ID GYS2_RAT Reviewed; 704 AA.
AC P17625; Q99MF8;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 2.
DT 27-MAR-2024, entry version 129.
DE RecName: Full=Glycogen [starch] synthase, liver {ECO:0000305|PubMed:2110561};
DE EC=2.4.1.11 {ECO:0000269|PubMed:1731614};
DE AltName: Full=Glycogen synthase 2 {ECO:0000312|RGD:2773};
GN Name=Gys2 {ECO:0000312|RGD:2773};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2110561; DOI=10.1016/s0021-9258(19)39007-6;
RA Bai G., Zhang Z., Werner R., Nuttall F.Q., Tan A.W.H., Lee E.Y.C.;
RT "The primary structure of rat liver glycogen synthase deduced by cDNA
RT cloning. Absence of phosphorylation sites 1a and 1b.";
RL J. Biol. Chem. 265:7843-7848(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Liver;
RA Ferrer J.C., Baque S., Guinovart J.J.;
RT "Glucose-regulated localization of liver glycogen synthase at the
RT hepatocyte periphery.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, PATHWAY, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=1731614; DOI=10.1016/0003-9861(92)90019-s;
RA Westphal S.A., Nuttall F.Q.;
RT "Comparative characterization of human and rat liver glycogen synthase.";
RL Arch. Biochem. Biophys. 292:479-486(1992).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8; SER-11 AND SER-627, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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:1731614}.
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:1731614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18550;
CC Evidence={ECO:0000269|PubMed:1731614};
CC -!- ACTIVITY REGULATION: Allosteric activation by glucose-6-phosphate
CC (PubMed:1731614). Phosphorylation reduces the activity towards UDP-
CC glucose (PubMed:1731614). When in the non-phosphorylated state,
CC glycogen synthase does not require glucose-6-phosphate as an allosteric
CC activator; when phosphorylated it does (PubMed:1731614).
CC {ECO:0000269|PubMed:1731614}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.4 mM for UDP-alpha-D-glucose (UDPG) (in the absence of glucose-
CC 6-phosphate) (poorly or non-phosphorylated state)
CC {ECO:0000269|PubMed:1731614};
CC KM=1.0 mM for UDP-alpha-D-glucose (UDPG) (in the presence of 50 uM
CC glucose-6-phosphate) (poorly or non-phosphorylated state)
CC {ECO:0000269|PubMed:1731614};
CC KM=0.2 mM for UDP-alpha-D-glucose (UDPG) (in the presence of 7.2 mM
CC glucose-6-phosphate) (poorly or non-phosphorylated state)
CC {ECO:0000269|PubMed:1731614};
CC KM=32.0 mM for UDP-alpha-D-glucose (UDPG) (in the absence of glucose-
CC 6-phosphate) (most phosphorylated state)
CC {ECO:0000269|PubMed:1731614};
CC KM=17 mM for UDP-alpha-D-glucose (UDPG) (in the presence of 70 uM of
CC glucose-6-phosphate) (most phosphorylated state)
CC {ECO:0000269|PubMed:1731614};
CC KM=11.0 mM for UDP-alpha-D-glucose (UDPG) (in the presence of 200 uM
CC of glucose-6-phosphate) (most phosphorylated state)
CC {ECO:0000269|PubMed:1731614};
CC KM=0.4 mM for UDP-alpha-D-glucose (UDPG) (in the presence of 7.2 mM
CC glucose-6-phosphate) (most phosphorylated state)
CC {ECO:0000269|PubMed:1731614};
CC pH dependence:
CC Optimum pH is 7.5-8.5 (at 25 degrees Celsius) (non-phosphorylated
CC state). Optimum pH is 8.5 (at 25 degrees Celsius) (most
CC phosphorylated state). {ECO:0000269|PubMed:1731614};
CC Temperature dependence:
CC Optimum temperature is 30-40 degrees Celsius.
CC {ECO:0000269|PubMed:1731614};
CC -!- PATHWAY: Glycan biosynthesis; glycogen biosynthesis.
CC {ECO:0000269|PubMed:1731614}.
CC -!- SUBUNIT: Part of the glycogen synthase (GS)-glycogenin complex, a
CC heterooctamer composed of a tetramer of GS and 2 dimers of glycogenin,
CC where each GS protomer binds to one glycogenin subunit (via glycogenin
CC C-terminus); the GS tetramer may dissociate from glycogenin dimers to
CC continue glycogen polymerization on its own (By similarity). May also
CC form a heterooctamer complex with GYG1 (via GYG1 C-terminus) (By
CC similarity). {ECO:0000250|UniProtKB:P13807,
CC ECO:0000250|UniProtKB:Q8VCB3}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in liver (at protein level).
CC {ECO:0000269|PubMed:1731614}.
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 -!- SIMILARITY: Belongs to the glycosyltransferase 3 family. {ECO:0000305}.
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DR EMBL; J05446; AAA41255.1; -; mRNA.
DR EMBL; AF346902; AAK16592.1; -; mRNA.
DR PIR; A35362; A35362.
DR AlphaFoldDB; P17625; -.
DR SMR; P17625; -.
DR IntAct; P17625; 1.
DR STRING; 10116.ENSRNOP00000074743; -.
DR CAZy; GT3; Glycosyltransferase Family 3.
DR iPTMnet; P17625; -.
DR PhosphoSitePlus; P17625; -.
DR PaxDb; 10116-ENSRNOP00000059573; -.
DR UCSC; RGD:2773; rat.
DR AGR; RGD:2773; -.
DR RGD; 2773; Gys2.
DR eggNOG; KOG3742; Eukaryota.
DR InParanoid; P17625; -.
DR PhylomeDB; P17625; -.
DR UniPathway; UPA00164; -.
DR PRO; PR:P17625; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0030864; C:cortical actin cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005536; F:glucose binding; IDA:RGD.
DR GO; GO:0004373; F:glycogen (starch) synthase activity; IDA:UniProtKB.
DR GO; GO:0005978; P:glycogen biosynthetic process; IDA:UniProtKB.
DR GO; GO:0005977; P:glycogen metabolic process; IDA:RGD.
DR GO; GO:0009749; P:response to glucose; 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:SF1; GLYCOGEN [STARCH] SYNTHASE, LIVER; 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; Glycogen biosynthesis; Glycosyltransferase;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..704
FT /note="Glycogen [starch] synthase, liver"
FT /id="PRO_0000194769"
FT REGION 620..704
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 659..673
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 690..704
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 40
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"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 627
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 641
FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:P13834"
FT MOD_RES 645
FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:P13834"
FT MOD_RES 649
FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:P13834"
FT MOD_RES 653
FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:P13834"
FT MOD_RES 657
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P13834"
FT MOD_RES 684
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54840"
FT CONFLICT 82
FT /note="E -> R (in Ref. 1; AAA41255)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="H -> D (in Ref. 1; AAA41255)"
FT /evidence="ECO:0000305"
FT CONFLICT 555..557
FT /note="RRF -> SV (in Ref. 1; AAA41255)"
FT /evidence="ECO:0000305"
FT CONFLICT 622
FT /note="H -> Y (in Ref. 1; AAA41255)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 704 AA; 80734 MW; 926BD3057470A1D4 CRC64;
MLRGRSLSVT SLGGLPAWEA ERLPVEDLLL FEVSWEVTNK VGGICTVIQS KAKTTANEWG
ENYFLIGPYF EHNVKTQVEP CEPANDAVRK AVDAMNKHGC QVHFGRWLIE GSPYVVLFDI
SSSVWNLDRW KGDFWEACGV GIPHDDREAN DMLIFGSLTA WFLKEVTDHA DGKHVIAQFH
EWQAGTGLIL SRARKLPIAT IFTTHATLLG RYLCAANIDF YNQLDKFNID KEAGERQIYH
RYCMERASVH CAHVFTTVSE ITAIEADHML KRKPDVVTPN GLNVKKFSAV HEFQNLHATY
KARIQDFVRG HFYGHLDFDL EKTLFLFIAG RYEFSNKGAD IFLESLSRLN FLLRMHKSNV
TVVVFFIMPA KTNNFNVETL KGQAVRKQLW DTVHCMKEKF GKKLYDGLLR GEIPDMNSIL
DRDDLTIMKR AIFSTQRHSL PPVTTHNMID DSTDPILSTI RRIGLFNNRT DRVKVILHPE
FLSSTSPLLP MDYEEFVRGC HLGVFPSYYE PWGYTPAECT VMGIPSVTTN LSGFGCFMQE
HVADPTAYGI YIVDRRFRSP DDSCNQLTQF LYGFCKQSRR QRIIQRNRTE RLSDLLDWRY
LGRYYQHARH LTLSRAFPDK FHLEPTSPPT TDGFKYPRPS SVPPSPSGSQ TSSPQSSDVE
NEGDEDERYD EEEEAERDRL NIKSPFSLNH IPKGKKKLHG EYKN
//
