GSK3_CAEEL
ID GSK3_CAEEL Reviewed; 362 AA.
AC Q9U2Q9; Q9Y0C2;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Glycogen synthase kinase-3 {ECO:0000303|PubMed:16251270};
DE EC=2.7.11.26;
GN Name=gsk-3 {ECO:0000312|WormBase:Y18D10A.5};
GN Synonyms=sgg-1 {ECO:0000303|PubMed:10444600};
GN ORFNames=Y18D10A.5 {ECO:0000312|WormBase:Y18D10A.5};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAD45354.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10444600; DOI=10.1101/gad.13.15.2028;
RA Schlesinger A., Shelton C.A., Maloof J.N., Meneghini M.D., Bowerman B.;
RT "Wnt pathway components orient a mitotic spindle in the early
RT Caenorhabditis elegans embryo without requiring gene transcription in the
RT responding cell.";
RL Genes Dev. 13:2028-2038(1999).
RN [2] {ECO:0000312|EMBL:CAA22311.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000305}
RP FUNCTION.
RX PubMed=11463373; DOI=10.1016/s1097-2765(01)00195-2;
RA Maduro M.F., Meneghini M.D., Bowerman B., Broitman-Maduro G., Rothman J.H.;
RT "Restriction of mesendoderm to a single blastomere by the combined action
RT of SKN-1 and a GSK-3beta homolog is mediated by MED-1 and -2 in C.
RT elegans.";
RL Mol. Cell 7:475-485(2001).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=15572126; DOI=10.1016/j.devcel.2004.10.008;
RA Walston T., Tuskey C., Edgar L., Hawkins N., Ellis G., Bowerman B.,
RA Wood W., Hardin J.;
RT "Multiple Wnt signaling pathways converge to orient the mitotic spindle in
RT early C. elegans embryos.";
RL Dev. Cell 7:831-841(2004).
RN [5] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16289132; DOI=10.1016/j.ydbio.2005.09.053;
RA Nishi Y., Lin R.;
RT "DYRK2 and GSK-3 phosphorylate and promote the timely degradation of OMA-1,
RT a key regulator of the oocyte-to-embryo transition in C. elegans.";
RL Dev. Biol. 288:139-149(2005).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=16251270; DOI=10.1073/pnas.0508105102;
RA An J.H., Vranas K., Lucke M., Inoue H., Hisamoto N., Matsumoto K.,
RA Blackwell T.K.;
RT "Regulation of the Caenorhabditis elegans oxidative stress defense protein
RT SKN-1 by glycogen synthase kinase-3.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:16275-16280(2005).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=16343905; DOI=10.1016/j.cub.2005.11.070;
RA Shirayama M., Soto M.C., Ishidate T., Kim S., Nakamura K., Bei Y.,
RA van den Heuvel S., Mello C.C.;
RT "The conserved kinases CDK-1, GSK-3, KIN-19, and MBK-2 promote OMA-1
RT destruction to regulate the oocyte-to-embryo transition in C. elegans.";
RL Curr. Biol. 16:47-55(2006).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=16930586; DOI=10.1016/j.ydbio.2006.06.050;
RA Gleason J.E., Szyleyko E.A., Eisenmann D.M.;
RT "Multiple redundant Wnt signaling components function in two processes
RT during C. elegans vulval development.";
RL Dev. Biol. 298:442-457(2006).
RN [9] {ECO:0000305}
RP INTERACTION WITH AXL-1.
RX PubMed=17601533; DOI=10.1016/j.ydbio.2007.05.043;
RA Oosterveen T., Coudreuse D.Y.M., Yang P.-T., Fraser E., Bergsma J.,
RA Dale T.C., Korswagen H.C.;
RT "Two functionally distinct axin-like proteins regulate canonical Wnt
RT signaling in C. elegans.";
RL Dev. Biol. 308:438-448(2007).
RN [10] {ECO:0000305}
RP FUNCTION.
RX PubMed=17959600; DOI=10.1074/jbc.m705028200;
RA McColl G., Killilea D.W., Hubbard A.E., Vantipalli M.C., Melov S.,
RA Lithgow G.J.;
RT "Pharmacogenetic analysis of lithium-induced delayed aging in
RT Caenorhabditis elegans.";
RL J. Biol. Chem. 283:350-357(2008).
CC -!- FUNCTION: Phosphorylates oma-1, a regulator of the oocyte-to-embryo
CC transition, enabling its degradation (PubMed:16343905,
CC PubMed:16289132). Phosphorylates skn-1, preventing it from accumulating
CC in nuclei and thus inhibiting phase II gene expression in the oxidative
CC stress defense (PubMed:16251270). Involved in mesendoderm specification
CC and mitotic spindle orientation in EMS blastomeres (PubMed:11463373).
CC Thought to be a branch point in these processes as proteins downstream
CC are not required (PubMed:10444600). Negatively regulates Wnt signaling
CC in vulval precursor cells and acts as a Wnt-independent repressor of
CC med-1 and med-2 in the C lineage inhibiting mesoderm development
CC (PubMed:10444600, PubMed:11463373, PubMed:15572126). Required for
CC normal lifespan and LiCl-induced lifespan extension (PubMed:17959600).
CC {ECO:0000269|PubMed:10444600, ECO:0000269|PubMed:11463373,
CC ECO:0000269|PubMed:15572126, ECO:0000269|PubMed:16251270,
CC ECO:0000269|PubMed:16289132, ECO:0000269|PubMed:16343905,
CC ECO:0000269|PubMed:16930586, ECO:0000269|PubMed:17959600}.
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:0000250|UniProtKB:P49841};
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:0000250|UniProtKB:P49841};
CC -!- SUBUNIT: Monomer (By similarity). Interacts with axl-1.
CC {ECO:0000250|UniProtKB:Q9WV60, ECO:0000269|PubMed:17601533}.
CC -!- INTERACTION:
CC Q9U2Q9; Q3LRZ3: axl-1; NbExp=4; IntAct=EBI-330089, EBI-327368;
CC Q9U2Q9; Q9NAG4: mac-1; NbExp=3; IntAct=EBI-330089, EBI-2005767;
CC Q9U2Q9; O62090: pry-1; NbExp=6; IntAct=EBI-330089, EBI-2917690;
CC -!- DISRUPTION PHENOTYPE: Worms exhibit defects in endoderm specification
CC and mitotic spindle alignment (PubMed:10444600). RNAi-mediated
CC knockdown results in stability and delayed degradation of the maternal
CC oocyte protein oma-1 in embryos beyond the 2-cell stage
CC (PubMed:16289132). {ECO:0000269|PubMed:10444600,
CC ECO:0000269|PubMed:16289132}.
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; AF159950; AAD45354.1; -; mRNA.
DR EMBL; AL034393; CAA22311.1; -; Genomic_DNA.
DR PIR; T26520; T26520.
DR RefSeq; NP_493243.1; NM_060842.5.
DR AlphaFoldDB; Q9U2Q9; -.
DR SMR; Q9U2Q9; -.
DR BioGRID; 38546; 37.
DR DIP; DIP-25216N; -.
DR IntAct; Q9U2Q9; 13.
DR MINT; Q9U2Q9; -.
DR STRING; 6239.Y18D10A.5; -.
DR iPTMnet; Q9U2Q9; -.
DR EPD; Q9U2Q9; -.
DR PaxDb; Q9U2Q9; -.
DR PeptideAtlas; Q9U2Q9; -.
DR EnsemblMetazoa; Y18D10A.5.1; Y18D10A.5.1; WBGene00001746.
DR GeneID; 173149; -.
DR UCSC; Y18D10A.5; c. elegans.
DR CTD; 173149; -.
DR WormBase; Y18D10A.5; CE21401; WBGene00001746; gsk-3.
DR eggNOG; KOG0658; Eukaryota.
DR GeneTree; ENSGT00520000055635; -.
DR HOGENOM; CLU_000288_181_20_1; -.
DR InParanoid; Q9U2Q9; -.
DR OMA; CLHAFFD; -.
DR OrthoDB; 990896at2759; -.
DR PhylomeDB; Q9U2Q9; -.
DR Reactome; R-CEL-195253; Degradation of beta-catenin by the destruction complex.
DR Reactome; R-CEL-196299; Beta-catenin phosphorylation cascade.
DR Reactome; R-CEL-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-CEL-399956; CRMPs in Sema3A signaling.
DR Reactome; R-CEL-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR Reactome; R-CEL-9762114; GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2.
DR SignaLink; Q9U2Q9; -.
DR PRO; PR:Q9U2Q9; -.
DR Proteomes; UP000001940; Chromosome I.
DR GO; GO:0005737; C:cytoplasm; ISS:WormBase.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:WormBase.
DR GO; GO:0050321; F:tau-protein kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0043652; P:engulfment of apoptotic cell; IMP:WormBase.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IMP:UniProtKB.
DR GO; GO:0007281; P:germ cell development; IGI:WormBase.
DR GO; GO:0070986; P:left/right axis specification; IMP:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:WormBase.
DR GO; GO:1903356; P:positive regulation of distal tip cell migration; IMP:UniProtKB.
DR GO; GO:1901076; P:positive regulation of engulfment of apoptotic cell; IMP:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:WormBase.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0060069; P:Wnt signaling pathway, regulating spindle positioning; IMP:WormBase.
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; Developmental protein; Kinase; Nucleotide-binding;
KW Reference proteome; Serine/threonine-protein kinase; Stress response;
KW Transferase; Wnt signaling pathway.
FT CHAIN 1..362
FT /note="Glycogen synthase kinase-3"
FT /id="PRO_0000349136"
FT DOMAIN 36..320
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 325..362
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 347..362
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 161
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 42..50
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 65
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT CONFLICT 350
FT /note="V -> I (in Ref. 1; AAD45354)"
FT /evidence="ECO:0000305"
FT CONFLICT 352
FT /note="T -> P (in Ref. 1; AAD45354)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 362 AA; 40882 MW; ABDD2F49CC475BF5 CRC64;
MNKQLLSCSL KSGKQVTMVV ASVATDGVDQ QVEISYYDQK VIGNGSFGVV FLAKLSTTNE
MVAIKKVLQD KRFKNRELQI MRKLNHPNIV KLKYFFYSSG EKKDELYLNL ILEYVPETVY
RVARHYSKQR QQIPMIYVKL YMYQLLRSLA YIHSIGICHR DIKPQNLLID PESGVLKLCD
FGSAKYLVRN EPNVSYICSR YYRAPELIFG ATNYTNSIDV WSAGTVMAEL LLGQPIFPGD
SGVDQLVEII KVLGTPTREQ IQSMNPNYKE FKFPQIKAHP WNKVFRVHTP AEAIDLISKI
IEYTPTSRPT PQAACQHAFF DELRNPDARL PSGRPLPTLE MDGPMGTGEV STTSGDVAGP
SA
