P59241 (AURKA_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 104. History...
Names and origin
|Protein names||Recommended name:|
Aurora kinase A
Aurora/IPL1-related kinase 1
Short name=Aurora-related kinase 1
Serine/threonine-protein kinase 6
Serine/threonine-protein kinase aurora-A
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||397 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 stabilizating p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity By similarity. Necessary for proper cilia disassembly prior to mitosis By similarity. Ref.2
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. 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 By similarity.
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 FBXL7 and PIFO. Interacts with GADD45A, competing with its oligomerization By similarity. 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 By similarity.
Cytoplasm › cytoskeleton › microtubule organizing center › centrosome By similarity. Cytoplasm › cytoskeleton › spindle pole By similarity. Note: Localizes on centrosomes in interphase cells and at each spindle pole in mitosis. Associates with both the pericentriolar material (PCM) and centrioles. Detected at the neurite hillock in developing neurons By similarity.
Detected in neurons in brain cortex and hippocampus (at protein level). Expressed in mammary gland and tumor. Ref.2
Activated by progesterone.
Activated by phosphorylation at Thr-281; this brings about a change in the conformation of the activation segment. Phosphorylation at Thr-281 varies during the cell cycle and is highest during M phase. Autophosphorylated at Thr-281 upon TPX2 binding. Thr-281 can be phosphorylated by several kinases, including PAK and PKA. Protein phosphatase type 1 (PP1) binds AURKA and inhibits its activity by dephosphorylating Thr-281 during mitosis. Phosphorylation at Ser-335 decreases the kinase activity. PPP2CA controls degradation by dephosphorylating Ser-52 at the end of mitosis By similarity. Phosphorylated in embryonic brain neurons. Ref.2
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 By similarity.
Contains 1 protein kinase domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 397||397||Aurora kinase A||PRO_0000086694|
|Domain||126 – 376||251||Protein kinase|
|Nucleotide binding||203 – 206||4||ATP By similarity|
|Region||273 – 286||14||Activation segment By similarity|
|Active site||249||1||Proton acceptor By similarity|
|Binding site||136||1||ATP; via amide nitrogen By similarity|
|Binding site||155||1||ATP By similarity|
|Binding site||267||1||ATP By similarity|
Amino acid modifications
|Modified residue||40||1||Phosphoserine By similarity|
|Modified residue||50||1||Phosphoserine By similarity|
|Modified residue||280||1||Phosphothreonine By similarity|
|Modified residue||281||1||Phosphothreonine By similarity|
|Modified residue||335||1||Phosphoserine; by PKA and PAK By similarity|
|||"Centrosome amplification and overexpression of aurora A are early events in rat mammary carcinogenesis."|
Goepfert T.M., Adigun Y.E., Zhong L., Gay J., Medina D., Brinkley W.R.
Cancer Res. 62:4115-4122(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Wistar Furth.
Tissue: Mammary gland.
|||"Phosphorylation of the par polarity complex protein Par3 at serine 962 is mediated by aurora A and regulates its function in neuronal polarity."|
Khazaei M.R., Puschel A.W.
J. Biol. Chem. 284:33571-33579(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION, TISSUE SPECIFICITY.
|+||Additional computationally mapped references.|
|AF537333 mRNA. Translation: AAN06823.1.|
3D structure databases
|SMR||P59241. Positions 119-383. |
Protein-protein interaction databases
Protocols and materials databases
|RGD||628895. 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: P59241|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families