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Protein

Glycogen [starch] synthase, liver

Gene

GYS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transfers the glycosyl residue from UDP-Glc to the non-reducing end of alpha-1,4-glucan.

Catalytic activityi

UDP-alpha-D-glucose + ((1->4)-alpha-D-glucosyl)(n) = UDP + ((1->4)-alpha-D-glucosyl)(n+1).

Enzyme regulationi

Allosteric activation by glucose-6-phosphate. Phosphorylation reduces the activity towards UDP-glucose. When in the non-phosphorylated state, glycogen synthase does not require glucose-6-phosphate as an allosteric activator; when phosphorylated it does (By similarity).By similarity

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei40 – 401UDP-glucoseBy similarity

GO - Molecular functioni

  1. glycogen (starch) synthase activity Source: UniProtKB
  2. glycogen synthase activity, transferring glucose-1-phosphate Source: Reactome
  3. protein homodimerization activity Source: UniProtKB

GO - Biological processi

  1. carbohydrate metabolic process Source: Reactome
  2. generation of precursor metabolites and energy Source: ProtInc
  3. glucose metabolic process Source: Reactome
  4. glycogen biosynthetic process Source: UniProtKB
  5. pathogenesis Source: Reactome
  6. response to glucose Source: UniProtKB
  7. small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Glycosyltransferase, Transferase

Keywords - Biological processi

Glycogen biosynthesis

Enzyme and pathway databases

ReactomeiREACT_169208. Glycogen synthesis.
REACT_200783. Myoclonic epilepsy of Lafora.
UniPathwayiUPA00164.

Protein family/group databases

CAZyiGT3. Glycosyltransferase Family 3.

Names & Taxonomyi

Protein namesi
Recommended name:
Glycogen [starch] synthase, liver (EC:2.4.1.11)
Gene namesi
Name:GYS2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:4707. GYS2.

Subcellular locationi

GO - Cellular componenti

  1. cell cortex Source: UniProtKB
  2. cortical actin cytoskeleton Source: UniProtKB
  3. cytoplasm Source: UniProtKB
  4. cytoskeleton Source: UniProtKB
  5. cytosol Source: UniProtKB
  6. ectoplasm Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Glycogen storage disease 01 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA metabolic disorder characterized by fasting hypoglycemia presenting in infancy or early childhood, high blood ketones and low alanine and lactate concentrations. Although feeding relieves symptoms, it often results in postprandial hyperglycemia and hyperlactatemia.

See also OMIM:240600
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti39 – 391N → S in GSD0. 1 Publication
VAR_007860
Natural varianti339 – 3391A → P in GSD0. 1 Publication
VAR_007861
Natural varianti446 – 4461H → D in GSD0. 1 Publication
VAR_007862
Natural varianti479 – 4791P → Q in GSD0. 1 Publication
VAR_007863
Natural varianti483 – 4831S → P in GSD0. 1 Publication
VAR_007864
Natural varianti491 – 4911M → R in GSD0. 1 Publication
VAR_007865

Keywords - Diseasei

Disease mutation, Glycogen storage disease

Organism-specific databases

MIMi240600. phenotype.
Orphaneti2089. Glycogen storage disease due to hepatic glycogen synthase deficiency.
PharmGKBiPA29085.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 703703Glycogen [starch] synthase, liverPRO_0000194768Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei8 – 81Phosphoserine; by PKABy similarity
Modified residuei627 – 6271Phosphoserine1 Publication
Modified residuei641 – 6411Phosphoserine; by GSK3-alpha and GSK3-betaBy similarity
Modified residuei645 – 6451Phosphoserine; by GSK3-alpha and GSK3-betaBy similarity
Modified residuei649 – 6491Phosphoserine; by GSK3-alpha and GSK3-betaBy similarity
Modified residuei653 – 6531Phosphoserine; by GSK3-alpha and GSK3-betaBy similarity
Modified residuei657 – 6571Phosphoserine; by CK2By similarity
Modified residuei683 – 6831Phosphoserine1 Publication

Post-translational modificationi

Primed phosphorylation at Ser-657 (site 5) by CSNK2A1 and CSNK2A2 is required for inhibitory phosphorylation at Ser-641 (site 3a), Ser-645 (site 3b), Ser-649 (site 3c) and Ser-653 (site 4) by GSK3A an GSK3B. Dephosphorylation at Ser-641 and Ser-645 by PP1 activates the enzyme (By similarity). Phosphorylation at Ser-8 is not required for interaction with GYG1 (By similarity). Interaction with GYG1 does not regulate the phosphorylation at Ser-8 and Ser-641 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP54840.
PaxDbiP54840.
PRIDEiP54840.

PTM databases

PhosphoSiteiP54840.

Expressioni

Gene expression databases

BgeeiP54840.
CleanExiHS_GYS2.
GenevestigatoriP54840.

Organism-specific databases

HPAiHPA039482.

Interactioni

Subunit structurei

Interacts with GYG1 (via C-terminus); required for GYS2-mediated glycogen synthesis.By similarity

Protein-protein interaction databases

BioGridi109253. 7 interactions.
IntActiP54840. 3 interactions.
STRINGi9606.ENSP00000261195.

Structurei

3D structure databases

ProteinModelPortaliP54840.
SMRiP54840. Positions 26-619.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the glycosyltransferase 3 family.Curated

Phylogenomic databases

eggNOGiCOG0438.
GeneTreeiENSGT00390000018612.
HOGENOMiHOG000160890.
HOVERGENiHBG001960.
InParanoidiP54840.
KOiK00693.
OMAiIMKRAIY.
OrthoDBiEOG741Z1N.
PhylomeDBiP54840.
TreeFamiTF300306.

Family and domain databases

InterProiIPR008631. Glycogen_synth.
[Graphical view]
PANTHERiPTHR10176. PTHR10176. 1 hit.
PfamiPF05693. Glycogen_syn. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P54840-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLRGRSLSVT SLGGLPQWEV EELPVEELLL FEVAWEVTNK VGGIYTVIQT
60 70 80 90 100
KAKTTADEWG ENYFLIGPYF EHNMKTQVEQ CEPVNDAVRR AVDAMNKHGC
110 120 130 140 150
QVHFGRWLIE GSPYVVLFDI GYSAWNLDRW KGDLWEACSV GIPYHDREAN
160 170 180 190 200
DMLIFGSLTA WFLKEVTDHA DGKYVVAQFH EWQAGIGLIL SRARKLPIAT
210 220 230 240 250
IFTTHATLLG RYLCAANIDF YNHLDKFNID KEAGERQIYH RYCMERASVH
260 270 280 290 300
CAHVFTTVSE ITAIEAEHML KRKPDVVTPN GLNVKKFSAV HEFQNLHAMY
310 320 330 340 350
KARIQDFVRG HFYGHLDFDL EKTLFLFIAG RYEFSNKGAD IFLESLSRLN
360 370 380 390 400
FLLRMHKSDI TVMVFFIMPA KTNNFNVETL KGQAVRKQLW DVAHSVKEKF
410 420 430 440 450
GKKLYDALLR GEIPDLNDIL DRDDLTIMKR AIFSTQRQSL PPVTTHNMID
460 470 480 490 500
DSTDPILSTI RRIGLFNNRT DRVKVILHPE FLSSTSPLLP MDYEEFVRGC
510 520 530 540 550
HLGVFPSYYE PWGYTPAECT VMGIPSVTTN LSGFGCFMQE HVADPTAYGI
560 570 580 590 600
YIVDRRFRSP DDSCNQLTKF LYGFCKQSRR QRIIQRNRTE RLSDLLDWRY
610 620 630 640 650
LGRYYQHARH LTLSRAFPDK FHVELTSPPT TEGFKYPRPS SVPPSPSGSQ
660 670 680 690 700
ASSPQSSDVE DEVEDERYDE EEEAERDRLN IKSPFSLSHV PHGKKKLHGE

YKN
Length:703
Mass (Da):80,989
Last modified:February 9, 2010 - v2
Checksum:i718F000D6D00CA4A
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti97 – 971K → M in BAA06154 (Ref. 3) Curated
Sequence conflicti178 – 1781Q → R in BAA06154 (Ref. 3) Curated
Sequence conflicti186 – 1861I → V in BAA06154 (Ref. 3) Curated
Sequence conflicti335 – 3362SN → FKT in BAA06154 (Ref. 3) Curated
Sequence conflicti344 – 3441E → D in BAA06154 (Ref. 3) Curated
Sequence conflicti441 – 4411P → A in BAA06154 (Ref. 3) Curated
Sequence conflicti576 – 5772KQ → NM in BAA06154 (Ref. 3) Curated
Sequence conflicti583 – 5831I → F in BAA06154 (Ref. 3) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti39 – 391N → S in GSD0. 1 Publication
VAR_007860
Natural varianti193 – 1931A → T.
Corresponds to variant rs16924038 [ dbSNP | Ensembl ].
VAR_055885
Natural varianti339 – 3391A → P in GSD0. 1 Publication
VAR_007861
Natural varianti363 – 3631M → V.4 Publications
Corresponds to variant rs2306180 [ dbSNP | Ensembl ].
VAR_058848
Natural varianti415 – 4151D → E.
Corresponds to variant rs16924002 [ dbSNP | Ensembl ].
VAR_055886
Natural varianti446 – 4461H → D in GSD0. 1 Publication
VAR_007862
Natural varianti479 – 4791P → Q in GSD0. 1 Publication
VAR_007863
Natural varianti483 – 4831S → P in GSD0. 1 Publication
VAR_007864
Natural varianti491 – 4911M → R in GSD0. 1 Publication
VAR_007865

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S70004 mRNA. Translation: AAB30886.1.
AJ003087
, AJ003088, AJ003089, AJ003090, AJ003091, AJ003092, AJ003093, AJ003094, AJ003095, AJ003096, AJ003097, AJ003098, AJ003099, AJ003100, AJ003101, AJ003102 Genomic DNA. Translation: CAA05859.1.
D29685 mRNA. Translation: BAA06154.1.
AC006559 Genomic DNA. No translation available.
AC010197 Genomic DNA. No translation available.
AC022072 Genomic DNA. No translation available.
BC126310 mRNA. Translation: AAI26311.1.
BC126312 mRNA. Translation: AAI26313.1.
CCDSiCCDS8690.1.
PIRiS45686.
RefSeqiNP_068776.2. NM_021957.3.
XP_005253409.1. XM_005253352.1.
XP_006719125.1. XM_006719062.1.
UniGeneiHs.82614.

Genome annotation databases

EnsembliENST00000261195; ENSP00000261195; ENSG00000111713.
GeneIDi2998.
KEGGihsa:2998.
UCSCiuc001rfb.3. human.

Polymorphism databases

DMDMi288558811.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S70004 mRNA. Translation: AAB30886.1.
AJ003087
, AJ003088, AJ003089, AJ003090, AJ003091, AJ003092, AJ003093, AJ003094, AJ003095, AJ003096, AJ003097, AJ003098, AJ003099, AJ003100, AJ003101, AJ003102 Genomic DNA. Translation: CAA05859.1.
D29685 mRNA. Translation: BAA06154.1.
AC006559 Genomic DNA. No translation available.
AC010197 Genomic DNA. No translation available.
AC022072 Genomic DNA. No translation available.
BC126310 mRNA. Translation: AAI26311.1.
BC126312 mRNA. Translation: AAI26313.1.
CCDSiCCDS8690.1.
PIRiS45686.
RefSeqiNP_068776.2. NM_021957.3.
XP_005253409.1. XM_005253352.1.
XP_006719125.1. XM_006719062.1.
UniGeneiHs.82614.

3D structure databases

ProteinModelPortaliP54840.
SMRiP54840. Positions 26-619.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109253. 7 interactions.
IntActiP54840. 3 interactions.
STRINGi9606.ENSP00000261195.

Protein family/group databases

CAZyiGT3. Glycosyltransferase Family 3.

PTM databases

PhosphoSiteiP54840.

Polymorphism databases

DMDMi288558811.

Proteomic databases

MaxQBiP54840.
PaxDbiP54840.
PRIDEiP54840.

Protocols and materials databases

DNASUi2998.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261195; ENSP00000261195; ENSG00000111713.
GeneIDi2998.
KEGGihsa:2998.
UCSCiuc001rfb.3. human.

Organism-specific databases

CTDi2998.
GeneCardsiGC12M021689.
H-InvDBHIX0036868.
HGNCiHGNC:4707. GYS2.
HPAiHPA039482.
MIMi138571. gene.
240600. phenotype.
neXtProtiNX_P54840.
Orphaneti2089. Glycogen storage disease due to hepatic glycogen synthase deficiency.
PharmGKBiPA29085.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0438.
GeneTreeiENSGT00390000018612.
HOGENOMiHOG000160890.
HOVERGENiHBG001960.
InParanoidiP54840.
KOiK00693.
OMAiIMKRAIY.
OrthoDBiEOG741Z1N.
PhylomeDBiP54840.
TreeFamiTF300306.

Enzyme and pathway databases

UniPathwayiUPA00164.
ReactomeiREACT_169208. Glycogen synthesis.
REACT_200783. Myoclonic epilepsy of Lafora.

Miscellaneous databases

ChiTaRSiGYS2. human.
GenomeRNAii2998.
NextBioi11888.
PROiP54840.
SOURCEiSearch...

Gene expression databases

BgeeiP54840.
CleanExiHS_GYS2.
GenevestigatoriP54840.

Family and domain databases

InterProiIPR008631. Glycogen_synth.
[Graphical view]
PANTHERiPTHR10176. PTHR10176. 1 hit.
PfamiPF05693. Glycogen_syn. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Primary structure of human liver glycogen synthase deduced by cDNA cloning."
    Nuttall F.Q., Gannon M.C., Bai G., Lee E.Y.
    Arch. Biochem. Biophys. 311:443-449(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-363.
    Tissue: Liver.
  2. "Mutations in the liver glycogen synthase gene in children with hypoglycemia due to glycogen storage disease type 0."
    Orho M., Bosshard N.U., Buist N.R.M., Gitzelmann R., Aynsley-Green A., Blumel P., Gannon M.C., Nuttall F.Q., Groop L.C.
    J. Clin. Invest. 102:507-515(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GSD0 SER-39; PRO-339; VAL-363; ASP-446; GLN-479; PRO-483 AND ARG-491.
  3. "Human liver glycogen synthase cDNA."
    Nakabayashi H., Nakayama T.
    Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-363.
    Tissue: Liver.
  4. "The finished DNA sequence of human chromosome 12."
    Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
    , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
    Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-363.
  6. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-627 AND SER-683, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiGYS2_HUMAN
AccessioniPrimary (citable) accession number: P54840
Secondary accession number(s): A0AVD8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: February 9, 2010
Last modified: March 4, 2015
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.