ID GYS1_RABIT Reviewed; 735 AA. AC P13834; O18817; DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 4. DT 24-JAN-2024, entry version 142. DE RecName: Full=Glycogen [starch] synthase, muscle {ECO:0000250|UniProtKB:P13807}; DE EC=2.4.1.11 {ECO:0000269|PubMed:14593110, ECO:0000269|PubMed:16275910}; DE AltName: Full=Glycogen synthase 1 {ECO:0000250|UniProtKB:P13807}; GN Name=GYS1 {ECO:0000250|UniProtKB:P13807}; Synonyms=GYS; OS Oryctolagus cuniculus (Rabbit). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus. OX NCBI_TaxID=9986; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=New Zealand white; TISSUE=Skeletal muscle; RX PubMed=2509275; DOI=10.1096/fasebj.3.13.2509275; RA Zhang W.M., Browner M.F., Fletterick R.J., DePaoli-Roach A.A., Roach P.J.; RT "Primary structure of rabbit skeletal muscle glycogen synthase deduced from RT cDNA clones."; RL FASEB J. 3:2532-2536(1989). RN [2] RP PROTEIN SEQUENCE OF 2-30 AND 612-735. RX PubMed=3087361; DOI=10.1016/0006-291x(86)91244-1; RA Cohen P., Holmes C.F.B.; RT "Identification of the C-terminus of rabbit skeletal muscle glycogen RT synthase."; RL Biochem. Biophys. Res. Commun. 137:542-545(1986). RN [3] RP PROTEIN SEQUENCE OF 2-30, AND PHOSPHORYLATION AT SER-8; SER-641; SER-645 RP AND SER-649. RX PubMed=6772446; RA Rylatt D.B., Aitken A., Bilham T., Condon G.D., Embi N., Cohen P.; RT "Glycogen synthase from rabbit skeletal muscle. Amino acid sequence at the RT sites phosphorylated by glycogen synthase kinase-3, and extension of the N- RT terminal sequence containing the site phosphorylated by phosphorylase RT kinase."; RL Eur. J. Biochem. 107:529-537(1980). RN [4] RP PROTEIN SEQUENCE OF 2-16. RX PubMed=107043; DOI=10.1016/0014-5793(79)80153-2; RA Huang T.S., Krebs E.G.; RT "Effect of proteases on the structure and activity of rabbit skeletal RT muscle glycogen synthetase."; RL FEBS Lett. 98:66-70(1979). RN [5] RP PROTEIN SEQUENCE OF 2-15; 639-662 AND 694-735, AND PHOSPHORYLATION AT RP SER-8; SER-11; SER-641; SER-645; SER-649; SER-653; SER-657 AND SER-698. RX PubMed=2842154; DOI=10.1111/j.1432-1033.1988.tb14222.x; RA Poulter L., Ang S.G., Gibson B.W., Williams D.H., Holmes C.F., RA Caudwell F.B., Pitcher J., Cohen P.; RT "Analysis of the in vivo phosphorylation state of rabbit skeletal muscle RT glycogen synthase by fast-atom-bombardment mass spectrometry."; RL Eur. J. Biochem. 175:497-510(1988). RN [6] RP PROTEIN SEQUENCE OF 6-21; 31-44 AND 286-300. RX PubMed=3134350; DOI=10.1016/s0021-9258(18)38007-4; RA Mahrenholz A.M., Wang Y.H., Roach P.J.; RT "Catalytic site of rabbit glycogen synthase isozymes. Identification of an RT active site lysine close to the amino terminus of the subunit."; RL J. Biol. Chem. 263:10561-10567(1988). RN [7] RP PROTEIN SEQUENCE OF 665-683. RX PubMed=2117608; DOI=10.1016/s0021-9258(18)77295-5; RA Flotow H., Graves P.R., Wang A.Q., Fiol C.J., Roeske R.W., Roach P.J.; RT "Phosphate groups as substrate determinants for casein kinase I action."; RL J. Biol. Chem. 265:14264-14269(1990). RN [8] RP PARTIAL PROTEIN SEQUENCE. RX PubMed=3928373; DOI=10.1111/j.1432-1033.1985.tb09066.x; RA Kuret J., Woodgett J.R., Cohen P.; RT "Multisite phosphorylation of glycogen synthase from rabbit skeletal RT muscle. Identification of the sites phosphorylated by casein kinase-I."; RL Eur. J. Biochem. 151:39-48(1985). RN [9] RP PROTEIN SEQUENCE OF 665-683. RX PubMed=3137939; DOI=10.1016/s0006-291x(88)81048-9; RA Mahrenholz A.M., Votaw P., Roach P.J., Depaoli-Roach A.A., Zioncheck T.F., RA Harrison M.L., Geahlen R.L.; RT "Phosphorylation of glycogen synthase by a bovine thymus protein-tyrosine RT kinase, p40."; RL Biochem. Biophys. Res. Commun. 155:52-58(1988). RN [10] RP PHOSPHORYLATION AT SER-641; SER-645; SER-649; SER-653 AND SER-657. RX PubMed=2820993; DOI=10.1016/s0021-9258(18)47901-x; RA Fiol C.J., Mahrenholz A.M., Wang Y., Roeske R.W., Roach P.J.; RT "Formation of protein kinase recognition sites by covalent modification of RT the substrate. Molecular mechanism for the synergistic action of casein RT kinase II and glycogen synthase kinase 3."; RL J. Biol. Chem. 262:14042-14048(1987). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, PHOSPHORYLATION AT SER-641, ACTIVITY RP REGULATION, AND MUTAGENESIS OF SER-641. RX PubMed=14593110; DOI=10.1074/jbc.m301769200; RA Skurat A.V., Dietrich A.D.; RT "Phosphorylation of Ser640 in muscle glycogen synthase by DYRK family RT protein kinases."; RL J. Biol. Chem. 279:2490-2498(2004). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY, PHOSPHORYLATION RP AT SER-641, AND MUTAGENESIS OF SER-641 AND SER-645. RX PubMed=16275910; DOI=10.1073/pnas.0508481102; RA Wilson W.A., Skurat A.V., Probst B., de Paoli-Roach A., Roach P.J., RA Rutter J.; RT "Control of mammalian glycogen synthase by PAS kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 102:16596-16601(2005). 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:14593110, CC ECO:0000269|PubMed:16275910}. 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:14593110, ECO:0000269|PubMed:16275910}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18550; CC Evidence={ECO:0000269|PubMed:14593110, ECO:0000269|PubMed:16275910}; 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. CC {ECO:0000269|PubMed:14593110}. CC -!- PATHWAY: Glycan biosynthesis; glycogen biosynthesis. CC {ECO:0000269|PubMed:14593110, ECO:0000269|PubMed:16275910}. 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:0000250|UniProtKB:P13807}. CC -!- PTM: Phosphorylation at Ser-8 is required for modification of Ser-11 by CC casein kinase I. {ECO:0000269|PubMed:2842154, CC ECO:0000269|PubMed:6772446}. CC -!- PTM: Phosphorylated at Ser-641 by PASK, leading to inactivation; CC phosphorylation by PASK is inhibited by glycogen. Dephosphorylation at CC Ser-641 and Ser-645 by PP1 activates the enzyme (By similarity). CC Phosphorylation at Ser-8 by AMPK inactivates the enzyme activity (By CC similarity). Phosphorylated at Ser-641 by DYRK2, leading to CC inactivation. Primed phosphorylation at Ser-657 (site 5) by CSNK2A1 and CC CSNK2A2 is required for inhibitory phosphorylation at Ser-641 (site CC 3a), Ser-645 (site 3b), Ser-649 (site 3c) and Ser-653 (site 4) by GSK3A CC and GSK3B. {ECO:0000250, ECO:0000269|PubMed:14593110, CC ECO:0000269|PubMed:2820993, ECO:0000269|PubMed:2842154, CC ECO:0000269|PubMed:6772446}. CC -!- SIMILARITY: Belongs to the glycosyltransferase 3 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF017114; AAB69872.1; -; mRNA. DR PIR; A33369; A33369. DR RefSeq; NP_001075492.1; NM_001082023.1. DR RefSeq; XP_017195288.1; XM_017339799.1. DR AlphaFoldDB; P13834; -. DR SMR; P13834; -. DR BioGRID; 1171683; 4. DR CORUM; P13834; -. DR IntAct; P13834; 4. DR MINT; P13834; -. DR STRING; 9986.ENSOCUP00000000015; -. DR CAZy; GT3; Glycosyltransferase Family 3. DR iPTMnet; P13834; -. DR PaxDb; 9986-ENSOCUP00000000015; -. DR GeneID; 100008660; -. DR KEGG; ocu:100008660; -. DR CTD; 2997; -. DR eggNOG; KOG3742; Eukaryota. DR InParanoid; P13834; -. DR OrthoDB; 9432at2759; -. DR UniPathway; UPA00164; -. DR Proteomes; UP000001811; Unplaced. DR GO; GO:0098723; C:skeletal muscle myofibril; IDA:CAFA. DR GO; GO:0004373; F:glycogen (starch) synthase activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0005978; P:glycogen biosynthetic process; IDA:UniProtKB. 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 Allosteric enzyme; Direct protein sequencing; Glycogen biosynthesis; KW Glycosyltransferase; Phosphoprotein; Reference proteome; Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:107043, FT ECO:0000269|PubMed:2842154, ECO:0000269|PubMed:3087361, FT ECO:0000269|PubMed:6772446" FT CHAIN 2..735 FT /note="Glycogen [starch] synthase, muscle" FT /id="PRO_0000194767" FT REGION 629..735 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 663..677 FT /note="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..728 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:0000250|UniProtKB:P13807" FT BINDING 205 FT /ligand="UDP-alpha-D-glucose" FT /ligand_id="ChEBI:CHEBI:58885" FT /evidence="ECO:0000250|UniProtKB:P13807" FT BINDING 211 FT /ligand="UDP-alpha-D-glucose" FT /ligand_id="ChEBI:CHEBI:58885" FT /evidence="ECO:0000250|UniProtKB:P13807" 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:0000250|UniProtKB:P13807" 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:0000250|UniProtKB:P13807" 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:0000250|UniProtKB:P13807" 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:0000250|UniProtKB:P13807" 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:0000250|UniProtKB:P13807" FT BINDING 331 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:P13807" FT BINDING 331 FT /ligand="UDP-alpha-D-glucose" FT /ligand_id="ChEBI:CHEBI:58885" FT /evidence="ECO:0000250|UniProtKB:P13807" 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:0000250|UniProtKB:P13807" FT BINDING 510 FT /ligand="UDP-alpha-D-glucose" FT /ligand_id="ChEBI:CHEBI:58885" FT /evidence="ECO:0000250|UniProtKB:P13807" FT BINDING 512 FT /ligand="UDP-alpha-D-glucose" FT /ligand_id="ChEBI:CHEBI:58885" FT /evidence="ECO:0000250|UniProtKB:P13807" FT BINDING 513 FT /ligand="UDP-alpha-D-glucose" FT /ligand_id="ChEBI:CHEBI:58885" FT /evidence="ECO:0000250|UniProtKB:P13807" FT BINDING 515 FT /ligand="UDP" FT /ligand_id="ChEBI:CHEBI:58223" FT /evidence="ECO:0000250|UniProtKB:P13807" 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:0000250|UniProtKB:P13807" 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:0000250|UniProtKB:P13807" FT MOD_RES 8 FT /note="Phosphoserine; by AMPK and PKA" FT /evidence="ECO:0000269|PubMed:2842154, FT ECO:0000269|PubMed:6772446" FT MOD_RES 11 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:2842154, FT ECO:0000269|PubMed:3928373" FT MOD_RES 412 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P13807" FT MOD_RES 641 FT /note="Phosphoserine; by DYRK2, GSK3-alpha, GSK3-beta and FT PASK" FT /evidence="ECO:0000269|PubMed:14593110, FT ECO:0000269|PubMed:16275910, ECO:0000269|PubMed:2820993, FT ECO:0000269|PubMed:2842154, ECO:0000269|PubMed:6772446" FT MOD_RES 645 FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta" FT /evidence="ECO:0000269|PubMed:2820993, FT ECO:0000269|PubMed:2842154, ECO:0000269|PubMed:6772446" FT MOD_RES 649 FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta" FT /evidence="ECO:0000269|PubMed:2820993, FT ECO:0000269|PubMed:2842154, ECO:0000269|PubMed:6772446" FT MOD_RES 652 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:A2RRU1" FT MOD_RES 653 FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta" FT /evidence="ECO:0000269|PubMed:2820993, FT ECO:0000269|PubMed:2842154" FT MOD_RES 657 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:2820993, FT ECO:0000269|PubMed:2842154" FT MOD_RES 698 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:2842154, FT ECO:0000269|PubMed:3928373" FT MOD_RES 700 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P13807" FT MOD_RES 709 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1E4" FT MOD_RES 711 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P13807" FT MOD_RES 719 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1E4" FT MOD_RES 725 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P13807" FT MOD_RES 729 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P13807" FT MUTAGEN 641 FT /note="S->A: Loss of an inhibitory phosphorylation site. FT Abolishes phosphorylation by DYRK2.Abolishes PASK-mediated FT phosphorylation." FT /evidence="ECO:0000269|PubMed:14593110, FT ECO:0000269|PubMed:16275910" FT MUTAGEN 645 FT /note="S->A: Does not affect PASK-mediated FT phosphorylation." FT /evidence="ECO:0000269|PubMed:16275910" FT CONFLICT 692 FT /note="E -> Q (in Ref. 2; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 726 FT /note="P -> S (in Ref. 2; AA sequence and 5; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 728 FT /note="S -> P (in Ref. 2; AA sequence and 5; AA sequence)" FT /evidence="ECO:0000305" SQ SEQUENCE 735 AA; 83601 MW; 53ABE9DBE769ADBC CRC64; MPLSRTLSVS SLPGLEDWED EFDLENSVLF EVAWEVANKV GGIYTVLQTK AKVTGDEWGD NYFLVGPYTE QGVRTQVELL EPPTPALKRT LDSMNSKGCK VYFGRWLIEG GPLVVLLDVG ASAWALERWK GELWDTCNIG VPWYDREAND AVLFGFLTTW FLGEFLAQNE EKPHVVAHFH EWLAGIGLCL 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 MALAKAFPDH FTYEPHEADA TQGYRYPRPA SVPPSPSLSR HSSPHQSEDE EEPRDGLPEE DGERYDEDEE AAKDRRNIRA PEWPRRASCT SSSGGSKRSN SVDTSSLSTP SEPLSPASSL GEERN //