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Title: Cenpj  
Author: World Heritage Encyclopedia
Language: English
Subject: Centrosome, Mouse Genetics Project, Pericentriolar material, Centriole, Telomere-binding protein
Collection: Genes Mutated in Mice
Publisher: World Heritage Encyclopedia


Centromere protein J
Symbols  ; BM032; CENP-J; CPAP; LAP; LIP1; MCPH6; SASS4; SCKL4; Sas-4
External IDs GeneCards:
RNA expression pattern
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

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 1
  • Interactions 2
  • References 3
  • Further reading 4

Model organisms

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]


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


  1. ^ a b 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 γ-Tubulin Complex". Mol Cell Biol 20 (20): 7813–25.  
  2. ^ a b "Entrez Gene: CENPJ centromere protein J". 
  3. ^ Al-Dosari MS, Shaheen R, Colak D, Alkuraya FS (2010). "Novel CENPJ mutation causes Seckel syndrome.". J Med Genet 47 (6): 411–4.  
  4. ^ Gul A, Hassan MJ, Hussain S, et al. (2006). "A novel deletion mutation in CENPJ gene in a Pakistani family with autosomal recessive primary microcephaly". J. Hum. Genet. 51 (9): 760–4.  
  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". Nat Commun 2: 359.  
  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. ^ infection data for Cenpj"Salmonella". Wellcome Trust Sanger Institute. 
  16. ^ infection data for Cenpj"Citrobacter". Wellcome Trust Sanger Institute. 
  17. ^ a b c Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7.  
  18. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  19. ^ "International Knockout Mouse Consortium". 
  20. ^ "Mouse Genome Informatics". 
  21. ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342.  
  22. ^ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3.  
  23. ^ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13.  
  24. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224.  
  25. ^ McIntyre RE, Lakshminarasimhan Chavali P, Ismail O, Carragher DM, Sanchez-Andrade G, Forment JV et al. (2012). "Disruption of mouse cenpj, a regulator of centriole biogenesis, phenocopies seckel syndrome.". PLoS Genet 8 (11): e1003022.  

Further reading

  • Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806.  
  • Iouzalen N, Andreae S, Hannier S, Triebel F (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". Eur. J. Immunol. 31 (10): 2885–91.  
  • Tchernev VT, Mansfield TA, Giot L, et al. (2002). "The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins". Mol. Med. 8 (1): 56–64.  
  • Peng B, Sutherland KD, Sum EY, et al. (2003). "CPAP is a novel stat5-interacting cofactor that augments stat5-mediated transcriptional activity". Mol. Endocrinol. 16 (9): 2019–33.  
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903.  
  • Leal GF, Roberts E, Silva EO, et al. (2003). "A novel locus for autosomal recessive primary microcephaly (MCPH6) maps to 13q12.2". J. Med. Genet. 40 (7): 540–2.  
  • Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5.  
  • Hung LY, Chen HL, Chang CW, et al. (2004). "Identification of a Novel Microtubule-destabilizing Motif in CPAP That Binds to Tubulin Heterodimers and Inhibits Microtubule Assembly". Mol. Biol. Cell 15 (6): 2697–706.  
  • Dunham A, Matthews LH, Burton J, et al. (2004). "The DNA sequence and analysis of human chromosome 13". Nature 428 (6982): 522–8.  
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7.  
  • Koyanagi M, Hijikata M, Watashi K, et al. (2005). "Centrosomal P4.1-associated protein is a new member of transcriptional coactivators for nuclear factor-kappaB". J. Biol. Chem. 280 (13): 12430–7.  
  • Bond J, Roberts E, Springell K, et al. (2005). "A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size". Nat. Genet. 37 (4): 353–5.  
  • Cho JH, Chang CJ, Chen CY, Tang TK (2006). "Depletion of CPAP by RNAi disrupts centrosome integrity and induces  
  • Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65.  
  • Chen CY, Olayioye MA, Lindeman GJ, Tang TK (2006). "CPAP interacts with 14-3-3 in a cell cycle-dependent manner". Biochem. Biophys. Res. Commun. 342 (4): 1203–10.  
  • Evans PD, Vallender EJ, Lahn BT (2006). "Molecular evolution of the brain size regulator genes CDK5RAP2 and CENPJ". Gene 375: 75–9.  
  • Lim J, Hao T, Shaw C, et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell 125 (4): 801–14.  
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