Recombinant Human Aurora kinase A (AURKA)

Function

Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression (PubMed:11039908, PubMed:12390251, PubMed:17125279, PubMed:17360485, PubMed:18615013, PubMed:26246606). 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 (PubMed:14523000, PubMed:26246606). Required for normal spindle positioning during mitosis and for the localization of NUMA1 and DCTN1 to the cell cortex during metaphase (PubMed:27335426). Required for initial activation of CDK1 at centrosomes (PubMed:13678582, PubMed:15128871). Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2 (PubMed:11551964, PubMed:14702041, PubMed:15128871, PubMed:15147269, PubMed:15987997, PubMed:17604723, PubMed:18056443, PubMed:18615013). Phosphorylates MCRS1 which is required for MCRS1-mediated kinetochore fiber assembly and mitotic progression (PubMed:27192185). Regulates KIF2A tubulin depolymerase activity (PubMed:19351716). Important for microtubule formation and/or stabilization (PubMed:18056443). Required for normal axon formation (PubMed:19812038). Plays a role in microtubule remodeling during neurite extension (PubMed:19668197). 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 destabilizing p53/TP53 (PubMed:14702041). Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity (PubMed:11551964). Inhibits cilia outgrowth (By similarity). Required for cilia disassembly via phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin (PubMed:17604723, PubMed:20643351). Regulates protein levels of the anti-apoptosis protein BIRC5 by suppressing the expression of the SCF(FBXL7) E3 ubiquitin-protein ligase substrate adapter FBXL7 through the phosphorylation of the transcription factor FOXP1 (PubMed:28218735)

Subcellular Location

Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, spindle pole; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole; Cell projection, neuron projection; Cell projection, cilium; Cytoplasm, cytoskeleton, cilium basal body; Basolateral cell membrane

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

Subunit

Part of a complex composed of NEDD9, AURKA and CTTN; within the complex NEDD9 acts as a scaffold protein and is required for complex formation (PubMed:24574519). Identified in a complex with AUNIP and NIN (PubMed:20596670). Interacts with FBXL7 (By similarity). Interacts with CPEB1, JTB, TACC1, TPX2, PPP2CA, as well as with the protein phosphatase type 1 (PP1) isoforms PPP1CA, PPP1CB and PPP1CC (PubMed:11551964, PubMed:14580337, PubMed:14603251, PubMed:15966895, PubMed:17229885, PubMed:18662907, PubMed:19357306, PubMed:19668197, PubMed:19801554, PubMed:21225229, PubMed:27837025). Also interacts with its substrates ARHGEF2, BORA, KIF2A, PARD3, and p53/TP53 (PubMed:14702041, PubMed:16890155, PubMed:17488622, PubMed:19351716, PubMed:19812038). Interaction with BORA promotes phosphorylation of PLK1 (By similarity). Interacts with CIMAP3 (PubMed:20643351). Interacts with GADD45A, competing with its oligomerization (PubMed:20460379). Interacts (via C-terminus) with AUNIP (via C-terminus) (PubMed:20596670). Interacts with FRY; this interaction facilitates AURKA-mediated PLK1 phosphorylation (PubMed:22753416). Interacts with SIRT2 (PubMed:17726514, PubMed:22014574). Interacts with MYCN; interaction is phospho-independent and triggers AURKA activation; AURKA competes with FBXW7 for binding to unphosphorylated MYCN but not for binding to phosphorylated MYCN (PubMed:27837025). Interacts with HNRNPU (PubMed:21242313, PubMed:25986610). Interacts with AAAS (PubMed:26246606). Interacts with KLHL18 and CUL3 (PubMed:23213400). Interacts with FOXP1 (PubMed:28218735). Interacts with HDAC6; AURKA-mediated phosphorylation of HDAC6 promotes deacetylation of alpha-tubulin (PubMed:17604723)

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• Shindo M. et al. cDNA cloning, expression, subcellular localization, and chromosomal assignment of mammalian aurora homologues, aurora-related kinase (ARK) 1 and 2. — Biochem. Biophys. Res. Commun. (1998)
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• Deloukas P. et al. The DNA sequence and comparative analysis of human chromosome 20. — Nature (2001)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Bischoff J.R. et al. A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. — EMBO J. (1998)