P97477 (AURKA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Aurora kinase A
EC=2.7.11.1

Alternative name(s):
Aurora 2
Aurora family kinase 1
Aurora/IPL1-related kinase 1
Short name=ARK-1
Short name=Aurora-related kinase 1
Ipl1- and aurora-related kinase 1
Serine/threonine-protein kinase 6
Serine/threonine-protein kinase Ayk1
Serine/threonine-protein kinase aurora-A

Gene names

Name:	Aurka
Synonyms:	Aik, Airk, Ark1, Aura, Ayk1, Btak, Iak1, Stk15, Stk6

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	395 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.1 Ref.7 Ref.8 Ref.9
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 By similarity. Activated during the early phase of cilia disassembly in the presence of PIFO.
Subunit structure	Interacts with CPEB1, JTB, TACC1, TPX2, PPP2CA, as well as with the protein phosphatase type 1 (PP1) isoforms PPP1CA, PPP1CB and PPP1CC By similarity. Interacts also with its substrates ARHGEF2, BORA, BRCA1, KIF2A, PARD3, and p53/TP53. Interaction with BORA promotes phosphorylation of PLK1 By similarity. Interacts with PIFO. Ref.9
Subcellular location	Cytoplasm › cytoskeleton › centrosome. Cytoplasm › cytoskeleton › spindle pole. Note: Localizes on centrosomes in interphase cells and at each spindle pole in mitosis. Associates with both the pericentriolar material (PCM) and centrioles By similarity. Detected at the neurite hillock in developing neurons. Ref.1 Ref.7 Ref.8
Tissue specificity	Detected in embryonic neurons in dorsal root ganglia and brain cortex (at protein level). Highly expressed in testis, in about one third of the seminiferous tubules. Expression is restricted to specific spermatocytes nearing completion of prophase, with levels falling off on transition to elongated spermatids. Highly expressed in the ovary, expression in the oocyte starts around the transition to large growing follicle. Abundant expression is seen in the proliferating granulosa and thecal cells of the growing follicle, and in the young corpus luteum. Very weakly expressed in spleen and intestine. Ref.1 Ref.8
Developmental stage	At 7.5-9.5 dpc expressed evenly all over the embryo. At later stages, expression is mainly restricted to proliferating zones. The highest levels of expression at mid-embryonic development (13.5 dpc) were observed in the liver, lung, kidney and back (trapezius) muscle and all regions in active proliferation.
Induction	expression is cell cycle regulated and peaks at phase G2/M. Ref.1
Post-translational modification	Activated by phosphorylation at Thr-279; this brings about a change in the conformation of the activation segment. Phosphorylation at Thr-279 varies during the cell cycle and is highest during M phase. Autophosphorylated at Thr-279 upon TPX2 binding. Thr-279 can be phosphorylated by several kinases, including PAK and PKA. Protein phosphatase type 1 (PP1) binds AURKA and inhibits its activity by dephosphorylating Thr-279 during mitosis. Phosphorylation at Ser-333 decreases the kinase activity. Phosphorylated upon DNA damage, probably by ATM or ATR. PPP2CA controls degradation by dephosphorylating Ser-52 at the end of mitosis By similarity. Ubiquitinated by the anaphase-promoting complex (APC), leading to its degradation by the proteasome By similarity. Ubiquitinated by CHFR, leading to its degradation by the proteasome. Ref.6
Disruption phenotype	Death at the blastocyst stage due to mitotic defects and failure of cell proliferation. Ref.7
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.
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence BAC39557.1 differs from that shown. Reason: Frameshift at position 382.

Ontologies

Keywords
Biological process	Cell cycle Cell division Cilium biogenesis/degradation Mitosis
Cellular component	Cytoplasm Cytoskeleton Microtubule
Coding sequence diversity	Alternative splicing
Disease	Proto-oncogene
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell division Inferred from electronic annotation. Source: UniProtKB-KW cell projection organization Inferred from electronic annotation. Source: UniProtKB-KW mitosis Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin protein ligase binding Inferred from physical interaction Ref.6. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P97477-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P97477-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MAVEGEPGCCKRIGKAVWRRGDM

Note: May be less abundant or less stable.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 395

395

Aurora kinase A

PRO_0000086693

Regions

Domain

124 – 374

251

Protein kinase

Nucleotide binding

201 – 204

4

ATP By similarity

Region

271 – 284

14

Activation segment By similarity

Sites

Active site

247

1

Proton acceptor By similarity

Binding site

134

1

ATP; via amide nitrogen By similarity

Binding site

153

1

ATP By similarity

Binding site

265

1

ATP By similarity

Amino acid modifications

Modified residue

40

1

Phosphoserine By similarity

Modified residue

50

1

Phosphoserine By similarity

Modified residue

52

1

Phosphoserine By similarity

Modified residue

77

1

Phosphoserine By similarity

Modified residue

278

1

Phosphothreonine By similarity

Modified residue

279

1

Phosphothreonine By similarity

Modified residue

333

1

Phosphoserine; by PKA and PAK By similarity

Modified residue

360

1

Phosphoserine By similarity

Natural variations

Alternative sequence

1

1

M → MAVEGEPGCCKRIGKAVWRR GDM in isoform 2.

VSP_004871

Experimental info

Sequence conflict

234

1

A → T in AAB63205. Ref.1

Secondary structure

1

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395

Helix Strand Turn

Details...

Helix

121 – 123

3

Beta strand

138 – 143

6

Turn

144 – 146

3

Beta strand

149 – 156

8

Helix

157 – 162

6

Helix

166 – 176

11

Beta strand

194 – 201

8

Helix

209 – 216

8

Helix

221 – 240

20

Helix

250 – 252

3

Helix

284 – 286

3

Helix

289 – 292

4

Helix

299 – 305

7

Helix

309 – 314

6

Helix

325 – 334

10

Helix

348 – 354

7

Helix

359 – 361

3

Helix

365 – 370

6

Helix

372 – 377

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 26B6B65105A1A812	FASTA	395	44,772
	10 20 30 40 50 60 MDRCKENCVS RPVKTTVPFG PKRVLVTEQI PSQNLGSASS GQAQRVLCPS NSQRVPSQAQ 70 80 90 100 110 120 KLGAGQKPAP KQLPAASVPR PVSRLNNPQK NEQPAASGND SEKEQASLQK TEDTKKRQWT 130 140 150 160 170 180 LEDFDIGRPL GKGKFGNVYL ARERQSKFIL ALKVLFKTQL EKANVEHQLR REVEIQSHLR 190 200 210 220 230 240 HPNILRLYGY FHDATRVYLI LEYAPLGTVY RELQKLSKFD EQRTATYITE LANALSYCHS 250 260 270 280 290 300 KRVIHRDIKP ENLLLGSNGE LKIADFGWSV HAPSSRRTTM CGTLDYLPPE MIEGRMHDEK 310 320 330 340 350 360 VDLWSLGVLC YEFLVGMPPF EAHTYQETYR RISRVEFTFP DFVTEGARDL ISRLLKHNAS 370 380 390 QRLTLAEVLE HPWIKANSSK PPTGHTSKEP TSKSS
	Isoform 2 [UniParc]. Checksum: C9FD861C803EF5C5	FASTA	417	47,173
	10 20 30 40 50 60 MAVEGEPGCC KRIGKAVWRR GDMDRCKENC VSRPVKTTVP FGPKRVLVTE QIPSQNLGSA 70 80 90 100 110 120 SSGQAQRVLC PSNSQRVPSQ AQKLGAGQKP APKQLPAASV PRPVSRLNNP QKNEQPAASG 130 140 150 160 170 180 NDSEKEQASL QKTEDTKKRQ WTLEDFDIGR PLGKGKFGNV YLARERQSKF ILALKVLFKT 190 200 210 220 230 240 QLEKANVEHQ LRREVEIQSH LRHPNILRLY GYFHDATRVY LILEYAPLGT VYRELQKLSK 250 260 270 280 290 300 FDEQRTATYI TELANALSYC HSKRVIHRDI KPENLLLGSN GELKIADFGW SVHAPSSRRT 310 320 330 340 350 360 TMCGTLDYLP PEMIEGRMHD EKVDLWSLGV LCYEFLVGMP PFEAHTYQET YRRISRVEFT 370 380 390 400 410 FPDFVTEGAR DLISRLLKHN ASQRLTLAEV LEHPWIKANS SKPPTGHTSK EPTSKSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel mammalian, mitotic spindle-associated kinase is related to yeast and fly chromosome segregation regulators." Gopalan G., Chan C.S.M., Donovan P.J. J. Cell Biol. 138:643-656(1997) [PubMed: 9245792] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INDUCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, FUNCTION. Strain: BALB/c. Tissue: Testis.
[2]	"ayk1, a novel mammalian gene related to Drosophila aurora centrosome separation kinase, is specifically expressed during meiosis." Yanai A., Arama E., Kilfin G., Motro B. Oncogene 14:2943-2950(1997) [PubMed: 9205101] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Testis.
[3]	"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] (ISOFORM 1). Strain: BALB/c.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Heart.
[5]	"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] (ISOFORMS 1 AND 2). Tissue: Mammary gland.
[6]	"Chfr is required for tumor suppression and Aurora A regulation." Yu X., Minter-Dykhouse K., Malureanu L., Zhao W.-M., Zhang D., Merkle C.J., Ward I.M., Saya H., Fang G., van Deursen J., Chen J. Nat. Genet. 37:401-406(2005) [PubMed: 15793587] [Abstract] Cited for: UBIQUITINATION BY CHFR.
[7]	"Aurora-A kinase is essential for bipolar spindle formation and early development." Cowley D.O., Rivera-Perez J.A., Schliekelman M., He Y.J., Oliver T.G., Lu L., O'Quinn R., Salmon E.D., Magnuson T., Van Dyke T. Mol. Cell. Biol. 29:1059-1071(2009) [PubMed: 19075002] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
[8]	"An essential role of the aPKC-Aurora A-NDEL1 pathway in neurite elongation by modulation of microtubule dynamics." Mori D., Yamada M., Mimori-Kiyosue Y., Shirai Y., Suzuki A., Ohno S., Saya H., Wynshaw-Boris A., Hirotsune S. Nat. Cell Biol. 11:1057-1068(2009) [PubMed: 19668197] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]	"Pitchfork regulates primary cilia disassembly and left-right asymmetry." Kinzel D., Boldt K., Davis E.E., Burtscher I., Trumbach D., Diplas B., Attie-Bitach T., Wurst W., Katsanis N., Ueffing M., Lickert H. Dev. Cell 19:66-77(2010) [PubMed: 20643351] [Abstract] Cited for: FUNCTION, INTERACTION WITH PIFO, ACTIVATION BY PIFO.
[10]	"Discovery of an Aurora kinase inhibitor through site-specific dynamic combinatorial chemistry." Cancilla M.T., He M.M., Viswanathan N., Simmons R.L., Taylor M., Fung A.D., Cao K., Erlanson D.A. Bioorg. Med. Chem. Lett. 18:3978-3981(2008) [PubMed: 18579375] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 116-381 IN COMPLEX WITH SYNTHETIC INHIBITOR.
[11]	"Discovery of a potent and selective aurora kinase inhibitor." Oslob J.D., Romanowski M.J., Allen D.A., Baskaran S., Bui M., Elling R.A., Flanagan W.M., Fung A.D., Hanan E.J., Harris S., Heumann S.A., Hoch U., Jacobs J.W., Lam J., Lawrence C.E., McDowell R.S., Nannini M.A., Shen W. , Silverman J.A., Sopko M.M., Tangonan B.T., Teague J., Yoburn J.C., Yu C.H., Zhong M., Zimmerman K.M., O'Brien T., Lew W. Bioorg. Med. Chem. Lett. 18:4880-4884(2008) [PubMed: 18678489] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 116-381 IN COMPLEX WITH SYNTHETIC INHIBITOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U80932 mRNA. Translation: AAB62982.1.
AF007817 mRNA. Translation: AAB63205.1.
U69106 mRNA. Translation: AAC12682.1.
AK085861 mRNA. Translation: BAC39557.1. Frameshift.
BC005425 mRNA. Translation: AAH05425.1.
BC014711 mRNA. Translation: AAH14711.1.

IPI

IPI00125590.
IPI00230633.

PIR

JC5975.

RefSeq

NP_035627.1. NM_011497.3.

UniGene

Mm.249363.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3D14	X-ray	1.90	A	116-381	[»]
3D15	X-ray	2.30	A	116-381	[»]
3D2I	X-ray	2.90	A	116-381	[»]
3D2K	X-ray	2.50	A	116-381	[»]
3DAJ	X-ray	2.00	A	116-381	[»]
3DJ5	X-ray	1.80	A	116-381	[»]
3DJ6	X-ray	1.70	A	116-381	[»]
3DJ7	X-ray	2.80	A	116-381	[»]

ProteinModelPortal

P97477.

SMR

P97477. Positions 117-379.

ModBase

Search...

Protein-protein interaction databases

STRING

P97477.

PTM databases

PhosphoSite

P97477.

Proteomic databases

PRIDE

P97477.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000028997; ENSMUSP00000028997; ENSMUSG00000027496.
ENSMUST00000109139; ENSMUSP00000104767; ENSMUSG00000027496.
ENSMUST00000109140; ENSMUSP00000104768; ENSMUSG00000027496.

GeneID

20878.

KEGG

mmu:20878.

UCSC

uc008ocn.1. mouse.

Organism-specific databases

CTD

6790.

MGI

MGI:894678. Aurka.

Phylogenomic databases

eggNOG

roNOG06115.

HOGENOM

HBG755340.

HOVERGEN

HBG108519.

InParanoid

P97477.

OMA

RSKENCI.

OrthoDB

EOG4HX512.

PhylomeDB

P97477.

Gene expression databases

ArrayExpress

P97477.

Bgee

P97477.

CleanEx

MM_AURKA.

Genevestigator

P97477.

GermOnline

ENSMUSG00000027496. Mus musculus.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR002290. Ser/Thr_kinase_dom.
[Graphical view]

KO

K11481.

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P97477.

SOURCE

Search...

Entry information

Entry name

AURKA_MOUSE

Accession

Primary (citable) accession number: P97477
Secondary accession number(s): O35624, Q8C3H8, Q91YU4

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 27, 2003
Last sequence update:	May 1, 1997
Last modified:	January 25, 2012
This is version 118 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program