WEE1_HUMAN
ID WEE1_HUMAN Reviewed; 646 AA.
AC P30291; B3KVE1; D3DQV0;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=Wee1-like protein kinase;
DE Short=WEE1hu;
DE EC=2.7.10.2;
DE AltName: Full=Wee1A kinase;
GN Name=WEE1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHARACTERIZATION.
RX PubMed=7743995; DOI=10.1002/j.1460-2075.1995.tb07180.x;
RA Watanabe N., Broome M., Hunter T.;
RT "Regulation of the human WEE1Hu CDK tyrosine 15-kinase during the cell
RT cycle.";
RL EMBO J. 14:1878-1891(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Blood;
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] (ISOFORM 2).
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-214 (ISOFORM 1).
RA Igarashi M.;
RL Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 215-646 (ISOFORM 1).
RX PubMed=1840647; DOI=10.1038/353080a0;
RA Igarashi M., Nagata A., Jinno S., Suto K., Okayama H.;
RT "Wee1(+)-like gene in human cells.";
RL Nature 353:80-83(1991).
RN [8]
RP CHARACTERIZATION, AND MUTAGENESIS OF LYS-328.
RX PubMed=8428596; DOI=10.1002/j.1460-2075.1993.tb05633.x;
RA McGowan C.H., Russell P.;
RT "Human Wee1 kinase inhibits cell division by phosphorylating p34cdc2
RT exclusively on Tyr15.";
RL EMBO J. 12:75-85(1993).
RN [9]
RP PHOSPHORYLATION AT SER-642.
RC TISSUE=Testis;
RX PubMed=15150265; DOI=10.1074/jbc.m404728200;
RA Lu R., Niida H., Nakanishi M.;
RT "Human SAD1 kinase is involved in UV-induced DNA damage checkpoint
RT function.";
RL J. Biol. Chem. 279:31164-31170(2004).
RN [10]
RP PHOSPHORYLATION AT SER-53 AND SER-123, UBIQUITINATION, AND MUTAGENESIS OF
RP SER-53; 116-GLU-GLU-117 AND SER-123.
RX PubMed=15070733; DOI=10.1073/pnas.0307700101;
RA Watanabe N., Arai H., Nishihara Y., Taniguchi M., Watanabe N., Hunter T.,
RA Osada H.;
RT "M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by
RT SCFbeta-TrCP.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:4419-4424(2004).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-150; THR-190 AND
RP SER-312, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP PHOSPHORYLATION AT SER-642, AND MUTAGENESIS OF SER-642.
RX PubMed=20026642; DOI=10.1242/jcs.058230;
RA Muller M., Lutter D., Puschel A.W.;
RT "Persistence of the cell-cycle checkpoint kinase Wee1 in SadA- and SadB-
RT deficient neurons disrupts neuronal polarity.";
RL J. Cell Sci. 123:286-294(2010).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127 AND SER-139, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP PHOSPHORYLATION AT THR-239, AND DEPHOSPHORYLATION.
RX PubMed=22692537; DOI=10.1038/ncomms1886;
RA Visconti R., Palazzo L., Della Monica R., Grieco D.;
RT "Fcp1-dependent dephosphorylation is required for M-phase-promoting factor
RT inactivation at mitosis exit.";
RL Nat. Commun. 3:894-894(2012).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-137; SER-139; THR-187;
RP THR-190; SER-270; SER-307 AND SER-312, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [18]
RP DEPHOSPHORYLATION AT SER-53 AND SER-123 BY SERINE/THREONINE-PROTEIN
RP PHOSPHATASE 2A.
RX PubMed=33108758; DOI=10.1016/j.molcel.2020.10.008;
RA Li F., Kozono D., Deraska P., Branigan T., Dunn C., Zheng X.F., Parmar K.,
RA Nguyen H., DeCaprio J., Shapiro G.I., Chowdhury D., D'Andrea A.D.;
RT "CHK1 Inhibitor Blocks Phosphorylation of FAM122A and Promotes Replication
RT Stress.";
RL Mol. Cell 0:0-0(2020).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.81 ANGSTROMS) OF 291-575 IN COMPLEX WITH MAGNESIUM
RP AND AN INHIBITOR.
RX PubMed=15837193; DOI=10.1016/j.str.2004.12.017;
RA Squire C.J., Dickson J.M., Ivanovic I., Baker E.N.;
RT "Structure and inhibition of the human cell cycle checkpoint kinase, Wee1A
RT kinase: an atypical tyrosine kinase with a key role in CDK1 regulation.";
RL Structure 13:541-550(2005).
RN [20]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-210 AND ILE-472.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
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.
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;
CC Note=Binds 2 magnesium ions per subunit.;
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.
CC -!- INTERACTION:
CC P30291; Q9Y297: BTRC; NbExp=2; IntAct=EBI-914695, EBI-307461;
CC P30291; Q9UKB1: FBXW11; NbExp=3; IntAct=EBI-914695, EBI-355189;
CC P30291; P53350: PLK1; NbExp=2; IntAct=EBI-914695, EBI-476768;
CC P30291; P63104: YWHAZ; NbExp=3; IntAct=EBI-914695, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P30291-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P30291-2; Sequence=VSP_044959;
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-53 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. {ECO:0000269|PubMed:15070733,
CC ECO:0000269|PubMed:15150265, ECO:0000269|PubMed:20026642,
CC ECO:0000269|PubMed:22692537}.
CC -!- PTM: Dephosphorylated at Thr-239 by CTDP1 (PubMed:22692537).
CC Dephosphorylated at Ser-53 and Ser-123 by the serine/threonine-protein
CC phosphatase 2A preventing its ubiquitin-mediated degradation
CC (PubMed:33108758). {ECO:0000269|PubMed:22692537,
CC ECO:0000269|PubMed:33108758}.
CC -!- PTM: Ubiquitinated and degraded at the onset of G2/M phase.
CC {ECO:0000269|PubMed:15070733}.
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; U10564; AAB60401.1; -; mRNA.
DR EMBL; AJ277546; CAC14173.1; -; Genomic_DNA.
DR EMBL; AK122837; BAG53753.1; -; mRNA.
DR EMBL; AC011979; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC122179; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68586.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68587.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68588.1; -; Genomic_DNA.
DR EMBL; X62048; CAA43979.1; -; mRNA.
DR CCDS; CCDS44536.1; -. [P30291-2]
DR CCDS; CCDS7800.1; -. [P30291-1]
DR PIR; S55048; S55048.
DR RefSeq; NP_001137448.1; NM_001143976.1. [P30291-2]
DR RefSeq; NP_003381.1; NM_003390.3. [P30291-1]
DR PDB; 1X8B; X-ray; 1.81 A; A=291-575.
DR PDB; 2IN6; X-ray; 1.90 A; A=291-575.
DR PDB; 2IO6; X-ray; 2.20 A; A=291-575.
DR PDB; 2Z2W; X-ray; 2.22 A; A=291-575.
DR PDB; 3BI6; X-ray; 2.20 A; A=291-575.
DR PDB; 3BIZ; X-ray; 2.20 A; A=291-575.
DR PDB; 3CQE; X-ray; 2.50 A; A=291-575.
DR PDB; 3CR0; X-ray; 2.30 A; A=291-575.
DR PDB; 5V5Y; X-ray; 1.90 A; A=291-575.
DR PDB; 5VC3; X-ray; 1.97 A; A=291-575.
DR PDB; 5VC4; X-ray; 2.10 A; A=291-575.
DR PDB; 5VC5; X-ray; 1.93 A; A=291-575.
DR PDB; 5VC6; X-ray; 2.00 A; A=291-575.
DR PDB; 5VD2; X-ray; 2.05 A; A=291-575.
DR PDB; 5VD4; X-ray; 2.02 A; A=291-575.
DR PDB; 5VD5; X-ray; 2.05 A; A=291-575.
DR PDB; 5VD7; X-ray; 2.08 A; A=291-575.
DR PDB; 5VD8; X-ray; 1.85 A; A=291-575.
DR PDB; 5VD9; X-ray; 1.87 A; A=291-575.
DR PDB; 5VDA; X-ray; 2.10 A; A=291-575.
DR PDB; 7N3U; X-ray; 2.65 A; A=291-575.
DR PDBsum; 1X8B; -.
DR PDBsum; 2IN6; -.
DR PDBsum; 2IO6; -.
DR PDBsum; 2Z2W; -.
DR PDBsum; 3BI6; -.
DR PDBsum; 3BIZ; -.
DR PDBsum; 3CQE; -.
DR PDBsum; 3CR0; -.
DR PDBsum; 5V5Y; -.
DR PDBsum; 5VC3; -.
DR PDBsum; 5VC4; -.
DR PDBsum; 5VC5; -.
DR PDBsum; 5VC6; -.
DR PDBsum; 5VD2; -.
DR PDBsum; 5VD4; -.
DR PDBsum; 5VD5; -.
DR PDBsum; 5VD7; -.
DR PDBsum; 5VD8; -.
DR PDBsum; 5VD9; -.
DR PDBsum; 5VDA; -.
DR PDBsum; 7N3U; -.
DR AlphaFoldDB; P30291; -.
DR SMR; P30291; -.
DR BioGRID; 113303; 101.
DR DIP; DIP-37969N; -.
DR IntAct; P30291; 29.
DR MINT; P30291; -.
DR STRING; 9606.ENSP00000402084; -.
DR BindingDB; P30291; -.
DR ChEMBL; CHEMBL5491; -.
DR DrugBank; DB07265; 3-(9-HYDROXY-1,3-DIOXO-4-PHENYL-2,3-DIHYDROPYRROLO[3,4-C]CARBAZOL-6(1H)-YL)PROPANOIC ACID.
DR DrugBank; DB07257; 4-(2-chlorophenyl)-8-(2-hydroxyethyl)-6-methylpyrrolo[3,4-e]indole-1,3(2H,6H)-dione.
DR DrugBank; DB08365; 8-bromo-4-(2-chlorophenyl)-N-(2-hydroxyethyl)-6-methyl-1,3-dioxo-1,2,3,6-tetrahydropyrrolo[3,4-e]indole-7-carboxamide.
DR DrugBank; DB04608; 9-HYDROXY-4-PHENYL-6H-PYRROLO[3,4-C]CARBAZOLE-1,3-DIONE.
DR DrugBank; DB07006; 9-HYDROXY-6-(3-HYDROXYPROPYL)-4-(2-METHOXYPHENYL)PYRROLO[3,4-C]CARBAZOLE-1,3(2H,6H)-DIONE.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB11740; MK-1775.
DR DrugBank; DB07226; N-[4-(2-CHLOROPHENYL)-1,3-DIOXO-1,2,3,6-TETRAHYDROPYRROLO[3,4-C]CARBAZOL-9-YL]FORMAMIDE.
DR DrugCentral; P30291; -.
DR GuidetoPHARMACOLOGY; 2278; -.
DR iPTMnet; P30291; -.
DR PhosphoSitePlus; P30291; -.
DR BioMuta; WEE1; -.
DR DMDM; 1351419; -.
DR EPD; P30291; -.
DR jPOST; P30291; -.
DR MassIVE; P30291; -.
DR MaxQB; P30291; -.
DR PaxDb; P30291; -.
DR PeptideAtlas; P30291; -.
DR PRIDE; P30291; -.
DR ProteomicsDB; 3755; -.
DR ProteomicsDB; 54650; -. [P30291-1]
DR Antibodypedia; 3903; 677 antibodies from 39 providers.
DR DNASU; 7465; -.
DR Ensembl; ENST00000299613.10; ENSP00000299613.5; ENSG00000166483.12. [P30291-2]
DR Ensembl; ENST00000450114.7; ENSP00000402084.2; ENSG00000166483.12. [P30291-1]
DR Ensembl; ENST00000681684.1; ENSP00000506667.1; ENSG00000166483.12. [P30291-2]
DR GeneID; 7465; -.
DR KEGG; hsa:7465; -.
DR MANE-Select; ENST00000450114.7; ENSP00000402084.2; NM_003390.4; NP_003381.1.
DR UCSC; uc001mhs.4; human. [P30291-1]
DR CTD; 7465; -.
DR DisGeNET; 7465; -.
DR GeneCards; WEE1; -.
DR HGNC; HGNC:12761; WEE1.
DR HPA; ENSG00000166483; Low tissue specificity.
DR MIM; 193525; gene.
DR neXtProt; NX_P30291; -.
DR OpenTargets; ENSG00000166483; -.
DR PharmGKB; PA366; -.
DR VEuPathDB; HostDB:ENSG00000166483; -.
DR eggNOG; KOG0601; Eukaryota.
DR GeneTree; ENSGT00940000157939; -.
DR HOGENOM; CLU_000288_25_1_1; -.
DR InParanoid; P30291; -.
DR OMA; NSEGKCR; -.
DR PhylomeDB; P30291; -.
DR TreeFam; TF101088; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; P30291; -.
DR Reactome; R-HSA-156711; Polo-like kinase mediated events.
DR Reactome; R-HSA-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-HSA-69273; Cyclin A/B1/B2 associated events during G2/M transition.
DR Reactome; R-HSA-69478; G2/M DNA replication checkpoint.
DR Reactome; R-HSA-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR Reactome; R-HSA-75035; Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex.
DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR SignaLink; P30291; -.
DR SIGNOR; P30291; -.
DR BioGRID-ORCS; 7465; 806 hits in 1124 CRISPR screens.
DR ChiTaRS; WEE1; human.
DR EvolutionaryTrace; P30291; -.
DR GeneWiki; Wee1-like_protein_kinase; -.
DR GenomeRNAi; 7465; -.
DR Pharos; P30291; Tchem.
DR PRO; PR:P30291; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P30291; protein.
DR Bgee; ENSG00000166483; Expressed in ventricular zone and 182 other tissues.
DR ExpressionAtlas; P30291; baseline and differential.
DR Genevisible; P30291; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
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; IBA:GO_Central.
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; IEA:Ensembl.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IEA:Ensembl.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0048812; P:neuron projection morphogenesis; IEA:Ensembl.
DR DisProt; DP00611; -.
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 3D-structure; Alternative splicing; ATP-binding; Cell cycle; Cell division;
KW Kinase; Magnesium; Metal-binding; Mitosis; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase; Tyrosine-protein kinase;
KW Ubl conjugation.
FT CHAIN 1..646
FT /note="Wee1-like protein kinase"
FT /id="PRO_0000086810"
FT DOMAIN 299..569
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 32..46
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 61..80
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 157..181
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 426
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 305..313
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 328
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 431
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:15837193"
FT BINDING 463
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:15837193"
FT MOD_RES 53
FT /note="Phosphoserine; by PLK1"
FT /evidence="ECO:0000269|PubMed:15070733"
FT MOD_RES 78
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63802"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 123
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:15070733"
FT MOD_RES 127
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47810"
FT MOD_RES 187
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 190
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 239
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:22692537"
FT MOD_RES 270
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 642
FT /note="Phosphoserine; by BRSK1 and BRSK2"
FT /evidence="ECO:0000269|PubMed:15150265,
FT ECO:0000269|PubMed:20026642"
FT VAR_SEQ 1..214
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044959"
FT VARIANT 210
FT /note="G -> C (in dbSNP:rs34412975)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041302"
FT VARIANT 472
FT /note="S -> I (in dbSNP:rs56411856)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041303"
FT MUTAGEN 53
FT /note="S->A: Abolishes phosphorylation by PLK1 and CDK1 and
FT binding of the SCF(BTRC) complex, leading to stabilization
FT of the protein; when associated with A-123."
FT /evidence="ECO:0000269|PubMed:15070733"
FT MUTAGEN 116..117
FT /note="EE->AA: Impairs binding of the SCF(BTRC) complex."
FT /evidence="ECO:0000269|PubMed:15070733"
FT MUTAGEN 123
FT /note="S->A: Abolishes phosphorylation by PLK1 and CDK1 and
FT binding of the SCF(BTRC) complex, leading to stabilization
FT of the protein; when associated with A-53."
FT /evidence="ECO:0000269|PubMed:15070733"
FT MUTAGEN 328
FT /note="K->R: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:8428596"
FT MUTAGEN 642
FT /note="S->A: Abolishes phosphorylation by BRSK1 and BRSK2."
FT /evidence="ECO:0000269|PubMed:20026642"
FT CONFLICT 65
FT /note="A -> E (in Ref. 6; CAA43979)"
FT /evidence="ECO:0000305"
FT HELIX 294..298
FT /evidence="ECO:0007829|PDB:1X8B"
FT STRAND 299..308
FT /evidence="ECO:0007829|PDB:1X8B"
FT STRAND 311..318
FT /evidence="ECO:0007829|PDB:1X8B"
FT TURN 319..321
FT /evidence="ECO:0007829|PDB:1X8B"
FT STRAND 324..331
FT /evidence="ECO:0007829|PDB:1X8B"
FT STRAND 335..337
FT /evidence="ECO:0007829|PDB:5VD5"
FT HELIX 338..352
FT /evidence="ECO:0007829|PDB:1X8B"
FT STRAND 362..368
FT /evidence="ECO:0007829|PDB:1X8B"
FT STRAND 371..377
FT /evidence="ECO:0007829|PDB:1X8B"
FT HELIX 384..394
FT /evidence="ECO:0007829|PDB:1X8B"
FT HELIX 400..419
FT /evidence="ECO:0007829|PDB:1X8B"
FT HELIX 429..431
FT /evidence="ECO:0007829|PDB:1X8B"
FT STRAND 432..435
FT /evidence="ECO:0007829|PDB:1X8B"
FT STRAND 458..461
FT /evidence="ECO:0007829|PDB:1X8B"
FT HELIX 464..466
FT /evidence="ECO:0007829|PDB:5V5Y"
FT STRAND 468..472
FT /evidence="ECO:0007829|PDB:5VD8"
FT HELIX 480..482
FT /evidence="ECO:0007829|PDB:1X8B"
FT HELIX 485..488
FT /evidence="ECO:0007829|PDB:1X8B"
FT HELIX 495..510
FT /evidence="ECO:0007829|PDB:1X8B"
FT STRAND 518..520
FT /evidence="ECO:0007829|PDB:1X8B"
FT HELIX 521..527
FT /evidence="ECO:0007829|PDB:1X8B"
FT HELIX 540..549
FT /evidence="ECO:0007829|PDB:1X8B"
FT HELIX 554..556
FT /evidence="ECO:0007829|PDB:1X8B"
FT HELIX 560..564
FT /evidence="ECO:0007829|PDB:1X8B"
FT TURN 567..569
FT /evidence="ECO:0007829|PDB:5VD8"
SQ SEQUENCE 646 AA; 71597 MW; DB00623D304562A0 CRC64;
MSFLSRQQPP PPRRAGAACT LRQKLIFSPC SDCEEEEEEE EEEGSGHSTG EDSAFQEPDS
PLPPARSPTE PGPERRRSPG PAPGSPGELE EDLLLPGACP GADEAGGGAE GDSWEEEGFG
SSSPVKSPAA PYFLGSSFSP VRCGGPGDAS PRGCGARRAG EGRRSPRPDH PGTPPHKTFR
KLRLFDTPHT PKSLLSKARG IDSSSVKLRG SSLFMDTEKS GKREFDVRQT PQVNINPFTP
DSLLLHSSGQ CRRRKRTYWN DSCGEDMEAS DYELEDETRP AKRITITESN MKSRYTTEFH
ELEKIGSGEF GSVFKCVKRL DGCIYAIKRS KKPLAGSVDE QNALREVYAH AVLGQHSHVV
RYFSAWAEDD HMLIQNEYCN GGSLADAISE NYRIMSYFKE AELKDLLLQV GRGLRYIHSM
SLVHMDIKPS NIFISRTSIP NAASEEGDED DWASNKVMFK IGDLGHVTRI SSPQVEEGDS
RFLANEVLQE NYTHLPKADI FALALTVVCA AGAEPLPRNG DQWHEIRQGR LPRIPQVLSQ
EFTELLKVMI HPDPERRPSA MALVKHSVLL SASRKSAEQL RIELNAEKFK NSLLQKELKK
AQMAKAAAEE RALFTDRMAT RSTTQSNRTS RLIGKKMNRS VSLTIY
