Aurora kinase B
Also known as: AIK2, AIM1, AIRK2, ARK2, AURKB, STK1, STK12, STK5
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. 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 histones H1.4 and 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). 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 (By similarity). Acts as an inhibitor of CGAS during mitosis: catalyzes phosphorylation of the N-terminus of CGAS during the G2-M transition, blocking CGAS liquid phase separation and activation, and thereby preventing CGAS-induced autoimmunity. Phosphorylates KRT5 during anaphase and telophase (By similarity). Phosphorylates ATXN10 which promotes phosphorylation of ATXN10 by PLK1 and may play a role in the regulation of cytokinesis and stimulating the proteasomal degradation of ATXN10.
Classification
- Family (Pfam)
- PF00069 Pkinase
- InterPro
- Aur-like, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS
- Functional cluster
- Serine/Threonine Protein Kinases
Experimental structures · PDB · 1
- 4AF3 X-ray 2.75A
A predicted model is available from AlphaFold.
Gene Ontology · 56
- GO:0005813 centrosome
- GO:0000785 chromatin
- GO:0010369 chromocenter
- GO:0032133 chromosome passenger complex
- GO:0000779 condensed chromosome, centromeric region
- GO:0005829 cytosol
- GO:0000776 kinetochore
- GO:0015630 microtubule cytoskeleton
- GO:0030496 midbody
- GO:1990023 mitotic spindle midzone
- GO:0097431 mitotic spindle pole
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0005819 spindle
- GO:0005876 spindle microtubule
- GO:0051233 spindle midzone
- GO:0000922 spindle pole
- GO:0005524 ATP binding
- GO:0140197 histone H1-4S27 kinase activity
- GO:0019900 kinase binding
- GO:0106310 protein serine kinase activity
- GO:0004674 protein serine/threonine kinase activity
- GO:0004712 protein serine/threonine/tyrosine kinase activity
- GO:0044839 cell cycle G2/M phase transition
- GO:0034644 cellular response to UV
- GO:0036089 cleavage furrow formation
- GO:0061952 midbody abscission
- GO:0000278 mitotic cell cycle
- GO:0000281 mitotic cytokinesis
- GO:0044878 mitotic cytokinesis checkpoint signaling
- GO:1990758 mitotic sister chromatid biorientation
- GO:0090307 mitotic spindle assembly
- GO:0051256 mitotic spindle midzone assembly
- GO:0007052 mitotic spindle organization
- GO:0002903 negative regulation of B cell apoptotic process
- GO:0160049 negative regulation of cGAS/STING signaling pathway
- GO:0032466 negative regulation of cytokinesis
- GO:0045824 negative regulation of innate immune response
- GO:0120186 negative regulation of protein localization to chromatin
- GO:0000122 negative regulation of transcription by RNA polymerase II
- GO:1902425 positive regulation of attachment of mitotic spindle microtubules to kinetochore
- GO:0032467 positive regulation of cytokinesis
- GO:1905116 positive regulation of lateral attachment of mitotic spindle microtubules to kinetochore
- GO:0031117 positive regulation of microtubule depolymerization
- GO:0090267 positive regulation of mitotic cell cycle spindle assembly checkpoint
- GO:1903490 positive regulation of mitotic cytokinesis
- GO:0062033 positive regulation of mitotic sister chromatid segregation
- GO:1901970 positive regulation of mitotic sister chromatid separation
- GO:0032206 positive regulation of telomere maintenance
- GO:0043687 post-translational protein modification
- GO:0034501 protein localization to kinetochore
- GO:0051983 regulation of chromosome segregation
- GO:0032465 regulation of cytokinesis
- GO:1901796 regulation of signal transduction by p53 class mediator
- GO:0140273 repair of mitotic kinetochore microtubule attachment defect
- GO:0007051 spindle organization
Drugs targeting this protein · 16
- GSK-1070916 inhibitor
- KW-2449 inhibitor
- CENISERTIB inhibitor
- ILORASERTIB inhibitor
- AMG-900 inhibitor
- TAK-901 inhibitor
- MK-6592 inhibitor
- DANUSERTIB inhibitor
- BARASERTIB inhibitor
- PF-03814735 inhibitor
- SNS-314 inhibitor
- CYC-116 inhibitor
- ENMD-2076 inhibitor
- AT-9283 inhibitor
- IBCASERTIB inhibitor
- TOZASERTIB inhibitor
Related proteins · sequence + function similarity
- Aurora kinase B 0.98
- Aurora kinase B 0.98
- Aurora kinase B 0.96
- Aurora kinase C 0.96
- Aurora kinase B 0.95
- Aurora kinase B 0.94
- Aurora kinase B 0.94
- Aurora kinase B-A 0.94
- Aurora kinase B-B 0.92
- Aurora kinase C 0.92
- Serine/threonine-protein kinase Aurora-2 0.91
- Aurora kinase 0.90
Co-cited proteins · studied together in the literature
- Inner centromere protein 8 shared papers
- Speedy protein C 1 shared papers
- Aurora kinase B 2 shared papers
- Serine/threonine-protein kinase haspin 2 shared papers
- Inner centromere protein 1 shared papers
- Tetratricopeptide repeat protein 28 1 shared papers
- Tetratricopeptide repeat protein 28 1 shared papers
- Septin-1 1 shared papers
- Ubiquitin carboxyl-terminal hydrolase 35 1 shared papers
- Ataxin-10 1 shared papers
- Baculoviral IAP repeat-containing protein 5 7 shared papers
- Aurora kinase A 4 shared papers
Literature · 56 cited papers
- Phosphorylation and chromatin tethering prevent cGAS activation during mitosis. Science · 2021
- USP35 regulates mitotic progression by modulating the stability of Aurora B. Nat. Commun. · 2018
- Aurora-C interactions with survivin and INCENP reveal shared and distinct features compared with Aurora-B chromosome passenger protein complex. PLoS ONE · 2016
- Acetylation of Aurora B by TIP60 ensures accurate chromosomal segregation. Nat. Chem. Biol. · 2016
- Aurora B-dependent phosphorylation of Ataxin-10 promotes the interaction between Ataxin-10 and Plk1 in cytokinesis. Sci. Rep. · 2015
- ANCHR mediates Aurora-B-dependent abscission checkpoint control through retention of VPS4. Nat. Cell Biol. · 2014
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- A novel big protein TPRBK possessing 25 units of TPR motif is essential for the progress of mitosis and cytokinesis. Gene · 2012
- Crystal structure of human aurora B in complex with INCENP and VX-680. J. Med. Chem. · 2012
- ESCRT-III governs the Aurora B-mediated abscission checkpoint through CHMP4C. Science · 2012
- A positive feedback loop involving Haspin and Aurora B promotes CPC accumulation at centromeres in mitosis. Curr. Biol. · 2011
- Isoform-specific phosphorylation of human linker histone H1.4 in mitosis by the kinase Aurora B. J. Cell Sci. · 2011
- … and 44 more in the literature graph