype
| summary_text = This gene encodes a protein that belongs to the centromere protein family. During cell division, this protein plays a structural role in the maintenance of centrosome integrity and normal spindle morphology, and it is involved in microtubule disassembly at the centrosome. This protein can function as a transcriptional coactivator in the Stat5 signaling pathway, and also as a coactivator of NF-kappaB-mediated transcription, likely via its interaction with the coactivator p300/CREB-binding protein. Mutations in this gene are associated with primary autosomal recessive microcephaly, a disorder characterized by severely reduced brain size and mental retardation.<ref name="entrez">{{cite web | title = Entrez Gene: CENPJ centromere protein J| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55835| accessdate = }}</ref>
|-
}}
! Characteristic!! Phenotype


==References==
|-
{{reflist|2}}
| [[Homozygote]] viability || bgcolor="#C40000"|Abnormal
==Further reading==
|-
{{refbegin | 2}}
| [[Recessive]] lethal study || bgcolor="#488ED3"|Normal
{{PBB_Further_reading
|-
| citations =  
| Homozygous Fertility || bgcolor="#488ED3"|Normal
*{{cite journal  | author=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= }}
|-
*{{cite journal  | author=Hung LY, Tang CJ, Tang TK |title=Protein 4.1 R-135 interacts with a novel centrosomal protein (CPAP) which is associated with the gamma-tubulin complex. |journal=Mol. Cell. Biol. |volume=20 |issue= 20 |pages= 7813-25 |year= 2000 |pmid= 11003675 |doi=  }}
| Body weight || bgcolor="#C40000"|Abnormal<ref name="Body weight">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBKA/weight-curves/ |title=Body weight data for Cenpj |publisher=Wellcome Trust Sanger Institute}}</ref>
*{{cite journal  | author=Iouzalen N, Andreae S, Hannier S, Triebel F |title=LAP, a lymphocyte activation gene-3 (LAG-3)-associated protein that binds to a repeated EP motif in the intracellular region of LAG-3, may participate in the down-regulation of the CD3/TCR activation pathway. |journal=Eur. J. Immunol. |volume=31 |issue= 10 |pages= 2885-91 |year= 2001 |pmid= 11592063 |doi= }}
|-
*{{cite journal  | author=Tchernev VT, Mansfield TA, Giot L, ''et al.'' |title=The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins. |journal=Mol. Med. |volume=8 |issue= 1 |pages= 56-64 |year= 2002 |pmid= 11984006 |doi= }}
| [[Open Field (animal test)|Anxiety]] || bgcolor="#C40000"|Abnormal<ref name="Anxiety">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBKA/open-field/ |title=Anxiety data for Cenpj |publisher=Wellcome Trust Sanger Institute}}</ref>
*{{cite journal  | author=Peng B, Sutherland KD, Sum EY, ''et al.'' |title=CPAP is a novel stat5-interacting cofactor that augments stat5-mediated transcriptional activity. |journal=Mol. Endocrinol. |volume=16 |issue= 9 |pages= 2019-33 |year= 2003 |pmid= 12198240 |doi= }}
|-
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |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 }}
| Neurological assessment || bgcolor="#488ED3"|Normal
*{{cite journal  | author=Leal GF, Roberts E, Silva EO, ''et al.'' |title=A novel locus for autosomal recessive primary microcephaly (MCPH6) maps to 13q12.2. |journal=J. Med. Genet. |volume=40 |issue= 7 |pages= 540-2 |year= 2003 |pmid= 12843329 |doi=  }}
|-
*{{cite journal  | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |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 }}
| Grip strength || bgcolor="#488ED3"|Normal
*{{cite journal  | author=Hung LY, Chen HL, Chang CW, ''et al.'' |title=Identification of a novel microtubule-destabilizing motif in CPAP that binds to tubulin heterodimers and inhibits microtubule assembly. |journal=Mol. Biol. Cell |volume=15 |issue= 6 |pages= 2697-706 |year= 2004 |pmid= 15047868 |doi= 10.1091/mbc.E04-02-0121 }}
|-
*{{cite journal  | author=Dunham A, Matthews LH, Burton J, ''et al.'' |title=The DNA sequence and analysis of human chromosome 13. |journal=Nature |volume=428 |issue= 6982 |pages= 522-8 |year= 2004 |pmid= 15057823 |doi= 10.1038/nature02379 }}
| [[Hot plate test|Hot plate]] || bgcolor="#488ED3"|Normal
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |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 }}
|-
*{{cite journal  | author=Koyanagi M, Hijikata M, Watashi K, ''et al.'' |title=Centrosomal P4.1-associated protein is a new member of transcriptional coactivators for nuclear factor-kappaB. |journal=J. Biol. Chem. |volume=280 |issue= 13 |pages= 12430-7 |year= 2005 |pmid= 15687488 |doi= 10.1074/jbc.M410420200 }}
| [[Dysmorphology]] || bgcolor="#C40000"|Abnormal<ref name="Dysmorphology">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBKA/dysmorphology/ |title=Dysmorphology data for Cenpj |publisher=Wellcome Trust Sanger Institute}}</ref>
*{{cite journal | author=Bond J, Roberts E, Springell K, ''et al.'' |title=A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size. |journal=Nat. Genet. |volume=37 |issue= 4 |pages= 353-5 |year= 2005 |pmid= 15793586 |doi= 10.1038/ng1539 }}
|-
*{{cite journal | author=Cho JH, Chang CJ, Chen CY, Tang TK |title=Depletion of CPAP by RNAi disrupts centrosome integrity and induces multipolar spindles. |journal=Biochem. Biophys. Res. Commun. |volume=339 |issue= 3 |pages= 742-7 |year= 2006 |pmid= 16316625 |doi= 10.1016/j.bbrc.2005.11.074 }}
| [[Indirect calorimetry]] || bgcolor="#C40000"|Abnormal<ref name="Indirect calorimetry">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBKA/indirect-calorimetry/ |title=Indirect calorimetry data for Cenpj |publisher=Wellcome Trust Sanger Institute}}</ref>
*{{cite journal | author=Kimura K, Wakamatsu A, Suzuki Y, ''et al.'' |title=Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. |journal=Genome Res. |volume=16 |issue= 1 |pages= 55-65 |year= 2006 |pmid= 16344560 |doi= 10.1101/gr.4039406 }}
|-
*{{cite journal  | author=Chen CY, Olayioye MA, Lindeman GJ, Tang TK |title=CPAP interacts with 14-3-3 in a cell cycle-dependent manner. |journal=Biochem. Biophys. Res. Commun. |volume=342 |issue= 4 |pages= 1203-10 |year= 2006 |pmid= 16516142 |doi= 10.1016/j.bbrc.2006.02.089 }}
| [[Glucose tolerance test]] || bgcolor="#C40000"|Abnormal<ref name="Glucose tolerance test">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBKA/glucose-tolerance-ip/ |title=Glucose tolerance test data for Cenpj |publisher=Wellcome Trust Sanger Institute}}</ref>
*{{cite journal  | author=Evans PD, Vallender EJ, Lahn BT |title=Molecular evolution of the brain size regulator genes CDK5RAP2 and CENPJ. |journal=Gene |volume=375 |issue= |pages= 75-9 |year= 2006 |pmid= 16631324 |doi= 10.1016/j.gene.2006.02.019 }}
|-
*{{cite journal  | author=Lim J, Hao T, Shaw C, ''et al.'' |title=A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. |journal=Cell |volume=125 |issue= 4 |pages= 801-14 |year= 2006 |pmid= 16713569 |doi= 10.1016/j.cell.2006.03.032 }}
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
*{{cite journal | author=Gul A, Hassan MJ, Hussain S, ''et al.'' |title=A novel deletion mutation in CENPJ gene in a Pakistani family with autosomal recessive primary microcephaly. |journal=J. Hum. Genet. |volume=51 |issue= 9 |pages= 760-4 |year= 2006 |pmid= 16900296 |doi= 10.1007/s10038-006-0017-1 }}
|-
}}
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#C40000"|Abnormal<ref name="DEXA">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBKA/body-composition-dexa/ |title=DEXA data for Cenpj |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Radiography]] || bgcolor="#C40000"|Abnormal<ref name="Radiography">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBKA/x-ray-imaging/ |title=Radiography data for Cenpj |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| Body temperature || bgcolor="#488ED3"|Normal
|-
| Eye morphology || bgcolor="#488ED3"|Normal
|-
| [[Clinical chemistry]] || bgcolor="#C40000"|Abnormal<ref name="Clinical chemistry">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBKA/plasma-chemistry/ |title=Clinical chemistry data for Cenpj |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Haematology]] || bgcolor="#488ED3"|Normal
|-
| [[Peripheral blood lymphocyte]]s || bgcolor="#C40000"|Abnormal<ref name="Peripheral blood lymphocytes">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBKA/peripheral-blood-lymphocytes/ |title=Peripheral blood lymphocytes data for Cenpj |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Micronucleus test]] || bgcolor="#C40000"|Abnormal
|-
| Heart weight || bgcolor="#488ED3"|Normal
|-
| Brain histopathology || bgcolor="#C40000"|Abnormal
|-
| Eye Histopathology || bgcolor="#C40000"|Abnormal
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Salmonella'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBKA/salmonella-challenge/ |title=''Salmonella'' infection data for Cenpj |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/MBKA/citrobacter-challenge/ |title=''Citrobacter'' infection data for Cenpj |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 CENPJ function. A conditional [[knockout mouse]] line, called ''Cenpj<sup>tm1a(EUCOMM)Wtsi</sup>''<ref name="allele_ref">{{cite web |url=http://www.knockoutmouse.org/martsearch/search?query=Cenpj |title=International Knockout Mouse Consortium}}</ref><ref name="mgi_allele_ref">{{cite web |url=http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4432238 |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 = 337–342 | 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 thirteen significant abnormalities were observed. [[Homozygous]] mutants were [[Perinatal mortality|subviable]], had a decreased body weight, abnormal [[Open Field (animal test)|open field]], body composition, X-ray imaging, peripheral blood lymphocytes and [[indirect calorimetry]] parameters, abnormal head, genitalia and tail morphology, an impaired [[glucose tolerance]], [[hypoalbuminemia]], a 1.5 fold increase in [[micronucleus test|micronuclei]], a reduction in [[dentate gyrus]] length and abnormal [[corneal epithelium]] and endothelium.<ref name="mgp_reference" />
 
A more detailed analysis revealed this mutant to model a number of aspects of Seckel syndrome (type 4). The authors concluded that, "increased cell death due to mitotic failure during [[embryonic development]] is likely to contribute to the proportionate [[dwarfism]]" that is characteristic of the disorder.<ref name="pmid23166506">{{cite journal | vauthors = McIntyre RE, Lakshminarasimhan Chavali P, Ismail O, Carragher DM, Sanchez-Andrade G, Forment JV, Fu B, Del Castillo Velasco-Herrera M, Edwards A, van der Weyden L, Yang F, Ramirez-Solis R, Estabel J, Gallagher FA, Logan DW, Arends MJ, Tsang SH, Mahajan VB, Scudamore CL, White JK, Jackson SP, Gergely F, Adams DJ | title = Disruption of mouse Cenpj, a regulator of centriole biogenesis, phenocopies Seckel syndrome | journal = PLoS Genetics | volume = 8 | issue = 11 | pages = e1003022 | year = 2012 | pmid = 23166506 | pmc = 3499256 | doi = 10.1371/journal.pgen.1003022 }}</ref>
 
== Interactions ==
 
CENPJ has been shown to [[Protein-protein interaction|interact]] with [[EPB41]].<ref name="pmid11003675"/>
 
== References ==
{{reflist|32em}}
 
== Further reading ==
{{refbegin|32em}}
* {{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 = Sep 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 }}
* {{cite journal | vauthors = Iouzalen N, Andreae S, Hannier S, Triebel F | title = LAP, a lymphocyte activation gene-3 (LAG-3)-associated protein that binds to a repeated EP motif in the intracellular region of LAG-3, may participate in the down-regulation of the CD3/TCR activation pathway | journal = European Journal of Immunology | volume = 31 | issue = 10 | pages = 2885–91 | date = Oct 2001 | pmid = 11592063 | doi = 10.1002/1521-4141(2001010)31:10<2885::AID-IMMU2885>3.0.CO;2-2 }}
* {{cite journal | vauthors = Tchernev VT, Mansfield TA, Giot L, Kumar AM, Nandabalan K, Li Y, Mishra VS, Detter JC, Rothberg JM, Wallace MR, Southwick FS, Kingsmore SF | title = The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins | journal = Molecular Medicine | volume = 8 | issue = 1 | pages = 56–64 | date = Jan 2002 | pmid = 11984006 | pmc = 2039936 | doi =  }}
* {{cite journal | vauthors = Peng B, Sutherland KD, Sum EY, Olayioye M, Wittlin S, Tang TK, Lindeman GJ, Visvader JE | title = CPAP is a novel stat5-interacting cofactor that augments stat5-mediated transcriptional activity | journal = Molecular Endocrinology | volume = 16 | issue = 9 | pages = 2019–33 | date = Sep 2002 | pmid = 12198240 | doi = 10.1210/me.2002-0108 }}
* {{cite journal | vauthors = Leal GF, Roberts E, Silva EO, Costa SM, Hampshire DJ, Woods CG | title = A novel locus for autosomal recessive primary microcephaly (MCPH6) maps to 13q12.2 | journal = Journal of Medical Genetics | volume = 40 | issue = 7 | pages = 540–2 | date = Jul 2003 | pmid = 12843329 | pmc = 1735531 | doi = 10.1136/jmg.40.7.540 }}
* {{cite journal | vauthors = Hung LY, Chen HL, Chang CW, Li BR, Tang TK | title = Identification of a novel microtubule-destabilizing motif in CPAP that binds to tubulin heterodimers and inhibits microtubule assembly | journal = Molecular Biology of the Cell | volume = 15 | issue = 6 | pages = 2697–706 | date = Jun 2004 | pmid = 15047868 | pmc = 420094 | doi = 10.1091/mbc.E04-02-0121 }}
* {{cite journal | vauthors = Koyanagi M, Hijikata M, Watashi K, Masui O, Shimotohno K | title = Centrosomal P4.1-associated protein is a new member of transcriptional coactivators for nuclear factor-kappaB | journal = The Journal of Biological Chemistry | volume = 280 | issue = 13 | pages = 12430–7 | date = Apr 2005 | pmid = 15687488 | doi = 10.1074/jbc.M410420200 }}
* {{cite journal | vauthors = Bond J, Roberts E, Springell K, Lizarraga SB, Lizarraga S, Scott S, Higgins J, Hampshire DJ, Morrison EE, Leal GF, Silva EO, Costa SM, Baralle D, Raponi M, Karbani G, Rashid Y, Jafri H, Bennett C, Corry P, Walsh CA, Woods CG | title = A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size | journal = Nature Genetics | volume = 37 | issue = 4 | pages = 353–5 | date = Apr 2005 | pmid = 15793586 | doi = 10.1038/ng1539 }}
* {{cite journal | vauthors = Cho JH, Chang CJ, Chen CY, Tang TK | title = Depletion of CPAP by RNAi disrupts centrosome integrity and induces multipolar spindles | journal = Biochemical and Biophysical Research Communications | volume = 339 | issue = 3 | pages = 742–7 | date = Jan 2006 | pmid = 16316625 | doi = 10.1016/j.bbrc.2005.11.074 }}
* {{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 = Chen CY, Olayioye MA, Lindeman GJ, Tang TK | title = CPAP interacts with 14-3-3 in a cell cycle-dependent manner | journal = Biochemical and Biophysical Research Communications | volume = 342 | issue = 4 | pages = 1203–10 | date = Apr 2006 | pmid = 16516142 | doi = 10.1016/j.bbrc.2006.02.089 }}
* {{cite journal | vauthors = Evans PD, Vallender EJ, Lahn BT | title = Molecular evolution of the brain size regulator genes CDK5RAP2 and CENPJ | journal = Gene | volume = 375 | issue =  | pages = 75–9 | date = Jun 2006 | pmid = 16631324 | doi = 10.1016/j.gene.2006.02.019 }}
* {{cite journal | vauthors = Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY | title = A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration | journal = Cell | volume = 125 | issue = 4 | pages = 801–14 | date = May 2006 | pmid = 16713569 | doi = 10.1016/j.cell.2006.03.032 }}
{{refend}}
{{refend}}


{{protein-stub}}
==External links==
* {{UCSC gene info|CENPJ}}
{{Chromosome genetics}}
{{Chromosome genetics}}
{{WikiDoc Sources}}
 
[[Category:Genes mutated in mice]]

Latest revision as of 11:32, 9 January 2019

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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Wikidata
View/Edit Human

Centromere protein J is a protein that in humans is encoded by the CENPJ gene.[1][2] It is also known as centrosomal P4.1-associated protein (CPAP). During cell division, this protein plays a structural role in the maintenance of centrosome integrity and normal spindle morphology, and it is involved in microtubule disassembly at the centrosome. This protein can function as a transcriptional coactivator in the Stat5 signaling pathway, and also as a coactivator of NF-kappaB-mediated transcription, likely via its interaction with the coactivator p300/CREB-binding protein. Mutations in this gene are associated with Seckel syndrome and primary autosomal recessive microcephaly, a disorder characterized by severely reduced brain size and mental retardation.[2][3][4]

The Drosophila ortholog, sas-4, has been shown to be a scaffold for a cytoplasmic complex of Cnn, Asl, CP-190, tubulin and D-PLP (similar to the human proteins PCNT and AKAP9). These complexes are then anchored at the centriole to begin formation of the centrosome.[5]

Model organisms

Model organisms have been used in the study of CENPJ function. A conditional knockout mouse line, called Cenpjtm1a(EUCOMM)Wtsi[19][20] 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.[21][22][23]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[17][24] Twenty five tests were carried out on mutant mice and thirteen significant abnormalities were observed. Homozygous mutants were subviable, had a decreased body weight, abnormal open field, body composition, X-ray imaging, peripheral blood lymphocytes and indirect calorimetry parameters, abnormal head, genitalia and tail morphology, an impaired glucose tolerance, hypoalbuminemia, a 1.5 fold increase in micronuclei, a reduction in dentate gyrus length and abnormal corneal epithelium and endothelium.[17]

A more detailed analysis revealed this mutant to model a number of aspects of Seckel syndrome (type 4). The authors concluded that, "increased cell death due to mitotic failure during embryonic development is likely to contribute to the proportionate dwarfism" that is characteristic of the disorder.[25]

Interactions

CENPJ has been shown to interact with EPB41.[1]

References

  1. ↑ 1.0 1.1 Hung LY, Tang CJ, Tang TK (Oct 2000). "Protein 4.1 R-135 interacts with a novel centrosomal protein (CPAP) which is associated with the gamma-tubulin complex". Molecular and Cellular Biology. 20 (20): 7813–25. doi:10.1128/MCB.20.20.7813-7825.2000. PMC 86375. PMID 11003675.
  2. ↑ 2.0 2.1 "Entrez Gene: CENPJ centromere protein J".
  3. ↑ Al-Dosari MS, Shaheen R, Colak D, Alkuraya FS (Jun 2010). "Novel CENPJ mutation causes Seckel syndrome". Journal of Medical Genetics. 47 (6): 411–4. doi:10.1136/jmg.2009.076646. PMID 20522431.
  4. ↑ Gul A, Hassan MJ, Hussain S, Raza SI, Chishti MS, Ahmad W (2006). "A novel deletion mutation in CENPJ gene in a Pakistani family with autosomal recessive primary microcephaly". Journal of Human Genetics. 51 (9): 760–4. doi:10.1007/s10038-006-0017-1. PMID 16900296.
  5. ↑ Gopalakrishnan J, Mennella V, Blachon S, Zhai B, Smith AH, Megraw TL, Nicastro D, Gygi SP, Agard DA, Avidor-Reiss T (2011). "Sas-4 provides a scaffold for cytoplasmic complexes and tethers them in a centrosome". Nature Communications. 2: 359. Bibcode:2011NatCo...2E.359G. doi:10.1038/ncomms1367. PMC 3677532. PMID 21694707.
  6. ↑ "Body weight data for Cenpj". Wellcome Trust Sanger Institute.
  7. ↑ "Anxiety data for Cenpj". Wellcome Trust Sanger Institute.
  8. ↑ "Dysmorphology data for Cenpj". Wellcome Trust Sanger Institute.
  9. ↑ "Indirect calorimetry data for Cenpj". Wellcome Trust Sanger Institute.
  10. ↑ "Glucose tolerance test data for Cenpj". Wellcome Trust Sanger Institute.
  11. ↑ "DEXA data for Cenpj". Wellcome Trust Sanger Institute.
  12. ↑ "Radiography data for Cenpj". Wellcome Trust Sanger Institute.
  13. ↑ "Clinical chemistry data for Cenpj". Wellcome Trust Sanger Institute.
  14. ↑ "Peripheral blood lymphocytes data for Cenpj". Wellcome Trust Sanger Institute.
  15. ↑ "Salmonella infection data for Cenpj". Wellcome Trust Sanger Institute.
  16. ↑ "Citrobacter infection data for Cenpj". Wellcome Trust Sanger Institute.
  17. ↑ 17.0 17.1 17.2 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  18. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  19. ↑ "International Knockout Mouse Consortium".
  20. ↑ "Mouse Genome Informatics".
  21. ↑ 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 (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  22. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  23. ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  24. ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
  25. ↑ McIntyre RE, Lakshminarasimhan Chavali P, Ismail O, Carragher DM, Sanchez-Andrade G, Forment JV, Fu B, Del Castillo Velasco-Herrera M, Edwards A, van der Weyden L, Yang F, Ramirez-Solis R, Estabel J, Gallagher FA, Logan DW, Arends MJ, Tsang SH, Mahajan VB, Scudamore CL, White JK, Jackson SP, Gergely F, Adams DJ (2012). "Disruption of mouse Cenpj, a regulator of centriole biogenesis, phenocopies Seckel syndrome". PLoS Genetics. 8 (11): e1003022. doi:10.1371/journal.pgen.1003022. PMC 3499256. PMID 23166506.

Further reading

External links

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