WEE1_RAT
ID WEE1_RAT Reviewed; 646 AA.
AC Q63802; Q5EAN3;
DT 13-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Wee1-like protein kinase;
DE EC=2.7.10.2;
DE AltName: Full=Wee1A kinase;
GN Name=Wee1;
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].
RA Furunobu A.;
RL Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78 AND SER-85, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Acts as a negative regulator of entry into mitosis (G2 to M
CC transition) by protecting the nucleus from cytoplasmically activated
CC cyclin B1-complexed CDK1 before the onset of mitosis by mediating
CC phosphorylation of CDK1 on 'Tyr-15'. Specifically phosphorylates and
CC inactivates cyclin B1-complexed CDK1 reaching a maximum during G2 phase
CC and a minimum as cells enter M phase. Phosphorylation of cyclin B1-CDK1
CC occurs exclusively on 'Tyr-15' and phosphorylation of monomeric CDK1
CC does not occur. Its activity increases during S and G2 phases and
CC decreases at M phase when it is hyperphosphorylated. A correlated
CC decrease in protein level occurs at M/G1 phase, probably due to its
CC degradation (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10027};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Note=Binds 2 magnesium ions per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Synthesis is increased during S and G2 phases,
CC presumably by an increase in transcription; activity is decreased by
CC phosphorylation during m phase. Protein levels fall in M phase as a
CC result of decreased synthesis combined with degradation. Activity seems
CC to be negatively regulated by phosphorylation upon entry into mitosis,
CC although N-terminal phosphorylation might also regulate the protein
CC stability via protection from proteolysis or might regulate the
CC subcellular location (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Binds to 14-3-3 protein zeta.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- PTM: Phosphorylated during M and G1 phases. Also autophosphorylated.
CC Phosphorylation at Ser-642 by BRSK1 and BRSK2 in post-mitotic neurons,
CC leads to down-regulate WEE1 activity in polarized neurons.
CC Phosphorylated at Ser-52 and Ser-123 by PLK1 and CDK1, respectively,
CC generating an signal for degradation that can be recognized by the
CC SCF(BTRC) complex, leading to its ubiquitination and degradation at the
CC onset of G2/M phase (By similarity). {ECO:0000250}.
CC -!- PTM: Dephosphorylated at Thr-239 by CTDP1 (By similarity).
CC Dephosphorylated at Ser-52 and Ser-123 by the serine/threonine-protein
CC phosphatase 2A preventing its ubiquitin-mediated degradation (By
CC similarity). {ECO:0000250|UniProtKB:P30291}.
CC -!- PTM: Ubiquitinated and degraded at the onset of G2/M phase.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. WEE1 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; D31838; BAA06624.1; -; mRNA.
DR EMBL; BC090346; AAH90346.1; -; mRNA.
DR RefSeq; NP_001012760.1; NM_001012742.1.
DR AlphaFoldDB; Q63802; -.
DR SMR; Q63802; -.
DR STRING; 10116.ENSRNOP00000013362; -.
DR iPTMnet; Q63802; -.
DR PhosphoSitePlus; Q63802; -.
DR jPOST; Q63802; -.
DR PaxDb; Q63802; -.
DR Ensembl; ENSRNOT00000013362; ENSRNOP00000013362; ENSRNOG00000010017.
DR GeneID; 308937; -.
DR KEGG; rno:308937; -.
DR UCSC; RGD:1307895; rat.
DR CTD; 7465; -.
DR RGD; 1307895; Wee1.
DR eggNOG; KOG0601; Eukaryota.
DR GeneTree; ENSGT00940000157939; -.
DR HOGENOM; CLU_000288_25_1_1; -.
DR InParanoid; Q63802; -.
DR OMA; NSEGKCR; -.
DR OrthoDB; 1063695at2759; -.
DR PhylomeDB; Q63802; -.
DR TreeFam; TF101088; -.
DR BRENDA; 2.7.11.1; 5301.
DR Reactome; R-RNO-156711; Polo-like kinase mediated events.
DR Reactome; R-RNO-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-RNO-69273; Cyclin A/B1/B2 associated events during G2/M transition.
DR Reactome; R-RNO-69478; G2/M DNA replication checkpoint.
DR Reactome; R-RNO-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR Reactome; R-RNO-75035; Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex.
DR PRO; PR:Q63802; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000010017; Expressed in testis and 18 other tissues.
DR Genevisible; Q63802; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004672; F:protein kinase activity; ISO:RGD.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0030010; P:establishment of cell polarity; ISO:RGD.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; ISO:RGD.
DR GO; GO:0000278; P:mitotic cell cycle; IEA:InterPro.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISO:RGD.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
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 InterPro; IPR017164; Wee1-like_protein_kinase.
DR Pfam; PF00069; Pkinase; 1.
DR PIRSF; PIRSF037281; Wee1-like_protein_kinase; 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; Kinase; Magnesium; Metal-binding;
KW Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Transferase; Tyrosine-protein kinase; Ubl conjugation.
FT CHAIN 1..646
FT /note="Wee1-like protein kinase"
FT /id="PRO_0000086812"
FT DOMAIN 298..568
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 27..175
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 120..136
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 425
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 304..312
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 327
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 430
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 462
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT MOD_RES 52
FT /note="Phosphoserine; by PLK1"
FT /evidence="ECO:0000250|UniProtKB:P30291"
FT MOD_RES 78
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 123
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:P30291"
FT MOD_RES 127
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30291"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30291"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30291"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30291"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47810"
FT MOD_RES 187
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P30291"
FT MOD_RES 190
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P30291"
FT MOD_RES 239
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P30291"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30291"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30291"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30291"
FT MOD_RES 642
FT /note="Phosphoserine; by BRSK1 and BRSK2"
FT /evidence="ECO:0000250|UniProtKB:P30291"
SQ SEQUENCE 646 AA; 71496 MW; 740120F51C811DAF CRC64;
MSFLSRQQPP PTRRAAAACS LRQKLIFSPG SDCEEEEEEE EEGSGHSTGE DSAFQEPDSP
LPSARSPAEA EAERRRRSPG AEPSSPGELE EDLLLRGGGG GAQAAGGGAE GDSWEEEGFG
SSSPVKSPTT AYFLGSSFSP VRCGGPGDAS PRGCGVPRAM DDPCSPQPDY PSTPPHKTFR
KLRLFDTPHT PKSLLSKARV IDSSSVKLRG SSLFMDTEKS GKREFDTRQT PQVNINPFTP
DPVMLHSSGQ CRGRKRAYFN DSSEDMEASD YEFEDETRPA KRITITESNM KSRYTTEFHE
LEKIGSGEFG SVFKCVKRLD GCIYAIKRSK KPLAGSVDEQ NALREVYAHA VLGQHPHVVR
YFSAWAEDDH MLIQNEYCNG GSLADAVSEN YRVMSYFTEA ELKDLLLQVG RGLRYIHSMS
LVHMDIKPSN IFISRTSIPN AVSEEGDEDD WISNKVMFKI GDLGHVTRIS SPQVEEGDSR
FLANEVLQEN YSHLPKADIF ALALTVVCAA GAEPLPRNGD QWHEIRQGRL PRIPQVLSQE
LTELLKVMIH PDPERRPSAM VLVKHSVLLS ASRKSAEQLR IELNAEKFKN SLLQKELKKA
QMAAKVAAEE RALLTDRMAT RSTTQSNRTS RLIGKKMNRS VSLTIY
