P97477 (AURKA_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified November 13, 2013. Version 134. History...
Names and origin
|Protein names||Recommended name:|
Aurora kinase A
Aurora family kinase 1
Aurora/IPL1-related kinase 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
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||395 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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 stabilizing 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
ATP + a protein = ADP + a phosphoprotein.
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.
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. Interacts with GADD45A, competing with its oligomerization By similarity. Interacts with FBXL7 and PIFO. Interacts (via C-terminus) with AUNIP (via C-terminus) By similarity. Identified in a complex with AUNIP and NIN By similarity. Interacts with FRY; this interaction facilitates AURKA-mediated PLK1 phosphorylation. Ref.9 Ref.10 Ref.11
Cytoplasm › cytoskeleton › microtubule organizing center › 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
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
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.
expression is cell cycle regulated and peaks at phase G2/M. Ref.1
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. 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. Ubiquitinated by the E3 ubiquitin-protein ligase complex SCF(FBXL7) during mitosis, leading to its degradation by the proteasome. Ref.6 Ref.10
Death at the blastocyst stage due to mitotic defects and failure of cell proliferation. Ref.7
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.
Contains 1 protein kinase domain.
|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|
|Chain||1 – 395||395||Aurora kinase A||PRO_0000086693|
|Domain||124 – 374||251||Protein kinase|
|Nucleotide binding||201 – 204||4||ATP By similarity|
|Region||271 – 284||14||Activation segment By similarity|
|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||278||1||Phosphothreonine By similarity|
|Modified residue||279||1||Phosphothreonine By similarity|
|Modified residue||333||1||Phosphoserine; by PKA and PAK By similarity|
|Alternative sequence||1||1||M → MAVEGEPGCCKRIGKAVWRR GDM in isoform 2.||VSP_004871|
|Sequence conflict||234||1||A → T in AAB63205. Ref.1|
Helix Strand Turn
|Helix||121 – 123||3|
|Beta strand||124 – 129||6|
|Helix||131 – 133||3|
|Beta strand||136 – 143||8|
|Turn||144 – 146||3|
|Beta strand||149 – 156||8|
|Helix||157 – 163||7|
|Helix||166 – 176||11|
|Beta strand||187 – 192||6|
|Beta strand||194 – 201||8|
|Helix||209 – 216||8|
|Helix||221 – 240||20|
|Helix||250 – 252||3|
|Beta strand||253 – 255||3|
|Beta strand||261 – 263||3|
|Beta strand||270 – 272||3|
|Helix||284 – 286||3|
|Helix||289 – 292||4|
|Helix||299 – 315||17|
|Helix||325 – 333||9|
|Helix||345 – 354||10|
|Helix||359 – 361||3|
|Helix||365 – 370||6|
|Helix||372 – 377||6|
|||"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INDUCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, FUNCTION.
|||"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
|||"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
|||"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. Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
|||"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Mammary gland.
|||"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] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY CHFR.
|||"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
|||"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
|||"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PIFO, ACTIVATION BY PIFO.
|||"Novel E3 ligase component FBXL7 ubiquitinates and degrades Aurora A, causing mitotic arrest."|
Coon T.A., Glasser J.R., Mallampalli R.K., Chen B.B.
Cell Cycle 11:721-729(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH FBXL7.
|||"Furry protein promotes Aurora A-mediated polo-like kinase 1 activation."|
Ikeda M., Chiba S., Ohashi K., Mizuno K.
J. Biol. Chem. 287:27670-27681(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FRY.
|||"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 116-381 IN COMPLEX WITH SYNTHETIC INHIBITOR.
|||"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. Lew W.
Bioorg. Med. Chem. Lett. 18:4880-4884(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 116-381 IN COMPLEX WITH SYNTHETIC INHIBITOR.
|+||Additional computationally mapped references.|
|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.
|RefSeq||NP_035627.1. NM_011497.3. |
3D structure databases
|SMR||P97477. Positions 5-379. |
Protein-protein interaction databases
|IntAct||P97477. 1 interaction.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000028997; ENSMUSP00000028997; ENSMUSG00000027496. |
ENSMUST00000109139; ENSMUSP00000104767; ENSMUSG00000027496.
ENSMUST00000109140; ENSMUSP00000104768; ENSMUSG00000027496.
|UCSC||uc008ocn.1. mouse. |
|MGI||MGI:894678. Aurka. |
Gene expression databases
Family and domain databases
|InterPro||IPR011009. Kinase-like_dom. |
|Pfam||PF00069. Pkinase. 1 hit. |
|SMART||SM00220. S_TKc. 1 hit. |
|SUPFAM||SSF56112. SSF56112. 1 hit. |
|PROSITE||PS00107. PROTEIN_KINASE_ATP. 1 hit. |
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
|Accession||Primary (citable) accession number: P97477|
Secondary accession number(s): O35624, Q8C3H8, Q91YU4
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
|Human and mouse protein kinases|
Human and mouse protein kinases: classification and index
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
Index of Protein Data Bank (PDB) cross-references
Index of protein domains and families