ID:AURKA_HUMAN DESCRIPTION: RecName: Full=Aurora kinase A; EC=2.7.11.1; AltName: Full=Aurora 2; AltName: Full=Aurora/IPL1-related kinase 1; Short=ARK-1; Short=Aurora-related kinase 1; Short=hARK1; AltName: Full=Breast tumor-amplified kinase; AltName: Full=Serine/threonine-protein kinase 15; AltName: Full=Serine/threonine-protein kinase 6; AltName: Full=Serine/threonine-protein kinase aurora-A; 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 stabilizating 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. 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. 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. INTERACTION: Q9NWT8:AURKAIP1; NbExp=2; IntAct=EBI-448680, EBI-448665; P04198:MYCN; NbExp=2; IntAct=EBI-448680, EBI-878369; Q8VDQ8:Sirt2 (xeno); NbExp=5; IntAct=EBI-448680, EBI-911012; O15350:TP73; NbExp=11; IntAct=EBI-448680, EBI-389606; SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, 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. Moves to the midbody during both telophase and cytokinesis. Associates with both the pericentriolar material (PCM) and centrioles. 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. Phosphorylated upon DNA damage, probably by ATM or ATR. 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. 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. 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. SIMILARITY: Contains 1 protein kinase domain. CAUTION: Authors initially considered AURKA/STK6 and STK15 as 2 different proteins (PubMed:9771714). It is clear that they are the same protein. SEQUENCE CAUTION: Sequence=BAA23592.1; Type=Frameshift; Positions=105, 125, 129, 235, 241; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/AURKAID730ch20q13.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O14965
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AF011468 - Homo sapiens serine/threonine kinase (BTAK) mRNA, complete cds. LF383778 - JP 2014500723-A/191281: Polycomb-Associated Non-Coding RNAs. BC002499 - Homo sapiens aurora kinase A, mRNA (cDNA clone MGC:1605 IMAGE:3051177), complete cds. BC006423 - Homo sapiens aurora kinase A, mRNA (cDNA clone MGC:12769 IMAGE:3532438), complete cds. BC001280 - Homo sapiens aurora kinase A, mRNA (cDNA clone MGC:5133 IMAGE:3456017), complete cds. BC027464 - Homo sapiens aurora kinase A, mRNA (cDNA clone MGC:34538 IMAGE:4449474), complete cds. D84212 - Homo sapiens mRNA for aurora/IPL1-related kinase, complete cds. JD102605 - Sequence 83629 from Patent EP1572962. JD563566 - Sequence 544590 from Patent EP1572962. JD079856 - Sequence 60880 from Patent EP1572962. JD294824 - Sequence 275848 from Patent EP1572962. AK301769 - Homo sapiens cDNA FLJ58295 complete cds, highly similar to Serine/threonine-protein kinase 6 (EC 2.7.11.1). LF350763 - JP 2014500723-A/158266: Polycomb-Associated Non-Coding RNAs. JD128250 - Sequence 109274 from Patent EP1572962. JD085538 - Sequence 66562 from Patent EP1572962. JD238690 - Sequence 219714 from Patent EP1572962. JD115208 - Sequence 96232 from Patent EP1572962. JD167712 - Sequence 148736 from Patent EP1572962. JD133821 - Sequence 114845 from Patent EP1572962. JD082586 - Sequence 63610 from Patent EP1572962. DQ891270 - Synthetic construct clone IMAGE:100003900; FLH170609.01X; RZPDo839H0498D aurora kinase A (AURKA) gene, encodes complete protein. DQ894458 - Synthetic construct Homo sapiens clone IMAGE:100008918; FLH170605.01L; RZPDo839H0497D aurora kinase A (AURKA) gene, encodes complete protein. AF008551 - Homo sapiens aurora-related kinase 1 (ARK1) mRNA, complete cds. AK312776 - Homo sapiens cDNA, FLJ93192, highly similar to Homo sapiens serine/threonine kinase 6 (STK6), mRNA. AB463424 - Synthetic construct DNA, clone: pF1KB8310, Homo sapiens AURKA gene for aurora kinase A, without stop codon, in Flexi system. AM392948 - Synthetic construct Homo sapiens clone IMAGE:100002030 for hypothetical protein (AURKA gene). LF350764 - JP 2014500723-A/158267: Polycomb-Associated Non-Coding RNAs. LF350766 - JP 2014500723-A/158269: Polycomb-Associated Non-Coding RNAs. LF350767 - JP 2014500723-A/158270: Polycomb-Associated Non-Coding RNAs. LF350768 - JP 2014500723-A/158271: Polycomb-Associated Non-Coding RNAs. LF350769 - JP 2014500723-A/158272: Polycomb-Associated Non-Coding RNAs. LF350770 - JP 2014500723-A/158273: Polycomb-Associated Non-Coding RNAs. JD544843 - Sequence 525867 from Patent EP1572962. JD436218 - Sequence 417242 from Patent EP1572962. MA619355 - JP 2018138019-A/191281: Polycomb-Associated Non-Coding RNAs. MA586340 - JP 2018138019-A/158266: Polycomb-Associated Non-Coding RNAs. MA586341 - JP 2018138019-A/158267: Polycomb-Associated Non-Coding RNAs. MA586343 - JP 2018138019-A/158269: Polycomb-Associated Non-Coding RNAs. MA586344 - JP 2018138019-A/158270: Polycomb-Associated Non-Coding RNAs. MA586345 - JP 2018138019-A/158271: Polycomb-Associated Non-Coding RNAs. MA586346 - JP 2018138019-A/158272: Polycomb-Associated Non-Coding RNAs. MA586347 - JP 2018138019-A/158273: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_ranMSpathway - Role of Ran in mitotic spindle regulation
Reactome (by CSHL, EBI, and GO)
Protein O14965 (Reactome details) participates in the following event(s):
R-HSA-8853429 PHLDA1 binds AURKA R-HSA-8853496 SCF:FBXL7 binds AURKA R-HSA-8853444 AURKA phosphorylates PHLDA1 R-HSA-6791235 GADD45A binds AURKA R-HSA-2574845 AJUBA binds centrosome-associated AURKA R-HSA-8853405 TPX2 binds AURKA at centrosomes R-HSA-8854041 SCF-FBXL7 ubiquitinates AURKA R-HSA-174088 Association of cell cycle proteins with the APC/C:Cdh1 complex R-HSA-3000319 BORA binds PLK1 and AURKA R-HSA-2574840 AJUBA facilitates AURKA autophosphorylation R-HSA-3000310 AURKA phosphorylates PLK1 R-HSA-8853419 TPX2 promotes AURKA autophosphorylation R-HSA-174195 Ubiquitination of cell cycle proteins targeted by the APC/C:Cdh1complex R-HSA-6805103 AURKA phosphorylates TP53 R-HSA-8854521 Interaction between PHLDA1 and AURKA R-HSA-8854050 FBXL7 down-regulates AURKA during mitotic entry and in early mitosis R-HSA-4615885 SUMOylation of DNA replication proteins R-HSA-6804114 TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition R-HSA-8854518 AURKA Activation by TPX2 R-HSA-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 R-HSA-69275 G2/M Transition R-HSA-3108232 SUMO E3 ligases SUMOylate target proteins R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes R-HSA-174143 APC/C-mediated degradation of cell cycle proteins R-HSA-453274 Mitotic G2-G2/M phases R-HSA-2990846 SUMOylation R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation R-HSA-453276 Regulation of mitotic cell cycle R-HSA-69278 Cell Cycle (Mitotic) R-HSA-597592 Post-translational protein modification R-HSA-212436 Generic Transcription Pathway R-HSA-5633007 Regulation of TP53 Activity R-HSA-1640170 Cell Cycle R-HSA-392499 Metabolism of proteins R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
