ID STK6_HUMAN Reviewed; 403 AA. AC O14965; E1P5F9; O60445; O75873; Q9BQD6; Q9UPG5; DT 27-JAN-2003, integrated into UniProtKB/Swiss-Prot. DT 27-JAN-2003, sequence version 2. DT 08-FEB-2011, entry version 129. DE RecName: Full=Serine/threonine-protein kinase 6; DE EC=2.7.11.1; DE AltName: Full=Aurora kinase A; DE AltName: Full=Aurora/IPL1-related kinase 1; DE Short=ARK-1; DE Short=Aurora-related kinase 1; DE Short=hARK1; DE AltName: Full=Breast tumor-amplified kinase; DE AltName: Full=Serine/threonine-protein kinase 15; DE AltName: Full=Serine/threonine-protein kinase aurora-A; GN Name=AURKA; Synonyms=AIK, ARK1, AURA, BTAK, STK15, STK6; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Blood; RX MEDLINE=97298083; PubMed=9153231; DOI=10.1074/jbc.272.21.13766; RA Kimura M., Kotani S., Hattori T., Sumi N., Yoshioka T., Todokoro K., RA Okano Y.; RT "Cell cycle-dependent expression and spindle pole localization of a RT novel human protein kinase, Aik, related to Aurora of Drosophila and RT yeast Ipl1."; RL J. Biol. Chem. 272:13766-13771(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ILE-57. RX MEDLINE=98183439; PubMed=9514916; DOI=10.1006/bbrc.1998.8250; RA Shindo M., Nakano H., Kuroyanagi H., Shirasawa T., Mihara M., RA Gilbert D.J., Jenkins N.A., Copeland N.G., Yagita H., Okumura K.; RT "cDNA cloning, expression, subcellular localization, and chromosomal RT assignment of mammalian aurora homologues, aurora-related kinase (ARK) RT 1 and 2."; RL Biochem. Biophys. Res. Commun. 244:285-292(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ILE-31. RC TISSUE=Mammary gland; RX MEDLINE=98442657; PubMed=9771714; DOI=10.1038/2496; RA Zhou H., Kuang J., Zhong L., Kuo W.-L., Gray J.W., Sahin A., RA Brinkley B.R., Sen S.; RT "Tumour amplified kinase STK15/BTAK induces centrosome amplification, RT aneuploidy and transformation."; RL Nat. Genet. 20:189-193(1998). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Wang L., Thibodeau S.N.; RT "Mutational analysis of the STK15 gene in human tumors."; RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=21638749; PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., RA Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cervix, Colon, Kidney, and Muscle; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP UBIQUITINATION, PROTEASOMAL DEGRADATION, AND MUTAGENESIS OF ARG-205. RX PubMed=10851084; DOI=10.1038/sj.onc.1203609; RA Honda K., Mihara H., Kato Y., Yamaguchi A., Tanaka H., Yasuda H., RA Furukawa K., Urano T.; RT "Degradation of human Aurora2 protein kinase by the anaphase-promoting RT complex-ubiquitin-proteasome pathway."; RL Oncogene 19:2812-2819(2000). RN [9] RP INDUCTION. RX MEDLINE=21895866; PubMed=11790771; DOI=10.1074/jbc.M108252200; RA Tanaka M., Ueda A., Kanamori H., Ideguchi H., Yang J., Kitajima S., RA Ishigatsubo Y.; RT "Cell-cycle-dependent regulation of human aurora A transcription is RT mediated by periodic repression of E4TF1."; RL J. Biol. Chem. 277:10719-10726(2002). RN [10] RP INTERACTION WITH TACC1. RX PubMed=14603251; DOI=10.1038/sj.onc.1206972; RA Conte N., Delaval B., Ginestier C., Ferrand A., Isnardon D., RA Larroque C., Prigent C., Seraphin B., Jacquemier J., Birnbaum D.; RT "TACC1-chTOG-Aurora A protein complex in breast cancer."; RL Oncogene 22:8102-8116(2003). RN [11] RP FUNCTION, INTERACTION WITH BRCA1, PHOSPHORYLATION AT THR-288, AND RP MUTAGENESIS OF LYS-162. RX PubMed=14990569; DOI=10.1074/jbc.M311780200; RA Ouchi M., Fujiuchi N., Sasai K., Katayama H., Minamishima Y.A., RA Ongusaha P.P., Deng C., Sen S., Lee S.W., Ouchi T.; RT "BRCA1 phosphorylation by Aurora-A in the regulation of G2 to M RT transition."; RL J. Biol. Chem. 279:19643-19648(2004). RN [12] RP INTERACTION WITH CPEB1. RX PubMed=15966895; DOI=10.1111/j.1365-2443.2005.00870.x; RA Sasayama T., Marumoto T., Kunitoku N., Zhang D., Tamaki N., RA Kohmura E., Saya H., Hirota T.; RT "Over-expression of Aurora-A targets cytoplasmic polyadenylation RT element binding protein and promotes mRNA polyadenylation of Cdk1 and RT cyclin B1."; RL Genes Cells 10:627-638(2005). RN [13] RP INTERACTION WITH BORA. RX PubMed=16890155; DOI=10.1016/j.devcel.2006.06.002; RA Hutterer A., Berdnik D., Wirtz-Peitz F., Zigman M., Schleiffer A., RA Knoblich J.A.; RT "Mitotic activation of the kinase Aurora-A requires its binding RT partner Bora."; RL Dev. Cell 11:147-157(2006). RN [14] RP FUNCTION. RX PubMed=18056443; DOI=10.1158/0008-5472.CAN-07-2578; RA Sankaran S., Crone D.E., Palazzo R.E., Parvin J.D.; RT "Aurora-A kinase regulates breast cancer associated gene 1 inhibition RT of centrosome-dependent microtubule nucleation."; RL Cancer Res. 67:11186-11194(2007). RN [15] RP INTERACTION WITH ARHGEF2. RX PubMed=17488622; DOI=10.1016/j.devcel.2007.03.014; RA Birkenfeld J., Nalbant P., Bohl B.P., Pertz O., Hahn K.M., RA Bokoch G.M.; RT "GEF-H1 modulates localized RhoA activation during cytokinesis under RT the control of mitotic kinases."; RL Dev. Cell 12:699-712(2007). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-369, AND MASS RP SPECTROMETRY. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=19007248; DOI=10.1021/ac801708p; RA Wang B., Malik R., Nigg E.A., Korner R.; RT "Evaluation of the low-specificity protease elastase for large-scale RT phosphoproteome analysis."; RL Anal. Chem. 80:9526-9533(2008). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41; SER-51 AND SER-83, RP AND MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [19] RP FUNCTION. RX PubMed=18615013; DOI=10.1038/nature07185; RA Macurek L., Lindqvist A., Lim D., Lampson M.A., Klompmaker R., RA Freire R., Clouin C., Taylor S.S., Yaffe M.B., Medema R.H.; RT "Polo-like kinase-1 is activated by aurora A to promote checkpoint RT recovery."; RL Nature 455:119-123(2008). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RA Colinge J., Superti-Furga G., Bennett K.L.; RL Submitted (OCT-2008) to UniProtKB. RN [21] RP FUNCTION, AUTOPHOSPHORYLATION, AND INTERACTION WITH PARD3. RX PubMed=19812038; DOI=10.1074/jbc.M109.055897; RA Khazaei M.R., Puschel A.W.; RT "Phosphorylation of the par polarity complex protein Par3 at serine RT 962 is mediated by aurora A and regulates its function in neuronal RT polarity."; RL J. Biol. Chem. 284:33571-33579(2009). RN [22] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH KIF2A. RX PubMed=19351716; DOI=10.1242/jcs.044321; RA Jang C.Y., Coppinger J.A., Seki A., Yates J.R. III, Fang G.; RT "Plk1 and Aurora A regulate the depolymerase activity and the cellular RT localization of Kif2a."; RL J. Cell Sci. 122:1334-1341(2009). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-53, AND MASS RP SPECTROMETRY. RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [24] RP FUNCTION, INTERACTION WITH TPX2, PHOSPHORYLATION AT THR-287 AND RP THR-288, AND MUTAGENESIS OF THR287. RX PubMed=19668197; DOI=10.1038/ncb1919; RA Mori D., Yamada M., Mimori-Kiyosue Y., Shirai Y., Suzuki A., Ohno S., RA Saya H., Wynshaw-Boris A., Hirotsune S.; RT "An essential role of the aPKC-Aurora A-NDEL1 pathway in neurite RT elongation by modulation of microtubule dynamics."; RL Nat. Cell Biol. 11:1057-1068(2009). RN [25] RP INTERACTION WITH TPX2, MUTAGENESIS OF GLY-198, SUBCELLULAR LOCATION, RP AND FUNCTION. RX PubMed=19357306; DOI=10.1073/pnas.0900833106; RA Fu J., Bian M., Liu J., Jiang Q., Zhang C.; RT "A single amino acid change converts Aurora-A into Aurora-B-like RT kinase in terms of partner specificity and cellular function."; RL Proc. Natl. Acad. Sci. U.S.A. 106:6939-6944(2009). RN [26] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 107-403 IN COMPLEX WITH RP ADENOSINE, AND CATALYTIC ACTIVITY. RX PubMed=12237287; DOI=10.1074/jbc.C200426200; RA Cheetham G.M., Knegtel R.M., Coll J.T., Renwick S.B., Swenson L., RA Weber P., Lippke J.A., Austen D.A.; RT "Crystal structure of aurora-2, an oncogenic serine/threonine RT kinase."; RL J. Biol. Chem. 277:42419-42422(2002). RN [27] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 125-391 IN COMPLEX WITH ADP. RX MEDLINE=22357219; PubMed=12467573; DOI=10.1016/S0969-2126(02)00907-3; RA Nowakowski J., Cronin C.N., McRee D.E., Knuth M.W., Nelson C.G., RA Pavletich N.P., Rogers J., Sang B.C., Scheibe D.N., Swanson R.V., RA Thompson D.A.; RT "Structures of the cancer-related Aurora-A, FAK, and EphA2 protein RT kinases from nanovolume crystallography."; RL Structure 10:1659-1667(2002). RN [28] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 122-403 IN COMPLEX WITH TPX2, RP MUTAGENESIS OF ASP-274, ACTIVE SITE, AND PHOSPHORYLATION AT THR-287 RP AND THR-288. RX PubMed=14580337; DOI=10.1016/S1097-2765(03)00392-7; RA Bayliss R., Sardon T., Vernos I., Conti E.; RT "Structural basis of Aurora-A activation by TPX2 at the mitotic RT spindle."; RL Mol. Cell 12:851-862(2003). RN [29] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 123-401 IN COMPLEXES WITH RP ADPNP AND 5-AMINOPYRIMIDINYL QUINAZOLINE INHIBITOR, AND CATALYTIC RP ACTIVITY. RX PubMed=16337122; DOI=10.1016/j.bmcl.2005.11.053; RA Heron N.M., Anderson M., Blowers D.P., Breed J., Eden J.M., Green S., RA Hill G.B., Johnson T., Jung F.H., McMiken H.H., Mortlock A.A., RA Pannifer A.D., Pauptit R.A., Pink J., Roberts N.J., Rowsell S.; RT "SAR and inhibitor complex structure determination of a novel class of RT potent and specific Aurora kinase inhibitors."; RL Bioorg. Med. Chem. Lett. 16:1320-1323(2006). RN [30] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 100-403 IN COMPLEXES WITH RP SYNTHETIC INHIBITORS, AND FUNCTION. RX PubMed=17125279; DOI=10.1021/jm060897w; RA Fancelli D., Moll J., Varasi M., Bravo R., Artico R., Berta D., RA Bindi S., Cameron A., Candiani I., Cappella P., Carpinelli P., RA Croci W., Forte B., Giorgini M.L., Klapwijk J., Marsiglio A., RA Pesenti E., Rocchetti M., Roletto F., Severino D., Soncini C., RA Storici P., Tonani R., Zugnoni P., Vianello P.; RT "1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: identification of a potent RT aurora kinase inhibitor with a favorable antitumor kinase inhibition RT profile."; RL J. Med. Chem. 49:7247-7251(2006). RN [31] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 125-391 IN COMPLEX WITH RP VX-680 AND TPX2, PHOSPHORYLATION AT THR-288, MASS SPECTROMETRY, AND RP SUBUNIT. RX PubMed=18662907; DOI=10.1110/ps.036590.108; RA Zhao B., Smallwood A., Yang J., Koretke K., Nurse K., Calamari A., RA Kirkpatrick R.B., Lai Z.; RT "Modulation of kinase-inhibitor interactions by auxiliary protein RT binding: crystallography studies on Aurora A interactions with VX-680 RT and with TPX2."; RL Protein Sci. 17:1791-1797(2008). RN [32] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 127-388 IN COMPLEX WITH ADP, RP CHARACTERIZATION OF VARIANTS ARG-155 AND MET-174, AND INTERACTION WITH RP TPX2. RX PubMed=19801554; DOI=10.1074/jbc.M109.032722; RA Bibby R.A., Tang C., Faisal A., Drosopoulos K., Lubbe S., Houlston R., RA Bayliss R., Linardopoulos S.; RT "A cancer-associated aurora A mutant is mislocalized and misregulated RT due to loss of interaction with TPX2."; RL J. Biol. Chem. 284:33177-33184(2009). RN [33] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 123-401 IN COMPLEX WITH RP SYNTHETIC INHIBITOR, AND CATALYTIC ACTIVITY. RX PubMed=19140666; DOI=10.1021/jm801270e; RA Coumar M.S., Leou J.S., Shukla P., Wu J.S., Dixit A.K., Lin W.H., RA Chang C.Y., Lien T.W., Tan U.K., Chen C.H., Hsu J.T., Chao Y.S., RA Wu S.Y., Hsieh H.P.; RT "Structure-based drug design of novel Aurora kinase A inhibitors: RT structural basis for potency and specificity."; RL J. Med. Chem. 52:1050-1062(2009). RN [34] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 125-391 IN COMPLEX WITH RP SYNTHETIC INHIBITOR, AND CATALYTIC ACTIVITY. RX PubMed=19402633; DOI=10.1021/jm9000314; RA Aliagas-Martin I., Burdick D., Corson L., Dotson J., Drummond J., RA Fields C., Huang O.W., Hunsaker T., Kleinheinz T., Krueger E., RA Liang J., Moffat J., Phillips G., Pulk R., Rawson T.E., Ultsch M., RA Walker L., Wiesmann C., Zhang B., Zhu B.Y., Cochran A.G.; RT "A class of 2,4-bisanilinopyrimidine Aurora A inhibitors with RT unusually high selectivity against Aurora B."; RL J. Med. Chem. 52:3300-3307(2009). RN [35] RP VARIANTS ILE-31 AND ILE-57. RX PubMed=15867347; DOI=10.1158/0008-5472.CAN-04-2149; RA Kimura M.T., Mori T., Conroy J., Nowak N.J., Satomi S., Tamai K., RA Nagase H.; RT "Two functional coding single nucleotide polymorphisms in STK15 RT (Aurora-A) coordinately increase esophageal cancer risk."; RL Cancer Res. 65:3548-3554(2005). RN [36] RP VARIANTS ILE-31 AND ILE-57. RX PubMed=16011022; RA Chen L., Ao X., Ren Q., Wang Z.N., Lu C., Xu Y., Jiang L., Luo Y., RA Xu H.M., Zhang X.; RT "Linkage disequilibrium and haplotype analysis of two single RT nucleotide polymorphisms in STK15 in Chinese."; RL Yi Chuan Xue Bao 32:331-336(2005). RN [37] RP VARIANT ILE-31. RX PubMed=16762494; DOI=10.1016/j.canlet.2006.05.002; RA Tchatchou S., Wirtenberger M., Hemminki K., Sutter C., Meindl A., RA Wappenschmidt B., Kiechle M., Bugert P., Schmutzler R.K., RA Bartram C.R., Burwinkel B.; RT "Aurora kinases A and B and familial breast cancer risk."; RL Cancer Lett. 247:266-272(2007). RN [38] RP VARIANTS [LARGE SCALE ANALYSIS] ILE-31; LEU-50; ILE-57; ARG-155; RP MET-174 AND VAL-373. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Contributes to the regulation of cell cycle progression. CC Required for normal mitosis. Associates with the centrosome and CC the spindle microtubules during mitosis and functions in CC centrosome maturation, spindle assembly, maintenance of spindle CC bipolarity, centrosome separation and mitotic checkpoint control. CC Phosphorylates numerous target proteins, including ARHGEF2, BRCA1, CC KIF2A, NDEL1, PARD3, PLK1 and BORA. Regulates KIF2A tubulin CC depolymerase activity (By similarity). Required for normal axon CC formation. Plays a role in microtubule remodeling during neurite CC extension. Important for microtubule formation and/or CC stabilization. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- SUBUNIT: Interacts with TPX2. Interacts with TACC1 and CPEB1. CC Interacts with its substrates BORA, BRCA1, KIF2A, PARD3 and CC ARHGEF2. Interaction with BORA promotes phosphorylation of PLK1. CC -!- INTERACTION: CC Q9NWT8:AURKAIP1; NbExp=2; IntAct=EBI-448680, EBI-448665; CC P42771:CDKN2A; NbExp=1; IntAct=EBI-448680, EBI-375053; CC Q01469:FABP5; NbExp=1; IntAct=EBI-448680, EBI-1054073; CC P04198:MYCN; NbExp=2; IntAct=EBI-448680, EBI-878369; CC P61026:RAB10; NbExp=1; IntAct=EBI-448680, EBI-726075; CC P04179:SOD2; NbExp=1; IntAct=EBI-448680, EBI-716989; CC O75410-1:TACC1; NbExp=1; IntAct=EBI-448680, EBI-624252; CC Q9ULW0:TPX2; NbExp=1; IntAct=EBI-448680, EBI-1037322; CC P68036:UBE2L3; NbExp=1; IntAct=EBI-448680, EBI-711173; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, centrosome. CC Cytoplasm, cytoskeleton, spindle pole. Note=Detected at the CC neurite hillock in developing neurons (By similarity). Localizes CC on centrosomes in interphase cells and at each spindle pole in CC mitosis. CC -!- TISSUE SPECIFICITY: Highly expressed in testis and weakly in CC skeletal muscle, thymus and spleen. Also highly expressed in CC colon, ovarian, prostate, neuroblastoma, breast and cervical CC cancer cell lines. CC -!- INDUCTION: Expression is cell-cycle regulated, low in G1/S, CC accumulates during G2/M, and decreases rapidly after. CC -!- PTM: Activated by phosphorylation at Thr-288; this brings about a CC change in the conformation of the activation segment. CC Phosphorylation at Thr-288 varies during the cell cycle and is CC highest during M phase. Autophosphorylated at Thr-288 upon TPX2 CC binding. Phosphorylated upon DNA damage, probably by ATM or ATR. CC -!- PTM: Ubiquitinated by CHFR, leading to its degradation by the CC proteasome (By similarity). Ubiquitinated by the anaphase- CC promoting complex (APC), leading to its degradation by the CC proteasome. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr CC protein kinase family. Aurora subfamily. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- CAUTION: Although authors have considered STK6 and STK15 as two CC different proteins, it is clear that they are the same protein. CC -!- SEQUENCE CAUTION: CC Sequence=BAA23592.1; Type=Frameshift; Positions=105, 125, 129, 235, 241; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/AURKAID730ch20q13.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D84212; BAA23592.1; ALT_FRAME; mRNA. DR EMBL; AF008551; AAC12708.1; -; mRNA. DR EMBL; AF011467; AAC23448.1; -; Genomic_DNA. DR EMBL; AF011468; AAC63902.1; -; mRNA. DR EMBL; AF195947; AAF29508.1; -; Genomic_DNA. DR EMBL; AF195942; AAF29508.1; JOINED; Genomic_DNA. DR EMBL; AF195943; AAF29508.1; JOINED; Genomic_DNA. DR EMBL; AF195944; AAF29508.1; JOINED; Genomic_DNA. DR EMBL; AF195945; AAF29508.1; JOINED; Genomic_DNA. DR EMBL; AF195946; AAF29508.1; JOINED; Genomic_DNA. DR EMBL; AL121914; CAC12717.1; -; Genomic_DNA. DR EMBL; CH471077; EAW75550.1; -; Genomic_DNA. DR EMBL; CH471077; EAW75551.1; -; Genomic_DNA. DR EMBL; CH471077; EAW75552.1; -; Genomic_DNA. DR EMBL; CH471077; EAW75553.1; -; Genomic_DNA. DR EMBL; CH471077; EAW75554.1; -; Genomic_DNA. DR EMBL; CH471077; EAW75555.1; -; Genomic_DNA. DR EMBL; CH471077; EAW75556.1; -; Genomic_DNA. DR EMBL; CH471077; EAW75557.1; -; Genomic_DNA. DR EMBL; CH471077; EAW75558.1; -; Genomic_DNA. DR EMBL; CH471077; EAW75559.1; -; Genomic_DNA. DR EMBL; CH471077; EAW75561.1; -; Genomic_DNA. DR EMBL; CH471077; EAW75562.1; -; Genomic_DNA. DR EMBL; BC001280; AAH01280.1; -; mRNA. DR EMBL; BC002499; AAH02499.1; -; mRNA. DR EMBL; BC006423; AAH06423.1; -; mRNA. DR EMBL; BC027464; AAH27464.1; -; mRNA. DR IPI; IPI00298940; -. DR PIR; JC5974; JC5974. DR RefSeq; NP_003591.2; NM_003600.2. DR RefSeq; NP_940835.1; NM_198433.1. DR RefSeq; NP_940836.1; NM_198434.1. DR RefSeq; NP_940837.1; NM_198435.1. DR RefSeq; NP_940838.1; NM_198436.1. DR RefSeq; NP_940839.1; NM_198437.1. DR UniGene; Hs.250822; -. DR PDB; 1MQ4; X-ray; 1.90 A; A=125-391. DR PDB; 1MUO; X-ray; 2.90 A; A=107-403. DR PDB; 1OL5; X-ray; 2.50 A; A=122-403. DR PDB; 1OL6; X-ray; 3.00 A; A=122-403. DR PDB; 1OL7; X-ray; 2.75 A; A=122-403. DR PDB; 2BMC; X-ray; 2.60 A; A/B/C/D/E/F=100-403. DR PDB; 2C6D; X-ray; 2.20 A; A=124-398. DR PDB; 2C6E; X-ray; 2.10 A; A/B=123-401. DR PDB; 2DWB; X-ray; 2.50 A; A=122-403. DR PDB; 2J4Z; X-ray; 2.00 A; A/B=100-403. DR PDB; 2J50; X-ray; 3.00 A; A/B=126-403. DR PDB; 2NP8; X-ray; 2.25 A; A=125-391. DR PDB; 2W1C; X-ray; 3.24 A; A=122-389. DR PDB; 2W1D; X-ray; 2.97 A; A=122-389. DR PDB; 2W1E; X-ray; 2.93 A; A=122-389. DR PDB; 2W1F; X-ray; 2.85 A; A=122-389. DR PDB; 2W1G; X-ray; 2.71 A; A=122-389. DR PDB; 2WQE; X-ray; 2.50 A; A=127-388. DR PDB; 2WTV; X-ray; 2.40 A; A/B/C/D=122-403. DR PDB; 2WTW; X-ray; 3.30 A; A=122-403. DR PDB; 2X6D; X-ray; 2.80 A; A=122-403. DR PDB; 2X6E; X-ray; 3.35 A; A=122-403. DR PDB; 2X81; X-ray; 2.91 A; A=125-391. DR PDB; 2XNE; X-ray; 2.80 A; A=122-392. DR PDB; 2XNG; X-ray; 2.60 A; A=122-403. DR PDB; 2XRU; X-ray; 2.90 A; A=126-403. DR PDB; 3COH; X-ray; 2.70 A; A/B=125-391. DR PDB; 3E5A; X-ray; 2.30 A; A=125-391. DR PDB; 3EFW; X-ray; 2.29 A; A/B=1-403. DR PDB; 3FDN; X-ray; 1.90 A; A=123-401. DR PDB; 3H0Y; X-ray; 2.50 A; A=125-391. DR PDB; 3H0Z; X-ray; 2.92 A; A/B/C=125-391. DR PDB; 3H10; X-ray; 2.20 A; A/B/D=125-391. DR PDB; 3HA6; X-ray; 2.36 A; A=125-391. DR PDB; 3K5U; X-ray; 2.35 A; A=123-401. DR PDB; 3LAU; X-ray; 2.10 A; A=125-399. DR PDB; 3MYG; X-ray; 2.40 A; A=125-391. DR PDB; 3NRM; X-ray; 3.05 A; A=126-403. DR PDBsum; 1MQ4; -. DR PDBsum; 1MUO; -. DR PDBsum; 1OL5; -. DR PDBsum; 1OL6; -. DR PDBsum; 1OL7; -. DR PDBsum; 2BMC; -. DR PDBsum; 2C6D; -. DR PDBsum; 2C6E; -. DR PDBsum; 2DWB; -. DR PDBsum; 2J4Z; -. DR PDBsum; 2J50; -. DR PDBsum; 2NP8; -. DR PDBsum; 2W1C; -. DR PDBsum; 2W1D; -. DR PDBsum; 2W1E; -. DR PDBsum; 2W1F; -. DR PDBsum; 2W1G; -. DR PDBsum; 2WQE; -. DR PDBsum; 2WTV; -. DR PDBsum; 2WTW; -. DR PDBsum; 2X6D; -. DR PDBsum; 2X6E; -. DR PDBsum; 2X81; -. DR PDBsum; 2XNE; -. DR PDBsum; 2XNG; -. DR PDBsum; 2XRU; -. DR PDBsum; 3COH; -. DR PDBsum; 3E5A; -. DR PDBsum; 3EFW; -. DR PDBsum; 3FDN; -. DR PDBsum; 3H0Y; -. DR PDBsum; 3H0Z; -. DR PDBsum; 3H10; -. DR PDBsum; 3HA6; -. DR PDBsum; 3K5U; -. DR PDBsum; 3LAU; -. DR PDBsum; 3MYG; -. DR PDBsum; 3NRM; -. DR ProteinModelPortal; O14965; -. DR SMR; O14965; 126-394. DR DIP; DIP-33068N; -. DR IntAct; O14965; 30. DR STRING; O14965; -. DR PhosphoSite; O14965; -. DR PRIDE; O14965; -. DR Ensembl; ENST00000312783; ENSP00000321591; ENSG00000087586. DR Ensembl; ENST00000347343; ENSP00000216911; ENSG00000087586. DR Ensembl; ENST00000371356; ENSP00000360407; ENSG00000087586. DR Ensembl; ENST00000395909; ENSP00000379245; ENSG00000087586. DR Ensembl; ENST00000395911; ENSP00000379247; ENSG00000087586. DR Ensembl; ENST00000395913; ENSP00000379249; ENSG00000087586. DR Ensembl; ENST00000395914; ENSP00000379250; ENSG00000087586. DR Ensembl; ENST00000395915; ENSP00000379251; ENSG00000087586. DR GeneID; 6790; -. DR KEGG; hsa:6790; -. DR CTD; 6790; -. DR GeneCards; GC20M054944; -. DR H-InvDB; HIX0015930; -. DR HGNC; HGNC:11393; AURKA. DR HPA; CAB001454; -. DR HPA; HPA002636; -. DR MIM; 603072; gene. DR neXtProt; NX_O14965; -. DR PharmGKB; PA36201; -. DR HOGENOM; HBG755340; -. DR HOVERGEN; HBG108519; -. DR InParanoid; O14965; -. DR PhylomeDB; O14965; -. DR BRENDA; 2.7.11.1; 247. DR Pathway_Interaction_DB; aurora_a_pathway; Aurora A signaling. DR Pathway_Interaction_DB; aurora_b_pathway; Aurora B signaling. DR Pathway_Interaction_DB; aurora_kinase_pathway; Signaling by Aurora kinases. DR Reactome; REACT_152; Cell Cycle, Mitotic. DR BindingDB; O14965; -. DR NextBio; 26512; -. DR ArrayExpress; O14965; -. DR Bgee; O14965; -. DR CleanEx; HS_AURKA; -. DR Genevestigator; O14965; -. DR GermOnline; ENSG00000087586; Homo sapiens. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL. DR GO; GO:0005876; C:spindle microtubule; IDA:BHF-UCL. DR GO; GO:0031616; C:spindle pole centrosome; IDA:BHF-UCL. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW. DR GO; GO:0031145; P:anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; TAS:Reactome. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0007067; P:mitosis; TAS:ProtInc. DR GO; GO:0048015; P:phosphoinositide-mediated signaling; NAS:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc. DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB. DR GO; GO:0007051; P:spindle organization; NAS:UniProtKB. DR InterPro; IPR020636; Ca/CaM-dep_prot_kinase-like. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_cat_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR017442; Se/Thr_prot_kinase-like_dom. DR InterPro; IPR008271; Ser/Thr_prot_kinase_AS. DR InterPro; IPR002290; Ser/Thr_prot_kinase_dom. DR InterPro; IPR020663; Spindle_assmbl_checkpoint_kin. DR PANTHER; PTHR22982; Ca/CaM-dep_prot_kinase-like; 1. DR PANTHER; PTHR22982:SF49; Spindle_assmbl_checkpoint_kin; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Kinase_like; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Cell cycle; Cell division; KW Complete proteome; Cytoplasm; Cytoskeleton; Kinase; Microtubule; KW Mitosis; Nucleotide-binding; Phosphoprotein; Polymorphism; KW Proto-oncogene; Serine/threonine-protein kinase; Transferase; KW Ubl conjugation. FT CHAIN 1 403 Serine/threonine-protein kinase 6. FT /FTId=PRO_0000086692. FT DOMAIN 133 383 Protein kinase. FT NP_BIND 210 213 ATP. FT REGION 280 293 Activation segment. FT ACT_SITE 256 256 Proton acceptor. FT BINDING 143 143 ATP; via amide nitrogen. FT BINDING 162 162 ATP. FT BINDING 274 274 ATP. FT MOD_RES 41 41 Phosphoserine. FT MOD_RES 51 51 Phosphoserine. FT MOD_RES 53 53 Phosphoserine. FT MOD_RES 83 83 Phosphoserine. FT MOD_RES 287 287 Phosphothreonine. FT MOD_RES 288 288 Phosphothreonine. FT MOD_RES 369 369 Phosphoserine. FT VARIANT 11 11 G -> R (in dbSNP:rs6069717). FT /FTId=VAR_030840. FT VARIANT 31 31 F -> I (in dbSNP:rs2273535). FT /FTId=VAR_030841. FT VARIANT 50 50 P -> L (in dbSNP:rs34572020). FT /FTId=VAR_041127. FT VARIANT 57 57 V -> I (in dbSNP:rs1047972). FT /FTId=VAR_030842. FT VARIANT 104 104 S -> L (in dbSNP:rs2230743). FT /FTId=VAR_061745. FT VARIANT 155 155 S -> R (in a colorectal adenocarcinoma FT sample; somatic mutation; reduces FT interaction with TPX2). FT /FTId=VAR_041128. FT VARIANT 174 174 V -> M (in a metastatic melanoma sample; FT somatic mutation; constitutively enhanced FT kinase activity). FT /FTId=VAR_041129. FT VARIANT 373 373 M -> V (in dbSNP:rs33923703). FT /FTId=VAR_041130. FT MUTAGEN 162 162 K->R: Loss of kinase activity. FT MUTAGEN 198 198 G->N: Reduces interaction with TPX2. FT Reduces kinase activity tenfold. Promotes FT interaction with the AURKB binding FT partners INCENP and BIRC5 that are FT normally not bound by AURKA. FT MUTAGEN 205 205 R->A: Reduces ubiquitination and FT proteasomal degradation. FT MUTAGEN 274 274 D->N: Abolishes autophosphorylation. FT MUTAGEN 287 287 T->A: No direct effect on catalytic FT activity. FT MUTAGEN 287 287 T->E: Enhances interaction with TPX2. FT HELIX 130 132 FT STRAND 133 141 FT STRAND 143 152 FT TURN 153 155 FT STRAND 158 165 FT HELIX 166 172 FT HELIX 175 187 FT STRAND 196 201 FT STRAND 203 210 FT HELIX 218 225 FT HELIX 230 249 FT HELIX 259 261 FT STRAND 262 264 FT STRAND 270 272 FT HELIX 275 277 FT STRAND 279 283 FT HELIX 298 301 FT HELIX 309 324 FT HELIX 334 343 FT HELIX 354 363 FT HELIX 368 370 FT HELIX 374 378 FT HELIX 381 386 SQ SEQUENCE 403 AA; 45809 MW; 125F3594834CD157 CRC64; MDRSKENCIS GPVKATAPVG GPKRVLVTQQ FPCQNPLPVN SGQAQRVLCP SNSSQRVPLQ AQKLVSSHKP VQNQKQKQLQ ATSVPHPVSR PLNNTQKSKQ PLPSAPENNP EEELASKQKN EESKKRQWAL EDFEIGRPLG KGKFGNVYLA REKQSKFILA LKVLFKAQLE KAGVEHQLRR EVEIQSHLRH PNILRLYGYF HDATRVYLIL EYAPLGTVYR ELQKLSKFDE QRTATYITEL ANALSYCHSK RVIHRDIKPE NLLLGSAGEL KIADFGWSVH APSSRRTTLC GTLDYLPPEM IEGRMHDEKV DLWSLGVLCY EFLVGKPPFE ANTYQETYKR ISRVEFTFPD FVTEGARDLI SRLLKHNPSQ RPMLREVLEH PWITANSSKP SNCQNKESAS KQS //