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serine/threonine protein kinase 6; Aurora kinase A; Aurora/IPL1-related kinase 1; ARK-1; Aurora-related kinase 1; hARK1; breast tumor-amplified kinase; serine/threonine protein kinase 15; serine/threonine protein kinase aurora-A (AURKA, AIK, ARK1, AURA, BTAK, STK15, STK6)
Function:
- role in regulation of cell cycle progression
- required for normal mitosis
- associates with centrosome & spindle microtubules during mitosis & functions in centrosome maturation, spindle assembly, maintenance of spindle bipolarity, centrosome separation & mitotic checkpoint control
- phosphorylates numerous target proteins, including ARHGEF2, BRCA1, KIF2A, NDEL1, PARD3, PLK1 & BORA
- regulates KIF2A tubulin depolymerase activity (putative)
- required for normal axon formation
- role in microtubule remodeling during neurite extension
- important for microtubule formation &/or stabilization
- activated by phosphorylation at Thr-288; this brings about a conformational change in the activation segment
- phosphorylation at Thr-288 varies during the cell cycle & is highest during M phase
- autophosphorylated at Thr-288 upon TPX2 binding
- phosphorylated upon DNA damage, probably by ATM or ATR
- ubiquitinated by CHFR, leading to its degradation by the proteasome (putative)
- ubiquitinated by the anaphase-promoting complex (APC), leading to its degradation by the proteasome
- interacts with TPX2
- interacts with TACC1 & CPEB1
- interacts with its substrates BORA, BRCA1, KIF2A, PARD3 & ARHGEF2
- interaction with BORA promotes phosphorylation of PLK1
Structure:
- belongs to the protein kinase superfamily, Ser/Thr protein kinase family, Aurora subfamily
- contains 1 protein kinase domain
Compartment:
- cytoplasm, cytoskeleton, centrosome cytoplasm, cytoskeleton, spindle pole
- detected at the axon hillock in developing neurons (putative)
- localizes on centrosomes in interphase cells & at each spindle pole in mitosis
Expression:
- highly expressed in testis
- weakly expressed in skeletal muscle, thymus & spleen
- expression is cell-cycle regulated, low in G1/S, accumulates during G2/M, & decreases rapidly after
- highly expressed in tumor cell lines
- colon cancer
- ovarian cancer
- prostate cancer
- neuroblastoma
- breast cancer
- cervical cancer
Note:
- STK6 & STK15 are the same protein
General
aurora kinase
Properties
SIZE: entity length = 403 aa
MW = 46 kD
COMPARTMENT: cytoplasm
STATE: active state
MOTIF: Ser phosphorylation site {S41}
Ser phosphorylation site {S51}
Ser phosphorylation site {S53}
Ser phosphorylation site {S83}
kinase domain
SITE: 133-383
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 143-143
ATP-binding site
NAME: ATP-binding site
SITE: 162-162
ATP-binding site
NAME: ATP-binding site
SITE: 210-213
aspartate residue {D256}
ATP-binding site
NAME: ATP-binding site
SITE: 274-274
Activation segment {280-293}
Thr phosphorylation site {T287}
Thr phosphorylation site {T288}
Ser phosphorylation site {S369}
Database Correlations
OMIM 603072
MORBIDMAP 603072
UniProt O14965
Pfam PF00069
Entrez Gene 6790
Kegg hsa:6790
ENZYME 2.7.11.1
References
- UniProt :accession O14965
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/AURKAID730ch20q13.html