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 27-MAR-2024, entry version 170. DE RecName: Full=Wee1-like protein kinase; DE EC=2.7.10.2 {ECO:0000250|UniProtKB:P30291}; 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. {ECO:0000250|UniProtKB:P30291}. 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:0000250|UniProtKB:P30291, ECO:0000255|PROSITE- CC ProRule:PRU10027}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10597; CC Evidence={ECO:0000250|UniProtKB:P30291}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P30291}; CC Note=Binds 2 magnesium ions per subunit. CC {ECO:0000250|UniProtKB:P30291}; 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|UniProtKB:P30291}. CC -!- SUBUNIT: Binds to 14-3-3 protein zeta. {ECO:0000250|UniProtKB:P30291}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P30291}. 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|UniProtKB:P30291}. 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|UniProtKB:P30291}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein CC kinase family. WEE1 subfamily. {ECO:0000255|PROSITE-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; 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; 10116-ENSRNOP00000013362; -. DR Ensembl; ENSRNOT00000013362.6; ENSRNOP00000013362.3; ENSRNOG00000010017.7. DR Ensembl; ENSRNOT00055043927; ENSRNOP00055035911; ENSRNOG00055025448. DR Ensembl; ENSRNOT00060034200; ENSRNOP00060028040; ENSRNOG00060019803. DR Ensembl; ENSRNOT00065050766; ENSRNOP00065041728; ENSRNOG00065029399. DR GeneID; 308937; -. DR KEGG; rno:308937; -. DR UCSC; RGD:1307895; rat. DR AGR; RGD:1307895; -. 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; DDWVSNK; -. DR OrthoDB; 928649at2759; -. 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 cell types or tissues. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005730; C:nucleolus; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. 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; ISS:UniProtKB. 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:0010972; P:negative regulation of G2/M transition of mitotic cell cycle; ISS:UniProtKB. DR GO; GO:0048812; P:neuron projection morphogenesis; ISO:RGD. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR CDD; cd14138; PTKc_Wee1a; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR11042; EUKARYOTIC TRANSLATION INITIATION FACTOR 2-ALPHA KINASE EIF2-ALPHA KINASE -RELATED; 1. DR PANTHER; PTHR11042:SF72; WEE1-LIKE PROTEIN KINASE; 1. DR Pfam; PF00069; Pkinase; 1. DR PIRSF; PIRSF037281; Wee1-like_protein_kinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q63802; RN. 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 341 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P30291" FT BINDING 430 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P30291" FT BINDING 462 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P30291" FT BINDING 464 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P30291" 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 //