InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: BUB1

Summary

InnateDB Protein

IDBP-65672.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

BUB1

Protein Name

budding uninhibited by benzimidazoles 1 homolog (yeast)

Synonyms

BUB1A; BUB1L; hBUB1;

Species

Homo sapiens

Ensembl Protein

ENSP00000302530

InnateDB Gene

IDBG-65670 (BUB1)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:10198256, ECO:0000269PubMed:15020684, ECO:0000269PubMed:15525512, ECO:0000269PubMed:15723797, ECO:0000269PubMed:16760428, ECO:0000269PubMed:17158872, ECO:0000269PubMed:19487456}.

Subcellular Localization

Nucleus. Chromosome, centromere, kinetochore. Note=Nuclear in interphase cells. Accumulates gradually during G1 and S phase of the cell cycle, peaks at G2/M, and drops dramatically after mitosis. Localizes to the outer kinetochore. Kinetochore localization is required for normal mitotic timing and checkpoint response to spindle damage and occurs very early in prophase. AURKB, CASC5 and INCENP are required for kinetochore localization (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

High expression in testis and thymus, less in colon, spleen, lung and small intestine. Expressed in fetal thymus, bone marrow, heart, liver, spleen and thymus. Expression is associated with cells/tissues with a high mitotic index.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 51 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	51 [view]
Protein-Protein	49 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0000278	mitotic cell cycle
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007059	chromosome segregation
GO:0007063	regulation of sister chromatid cohesion
GO:0007067	mitotic nuclear division
GO:0007093	mitotic cell cycle checkpoint
GO:0007094	mitotic spindle assembly checkpoint
GO:0008283	cell proliferation
GO:0016032	viral process
GO:0051983	regulation of chromosome segregation
GO:0071173	spindle assembly checkpoint
GO:0071174	mitotic spindle checkpoint
GO:2001244	positive regulation of intrinsic apoptotic signaling pathway

Cellular Component

GO:0000775	chromosome, centromeric region
GO:0000776	kinetochore
GO:0000777	condensed chromosome kinetochore
GO:0000780	condensed nuclear chromosome, centromeric region
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0016020	membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR013212 Mad3/BUB1 homology region 1

PFAM

PF00069
PF07714
PF08311

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00777

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt