InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: AURKB

Summary

InnateDB Protein

IDBP-763205.3

Last Modified

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

Gene Symbol

AURKB

Protein Name

Synonyms

AIK2; AIM-1; AIM1; ARK2; AurB; aurkb-sv1; aurkb-sv2; IPL1; PPP1R48; STK12; STK5;

Species

Homo sapiens

Ensembl Protein

ENSP00000463999

InnateDB Gene

IDBG-28278 (AURKB)

Protein Structure

UniProt Annotation

Function

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, GSG2/Haspin, and histone H3. A positive feedback loop involving GSG2 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 GSG2 and AURKB contributes to CPC localization. AURKB is also required for kinetochore localization of BUB1 and SGOL1. 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. {ECO:0000269PubMed:11516652, ECO:0000269PubMed:11756469, ECO:0000269PubMed:11784863, ECO:0000269PubMed:11856369, ECO:0000269PubMed:12458200, ECO:0000269PubMed:12686604, ECO:0000269PubMed:12689593, ECO:0000269PubMed:12925766, ECO:0000269PubMed:14602875, ECO:0000269PubMed:14610074, ECO:0000269PubMed:14722118, ECO:0000269PubMed:15020684, ECO:0000269PubMed:15249581, ECO:0000269PubMed:16103226, ECO:0000269PubMed:17617734, ECO:0000269PubMed:20959462, ECO:0000269PubMed:21658950, ECO:0000269PubMed:22422861, ECO:0000269PubMed:24814515}.

Subcellular Localization

Nucleus. Chromosome. Chromosome, centromere. Cytoplasm, cytoskeleton, spindle. Midbody. Note=Localizes on chromosome arms and inner centromeres from prophase through metaphase and then transferring to the spindle midzone and midbody from anaphase through cytokinesis. Colocalized with gamma tubulin in the mid-body. Proper localization of the active, Thr-232- phosphorylated form during metaphase may be dependent upon interaction with SPDYC. Colocalized with SIRT2 during cytokinesis with the midbody.

Disease Associations

Note=Disruptive regulation of expression is a possible mechanism of the perturbation of chromosomal integrity in cancer cells through its dominant-negative effect on cytokinesis.

Tissue Specificity

High level expression seen in the thymus. It is also expressed in the spleen, lung, testis, colon, placenta and fetal liver. Expressed during S and G2/M phase and expression is up-regulated in cancer cells during M phase. {ECO:0000269PubMed:9809983, ECO:0000269PubMed:9858806}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 203 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	203 [view]
Protein-Protein	195 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	5 [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:0004712	protein serine/threonine/tyrosine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0035174	histone serine kinase activity
GO:0046872	metal ion binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0000278	mitotic cell cycle
GO:0002903	negative regulation of B cell apoptotic process
GO:0006468	protein phosphorylation
GO:0007067	mitotic nuclear division
GO:0008608	attachment of spindle microtubules to kinetochore
GO:0009838	abscission
GO:0016570	histone modification
GO:0031145	anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
GO:0031565	cytokinesis checkpoint
GO:0031577	spindle checkpoint
GO:0032091	negative regulation of protein binding
GO:0032466	negative regulation of cytokinesis
GO:0032467	positive regulation of cytokinesis
GO:0034501	protein localization to kinetochore
GO:0034644	cellular response to UV
GO:0036089	cleavage furrow formation
GO:0043146	spindle stabilization
GO:0043988	histone H3-S28 phosphorylation
GO:0046777	protein autophosphorylation
GO:0051256	spindle midzone assembly involved in mitosis
GO:0051983	regulation of chromosome segregation

Cellular Component

GO:0000779	condensed chromosome, centromeric region
GO:0000780	condensed nuclear chromosome, centromeric region
GO:0005634	nucleus
GO:0005819	spindle
GO:0005829	cytosol
GO:0030496	midbody
GO:0032133	chromosome passenger complex
GO:0045171	intercellular bridge

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
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt