Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

AURKA (O14965) - Overview - Molecular Target Synopsis

Protein


AURKA, Aurora kinase A
Enzyme Classification 2.7.11.1
UniProt O14965

Also Known as AURKA_HUMAN, AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6

Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression (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: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. 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. 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. Interacts also with its substrates ARHGEF2, BORA, BRCA1, KIF2A, PARD3, and p53/TP53. Interaction with BORA promotes phosphorylation of PLK1. Interacts with PIFO. Interacts with GADD45A, competing with its oligomerization. Interacts (via C-terminus) with AUNIP (via C-terminus). Identified in a complex with AUNIP and NIN. Interacts with FRY; this interaction facilitates AURKA-mediated PLK1 phosphorylation. 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).

2XNE
STRUCTURE OF AURORA-A BOUND TO AN IMIDAZOPYRAZINE INHIBITOR
RCSB/PDB
Inspect Structure
See all 3D Structures for AURKA

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: AURKA is active in the following subcellular-locations: centriole, centrosome, cilium basal body, cytoplasm, cytoskeleton, microtubule organizing center, spindle pole.
GO terms: AURKA is active in the following subcellular-locations: axon hillock, centriole, centrosome, chromosome passenger complex, cilium, condensed nuclear chromosome, cytosol, germinal vesicle, meiotic spindle, microtubule cytoskeleton, midbody, mitotic spindle pole, nucleoplasm, nucleus, perinuclear region of cytoplasm, pronucleus, spindle, spindle microtubule, spindle midzone, spindle pole centrosome.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project AURKA has gain in 13 cell-lines, loss in 0 cell-lines and no signal in 991 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MCF7, BT_549, SNB_19

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H322T, MDA-MB-157, OVCAR-8

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HeLa-S3, HSMM, A549

(see details)

RNA Interference


AURKA was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: CAL120, CAL51. (see details)

3D Structures


For AURKA there are:
154 structures (190 chains) solved
153 are solved in complex with at least one small molecule ligand
4 are solved with an approved drug

AURKA is solved in complex with the approved drug(s):

ADN/ADENOSINE (1MUO_A, 4O0S_A, 4O0U_A, 4O0W_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


AURKA has been screened with 5053 compounds (7037 bioactivities), 1931 compounds have bioactivities that show binding affinity of <= 500nM (2555 bioactivities). (see details)