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MGP003830

UniProt Annotations

Entry Information
Gene Nameaurora kinase B
Protein EntryAURKB_HUMAN
UniProt IDQ96GD4
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=5; Name=1; IsoId=Q96GD4-1; Sequence=Displayed; Name=2; Synonyms=aurkb-sv1; IsoId=Q96GD4-2; Sequence=VSP_044385; Name=3; Synonyms=aurkb-sv2; IsoId=Q96GD4-3; Sequence=VSP_044384, VSP_044386, VSP_044387; Note=Not expressed in normal liver, high expression in metastatic liver.; Name=4; IsoId=Q96GD4-4; Sequence=VSP_047103; Name=5; IsoId=Q96GD4-5; Sequence=VSP_044384;
Catalytic ActivityATP + a protein = ADP + a phosphoprotein.
CofactorName=Mg(2+); Xref=ChEBI:CHEBI:18420;
DiseaseNote=Disruptive regulation of expression is a possible mechanism of the perturbation of chromosomal integrity in cancer cells through its dominant-negative effect on cytokinesis.
Enzyme RegulationActivity is greatly increased when AURKB is within the CPC complex. In particular, AURKB-phosphorylated INCENP acts as an activator of AURKB. Positive feedback between GSG2 and AURKB contributes to CPC localization. {ECO:0000269|PubMed:12925766, ECO:0000269|PubMed:14722118, ECO:0000269|PubMed:15249581}.
FunctionSerine/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:0000269|PubMed:11516652, ECO:0000269|PubMed:11756469, ECO:0000269|PubMed:11784863, ECO:0000269|PubMed:11856369, ECO:0000269|PubMed:12458200, ECO:0000269|PubMed:12686604, ECO:0000269|PubMed:12689593, ECO:0000269|PubMed:12925766, ECO:0000269|PubMed:14602875, ECO:0000269|PubMed:14610074, ECO:0000269|PubMed:14722118, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15249581, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:20959462, ECO:0000269|PubMed:21658950, ECO:0000269|PubMed:22422861, ECO:0000269|PubMed:24814515}.
InductionExpression is cell cycle-regulated, with a low in G1/S, an increase during G2 and M. Expression decreases again after M phase. {ECO:0000269|PubMed:12925766}.
InteractionO15392:BIRC5; NbExp=7; IntAct=EBI-624291, EBI-518823; O15392-1:BIRC5; NbExp=2; IntAct=EBI-624291, EBI-518838; O15392-2:BIRC5; NbExp=2; IntAct=EBI-624291, EBI-518842; Q16543:CDC37; NbExp=2; IntAct=EBI-624291, EBI-295634; Q86XJ1:GAS2L3; NbExp=4; IntAct=EBI-624291, EBI-9248152; P08238:HSP90AB1; NbExp=2; IntAct=EBI-624291, EBI-352572; Q9NQS7:INCENP; NbExp=7; IntAct=EBI-624291, EBI-307907; P06748:NPM1; NbExp=5; IntAct=EBI-624291, EBI-78579; Q8WYJ6:SEPT1; NbExp=6; IntAct=EBI-624291, EBI-693002; O75410-6:TACC1; NbExp=2; IntAct=EBI-624291, EBI-624278;
PtmThe phosphorylation of Thr-232 requires the binding to INCENP and occurs by means of an autophosphorylation mechanism. Thr-232 phosphorylation is indispensable for the AURKB kinase activity. {ECO:0000269|PubMed:14722118, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:20068231}.
PtmUbiquitinated by different BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complexes. Ubiquitinated by the BCR(KLHL9-KLHL13) E3 ubiquitin ligase complex, ubiquitination leads to removal from mitotic chromosomes and is required for cytokinesis. During anaphase, the BCR(KLHL21) E3 ubiquitin ligase complex recruits the CPC complex from chromosomes to the spindle midzone and mediates the ubiquitination of AURKB. Ubiquitination of AURKB by BCR(KLHL21) E3 ubiquitin ligase complex may not lead to its degradation by the proteasome. {ECO:0000269|PubMed:17543862, ECO:0000269|PubMed:19995937}.
Sequence CautionSequence=AAH13300.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
SimilarityBelongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily. {ECO:0000255|PROSITE- ProRule:PRU00159}.
SimilarityContains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
Subcellular LocationNucleus. 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.
SubunitComponent of the chromosomal passenger complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, INCENP, AURKB and AURKC. 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. {ECO:0000269|PubMed:11516652, ECO:0000269|PubMed:12689593, ECO:0000269|PubMed:12925766, ECO:0000269|PubMed:14602875, ECO:0000269|PubMed:14674694, ECO:0000269|PubMed:14722118, ECO:0000269|PubMed:15064709, ECO:0000269|PubMed:15249581, ECO:0000269|PubMed:16179162, ECO:0000269|PubMed:16764853, ECO:0000269|PubMed:17726514, ECO:0000269|PubMed:18591255, ECO:0000269|PubMed:20562864, ECO:0000269|PubMed:20605920, ECO:0000269|PubMed:20959462, ECO:0000269|PubMed:21225229, ECO:0000269|PubMed:22422861, ECO:0000269|PubMed:23036704}.
Tissue SpecificityHigh 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:0000269|PubMed:9809983, ECO:0000269|PubMed:9858806}.
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