AURKA_BOVIN
ID AURKA_BOVIN Reviewed; 402 AA.
AC Q2TA06;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Aurora kinase A;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P04198};
DE AltName: Full=Aurora 2;
DE AltName: Full=Aurora/IPL1-related kinase 1;
DE Short=ARK-1;
DE Short=Aurora-related kinase 1;
DE AltName: Full=Serine/threonine-protein kinase 15;
DE AltName: Full=Serine/threonine-protein kinase 6;
DE AltName: Full=Serine/threonine-protein kinase aurora-A;
GN Name=AURKA; Synonyms=AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Uzbekova S., Uzbekov R., Dalbies-Tran R., Dupont J., Mermillod P.;
RT "Aurora-A kinase in bovine oocytes and preimplantation embryos.";
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Mitotic serine/threonine kinase that contributes to the
CC regulation of cell cycle progression. Associates with the centrosome
CC and the spindle microtubules during mitosis and plays a critical role
CC in various mitotic events including the establishment of mitotic
CC spindle, centrosome duplication, centrosome separation as well as
CC maturation, chromosomal alignment, spindle assembly checkpoint, and
CC cytokinesis. Required for normal spindle positioning during mitosis and
CC for the localization of NUMA1 and DCTN1 to the cell cortex during
CC metaphase. Required for initial activation of CDK1 at centrosomes.
CC Phosphorylates numerous target proteins, including ARHGEF2, BORA,
CC BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1,
CC RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase
CC activity. Required for normal axon formation. Plays a role in
CC microtubule remodeling during neurite extension. Important for
CC microtubule formation and/or stabilization. Also acts as a key
CC regulatory component of the p53/TP53 pathway, and particularly the
CC checkpoint-response pathways critical for oncogenic transformation of
CC cells, by phosphorylating and destabilizing p53/TP53. Phosphorylates
CC its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to
CC inhibit their activity. Necessary for proper cilia disassembly prior to
CC mitosis. Regulates protein levels of the anti-apoptosis protein BIRC5
CC by suppressing the expression of the SCF(FBXL7) E3 ubiquitin-protein
CC ligase substrate adapter FBXL7 through the phosphorylation of the
CC transcription factor FOXP1 (By similarity).
CC {ECO:0000250|UniProtKB:O14965}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:O14965};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:O14965};
CC -!- ACTIVITY REGULATION: Activation of CDK1, appears to be an upstream
CC event of AURKA activation (By similarity). Phosphatase inhibitor-2
CC (PPP1R2) and TPX2 act also as activators (By similarity). Inactivated
CC by the G2 checkpoint (By similarity). Inhibited by GADD45A and
CC p53/TP53, and through dephosphorylation by protein phosphatase type 1
CC (PP1) (By similarity). MLN8054 is also a potent and selective inhibitor
CC (By similarity). Activated during the early phase of cilia disassembly
CC in the presence of PIFO (By similarity). Inhibited by the small
CC molecule inhibitor VX-680 (By similarity).
CC {ECO:0000250|UniProtKB:O14965}.
CC -!- SUBUNIT: Interacts with CPEB1, JTB, TACC1, TPX2, PPP2CA, as well as
CC with the protein phosphatase type 1 (PP1) isoforms PPP1CA, PPP1CB and
CC PPP1CC (By similarity). Interacts also with its substrates ARHGEF2,
CC BORA, KIF2A, PARD3, and p53/TP53 (By similarity). Interaction with BORA
CC promotes phosphorylation of PLK1 (By similarity). Interacts with FBXL7
CC and PIFO (By similarity). Interacts with GADD45A, competing with its
CC oligomerization (By similarity). Interacts (via C-terminus) with AUNIP
CC (via C-terminus) (By similarity). Identified in a complex with AUNIP
CC and NIN (By similarity). Interacts with SIRT2 (By similarity).
CC Interacts with FRY; this interaction facilitates AURKA-mediated PLK1
CC phosphorylation (By similarity). Interacts with MYCN; interaction is
CC phospho-independent and triggers AURKA activation; AURKA competes with
CC FBXW7 for binding to unphosphorylated MYCN but not for binding to
CC phosphorylated MYCN (By similarity). Interacts with HNRNPU (By
CC similarity). Interacts with AAAS (By similarity). Interacts with KLHL18
CC and CUL3 (By similarity). Interacts with FOXP1 (By similarity).
CC {ECO:0000250|UniProtKB:O14965, ECO:0000250|UniProtKB:P97477}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000250|UniProtKB:O14965}. Cytoplasm,
CC cytoskeleton, spindle pole {ECO:0000250|UniProtKB:O14965}. Cytoplasm,
CC cytoskeleton, cilium basal body {ECO:0000250|UniProtKB:P97477}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome,
CC centriole {ECO:0000250|UniProtKB:P97477}. Cell projection, neuron
CC projection {ECO:0000250|UniProtKB:P97477}. Note=Detected at the neurite
CC hillock in developing neurons. Localizes at the centrosome in mitotic
CC cells from early prophase until telophase, but also localizes to the
CC spindle pole MTs from prophase to anaphase. Moves to the midbody during
CC both telophase and cytokinesis. Associates with both the pericentriolar
CC material (PCM) and centrioles. Colocalized with SIRT2 at centrosome.
CC The localization to the spindle poles is regulated by AAAS (By
CC similarity). {ECO:0000250|UniProtKB:O14965,
CC ECO:0000250|UniProtKB:P97477}.
CC -!- PTM: Activated by phosphorylation at Thr-288; this brings about a
CC change in the conformation of the activation segment (By similarity).
CC Phosphorylation at Thr-288 varies during the cell cycle and is highest
CC during M phase (By similarity). Autophosphorylated at Thr-288 upon TPX2
CC binding (By similarity). Thr-288 can be phosphorylated by several
CC kinases, including PAK and PKA (By similarity). Protein phosphatase
CC type 1 (PP1) binds AURKA and inhibits its activity by dephosphorylating
CC Thr-288 during mitosis (By similarity). Phosphorylation at Ser-342
CC decreases the kinase activity (By similarity).
CC {ECO:0000250|UniProtKB:O14965}.
CC -!- PTM: Ubiquitinated by CHFR, leading to its degradation by the
CC proteasome (By similarity). Ubiquitinated by the anaphase-promoting
CC complex (APC), leading to its degradation by the proteasome (By
CC similarity). Ubiquitinated by the E3 ubiquitin-protein ligase complex
CC SCF(FBXL7) during mitosis, leading to its degradation by the proteasome
CC (By similarity). Ubiquitinated by the CUL3-KLHL18 ligase leading to its
CC activation at the centrosome which is required for initiating mitotic
CC entry (By similarity). Ubiquitination mediated by CUL3-KLHL18 ligase
CC does not lead to its degradation by the proteasome (By similarity).
CC {ECO:0000250|UniProtKB:O14965, ECO:0000250|UniProtKB:P97477}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. Aurora subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; DQ334808; ABC61056.1; -; mRNA.
DR EMBL; BC111181; AAI11182.1; -; mRNA.
DR RefSeq; NP_001033117.1; NM_001038028.1.
DR RefSeq; XP_005214582.1; XM_005214525.3.
DR AlphaFoldDB; Q2TA06; -.
DR SMR; Q2TA06; -.
DR STRING; 9913.ENSBTAP00000042073; -.
DR PaxDb; Q2TA06; -.
DR PRIDE; Q2TA06; -.
DR Ensembl; ENSBTAT00000044590; ENSBTAP00000042073; ENSBTAG00000013009.
DR GeneID; 504437; -.
DR KEGG; bta:504437; -.
DR CTD; 6790; -.
DR VEuPathDB; HostDB:ENSBTAG00000013009; -.
DR VGNC; VGNC:26349; AURKA.
DR eggNOG; KOG0580; Eukaryota.
DR GeneTree; ENSGT00940000154900; -.
DR HOGENOM; CLU_000288_63_6_1; -.
DR InParanoid; Q2TA06; -.
DR OMA; PHTKNVD; -.
DR OrthoDB; 954262at2759; -.
DR TreeFam; TF105331; -.
DR Reactome; R-BTA-6804114; TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest.
DR Reactome; R-BTA-8854050; FBXL7 down-regulates AURKA during mitotic entry and in early mitosis.
DR Reactome; R-BTA-8854521; Interaction between PHLDA1 and AURKA.
DR Proteomes; UP000009136; Chromosome 13.
DR Bgee; ENSBTAG00000013009; Expressed in oocyte and 106 other tissues.
DR GO; GO:0043203; C:axon hillock; IEA:Ensembl.
DR GO; GO:0005814; C:centriole; IEA:UniProtKB-SubCell.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0032133; C:chromosome passenger complex; IBA:GO_Central.
DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR GO; GO:0070938; C:contractile ring; IDA:AgBase.
DR GO; GO:0005737; C:cytoplasm; IDA:AgBase.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0042585; C:germinal vesicle; IEA:Ensembl.
DR GO; GO:0072687; C:meiotic spindle; IEA:Ensembl.
DR GO; GO:0097431; C:mitotic spindle pole; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0045120; C:pronucleus; IEA:Ensembl.
DR GO; GO:0005876; C:spindle microtubule; IBA:GO_Central.
DR GO; GO:0051233; C:spindle midzone; IBA:GO_Central.
DR GO; GO:0000922; C:spindle pole; IDA:AgBase.
DR GO; GO:0031616; C:spindle pole centrosome; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0035174; F:histone serine kinase activity; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
DR GO; GO:0004672; F:protein kinase activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0009948; P:anterior/posterior axis specification; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IEA:Ensembl.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0051642; P:centrosome localization; IEA:Ensembl.
DR GO; GO:0061523; P:cilium disassembly; ISS:UniProtKB.
DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR GO; GO:0007100; P:mitotic centrosome separation; IEA:Ensembl.
DR GO; GO:0007052; P:mitotic spindle organization; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0032091; P:negative regulation of protein binding; IEA:Ensembl.
DR GO; GO:1990138; P:neuron projection extension; IEA:Ensembl.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; IEA:Ensembl.
DR GO; GO:1900195; P:positive regulation of oocyte maturation; IEA:Ensembl.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0071539; P:protein localization to centrosome; IEA:Ensembl.
DR GO; GO:0032465; P:regulation of cytokinesis; IBA:GO_Central.
DR GO; GO:0031647; P:regulation of protein stability; IEA:Ensembl.
DR GO; GO:0009611; P:response to wounding; IEA:Ensembl.
DR GO; GO:0007057; P:spindle assembly involved in female meiosis I; IEA:Ensembl.
DR CDD; cd14116; STKc_Aurora-A; 1.
DR InterPro; IPR030616; Aur.
DR InterPro; IPR030611; AURKA.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24350; PTHR24350; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell cycle; Cell division; Cell projection; Cilium;
KW Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton; Isopeptide bond;
KW Kinase; Microtubule; Mitosis; Nucleotide-binding; Phosphoprotein;
KW Proto-oncogene; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Ubl conjugation.
FT CHAIN 1..402
FT /note="Aurora kinase A"
FT /id="PRO_0000247317"
FT DOMAIN 133..383
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..126
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 280..293
FT /note="Activation segment"
FT /evidence="ECO:0000250|UniProtKB:O14965"
FT COMPBIAS 28..79
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 256
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 143
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 162
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 210..213
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 260..261
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O14965"
FT BINDING 274
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 41
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14965"
FT MOD_RES 287
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O14965"
FT MOD_RES 288
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O14965"
FT MOD_RES 342
FT /note="Phosphoserine; by PKA and PAK"
FT /evidence="ECO:0000250|UniProtKB:O14965"
FT CROSSLNK 258
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O14965"
SQ SEQUENCE 402 AA; 45462 MW; 36859B295D0FDDBD CRC64;
MDRCKENCIS GPKTAVPLSD GPKRVPVAQQ FPSQNPVSVN SGQAQRVLCP TNSSQRVPSQ
AQKLVSIQKP VQTLKQKPPQ AASAPRPVTR PPSNTQKSKQ PQPPAPGNNP EKEVASKQKN
EESKKRQWAL EDFEIGRPLG KGKFGNVYLA REKQSKFILA LKVLFKAQLE KAGVEHQLRR
EVEIQSHLRH PNILRLYGYF HDATRVYLIL EYAPLGAVYR ELQKLSKFDE QRTATYITEL
ANALSYCHSK RVIHRDIKPE NLLLGSAGEL KIADFGWSVH APSSRRTTLC GTLDYLPPEM
IEGRMHDEKV DLWSLGVLCY EFLVGKPPFE ADTYQETYRR ISRVEFTFPD CVPEGARDLI
SRLLKHNPSQ RPTLKEVLEH PWIIANSKPS SCQKKESTSK QS
