ID GYS1_HUMAN Reviewed; 737 AA.
AC P13807; Q9BTT9;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 24-JAN-2024, entry version 217.
DE RecName: Full=Glycogen [starch] synthase, muscle {ECO:0000305};
DE EC=2.4.1.11 {ECO:0000250|UniProtKB:P13834, ECO:0000305|PubMed:35835870};
DE AltName: Full=Glycogen synthase 1 {ECO:0000312|HGNC:HGNC:4706};
GN Name=GYS1 {ECO:0000312|HGNC:HGNC:4706}; Synonyms=GYS;
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] (ISOFORM 1).
RC TISSUE=Muscle;
RX PubMed=2493642; DOI=10.1073/pnas.86.5.1443;
RA Browner M.F., Nakano K., Bang A.G., Fletterick R.J.;
RT "Human muscle glycogen synthase cDNA sequence: a negatively charged protein
RT with an asymmetric charge distribution.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:1443-1447(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT NIDDM SER-464.
RX PubMed=7657035; DOI=10.2337/diab.44.9.1099;
RA Orho M., Nikula-Ijas P., Schalin-Jantti C., Permutt M.A., Groop L.C.;
RT "Isolation and characterization of the human muscle glycogen synthase
RT gene.";
RL Diabetes 44:1099-1105(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Endometrium;
RX PubMed=9010351; DOI=10.1016/s0960-0760(96)00138-0;
RA Su X., Schuler L., Shapiro S.S.;
RT "Cloning and characterization of a glycogen synthase cDNA from human
RT endometrium.";
RL J. Steroid Biochem. Mol. Biol. 59:459-465(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney, Lymph, and Skin;
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 [7]
RP INTERACTION WITH GYG1.
RX PubMed=17055998; DOI=10.1016/j.abb.2006.09.024;
RA Skurat A.V., Dietrich A.D., Roach P.J.;
RT "Interaction between glycogenin and glycogen synthase.";
RL Arch. Biochem. Biophys. 456:93-97(2006).
RN [8]
RP INVOLVEMENT IN GSD0B.
RX PubMed=17928598; DOI=10.1056/nejmoa066691;
RA Kollberg G., Tulinius M., Gilljam T., Oestman-Smith I., Forsander G.,
RA Jotorp P., Oldfors A., Holme E.;
RT "Cardiomyopathy and exercise intolerance in muscle glycogen storage disease
RT 0.";
RL N. Engl. J. Med. 357:1507-1514(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641; SER-645 AND SER-649, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP DEPHOSPHORYLATION AT SER-641 AND SER-645 BY PP1.
RX PubMed=21668450; DOI=10.1111/j.1471-4159.2011.07345.x;
RA Kelsall I.R., Voss M., Munro S., Cuthbertson D.J., Cohen P.T.;
RT "R3F, a novel membrane-associated glycogen targeting subunit of protein
RT phosphatase 1 regulates glycogen synthase in astrocytoma cells in response
RT to glucose and extracellular signals.";
RL J. Neurochem. 118:596-610(2011).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412; SER-710 AND SER-727, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412 AND THR-700, 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).
RN [18] {ECO:0000312|PDB:7ZBN}
RP STRUCTURE BY ELECTRON MICROSCOPY (2.62 ANGSTROMS) IN COMPLEX WITH GYG1,
RP ACTIVITY REGULATION, SUBUNIT, AND PHOSPHORYLATION AT SER-8; SER-412;
RP SER-641; SER-645; SER-652; SER-653; SER-657; SER-727 AND SER-731.
RX PubMed=35690592; DOI=10.1038/s41467-022-31109-6;
RA Marr L., Biswas D., Daly L.A., Browning C., Vial S.C.M., Maskell D.P.,
RA Hudson C., Bertrand J.A., Pollard J., Ranson N.A., Khatter H., Eyers C.E.,
RA Sakamoto K., Zeqiraj E.;
RT "Mechanism of glycogen synthase inactivation and interaction with
RT glycogenin.";
RL Nat. Commun. 13:3372-3372(2022).
RN [19] {ECO:0000312|PDB:7Q0B, ECO:0000312|PDB:7Q0S, ECO:0000312|PDB:7Q12, ECO:0000312|PDB:7Q13}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.0 ANGSTROMS) IN COMPLEX WITH GYG1; UDP;
RP ALPHA-D-GLUCOSE AND GLUCOSE-6-PHOSPHATE, FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, PATHWAY, AND SUBUNIT.
RX PubMed=35835870; DOI=10.1038/s41594-022-00799-3;
RA McCorvie T.J., Loria P.M., Tu M., Han S., Shrestha L., Froese D.S.,
RA Ferreira I.M., Berg A.P., Yue W.W.;
RT "Molecular basis for the regulation of human glycogen synthase by
RT phosphorylation and glucose-6-phosphate.";
RL Nat. Struct. Mol. Biol. 29:628-638(2022).
CC -!- FUNCTION: Glycogen synthase participates in the glycogen biosynthetic
CC process along with glycogenin and glycogen branching enzyme. Extends
CC the primer composed of a few glucose units formed by glycogenin by
CC adding new glucose units to it. In this context, glycogen synthase
CC transfers the glycosyl residue from UDP-Glc to the non-reducing end of
CC alpha-1,4-glucan. {ECO:0000269|PubMed:35835870}.
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 Evidence={ECO:0000269|PubMed:35835870};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18550;
CC Evidence={ECO:0000269|PubMed:35835870};
CC -!- ACTIVITY REGULATION: Allosteric activation by glucose-6-phosphate
CC (PubMed:35690592, PubMed:35835870). Phosphorylation reduces enzyme
CC activity by constraining a tense conformation of the tetramer through
CC inter-subunit interaction (PubMed:35690592, PubMed:35835870).
CC Phosphorylation reduces the activity towards UDP-glucose (By
CC similarity). When in the non-phosphorylated state, glycogen synthase
CC does not require glucose-6-phosphate as an allosteric activator; when
CC phosphorylated it does (By similarity). {ECO:0000250|UniProtKB:P13834,
CC ECO:0000250|UniProtKB:P54840, ECO:0000269|PubMed:35690592,
CC ECO:0000269|PubMed:35835870}.
CC -!- PATHWAY: Glycan biosynthesis; glycogen biosynthesis.
CC {ECO:0000269|PubMed:35835870}.
CC -!- SUBUNIT: Part of the GYS1-GYG1 complex, a heterooctamer composed of a
CC tetramer of GYS1 and 2 dimers of GYG1, where each GYS1 protomer binds
CC to one GYG1 subunit (via GYG1 C-terminus); the GYS1 tetramer may
CC dissociate from GYG1 dimers to continue glycogen polymerization on its
CC own. {ECO:0000269|PubMed:17055998, ECO:0000269|PubMed:35690592,
CC ECO:0000269|PubMed:35835870}.
CC -!- INTERACTION:
CC P13807; Q13155: AIMP2; NbExp=3; IntAct=EBI-740553, EBI-745226;
CC P13807; Q8N7W2-2: BEND7; NbExp=3; IntAct=EBI-740553, EBI-10181188;
CC P13807; Q53HL2: CDCA8; NbExp=3; IntAct=EBI-740553, EBI-979174;
CC P13807; Q5SYC1: CLVS2; NbExp=3; IntAct=EBI-740553, EBI-12357161;
CC P13807; O43186: CRX; NbExp=3; IntAct=EBI-740553, EBI-748171;
CC P13807; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-740553, EBI-2349927;
CC P13807; Q86W67: FAM228A; NbExp=3; IntAct=EBI-740553, EBI-12958227;
CC P13807; P49841: GSK3B; NbExp=4; IntAct=EBI-740553, EBI-373586;
CC P13807; P46976: GYG1; NbExp=7; IntAct=EBI-740553, EBI-740533;
CC P13807; P46976-2: GYG1; NbExp=3; IntAct=EBI-740553, EBI-12017394;
CC P13807; P17509: HOXB6; NbExp=3; IntAct=EBI-740553, EBI-741308;
CC P13807; P31273: HOXC8; NbExp=3; IntAct=EBI-740553, EBI-1752118;
CC P13807; Q8IYA8: IHO1; NbExp=6; IntAct=EBI-740553, EBI-8638439;
CC P13807; Q0VD86: INCA1; NbExp=3; IntAct=EBI-740553, EBI-6509505;
CC P13807; Q9H079: KATNBL1; NbExp=5; IntAct=EBI-740553, EBI-715394;
CC P13807; Q13351: KLF1; NbExp=3; IntAct=EBI-740553, EBI-8284732;
CC P13807; O43474: KLF4; NbExp=5; IntAct=EBI-740553, EBI-7232405;
CC P13807; P50221: MEOX1; NbExp=3; IntAct=EBI-740553, EBI-2864512;
CC P13807; P17568: NDUFB7; NbExp=3; IntAct=EBI-740553, EBI-1246238;
CC P13807; P49585: PCYT1A; NbExp=3; IntAct=EBI-740553, EBI-2563309;
CC P13807; Q96BK5: PINX1; NbExp=3; IntAct=EBI-740553, EBI-721782;
CC P13807; Q9UPG8: PLAGL2; NbExp=3; IntAct=EBI-740553, EBI-2876622;
CC P13807; Q96PV4: PNMA5; NbExp=3; IntAct=EBI-740553, EBI-10171633;
CC P13807; Q9UQK1: PPP1R3C; NbExp=2; IntAct=EBI-740553, EBI-2506727;
CC P13807; Q5RL73: RBM48; NbExp=3; IntAct=EBI-740553, EBI-473821;
CC P13807; Q8TAD8: SNIP1; NbExp=3; IntAct=EBI-740553, EBI-749336;
CC P13807; O60504: SORBS3; NbExp=3; IntAct=EBI-740553, EBI-741237;
CC P13807; Q7Z6R9: TFAP2D; NbExp=3; IntAct=EBI-740553, EBI-11952651;
CC P13807; Q08117-2: TLE5; NbExp=5; IntAct=EBI-740553, EBI-11741437;
CC P13807; Q86T24: ZBTB33; NbExp=3; IntAct=EBI-740553, EBI-2515625;
CC P13807; Q9UDV6: ZNF212; NbExp=3; IntAct=EBI-740553, EBI-1640204;
CC P13807; Q5BKZ1: ZNF326; NbExp=3; IntAct=EBI-740553, EBI-2560158;
CC P13807; Q6S9Z5: ZNF474; NbExp=3; IntAct=EBI-740553, EBI-17269964;
CC P13807; Q9H707: ZNF552; NbExp=3; IntAct=EBI-740553, EBI-2555731;
CC P13807; Q6ZNG0: ZNF620; NbExp=3; IntAct=EBI-740553, EBI-4395669;
CC P13807; Q6NX45: ZNF774; NbExp=3; IntAct=EBI-740553, EBI-10251462;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P13807-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P13807-2; Sequence=VSP_042745;
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle and most other cell
CC types where glycogen is present. {ECO:0000305|PubMed:2493642}.
CC -!- PTM: Phosphorylation at Ser-8 by AMPK inactivates the enzyme activity.
CC Primed phosphorylation at Ser-657 (site 5) by CSNK2A1 and CSNK2A2 is
CC required for inhibitory phosphorylation at Ser-641 (site 3a), Ser-645
CC (site 3b), Ser-649 (site 3c) and Ser-653 (site 4) by GSK3A an GSK3B (By
CC similarity). Phosphorylated at Ser-641 by DYRK2, leading to
CC inactivation (By similarity). Phosphorylated at Ser-641 by PASK,
CC leading to inactivation; phosphorylation by PASK is inhibited by
CC glycogen. Dephosphorylation at Ser-641 and Ser-645 by PP1 activates the
CC enzyme (PubMed:35835870). {ECO:0000250|UniProtKB:P13834,
CC ECO:0000305|PubMed:35835870}.
CC -!- DISEASE: Muscle glycogen storage disease 0 (GSD0b) [MIM:611556]:
CC Metabolic disorder characterized by fasting hypoglycemia presenting in
CC infancy or early childhood. The role of muscle glycogen is to provide
CC critical energy during bursts of activity and sustained muscle work.
CC {ECO:0000269|PubMed:17928598}. 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; J04501; AAA88046.1; -; mRNA.
DR EMBL; Z33622; CAA83916.1; -; Genomic_DNA.
DR EMBL; Z33623; CAA83916.1; JOINED; Genomic_DNA.
DR EMBL; Z33609; CAA83916.1; JOINED; Genomic_DNA.
DR EMBL; Z33624; CAA83916.1; JOINED; Genomic_DNA.
DR EMBL; Z33625; CAA83916.1; JOINED; Genomic_DNA.
DR EMBL; Z33626; CAA83916.1; JOINED; Genomic_DNA.
DR EMBL; Z33610; CAA83916.1; JOINED; Genomic_DNA.
DR EMBL; Z33627; CAA83916.1; JOINED; Genomic_DNA.
DR EMBL; Z33628; CAA83916.1; JOINED; Genomic_DNA.
DR EMBL; Z33629; CAA83916.1; JOINED; Genomic_DNA.
DR EMBL; Z33630; CAA83916.1; JOINED; Genomic_DNA.
DR EMBL; Z33631; CAA83916.1; JOINED; Genomic_DNA.
DR EMBL; Z33633; CAA83916.1; JOINED; Genomic_DNA.
DR EMBL; U32573; AAB60385.1; -; mRNA.
DR EMBL; AC008687; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026803; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC098792; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471177; EAW52424.1; -; Genomic_DNA.
DR EMBL; BC002617; AAH02617.1; -; mRNA.
DR EMBL; BC003182; AAH03182.1; -; mRNA.
DR EMBL; BC007688; AAH07688.1; -; mRNA.
DR CCDS; CCDS12747.1; -. [P13807-1]
DR CCDS; CCDS54292.1; -. [P13807-2]
DR PIR; A32156; A32156.
DR RefSeq; NP_001155059.1; NM_001161587.1. [P13807-2]
DR RefSeq; NP_002094.2; NM_002103.4. [P13807-1]
DR PDB; 7Q0B; EM; 3.00 A; A/B/C/D=1-737.
DR PDB; 7Q0S; EM; 4.00 A; A/B/C/D=1-737.
DR PDB; 7Q12; EM; 3.70 A; A/B/C/D=1-737.
DR PDB; 7Q13; EM; 3.00 A; A/B/C/D=1-737.
DR PDB; 7ZBN; EM; 2.62 A; A/B/C/D=1-737.
DR PDB; 8CVX; EM; 3.50 A; A/B/C/D=1-634.
DR PDB; 8CVY; EM; 3.60 A; A/B/C/D=1-634.
DR PDB; 8CVZ; EM; 3.52 A; A/B/C/D=1-634.
DR PDBsum; 7Q0B; -.
DR PDBsum; 7Q0S; -.
DR PDBsum; 7Q12; -.
DR PDBsum; 7Q13; -.
DR PDBsum; 7ZBN; -.
DR PDBsum; 8CVX; -.
DR PDBsum; 8CVY; -.
DR PDBsum; 8CVZ; -.
DR AlphaFoldDB; P13807; -.
DR EMDB; EMD-13743; -.
DR EMDB; EMD-13751; -.
DR EMDB; EMD-13752; -.
DR EMDB; EMD-13753; -.
DR EMDB; EMD-14587; -.
DR EMDB; EMD-27020; -.
DR EMDB; EMD-27021; -.
DR EMDB; EMD-27022; -.
DR SMR; P13807; -.
DR BioGRID; 109252; 110.
DR IntAct; P13807; 80.
DR MINT; P13807; -.
DR STRING; 9606.ENSP00000317904; -.
DR BindingDB; P13807; -.
DR ChEMBL; CHEMBL4000; -.
DR CAZy; GT3; Glycosyltransferase Family 3.
DR GlyGen; P13807; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P13807; -.
DR PhosphoSitePlus; P13807; -.
DR SwissPalm; P13807; -.
DR BioMuta; GYS1; -.
DR DMDM; 1351366; -.
DR EPD; P13807; -.
DR jPOST; P13807; -.
DR MassIVE; P13807; -.
DR MaxQB; P13807; -.
DR PaxDb; 9606-ENSP00000317904; -.
DR PeptideAtlas; P13807; -.
DR ProteomicsDB; 52994; -. [P13807-1]
DR ProteomicsDB; 52995; -. [P13807-2]
DR Pumba; P13807; -.
DR Antibodypedia; 3582; 497 antibodies from 39 providers.
DR DNASU; 2997; -.
DR Ensembl; ENST00000263276.6; ENSP00000263276.6; ENSG00000104812.15. [P13807-2]
DR Ensembl; ENST00000323798.8; ENSP00000317904.3; ENSG00000104812.15. [P13807-1]
DR GeneID; 2997; -.
DR KEGG; hsa:2997; -.
DR MANE-Select; ENST00000323798.8; ENSP00000317904.3; NM_002103.5; NP_002094.2.
DR UCSC; uc002plp.4; human. [P13807-1]
DR AGR; HGNC:4706; -.
DR CTD; 2997; -.
DR DisGeNET; 2997; -.
DR GeneCards; GYS1; -.
DR HGNC; HGNC:4706; GYS1.
DR HPA; ENSG00000104812; Group enriched (heart muscle, skeletal muscle, tongue).
DR MalaCards; GYS1; -.
DR MIM; 138570; gene.
DR MIM; 611556; phenotype.
DR neXtProt; NX_P13807; -.
DR OpenTargets; ENSG00000104812; -.
DR Orphanet; 137625; Glycogen storage disease due to muscle and heart glycogen synthase deficiency.
DR PharmGKB; PA29084; -.
DR VEuPathDB; HostDB:ENSG00000104812; -.
DR eggNOG; KOG3742; Eukaryota.
DR GeneTree; ENSGT00390000018612; -.
DR HOGENOM; CLU_015910_1_0_1; -.
DR InParanoid; P13807; -.
DR OMA; RDVRNHI; -.
DR OrthoDB; 9432at2759; -.
DR PhylomeDB; P13807; -.
DR TreeFam; TF300306; -.
DR BioCyc; MetaCyc:HS02622-MONOMER; -.
DR BRENDA; 2.4.1.11; 2681.
DR PathwayCommons; P13807; -.
DR Reactome; R-HSA-3322077; Glycogen synthesis.
DR Reactome; R-HSA-3785653; Myoclonic epilepsy of Lafora.
DR Reactome; R-HSA-3814836; Glycogen storage disease type XV (GYG1).
DR Reactome; R-HSA-3828062; Glycogen storage disease type 0 (muscle GYS1).
DR SignaLink; P13807; -.
DR SIGNOR; P13807; -.
DR UniPathway; UPA00164; -.
DR BioGRID-ORCS; 2997; 106 hits in 1157 CRISPR screens.
DR ChiTaRS; GYS1; human.
DR GenomeRNAi; 2997; -.
DR Pharos; P13807; Tchem.
DR PRO; PR:P13807; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P13807; Protein.
DR Bgee; ENSG00000104812; Expressed in hindlimb stylopod muscle and 167 other cell types or tissues.
DR ExpressionAtlas; P13807; baseline and differential.
DR Genevisible; P13807; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016234; C:inclusion body; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005536; F:glucose binding; IEA:Ensembl.
DR GO; GO:0004373; F:glycogen (starch) synthase activity; EXP:Reactome.
DR GO; GO:0061547; F:glycogen synthase activity, transferring glucose-1-phosphate; EXP:Reactome.
DR GO; GO:0005978; P:glycogen biosynthetic process; IBA:GO_Central.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR CDD; cd03793; GT3_GSY2-like; 1.
DR Gene3D; 3.40.50.2000; Glycogen Phosphorylase B; 2.
DR InterPro; IPR008631; Glycogen_synth.
DR PANTHER; PTHR10176:SF2; GLYCOGEN [STARCH] SYNTHASE, MUSCLE; 1.
DR PANTHER; PTHR10176; GLYCOGEN SYNTHASE; 1.
DR Pfam; PF05693; Glycogen_syn; 1.
DR SUPFAM; SSF53756; UDP-Glycosyltransferase/glycogen phosphorylase; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; Alternative splicing; Diabetes mellitus;
KW Disease variant; Glycogen biosynthesis; Glycosyltransferase;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..737
FT /note="Glycogen [starch] synthase, muscle"
FT /id="PRO_0000194763"
FT REGION 634..737
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 653..671
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 678..692
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 696..737
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 39
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000269|PubMed:35835870,
FT ECO:0007744|PDB:7Q13"
FT BINDING 205
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000305|PubMed:35835870,
FT ECO:0007744|PDB:7Q13"
FT BINDING 211
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000305|PubMed:35835870,
FT ECO:0007744|PDB:7Q13"
FT BINDING 291
FT /ligand="alpha-D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:58225"
FT /ligand_note="allosteric activator; ligand shared between
FT two neighboring subunits"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:35835870,
FT ECO:0007744|PDB:7Q13"
FT BINDING 292
FT /ligand="alpha-D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:58225"
FT /ligand_note="allosteric activator; ligand shared between
FT two neighboring subunits"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:35835870,
FT ECO:0007744|PDB:7Q13"
FT BINDING 294
FT /ligand="alpha-D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:58225"
FT /ligand_note="allosteric activator; ligand shared between
FT two neighboring subunits"
FT /evidence="ECO:0000269|PubMed:35835870,
FT ECO:0007744|PDB:7Q12, ECO:0007744|PDB:7Q13"
FT BINDING 297
FT /ligand="alpha-D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:58225"
FT /ligand_note="allosteric activator; ligand shared between
FT two neighboring subunits"
FT /evidence="ECO:0000269|PubMed:35835870,
FT ECO:0007744|PDB:7Q13"
FT BINDING 301
FT /ligand="alpha-D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:58225"
FT /ligand_note="allosteric activator; ligand shared between
FT two neighboring subunits"
FT /evidence="ECO:0000269|PubMed:35835870,
FT ECO:0007744|PDB:7Q13"
FT BINDING 331
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000269|PubMed:35835870,
FT ECO:0007744|PDB:7Q13"
FT BINDING 331
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000305|PubMed:35835870,
FT ECO:0007744|PDB:7Q13"
FT BINDING 501
FT /ligand="alpha-D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:58225"
FT /ligand_note="allosteric activator; ligand shared between
FT two neighboring subunits"
FT /evidence="ECO:0000269|PubMed:35835870,
FT ECO:0007744|PDB:7Q12, ECO:0007744|PDB:7Q13"
FT BINDING 510
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000305|PubMed:35835870,
FT ECO:0007744|PDB:7Q13"
FT BINDING 512
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000305|PubMed:35835870,
FT ECO:0007744|PDB:7Q13"
FT BINDING 513
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000305|PubMed:35835870,
FT ECO:0007744|PDB:7Q13"
FT BINDING 515
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000269|PubMed:35835870,
FT ECO:0007744|PDB:7Q13"
FT BINDING 582
FT /ligand="alpha-D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:58225"
FT /ligand_note="allosteric activator; ligand shared between
FT two neighboring subunits"
FT /evidence="ECO:0000269|PubMed:35835870,
FT ECO:0007744|PDB:7Q12, ECO:0007744|PDB:7Q13"
FT BINDING 586
FT /ligand="alpha-D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:58225"
FT /ligand_note="allosteric activator; ligand shared between
FT two neighboring subunits"
FT /evidence="ECO:0000269|PubMed:35835870,
FT ECO:0007744|PDB:7Q12, ECO:0007744|PDB:7Q13"
FT MOD_RES 8
FT /note="Phosphoserine; by AMPK and PKA"
FT /evidence="ECO:0000269|PubMed:35690592"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13834"
FT MOD_RES 412
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:35690592,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 641
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:35690592,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 645
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:35690592,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 649
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 652
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:35690592"
FT MOD_RES 653
FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta"
FT /evidence="ECO:0000269|PubMed:35690592"
FT MOD_RES 657
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:35690592"
FT MOD_RES 698
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13834"
FT MOD_RES 700
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 710
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 721
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1E4"
FT MOD_RES 727
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:35690592,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 731
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:35690592"
FT VAR_SEQ 101..164
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_042745"
FT VARIANT 108
FT /note="I -> M (in dbSNP:rs5455)"
FT /id="VAR_037958"
FT VARIANT 130
FT /note="K -> E (in dbSNP:rs5456)"
FT /id="VAR_014727"
FT VARIANT 283
FT /note="N -> S (in dbSNP:rs5461)"
FT /id="VAR_014728"
FT VARIANT 359
FT /note="E -> G (in dbSNP:rs5465)"
FT /id="VAR_014729"
FT VARIANT 416
FT /note="M -> V (in dbSNP:rs5447)"
FT /id="VAR_014730"
FT VARIANT 464
FT /note="G -> S (in NIDDM; dbSNP:rs200862074)"
FT /evidence="ECO:0000269|PubMed:7657035"
FT /id="VAR_007859"
FT VARIANT 619
FT /note="E -> Q (in dbSNP:rs5450)"
FT /id="VAR_014731"
FT VARIANT 691
FT /note="P -> A (in dbSNP:rs5453)"
FT /id="VAR_014732"
FT CONFLICT 136
FT /note="T -> I (in Ref. 1; AAA88046 and 3; AAB60385)"
FT /evidence="ECO:0000305"
FT CONFLICT 462
FT /note="Missing (in Ref. 3; AAB60385)"
FT /evidence="ECO:0000305"
FT CONFLICT 608
FT /note="A -> D (in Ref. 3; AAB60385)"
FT /evidence="ECO:0000305"
FT CONFLICT 706
FT /note="S -> R (in Ref. 1; AAA88046 and 3; AAB60385)"
FT /evidence="ECO:0000305"
FT TURN 16..21
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 28..32
FT /evidence="ECO:0007829|PDB:7ZBN"
FT TURN 34..37
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 43..58
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 61..67
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 70..75
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 85..96
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 100..106
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:7Q0B"
FT STRAND 113..118
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 120..125
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 126..137
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 146..167
FT /evidence="ECO:0007829|PDB:7ZBN"
FT TURN 169..171
FT /evidence="ECO:0007829|PDB:7Q13"
FT STRAND 175..179
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 182..194
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 197..206
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 208..216
FT /evidence="ECO:0007829|PDB:7ZBN"
FT TURN 218..226
FT /evidence="ECO:0007829|PDB:8CVX"
FT HELIX 229..235
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 239..250
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 253..259
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 260..269
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 275..277
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 284..286
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 294..311
FT /evidence="ECO:0007829|PDB:7ZBN"
FT TURN 312..314
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 323..331
FT /evidence="ECO:0007829|PDB:7ZBN"
FT TURN 334..338
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 339..355
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 361..367
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 372..375
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 377..409
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 416..419
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 422..435
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 443..448
FT /evidence="ECO:0007829|PDB:7ZBN"
FT TURN 449..453
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 455..463
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 472..477
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 483..485
FT /evidence="ECO:0007829|PDB:8CVX"
FT STRAND 487..490
FT /evidence="ECO:0007829|PDB:8CVX"
FT HELIX 493..498
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 501..504
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 508..512
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 514..521
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 526..529
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 533..541
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 542..544
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 545..548
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 550..553
FT /evidence="ECO:0007829|PDB:7ZBN"
FT STRAND 556..558
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 560..576
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 579..591
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 592..596
FT /evidence="ECO:0007829|PDB:7ZBN"
FT HELIX 598..616
FT /evidence="ECO:0007829|PDB:7ZBN"
FT TURN 618..620
FT /evidence="ECO:0007829|PDB:7ZBN"
SQ SEQUENCE 737 AA; 83786 MW; 0E321BBFDEB0BD7F CRC64;
MPLNRTLSMS SLPGLEDWED EFDLENAVLF EVAWEVANKV GGIYTVLQTK AKVTGDEWGD
NYFLVGPYTE QGVRTQVELL EAPTPALKRT LDSMNSKGCK VYFGRWLIEG GPLVVLLDVG
ASAWALERWK GELWDTCNIG VPWYDREAND AVLFGFLTTW FLGEFLAQSE EKPHVVAHFH
EWLAGVGLCL CRARRLPVAT IFTTHATLLG RYLCAGAVDF YNNLENFNVD KEAGERQIYH
RYCMERAAAH CAHVFTTVSQ ITAIEAQHLL KRKPDIVTPN GLNVKKFSAM HEFQNLHAQS
KARIQEFVRG HFYGHLDFNL DKTLYFFIAG RYEFSNKGAD VFLEALARLN YLLRVNGSEQ
TVVAFFIMPA RTNNFNVETL KGQAVRKQLW DTANTVKEKF GRKLYESLLV GSLPDMNKML
DKEDFTMMKR AIFATQRQSF PPVCTHNMLD DSSDPILTTI RRIGLFNSSA DRVKVIFHPE
FLSSTSPLLP VDYEEFVRGC HLGVFPSYYE PWGYTPAECT VMGIPSISTN LSGFGCFMEE
HIADPSAYGI YILDRRFRSL DDSCSQLTSF LYSFCQQSRR QRIIQRNRTE RLSDLLDWKY
LGRYYMSARH MALSKAFPEH FTYEPNEADA AQGYRYPRPA SVPPSPSLSR HSSPHQSEDE
EDPRNGPLEE DGERYDEDEE AAKDRRNIRA PEWPRRASCT SSTSGSKRNS VDTATSSSLS
TPSEPLSPTS SLGEERN
//