ID   WEE2A_XENLA             Reviewed;         555 AA.
AC   P47817; Q66J76;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   31-MAY-2011, sequence version 2.
DT   27-MAR-2024, entry version 133.
DE   RecName: Full=Wee1-like protein kinase 2-A;
DE            EC=2.7.10.2;
DE   AltName: Full=Maternally supplied wee1-like protein kinase 1A;
DE            Short=Xe-wee1A;
GN   Name=wee2-a; Synonyms=wee1a;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, AND
RP   PHOSPHORYLATION.
RC   TISSUE=Oocyte;
RX   PubMed=7749193; DOI=10.1091/mbc.6.1.119;
RA   Mueller P.R., Coleman T.R., Dunphy W.G.;
RT   "Cell cycle regulation of a Xenopus Wee1-like kinase.";
RL   Mol. Biol. Cell 6:119-134(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=10673504;
RA   Nakajo N., Yoshitome S., Iwashita J., Iida M., Uto K., Ueno S., Okamoto K.,
RA   Sagata N.;
RT   "Absence of Wee1 ensures the meiotic cell cycle in Xenopus oocytes.";
RL   Genes Dev. 14:328-338(2000).
RN   [4]
RP   FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=12006499; DOI=10.1093/emboj/21.10.2472;
RA   Okamoto K., Nakajo N., Sagata N.;
RT   "The existence of two distinct Wee1 isoforms in Xenopus: implications for
RT   the developmental regulation of the cell cycle.";
RL   EMBO J. 21:2472-2484(2002).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH PRMT5, SUBCELLULAR LOCATION,
RP   PROTEASOMAL DEGRADATION, AND TISSUE SPECIFICITY.
RX   PubMed=15583029; DOI=10.1083/jcb.200406048;
RA   Yamada A., Duffy B., Perry J.A., Kornbluth S.;
RT   "DNA replication checkpoint control of Wee1 stability by vertebrate Hsl7.";
RL   J. Cell Biol. 167:841-849(2004).
RN   [6]
RP   PHOSPHORYLATION AT SER-549.
RX   PubMed=16195348; DOI=10.1091/mbc.e05-06-0541;
RA   Stanford J.S., Ruderman J.V.;
RT   "Changes in regulatory phosphorylation of Cdc25C Ser287 and Wee1 Ser549
RT   during normal cell cycle progression and checkpoint arrests.";
RL   Mol. Biol. Cell 16:5749-5760(2005).
CC   -!- FUNCTION: Oocyte-specific protein tyrosine kinase that phosphorylates
CC       and inhibits cdk1 and acts as a key regulator of meiosis. Required to
CC       maintain meiotic arrest in oocytes by phosphorylating cdk1 at 'Tyr-15',
CC       which inhibits cdk1 activity and prevents meiotic reentry. Negative
CC       regulator of mitosis. Involved in the mitotic DNA replication
CC       checkpoint. {ECO:0000269|PubMed:10673504, ECO:0000269|PubMed:12006499,
CC       ECO:0000269|PubMed:15583029, ECO:0000269|PubMed:7749193}.
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         ECO:0000269|PubMed:15583029, ECO:0000269|PubMed:7749193};
CC   -!- SUBUNIT: Interacts with prmt5; this promotes protesomal degradation of
CC       wee2-a in the nucleus. The interaction with prmt5 is disrupted upon
CC       activation of the DNA replication checkpoint.
CC       {ECO:0000269|PubMed:15583029}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15583029}. Cytoplasm,
CC       cytosol {ECO:0000269|PubMed:15583029}.
CC   -!- TISSUE SPECIFICITY: Detected in egg (at protein level). Oocyte-specific
CC       maternally supplied protein. Present in immature and mature oocytes and
CC       in early (pregastrula) embryos, but not in post-gastrula embryos.
CC       {ECO:0000269|PubMed:10673504, ECO:0000269|PubMed:12006499,
CC       ECO:0000269|PubMed:15583029}.
CC   -!- DEVELOPMENTAL STAGE: Expressed only after meiosis I. Not detected in
CC       full-grown stage VI immature oocytes (arrested at prophase I) and in
CC       oocytes undergoing germinal vesicle breakdown (GVBD) or meiosis I,
CC       while it is present in oocytes from 1-1.5 hour after GVBD, or from the
CC       onset of meiosis II. {ECO:0000269|PubMed:10673504,
CC       ECO:0000269|PubMed:12006499}.
CC   -!- PTM: Subject to proteasomal degradation in the nucleus.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC       kinase family. WEE1 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC   -!- CAUTION: Was initially assigned as wee1 (PubMed:7749193). However, it
CC       corresponds to the meiosis-specific protein WEE2 in mammals.
CC       {ECO:0000305|PubMed:7749193}.
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DR   EMBL; U13962; AAC59664.1; -; mRNA.
DR   EMBL; BC081031; AAH81031.1; -; mRNA.
DR   PIR; I51671; I51671.
DR   RefSeq; NP_001081784.1; NM_001088315.1.
DR   AlphaFoldDB; P47817; -.
DR   SMR; P47817; -.
DR   BioGRID; 99384; 2.
DR   iPTMnet; P47817; -.
DR   DNASU; 398049; -.
DR   GeneID; 398049; -.
DR   KEGG; xla:398049; -.
DR   AGR; Xenbase:XB-GENE-6538740; -.
DR   CTD; 398049; -.
DR   Xenbase; XB-GENE-6538740; wee2.L.
DR   OrthoDB; 928649at2759; -.
DR   BRENDA; 2.7.10.2; 6725.
DR   Proteomes; UP000186698; Chromosome 3L.
DR   Bgee; 398049; Expressed in egg cell and 15 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA: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:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR   GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR   GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0033314; P:mitotic DNA replication checkpoint signaling; IMP:UniProtKB.
DR   GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR   GO; GO:0007088; P:regulation of mitotic nuclear division; 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.
PE   1: Evidence at protein level;
KW   ATP-binding; Cell cycle; Cell division; Coiled coil; Cytoplasm; Kinase;
KW   Magnesium; Meiosis; Metal-binding; Mitosis; Nucleotide-binding; Nucleus;
KW   Phosphoprotein; Reference proteome; Transferase; Tyrosine-protein kinase.
FT   CHAIN           1..555
FT                   /note="Wee1-like protein kinase 2-A"
FT                   /id="PRO_0000086813"
FT   DOMAIN          210..480
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          1..81
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          149..175
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          487..513
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        22..75
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        159..175
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        337
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         216..224
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         239
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         342
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         374
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         549
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:16195348"
FT   CONFLICT        228
FT                   /note="I -> V (in Ref. 1; AAC59664)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        452
FT                   /note="I -> V (in Ref. 1; AAC59664)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   555 AA;  61716 MW;  F51CBA73B0CDA448 CRC64;
     MRTAMSCGGG LVQRLDFSSS DEEDGLSNGI NEGPQKGSPV SSWRTNNCPF PITPQRNERE
     LSPTQELSPS SDYSPDPSVG AECPGTPLHY STWKKLKLCD TPYTPKSLLY KTLPSPGSRV
     HCRGQRLLRF VAGTGAELDD PSLVNINPFT PESYRQTHFQ PNGKRKERPE DDCRTDRQMK
     YAEKEHPAVF QSKRFVLRET NMGSRYKTEF LEIEKIGAGE FGSVFKCIKR LDGCFYAIKR
     SKKPLAGSTD EQLALREVYA HAVLGHHPHV VRYYSAWAED DHMIIQNEYC NGGSLQDLIV
     DNNKEGQFVL EQELKEILLQ VSMGLKYIHG SGLVHMDIKP SNIFICRKQT ELGQEESDGE
     DDLSSGSVLY KIGDLGHVTS ILNPQVEEGD SRFLANEILQ EDYSQLPKAD IFALGLTIAL
     AAGAAPLPCN EDSWHHIRKG NLPHVPQLLT PIFLALLKLL VHPDPVMRPP AASLAKNSVL
     RRCVGKAAQL QKQLNVEKFK TAMLERELKA AKLAQTSGKD ECSDLPPMSG FSCRGRKRLV
     GAKNTRSLSF TCGGY
//