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   24-JAN-2024, entry version 143.
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; 10090-ENSMUSP00000038754; -.
DR   PeptideAtlas; Q66JT0; -.
DR   Antibodypedia; 32491; 131 antibodies from 24 providers.
DR   DNASU; 381759; -.
DR   Ensembl; ENSMUST00000038907.9; ENSMUSP00000038754.9; ENSMUSG00000037159.12.
DR   GeneID; 381759; -.
DR   KEGG; mmu:381759; -.
DR   UCSC; uc009bmq.2; mouse.
DR   AGR; MGI:3027899; -.
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; HEKMPRS; -.
DR   OrthoDB; 928649at2759; -.
DR   PhylomeDB; Q66JT0; -.
DR   TreeFam; TF101088; -.
DR   BioGRID-ORCS; 381759; 2 hits in 78 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 26 other cell types or tissues.
DR   ExpressionAtlas; Q66JT0; baseline and differential.
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: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:0016310; P:phosphorylation; IEA:UniProtKB-KW.
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   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:SF75; WEE1-LIKE PROTEIN KINASE 2; 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; Q66JT0; MM.
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
//