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MGP003013

UniProt Annotations

Entry Information

Gene Name	aurora kinase A
Protein Entry	AURKA_HUMAN
UniProt ID	O14965
Species	Human

Comments

Comment type	Description
Catalytic Activity	ATP + a protein = ADP + a phosphoprotein. {ECO:0000269\|PubMed:12237287, ECO:0000269\|PubMed:16337122, ECO:0000269\|PubMed:19140666, ECO:0000269\|PubMed:19402633}.
Caution	Authors initially considered AURKA/STK6 and STK15 as 2 different proteins (PubMed:9771714). It is clear that they are the same protein. {ECO:0000305\|PubMed:9771714}.
Enzyme 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 PIFO. {ECO:0000269\|PubMed:11039908, ECO:0000269\|PubMed:12390251, ECO:0000269\|PubMed:17360485}.
Function	Mitotic serine/threonine kinases 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 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. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. 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 stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis. {ECO:0000269\|PubMed:11039908, ECO:0000269\|PubMed:11551964, ECO:0000269\|PubMed:12390251, ECO:0000269\|PubMed:13678582, ECO:0000269\|PubMed:14523000, ECO:0000269\|PubMed:14702041, ECO:0000269\|PubMed:14990569, ECO:0000269\|PubMed:15128871, ECO:0000269\|PubMed:15147269, ECO:0000269\|PubMed:15987997, ECO:0000269\|PubMed:17125279, ECO:0000269\|PubMed:17360485, ECO:0000269\|PubMed:17604723, ECO:0000269\|PubMed:18056443, ECO:0000269\|PubMed:18615013, ECO:0000269\|PubMed:19351716, ECO:0000269\|PubMed:19357306, ECO:0000269\|PubMed:19668197, ECO:0000269\|PubMed:19812038, ECO:0000269\|PubMed:20643351, ECO:0000269\|PubMed:9606188}.
Induction	Expression is cell-cycle regulated, low in G1/S, accumulates during G2/M, and decreases rapidly after. {ECO:0000269\|PubMed:11790771, ECO:0000269\|PubMed:12390251, ECO:0000269\|PubMed:15987997, ECO:0000269\|PubMed:9153231, ECO:0000269\|PubMed:9606188}.
Interaction	Q9NWT8:AURKAIP1; NbExp=2; IntAct=EBI-448680, EBI-448665; P00533:EGFR; NbExp=4; IntAct=EBI-448680, EBI-297353; P61978:HNRNPK; NbExp=2; IntAct=EBI-448680, EBI-304185; Q13123:IK; NbExp=3; IntAct=EBI-448680, EBI-713456; P04198:MYCN; NbExp=9; IntAct=EBI-448680, EBI-878369; P06748:NPM1; NbExp=3; IntAct=EBI-448680, EBI-78579; Q8VDQ8:Sirt2 (xeno); NbExp=5; IntAct=EBI-448680, EBI-911012; O15350:TP73; NbExp=11; IntAct=EBI-448680, EBI-389606;
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.
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. {ECO:0000269\|PubMed:11039908, ECO:0000269\|PubMed:11551964, ECO:0000269\|PubMed:12390251, ECO:0000269\|PubMed:13678582, ECO:0000269\|PubMed:14580337, ECO:0000269\|PubMed:14990569, ECO:0000269\|PubMed:16246726, ECO:0000269\|PubMed:17229885, ECO:0000269\|PubMed:18662907, ECO:0000269\|PubMed:18691976, ECO:0000269\|PubMed:19668197}.
Ptm	Ubiquitinated by the E3 ubiquitin-protein ligase complex SCF(FBXL7) during mitosis, leading to its degradation by the proteasome. 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. {ECO:0000250, ECO:0000269\|PubMed:10851084, ECO:0000269\|PubMed:11039908}.
Sequence Caution	Sequence=BAA23592.1; Type=Frameshift; Positions=105, 125, 129, 235, 241; Evidence={ECO:0000305};
Similarity	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily. {ECO:0000255\|PROSITE- ProRule:PRU00159}.
Similarity	Contains 1 protein kinase domain. {ECO:0000255\|PROSITE-ProRule:PRU00159}.
Subcellular Location	Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle pole. Note=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. Colocalized with SIRT2 at centrosome. Moves to the midbody during both telophase and cytokinesis. Associates with both the pericentriolar material (PCM) and centrioles. {ECO:0000250}.
Subunit	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. Interacts also with its substrates ARHGEF2, BORA, BRCA1, KIF2A, PARD3, and p53/TP53. Interaction with BORA promotes phosphorylation of PLK1. Interacts with PIFO. Interacts with GADD45A, competing with its oligomerization. Interacts (via C- terminus) with AUNIP (via C-terminus). Identified in a complex with AUNIP and NIN. Interacts with FRY; this interaction facilitates AURKA-mediated PLK1 phosphorylation. Interacts with SIRT2. {ECO:0000250, ECO:0000269\|PubMed:11551964, ECO:0000269\|PubMed:12237287, ECO:0000269\|PubMed:12467573, ECO:0000269\|PubMed:14580337, ECO:0000269\|PubMed:14603251, ECO:0000269\|PubMed:14702041, ECO:0000269\|PubMed:14990569, ECO:0000269\|PubMed:15966895, ECO:0000269\|PubMed:16890155, ECO:0000269\|PubMed:17229885, ECO:0000269\|PubMed:17488622, ECO:0000269\|PubMed:17726514, ECO:0000269\|PubMed:18662907, ECO:0000269\|PubMed:19140666, ECO:0000269\|PubMed:19351716, ECO:0000269\|PubMed:19357306, ECO:0000269\|PubMed:19402633, ECO:0000269\|PubMed:19668197, ECO:0000269\|PubMed:19801554, ECO:0000269\|PubMed:19812038, ECO:0000269\|PubMed:20460379, ECO:0000269\|PubMed:20596670, ECO:0000269\|PubMed:20643351, ECO:0000269\|PubMed:21225229, ECO:0000269\|PubMed:22014574, ECO:0000269\|PubMed:22753416}.
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.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/AURKAID730ch20q13.html";