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 12-OCT-2022, entry version 181. 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., 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., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., 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., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA 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 project: RT 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., 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). 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 = [(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 -!- 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 (By CC 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 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 -!- DISEASE: Glycogen storage disease 0 (GSD0) [MIM:240600]: A metabolic CC disorder characterized by fasting hypoglycemia presenting in infancy or CC early childhood, high blood ketones and low alanine and lactate CC concentrations. Although feeding relieves symptoms, it often results in CC postprandial hyperglycemia and hyperlactatemia. CC {ECO:0000269|PubMed:9691087}. 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}. 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; 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 AlphaFoldDB; P54840; -. DR SMR; P54840; -. DR BioGRID; 109253; 9. DR IntAct; P54840; 7. DR MINT; P54840; -. DR STRING; 9606.ENSP00000261195; -. DR BindingDB; P54840; -. DR ChEMBL; CHEMBL4523243; -. DR DrugCentral; P54840; -. DR CAZy; GT3; Glycosyltransferase Family 3. DR GlyGen; P54840; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P54840; -. DR PhosphoSitePlus; P54840; -. DR BioMuta; GYS2; -. DR DMDM; 288558811; -. DR EPD; P54840; -. DR jPOST; P54840; -. DR MassIVE; P54840; -. DR MaxQB; P54840; -. DR PaxDb; P54840; -. DR PeptideAtlas; P54840; -. DR PRIDE; P54840; -. DR ProteomicsDB; 56737; -. DR Antibodypedia; 24071; 109 antibodies from 24 providers. DR DNASU; 2998; -. DR Ensembl; ENST00000261195.3; ENSP00000261195.2; ENSG00000111713.3. DR GeneID; 2998; -. DR KEGG; hsa:2998; -. DR MANE-Select; ENST00000261195.3; ENSP00000261195.2; NM_021957.4; NP_068776.2. DR UCSC; uc001rfb.3; human. DR CTD; 2998; -. DR DisGeNET; 2998; -. DR GeneCards; GYS2; -. DR HGNC; HGNC:4707; GYS2. DR HPA; ENSG00000111713; Tissue enriched (liver). 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 VEuPathDB; HostDB:ENSG00000111713; -. DR eggNOG; KOG3742; Eukaryota. DR GeneTree; ENSGT00390000018612; -. DR HOGENOM; CLU_015910_1_0_1; -. DR InParanoid; P54840; -. DR OMA; WEACGVG; -. DR OrthoDB; 264593at2759; -. DR PhylomeDB; P54840; -. DR TreeFam; TF300306; -. DR PathwayCommons; P54840; -. 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 SignaLink; P54840; -. DR SIGNOR; P54840; -. DR UniPathway; UPA00164; -. DR BioGRID-ORCS; 2998; 10 hits in 1067 CRISPR screens. DR ChiTaRS; GYS2; human. DR GenomeRNAi; 2998; -. DR Pharos; P54840; Tbio. DR PRO; PR:P54840; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P54840; protein. DR Bgee; ENSG00000111713; Expressed in right lobe of liver and 39 other tissues. 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: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 InterPro; IPR008631; Glycogen_synth. DR PANTHER; PTHR10176; PTHR10176; 1. DR Pfam; PF05693; Glycogen_syn; 1. PE 1: Evidence at protein level; KW Allosteric enzyme; Disease variant; Glycogen biosynthesis; KW Glycogen storage disease; Glycosyltransferase; Phosphoprotein; KW Reference proteome; Transferase. FT CHAIN 1..703 FT /note="Glycogen [starch] synthase, liver" FT /id="PRO_0000194768" FT REGION 628..703 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 658..672 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 689..703 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 40 FT /ligand="UDP-alpha-D-glucose" FT /ligand_id="ChEBI:CHEBI:58885" FT /evidence="ECO:0000250" FT MOD_RES 8 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000250|UniProtKB:P17625" FT MOD_RES 11 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8VCB3" FT MOD_RES 627 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 641 FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta" FT /evidence="ECO:0000250" FT MOD_RES 645 FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta" FT /evidence="ECO:0000250" FT MOD_RES 649 FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta" FT /evidence="ECO:0000250" FT MOD_RES 653 FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta" FT /evidence="ECO:0000250" FT MOD_RES 657 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000250" FT MOD_RES 683 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT VARIANT 39 FT /note="N -> S (in GSD0; dbSNP:rs121918423)" FT /evidence="ECO:0000269|PubMed:9691087" FT /id="VAR_007860" FT VARIANT 193 FT /note="A -> T (in dbSNP:rs16924038)" FT /id="VAR_055885" FT VARIANT 339 FT /note="A -> P (in GSD0; dbSNP:rs121918421)" FT /evidence="ECO:0000269|PubMed:9691087" FT /id="VAR_007861" FT VARIANT 363 FT /note="M -> V (in dbSNP:rs2306180)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:8203908, ECO:0000269|PubMed:9691087, FT ECO:0000269|Ref.3" FT /id="VAR_058848" FT VARIANT 415 FT /note="D -> E (in dbSNP:rs16924002)" FT /id="VAR_055886" FT VARIANT 446 FT /note="H -> D (in GSD0; dbSNP:rs121918425)" FT /evidence="ECO:0000269|PubMed:9691087" FT /id="VAR_007862" FT VARIANT 479 FT /note="P -> Q (in GSD0; dbSNP:rs121918420)" FT /evidence="ECO:0000269|PubMed:9691087" FT /id="VAR_007863" FT VARIANT 483 FT /note="S -> P (in GSD0; dbSNP:rs121918424)" FT /evidence="ECO:0000269|PubMed:9691087" FT /id="VAR_007864" FT VARIANT 491 FT /note="M -> R (in GSD0; dbSNP:rs121918422)" FT /evidence="ECO:0000269|PubMed:9691087" FT /id="VAR_007865" FT CONFLICT 97 FT /note="K -> M (in Ref. 3; BAA06154)" FT /evidence="ECO:0000305" FT CONFLICT 178 FT /note="Q -> R (in Ref. 3; BAA06154)" FT /evidence="ECO:0000305" FT CONFLICT 186 FT /note="I -> V (in Ref. 3; BAA06154)" FT /evidence="ECO:0000305" FT CONFLICT 335..336 FT /note="SN -> FKT (in Ref. 3; BAA06154)" FT /evidence="ECO:0000305" FT CONFLICT 344 FT /note="E -> D (in Ref. 3; BAA06154)" FT /evidence="ECO:0000305" FT CONFLICT 441 FT /note="P -> A (in Ref. 3; BAA06154)" FT /evidence="ECO:0000305" FT CONFLICT 576..577 FT /note="KQ -> NM (in Ref. 3; BAA06154)" FT /evidence="ECO:0000305" FT CONFLICT 583 FT /note="I -> F (in Ref. 3; BAA06154)" FT /evidence="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 //