WEE2A_XENLA
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 03-AUG-2022, entry version 128.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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; 1.
DR iPTMnet; P47817; -.
DR PRIDE; P47817; -.
DR DNASU; 398049; -.
DR GeneID; 398049; -.
DR KEGG; xla:398049; -.
DR CTD; 398049; -.
DR Xenbase; XB-GENE-6538740; wee2.L.
DR OrthoDB; 1063695at2759; -.
DR BRENDA; 2.7.10.2; 6725.
DR Proteomes; UP000186698; Chromosome 3L.
DR Bgee; 398049; Expressed in egg cell and 15 other 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 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; 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
