GSK3_DICDI
ID GSK3_DICDI Reviewed; 467 AA.
AC P51136; Q55A28; Q86KY0;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Glycogen synthase kinase-3;
DE Short=GSK-3;
DE EC=2.7.11.26;
GN Name=gskA; Synonyms=gsk3; ORFNames=DDB_G0272110;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=AX2;
RX PubMed=7813009; DOI=10.1016/0092-8674(95)90458-1;
RA Harwood A.J., Plyte S.E., Woodgett J., Strutt H., Kay R.R.;
RT "Glycogen synthase kinase 3 regulates cell fate in Dictyostelium.";
RL Cell 80:139-148(1995).
RN [2]
RP SEQUENCE REVISION.
RA Harwood A.J., Plyte S.E., Woodgett J., Strutt H., Kay R.R.;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=12097910; DOI=10.1038/nature00847;
RA Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA Noegel A.A.;
RT "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL Nature 418:79-85(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [5]
RP CATALYTIC ACTIVITY, AND INHIBITION BY LITHIUM.
RX PubMed=9169052; DOI=10.1006/dbio.1997.8552;
RA Hedgepeth C.M., Conrad L.J., Zhang J., Huang H.-C., Lee V.M.Y., Klein P.S.;
RT "Activation of the Wnt signaling pathway: a molecular mechanism for lithium
RT action.";
RL Dev. Biol. 185:82-91(1997).
RN [6]
RP FUNCTION.
RX PubMed=9284050; DOI=10.1101/gad.11.16.2112;
RA Ginsburg G.T., Kimmel A.R.;
RT "Autonomous and nonautonomous regulation of axis formation by antagonistic
RT signaling via 7-span cAMP receptors and GSK3 in Dictyostelium.";
RL Genes Dev. 11:2112-2123(1997).
RN [7]
RP CATALYTIC ACTIVITY, AND INHIBITION BY LITHIUM.
RX PubMed=9784196; DOI=10.1006/abio.1998.2832;
RA Ryves W.J., Fryer L., Dale T., Harwood A.J.;
RT "An assay for glycogen synthase kinase 3 (GSK-3) for use in crude cell
RT extracts.";
RL Anal. Biochem. 264:124-127(1998).
RN [8]
RP FUNCTION.
RX PubMed=10571182; DOI=10.1016/s0092-8674(00)81526-3;
RA Kim L., Liu J., Kimmel A.R.;
RT "The novel tyrosine kinase ZAK1 activates GSK3 to direct cell fate
RT specification.";
RL Cell 99:399-408(1999).
RN [9]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=9847246; DOI=10.1242/dev.126.2.325;
RA Plyte S.E., O'Donovan E., Woodgett J.R., Harwood A.J.;
RT "Glycogen synthase kinase-3 (GSK-3) is regulated during Dictyostelium
RT development via the serpentine receptor cAR3.";
RL Development 126:325-333(1999).
RN [10]
RP CATALYTIC ACTIVITY, COFACTOR REQUIREMENT, AND INHIBITION BY LITHIUM.
RX PubMed=11162580; DOI=10.1006/bbrc.2000.4169;
RA Ryves W.J., Harwood A.J.;
RT "Lithium inhibits glycogen synthase kinase-3 by competition for
RT magnesium.";
RL Biochem. Biophys. Res. Commun. 280:720-725(2001).
RN [11]
RP FUNCTION, MUTAGENESIS OF LYS-85; LYS-86; TYR-214 AND TYR-220, AND
RP PHOSPHORYLATION AT TYR-214 AND TYR-220.
RX PubMed=12408804; DOI=10.1016/s1534-5807(02)00269-1;
RA Kim L., Harwood A.J., Kimmel A.R.;
RT "Receptor-dependent and tyrosine phosphatase-mediated inhibition of GSK3
RT regulates cell fate choice.";
RL Dev. Cell 3:523-532(2002).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15342480; DOI=10.1242/dev.01330;
RA Schilde C., Araki T., Williams H., Harwood A.J., Williams J.G.;
RT "GSK3 is a multifunctional regulator of Dictyostelium development.";
RL Development 131:4555-4565(2004).
RN [13]
RP FUNCTION.
RX PubMed=21205787; DOI=10.1242/dev.055335;
RA Kim L., Brzostowski J., Majithia A., Lee N.S., McMains V., Kimmel A.R.;
RT "Combinatorial cell-specific regulation of GSK3 directs cell
RT differentiation and polarity in Dictyostelium.";
RL Development 138:421-430(2011).
CC -!- FUNCTION: During cellular differentiation, may mediate an extracellular
CC cyclic AMP stimulated signal transduction pathway that regulates
CC prespore and prestalk B-cell proportions through inhibition of stalk
CC cell formation and induction of prespore cell differentiation. The cAMP
CC receptor carC appears to activate gskA via the tyrosine kinases zakA
CC and zak2, to stimulate prespore differentiation, while carD appears to
CC negatively regulate gskA, to promote prestalk formation.
CC {ECO:0000269|PubMed:10571182, ECO:0000269|PubMed:12408804,
CC ECO:0000269|PubMed:15342480, ECO:0000269|PubMed:21205787,
CC ECO:0000269|PubMed:7813009, ECO:0000269|PubMed:9284050,
CC ECO:0000269|PubMed:9847246}.
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:11162580, ECO:0000269|PubMed:9169052,
CC ECO:0000269|PubMed:9784196};
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:11162580,
CC ECO:0000269|PubMed:9169052, ECO:0000269|PubMed:9784196};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11162580};
CC -!- ACTIVITY REGULATION: Inhibited by lithium. Lithium inhibition is
CC competitive with respect to magnesium but non-competitive with respect
CC to the peptide substrate.
CC -!- DEVELOPMENTAL STAGE: Expressed in growing cells and throughout
CC development. Levels increase during mound formation (12 hours) and peak
CC at approximately twice the level seen in growing cells before
CC decreasing again at the start of culmination (16 hours).
CC {ECO:0000269|PubMed:9847246}.
CC -!- DISRUPTION PHENOTYPE: Cells grow normally in both axenic medium and
CC with bacteria. Under starvation conditions, mutants lacking gskA
CC aggregate more quickly and form smaller mounds than wild type, fail to
CC form slugs and take longer than wild type to reach culmination. At
CC culmination, mutants lacking gskA form abnormal fruiting bodies
CC characterized by an unusually large mound-like basal disk. Prestalk B
CC (pstB) cells are formed at the expense of prespore cells, and the
CC proportion of gskA null cells that differentiate into spores is greatly
CC reduced when compared to wild-type cells. {ECO:0000269|PubMed:15342480,
CC ECO:0000269|PubMed:7813009}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. GSK-3 subfamily. {ECO:0000305}.
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DR EMBL; L34674; AAA65968.2; -; mRNA.
DR EMBL; AAFI02000008; EAL71207.1; -; Genomic_DNA.
DR PIR; A55476; A55476.
DR RefSeq; XP_645156.1; XM_640064.1.
DR AlphaFoldDB; P51136; -.
DR SMR; P51136; -.
DR STRING; 44689.DDB0185150; -.
DR BindingDB; P51136; -.
DR ChEMBL; CHEMBL2311226; -.
DR iPTMnet; P51136; -.
DR PaxDb; P51136; -.
DR EnsemblProtists; EAL71207; EAL71207; DDB_G0272110.
DR GeneID; 8618327; -.
DR KEGG; ddi:DDB_G0272110; -.
DR dictyBase; DDB_G0272110; gskA.
DR eggNOG; KOG0658; Eukaryota.
DR HOGENOM; CLU_000288_181_20_1; -.
DR InParanoid; P51136; -.
DR OMA; CLHAFFD; -.
DR PhylomeDB; P51136; -.
DR BRENDA; 2.7.11.26; 1939.
DR Reactome; R-DDI-3371453; Regulation of HSF1-mediated heat shock response.
DR PRO; PR:P51136; -.
DR Proteomes; UP000002195; Chromosome 2.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0072686; C:mitotic spindle; IDA:dictyBase.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:dictyBase.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:dictyBase.
DR GO; GO:0050321; F:tau-protein kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0140582; P:adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway; IMP:dictyBase.
DR GO; GO:0031152; P:aggregation involved in sorocarp development; IMP:dictyBase.
DR GO; GO:0030154; P:cell differentiation; IMP:dictyBase.
DR GO; GO:0043327; P:chemotaxis to cAMP; IMP:dictyBase.
DR GO; GO:0043326; P:chemotaxis to folate; IMP:dictyBase.
DR GO; GO:0031154; P:culmination involved in sorocarp development; IMP:UniProtKB.
DR GO; GO:0000281; P:mitotic cytokinesis; IMP:dictyBase.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IMP:dictyBase.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:dictyBase.
DR GO; GO:1902846; P:positive regulation of mitotic spindle elongation; IMP:dictyBase.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; IDA:dictyBase.
DR GO; GO:1904515; P:positive regulation of TORC2 signaling; IDA:dictyBase.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0060176; P:regulation of aggregation involved in sorocarp development; IMP:dictyBase.
DR GO; GO:0030155; P:regulation of cell adhesion; TAS:dictyBase.
DR GO; GO:0043087; P:regulation of GTPase activity; IMP:dictyBase.
DR GO; GO:0043520; P:regulation of myosin II filament assembly; IMP:dictyBase.
DR GO; GO:0061118; P:regulation of positive chemotaxis to cAMP; IMP:dictyBase.
DR GO; GO:0045859; P:regulation of protein kinase activity; IMP:dictyBase.
DR GO; GO:1904776; P:regulation of protein localization to cell cortex; IMP:dictyBase.
DR GO; GO:0007165; P:signal transduction; IMP:dictyBase.
DR GO; GO:0031288; P:sorocarp morphogenesis; IMP:dictyBase.
DR GO; GO:0030435; P:sporulation resulting in formation of a cellular spore; IMP:UniProtKB.
DR GO; GO:0031929; P:TOR signaling; IMP:dictyBase.
DR CDD; cd14137; STKc_GSK3; 1.
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; IPR039192; STKc_GSK3.
DR Pfam; PF00069; Pkinase; 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; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..467
FT /note="Glycogen synthase kinase-3"
FT /id="PRO_0000085983"
FT DOMAIN 56..339
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 400..467
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..20
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 21..42
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 179
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 62..70
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 85
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 214
FT /note="Phosphotyrosine; by zakA"
FT /evidence="ECO:0000269|PubMed:12408804"
FT MOD_RES 220
FT /note="Phosphotyrosine; by zakA"
FT /evidence="ECO:0000269|PubMed:12408804"
FT MUTAGEN 85
FT /note="K->M: Inactive kinase."
FT /evidence="ECO:0000269|PubMed:12408804"
FT MUTAGEN 86
FT /note="K->M: Inactive kinase."
FT /evidence="ECO:0000269|PubMed:12408804"
FT MUTAGEN 214
FT /note="Y->F: Not phosphorylated or activated by zakA."
FT /evidence="ECO:0000269|PubMed:12408804"
FT MUTAGEN 220
FT /note="Y->F: Not phosphorylated or activated by zakA."
FT /evidence="ECO:0000269|PubMed:12408804"
SQ SEQUENCE 467 AA; 51483 MW; EF6C00122B90C61D CRC64;
MSSKDQILEK DKKETDDNGN KKTTTTTSSS SSSSSSSKPR SNKFDKVIIK SNGVCYITEG
VIGNGSFGVV TQAIVADTKE VVAIKKVLQD QRYKNRELQI MKMLNHINIV SLKNSFYTSD
NDEVYLNLVL EYVPDTVYRV SRHYSMSKQP VPNIFVKLYI YQLCRSINYI HSLGICHRDI
KPQNLLLDTS TSTLKLCDFG SAKILIKGET NVSYICSRHY RAPELIFGST NYTTTIDVWS
LGCVLAELLL GQPLFPGENG IDQLVEIIKV LGTPTKEQIH AMNPYYTSFK FPEIKANPWP
RVFKAKDVPA ESIDLISKIL LYDPSSRLKP VEICAHPFFD ELRDPKTCLP DGKPLPPLFN
FTIAEQTSIG PKLAKTLIPS HAMNQIELPS PLFPNLAISS SNQSSSSNSN ANVSSNLNSH
SASPSTTSSS SSTPNSIPVQ SPSTTNTTSS TTNNTTTTTT TTTTSNH
