WEE1_MOUSE
ID WEE1_MOUSE Reviewed; 646 AA.
AC P47810; Q9EPL7;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Wee1-like protein kinase;
DE EC=2.7.10.2;
DE AltName: Full=Wee1A kinase;
GN Name=Wee1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Calvaria;
RX PubMed=7551544; DOI=10.1007/bf00713068;
RA Honda R., Tanaka H., Ohba Y., Yasuda H.;
RT "Mouse p87wee1 kinase is regulated by M-phase specific phosphorylation.";
RL Chromosome Res. 3:300-308(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11528126; DOI=10.1159/000056998;
RA Cichutek A., Brueckmann T., Seipel B., Hauser H., Schlaubitz S.,
RA Prawitt D., Hankeln T., Schmidt E.R., Winterpacht A., Zabel B.U.;
RT "Comparative architectural aspects of regions of conserved synteny on human
RT chromosome 11p15.3 and mouse chromosome 7 (including genes WEE1 and
RT LMO1).";
RL Cytogenet. Cell Genet. 93:277-283(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP INTERACTION WITH 14-3-3 ZETA.
RX PubMed=9016762; DOI=10.1006/bbrc.1996.5933;
RA Honda R., Ohba Y., Yasuda H.;
RT "14-3-3 zeta protein binds to the carboxyl half of mouse wee1 kinase.";
RL Biochem. Biophys. Res. Commun. 230:262-265(1997).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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; D30743; BAA06404.1; -; mRNA.
DR EMBL; AJ278435; CAC17145.1; -; Genomic_DNA.
DR EMBL; AK011212; BAB27471.1; -; mRNA.
DR EMBL; BC006852; AAH06852.1; -; mRNA.
DR CCDS; CCDS21743.1; -.
DR RefSeq; NP_033542.2; NM_009516.3.
DR AlphaFoldDB; P47810; -.
DR SMR; P47810; -.
DR BioGRID; 204556; 3.
DR MINT; P47810; -.
DR STRING; 10090.ENSMUSP00000033326; -.
DR iPTMnet; P47810; -.
DR PhosphoSitePlus; P47810; -.
DR EPD; P47810; -.
DR MaxQB; P47810; -.
DR PaxDb; P47810; -.
DR PeptideAtlas; P47810; -.
DR PRIDE; P47810; -.
DR ProteomicsDB; 299762; -.
DR Antibodypedia; 3903; 677 antibodies from 39 providers.
DR DNASU; 22390; -.
DR Ensembl; ENSMUST00000033326; ENSMUSP00000033326; ENSMUSG00000031016.
DR GeneID; 22390; -.
DR KEGG; mmu:22390; -.
DR UCSC; uc009jey.1; mouse.
DR CTD; 7465; -.
DR MGI; MGI:103075; Wee1.
DR VEuPathDB; HostDB:ENSMUSG00000031016; -.
DR eggNOG; KOG0601; Eukaryota.
DR GeneTree; ENSGT00940000157939; -.
DR HOGENOM; CLU_000288_25_1_1; -.
DR InParanoid; P47810; -.
DR OMA; NSEGKCR; -.
DR OrthoDB; 1063695at2759; -.
DR PhylomeDB; P47810; -.
DR TreeFam; TF101088; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-156711; Polo-like kinase mediated events.
DR Reactome; R-MMU-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-MMU-69273; Cyclin A/B1/B2 associated events during G2/M transition.
DR Reactome; R-MMU-69478; G2/M DNA replication checkpoint.
DR Reactome; R-MMU-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR Reactome; R-MMU-75035; Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex.
DR BioGRID-ORCS; 22390; 27 hits in 74 CRISPR screens.
DR PRO; PR:P47810; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P47810; protein.
DR Bgee; ENSMUSG00000031016; Expressed in endoderm of midgut and 252 other tissues.
DR Genevisible; P47810; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
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; IDA:MGI.
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; IMP:MGI.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IMP:MGI.
DR GO; GO:0000278; P:mitotic cell cycle; IEA:InterPro.
DR GO; GO:0048812; P:neuron projection morphogenesis; IMP:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
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_0000086811"
FT DOMAIN 298..568
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..178
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:0000250|UniProtKB:Q63802"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30291"
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 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:0007744|PubMed:21183079"
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"
FT CONFLICT 73
FT /note="E -> Q (in Ref. 1; BAA06404)"
FT /evidence="ECO:0000305"
FT CONFLICT 449
FT /note="D -> Y (in Ref. 1; BAA06404)"
FT /evidence="ECO:0000305"
FT CONFLICT 466
FT /note="V -> D (in Ref. 1; BAA06404)"
FT /evidence="ECO:0000305"
FT CONFLICT 474
FT /note="V -> L (in Ref. 1; BAA06404)"
FT /evidence="ECO:0000305"
FT CONFLICT 521
FT /note="Q -> H (in Ref. 1; BAA06404)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 646 AA; 71578 MW; 80B7A156238E8AEA CRC64;
MSFLSRQQPP PTRRVGAAYS LRQKLIFSPG SDCEEEEEEE EEGSGHSTGE DSAFQEPDSP
LPSARSPAEA EAERRRRSPG AEPSSPGELE DDLLLQGGGG GAQAAGGGAE GDSWEEEGFG
SSSPVKSPST AYFLSSPFSP VRCGGPGDAS PQGCGAPRAM DDPCSPQPDY PSTPPHKTFR
KLRLFDTPHT PKSLLSKARV IDSGSVKLRG SSLFMDTEKS GKREFDTRQT PQVNINPFTP
DPVLLHSSGR CRGRKRAYFN DSSEDMEASD YEFEDETRPA KRITITESNM KSRYTTEFHE
LEKIGSGEFG SVFKCVKRLD GCIYAIKRSK KPLAGSVDEQ NALREVYAHA VLGQHPHVVR
YFSAWAEDDH MLIQNEYCNG GSLADAISEN YRVMSYLTEV ELKDLLLQVG RGLRYIHSMS
LVHMDIKPSN IFISRTSIPN AVSEEGDEDD WISNKVMFKI GDLGHVTRIS SPQVEEGDSR
FLANEVLQEN YSHLPKADIF ALALTVVCAA GAEPLPRNGE QWHEIRQGRL PRIPQVLSQE
VTELLRVMIH PDPERRPSAM ELVKHSVLLS ASRKSAEQLR IELNAEKFKN SLLQKELKKA
QMAAKVAAEE RALFTDRMAT RSTTQSNRTS RLIGKKMNRS VSLTIY
