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   27-MAR-2024, entry version 104.
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; 185431.Q388M1; -.
DR   PaxDb; 5691-EAN78749; -.
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; MKTTMPM; -.
DR   OrthoDB; 2872909at2759; -.
DR   SABIO-RK; Q388M1; -.
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   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; IPR008271; Ser/Thr_kinase_AS.
DR   InterPro; IPR039192; STKc_GSK3.
DR   PANTHER; PTHR24057; GLYCOGEN SYNTHASE KINASE-3 ALPHA; 1.
DR   PANTHER; PTHR24057:SF0; PROTEIN KINASE SHAGGY-RELATED; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 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
//