Linked Life Data

O60566

Source:http://identifiers.org/uniprot/O60566

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
biopax3:comment
FUNCTION: 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION: Kinase activity stimulated by CENPE. SUBUNIT: Interacts with CENPE, CENPF, mitosin, PLK1 and BUB3. Part of a complex containing BUB3, CDC20 and BUB1B. Interacts with anaphase-promoting complex/cyclosome (APC/C). Interacts with CASC5. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Chromosome, centromere, kinetochore. Cytoplasm, cytoskeleton, centrosome. Note=Cytoplasmic in interphase cells. Associates with the kinetochores in early prophase. Kinetochore localization requires BUB1, PLK1 and CASC5. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=O60566-1; Sequence=Displayed; Name=2; IsoId=O60566-2; Sequence=VSP_036474, VSP_036475, VSP_036476; Note=No experimental confirmation available; Name=3; IsoId=O60566-3; Sequence=VSP_036473; Note=No experimental confirmation available; TISSUE SPECIFICITY: Highly expressed in thymus followed by spleen. Preferentially expressed in tissues with a high mitotic index. INDUCTION: Induced during mitosis. DOMAIN: The D-box targets the protein for rapid degradation by ubiquitin-dependent proteolysis during the transition from mitosis to interphase (Potential). DOMAIN: The BUB1 N-terminal domain directs kinetochore localization and binding to BUB3. PTM: Proteolytically cleaved by caspase-3 in a cell cycle specific manner. The cleavage might be involved in the durability of the cell cycle delay. Caspase-3 cleavage is associated with abrogation of the mitotic checkpoint. The major site of cleavage is at Asp- 610. PTM: Acetylation at Lys-250 regulates its degradation and timing in anaphase entry. PTM: Ubiquitinated. Degradated by the proteasome. PTM: Sumoylated by SUMO2 and SUMO3. The sumoylation mediates the association with CENPE at the kinetochore. PTM: Autophosphorylated in vitro. Intramolecular autophosphorylation is stimulated by CENPE. Phosphorylated during mitosis and hyperphosphorylated in mitotically arrested cells. Phosphorylation at Ser-670 and Ser-1043 occurs at kinetochores upon mitotic entry with dephosphorylation at the onset of anaphase. DISEASE: Note=Defects in BUB1B are associated with tumor formation. DISEASE: Defects in BUB1B are the cause of premature chromatid separation trait (PCS) [MIM:176430]. PCS consists of separate and splayed chromatids with discernible centromeres and involves all or most chromosomes of a metaphase. It is found in up to 2% of metaphases in cultured lymphocytes from approximately 40% of normal individuals. When PCS is present in 5% or more of cells, it is known as the heterozygous PCS trait and has no obvious phenotypic effect, although some have reported decreased fertility. Inheritance is autosomal dominant. DISEASE: Defects in BUB1B are the cause of mosaic variegated aneuploidy syndrome type 1 (MVA1) [MIM:257300]. A severe autosomal recessive developmental disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. The proportion of aneuploid cells varies but is usually more than 25% and is substantially greater than in normal individuals. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor and leukemia reported in several cases. Note=MVA1 is caused by biallelic mutations in the BUB1B gene. SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. BUB1 subfamily. SIMILARITY: Contains 1 BUB1 N-terminal domain. SIMILARITY: Contains 1 protein kinase domain. SEQUENCE CAUTION: Sequence=BAD92019.1; Type=Erroneous initiation; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/BUB1BID854ch15q15.html"; GENE SYNONYMS:BUB1B BUBR1 MAD3L SSK1. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., SEQUENCE 1050 AA; 119545 MW; F7871103A56E6B46 CRC64;
biopax3:xref
biopax3:displayName
BUB1B_HUMAN
biopax3:name
2.7.11.1, BUB1B, MAD3/BUB1-related protein kinase, Mitotic checkpoint kinase MAD3L, Protein SSK1, hBUBR1
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biopax3:organism
biopax3:sequence
MAAVKKEGGALSEAMSLEGDEWELSKENVQPLRQGRIMSTLQGALAQESACNNTLQQQKRAFEYEIRFYTGNDPLDVWDRYISWTEQNYPQGGKESNMSTLLERAVEALQGEKRYYSDPRFLNLWLKLGRLCNEPLDMYSYLHNQGIGVSLAQFYISWAEEYEARENFRKADAIFQEGIQQKAEPLERLQSQHRQFQARVSRQTLLALEKEEEEEVFESSVPQRSTLAELKSKGKKTARAPIIRVGGALKAPSQNRGLQNPFPQQMQNNSRITVFDENADEASTAELSKPTVQPWIAPPMPRAKENELQAGPWNTGRSLEHRPRGNTASLIAVPAVLPSFTPYVEETARQPVMTPCKIEPSINHILSTRKPGKEEGDPLQRVQSHQQASEEKKEKMMYCKEKIYAGVGEFSFEEIRAEVFRKKLKEQREAELLTSAEKRAEMQKQIEEMEKKLKEIQTTQQERTGDQQEETMPTKETTKLQIASESQKIPGMTLSSSVCQVNCCARETSLAENIWQEQPHSKGPSVPFSIFDEFLLSEKKNKSPPADPPRVLAQRRPLAVLKTSESITSNEDVSPDVCDEFTGIEPLSEDAIITGFRNVTICPNPEDTCDFARAARFVSTPFHEIMSLKDLPSDPERLLPEEDLDVKTSEDQQTACGTIYSQTLSIKKLSPIIEDSREATHSSGFSGSSASVASTSSIKCLQIPEKLELTNETSENPTQSPWCSQYRRQLLKSLPELSASAELCIEDRPMPKLEIEKEIELGNEDYCIKREYLICEDYKLFWVAPRNSAELTVIKVSSQPVPWDFYINLKLKERLNEDFDHFCSCYQYQDGCIVWHQYINCFTLQDLLQHSEYITHEITVLIIYNLLTIVEMLHKAEIVHGDLSPRCLILRNRIHDPYDCNKNNQALKIVDFSYSVDLRVQLDVFTLSGFRTVQILEGQKILANCSSPYQVDLFGIADLAHLLLFKEHLQVFWDGSFWKLSQNISELKDGELWNKFFVRILNANDEATVSVLGELAAEMNGVFDTTFQSHLNKALWKVGKLTSPGALLFQ
biopax3:standardName
Mitotic checkpoint serine/threonine-protein kinase BUB1 beta