GWL_DANRE
ID GWL_DANRE Reviewed; 860 AA.
AC Q6DBX4;
DT 03-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 116.
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 Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND SUBCELLULAR LOCATION.
RX PubMed=19460416; DOI=10.1016/j.exphem.2009.05.005;
RA Johnson H.J., Gandhi M.J., Shafizadeh E., Langer N.B., Pierce E.L.,
RA Paw B.H., Gilligan D.M., Drachman J.G.;
RT "In vivo inactivation of MASTL kinase results in thrombocytopenia.";
RL Exp. Hematol. 37:901-908(2009).
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 62' and 'Ser-74', respectively. ARPP19 and ENSA are phosphatase
CC inhibitors that specifically inhibit the ppp2r2d (PR55-delta) subunit
CC of PP2A. Inactivation of PP2A during M phase is essential to keep
CC cyclin-B1-CDK1 activity high. Following DNA damage, it is also involved
CC in checkpoint recovery by being inhibited (By similarity). May be
CC involved in megakaryocyte differentiation (PubMed:19460416).
CC {ECO:0000250, ECO:0000269|PubMed:19460416}.
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 -!- 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;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000250}. Nucleus
CC {ECO:0000269|PubMed:19460416}. Cleavage furrow {ECO:0000250}.
CC Note=During interphase is mainly nuclear, upon nuclear envelope
CC breakdown localizes at the cytoplasm and during mitosis at the
CC centrosomes (By similarity). Upon mitotic exit moves to the cleavage
CC furrow. {ECO:0000250}.
CC -!- PTM: Phosphorylation at Thr-722 by CDK1 during M phase activates its
CC kinase activity. Maximum phosphorylation occurs in prometaphase (By
CC similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein results in
CC reduced number of circulating thrombocytes, distinguishable at 3 days
CC post fertilization. {ECO:0000269|PubMed:19460416}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; BC078324; AAH78324.1; -; mRNA.
DR AlphaFoldDB; Q6DBX4; -.
DR SMR; Q6DBX4; -.
DR STRING; 7955.ENSDARP00000072407; -.
DR PaxDb; Q6DBX4; -.
DR ZFIN; ZDB-GENE-040801-128; mastl.
DR eggNOG; KOG0606; Eukaryota.
DR InParanoid; Q6DBX4; -.
DR PhylomeDB; Q6DBX4; -.
DR Reactome; R-DRE-2465910; MASTL Facilitates Mitotic Progression.
DR PRO; PR:Q6DBX4; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
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:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051721; F:protein phosphatase 2A binding; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0000278; P:mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0032515; P:negative regulation of phosphoprotein phosphatase activity; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0002574; P:thrombocyte differentiation; IMP:ZFIN.
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 2: Evidence at transcript level;
KW ATP-binding; Cell cycle; Cell division; Cytoplasm; Cytoskeleton; Kinase;
KW Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..860
FT /note="Serine/threonine-protein kinase greatwall"
FT /id="PRO_0000408317"
FT DOMAIN 23..816
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 817..860
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 514..537
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 520..536
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 146
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 29..37
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 52
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 722
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000250"
SQ SEQUENCE 860 AA; 95726 MW; 04C19252A9D50176 CRC64;
MEARGLACES SNSAVKAPSI EDFVLVKPIS RGAFGKVYLA RKKCNSKLYA IKVVKKAEMV
DKNMTEQMRA ERDALALSKS PFIVHLFYSL QTATKVYLVM EYLIGGDVKS LLHIYGYFDE
DMSLKYISEV ALALDYLHRH SIIHRDLKPD NMLISNEGHI KLTDFGLSKV KLDRELNLMD
ILTTPSLVKP TKDYFRTPGQ VLSLISSLGL NTPVIEGKRH SSTVLGSPMS CGKVKQRNRS
LGSPLMKRRA EYMNSPVCTS RALASNSVFS PVLLARSLTP RLLKSGKRLD TMSVGSTHSC
MLPSTTDSEN CVSPMWEDEQ NLHDVENIPQ LNGREVDNRK SRNVPLTPVE KRKTLPARAQ
DHRPVFTPLN NQVTNSRNIK PDLSAKRLQF GATDNSATPL EKTVPHQSVG NGLIKPEPLK
ELKSSVKRAF EEVEKSPEQA EILFKKNDAA YERSFQIPEK TSRAHTGLTG IFSIVGLDDV
KSAPKCQQFN ERTGPKQSSP IAVAKNLFCE LEDQGEEGGK AEPNSSSSTS PGDERNIRRS
LSLESDVSAH EMSLVANTPQ KLSDAKQEVL SSSFEELDEN EISAVTPMAR PTVATPKHSS
AKQRRGECER SLLDHPHGLS DSMIKSPGFL KPKNVVAFRS YCSSINRSCT SHLSLASFDA
MEMSASASFH NAVTPVQKKR PSLSNSLYQT PQQMVVSHTP YRTPKSVRRG PERVEGAPIL
GTPDYLAPEL LLGKPHDFMV DWWALGVCLF EFLTGVPPFN DETPQLVFQN ILNRDIPWPD
GEEELTLNSR NAIEILLTMD TLKRAGLKEL KDHPFFDGVD WENLHHQTMP FIPQPDNETD
TSYFEARNTA QHLTVSGFSL
