Reviewed, UniProtKB/Swiss-Prot O14965 (STK6_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase 6
    EC=2.7.11.1
Alternative name(s):
    Aurora kinase A
      Short name=Aurora-A
    Serine/threonine kinase 15
    Aurora/IPL1-related kinase 1
      Short name=Aurora-related kinase 1
      Short name=hARK1
    Breast tumor-amplified kinase

Gene names

Name:	AURKA
Synonyms:	AIK, ARK1, AURA, BTAK, STK15, STK6

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	403 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May play a role in cell cycle regulation during anaphase and/or telophase, in relation to the function of the centrosome/spindle pole region during chromosome segregation. May be involved in microtubule formation and/or stabilization. May play a key role during tumor development and progression. Phosphorylates ARHGEF2 and BORA.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Interacts with TACC1 and CPEB1. Interacts with its substrates BORA and ARHGEF2.
Subcellular location	Centrosome. Spindle. Note= Localizes on centrosomes in interphase cells and at each spindle pole in mitosis.
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. Expression is cell-cycle regulated, low in G1/S, accumulates during G2/M, and decreases rapidly after.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR.
Involvement in disease	Defects in AURKA are responsible for numerical centrosome aberrations including aneuploidy.
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily. Contains 1 protein kinase domain.
Caution	Although authors have considered STK6 and STK15 as two different proteins, it is clear that they are the same protein.
Sequence caution	The sequence BAA23592.1 differs from that shown. Reason: Frameshift at positions 105, 125, 129, 235 and 241.

Ontologies

Keywords
Biological process	Cell cycle
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	mitosis Ref.1 Traceable author statement. Source: ProtInc phosphoinositide-mediated signaling Non-traceable author statement. Source: UniProtKB protein amino acid phosphorylation Ref.1 Traceable author statement. Source: ProtInc regulation of protein stability Inferred from mutant phenotype. Source: UniProtKB spindle organization and biogenesis Non-traceable author statement. Source: UniProtKB
Cellular component	nucleus Ref.1 Traceable author statement. Source: ProtInc spindle Ref.1 Traceable author statement. Source: ProtInc
Molecular function	protein binding Ref.10 Ref.16 Inferred from direct assay. Source: UniProtKB protein kinase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AURKAIP1	Q9NWT8	2	EBI-448680,EBI-448665
CDKN2A	P42771	1	EBI-448680,EBI-375053
FABP5	Q01469	1	EBI-448680,EBI-1054073
RAB10	P61026	1	EBI-448680,EBI-726075
TACC1	O75410-1	1	EBI-448680,EBI-624252
TPX2	Q9ULW0	1	EBI-448680,EBI-1037322
UBE2L3	P68036	1	EBI-448680,EBI-711173

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 403

403

Serine/threonine-protein kinase 6

Regions

Domain

133 – 383

251

Protein kinase

Nucleotide binding

139 – 147

9

ATP By similarity

Sites

Active site

256

1

Proton acceptor By similarity

Binding site

162

1

ATP By similarity

Amino acid modifications

Modified residue

287

1

Phosphothreonine

Modified residue

288

1

Phosphothreonine

Modified residue

369

1

Phosphoserine

Natural variations

Natural variant

11

1

G → R: dbSNP rs6069717.

Natural variant

31

1

F → I: dbSNP rs2273535.

Natural variant

50

1

P → L

Natural variant

57

1

V → I: dbSNP rs1047972.

Natural variant

155

1

S → R in a colorectal adenocarcinoma sample; somatic mutation.

Natural variant

174

1

V → M in a metastatic melanoma sample; somatic mutation.

Natural variant

373

1

M → V

Secondary structure

1

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403

Helix Strand Turn

Details...

Helix

130 – 132

3

Beta strand

133 – 141

9

Beta strand

143 – 152

10

Turn

153 – 155

3

Beta strand

158 – 165

8

Helix

166 – 172

7

Helix

175 – 187

13

Beta strand

196 – 201

6

Beta strand

203 – 210

8

Helix

218 – 225

8

Helix

230 – 249

20

Helix

259 – 261

3

Beta strand

262 – 264

3

Beta strand

270 – 272

3

Helix

275 – 277

3

Beta strand

279 – 283

5

Helix

298 – 301

4

Helix

309 – 324

16

Helix

334 – 343

10

Helix

354 – 363

10

Helix

368 – 370

3

Helix

374 – 378

5

Helix

381 – 386

6

Sequences

	Sequence		Length	Mass (Da)
	O14965-1 [UniParc]. Last modified January 27, 2003. Version 2. Checksum: 125F3594834CD157	FASTA	403	45,809
	10 20 30 40 50 60 MDRSKENCIS GPVKATAPVG GPKRVLVTQQ FPCQNPLPVN SGQAQRVLCP SNSSQRVPLQ 70 80 90 100 110 120 AQKLVSSHKP VQNQKQKQLQ ATSVPHPVSR PLNNTQKSKQ PLPSAPENNP EEELASKQKN 130 140 150 160 170 180 EESKKRQWAL EDFEIGRPLG KGKFGNVYLA REKQSKFILA LKVLFKAQLE KAGVEHQLRR 190 200 210 220 230 240 EVEIQSHLRH PNILRLYGYF HDATRVYLIL EYAPLGTVYR ELQKLSKFDE QRTATYITEL 250 260 270 280 290 300 ANALSYCHSK RVIHRDIKPE NLLLGSAGEL KIADFGWSVH APSSRRTTLC GTLDYLPPEM 310 320 330 340 350 360 IEGRMHDEKV DLWSLGVLCY EFLVGKPPFE ANTYQETYKR ISRVEFTFPD FVTEGARDLI 370 380 390 400 SRLLKHNPSQ RPMLREVLEH PWITANSSKP SNCQNKESAS KQS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cell cycle-dependent expression and spindle pole localization of a novel human protein kinase, Aik, related to Aurora of Drosophila and yeast Ipl1." Kimura M., Kotani S., Hattori T., Sumi N., Yoshioka T., Todokoro K., Okano Y. J. Biol. Chem. 272:13766-13771(1997) [PubMed: 9153231] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Blood.
[2]	"cDNA cloning, expression, subcellular localization, and chromosomal assignment of mammalian aurora homologues, aurora-related kinase (ARK) 1 and 2." Shindo M., Nakano H., Kuroyanagi H., Shirasawa T., Mihara M., Gilbert D.J., Jenkins N.A., Copeland N.G., Yagita H., Okumura K. Biochem. Biophys. Res. Commun. 244:285-292(1998) [PubMed: 9514916] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-57.
[3]	"Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation." Zhou H., Kuang J., Zhong L., Kuo W.-L., Gray J.W., Sahin A., Brinkley B.R., Sen S. Nat. Genet. 20:189-193(1998) [PubMed: 9771714] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-31. Tissue: Mammary gland.
[4]	"Mutational analysis of the STK15 gene in human tumors." Wang L., Thibodeau S.N. Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cervix, Colon, Kidney and Muscle.
[7]	"Cell-cycle-dependent regulation of human aurora A transcription is mediated by periodic repression of E4TF1." Tanaka M., Ueda A., Kanamori H., Ideguchi H., Yang J., Kitajima S., Ishigatsubo Y. J. Biol. Chem. 277:10719-10726(2002) [PubMed: 11790771] [Abstract] Cited for: CELL-CYCLE REGULATION.
[8]	"GEF-H1 modulates localized RhoA activation during cytokinesis under the control of mitotic kinases." Birkenfeld J., Nalbant P., Bohl B.P., Pertz O., Hahn K.M., Bokoch G.M. Dev. Cell 12:699-712(2007) [PubMed: 17488622] [Abstract] Cited for: INTERACTION WITH ARHGEF2.
[9]	"Mitotic kinases as regulators of cell division and its checkpoints." Nigg E.A. Nat. Rev. Mol. Cell Biol. 2:21-32(2001) [PubMed: 11413462] [Abstract] Cited for: REVIEW.
[10]	"TACC1-chTOG-Aurora A protein complex in breast cancer." Conte N., Delaval B., Ginestier C., Ferrand A., Isnardon D., Larroque C., Prigent C., Seraphin B., Jacquemier J., Birnbaum D. Oncogene 22:8102-8116(2003) [PubMed: 14603251] [Abstract] Cited for: INTERACTION WITH TACC1.
[11]	"Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1." Sasayama T., Marumoto T., Kunitoku N., Zhang D., Tamaki N., Kohmura E., Saya H., Hirota T. Genes Cells 10:627-638(2005) [PubMed: 15966895] [Abstract] Cited for: INTERACTION WITH CPEB1.
[12]	"Mitotic activation of the kinase Aurora-A requires its binding partner Bora." Hutterer A., Berdnik D., Wirtz-Peitz F., Zigman M., Schleiffer A., Knoblich J.A. Dev. Cell 11:147-157(2006) [PubMed: 16890155] [Abstract] Cited for: INTERACTION WITH BORA.
[13]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-369, MASS SPECTROMETRY.
[14]	"Crystal structure of aurora-2, an oncogenic serine/threonine kinase." Cheetham G.M., Knegtel R.M., Coll J.T., Renwick S.B., Swenson L., Weber P., Lippke J.A., Austen D.A. J. Biol. Chem. 277:42419-42422(2002) [PubMed: 12237287] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 107-403.
[15]	"Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography." Nowakowski J., Cronin C.N., McRee D.E., Knuth M.W., Nelson C.G., Pavletich N.P., Rogers J., Sang B.C., Scheibe D.N., Swanson R.V., Thompson D.A. Structure 10:1659-1667(2002) [PubMed: 12467573] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 125-391.
[16]	"Structural basis of Aurora-A activation by TPX2 at the mitotic spindle." Bayliss R., Sardon T., Vernos I., Conti E. Mol. Cell 12:851-862(2003) [PubMed: 14580337] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 122-403, PHOSPHORYLATION AT THR-287 AND THR-288.
[17]	"SAR and inhibitor complex structure determination of a novel class of potent and specific Aurora kinase inhibitors." Heron N.M., Anderson M., Blowers D.P., Breed J., Eden J.M., Green S., Hill G.B., Johnson T., Jung F.H., McMiken H.H., Mortlock A.A., Pannifer A.D., Pauptit R.A., Pink J., Roberts N.J., Rowsell S. Bioorg. Med. Chem. Lett. 16:1320-1323(2006) [PubMed: 16337122] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 123-401.
[18]	"1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: identification of a potent aurora kinase inhibitor with a favorable antitumor kinase inhibition profile." 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 M.L., Klapwijk J., Marsiglio A., Pesenti E., Rocchetti M. , Roletto F., Severino D., Soncini C., Storici P., Tonani R., Zugnoni P., Vianello P. J. Med. Chem. 49:7247-7251(2006) [PubMed: 17125279] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 100-403.
[19]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., 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 D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A.,