AURKA_RAT
ID AURKA_RAT Reviewed; 397 AA.
AC P59241;
DT 27-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JAN-2003, sequence version 1.
DT 03-AUG-2022, entry version 146.
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 6;
DE AltName: Full=Serine/threonine-protein kinase aurora-A;
DE Short=ratAurA;
GN Name=Aurka; Synonyms=Aik, Airk, Ark1, Aura, Ayk1, Btak, Iak1, Stk15, Stk6;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar Furth; TISSUE=Mammary gland;
RX PubMed=12124350;
RA Goepfert T.M., Adigun Y.E., Zhong L., Gay J., Medina D., Brinkley W.R.;
RT "Centrosome amplification and overexpression of aurora A are early events
RT in rat mammary carcinogenesis.";
RL Cancer Res. 62:4115-4122(2002).
RN [2]
RP FUNCTION, PHOSPHORYLATION, AND TISSUE SPECIFICITY.
RX PubMed=19812038; DOI=10.1074/jbc.m109.055897;
RA Khazaei M.R., Puschel A.W.;
RT "Phosphorylation of the par polarity complex protein Par3 at serine 962 is
RT mediated by aurora A and regulates its function in neuronal polarity.";
RL J. Biol. Chem. 284:33571-33579(2009).
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 (By similarity). Required for initial activation of CDK1 at
CC centrosomes. Phosphorylates numerous target proteins, including
CC ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3,
CC PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin
CC depolymerase activity. Required for normal axon formation. Plays a role
CC in 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 stabilizing p53/TP53. Phosphorylates its
CC own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to
CC inhibit their activity (By similarity). Necessary for proper cilia
CC disassembly prior to mitosis (By similarity). Regulates protein levels
CC of the anti-apoptosis protein BIRC5 by suppressing the expression of
CC the SCF(FBXL7) E3 ubiquitin-protein ligase substrate adapter FBXL7
CC through the phosphorylation of the transcription factor FOXP1 (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:O14965,
CC ECO:0000269|PubMed:19812038}.
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 FBXL7 and PIFO (By similarity). Inhibited by the
CC small 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=Localizes on
CC centrosomes in interphase cells and at each spindle pole in mitosis.
CC Associates with both the pericentriolar material (PCM) and centrioles.
CC Detected at the neurite hillock in developing neurons. Colocalized with
CC SIRT2 at centrosome. The localization to the spindle poles is regulated
CC by AAAS (By similarity). {ECO:0000250|UniProtKB:O14965,
CC ECO:0000250|UniProtKB:P97477}.
CC -!- TISSUE SPECIFICITY: Detected in neurons in brain cortex and hippocampus
CC (at protein level). Expressed in mammary gland and tumor.
CC {ECO:0000269|PubMed:19812038}.
CC -!- INDUCTION: Activated by progesterone.
CC -!- PTM: Activated by phosphorylation at Thr-281; this brings about a
CC change in the conformation of the activation segment (By similarity).
CC Phosphorylation at Thr-281 varies during the cell cycle and is highest
CC during M phase (By similarity). Autophosphorylated at Thr-281 upon TPX2
CC binding (By similarity). Thr-281 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-281 during mitosis (By similarity). Phosphorylation at Ser-335
CC decreases the kinase activity (By similarity). PPP2CA controls
CC degradation by dephosphorylating Ser-52 at the end of mitosis (By
CC similarity). Phosphorylated in embryonic brain neurons
CC (PubMed:19812038). {ECO:0000250|UniProtKB:O14965,
CC ECO:0000269|PubMed:19812038}.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF537333; AAN06823.1; -; mRNA.
DR AlphaFoldDB; P59241; -.
DR SMR; P59241; -.
DR STRING; 10116.ENSRNOP00000051977; -.
DR iPTMnet; P59241; -.
DR PhosphoSitePlus; P59241; -.
DR PaxDb; P59241; -.
DR RGD; 628895; Aurka.
DR eggNOG; KOG0580; Eukaryota.
DR InParanoid; P59241; -.
DR PhylomeDB; P59241; -.
DR Reactome; R-RNO-174178; APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
DR Reactome; R-RNO-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-RNO-6804114; TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest.
DR Reactome; R-RNO-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-RNO-8854050; FBXL7 down-regulates AURKA during mitotic entry and in early mitosis.
DR Reactome; R-RNO-8854518; AURKA Activation by TPX2.
DR Reactome; R-RNO-8854521; Interaction between PHLDA1 and AURKA.
DR PRO; PR:P59241; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0043203; C:axon hillock; ISO:RGD.
DR GO; GO:0005814; C:centriole; IEA:UniProtKB-SubCell.
DR GO; GO:0005813; C:centrosome; IDA:RGD.
DR GO; GO:0032133; C:chromosome passenger complex; IBA:GO_Central.
DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR GO; GO:0042585; C:germinal vesicle; ISO:RGD.
DR GO; GO:0072687; C:meiotic spindle; ISO:RGD.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:RGD.
DR GO; GO:0005815; C:microtubule organizing center; ISO:RGD.
DR GO; GO:0072686; C:mitotic spindle; ISO:RGD.
DR GO; GO:0097431; C:mitotic spindle pole; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0045120; C:pronucleus; ISO:RGD.
DR GO; GO:0005819; C:spindle; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0031616; C:spindle pole centrosome; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0035174; F:histone serine kinase activity; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0004672; F:protein kinase activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0009948; P:anterior/posterior axis specification; ISO:RGD.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007098; P:centrosome cycle; ISO:RGD.
DR GO; GO:0051642; P:centrosome localization; ISO:RGD.
DR GO; GO:0061523; P:cilium disassembly; ISS:UniProtKB.
DR GO; GO:0097421; P:liver regeneration; ISO:RGD.
DR GO; GO:0051321; P:meiotic cell cycle; ISO:RGD.
DR GO; GO:0000212; P:meiotic spindle organization; ISO:RGD.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; ISO:RGD.
DR GO; GO:0000278; P:mitotic cell cycle; ISO:RGD.
DR GO; GO:0007100; P:mitotic centrosome separation; ISO:RGD.
DR GO; GO:0007052; P:mitotic spindle organization; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0032091; P:negative regulation of protein binding; ISO:RGD.
DR GO; GO:1990138; P:neuron projection extension; ISO:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; ISO:RGD.
DR GO; GO:1900195; P:positive regulation of oocyte maturation; ISO:RGD.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0071539; P:protein localization to centrosome; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0032465; P:regulation of cytokinesis; IBA:GO_Central.
DR GO; GO:0031647; P:regulation of protein stability; ISO:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0009611; P:response to wounding; ISO:RGD.
DR GO; GO:0007057; P:spindle assembly involved in female meiosis I; ISO:RGD.
DR GO; GO:0007051; P:spindle organization; ISO:RGD.
DR InterPro; IPR030616; Aur.
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 1: Evidence at protein 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..397
FT /note="Aurora kinase A"
FT /id="PRO_0000086694"
FT DOMAIN 126..376
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 273..286
FT /note="Activation segment"
FT /evidence="ECO:0000250|UniProtKB:O14965"
FT REGION 378..397
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 30..59
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 82..107
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 381..397
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 249
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 136
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 155
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 203..206
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 253..254
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O14965"
FT BINDING 267
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 40
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14965"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14965"
FT MOD_RES 280
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O14965"
FT MOD_RES 281
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O14965"
FT MOD_RES 335
FT /note="Phosphoserine; by PKA and PAK"
FT /evidence="ECO:0000250|UniProtKB:O14965"
FT CROSSLNK 251
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O14965"
SQ SEQUENCE 397 AA; 44874 MW; 95DECA2198DCED85 CRC64;
MDRCKENCVS RPVKSTVPFG PKRVLVTEQI PSQHPGSASS GQAQRVLCPS NSQRVPPQAQ
KPVAGQKPVL KQLPAASGPR PASRLSNPQK SEQPQPAASG NNSEKEQTSI QKTEDSKKRQ
WTLEDFDIGR PLGKGKFGNV YLAREKQSKF ILALKVLFKV QLEKAGVEHQ LRREVEIQSH
LRHPNILRLY GYFHDATRVY LILEYAPLGT VYRELQKLSK FDEQRTATYI TELANALSYC
HSKRVIHRDI KPENLLLGSN GELKIADFGW SVHAPSSRRT TLCGTLDYQP PEMIEGRMHD
EKVDLWSLGV LCYEFLVGMP PFEAHTYQET YRRISRVEFT FPDFVTEGAR DLISRLLKHN
SSQRLTLAEV LEHPWIKANS SKPPTGHNSK EATSKSS
