ID STK6_HUMAN Reviewed; 403 AA. AC O14965; O60445; O75873; Q9BQD6; Q9UPG5; DT 27-JAN-2003, integrated into UniProtKB/Swiss-Prot. DT 27-JAN-2003, sequence version 2. DT 22-JUL-2008, entry version 98. DE RecName: Full=Serine/threonine-protein kinase 6; DE EC=2.7.11.1; DE AltName: Full=Aurora kinase A; DE Short=Aurora-A; DE AltName: Full=Serine/threonine kinase 15; DE AltName: Full=Aurora/IPL1-related kinase 1; DE Short=Aurora-related kinase 1; DE Short=hARK1; DE AltName: Full=Breast tumor-amplified kinase; 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 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 [7] RP CELL-CYCLE REGULATION. 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 [8] 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 [9] RP REVIEW. RX MEDLINE=21306577; PubMed=11413462; DOI=10.1038/35048096; RA Nigg E.A.; RT "Mitotic kinases as regulators of cell division and its checkpoints."; RL Nat. Rev. Mol. Cell Biol. 2:21-32(2001). 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 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 [12] 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 [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-369, AND MASS RP SPECTROMETRY. 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 [14] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 107-403. 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 [15] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 125-391. 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 [16] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 122-403, AND PHOSPHORYLATION RP AT THR-287 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 [17] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 123-401. 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 [18] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 100-403. 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 [19] 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: May play a role in cell cycle regulation during anaphase CC and/or telophase, in relation to the function of the CC centrosome/spindle pole region during chromosome segregation. May CC be involved in microtubule formation and/or stabilization. May CC play a key role during tumor development and progression. CC Phosphorylates ARHGEF2 and BORA. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- SUBUNIT: Interacts with TACC1 and CPEB1. Interacts with its CC substrates BORA and ARHGEF2. 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 P61026:RAB10; NbExp=1; IntAct=EBI-448680, EBI-726075; 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: Centrosome. Spindle. Note=Localizes on CC 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. Expression is cell-cycle regulated, low in CC G1/S, accumulates during G2/M, and decreases rapidly after. CC -!- PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. CC -!- DISEASE: Defects in AURKA are responsible for numerical centrosome CC aberrations including aneuploidy. 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 --------------------------------------------------------------------------- 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; BC001280; AAH01280.1; -; mRNA. DR EMBL; BC002499; AAH02499.1; -; mRNA. DR EMBL; BC006423; AAH06423.1; -; mRNA. DR EMBL; BC027464; AAH27464.1; -; mRNA. DR PIR; JC5974; JC5974. DR RefSeq; NP_003591.2; -. DR RefSeq; NP_940835.1; -. DR RefSeq; NP_940836.1; -. DR RefSeq; NP_940837.1; -. DR RefSeq; NP_940838.1; -. DR RefSeq; NP_940839.1; -. 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/B=125-391. 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 IntAct; O14965; -. DR PhosphoSite; O14965; -. DR Ensembl; ENSG00000087586; Homo sapiens. DR GeneID; 6790; -. DR KEGG; hsa:6790; -. DR H-InvDB; HIX0015930; -. DR HGNC; HGNC:11393; AURKA. DR HPA; CAB001454; -. DR HPA; HPA002636; -. DR MIM; 603072; gene. DR PharmGKB; PA36201; -. DR HOGENOM; O14965; -. DR HOVERGEN; O14965; -. DR Reactome; REACT_152; Cell Cycle, Mitotic. DR BindingDB; O14965; -. DR LinkHub; O14965; -. DR CleanEx; HS_AURKA; -. DR GermOnline; ENSG00000087586; Homo sapiens. DR GO; GO:0005634; C:nucleus; TAS:ProtInc. DR GO; GO:0005819; C:spindle; TAS:ProtInc. DR GO; GO:0005515; F:protein binding; IDA:UniProtKB. DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc. DR GO; GO:0007067; P:mitosis; TAS:ProtInc. DR GO; GO:0048015; P:phosphoinositide-mediated signaling; NAS:UniProtKB. DR GO; GO:0006468; P:protein amino acid phosphorylation; TAS:ProtInc. DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB. DR GO; GO:0007051; P:spindle organization and biogenesis; NAS:UniProtKB. DR InterPro; IPR000719; Prot_kinase_core. DR InterPro; IPR017441; Protein_kinase_ATP_bd_CS. DR InterPro; IPR017442; Se/Thr_pkinase-rel. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR InterPro; IPR002290; Ser_thr_pkinase. DR Pfam; PF00069; Pkinase; 1. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00220; S_TKc; 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; Kinase; Nucleotide-binding; KW Phosphoprotein; Polymorphism; Serine/threonine-protein kinase; KW Transferase. FT CHAIN 1 403 Serine/threonine-protein kinase 6. FT /FTId=PRO_0000086692. FT DOMAIN 133 383 Protein kinase. FT NP_BIND 139 147 ATP (By similarity). FT ACT_SITE 256 256 Proton acceptor (By similarity). FT BINDING 162 162 ATP (By similarity). 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. FT /FTId=VAR_041127. FT VARIANT 57 57 V -> I (in dbSNP:rs1047972). FT /FTId=VAR_030842. FT VARIANT 155 155 S -> R (in a colorectal adenocarcinoma FT sample; somatic mutation). FT /FTId=VAR_041128. FT VARIANT 174 174 V -> M (in a metastatic melanoma sample; FT somatic mutation). FT /FTId=VAR_041129. FT VARIANT 373 373 M -> V. FT /FTId=VAR_041130. 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 //