| Structural highlights
Function
BCCIP_HUMAN During interphase, required for microtubule organizing and anchoring activities. During mitosis, required for the organization and stabilization of the spindle pole (PubMed:28394342). Isoform 2/alpha is particularly important for the regulation of microtubule anchoring, microtubule stability, spindle architecture and spindle orientation, compared to isoform 1/beta (PubMed:28394342). May promote cell cycle arrest by enhancing the inhibition of CDK2 activity by CDKN1A. May be required for repair of DNA damage by homologous recombination in conjunction with BRCA2. May not be involved in non-homologous end joining (NHEJ).[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
BCCIP was isolated based on its interactions with tumor suppressors BRCA2 and p21. Knockdown or knockout of BCCIP causes embryonic lethality in mice. BCCIP deficient cells exhibit impaired cell proliferation and chromosome instability. BCCIP also plays a key role in biogenesis of ribosome 60S subunits. BCCIP is conserved from yeast to humans, but it has no discernible sequence similarity to proteins of known structures. Here we report two crystal structures of an N-terminal truncated human BCCIPbeta, consisting of residues 61-314. Structurally BCCIP is similar to GCN5-related acetyltransferases (GNATs) but contains different sequence motifs. Moreover, both acetyl-CoA and substrate-binding grooves are altered in BCCIP. A large 19-residue flap over the putative CoA binding site adopts either an open or closed conformation in BCCIP. The substrate binding groove is significantly reduced in size and is positively charged despite the acidic isoelectric point of BCCIP. BCCIP has potential binding sites for partner proteins and may have enzymatic activity.
Structure of human BCCIP and implications for binding and modification of partner proteins.,Choi WS, Liu B, Shen Z, Yang W Protein Sci. 2021 Mar;30(3):693-699. doi: 10.1002/pro.4026. Epub 2021 Jan 29. PMID:33452718[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. 2000 Oct 6;275(40):31145-54. PMID:10878006 doi:10.1074/jbc.M003031200
- ↑ Meng X, Liu J, Shen Z. Inhibition of G1 to S cell cycle progression by BCCIP beta. Cell Cycle. 2004 Mar;3(3):343-8. Epub 2004 Mar 1 PMID:14726710
- ↑ Meng X, Lu H, Shen Z. BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1. Cell Cycle. 2004 Nov;3(11):1457-62. PMID:15539944 doi:10.4161/cc.3.11.1213
- ↑ Lu H, Guo X, Meng X, Liu J, Allen C, Wray J, Nickoloff JA, Shen Z. The BRCA2-interacting protein BCCIP functions in RAD51 and BRCA2 focus formation and homologous recombinational repair. Mol Cell Biol. 2005 Mar;25(5):1949-57. PMID:15713648 doi:10.1128/MCB.25.5.1949-1957.2005
- ↑ Lu H, Yue J, Meng X, Nickoloff JA, Shen Z. BCCIP regulates homologous recombination by distinct domains and suppresses spontaneous DNA damage. Nucleic Acids Res. 2007;35(21):7160-70. PMID:17947333 doi:10.1093/nar/gkm732
- ↑ Huhn SC, Liu J, Ye C, Lu H, Jiang X, Feng X, Ganesan S, White E, Shen Z. Regulation of spindle integrity and mitotic fidelity by BCCIP. Oncogene. 2017 Aug 17;36(33):4750-4766. PMID:28394342 doi:10.1038/onc.2017.92
- ↑ Choi WS, Liu B, Shen Z, Yang W. Structure of human BCCIP and implications for binding and modification of partner proteins. Protein Sci. 2021 Mar;30(3):693-699. PMID:33452718 doi:10.1002/pro.4026
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