Aurora kinase A
Also known as: AIK, AIRK1, ARK1, AURA, AURKA, AYK1, BTAK, IAK1, STK15, STK6
Function
Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for normal spindle positioning during mitosis and for the localization of NUMA1 and DCTN1 to the cell cortex during metaphase. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Phosphorylates MCRS1 which is required for MCRS1-mediated kinetochore fiber assembly and mitotic progression. Regulates KIF2A tubulin depolymerase activity. Important for microtubule formation and/or stabilization. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and destabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Inhibits cilia outgrowth (By similarity). Required for cilia disassembly via phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin. Regulates protein levels of the anti-apoptosis protein BIRC5 by suppressing the expression of the SCF(FBXL7) E3 ubiquitin-protein ligase substrate adapter FBXL7 through the phosphorylation of the transcription factor FOXP1.
Classification
- Family (Pfam)
- PF00069 Pkinase
- InterPro
- Aur-like, AURKA, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS
- Functional cluster
- Homeobox & Zinc-Finger Transcription Factors
Experimental structures · PDB · 191
- 1MQ4 X-ray 1.90A
- 1MUO X-ray 2.90A
- 1OL5 X-ray 2.50A
- 1OL6 X-ray 3.00A
- 1OL7 X-ray 2.75A
- 2BMC X-ray 2.60A
- 2C6D X-ray 2.20A
- 2C6E X-ray 2.10A
- 2DWB X-ray 2.50A
- 2J4Z X-ray 2.00A
- 2J50 X-ray 3.00A
- 2NP8 X-ray 2.25A
- … and 179 more
A predicted model is available from AlphaFold.
Gene Ontology · 57
- GO:0043203 axon hillock
- GO:0016323 basolateral plasma membrane
- GO:0005814 centriole
- GO:0005813 centrosome
- GO:0032133 chromosome passenger complex
- GO:0036064 ciliary basal body
- GO:0005829 cytosol
- GO:0042585 germinal vesicle
- GO:0098978 glutamatergic synapse
- GO:0000776 kinetochore
- GO:0072687 meiotic spindle
- GO:0005874 microtubule
- GO:0015630 microtubule cytoskeleton
- GO:0030496 midbody
- GO:0097431 mitotic spindle pole
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0048471 perinuclear region of cytoplasm
- GO:0014069 postsynaptic density
- GO:0045120 pronucleus
- GO:0005819 spindle
- GO:0051233 spindle midzone
- GO:0000922 spindle pole
- GO:0031616 spindle pole centrosome
- GO:0005524 ATP binding
- GO:0035175 histone H3S10 kinase activity
- GO:0140677 molecular function activator activity
- GO:0046982 protein heterodimerization activity
- GO:0004672 protein kinase activity
- GO:0019901 protein kinase binding
- GO:0106310 protein serine kinase activity
- GO:0004674 protein serine/threonine kinase activity
- GO:0004712 protein serine/threonine/tyrosine kinase activity
- GO:0031625 ubiquitin protein ligase binding
- GO:0051301 cell division
- GO:0061523 cilium disassembly
- GO:0000086 G2/M transition of mitotic cell cycle
- GO:0097421 liver regeneration
- GO:0000212 meiotic spindle organization
- GO:0000278 mitotic cell cycle
- GO:0007100 mitotic centrosome separation
- GO:0007052 mitotic spindle organization
- GO:0010629 negative regulation of gene expression
- GO:0032091 negative regulation of protein binding
- GO:0018105 peptidyl-serine phosphorylation
- GO:0090141 positive regulation of mitochondrial fission
- GO:0045931 positive regulation of mitotic cell cycle
- GO:0045840 positive regulation of mitotic nuclear division
- GO:0046777 protein autophosphorylation
- GO:0006468 protein phosphorylation
- GO:0046605 regulation of centrosome cycle
- GO:0032465 regulation of cytokinesis
- GO:0010389 regulation of G2/M transition of mitotic cell cycle
- GO:0031647 regulation of protein stability
- GO:1901796 regulation of signal transduction by p53 class mediator
- GO:0009611 response to wounding
- GO:0007051 spindle organization
Drugs targeting this protein · 18
- KW-2449 inhibitor
- CENISERTIB inhibitor
- ILORASERTIB inhibitor
- RG-1530 inhibitor
- AMG-900 inhibitor
- MLN-8054 inhibitor
- MK-6592 inhibitor
- MK-5108 inhibitor
- TAS-119 inhibitor
- DANUSERTIB inhibitor
- PF-03814735 inhibitor
- SNS-314 inhibitor
- CYC-116 inhibitor
- ENMD-2076 inhibitor
- ALISERTIB inhibitor
- AT-9283 inhibitor
- ENMD-981693 inhibitor
- TOZASERTIB inhibitor
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Aurora kinase A 0.98
- Aurora kinase A 0.97
- Aurora kinase A 0.97
- Aurora kinase A 0.96
- Aurora kinase A 0.96
- Aurora kinase A-A 0.92
- Aurora kinase A-B 0.91
- Aurora kinase B 0.89
- Aurora kinase B 0.86
- Aurora kinase B 0.85
- Aurora kinase B 0.85
- Aurora kinase 0.85
Co-cited proteins · studied together in the literature
- Targeting protein for Xklp2 4 shared papers
- Aurora kinase A 4 shared papers
- Protein aurora borealis 1 shared papers
- Protein aurora borealis 1 shared papers
- Growth arrest and DNA damage-inducible protein GADD45 alpha 1 shared papers
- Aurora kinase A 1 shared papers
- Cytoplasmic polyadenylation element-binding protein 1 1 shared papers
- Disks large-associated protein 5 1 shared papers
- Breast cancer type 1 susceptibility protein 3 shared papers
- Aurora kinase A- and ninein-interacting protein 1 shared papers
- Kelch-like protein 18 1 shared papers
- Rho guanine nucleotide exchange factor 2 1 shared papers
Literature · 70 cited papers
- Human nuclear RNAi-defective 2 (NRDE2) is an essential RNA splicing factor. RNA · 2019
- Aurora kinase A regulates Survivin stability through targeting FBXL7 in gastric cancer drug resistance and prognosis. Oncogenesis · 2017
- Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
- Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors. Proc. Natl. Acad. Sci. U.S.A. · 2016
- Aurora A kinase regulates proper spindle positioning in C. elegans and in human cells. J. Cell Sci. · 2016
- Aurora-A regulates MCRS1 function during mitosis. Cell Cycle · 2016
- PMID 26341884 J. Biol. Chem. · 2015
- The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation. Mol. Biol. Cell · 2015
- Phosphorylation of SAF-A/hnRNP-U serine 59 by polo-like kinase 1 is required for mitosis. Mol. Cell. Biol. · 2015
- CENP-32 is required to maintain centrosomal dominance in bipolar spindle assembly. Mol. Biol. Cell · 2015
- NEDD9 regulates actin dynamics through cortactin deacetylation in an AURKA/HDAC6-dependent manner. Mol. Cancer Res. · 2014
- The CUL3-KLHL18 ligase regulates mitotic entry and ubiquitylates Aurora-A. Biol. Open · 2012
- … and 58 more in the literature graph