GSK3B_TRYB2
ID GSK3B_TRYB2 Reviewed; 352 AA.
AC Q388M1;
DT 20-APR-2010, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2005, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Glycogen synthase kinase 3 {ECO:0000303|PubMed:18644955};
DE Short=GSK-3 short {ECO:0000303|PubMed:18644955};
DE EC=2.7.11.26;
GN Name=GSK3 {ECO:0000303|PubMed:18644955}; ORFNames=Tb927.10.13780;
OS Trypanosoma brucei brucei (strain 927/4 GUTat10.1).
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma.
OX NCBI_TaxID=185431;
RN [1] {ECO:0000312|EMBL:EAN78749.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=927/4 GUTat10.1 {ECO:0000312|Proteomes:UP000008524};
RX PubMed=16020726; DOI=10.1126/science.1112642;
RA Berriman M., Ghedin E., Hertz-Fowler C., Blandin G., Renauld H.,
RA Bartholomeu D.C., Lennard N.J., Caler E., Hamlin N.E., Haas B., Bohme U.,
RA Hannick L., Aslett M.A., Shallom J., Marcello L., Hou L., Wickstead B.,
RA Alsmark U.C.M., Arrowsmith C., Atkin R.J., Barron A.J., Bringaud F.,
RA Brooks K., Carrington M., Cherevach I., Chillingworth T.J., Churcher C.,
RA Clark L.N., Corton C.H., Cronin A., Davies R.M., Doggett J., Djikeng A.,
RA Feldblyum T., Field M.C., Fraser A., Goodhead I., Hance Z., Harper D.,
RA Harris B.R., Hauser H., Hostetler J., Ivens A., Jagels K., Johnson D.,
RA Johnson J., Jones K., Kerhornou A.X., Koo H., Larke N., Landfear S.,
RA Larkin C., Leech V., Line A., Lord A., Macleod A., Mooney P.J., Moule S.,
RA Martin D.M., Morgan G.W., Mungall K., Norbertczak H., Ormond D., Pai G.,
RA Peacock C.S., Peterson J., Quail M.A., Rabbinowitsch E., Rajandream M.A.,
RA Reitter C., Salzberg S.L., Sanders M., Schobel S., Sharp S., Simmonds M.,
RA Simpson A.J., Tallon L., Turner C.M., Tait A., Tivey A.R., Van Aken S.,
RA Walker D., Wanless D., Wang S., White B., White O., Whitehead S.,
RA Woodward J., Wortman J., Adams M.D., Embley T.M., Gull K., Ullu E.,
RA Barry J.D., Fairlamb A.H., Opperdoes F., Barrell B.G., Donelson J.E.,
RA Hall N., Fraser C.M., Melville S.E., El-Sayed N.M.A.;
RT "The genome of the African trypanosome Trypanosoma brucei.";
RL Science 309:416-422(2005).
RN [2] {ECO:0000305}
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, INHIBITION BY DRUGS, AND
RP IDENTIFICATION AS A DRUG TARGET.
RC STRAIN=427;
RX PubMed=18644955; DOI=10.1128/aac.00364-08;
RA Ojo K.K., Gillespie J.R., Riechers A.J., Napuli A.J., Verlinde C.L.,
RA Buckner F.S., Gelb M.H., Domostoj M.M., Wells S.J., Scheer A., Wells T.N.,
RA Van Voorhis W.C.;
RT "Glycogen synthase kinase 3 is a potential drug target for African
RT trypanosomiasis therapy.";
RL Antimicrob. Agents Chemother. 52:3710-3717(2008).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[tau protein] = ADP + H(+) + O-phospho-L-seryl-
CC [tau protein]; Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, Rhea:RHEA-
CC COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.26;
CC Evidence={ECO:0000269|PubMed:18644955};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[tau protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[tau protein]; Xref=Rhea:RHEA:53904, Rhea:RHEA-COMP:13703,
CC Rhea:RHEA-COMP:13704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.26; Evidence={ECO:0000269|PubMed:18644955};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.5 uM for ATP {ECO:0000269|PubMed:18644955};
CC -!- SUBUNIT: Inhibited by cyclin kinase 2 (CDK2) inhibitors, including
CC GW8510. {ECO:0000269|PubMed:18644955}.
CC -!- MISCELLANEOUS: Was identified as a drug target for the treatment of
CC African sleeping sickness. RNA interference leads to growth arrest and
CC altered parasite morphology, demonstrating requirement for cell
CC survival. {ECO:0000269|PubMed:18644955}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. GSK-3 subfamily. {ECO:0000255}.
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DR EMBL; CM000208; EAN78749.1; -; Genomic_DNA.
DR RefSeq; XP_827861.1; XM_822768.1.
DR AlphaFoldDB; Q388M1; -.
DR SMR; Q388M1; -.
DR STRING; 5691.EAN78749; -.
DR PaxDb; Q388M1; -.
DR GeneID; 3661993; -.
DR KEGG; tbr:Tb10.61.3140; -.
DR VEuPathDB; TriTrypDB:Tb11.v5.0718; -.
DR VEuPathDB; TriTrypDB:Tb927.10.13780; -.
DR eggNOG; KOG0658; Eukaryota.
DR InParanoid; Q388M1; -.
DR OMA; EMQYTQC; -.
DR Proteomes; UP000008524; Chromosome 10.
DR GO; GO:0005930; C:axoneme; IDA:GeneDB.
DR GO; GO:0036064; C:ciliary basal body; IDA:GeneDB.
DR GO; GO:0097014; C:ciliary plasm; IDA:GeneDB.
DR GO; GO:0097542; C:ciliary tip; IDA:GeneDB.
DR GO; GO:0005929; C:cilium; IDA:GeneDB.
DR GO; GO:0005737; C:cytoplasm; IDA:GeneDB.
DR GO; GO:0020023; C:kinetoplast; IDA:GeneDB.
DR GO; GO:0031981; C:nuclear lumen; IDA:GeneDB.
DR GO; GO:0005634; C:nucleus; IDA:GeneDB.
DR GO; GO:0005524; F:ATP binding; ISM:GeneDB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; EXP:GeneDB.
DR GO; GO:0050321; F:tau-protein kinase activity; IDA:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:GeneDB.
DR GO; GO:0000281; P:mitotic cytokinesis; IMP:GeneDB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd14137; STKc_GSK3; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR039192; STKc_GSK3.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Kinase; Nucleotide-binding; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..352
FT /note="Glycogen synthase kinase 3"
FT /id="PRO_0000393864"
FT DOMAIN 20..310
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 152
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 26..34
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
SQ SEQUENCE 352 AA; 40321 MW; 7613B9C53B119A4B CRC64;
MSLNLTDAAD DRSYKEMEKY TVERVAGQGT FGTVQLARDK STGSLVAIKK VIQDPRFKNR
ELQIMQHLAR LRHPNIVMLK NYFYTVGGEG RRNDVYLNVV MEFVPETLHR TCRNYYRRMT
NPPLILVKVF MFQLLRSIAC LHIPVINICH RDIKPHNVLV DEQTGELKLC DFGSAKRLAA
DEPNVAYICS RYYRAPELIF GNQFYTTAVD IWSVGCIFAE MLLGEPIFCG ENTSGQLREI
VKILGKPTKE ELHKLNGSST EINANAKATP WENVFKQPLP AEVYDLCGKI FKYVPDQRIT
PLDALCHPFF NELREPTTKL PSGNPLPAHL YQFTPDEVEA MTEAQREYLL KK
