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AURKB_HUMAN

OverviewProducts

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, SEPTIN1, 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.

Involvement in disease

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

Post-translational modifications

The 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.

Ubiquitinated 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.

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily.

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.

Cellular localization

  • Nucleus
  • Chromosome
  • Chromosome
  • Centromere
  • Cytoplasm
  • Cytoskeleton
  • Spindle
  • Midbody
  • 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 midbody. 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. Localization (and probably targeting of the CPC) to the inner centromere occurs predominantly in regions with overlapping mitosis-specific histone phosphorylations H3pT3 and H2ApT12.

Alternative names

  • Aurora kinase B
  • Aurora 1
  • Aurora- and IPL1-like midbody-associated protein 1
  • Aurora/IPL1-related kinase 2
  • STK-1
  • Serine/threonine-protein kinase 12
  • Serine/threonine-protein kinase 5
  • Serine/threonine-protein kinase aurora-B
  • AIM-1
  • ARK-2
  • Aurora-related kinase 2
  • AIK2
  • AURKB
  • AIM1
  • AIRK2
  • ARK2
  • STK1
  • STK12
  • STK5

Database links

Target type

Proteins

Primary research area

Epigenetics

Molecular weight

39311Da