GSK3B_XENLA
ID GSK3B_XENLA Reviewed; 420 AA.
AC Q91757; Q91627;
DT 27-JUL-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Glycogen synthase kinase-3 beta;
DE Short=GSK-3 beta;
DE EC=2.7.11.26;
DE AltName: Full=Xgsk-3 protein;
GN Name=gsk3b; Synonyms=Xgsk-3;
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, MUTAGENESIS OF LYS-85, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=7720580; DOI=10.1242/dev.121.3.755;
RA Pierce S.B., Kimelman D.;
RT "Regulation of Spemann organizer formation by the intracellular kinase
RT Xgsk-3.";
RL Development 121:755-765(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, MUTAGENESIS OF LYS-85, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=7667318; DOI=10.1073/pnas.92.18.8498;
RA Dominguez I., Itoh K., Sokol S.Y.;
RT "Role of glycogen synthase kinase 3 beta as a negative regulator of
RT dorsoventral axis formation in Xenopus embryos.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:8498-8502(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=9828091; DOI=10.1006/mcne.1998.0713;
RA Marcus E.A., Kintner C., Harris W.;
RT "The role of GSK3beta in regulating neuronal differentiation in Xenopus
RT laevis.";
RL Mol. Cell. Neurosci. 12:269-280(1998).
RN [5]
RP FUNCTION.
RX PubMed=11970861; DOI=10.1016/s0896-6273(02)00666-9;
RA Moore K.B., Schneider M.L., Vetter M.L.;
RT "Posttranslational mechanisms control the timing of bHLH function and
RT regulate retinal cell fate.";
RL Neuron 34:183-195(2002).
CC -!- FUNCTION: Plays a role in the organization of the formation of the main
CC body axis of developing embryo. Acts as an inhibitor of differentiation
CC of primary neurons. Inhibits the ability of ectopically expressed
CC NEUROD1 and other bHLH factors to promote early retinal cell
CC differentiation. May participate in the Wnt signaling pathway. May
CC regulate the circadian clock via phosphorylation of the major clock
CC components. {ECO:0000269|PubMed:11970861, ECO:0000269|PubMed:7667318,
CC ECO:0000269|PubMed:7720580, ECO:0000269|PubMed:9828091}.
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 -!- 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;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P49841}. Nucleus
CC {ECO:0000250|UniProtKB:P49841}. Cell membrane
CC {ECO:0000250|UniProtKB:P49841}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the unfertilized egg and throughout
CC the early embryonic stages. Expressed in the neural plate at stage 13.
CC Expressed throughout the eye primordia and cranial ganglia at stage 25.
CC Highly expressed in the differentiated retinal ganglion cell layer at
CC stage 40. {ECO:0000269|PubMed:7667318, ECO:0000269|PubMed:7720580,
CC ECO:0000269|PubMed:9828091}.
CC -!- PTM: Phosphorylated. Activated by phosphorylation at Tyr-216.
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; L38492; AAC42224.1; -; mRNA.
DR EMBL; U31862; AAA84444.1; -; mRNA.
DR EMBL; BC108581; AAI08582.1; -; mRNA.
DR PIR; I51425; I51425.
DR PIR; I51692; I51692.
DR RefSeq; NP_001083752.1; NM_001090283.1.
DR RefSeq; XP_018100414.1; XM_018244925.1.
DR AlphaFoldDB; Q91757; -.
DR SMR; Q91757; -.
DR ELM; Q91757; -.
DR DNASU; 399097; -.
DR GeneID; 399097; -.
DR KEGG; xla:399097; -.
DR CTD; 399097; -.
DR Xenbase; XB-GENE-865674; gsk3b.L.
DR OrthoDB; 990896at2759; -.
DR Proteomes; UP000186698; Chromosome 2L.
DR Bgee; 399097; Expressed in testis and 19 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0050321; F:tau-protein kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd14137; STKc_GSK3; 1.
DR InterPro; IPR033573; GSK3B.
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 PANTHER; PTHR24057:SF8; PTHR24057:SF8; 1.
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; Biological rhythms; Cell membrane; Cytoplasm;
KW Developmental protein; Differentiation; Kinase; Membrane; Neurogenesis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Wnt signaling pathway.
FT CHAIN 1..420
FT /note="Glycogen synthase kinase-3 beta"
FT /id="PRO_0000412070"
FT DOMAIN 56..340
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 384..420
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..28
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 181
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 /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MUTAGEN 85
FT /note="K->R: Inhibits enzymatic activity. Induces
FT duplication of the anterior dorsal axis."
FT /evidence="ECO:0000269|PubMed:7667318,
FT ECO:0000269|PubMed:7720580"
FT CONFLICT 55
FT /note="T -> S (in Ref. 2; AAA84444)"
FT /evidence="ECO:0000305"
FT CONFLICT 88
FT /note="L -> P (in Ref. 2; AAA84444)"
FT /evidence="ECO:0000305"
FT CONFLICT 336
FT /note="A -> V (in Ref. 2; AAA84444)"
FT /evidence="ECO:0000305"
FT CONFLICT 399
FT /note="D -> N (in Ref. 2; AAA84444)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 420 AA; 46903 MW; C02280BB8A35785D CRC64;
MSGRPRTTSF AESCKPVQQP SSFGSMKVSR DKDGSKVTTV VATPGQGPDR QQEVTYTDTK
VIGNGSFGVV YQAKLCDTGE LVAIKKVLQD KRFKNRELQI MRKLDHCNIV RLRYFFYSSG
EKKDEVYLNL VLDYVPETVY RVARHYSRAK QALPIIYVKL YMYQLFRSLA YIHSFGICHR
DIKPQNLLLD PETAVLKLCD FGSAKQLVRG EPNVSYICSR YYRAPELIFG ATDYTSSIDV
WSAGCVLAEL LLGQPIFPGD SGVDQLVEII KVLGTPTREQ IREMNPNYTE FKFPQIKAHP
WTKVFRARTP PEAIALCSRL LEYTPTSRLT PLDACAHSFF DELRDPNLKL PNGREFPALF
NFTTQELSSN PSLSSILIPA HARNQAAVST TSNTTSTSDS NTGERGSTNN AASASASNSS
