GYS2_HUMAN
ID GYS2_HUMAN Reviewed; 703 AA.
AC P54840; A0AVD8;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 09-FEB-2010, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Glycogen [starch] synthase, liver;
DE EC=2.4.1.11;
GN Name=GYS2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-363.
RC TISSUE=Liver;
RX PubMed=8203908; DOI=10.1006/abbi.1994.1260;
RA Nuttall F.Q., Gannon M.C., Bai G., Lee E.Y.;
RT "Primary structure of human liver glycogen synthase deduced by cDNA
RT cloning.";
RL Arch. Biochem. Biophys. 311:443-449(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GSD0 SER-39; PRO-339;
RP VAL-363; ASP-446; GLN-479; PRO-483 AND ARG-491.
RX PubMed=9691087; DOI=10.1172/jci2890;
RA Orho M., Bosshard N.U., Buist N.R.M., Gitzelmann R., Aynsley-Green A.,
RA Blumel P., Gannon M.C., Nuttall F.Q., Groop L.C.;
RT "Mutations in the liver glycogen synthase gene in children with
RT hypoglycemia due to glycogen storage disease type 0.";
RL J. Clin. Invest. 102:507-515(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-363.
RC TISSUE=Liver;
RA Nakabayashi H., Nakayama T.;
RT "Human liver glycogen synthase cDNA.";
RL Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-363.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-627 AND SER-683, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Transfers the glycosyl residue from UDP-Glc to the non-
CC reducing end of alpha-1,4-glucan.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[(1->4)-alpha-D-glucosyl](n) + UDP-alpha-D-glucose = [(1->4)-
CC alpha-D-glucosyl](n+1) + H(+) + UDP; Xref=Rhea:RHEA:18549, Rhea:RHEA-
CC COMP:9584, Rhea:RHEA-COMP:9587, ChEBI:CHEBI:15378, ChEBI:CHEBI:15444,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:58885; EC=2.4.1.11;
CC -!- ACTIVITY REGULATION: Allosteric activation by glucose-6-phosphate.
CC Phosphorylation reduces the activity towards UDP-glucose. When in the
CC non-phosphorylated state, glycogen synthase does not require glucose-6-
CC phosphate as an allosteric activator; when phosphorylated it does (By
CC similarity). {ECO:0000250}.
CC -!- PATHWAY: Glycan biosynthesis; glycogen biosynthesis.
CC -!- SUBUNIT: Interacts with GYG1 (via C-terminus); required for GYS2-
CC mediated glycogen synthesis. {ECO:0000250|UniProtKB:Q8VCB3}.
CC -!- PTM: Primed phosphorylation at Ser-657 (site 5) by CSNK2A1 and CSNK2A2
CC is required for inhibitory phosphorylation at Ser-641 (site 3a), Ser-
CC 645 (site 3b), Ser-649 (site 3c) and Ser-653 (site 4) by GSK3A an
CC GSK3B. Dephosphorylation at Ser-641 and Ser-645 by PP1 activates the
CC enzyme (By similarity). Phosphorylation at Ser-8 is not required for
CC interaction with GYG1 (By similarity). Interaction with GYG1 does not
CC regulate the phosphorylation at Ser-8 and Ser-641 (By similarity).
CC {ECO:0000250|UniProtKB:P13807, ECO:0000250|UniProtKB:P13834,
CC ECO:0000250|UniProtKB:Q8VCB3}.
CC -!- DISEASE: Glycogen storage disease 0 (GSD0) [MIM:240600]: A metabolic
CC disorder characterized by fasting hypoglycemia presenting in infancy or
CC early childhood, high blood ketones and low alanine and lactate
CC concentrations. Although feeding relieves symptoms, it often results in
CC postprandial hyperglycemia and hyperlactatemia.
CC {ECO:0000269|PubMed:9691087}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 3 family. {ECO:0000305}.
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DR EMBL; S70004; AAB30886.1; -; mRNA.
DR EMBL; AJ003087; CAA05859.1; -; Genomic_DNA.
DR EMBL; AJ003088; CAA05859.1; JOINED; Genomic_DNA.
DR EMBL; AJ003089; CAA05859.1; JOINED; Genomic_DNA.
DR EMBL; AJ003090; CAA05859.1; JOINED; Genomic_DNA.
DR EMBL; AJ003091; CAA05859.1; JOINED; Genomic_DNA.
DR EMBL; AJ003092; CAA05859.1; JOINED; Genomic_DNA.
DR EMBL; AJ003093; CAA05859.1; JOINED; Genomic_DNA.
DR EMBL; AJ003094; CAA05859.1; JOINED; Genomic_DNA.
DR EMBL; AJ003095; CAA05859.1; JOINED; Genomic_DNA.
DR EMBL; AJ003096; CAA05859.1; JOINED; Genomic_DNA.
DR EMBL; AJ003097; CAA05859.1; JOINED; Genomic_DNA.
DR EMBL; AJ003098; CAA05859.1; JOINED; Genomic_DNA.
DR EMBL; AJ003099; CAA05859.1; JOINED; Genomic_DNA.
DR EMBL; AJ003100; CAA05859.1; JOINED; Genomic_DNA.
DR EMBL; AJ003101; CAA05859.1; JOINED; Genomic_DNA.
DR EMBL; AJ003102; CAA05859.1; JOINED; Genomic_DNA.
DR EMBL; D29685; BAA06154.1; -; mRNA.
DR EMBL; AC006559; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010197; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022072; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC126310; AAI26311.1; -; mRNA.
DR EMBL; BC126312; AAI26313.1; -; mRNA.
DR CCDS; CCDS8690.1; -.
DR PIR; S45686; S45686.
DR RefSeq; NP_068776.2; NM_021957.3.
DR AlphaFoldDB; P54840; -.
DR SMR; P54840; -.
DR BioGRID; 109253; 9.
DR IntAct; P54840; 7.
DR MINT; P54840; -.
DR STRING; 9606.ENSP00000261195; -.
DR BindingDB; P54840; -.
DR ChEMBL; CHEMBL4523243; -.
DR DrugCentral; P54840; -.
DR CAZy; GT3; Glycosyltransferase Family 3.
DR GlyGen; P54840; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P54840; -.
DR PhosphoSitePlus; P54840; -.
DR BioMuta; GYS2; -.
DR DMDM; 288558811; -.
DR EPD; P54840; -.
DR jPOST; P54840; -.
DR MassIVE; P54840; -.
DR MaxQB; P54840; -.
DR PaxDb; P54840; -.
DR PeptideAtlas; P54840; -.
DR PRIDE; P54840; -.
DR ProteomicsDB; 56737; -.
DR Antibodypedia; 24071; 110 antibodies from 25 providers.
DR DNASU; 2998; -.
DR Ensembl; ENST00000261195.3; ENSP00000261195.2; ENSG00000111713.3.
DR GeneID; 2998; -.
DR KEGG; hsa:2998; -.
DR MANE-Select; ENST00000261195.3; ENSP00000261195.2; NM_021957.4; NP_068776.2.
DR UCSC; uc001rfb.3; human.
DR CTD; 2998; -.
DR DisGeNET; 2998; -.
DR GeneCards; GYS2; -.
DR HGNC; HGNC:4707; GYS2.
DR HPA; ENSG00000111713; Tissue enriched (liver).
DR MalaCards; GYS2; -.
DR MIM; 138571; gene.
DR MIM; 240600; phenotype.
DR neXtProt; NX_P54840; -.
DR OpenTargets; ENSG00000111713; -.
DR Orphanet; 2089; Glycogen storage disease due to hepatic glycogen synthase deficiency.
DR PharmGKB; PA29085; -.
DR VEuPathDB; HostDB:ENSG00000111713; -.
DR eggNOG; KOG3742; Eukaryota.
DR GeneTree; ENSGT00390000018612; -.
DR HOGENOM; CLU_015910_1_0_1; -.
DR InParanoid; P54840; -.
DR OMA; WEACGVG; -.
DR OrthoDB; 264593at2759; -.
DR PhylomeDB; P54840; -.
DR TreeFam; TF300306; -.
DR PathwayCommons; P54840; -.
DR Reactome; R-HSA-3322077; Glycogen synthesis.
DR Reactome; R-HSA-3858516; Glycogen storage disease type 0 (liver GYS2).
DR Reactome; R-HSA-3878781; Glycogen storage disease type IV (GBE1).
DR SignaLink; P54840; -.
DR SIGNOR; P54840; -.
DR UniPathway; UPA00164; -.
DR BioGRID-ORCS; 2998; 10 hits in 1067 CRISPR screens.
DR ChiTaRS; GYS2; human.
DR GenomeRNAi; 2998; -.
DR Pharos; P54840; Tbio.
DR PRO; PR:P54840; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P54840; protein.
DR Bgee; ENSG00000111713; Expressed in right lobe of liver and 39 other tissues.
DR Genevisible; P54840; HS.
DR GO; GO:0005938; C:cell cortex; ISS:UniProtKB.
DR GO; GO:0030864; C:cortical actin cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0043265; C:ectoplasm; ISS:UniProtKB.
DR GO; GO:0004373; F:glycogen (starch) synthase activity; IDA:UniProtKB.
DR GO; GO:0061547; F:glycogen synthase activity, transferring glucose-1-phosphate; TAS:Reactome.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc.
DR GO; GO:0005978; P:glycogen biosynthetic process; IDA:UniProtKB.
DR GO; GO:0009749; P:response to glucose; ISS:UniProtKB.
DR InterPro; IPR008631; Glycogen_synth.
DR PANTHER; PTHR10176; PTHR10176; 1.
DR Pfam; PF05693; Glycogen_syn; 1.
PE 1: Evidence at protein level;
KW Allosteric enzyme; Disease variant; Glycogen biosynthesis;
KW Glycogen storage disease; Glycosyltransferase; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..703
FT /note="Glycogen [starch] synthase, liver"
FT /id="PRO_0000194768"
FT REGION 628..703
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 658..672
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 689..703
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 40
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250"
FT MOD_RES 8
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P17625"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCB3"
FT MOD_RES 627
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 641
FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta"
FT /evidence="ECO:0000250"
FT MOD_RES 645
FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta"
FT /evidence="ECO:0000250"
FT MOD_RES 649
FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta"
FT /evidence="ECO:0000250"
FT MOD_RES 653
FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta"
FT /evidence="ECO:0000250"
FT MOD_RES 657
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250"
FT MOD_RES 683
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 39
FT /note="N -> S (in GSD0; dbSNP:rs121918423)"
FT /evidence="ECO:0000269|PubMed:9691087"
FT /id="VAR_007860"
FT VARIANT 193
FT /note="A -> T (in dbSNP:rs16924038)"
FT /id="VAR_055885"
FT VARIANT 339
FT /note="A -> P (in GSD0; dbSNP:rs121918421)"
FT /evidence="ECO:0000269|PubMed:9691087"
FT /id="VAR_007861"
FT VARIANT 363
FT /note="M -> V (in dbSNP:rs2306180)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8203908, ECO:0000269|PubMed:9691087,
FT ECO:0000269|Ref.3"
FT /id="VAR_058848"
FT VARIANT 415
FT /note="D -> E (in dbSNP:rs16924002)"
FT /id="VAR_055886"
FT VARIANT 446
FT /note="H -> D (in GSD0; dbSNP:rs121918425)"
FT /evidence="ECO:0000269|PubMed:9691087"
FT /id="VAR_007862"
FT VARIANT 479
FT /note="P -> Q (in GSD0; dbSNP:rs121918420)"
FT /evidence="ECO:0000269|PubMed:9691087"
FT /id="VAR_007863"
FT VARIANT 483
FT /note="S -> P (in GSD0; dbSNP:rs121918424)"
FT /evidence="ECO:0000269|PubMed:9691087"
FT /id="VAR_007864"
FT VARIANT 491
FT /note="M -> R (in GSD0; dbSNP:rs121918422)"
FT /evidence="ECO:0000269|PubMed:9691087"
FT /id="VAR_007865"
FT CONFLICT 97
FT /note="K -> M (in Ref. 3; BAA06154)"
FT /evidence="ECO:0000305"
FT CONFLICT 178
FT /note="Q -> R (in Ref. 3; BAA06154)"
FT /evidence="ECO:0000305"
FT CONFLICT 186
FT /note="I -> V (in Ref. 3; BAA06154)"
FT /evidence="ECO:0000305"
FT CONFLICT 335..336
FT /note="SN -> FKT (in Ref. 3; BAA06154)"
FT /evidence="ECO:0000305"
FT CONFLICT 344
FT /note="E -> D (in Ref. 3; BAA06154)"
FT /evidence="ECO:0000305"
FT CONFLICT 441
FT /note="P -> A (in Ref. 3; BAA06154)"
FT /evidence="ECO:0000305"
FT CONFLICT 576..577
FT /note="KQ -> NM (in Ref. 3; BAA06154)"
FT /evidence="ECO:0000305"
FT CONFLICT 583
FT /note="I -> F (in Ref. 3; BAA06154)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 703 AA; 80989 MW; 718F000D6D00CA4A CRC64;
MLRGRSLSVT SLGGLPQWEV EELPVEELLL FEVAWEVTNK VGGIYTVIQT KAKTTADEWG
ENYFLIGPYF EHNMKTQVEQ CEPVNDAVRR AVDAMNKHGC QVHFGRWLIE GSPYVVLFDI
GYSAWNLDRW KGDLWEACSV GIPYHDREAN DMLIFGSLTA WFLKEVTDHA DGKYVVAQFH
EWQAGIGLIL SRARKLPIAT IFTTHATLLG RYLCAANIDF YNHLDKFNID KEAGERQIYH
RYCMERASVH CAHVFTTVSE ITAIEAEHML KRKPDVVTPN GLNVKKFSAV HEFQNLHAMY
KARIQDFVRG HFYGHLDFDL EKTLFLFIAG RYEFSNKGAD IFLESLSRLN FLLRMHKSDI
TVMVFFIMPA KTNNFNVETL KGQAVRKQLW DVAHSVKEKF GKKLYDALLR GEIPDLNDIL
DRDDLTIMKR AIFSTQRQSL PPVTTHNMID DSTDPILSTI RRIGLFNNRT DRVKVILHPE
FLSSTSPLLP MDYEEFVRGC HLGVFPSYYE PWGYTPAECT VMGIPSVTTN LSGFGCFMQE
HVADPTAYGI YIVDRRFRSP DDSCNQLTKF LYGFCKQSRR QRIIQRNRTE RLSDLLDWRY
LGRYYQHARH LTLSRAFPDK FHVELTSPPT TEGFKYPRPS SVPPSPSGSQ ASSPQSSDVE
DEVEDERYDE EEEAERDRLN IKSPFSLSHV PHGKKKLHGE YKN
