GenomeNet

Database: UniProt/SWISS-PROT
Entry: GYS2_HUMAN
LinkDB: GYS2_HUMAN
Original site: 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   13-FEB-2019, entry version 163.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA   Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA   Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA   Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA   Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA   Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA   Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA   Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA   Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA   Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA   Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA   Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA   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.,
RA   Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA   Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA   Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA   Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA   Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA   Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA   Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA   Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA   Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA   Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA   Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA   Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA   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.,
RA   Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA   Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA   Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA   Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA   Kucherlapati R., Weinstock G., 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
RT   project: 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.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver 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 =
CC         [(1->4)-alpha-D-glucosyl](n+1) + H(+) + UDP;
CC         Xref=Rhea:RHEA:18549, Rhea:RHEA-COMP:9584, Rhea:RHEA-COMP:9587,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15444, ChEBI:CHEBI:58223,
CC         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
CC       the non-phosphorylated state, glycogen synthase does not require
CC       glucose-6-phosphate as an allosteric activator; when
CC       phosphorylated it does (By 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
CC       CSNK2A2 is required for inhibitory phosphorylation at Ser-641
CC       (site 3a), Ser-645 (site 3b), Ser-649 (site 3c) and Ser-653 (site
CC       4) by GSK3A an GSK3B. Dephosphorylation at Ser-641 and Ser-645 by
CC       PP1 activates the enzyme (By similarity). Phosphorylation at Ser-8
CC       is not required for interaction with GYG1 (By similarity).
CC       Interaction with GYG1 does not regulate the phosphorylation at
CC       Ser-8 and Ser-641 (By similarity). {ECO:0000250|UniProtKB:P13807,
CC       ECO:0000250|UniProtKB:P13834, ECO:0000250|UniProtKB:Q8VCB3}.
CC   -!- DISEASE: Glycogen storage disease 0 (GSD0) [MIM:240600]: A
CC       metabolic disorder characterized by fasting hypoglycemia
CC       presenting in infancy or early childhood, high blood ketones and
CC       low alanine and lactate concentrations. Although feeding relieves
CC       symptoms, it often results in postprandial hyperglycemia and
CC       hyperlactatemia. {ECO:0000269|PubMed:9691087}. Note=The disease is
CC       caused by mutations affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the glycosyltransferase 3 family.
CC       {ECO:0000305}.
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   UniGene; Hs.82614; -.
DR   ProteinModelPortal; P54840; -.
DR   SMR; P54840; -.
DR   BioGrid; 109253; 6.
DR   IntAct; P54840; 4.
DR   MINT; P54840; -.
DR   STRING; 9606.ENSP00000261195; -.
DR   CAZy; GT3; Glycosyltransferase Family 3.
DR   iPTMnet; P54840; -.
DR   PhosphoSitePlus; P54840; -.
DR   BioMuta; GYS2; -.
DR   DMDM; 288558811; -.
DR   EPD; P54840; -.
DR   jPOST; P54840; -.
DR   MaxQB; P54840; -.
DR   PaxDb; P54840; -.
DR   PeptideAtlas; P54840; -.
DR   PRIDE; P54840; -.
DR   ProteomicsDB; 56737; -.
DR   DNASU; 2998; -.
DR   Ensembl; ENST00000261195; ENSP00000261195; ENSG00000111713.
DR   GeneID; 2998; -.
DR   KEGG; hsa:2998; -.
DR   UCSC; uc001rfb.3; human.
DR   CTD; 2998; -.
DR   DisGeNET; 2998; -.
DR   EuPathDB; HostDB:ENSG00000111713.2; -.
DR   GeneCards; GYS2; -.
DR   H-InvDB; HIX0036868; -.
DR   HGNC; HGNC:4707; GYS2.
DR   HPA; HPA039482; -.
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   eggNOG; KOG3742; Eukaryota.
DR   eggNOG; COG0438; LUCA.
DR   GeneTree; ENSGT00390000018612; -.
DR   HOGENOM; HOG000160890; -.
DR   HOVERGEN; HBG001960; -.
DR   InParanoid; P54840; -.
DR   KO; K00693; -.
DR   OMA; TADEWGD; -.
DR   OrthoDB; 264593at2759; -.
DR   PhylomeDB; P54840; -.
DR   TreeFam; TF300306; -.
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   UniPathway; UPA00164; -.
DR   ChiTaRS; GYS2; human.
DR   GenomeRNAi; 2998; -.
DR   PRO; PR:P54840; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   Bgee; ENSG00000111713; Expressed in 65 organ(s), highest expression level in liver.
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:0042803; F:protein homodimerization activity; TAS:UniProtKB.
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   CDD; cd03793; GT1_Glycogen_synthase_GSY2_lik; 1.
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; Complete proteome; Disease mutation;
KW   Glycogen biosynthesis; Glycogen storage disease; Glycosyltransferase;
KW   Phosphoprotein; Polymorphism; Reference proteome; Transferase.
FT   CHAIN         1    703       Glycogen [starch] synthase, liver.
FT                                /FTId=PRO_0000194768.
FT   BINDING      40     40       UDP-glucose. {ECO:0000250}.
FT   MOD_RES       8      8       Phosphoserine; by PKA.
FT                                {ECO:0000250|UniProtKB:P17625}.
FT   MOD_RES      11     11       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q8VCB3}.
FT   MOD_RES     627    627       Phosphoserine.
FT                                {ECO:0000244|PubMed:24275569}.
FT   MOD_RES     641    641       Phosphoserine; by GSK3-alpha and GSK3-
FT                                beta. {ECO:0000250}.
FT   MOD_RES     645    645       Phosphoserine; by GSK3-alpha and GSK3-
FT                                beta. {ECO:0000250}.
FT   MOD_RES     649    649       Phosphoserine; by GSK3-alpha and GSK3-
FT                                beta. {ECO:0000250}.
FT   MOD_RES     653    653       Phosphoserine; by GSK3-alpha and GSK3-
FT                                beta. {ECO:0000250}.
FT   MOD_RES     657    657       Phosphoserine; by CK2. {ECO:0000250}.
FT   MOD_RES     683    683       Phosphoserine.
FT                                {ECO:0000244|PubMed:24275569}.
FT   VARIANT      39     39       N -> S (in GSD0; dbSNP:rs121918423).
FT                                {ECO:0000269|PubMed:9691087}.
FT                                /FTId=VAR_007860.
FT   VARIANT     193    193       A -> T (in dbSNP:rs16924038).
FT                                /FTId=VAR_055885.
FT   VARIANT     339    339       A -> P (in GSD0; dbSNP:rs121918421).
FT                                {ECO:0000269|PubMed:9691087}.
FT                                /FTId=VAR_007861.
FT   VARIANT     363    363       M -> V (in dbSNP:rs2306180).
FT                                {ECO:0000269|PubMed:15489334,
FT                                ECO:0000269|PubMed:8203908,
FT                                ECO:0000269|PubMed:9691087,
FT                                ECO:0000269|Ref.3}.
FT                                /FTId=VAR_058848.
FT   VARIANT     415    415       D -> E (in dbSNP:rs16924002).
FT                                /FTId=VAR_055886.
FT   VARIANT     446    446       H -> D (in GSD0; dbSNP:rs121918425).
FT                                {ECO:0000269|PubMed:9691087}.
FT                                /FTId=VAR_007862.
FT   VARIANT     479    479       P -> Q (in GSD0; dbSNP:rs121918420).
FT                                {ECO:0000269|PubMed:9691087}.
FT                                /FTId=VAR_007863.
FT   VARIANT     483    483       S -> P (in GSD0; dbSNP:rs121918424).
FT                                {ECO:0000269|PubMed:9691087}.
FT                                /FTId=VAR_007864.
FT   VARIANT     491    491       M -> R (in GSD0; dbSNP:rs121918422).
FT                                {ECO:0000269|PubMed:9691087}.
FT                                /FTId=VAR_007865.
FT   CONFLICT     97     97       K -> M (in Ref. 3; BAA06154).
FT                                {ECO:0000305}.
FT   CONFLICT    178    178       Q -> R (in Ref. 3; BAA06154).
FT                                {ECO:0000305}.
FT   CONFLICT    186    186       I -> V (in Ref. 3; BAA06154).
FT                                {ECO:0000305}.
FT   CONFLICT    335    336       SN -> FKT (in Ref. 3; BAA06154).
FT                                {ECO:0000305}.
FT   CONFLICT    344    344       E -> D (in Ref. 3; BAA06154).
FT                                {ECO:0000305}.
FT   CONFLICT    441    441       P -> A (in Ref. 3; BAA06154).
FT                                {ECO:0000305}.
FT   CONFLICT    576    577       KQ -> NM (in Ref. 3; BAA06154).
FT                                {ECO:0000305}.
FT   CONFLICT    583    583       I -> F (in Ref. 3; BAA06154).
FT                                {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
//
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