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4r8q

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Structure and substrate recruitment of the human spindle checkpoint kinase bub1

Structural highlights

4r8q is a 1 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 3e7e. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.31Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BUB1_HUMAN Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Plays an important role in defining SGOL1 localization and thereby affects sister chromatid cohesion. Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

References

↑ Seeley TW, Wang L, Zhen JY. Phosphorylation of human MAD1 by the BUB1 kinase in vitro. Biochem Biophys Res Commun. 1999 Apr 13;257(2):589-95. PMID:10198256 doi:http://dx.doi.org/S0006-291X(99)90514-4
↑ Johnson VL, Scott MI, Holt SV, Hussein D, Taylor SS. Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression. J Cell Sci. 2004 Mar 15;117(Pt 8):1577-89. PMID:15020684 doi:http://dx.doi.org/10.1242/jcs.01006
↑ Tang Z, Shu H, Oncel D, Chen S, Yu H. Phosphorylation of Cdc20 by Bub1 provides a catalytic mechanism for APC/C inhibition by the spindle checkpoint. Mol Cell. 2004 Nov 5;16(3):387-97. PMID:15525512 doi:http://dx.doi.org/10.1016/j.molcel.2004.09.031
↑ Kitajima TS, Hauf S, Ohsugi M, Yamamoto T, Watanabe Y. Human Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting Shugoshin localization. Curr Biol. 2005 Feb 22;15(4):353-9. PMID:15723797 doi:http://dx.doi.org/S0960982204010267
↑ Qi W, Tang Z, Yu H. Phosphorylation- and polo-box-dependent binding of Plk1 to Bub1 is required for the kinetochore localization of Plk1. Mol Biol Cell. 2006 Aug;17(8):3705-16. Epub 2006 Jun 7. PMID:16760428 doi:http://dx.doi.org/10.1091/mbc.E06-03-0240
↑ Qi W, Yu H. KEN-box-dependent degradation of the Bub1 spindle checkpoint kinase by the anaphase-promoting complex/cyclosome. J Biol Chem. 2007 Feb 9;282(6):3672-9. Epub 2006 Dec 11. PMID:17158872 doi:http://dx.doi.org/10.1074/jbc.M609376200
↑ Klebig C, Korinth D, Meraldi P. Bub1 regulates chromosome segregation in a kinetochore-independent manner. J Cell Biol. 2009 Jun 1;185(5):841-58. doi: 10.1083/jcb.200902128. PMID:19487456 doi:http://dx.doi.org/10.1083/jcb.200902128