GYS1_RABIT
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 03-AUG-2022, entry version 137.
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};
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, 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 PHOSPHORYLATION AT SER-641, MUTAGENESIS OF SER-641 AND SER-645, CATALYTIC
RP ACTIVITY, AND FUNCTION.
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: Transfers the glycosyl residue from UDP-Glc to the non-
CC reducing end of 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 -!- 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 -!- SUBUNIT: Interacts with GYG1. {ECO:0000250}.
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}.
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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 GeneID; 100008660; -.
DR KEGG; ocu:100008660; -.
DR CTD; 2997; -.
DR eggNOG; KOG3742; Eukaryota.
DR InParanoid; P13834; -.
DR OrthoDB; 264593at2759; -.
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; ISS:UniProtKB.
DR GO; GO:0005978; P:glycogen biosynthetic process; 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; 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-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250"
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 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
