WEE2_MOUSE
ID WEE2_MOUSE Reviewed; 555 AA.
AC Q66JT0; Q4U4S4; Q7TPV9;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Wee1-like protein kinase 2;
DE EC=2.7.10.2;
DE AltName: Full=Wee1-like protein kinase 1B;
DE AltName: Full=Wee1B kinase;
DE Short=mWee1B;
GN Name=Wee2; Synonyms=Wee1b;
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], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, PHOSPHORYLATION AT SER-15, AND MUTAGENESIS OF SER-15.
RC STRAIN=C57BL/6J;
RX PubMed=16169490; DOI=10.1016/j.cub.2005.07.056;
RA Han S.J., Chen R., Paronetto M.P., Conti M.;
RT "Wee1B is an oocyte-specific kinase involved in the control of meiotic
RT arrest in the mouse.";
RL Curr. Biol. 15:1670-1676(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Egg, and Ovary;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Egg;
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 [4]
RP SUBCELLULAR LOCATION.
RX PubMed=11029659; DOI=10.1046/j.1365-2443.2000.00367.x;
RA Nakanishi M., Ando H., Watanabe N., Kitamura K., Ito K., Okayama H.,
RA Miyamoto T., Agui T., Sasaki M.;
RT "Identification and characterization of human Wee1B, a new member of the
RT Wee1 family of Cdk-inhibitory kinases.";
RL Genes Cells 5:839-847(2000).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 167-LYS--LYS-169;
RP LYS-237; LEU-311; LEU-316; LEU-320 AND LEU-322.
RX PubMed=20083600; DOI=10.1083/jcb.200907161;
RA Oh J.S., Han S.J., Conti M.;
RT "Wee1B, Myt1, and Cdc25 function in distinct compartments of the mouse
RT oocyte to control meiotic resumption.";
RL J. Cell Biol. 188:199-207(2010).
RN [6]
RP FUNCTION, DEVELOPMENTAL STAGE, PHOSPHORYLATION AT SER-15, AND MUTAGENESIS
RP OF SER-15 AND LYS-237.
RX PubMed=21454751; DOI=10.1126/science.1199211;
RA Oh J.S., Susor A., Conti M.;
RT "Protein tyrosine kinase Wee1B is essential for metaphase II exit in mouse
RT oocytes.";
RL Science 332:462-465(2011).
CC -!- FUNCTION: Oocyte-specific protein tyrosine kinase that phosphorylates
CC and inhibits CDK1 and acts as a key regulator of meiosis during both
CC prophase I and metaphase II. Required to maintain meiotic arrest in
CC oocytes during the germinal vesicle (GV) stage, a long period of
CC quiescence at dictyate prophase I, by phosphorylating CDK1 at 'Tyr-15',
CC leading to inhibit CDK1 activity and prevent meiotic reentry. Also
CC required for metaphase II exit during egg activation by phosphorylating
CC CDK1 at 'Tyr-15', to ensure exit from meiosis in oocytes and promote
CC pronuclear formation. {ECO:0000269|PubMed:16169490,
CC ECO:0000269|PubMed:20083600, ECO:0000269|PubMed:21454751}.
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 -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Localizes mainly in the
CC nucleus. Exported from the nucleus to the cytoplasm before germinal
CC vesicle breakdown (GVBD), allowing meiosis resumption.
CC -!- TISSUE SPECIFICITY: Ovary-specific. {ECO:0000269|PubMed:16169490}.
CC -!- DEVELOPMENTAL STAGE: Detected only in the oocytes at all developmental
CC stages of the follicle including primary, secondary, preantral, and
CC antral follicles with an increase in signal during development. Readily
CC detectable at the mature oocyte, but disappears at 2.5 dpc. Detected in
CC germinal vesicle (GV) and metaphase II-stage oocyte (at protein level).
CC {ECO:0000269|PubMed:16169490, ECO:0000269|PubMed:21454751}.
CC -!- PTM: Phosphorylated by PKA at Ser-15 in vitro, leading to activate
CC kinase activity. Phosphorylation at Ser-15 by CaMK2, leading to
CC increase its activity and promote metaphase II exit during egg
CC activation. {ECO:0000269|PubMed:16169490, ECO:0000269|PubMed:21454751}.
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; DQ011691; AAY44075.1; -; mRNA.
DR EMBL; AK163344; BAE37310.1; -; mRNA.
DR EMBL; AK143336; BAE25345.1; -; mRNA.
DR EMBL; AK139573; BAE24069.1; -; mRNA.
DR EMBL; BC052883; AAH52883.1; -; mRNA.
DR EMBL; BC080784; AAH80784.1; -; mRNA.
DR CCDS; CCDS20029.1; -.
DR RefSeq; NP_958758.2; NM_201370.2.
DR RefSeq; XP_006506389.1; XM_006506326.3.
DR AlphaFoldDB; Q66JT0; -.
DR SMR; Q66JT0; -.
DR STRING; 10090.ENSMUSP00000038754; -.
DR iPTMnet; Q66JT0; -.
DR PhosphoSitePlus; Q66JT0; -.
DR MaxQB; Q66JT0; -.
DR PaxDb; Q66JT0; -.
DR PeptideAtlas; Q66JT0; -.
DR PRIDE; Q66JT0; -.
DR Antibodypedia; 32491; 112 antibodies from 24 providers.
DR DNASU; 381759; -.
DR Ensembl; ENSMUST00000038907; ENSMUSP00000038754; ENSMUSG00000037159.
DR GeneID; 381759; -.
DR KEGG; mmu:381759; -.
DR UCSC; uc009bmq.2; mouse.
DR CTD; 494551; -.
DR MGI; MGI:3027899; Wee2.
DR VEuPathDB; HostDB:ENSMUSG00000037159; -.
DR eggNOG; KOG0601; Eukaryota.
DR GeneTree; ENSGT00940000158803; -.
DR HOGENOM; CLU_000288_25_1_1; -.
DR InParanoid; Q66JT0; -.
DR OMA; GAAWHHI; -.
DR OrthoDB; 1063695at2759; -.
DR PhylomeDB; Q66JT0; -.
DR TreeFam; TF101088; -.
DR BioGRID-ORCS; 381759; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Wee2; mouse.
DR PRO; PR:Q66JT0; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q66JT0; protein.
DR Bgee; ENSMUSG00000037159; Expressed in animal zygote and 24 other tissues.
DR ExpressionAtlas; Q66JT0; baseline and differential.
DR Genevisible; Q66JT0; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
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:0007143; P:female meiotic nuclear division; IMP:UniProtKB.
DR GO; GO:0035038; P:female pronucleus assembly; IMP:UniProtKB.
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; IMP:UniProtKB.
DR GO; GO:1900194; P:negative regulation of oocyte maturation; IMP:UniProtKB.
DR GO; GO:0042327; P:positive regulation of phosphorylation; IDA:UniProtKB.
DR GO; GO:0080154; P:regulation of fertilization; IMP:UniProtKB.
DR GO; GO:0060631; P:regulation of meiosis I; IMP:UniProtKB.
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; Coiled coil; Cytoplasm; Kinase; Magnesium; Meiosis;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase; Tyrosine-protein kinase.
FT CHAIN 1..555
FT /note="Wee1-like protein kinase 2"
FT /id="PRO_0000248080"
FT DOMAIN 208..485
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 488..514
FT /evidence="ECO:0000255"
FT MOTIF 167..169
FT /note="Nuclear localization signal"
FT MOTIF 310..324
FT /note="Nuclear export signal"
FT COMPBIAS 21..37
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 42..74
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 96..112
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 334
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 214..222
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 237
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT BINDING 339
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 375
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT MOD_RES 15
FT /note="Phosphoserine; by CaMK2 and PKA"
FT /evidence="ECO:0000269|PubMed:16169490,
FT ECO:0000269|PubMed:21454751"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A4PES0"
FT MUTAGEN 15
FT /note="S->A: Abolishes phosphorylation and impairs ability
FT to maintain meiotic arrest in oocytes during the germinal
FT vesicle (GV) stage and metaphase II exit during egg
FT activation."
FT /evidence="ECO:0000269|PubMed:16169490,
FT ECO:0000269|PubMed:21454751"
FT MUTAGEN 15
FT /note="S->D: Mimicks phosphorylation state, lesading to
FT enhance kinase activity and promote pronuclear formation."
FT /evidence="ECO:0000269|PubMed:16169490,
FT ECO:0000269|PubMed:21454751"
FT MUTAGEN 167..169
FT /note="Missing: Abolishes nuclear localization."
FT /evidence="ECO:0000269|PubMed:20083600"
FT MUTAGEN 237
FT /note="K->M: Loss of function."
FT /evidence="ECO:0000269|PubMed:20083600,
FT ECO:0000269|PubMed:21454751"
FT MUTAGEN 311
FT /note="L->A: Abolishes the cytoplasmic localization; when
FT associated with A-316; A-320 and A-322."
FT /evidence="ECO:0000269|PubMed:20083600"
FT MUTAGEN 316
FT /note="L->A: Abolishes the cytoplasmic localization; when
FT associated with A-311; A-320 and A-322."
FT /evidence="ECO:0000269|PubMed:20083600"
FT MUTAGEN 320
FT /note="L->A: Abolishes the cytoplasmic localization; when
FT associated with A-311; A-316 and A-322."
FT /evidence="ECO:0000269|PubMed:20083600"
FT MUTAGEN 322
FT /note="L->A: Abolishes the cytoplasmic localization; when
FT associated with A-311; A-316 and A-320."
FT /evidence="ECO:0000269|PubMed:20083600"
FT CONFLICT 21
FT /note="E -> K (in Ref. 3; AAH80784)"
FT /evidence="ECO:0000305"
FT CONFLICT 70
FT /note="E -> G (in Ref. 3; AAH52883)"
FT /evidence="ECO:0000305"
FT CONFLICT 98
FT /note="L -> P (in Ref. 3; AAH52883)"
FT /evidence="ECO:0000305"
FT CONFLICT 118
FT /note="L -> R (in Ref. 3; AAH80784)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="M -> V (in Ref. 3; AAH52883)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 555 AA; 62343 MW; 0D3FA3972C626693 CRC64;
MADTETDQGL NKKLSFSFCE EDTESEGQMT AQDIGGAQSQ KPGREESEEL EGPVPPTRDE
LHTSLSRDKE SPGPDLWKSV SGPPKCPETP VLHSKSKLPV PTNFSTPKNS LGQPEISLLE
KLSSRSSRHM RLTPASLMDE KTSLSLVNIN PFTPETYRKL LLQSKGKRKT RDYLEETGEE
ESKSVQWLPA KRSILQETNM ASRYEKEFFE IEKIGVGEFG TVYKCIKRLD GCIYAIKRSA
KSFSGLSNEL DLHEVYAHAV LGHHPHVVRY YSSWIEDDHV VIQNEYCNGG SLQAAISENT
ASNNHFQEPK LKDILLQISL GLKYIHNSGM VHLDIKPSNI FICHKMQCDS PVGPEEAESE
ADWFLNASVM YKIGDLGHAT SISKPKVEEG DTRFLANEIL QENYQHLPKA DIFALGLTIA
VAAGAESLPI NGDMWHHIRK GNFPEISQEL SDDFYGLLKN MIHPAPKERP SAAALARSRI
LWPFLEKTDE LQKQLNLEKS KTATLKRELK KARHIQTPQR EVHHCYYQIC KGSRHLLVGG
RRKAPSSFTR GTSSV
