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Details on Person UniProt:O14965 AURKA
| Class:Id | ReferenceGeneProduct:69922 |
|---|---|
| _chainChangeLog | chain:1-403 added on Sat February 7 2015 |
| _displayName | UniProt:O14965 AURKA |
| _timestamp | 2025-08-15 21:43:34 |
| chain | chain:1-403 |
| checksum | 7C2E7B438D969187 |
| comment | FUNCTION Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression (PubMed:11039908, PubMed:12390251, PubMed:17125279, PubMed:17360485, PubMed:18615013, PubMed:26246606). 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 (PubMed:14523000, PubMed:26246606). Required for normal spindle positioning during mitosis and for the localization of NUMA1 and DCTN1 to the cell cortex during metaphase (PubMed:27335426). Required for initial activation of CDK1 at centrosomes (PubMed:13678582, PubMed:15128871). Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2 (PubMed:11551964, PubMed:14702041, PubMed:15128871, PubMed:15147269, PubMed:15987997, PubMed:17604723, PubMed:18056443, PubMed:18615013). Phosphorylates MCRS1 which is required for MCRS1-mediated kinetochore fiber assembly and mitotic progression (PubMed:27192185). Regulates KIF2A tubulin depolymerase activity (PubMed:19351716). Important for microtubule formation and/or stabilization (PubMed:18056443). Required for normal axon formation (PubMed:19812038). Plays a role in microtubule remodeling during neurite extension (PubMed:19668197). 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 (PubMed:14702041). Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity (PubMed:11551964). Inhibits cilia outgrowth (By similarity). Required for cilia disassembly via phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin (PubMed:17604723, PubMed:20643351). 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 (PubMed:28218735).CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)ACTIVITY REGULATION Activation of CDK1, appears to be an upstream event of AURKA activation. Phosphatase inhibitor-2 (PPP1R2) and TPX2 act also as activators. Inactivated by the G2 checkpoint. Inhibited by GADD45A and p53/TP53, and through dephosphorylation by protein phosphatase type 1 (PP1). MLN8054 is also a potent and selective inhibitor. Activated during the early phase of cilia disassembly in the presence of CIMAP3. Inhibited by the small molecule inhibitor VX-680 (PubMed:28218735).SUBUNIT Part of a complex composed of NEDD9, AURKA and CTTN; within the complex NEDD9 acts as a scaffold protein and is required for complex formation (PubMed:24574519). Identified in a complex with AUNIP and NIN (PubMed:20596670). Interacts with FBXL7 (By similarity). Interacts with CPEB1, JTB, TACC1, TPX2, PPP2CA, as well as with the protein phosphatase type 1 (PP1) isoforms PPP1CA, PPP1CB and PPP1CC (PubMed:11551964, PubMed:14580337, PubMed:14603251, PubMed:15966895, PubMed:17229885, PubMed:18662907, PubMed:19357306, PubMed:19668197, PubMed:19801554, PubMed:21225229, PubMed:27837025). Also interacts with its substrates ARHGEF2, BORA, KIF2A, PARD3, and p53/TP53 (PubMed:14702041, PubMed:16890155, PubMed:17488622, PubMed:19351716, PubMed:19812038). Interaction with BORA promotes phosphorylation of PLK1 (By similarity). Interacts with CIMAP3 (PubMed:20643351). Interacts with GADD45A, competing with its oligomerization (PubMed:20460379). Interacts (via C-terminus) with AUNIP (via C-terminus) (PubMed:20596670). Interacts with FRY; this interaction facilitates AURKA-mediated PLK1 phosphorylation (PubMed:22753416). Interacts with SIRT2 (PubMed:17726514, PubMed:22014574). Interacts with MYCN; interaction is phospho-independent and triggers AURKA activation; AURKA competes with FBXW7 for binding to unphosphorylated MYCN but not for binding to phosphorylated MYCN (PubMed:27837025). Interacts with HNRNPU (PubMed:21242313, PubMed:25986610). Interacts with AAAS (PubMed:26246606). Interacts with KLHL18 and CUL3 (PubMed:23213400). Interacts with FOXP1 (PubMed:28218735). Interacts with HDAC6; AURKA-mediated phosphorylation of HDAC6 promotes deacetylation of alpha-tubulin (PubMed:17604723).INTERACTION Detected at the neurite hillock in developing neurons (By similarity). Localizes at the centrosome in mitotic cells from early prophase until telophase, but also localizes to the spindle pole MTs from prophase to anaphase (PubMed:17229885, PubMed:21225229, PubMed:9606188). Colocalized with SIRT2 at centrosome (PubMed:22014574). Moves to the midbody during both telophase and cytokinesis (PubMed:17726514). Associates with both the pericentriolar material (PCM) and centrioles (PubMed:22014574). The localization to the spindle poles is regulated by AAAS (PubMed:26246606).TISSUE SPECIFICITY Highly expressed in testis and weakly in skeletal muscle, thymus and spleen. Also highly expressed in colon, ovarian, prostate, neuroblastoma, breast and cervical cancer cell lines.INDUCTION Expression is cell-cycle regulated, low in G1/S, accumulates during G2/M, and decreases rapidly after.PTM Activated by phosphorylation at Thr-288; this brings about a change in the conformation of the activation segment. Phosphorylation at Thr-288 varies during the cell cycle and is highest during M phase. Autophosphorylated at Thr-288 upon TPX2 binding. Thr-288 can be phosphorylated by several kinases, including PAK and PKA. Protein phosphatase type 1 (PP1) binds AURKA and inhibits its activity by dephosphorylating Thr-288 during mitosis. Phosphorylation at Ser-342 decreases the kinase activity. PPP2CA controls degradation by dephosphorylating Ser-51 at the end of mitosis.PTM Ubiquitinated by the E3 ubiquitin-protein ligase complex SCF(FBXL7) during mitosis, leading to its degradation by the proteasome (By similarity). Ubiquitinated by CHFR, leading to its degradation by the proteasome (By similarity). Ubiquitinated by the anaphase-promoting complex (APC), leading to its degradation by the proteasome (PubMed:10851084, PubMed:11039908). Ubiquitinated by the CUL3-KLHL18 ligase leading to its activation at the centrosome which is required for initiating mitotic entry (PubMed:23213400). Ubiquitination mediated by CUL3-KLHL18 ligase does not lead to its degradation by the proteasome (PubMed:23213400).MISCELLANEOUS Centrosome amplification can occur when the cycles are uncoupled, and this amplification is associated with cancer and with an increase in the levels of chromosomal instability.SIMILARITY Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily.CAUTION Authors initially considered AURKA/STK6 and STK15 as 2 different proteins (PubMed:9771714). It is clear that they are the same protein.CAUTION An article that concluded that AURKA-mediated phosphorylation of BRCA1 'Ser-308' plays a role in the normal cell cycle G2/M transition was withdrawn due to data manipulation of flow cytometry data. |
| description | recommendedName: fullName evidence="81"Aurora kinase A ecNumber evidence="12 29 42 45 61 63 64"2.7.11.1 alternativeName: fullName evidence="70"Aurora 2 alternativeName: fullName evidence="74"Aurora/IPL1-related kinase 1 shortName evidence="74"ARK-1 shortName evidence="75"Aurora-related kinase 1 alternativeName: fullName evidence="71"Breast tumor-amplified kinase alternativeName: fullName evidence="4"Ipl1- and aurora-related kinase 1 alternativeName: fullName evidence="72 73"Serine/threonine-protein kinase 15 alternativeName: fullName evidence="76"Serine/threonine-protein kinase 6 alternativeName: fullName evidence="4"Serine/threonine-protein kinase Ayk1 alternativeName: fullName evidence="3"Serine/threonine-protein kinase aurora-A |
| geneName | AURKA AIK AIRK1 ARK1 AURA AYK1 BTAK IAK1 STK15 STK6 |
| identifier | O14965 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure ATP-binding Cell cycle Cell division Cell membrane Cell projection Cilium Cilium biogenesis/degradation Cytoplasm Cytoskeleton Isopeptide bond Kinase Membrane Microtubule Mitosis Nucleotide-binding Phosphoprotein Proteomics identification Proto-oncogene Reference proteome Serine/threonine-protein kinase Transferase Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | AURKA |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8991144] ENSEMBL:ENSG00000087586 AURKA [Homo sapiens] |
| secondaryIdentifier | AURKA_HUMAN E1P5F9 O60445 O75873 Q9BQD6 Q9UPG5 |
| sequenceLength | 403 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:174254] AURKA [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:2574832] p-T288-AURKA [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:4655367] SUMO1-K258-AURKA [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:4655443] AURKA [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:6805089] p-T288-AURKA [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:8854040] PolyUb-AURKA [cytosol] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:2574829] O-phospho-L-threonine at 288 [GroupModifiedResidue:4655362] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 258 [GroupModifiedResidue:8854039] ubiquitinylated lysine (polyubiquitin chain [cytosol]) at unknown position |
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No pathways have been reviewed or authored by UniProt:O14965 AURKA (69922)
