Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

BUB1 (O43683) - Overview - Molecular Target Synopsis

Protein


BUB1, Mitotic checkpoint serine/threonine-protein kinase BUB1
Enzyme Classification 2.7.11.1
UniProt O43683

Also Known as BUB1_HUMAN, BUB1, BUB1L

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. Required for centromeric enrichment of AUKRB in prometaphase. Plays an important role in defining SGO1 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. Interacts with BUB3 and KNL1. Interacts (when phosphorylated) with PLK1. The BUB1-BUB3 complex interacts with MAD1L1.

6F7B
CRYSTAL STRUCTURE OF THE HUMAN BUB1 KINASE DOMAIN IN COMPLEX WITH BAY 1816032
RCSB/PDB
Inspect Structure
See all 3D Structures for BUB1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: BUB1 is active in the following subcellular-locations: centromere, chromosome, kinetochore, nucleus.
GO terms: BUB1 is active in the following subcellular-locations: condensed chromosome kinetochore, condensed nuclear chromosome kinetochore, condensed nuclear chromosome outer kinetochore, cytosol, kinetochore, membrane, nucleoplasm.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project BUB1 has gain in 0 cell-lines, loss in 1 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MDA_MB_231, RXF_393, RPMI_8226

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: OVCAR-8, WSU-FSCCL, Toledo

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: K562, HMEC, HSMM

(see details)

RNA Interference


BUB1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: C33A, DU4475. (see details)

3D Structures


For BUB1 there are:
6 structures (11 chains) solved
4 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


BUB1 has been screened with 22 compounds (22 bioactivities), 6 compounds have bioactivities that show binding affinity of <= 500nM (6 bioactivities). (see details)