BCCIP explained

BRCA2 and CDKN1A-interacting protein is a protein that is encoded by the BCCIP gene in humans.^{[1] [2] [3]}

This gene product was isolated based on its interaction with BRCA2 and p21 proteins. It is an evolutionarily conserved nuclear protein with multiple interacting domains. The N-terminal half shares moderate homology with regions of calmodulin and M-calpain, suggesting that it may also bind calcium. Functional studies indicate that this protein may be an important cofactor for BRCA2 in tumor suppression, and a modulator of CDK2 kinase activity via p21. Several transcript variants encoding different isoforms have been described for this gene.

Interactions

BCCIP has been shown to interact with BRCA2, P21, and PTPmu (PTPRM)^[4]

Further reading

• Coleman RA, Rao P, Fogelsong RJ, Bardes ES . 2-Bromopalmitoyl-CoA and 2-bromopalmitate: promiscuous inhibitors of membrane-bound enzymes. . Biochim. Biophys. Acta . 1125 . 2 . 203–9 . 1992 . 1571364 . 10.1016/0005-2760(92)90046-X.
• Machackova E, Damborsky J, Valik D, Foretova L . Novel germline BRCA1 and BRCA2 mutations in breast and breast/ovarian cancer families from the Czech Republic. . Hum. Mutat. . 18 . 6 . 545 . 2002 . 11748848 . 10.1002/humu.1232 . 8549550 . free .
• Armakolas A, Ladopoulou A, Konstantopoulou I . BRCA2 gene mutations in Greek patients with familial breast cancer. . Hum. Mutat. . 19 . 1 . 81–2 . 2002 . 11754111 . 10.1002/humu.9003 . 25598124 . etal. free .
• Robson M, Scheuer L, Nafa K . Unique de novo mutation of BRCA2 in a woman with early onset breast cancer. . J. Med. Genet. . 39 . 2 . 126–8 . 2002 . 11836363 . 10.1136/jmg.39.2.126. 1735025 . etal.
• Strausberg RL, Feingold EA, Grouse LH . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Meng X, Liu J, Shen Z . Genomic structure of the human BCCIP gene and its expression in cancer. . Gene . 302 . 1–2 . 139–46 . 2003 . 12527204 . 10.1016/S0378-1119(02)01098-3 .
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Meng X, Liu J, Shen Z . Inhibition of G1 to S cell cycle progression by BCCIP beta. . Cell Cycle . 3 . 3 . 343–8 . 2004 . 14726710 . 10.4161/cc.3.3.672. free .
• Deloukas P, Earthrowl ME, Grafham DV . The DNA sequence and comparative analysis of human chromosome 10. . Nature . 429 . 6990 . 375–81 . 2004 . 15164054 . 10.1038/nature02462 . 2004Natur.429..375D . etal. free .
• Colland F, Jacq X, Trouplin V . Functional proteomics mapping of a human signaling pathway. . Genome Res. . 14 . 7 . 1324–32 . 2004 . 15231748 . 10.1101/gr.2334104 . 442148 . etal.
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Meng X, Lu H, Shen Z . BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1. . Cell Cycle . 3 . 11 . 1457–62 . 2007 . 15539944 . 10.4161/cc.3.11.1213. free .
• Lu H, Guo X, Meng X . The BRCA2-interacting protein BCCIP functions in RAD51 and BRCA2 focus formation and homologous recombinational repair. . Mol. Cell. Biol. . 25 . 5 . 1949–57 . 2005 . 15713648 . 10.1128/MCB.25.5.1949-1957.2005 . 549367 . etal.
• Stelzl U, Worm U, Lalowski M . A human protein-protein interaction network: a resource for annotating the proteome. . Cell . 122 . 6 . 957–68 . 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . etal. 11858/00-001M-0000-0010-8592-0 . 8235923 . free .
• Rual JF, Venkatesan K, Hao T . Towards a proteome-scale map of the human protein-protein interaction network. . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 . etal.
• Olsen JV, Blagoev B, Gnad F . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. . Cell . 127 . 3 . 635–48 . 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . etal. free .
• Meng X, Yue J, Liu Z, Shen Z . Abrogation of the transactivation activity of p53 by BCCIP down-regulation. . J. Biol. Chem. . 282 . 3 . 1570–6 . 2007 . 17135243 . 10.1074/jbc.M607520200 . 2679999 . free .
• Ewing RM, Chu P, Elisma F . Large-scale mapping of human protein-protein interactions by mass spectrometry. . Mol. Syst. Biol. . 3 . 1. 89 . 2007 . 17353931 . 10.1038/msb4100134 . 1847948 . etal.

Notes and References

1. Liu J, Yuan Y, Huan J, Shen Z . Inhibition of breast and brain cancer cell growth by BCCIPalpha, an evolutionarily conserved nuclear protein that interacts with BRCA2 . Oncogene . 20 . 3 . 336–45 . Apr 2001 . 11313963 . 10.1038/sj.onc.1204098 . free .
2. Ono T, Kitaura H, Ugai H, Murata T, Yokoyama KK, Iguchi-Ariga SM, Ariga H . TOK-1, a novel p21Cip1-binding protein that cooperatively enhances p21-dependent inhibitory activity toward CDK2 kinase . J Biol Chem . 275 . 40 . 31145–54 . Oct 2000 . 10878006 . 10.1074/jbc.M003031200 . free .
3. Web site: Entrez Gene: BCCIP BRCA2 and CDKN1A interacting protein.
4. Phillips-Mason PJ, Mourton T, Major DL, Brady-Kalnay SM. BCCIP associates with the receptor protein tyrosine phosphatase PTPmu. . J Cell Biochem . 2008 . 105 . 4 . 1059–72 . 18773424 . 10.1002/jcb.21907 . 2758318 .