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Identification
HMDB Protein ID HMDBP01317
Secondary Accession Numbers
  • 6613
Name Serine/threonine-protein kinase 6
Synonyms
  1. ARK-1
  2. Aurora kinase A
  3. Aurora-related kinase 1
  4. Aurora/IPL1-related kinase 1
  5. Breast tumor-amplified kinase
  6. Serine/threonine-protein kinase 15
  7. Serine/threonine-protein kinase aurora-A
  8. hARK1
Gene Name AURKA
Protein Type Enzyme
Biological Properties
General Function Involved in protein kinase activity
Specific Function Contributes to the regulation of cell cycle progression. Required for normal mitosis. Associates with the centrosome and the spindle microtubules during mitosis and functions in centrosome maturation, spindle assembly, maintenance of spindle bipolarity, centrosome separation and mitotic checkpoint control. Phosphorylates numerous target proteins, including ARHGEF2, BRCA1, KIF2A, NDEL1, PARD3, PLK1 and BORA. 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
Pathways Not Available
Reactions Not Available
GO Classification
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein kinase activity
protein serine/threonine kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Cytoplasm
  2. Cytoplasm
  3. cytoskeleton
  4. cytoskeleton
  5. centrosome
  6. spindle pole
Gene Properties
Chromosome Location Chromosome:2
Locus 20q13
SNPs AURKA
Gene Sequence
>1212 bp
ATGGACCGATCTAAAGAAAACTGCATTTCAGGACCTGTTAAGGCTACAGCTCCAGTTGGA
GGTCCAAAACGTGTTCTCGTGACTCAGCAATTTCCTTGTCAGAATCCATTACCTGTAAAT
AGTGGCCAGGCTCAGCGGGTCTTGTGTCCTTCAAATTCTTCCCAGCGCATTCCTTTGCAA
GCACAAAAGCTTGTCTCCAGTCACAAGCCGGTTCAGAATCAGAAGCAGAAGCAATTGCAG
GCAACCAGTGTACCTCATCCTGTCTCCAGGCCACTGAATAACACCCAAAAGAGCAAGCAG
CCCCTGCCATCGGCACCTGAAAATAATCCTGAGGAGGAACTGGCATCAAAACAGAAAAAT
GAAGAATCAAAAAAGAGGCAGTGGGCTTTGGAAGACTTTGAAATTGGTCGCCCTCTGGGT
AAAGGAAAGTTTGGTAATGTTTATTTGGCAAGAGAAAAGCAAAGCAAGTTTATTCTGGCT
CTTAAAGTGTTATTTAAAGCTCAGCTGGAGAAAGCCGGAGTGGAGCATCAGCTCAGAAGA
GAAGTAGAAATACAGTCCCACCTTCGGCATCCTAATATTCTTAGACTGTATGGTTATTTC
CATGATGCTACCAGAGTCTACCTAATTCTGGAATATGCACCACTTGGAACAGTTTATAGA
GAACTTCAGAAACTTTCAAAGTTTGATGAGCAGAGAACTGCTACTTATATAACAGAATTG
GCAAATGCCCTGTCTTACTGCCATTCGAAGAGAGTTATTCATAGAGACATTAAGCCAGAG
AACTTACTTCTTGGATCAGCTGGAGAGCTTAAAATTGCAGATTTTGGGTGGTCAGTACAT
GCTCCATCTTCCAGGAGGACCACTCTCTGTGGCACCCTGGACTACCTGCCCCCTGAAATG
ATTGAAGGTCGGATGCATGATGAGAAGGTGGATCTCTGGAGCCTTGGAGTTCTTTGCTAT
GAATTTTTAGTTGGGAAGCCTCCTTTTGAGGCAAACACATACCAAGAGACCTACAAAAGA
ATATCACGGGTTGAATTCACATTCCCTGACTTTGTAACAGAGGGAGCCAGGGACCTCATT
TCAAGACTGTTGAAGCATAATCCCAGCCAGAGGCCAATGCTCAGAGAAGTACTTGAACAC
CCCTGGATCACAGCAAATTCATCAAAACCATCAAATTGCCAAAACAAAGAATCAGCTAGC
AAACAGTCTTAG
Protein Properties
Number of Residues 403
Molecular Weight 45809.0
Theoretical pI 9.9
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Serine/threonine-protein kinase 6
MDRSKENCISGPVKATAPVGGPKRVLVTQQFPCQNPLPVNSGQAQRVLCPSNSSQRVPLQ
AQKLVSSHKPVQNQKQKQLQATSVPHPVSRPLNNTQKSKQPLPSAPENNPEEELASKQKN
EESKKRQWALEDFEIGRPLGKGKFGNVYLAREKQSKFILALKVLFKAQLEKAGVEHQLRR
EVEIQSHLRHPNILRLYGYFHDATRVYLILEYAPLGTVYRELQKLSKFDEQRTATYITEL
ANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFGWSVHAPSSRRTTLCGTLDYLPPEM
IEGRMHDEKVDLWSLGVLCYEFLVGKPPFEANTYQETYKRISRVEFTFPDFVTEGARDLI
SRLLKHNPSQRPMLREVLEHPWITANSSKPSNCQNKESASKQS
GenBank ID Protein 2979628
UniProtKB/Swiss-Prot ID O14965
UniProtKB/Swiss-Prot Entry Name STK6_HUMAN
PDB IDs
GenBank Gene ID AF008551
GeneCard ID AURKA
GenAtlas ID AURKA
HGNC ID HGNC:11393
References
General References
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  2. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976 ]
  3. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195 ]
  4. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007 May 25;316(5828):1160-6. [PubMed:17525332 ]
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  6. Wang B, Malik R, Nigg EA, Korner R: Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis. Anal Chem. 2008 Dec 15;80(24):9526-33. doi: 10.1021/ac801708p. [PubMed:19007248 ]
  7. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [PubMed:17344846 ]
  8. Nowakowski J, Cronin CN, McRee DE, Knuth MW, Nelson CG, Pavletich NP, Rogers J, Sang BC, Scheibe DN, Swanson RV, Thompson DA: Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography. Structure. 2002 Dec;10(12):1659-67. [PubMed:12467573 ]
  9. Kimura M, Kotani S, Hattori T, Sumi N, Yoshioka T, Todokoro K, Okano Y: Cell cycle-dependent expression and spindle pole localization of a novel human protein kinase, Aik, related to Aurora of Drosophila and yeast Ipl1. J Biol Chem. 1997 May 23;272(21):13766-71. [PubMed:9153231 ]
  10. Shindo M, Nakano H, Kuroyanagi H, Shirasawa T, Mihara M, Gilbert DJ, Jenkins NA, Copeland NG, Yagita H, Okumura K: cDNA cloning, expression, subcellular localization, and chromosomal assignment of mammalian aurora homologues, aurora-related kinase (ARK) 1 and 2. Biochem Biophys Res Commun. 1998 Mar 6;244(1):285-92. [PubMed:9514916 ]
  11. Zhou H, Kuang J, Zhong L, Kuo WL, Gray JW, Sahin A, Brinkley BR, Sen S: Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet. 1998 Oct;20(2):189-93. [PubMed:9771714 ]
  12. Honda K, Mihara H, Kato Y, Yamaguchi A, Tanaka H, Yasuda H, Furukawa K, Urano T: Degradation of human Aurora2 protein kinase by the anaphase-promoting complex-ubiquitin-proteasome pathway. Oncogene. 2000 Jun 1;19(24):2812-9. [PubMed:10851084 ]
  13. Tanaka M, Ueda A, Kanamori H, Ideguchi H, Yang J, Kitajima S, Ishigatsubo Y: Cell-cycle-dependent regulation of human aurora A transcription is mediated by periodic repression of E4TF1. J Biol Chem. 2002 Mar 22;277(12):10719-26. Epub 2002 Jan 14. [PubMed:11790771 ]
  14. Conte N, Delaval B, Ginestier C, Ferrand A, Isnardon D, Larroque C, Prigent C, Seraphin B, Jacquemier J, Birnbaum D: TACC1-chTOG-Aurora A protein complex in breast cancer. Oncogene. 2003 Nov 6;22(50):8102-16. [PubMed:14603251 ]
  15. Ouchi M, Fujiuchi N, Sasai K, Katayama H, Minamishima YA, Ongusaha PP, Deng C, Sen S, Lee SW, Ouchi T: BRCA1 phosphorylation by Aurora-A in the regulation of G2 to M transition. J Biol Chem. 2004 May 7;279(19):19643-8. Epub 2004 Feb 27. [PubMed:14990569 ]
  16. Sasayama T, Marumoto T, Kunitoku N, Zhang D, Tamaki N, Kohmura E, Saya H, Hirota T: Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1. Genes Cells. 2005 Jul;10(7):627-38. [PubMed:15966895 ]
  17. Hutterer A, Berdnik D, Wirtz-Peitz F, Zigman M, Schleiffer A, Knoblich JA: Mitotic activation of the kinase Aurora-A requires its binding partner Bora. Dev Cell. 2006 Aug;11(2):147-57. [PubMed:16890155 ]
  18. Sankaran S, Crone DE, Palazzo RE, Parvin JD: Aurora-A kinase regulates breast cancer associated gene 1 inhibition of centrosome-dependent microtubule nucleation. Cancer Res. 2007 Dec 1;67(23):11186-94. [PubMed:18056443 ]
  19. Birkenfeld J, Nalbant P, Bohl BP, Pertz O, Hahn KM, Bokoch GM: GEF-H1 modulates localized RhoA activation during cytokinesis under the control of mitotic kinases. Dev Cell. 2007 May;12(5):699-712. [PubMed:17488622 ]
  20. Macurek L, Lindqvist A, Lim D, Lampson MA, Klompmaker R, Freire R, Clouin C, Taylor SS, Yaffe MB, Medema RH: Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery. Nature. 2008 Sep 4;455(7209):119-23. doi: 10.1038/nature07185. Epub 2008 Jul 9. [PubMed:18615013 ]
  21. Khazaei MR, Puschel AW: Phosphorylation of the par polarity complex protein Par3 at serine 962 is mediated by aurora a and regulates its function in neuronal polarity. J Biol Chem. 2009 Nov 27;284(48):33571-9. doi: 10.1074/jbc.M109.055897. Epub 2009 Oct 6. [PubMed:19812038 ]
  22. Jang CY, Coppinger JA, Seki A, Yates JR 3rd, Fang G: Plk1 and Aurora A regulate the depolymerase activity and the cellular localization of Kif2a. J Cell Sci. 2009 May 1;122(Pt 9):1334-41. doi: 10.1242/jcs.044321. Epub 2009 Apr 7. [PubMed:19351716 ]
  23. Mori D, Yamada M, Mimori-Kiyosue Y, Shirai Y, Suzuki A, Ohno S, Saya H, Wynshaw-Boris A, Hirotsune S: An essential role of the aPKC-Aurora A-NDEL1 pathway in neurite elongation by modulation of microtubule dynamics. Nat Cell Biol. 2009 Sep;11(9):1057-68. doi: 10.1038/ncb1919. Epub 2009 Aug 9. [PubMed:19668197 ]
  24. Fu J, Bian M, Liu J, Jiang Q, Zhang C: A single amino acid change converts Aurora-A into Aurora-B-like kinase in terms of partner specificity and cellular function. Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):6939-44. doi: 10.1073/pnas.0900833106. Epub 2009 Apr 8. [PubMed:19357306 ]
  25. Cheetham GM, Knegtel RM, Coll JT, Renwick SB, Swenson L, Weber P, Lippke JA, Austen DA: Crystal structure of aurora-2, an oncogenic serine/threonine kinase. J Biol Chem. 2002 Nov 8;277(45):42419-22. Epub 2002 Sep 16. [PubMed:12237287 ]
  26. Bayliss R, Sardon T, Vernos I, Conti E: Structural basis of Aurora-A activation by TPX2 at the mitotic spindle. Mol Cell. 2003 Oct;12(4):851-62. [PubMed:14580337 ]
  27. Heron NM, Anderson M, Blowers DP, Breed J, Eden JM, Green S, Hill GB, Johnson T, Jung FH, McMiken HH, Mortlock AA, Pannifer AD, Pauptit RA, Pink J, Roberts NJ, Rowsell S: SAR and inhibitor complex structure determination of a novel class of potent and specific Aurora kinase inhibitors. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1320-3. Epub 2005 Dec 5. [PubMed:16337122 ]
  28. Fancelli D, Moll J, Varasi M, Bravo R, Artico R, Berta D, Bindi S, Cameron A, Candiani I, Cappella P, Carpinelli P, Croci W, Forte B, Giorgini ML, Klapwijk J, Marsiglio A, Pesenti E, Rocchetti M, Roletto F, Severino D, Soncini C, Storici P, Tonani R, Zugnoni P, Vianello P: 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: identification of a potent Aurora kinase inhibitor with a favorable antitumor kinase inhibition profile. J Med Chem. 2006 Nov 30;49(24):7247-51. [PubMed:17125279 ]
  29. Zhao B, Smallwood A, Yang J, Koretke K, Nurse K, Calamari A, Kirkpatrick RB, Lai Z: Modulation of kinase-inhibitor interactions by auxiliary protein binding: crystallography studies on Aurora A interactions with VX-680 and with TPX2. Protein Sci. 2008 Oct;17(10):1791-7. doi: 10.1110/ps.036590.108. Epub 2008 Jul 28. [PubMed:18662907 ]
  30. Bibby RA, Tang C, Faisal A, Drosopoulos K, Lubbe S, Houlston R, Bayliss R, Linardopoulos S: A cancer-associated aurora A mutant is mislocalized and misregulated due to loss of interaction with TPX2. J Biol Chem. 2009 Nov 27;284(48):33177-84. doi: 10.1074/jbc.M109.032722. Epub 2009 Oct 2. [PubMed:19801554 ]
  31. Coumar MS, Leou JS, Shukla P, Wu JS, Dixit AK, Lin WH, Chang CY, Lien TW, Tan UK, Chen CH, Hsu JT, Chao YS, Wu SY, Hsieh HP: Structure-based drug design of novel Aurora kinase A inhibitors: structural basis for potency and specificity. J Med Chem. 2009 Feb 26;52(4):1050-62. doi: 10.1021/jm801270e. [PubMed:19140666 ]
  32. Aliagas-Martin I, Burdick D, Corson L, Dotson J, Drummond J, Fields C, Huang OW, Hunsaker T, Kleinheinz T, Krueger E, Liang J, Moffat J, Phillips G, Pulk R, Rawson TE, Ultsch M, Walker L, Wiesmann C, Zhang B, Zhu BY, Cochran AG: A class of 2,4-bisanilinopyrimidine Aurora A inhibitors with unusually high selectivity against Aurora B. J Med Chem. 2009 May 28;52(10):3300-7. doi: 10.1021/jm9000314. [PubMed:19402633 ]
  33. Kimura MT, Mori T, Conroy J, Nowak NJ, Satomi S, Tamai K, Nagase H: Two functional coding single nucleotide polymorphisms in STK15 (Aurora-A) coordinately increase esophageal cancer risk. Cancer Res. 2005 May 1;65(9):3548-54. [PubMed:15867347 ]
  34. Chen L, Ao X, Ren Q, Wang ZN, Lu C, Xu Y, Jiang L, Luo Y, Xu HM, Zhang X: Linkage disequilibrium and haplotype analysis of two single nucleotide polymorphisms in STK15 in Chinese. Yi Chuan Xue Bao. 2005 Apr;32(4):331-6. [PubMed:16011022 ]
  35. Tchatchou S, Wirtenberger M, Hemminki K, Sutter C, Meindl A, Wappenschmidt B, Kiechle M, Bugert P, Schmutzler RK, Bartram CR, Burwinkel B: Aurora kinases A and B and familial breast cancer risk. Cancer Lett. 2007 Mar 18;247(2):266-72. Epub 2006 Jun 9. [PubMed:16762494 ]