CENPJ

CENPJ
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5ITZ
Identifiers
Aliases	CENPJ , BM032, CENP-J, CPAP, LAP, LIP1, MCPH6, SASS4, SCKL4, Sas-4, centromere protein J
External IDs	OMIM: 609279 MGI: 2684927 HomoloGene: 10204 GeneCards: CENPJ
Gene location (Human) Chr. Chromosome 13 (human) [1] Band 13q12.12-q12.13 Start 24,882,279 bp [1] End 24,922,889 bp [1]
Gene location (Mouse) Chr. Chromosome 14 (mouse) [2] Band 14|14 C3 Start 56,764,218 bp [2] End 56,812,882 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sperm left lobe of thyroid gland right lobe of thyroid gland ganglionic eminence Brodmann area 23 cancellous bone rectum right uterine tube canal of the cervix tibial nerve Top expressed in secondary oocyte hand ganglionic eminence primitive streak thymus testicle seminiferous tubule maxillary prominence medial ganglionic eminence medullary collecting duct More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding protein kinase binding protein domain specific binding tubulin binding identical protein binding transcription corepressor activity Cellular component cytoplasm microtubule organizing center gamma-tubulin small complex cytosol centrosome microtubule cytoskeleton centriole nucleoplasm plasma membrane ciliary basal body nucleus Biological process regulation of centriole replication centriole replication microtubule polymerization G2/M transition of mitotic cell cycle microtubule nucleation centriole elongation cell division ciliary basal body-plasma membrane docking regulation of G2/M transition of mitotic cell cycle smoothened signaling pathway motile cilium assembly centrosome duplication centriole assembly positive regulation of non-motile cilium assembly non-motile cilium assembly positive regulation of centriole elongation positive regulation of establishment of protein localization negative regulation of nucleic acid-templated transcription Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 55835 219103 Ensembl ENSG00000151849 ENSMUSG00000064128 UniProt Q9HC77 Q569L8 RefSeq (mRNA) NM_018451 NM_001014996 RefSeq (protein) NP_060921 NP_001014996 NP_001390462 NP_001390463 Location (UCSC) Chr 13: 24.88 – 24.92 Mb Chr 14: 56.76 – 56.81 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Centromere protein J is a protein that in humans is encoded by the CENPJ gene. ^{[5] [6]} 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.

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. ^[7]

Model organisms

Cenpj knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Normal
Homozygous Fertility	Normal
Body weight	Abnormal [8]
Anxiety	Abnormal [9]
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Abnormal [10]
Indirect calorimetry	Abnormal [11]
Glucose tolerance test	Abnormal [12]
Auditory brainstem response	Normal
DEXA	Abnormal [13]
Radiography	Abnormal [14]
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal [15]
Haematology	Normal
Peripheral blood lymphocytes	Abnormal [16]
Micronucleus test	Abnormal
Heart weight	Normal
Brain histopathology	Abnormal
Eye Histopathology	Abnormal
Salmonella infection	Normal [17]
Citrobacter infection	Normal [18]
All tests and analysis from [19] [20]

Model organisms have been used in the study of CENPJ function. A conditional knockout mouse line, called Cenpj^{tm1a(EUCOMM)Wtsi [21] [22]} 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. ^{[23] [24] [25]}

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. ^{[19] [26]} 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. ^[19]

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. ^[27]

Clinical significance

Mutations in CENPJ are associated with Seckel syndrome type 4 and primary autosomal recessive microcephaly, a disorder characterized by severely reduced brain size and intellectual disability. ^{[6] [28] [29]} Interestingly, CENPJ interacts with other microcephaly aossciated proteins such as WDR62 and both coordinate a regulatory function neocortical development and brain growth. ^[30]

Interactions

CENPJ has been shown to interact with EPB41. ^[5]

See also

• CENPE
• CENPF
• CENPT

References

1. GRCh38: Ensembl release 89: ENSG00000151849 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000064128 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. "Entrez Gene: CENPJ centromere protein J".
7. 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...2..359G. doi:10.1038/ncomms1367. PMC   3677532 . PMID   21694707.
8. "Body weight data for Cenpj". Wellcome Trust Sanger Institute.
9. "Anxiety data for Cenpj". Wellcome Trust Sanger Institute.
10. "Dysmorphology data for Cenpj". Wellcome Trust Sanger Institute.
11. "Indirect calorimetry data for Cenpj". Wellcome Trust Sanger Institute.
12. "Glucose tolerance test data for Cenpj". Wellcome Trust Sanger Institute.
13. "DEXA data for Cenpj". Wellcome Trust Sanger Institute.
14. "Radiography data for Cenpj". Wellcome Trust Sanger Institute.
15. "Clinical chemistry data for Cenpj". Wellcome Trust Sanger Institute.
16. "Peripheral blood lymphocytes data for Cenpj". Wellcome Trust Sanger Institute.
17. "Salmonella infection data for Cenpj". Wellcome Trust Sanger Institute.
18. "Citrobacter infection data for Cenpj". Wellcome Trust Sanger Institute.
19. 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. S2CID   85911512.
20. Mouse Resources Portal, Wellcome Trust Sanger Institute.
21. "International Knockout Mouse Consortium".^{[ permanent dead link ]}
22. "Mouse Genome Informatics".
23. 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.
24. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi: 10.1038/474262a . PMID   21677718.
25. 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. S2CID   18872015.
26. 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.
27. 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.
28. 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. S2CID   35159613.
29. 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.
30. Shohayeb, B, et al. (January 2020). "The association of microcephaly protein WDR62 with CPAP/IFT88 is required for cilia formation and neocortical development". Human Molecular Genetics. 29 (2): 248–263. doi:10.1093/hmg/ddz281. PMID   31816041.

Further reading

• Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi: 10.1101/gr.6.9.791 . PMID   8889548.
• Iouzalen N, Andreae S, Hannier S, Triebel F (Oct 2001). "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". European Journal of Immunology. 31 (10): 2885–91. doi:10.1002/1521-4141(2001010)31:10<2885::AID-IMMU2885>3.0.CO;2-2. PMID   11592063. S2CID   26417417.
• Tchernev VT, Mansfield TA, Giot L, Kumar AM, Nandabalan K, Li Y, Mishra VS, Detter JC, Rothberg JM, Wallace MR, Southwick FS, Kingsmore SF (Jan 2002). "The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins". Molecular Medicine. 8 (1): 56–64. doi:10.1007/BF03402003. PMC   2039936 . PMID   11984006.
• Peng B, Sutherland KD, Sum EY, Olayioye M, Wittlin S, Tang TK, Lindeman GJ, Visvader JE (Sep 2002). "CPAP is a novel stat5-interacting cofactor that augments stat5-mediated transcriptional activity". Molecular Endocrinology. 16 (9): 2019–33. doi: 10.1210/me.2002-0108 . PMID   12198240.
• Leal GF, Roberts E, Silva EO, Costa SM, Hampshire DJ, Woods CG (Jul 2003). "A novel locus for autosomal recessive primary microcephaly (MCPH6) maps to 13q12.2". Journal of Medical Genetics. 40 (7): 540–2. doi:10.1136/jmg.40.7.540. PMC   1735531 . PMID   12843329.
• Hung LY, Chen HL, Chang CW, Li BR, Tang TK (Jun 2004). "Identification of a novel microtubule-destabilizing motif in CPAP that binds to tubulin heterodimers and inhibits microtubule assembly". Molecular Biology of the Cell. 15 (6): 2697–706. doi:10.1091/mbc.E04-02-0121. PMC   420094 . PMID   15047868.
• Koyanagi M, Hijikata M, Watashi K, Masui O, Shimotohno K (Apr 2005). "Centrosomal P4.1-associated protein is a new member of transcriptional coactivators for nuclear factor-kappaB". The Journal of Biological Chemistry. 280 (13): 12430–7. doi: 10.1074/jbc.M410420200 . PMID   15687488.
• 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 (Apr 2005). "A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size". Nature Genetics. 37 (4): 353–5. doi:10.1038/ng1539. PMID   15793586. S2CID   1763877.
• Cho JH, Chang CJ, Chen CY, Tang TK (Jan 2006). "Depletion of CPAP by RNAi disrupts centrosome integrity and induces multipolar spindles". Biochemical and Biophysical Research Communications. 339 (3): 742–7. doi:10.1016/j.bbrc.2005.11.074. PMID   16316625.
• 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 (Jan 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC   1356129 . PMID   16344560.
• Chen CY, Olayioye MA, Lindeman GJ, Tang TK (Apr 2006). "CPAP interacts with 14-3-3 in a cell cycle-dependent manner". Biochemical and Biophysical Research Communications. 342 (4): 1203–10. doi:10.1016/j.bbrc.2006.02.089. PMID   16516142.
• Evans PD, Vallender EJ, Lahn BT (Jun 2006). "Molecular evolution of the brain size regulator genes CDK5RAP2 and CENPJ". Gene. 375: 75–9. doi:10.1016/j.gene.2006.02.019. PMID   16631324.
• 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 (May 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi: 10.1016/j.cell.2006.03.032 . PMID   16713569. S2CID   13709685.

External links

• Human CENPJ genome location and CENPJ gene details page in the UCSC Genome Browser .
• Overview of all the structural information available in the PDB for UniProt : Q9HC77 (Centromere protein J) at the PDBe-KB .