WEE1_DROME
ID WEE1_DROME Reviewed; 609 AA.
AC P54350; Q9VM70;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Wee1-like protein kinase;
DE Short=Dwee1;
DE EC=2.7.10.2;
GN Name=Wee1 {ECO:0000312|FlyBase:FBgn0011737}; Synonyms=wee;
GN ORFNames=CG4488 {ECO:0000312|FlyBase:FBgn0011737};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=8573790; DOI=10.1091/mbc.6.10.1333;
RA Campbell S.D., Sprenger F., Edgar B.A., O'Farrell P.H.;
RT "Drosophila Wee1 kinase rescues fission yeast from mitotic catastrophe and
RT phosphorylates Drosophila Cdc2 in vitro.";
RL Mol. Biol. Cell 6:1333-1347(1995).
RN [2]
RP SEQUENCE REVISION TO C-TERMINUS.
RA Campbell S.D.;
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [6]
RP FUNCTION.
RX PubMed=15581871; DOI=10.1016/j.ydbio.2004.08.043;
RA Fichelson P., Gho M.;
RT "Mother-daughter precursor cell fate transformation after Cdc2 down-
RT regulation in the Drosophila bristle lineage.";
RL Dev. Biol. 276:367-377(2004).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23; SER-25; SER-27; THR-47;
RP SER-52; THR-165 AND SER-168, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
CC -!- FUNCTION: Acts as a negative regulator of entry into mitosis (G2 to M
CC transition) (PubMed:8573790, PubMed:15581871). This kinase specifically
CC phosphorylates and inactivates cyclin B1-complexed CDC2
CC (PubMed:8573790, PubMed:15581871). {ECO:0000269|PubMed:15581871,
CC ECO:0000269|PubMed:8573790}.
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 -!- 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: Negatively regulated by phosphorylation in the M-
CC phase.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in embryos; expression remains high in
CC the proliferating cells of the central nervous system well after cells
CC in the rest of the embryo have ceased dividing.
CC {ECO:0000269|PubMed:8573790}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically during
CC postblastoderm divisions of embryogenesis.
CC {ECO:0000269|PubMed:8573790}.
CC -!- PTM: Phosphorylated during M and G1 phases. {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; U17223; AAC46913.2; -; mRNA.
DR EMBL; AE014134; AAF52453.2; -; Genomic_DNA.
DR EMBL; AY118942; AAM50802.1; -; mRNA.
DR RefSeq; NP_001260167.1; NM_001273238.1.
DR RefSeq; NP_477035.1; NM_057687.4.
DR AlphaFoldDB; P54350; -.
DR SMR; P54350; -.
DR BioGRID; 60116; 20.
DR DIP; DIP-23536N; -.
DR IntAct; P54350; 3.
DR STRING; 7227.FBpp0304607; -.
DR iPTMnet; P54350; -.
DR PaxDb; P54350; -.
DR PRIDE; P54350; -.
DR DNASU; 33965; -.
DR EnsemblMetazoa; FBtr0079371; FBpp0078999; FBgn0011737.
DR EnsemblMetazoa; FBtr0332329; FBpp0304607; FBgn0011737.
DR GeneID; 33965; -.
DR KEGG; dme:Dmel_CG4488; -.
DR CTD; 7465; -.
DR FlyBase; FBgn0011737; Wee1.
DR VEuPathDB; VectorBase:FBgn0011737; -.
DR eggNOG; KOG0601; Eukaryota.
DR GeneTree; ENSGT00940000170756; -.
DR HOGENOM; CLU_000288_25_1_1; -.
DR InParanoid; P54350; -.
DR OMA; HSENLVT; -.
DR OrthoDB; 1063695at2759; -.
DR PhylomeDB; P54350; -.
DR BRENDA; 2.7.10.2; 1994.
DR Reactome; R-DME-156711; Polo-like kinase mediated events.
DR Reactome; R-DME-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-DME-69273; Cyclin A/B1/B2 associated events during G2/M transition.
DR Reactome; R-DME-69478; G2/M DNA replication checkpoint.
DR Reactome; R-DME-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR Reactome; R-DME-75035; Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex.
DR SignaLink; P54350; -.
DR BioGRID-ORCS; 33965; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 33965; -.
DR PRO; PR:P54350; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0011737; Expressed in cleaving embryo and 32 other tissues.
DR ExpressionAtlas; P54350; baseline and differential.
DR Genevisible; P54350; DM.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
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; IDA:FlyBase.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0051642; P:centrosome localization; IMP:FlyBase.
DR GO; GO:0051299; P:centrosome separation; IMP:FlyBase.
DR GO; GO:0001700; P:embryonic development via the syncytial blastoderm; TAS:FlyBase.
DR GO; GO:0000278; P:mitotic cell cycle; IEA:InterPro.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:FlyBase.
DR GO; GO:0010972; P:negative regulation of G2/M transition of mitotic cell cycle; IGI:FlyBase.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IMP:FlyBase.
DR GO; GO:0006468; P:protein phosphorylation; IDA:FlyBase.
DR GO; GO:0051225; P:spindle assembly; IMP:FlyBase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
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.
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.
FT CHAIN 1..609
FT /note="Wee1-like protein kinase"
FT /id="PRO_0000086814"
FT DOMAIN 239..517
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 147..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 7..30
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 35..49
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 52..70
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 151..166
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 361
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 245..253
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 268
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 366
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 412
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 27
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 47
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 165
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 168
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 35..36
FT /note="KL -> NV (in Ref. 1; AAC46913)"
FT /evidence="ECO:0000305"
FT CONFLICT 72
FT /note="D -> G (in Ref. 1; AAC46913)"
FT /evidence="ECO:0000305"
FT CONFLICT 275
FT /note="A -> R (in Ref. 1; AAC46913)"
FT /evidence="ECO:0000305"
FT CONFLICT 567
FT /note="N -> K (in Ref. 1; AAC46913)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 609 AA; 68809 MW; 7E371EFDA2A5CD96 CRC64;
MAFRQSEHEM SVTSLDSSVE LRSRSPSPQV FNPRKLRFAD DDFDKDTPEG ASPQHPLQQR
PKLSSGEEQQ LDSKIGKEGG DGDVSMSPPC QKVRALRLFS TPATPKTILQ KSTTQCSNHL
SAAAAAVNAS RRSDDLFRLS ERPRSLPLHN RKLPTQDTAN VNPFTPDSLM AHNKKRCRTQ
FGRENLNLNV NAMQKYLLSD ACDDDVTEEA GDSMREIHQQ APKRLALHDT NISRFKREFM
QVNVIGVGEF GVVFQCVNRL DGCIYAIKKS KKPVAGSSFE KRALNEVWAH AVLGKHDNVV
RYYSAWAEDD HMLIQNEFCD GGSLHARIQD HCLGEAELKI VLMHVIEGLR YIHSNDLVHM
DLKPENIFST MNPNAHKLVE VQPQQTKDDD GMDSVYEELR HSENLVTYKI GDLGHVTSVK
EPYVEEGDCR YLPKEILHED YSNLFKADIF SLGITLFEAA GGGPLPKNGP EWHNLRDGKV
PILPSLSRDF NELIAQMMHP YPDKRPTSQS IFSHPILSAV DSKSKLQLGL ELTVEKRKNE
ILMNKLREAK KQIKLLEQRV NLLAVTNNPD SLDGQRCLRS FTRRMRTPFS SHGKFDSISD
RNKNVITNI
