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

AURKB (Q96GD4) - Overview - Molecular Target Synopsis

Protein


AURKB, Aurora kinase B
Enzyme Classification 2.7.11.1
UniProt Q96GD4

Also Known as AURKB_HUMAN, AURKB, AIK2, AIM1, AIRK2, ARK2, STK1, STK12, STK5

Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Involved in the bipolar attachment of spindle microtubules to kinetochores and is a key regulator for the onset of cytokinesis during mitosis. Required for central/midzone spindle assembly and cleavage furrow formation. Key component of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage: phosphorylates CHMP4C, leading to retain abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis (PubMed:22422861, PubMed:24814515). AURKB phosphorylates the CPC complex subunits BIRC5/survivin, CDCA8/borealin and INCENP. Phosphorylation of INCENP leads to increased AURKB activity. Other known AURKB substrates involved in centromeric functions and mitosis are CENPA, DES/desmin, GPAF, KIF2C, NSUN2, RACGAP1, SEPT1, VIM/vimentin, HASPIN, and histone H3. A positive feedback loop involving HASPIN and AURKB contributes to localization of CPC to centromeres. Phosphorylation of VIM controls vimentin filament segregation in cytokinetic process, whereas histone H3 is phosphorylated at 'Ser-10' and 'Ser-28' during mitosis (H3S10ph and H3S28ph, respectively). A positive feedback between HASPIN and AURKB contributes to CPC localization. AURKB is also required for kinetochore localization of BUB1 and SGO1. Phosphorylation of p53/TP53 negatively regulates its transcriptional activity. Key regulator of active promoters in resting B- and T-lymphocytes: acts by mediating phosphorylation of H3S28ph at active promoters in resting B-cells, inhibiting RNF2/RING1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes. Component of the chromosomal passenger complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, INCENP, AURKB or AURKC; predominantly independent AURKB- and AURKC-containing complexes exist. Associates with RACGAP1 during M phase. Interacts with CDCA1, EVI5, JTB, NDC80, PSMA3, SEPT1, SIRT2 and TACC1. Interacts with SPDYC; this interaction may be required for proper localization of active, Thr-232-phosphorylated AURKB form during prometaphase and metaphase. Interacts with p53/TP53. Interacts (via the middle kinase domain) with NOC2L (via the N- and C-terminus domains). Interacts with TTC28. Interacts with RNF2/RING1B.

4AF3
HUMAN AURORA B KINASE IN COMPLEX WITH INCENP AND VX-680
RCSB/PDB
Inspect Structure
See all 3D Structures for AURKB

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: AURKB is active in the following subcellular-locations: centromere, chromosome, cytoplasm, cytoskeleton, midbody, nucleus, spindle.
GO terms: AURKB is active in the following subcellular-locations: chromocenter, chromosome passenger complex, condensed chromosome, condensed nuclear chromosome, cytosol, kinetochore, midbody, mitotic spindle midzone, nucleoplasm, nucleus, spindle, spindle microtubule, spindle midzone, spindle pole centrosome.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project AURKB has gain in 0 cell-lines, loss in 7 cell-lines and no signal in 997 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SNB_19, DU_145, SF_268

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SF268, SK-N-DZ, HCC1576

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: SK-N-SH, A549, K562

(see details)

RNA Interference


AURKB was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MCF7, MHM. (see details)

3D Structures


For AURKB there are:
1 structures (1 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


AURKB has been screened with 3041 compounds (4364 bioactivities), 1203 compounds have bioactivities that show binding affinity of <= 500nM (1548 bioactivities). (see details)