5lcw

Structural highlights

Disease

[BUB1B_HUMAN] Mosaic variegated aneuploidy syndrome. Defects in BUB1B are associated with tumor formation. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. MVA1 is caused by biallelic mutations in the BUB1B gene.

Function

[CDC27_HUMAN] Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.^[1] [APC13_HUMAN] Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.^{[2] [3]} [CDC23_HUMAN] Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.^[4] [CDC26_HUMAN] Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. May recruit the E2 ubiquitin-conjugating enzymes to the complex.^[5] [CDC16_HUMAN] Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.^[6] [APC11_HUMAN] Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. May recruit the E2 ubiquitin-conjugating enzymes to the complex.^{[7] [8]} [APC7_HUMAN] Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.^[9] [ANC2_HUMAN] Together with the RING-H2 protein ANAPC11, constitutes the catalytic component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 drives presynaptic differentiation.^{[10] [11]} [CDC20_HUMAN] Required for full ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) and may confer substrate specificity upon the complex. Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 induces presynaptic differentiation.^{[12] [13] [14]} [APC4_HUMAN] Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.^[15] [APC15_HUMAN] Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. In the complex, plays a role in the release of the mitotic checkpoint complex (MCC) from the APC/C: not required for APC/C activity itself, but promotes the turnover of CDC20 and MCC on the APC/C, thereby participating in the responsiveness of the spindle assembly checkpoint. Also required for degradation of CDC20.^[16] [APC1_HUMAN] Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.^[17] [MD2L1_HUMAN] Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Required for the execution of the mitotic checkpoint which monitors the process of kinetochore-spindle attachment and inhibits the activity of the anaphase promoting complex by sequestering CDC20 until all chromosomes are aligned at the metaphase plate.^{[18] [19] [20]} [APC10_HUMAN] Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.^[21] [APC5_HUMAN] Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.^[22] [BUB1B_HUMAN] Essential component of the mitotic checkpoint. Required for normal mitosis progression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. May play a role for tumor suppression.^{[23] [24] [25] [26] [27] [28]} [APC16_HUMAN] Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.^[29]

References

1. ↑ Jin L, Williamson A, Banerjee S, Philipp I, Rape M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell. 2008 May 16;133(4):653-65. doi: 10.1016/j.cell.2008.04.012. PMID:18485873 doi:http://dx.doi.org/10.1016/j.cell.2008.04.012
2. ↑ Schwickart M, Havlis J, Habermann B, Bogdanova A, Camasses A, Oelschlaegel T, Shevchenko A, Zachariae W. Swm1/Apc13 is an evolutionarily conserved subunit of the anaphase-promoting complex stabilizing the association of Cdc16 and Cdc27. Mol Cell Biol. 2004 Apr;24(8):3562-76. PMID:15060174
3. ↑ Jin L, Williamson A, Banerjee S, Philipp I, Rape M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell. 2008 May 16;133(4):653-65. doi: 10.1016/j.cell.2008.04.012. PMID:18485873 doi:http://dx.doi.org/10.1016/j.cell.2008.04.012
4. ↑ Jin L, Williamson A, Banerjee S, Philipp I, Rape M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell. 2008 May 16;133(4):653-65. doi: 10.1016/j.cell.2008.04.012. PMID:18485873 doi:http://dx.doi.org/10.1016/j.cell.2008.04.012
5. ↑ Jin L, Williamson A, Banerjee S, Philipp I, Rape M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell. 2008 May 16;133(4):653-65. doi: 10.1016/j.cell.2008.04.012. PMID:18485873 doi:http://dx.doi.org/10.1016/j.cell.2008.04.012
6. ↑ Jin L, Williamson A, Banerjee S, Philipp I, Rape M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell. 2008 May 16;133(4):653-65. doi: 10.1016/j.cell.2008.04.012. PMID:18485873 doi:http://dx.doi.org/10.1016/j.cell.2008.04.012
7. ↑ Tang Z, Li B, Bharadwaj R, Zhu H, Ozkan E, Hakala K, Deisenhofer J, Yu H. APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex. Mol Biol Cell. 2001 Dec;12(12):3839-51. PMID:11739784
8. ↑ Jin L, Williamson A, Banerjee S, Philipp I, Rape M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell. 2008 May 16;133(4):653-65. doi: 10.1016/j.cell.2008.04.012. PMID:18485873 doi:http://dx.doi.org/10.1016/j.cell.2008.04.012
9. ↑ Jin L, Williamson A, Banerjee S, Philipp I, Rape M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell. 2008 May 16;133(4):653-65. doi: 10.1016/j.cell.2008.04.012. PMID:18485873 doi:http://dx.doi.org/10.1016/j.cell.2008.04.012
10. ↑ Tang Z, Li B, Bharadwaj R, Zhu H, Ozkan E, Hakala K, Deisenhofer J, Yu H. APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex. Mol Biol Cell. 2001 Dec;12(12):3839-51. PMID:11739784
11. ↑ Jin L, Williamson A, Banerjee S, Philipp I, Rape M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell. 2008 May 16;133(4):653-65. doi: 10.1016/j.cell.2008.04.012. PMID:18485873 doi:http://dx.doi.org/10.1016/j.cell.2008.04.012
12. ↑ Kramer ER, Gieffers C, Holzl G, Hengstschlager M, Peters JM. Activation of the human anaphase-promoting complex by proteins of the CDC20/Fizzy family. Curr Biol. 1998 Nov 5;8(22):1207-10. PMID:9811605
13. ↑ Fang G, Yu H, Kirschner MW. Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1. Mol Cell. 1998 Aug;2(2):163-71. PMID:9734353
14. ↑ Fang G, Yu H, Kirschner MW. The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. Genes Dev. 1998 Jun 15;12(12):1871-83. PMID:9637688
15. ↑ Jin L, Williamson A, Banerjee S, Philipp I, Rape M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell. 2008 May 16;133(4):653-65. doi: 10.1016/j.cell.2008.04.012. PMID:18485873 doi:http://dx.doi.org/10.1016/j.cell.2008.04.012
16. ↑ Mansfeld J, Collin P, Collins MO, Choudhary JS, Pines J. APC15 drives the turnover of MCC-CDC20 to make the spindle assembly checkpoint responsive to kinetochore attachment. Nat Cell Biol. 2011 Sep 18;13(10):1234-43. doi: 10.1038/ncb2347. PMID:21926987 doi:http://dx.doi.org/10.1038/ncb2347
17. ↑ Jin L, Williamson A, Banerjee S, Philipp I, Rape M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell. 2008 May 16;133(4):653-65. doi: 10.1016/j.cell.2008.04.012. PMID:18485873 doi:http://dx.doi.org/10.1016/j.cell.2008.04.012
18. ↑ Luo X, Fang G, Coldiron M, Lin Y, Yu H, Kirschner MW, Wagner G. Structure of the Mad2 spindle assembly checkpoint protein and its interaction with Cdc20. Nat Struct Biol. 2000 Mar;7(3):224-9. PMID:10700282 doi:10.1038/73338
19. ↑ Luo X, Tang Z, Rizo J, Yu H. The Mad2 spindle checkpoint protein undergoes similar major conformational changes upon binding to either Mad1 or Cdc20. Mol Cell. 2002 Jan;9(1):59-71. PMID:11804586
20. ↑ Luo X, Tang Z, Xia G, Wassmann K, Matsumoto T, Rizo J, Yu H. The Mad2 spindle checkpoint protein has two distinct natively folded states. Nat Struct Mol Biol. 2004 Apr;11(4):338-45. Epub 2004 Mar 14. PMID:15024386 doi:10.1038/nsmb748
21. ↑ Jin L, Williamson A, Banerjee S, Philipp I, Rape M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell. 2008 May 16;133(4):653-65. doi: 10.1016/j.cell.2008.04.012. PMID:18485873 doi:http://dx.doi.org/10.1016/j.cell.2008.04.012
22. ↑ Jin L, Williamson A, Banerjee S, Philipp I, Rape M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell. 2008 May 16;133(4):653-65. doi: 10.1016/j.cell.2008.04.012. PMID:18485873 doi:http://dx.doi.org/10.1016/j.cell.2008.04.012
23. ↑ Chan GK, Jablonski SA, Sudakin V, Hittle JC, Yen TJ. Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC. J Cell Biol. 1999 Sep 6;146(5):941-54. PMID:10477750
24. ↑ Tang Z, Bharadwaj R, Li B, Yu H. Mad2-Independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1. Dev Cell. 2001 Aug;1(2):227-37. PMID:11702782
25. ↑ Shin HJ, Baek KH, Jeon AH, Park MT, Lee SJ, Kang CM, Lee HS, Yoo SH, Chung DH, Sung YC, McKeon F, Lee CW. Dual roles of human BubR1, a mitotic checkpoint kinase, in the monitoring of chromosomal instability. Cancer Cell. 2003 Dec;4(6):483-97. PMID:14706340
26. ↑ 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
27. ↑ Park SY, Kim S, Cho H, Kwon SH, Chae S, Kang D, Seong YS, Cho H. Depletion of BubR1 promotes premature centrosomal localization of cyclin B1 and accelerates mitotic entry. Cell Cycle. 2009 Jun 1;8(11):1754-64. Epub 2009 Jun 4. PMID:19411850
28. ↑ Izumi H, Matsumoto Y, Ikeuchi T, Saya H, Kajii T, Matsuura S. BubR1 localizes to centrosomes and suppresses centrosome amplification via regulating Plk1 activity in interphase cells. Oncogene. 2009 Aug 6;28(31):2806-20. doi: 10.1038/onc.2009.141. Epub 2009 Jun 8. PMID:19503101 doi:http://dx.doi.org/10.1038/onc.2009.141
29. ↑ Hutchins JR, Toyoda Y, Hegemann B, Poser I, Heriche JK, Sykora MM, Augsburg M, Hudecz O, Buschhorn BA, Bulkescher J, Conrad C, Comartin D, Schleiffer A, Sarov M, Pozniakovsky A, Slabicki MM, Schloissnig S, Steinmacher I, Leuschner M, Ssykor A, Lawo S, Pelletier L, Stark H, Nasmyth K, Ellenberg J, Durbin R, Buchholz F, Mechtler K, Hyman AA, Peters JM. Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science. 2010 Apr 30;328(5978):593-9. doi: 10.1126/science.1181348. Epub 2010 Apr, 1. PMID:20360068 doi:http://dx.doi.org/10.1126/science.1181348
30. ↑ Alfieri C, Chang L, Zhang Z, Yang J, Maslen S, Skehel M, Barford D. Molecular basis of APC/C regulation by the spindle assembly checkpoint. Nature. 2016 Aug 25;536(7617):431-6. PMID:27509861 doi:http://dx.doi.org/10.1038/nature19083