GWL_XENLA
ID GWL_XENLA Reviewed; 887 AA.
AC Q6NTJ3;
DT 03-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Serine/threonine-protein kinase greatwall;
DE Short=GW;
DE Short=GWL;
DE EC=2.7.11.1;
DE AltName: Full=Microtubule-associated serine/threonine-protein kinase-like;
DE Short=MAST-L;
GN Name=mastl; Synonyms=gw, gwl;
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], FUNCTION, PHOSPHORYLATION AT THR-221; THR-244;
RP SER-363; SER-465; SER-654; SER-677 AND THR-748, AND MUTAGENESIS OF GLY-41;
RP ASP-173; THR-221; THR-244; SER-363; SER-465; SER-654; SER-677 AND THR-748.
RX PubMed=16600872; DOI=10.1016/j.molcel.2006.02.022;
RA Yu J., Zhao Y., Li Z., Galas S., Goldberg M.L.;
RT "Greatwall kinase participates in the Cdc2 autoregulatory loop in Xenopus
RT egg extracts.";
RL Mol. Cell 22:83-91(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
RX PubMed=18199678; DOI=10.1091/mbc.e07-11-1099;
RA Zhao Y., Haccard O., Wang R., Yu J., Kuang J., Jessus C., Goldberg M.L.;
RT "Roles of Greatwall kinase in the regulation of cdc25 phosphatase.";
RL Mol. Biol. Cell 19:1317-1327(2008).
RN [4]
RP FUNCTION.
RX PubMed=19680222; DOI=10.1038/emboj.2009.228;
RA Vigneron S., Brioudes E., Burgess A., Labbe J.C., Lorca T., Castro A.;
RT "Greatwall maintains mitosis through regulation of PP2A.";
RL EMBO J. 28:2786-2793(2009).
RN [5]
RP FUNCTION.
RX PubMed=19793917; DOI=10.1091/mbc.e09-07-0643;
RA Castilho P.V., Williams B.C., Mochida S., Zhao Y., Goldberg M.L.;
RT "The M phase kinase Greatwall (Gwl) promotes inactivation of PP2A/B55delta,
RT a phosphatase directed against CDK phosphosites.";
RL Mol. Biol. Cell 20:4777-4789(2009).
RN [6]
RP FUNCTION.
RX PubMed=20980823; DOI=10.4161/cc.9.21.13632;
RA Peng A., Yamamoto T.M., Goldberg M.L., Maller J.L.;
RT "A novel role for greatwall kinase in recovery from DNA damage.";
RL Cell Cycle 9:4364-4369(2010).
RN [7]
RP FUNCTION.
RX PubMed=20554897; DOI=10.1242/jcs.064527;
RA Lorca T., Bernis C., Vigneron S., Burgess A., Brioudes E., Labbe J.C.,
RA Castro A.;
RT "Constant regulation of both the MPF amplification loop and the Greatwall-
RT PP2A pathway is required for metaphase II arrest and correct entry into the
RT first embryonic cell cycle.";
RL J. Cell Sci. 123:2281-2291(2010).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH ARPP19 AND ENSA.
RX PubMed=21164013; DOI=10.1126/science.1195689;
RA Mochida S., Maslen S.L., Skehel M., Hunt T.;
RT "Greatwall phosphorylates an inhibitor of protein phosphatase 2A that is
RT essential for mitosis.";
RL Science 330:1670-1673(2010).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH ARPP19 AND ENSA.
RX PubMed=21164014; DOI=10.1126/science.1197048;
RA Gharbi-Ayachi A., Labbe J.C., Burgess A., Vigneron S., Strub J.M.,
RA Brioudes E., Van-Dorsselaer A., Castro A., Lorca T.;
RT "The substrate of Greatwall kinase, Arpp19, controls mitosis by inhibiting
RT protein phosphatase 2A.";
RL Science 330:1673-1677(2010).
CC -!- FUNCTION: Serine/threonine kinase that plays a key role in M phase by
CC acting as a regulator of mitosis entry and maintenance. Acts by
CC promoting the inactivation of protein phosphatase 2A (PP2A) during M
CC phase: does not directly inhibit PP2A but acts by mediating
CC phosphorylation and subsequent activation of arpp19 and ensa at 'Ser-
CC 67', 2 phosphatase inhibitors that specifically inhibit the ppp2r2d
CC (PR55-delta) subunit of PP2A. Inactivation of PP2A during M phase is
CC essential to keep cyclin-B1-CDK1 activity high. Following DNA damage,
CC it is also involved in checkpoint recovery by being inhibited.
CC {ECO:0000269|PubMed:16600872, ECO:0000269|PubMed:18199678,
CC ECO:0000269|PubMed:19680222, ECO:0000269|PubMed:19793917,
CC ECO:0000269|PubMed:20554897, ECO:0000269|PubMed:20980823,
CC ECO:0000269|PubMed:21164013, ECO:0000269|PubMed:21164014}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:21164013, ECO:0000269|PubMed:21164014};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:21164013,
CC ECO:0000269|PubMed:21164014};
CC -!- SUBUNIT: Interacts with arpp19 and ensa, leading to their
CC phosphorylation. {ECO:0000269|PubMed:21164013,
CC ECO:0000269|PubMed:21164014}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000250}. Nucleus. Note=During interphase is
CC mainly nuclear, upon nuclear envelope breakdown localizes at the
CC cytoplasm and during mitosis at the centrosomes. {ECO:0000250}.
CC -!- PTM: Phosphorylation at Thr-748 by CDK1 during M phase activates its
CC kinase activity. Not active during other phases of the cell cycle. Has
CC the ability to autophosphorylate. {ECO:0000269|PubMed:16600872}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; AY644649; AAT65679.1; -; mRNA.
DR EMBL; BC068968; AAH68968.1; -; mRNA.
DR RefSeq; NP_001084629.1; NM_001091160.1.
DR AlphaFoldDB; Q6NTJ3; -.
DR SMR; Q6NTJ3; -.
DR BioGRID; 101007; 1.
DR IntAct; Q6NTJ3; 2.
DR MINT; Q6NTJ3; -.
DR iPTMnet; Q6NTJ3; -.
DR PRIDE; Q6NTJ3; -.
DR DNASU; 414585; -.
DR GeneID; 414585; -.
DR KEGG; xla:414585; -.
DR CTD; 414585; -.
DR Xenbase; XB-GENE-964551; mastl.L.
DR OrthoDB; 878671at2759; -.
DR Proteomes; UP000186698; Chromosome 6L.
DR Bgee; 414585; Expressed in blastula and 19 other tissues.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0032154; C:cleavage furrow; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0032515; P:negative regulation of phosphoprotein phosphatase activity; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; TAS:UniProtKB.
DR CDD; cd05610; STKc_MASTL; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR037638; MASTL_STKc.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 2.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 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; Cytoplasm; Cytoskeleton;
KW DNA damage; Kinase; Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..887
FT /note="Serine/threonine-protein kinase greatwall"
FT /id="PRO_0000408318"
FT DOMAIN 32..843
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 844..887
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 321..353
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 410..435
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 556..624
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 323..353
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 556..575
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 590..608
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 155
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 38..46
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT BINDING 61
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 221
FT /note="Phosphothreonine; by CDK1; in vitro"
FT /evidence="ECO:0000269|PubMed:16600872"
FT MOD_RES 244
FT /note="Phosphothreonine; by CDK1; in vitro"
FT /evidence="ECO:0000269|PubMed:16600872"
FT MOD_RES 363
FT /note="Phosphoserine; by CDK1; in vitro"
FT /evidence="ECO:0000269|PubMed:16600872"
FT MOD_RES 465
FT /note="Phosphoserine; by CDK1; in vitro"
FT /evidence="ECO:0000269|PubMed:16600872"
FT MOD_RES 654
FT /note="Phosphoserine; by CDK1; in vitro"
FT /evidence="ECO:0000269|PubMed:16600872"
FT MOD_RES 677
FT /note="Phosphoserine; by CDK1; in vitro"
FT /evidence="ECO:0000269|PubMed:16600872"
FT MOD_RES 748
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000269|PubMed:16600872"
FT MUTAGEN 41
FT /note="G->S: Abolishes serine/threonine-protein kinase
FT activity and ability to regulate mitosis."
FT /evidence="ECO:0000269|PubMed:16600872"
FT MUTAGEN 173
FT /note="D->A: Abolishes serine/threonine-protein kinase
FT activity and ability to regulate mitosis."
FT /evidence="ECO:0000269|PubMed:16600872"
FT MUTAGEN 221
FT /note="T->A: No effect."
FT /evidence="ECO:0000269|PubMed:16600872"
FT MUTAGEN 244
FT /note="T->A: No effect."
FT /evidence="ECO:0000269|PubMed:16600872"
FT MUTAGEN 363
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:16600872"
FT MUTAGEN 465
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:16600872"
FT MUTAGEN 654
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:16600872"
FT MUTAGEN 677
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:16600872"
FT MUTAGEN 748
FT /note="T->A: Abolishes the ability to regulate M phase."
FT /evidence="ECO:0000269|PubMed:16600872"
SQ SEQUENCE 887 AA; 98683 MW; 340C9133B11FA0FC CRC64;
MGIVAETSQN GDTSLCSEKK FTVPQPPSIE EFGIVKPISR GAFGKVYLAR RKNNSKLFAV
KVVKKADMIN KNMVQQVQAE RDALALSKSP FIVHLYYSLQ SANNIYLVME YLIGGDVKSL
LHIYGYFDEE MAVKYISEVA MALDYLHRHG IIHRDLKPDN MLISNKGHIK LTDFGLSKVT
LKRELCMMDI LTTPSMAKPK RDYSRTPGQV LSLISSLGFN TPAGGRTQGS LNQQTEGMRG
NASTPLLMKK RESLVKGNKL MISCPEASLS SPSIPVKCLT PNLLKCRTQF ATSSTSSQSR
ICLSSLESEC GSPRWENCSQ DAEAPPYFNS SRVKDSSSEQ ARSKKPTGSS ASQNLKRLEF
AFSPIVDRRT GKKAGFQDET GELSDTPLAT LNAKGVIRKC LYENKAQEKP KDFDKTGQGE
LGKFTSSPDS PPWLANGSVA PIQFNDEEKT EKMGVKRNYD LVEKSPEQEL LQDKKTNTDY
KRGCAITDYP VSQSTGLTME INSLFLSELR NSANKYASDR KSEDKYISAP RTLEKLDSGN
PVAKNLLCEL DDNCERDGEV SSTSEGEDRK ERLNQDSSST GMSVTENQID RDLSHVDKSI
KELSFEESQS ENSEEITPDN KGIPFMAEND ERVQSKYEPN TSILPDSLQN VLASPAPASA
MTNPRRKPMV AFRSYNSPIN VSNVSEPSKI SMNSADKIHF SLECTGSFPM AVTPAQNKVQ
GLIETPYRTP KSVRRGGIQV DHERILGTPD YLAPELLLRK SHGPAVDWWA LGVCLFEFLT
GIPPFNDETP SQVFQNILNR DIPWPEEEEE VLSVNAQSAI EILLTIDPTK RAGLKDLKAH
PLFHGMEWEE LQYQPMSFIP QPDDETDTTY FEARNNAQHL KVSGFSL
