CENPJ

CENPJ
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases CENPJ, BM032, CENP-J, CPAP, LAP, LIP1, MCPH6, SASS4, SCKL4, Sas-4, centromere protein J
External IDs MGI: 2684927 HomoloGene: 10204 GeneCards: CENPJ
RNA expression pattern




More reference expression data
Orthologs
Species Human Mouse
Entrez

55835

219103

Ensembl

ENSG00000151849

ENSMUSG00000064128

UniProt

Q9HC77

Q569L8

RefSeq (mRNA)

NM_018451

NM_001014996

RefSeq (protein)

NP_060921.3

NP_001014996.2

Location (UCSC) Chr 13: 24.88 – 24.92 Mb Chr 14: 56.53 – 56.57 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

Centromere protein J is a protein that in humans is encoded by the CENPJ gene.[3][4] 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.[4][5][6]

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

Model organisms have been used in the study of CENPJ function. A conditional knockout mouse line, called Cenpjtm1a(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]

Interactions

CENPJ has been shown to interact with EPB41.[3]

References

  1. "Human PubMed Reference:".
  2. "Mouse PubMed Reference:".
  3. 1 2 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 86375Freely accessible. PMID 11003675.
  4. 1 2 "Entrez Gene: CENPJ centromere protein J".
  5. 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.
  6. 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.
  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. doi:10.1038/ncomms1367. 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. 1 2 3 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.
  20. Mouse Resources Portal, Wellcome Trust Sanger Institute.
  21. "International Knockout Mouse Consortium".
  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 3572410Freely accessible. 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.
  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 3218837Freely accessible. 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 3499256Freely accessible. PMID 23166506.

Further reading

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