P13807 (GYS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glycogen [starch] synthase, muscle
EC=2.4.1.11

Gene names

Name:	GYS1
Synonyms:	GYS

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	737 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transfers the glycosyl residue from UDP-Glc to the non-reducing end of alpha-1,4-glucan.
Catalytic activity	UDP-glucose ((1->4)-alpha-D-glucosyl)(n) = UDP + ((1->4)-alpha-D-glucosyl)(n+1).
Enzyme regulation	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.
Pathway	Glycan biosynthesis; glycogen biosynthesis.
Subunit structure	Interacts with GYG1. Ref.8
Post-translational modification	Phosphorylation at Ser-8 by AMPK inactivates the enzyme activity. 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 By similarity. Phosphorylated at Ser-641 by DYRK2, leading to inactivation By similarity. Phosphorylated at Ser-641 by PASK, leading to inactivation; phosphorylation by PASK is inhibited by glycogen. Dephosphorylation at Ser-641 and Ser-645 by PP1 activates the enzyme. Ref.7 Ref.14
Involvement in disease	Muscle glycogen storage disease 0 (GSD0b) [MIM:611556]: Metabolic disorder characterized by fasting hypoglycemia presenting in infancy or early childhood. The role of muscle glycogen is to provide critical energy during bursts of activity and sustained muscle work. Note: The disease is caused by mutations affecting the gene represented in this entry.
Sequence similarities	Belongs to the glycosyltransferase 3 family.

Ontologies

Keywords
Biological process	Glycogen biosynthesis
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Diabetes mellitus Disease mutation
Molecular function	Glycosyltransferase Transferase
PTM	Phosphoprotein
Technical term	Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glucose metabolic process Traceable author statement. Source: Reactome glycogen biosynthetic process Inferred from direct assay Ref.7. Source: UniProtKB heart development Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome inclusion body Inferred from electronic annotation. Source: Compara
Molecular_function	glucose binding Inferred from electronic annotation. Source: Compara glycogen (starch) synthase activity Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GYG1	P46976	4	EBI-740553,EBI-740533

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P13807-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P13807-2)

The sequence of this isoform differs from the canonical sequence as follows:
     101-164: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 737	736	Glycogen [starch] synthase, muscle		PRO_0000194763
Sites
	Binding site	39	1	UDP-glucose By similarity
Amino acid modifications
	Modified residue	8	1	Phosphoserine; by AMPK and PKA By similarity
	Modified residue	11	1	Phosphoserine By similarity
	Modified residue	641	1	Phosphoserine Ref.7 Ref.11 Ref.14
	Modified residue	645	1	Phosphoserine Ref.11 Ref.14
	Modified residue	649	1	Phosphoserine Ref.11
	Modified residue	653	1	Phosphoserine; by GSK3-alpha and GSK3-beta By similarity
	Modified residue	657	1	Phosphoserine; by CK2 By similarity
	Modified residue	698	1	Phosphoserine By similarity
	Modified residue	727	1	Phosphoserine Ref.12
Natural variations
	Alternative sequence	101 – 164	64	Missing in isoform 2.		VSP_042745
	Natural variant	108	1	I → M. Corresponds to variant rs5455 [ dbSNP | Ensembl ].		VAR_037958
	Natural variant	130	1	K → E. Corresponds to variant rs5456 [ dbSNP | Ensembl ].		VAR_014727
	Natural variant	283	1	N → S. Corresponds to variant rs5461 [ dbSNP | Ensembl ].		VAR_014728
	Natural variant	359	1	E → G. Corresponds to variant rs5465 [ dbSNP | Ensembl ].		VAR_014729
	Natural variant	416	1	M → V. Corresponds to variant rs5447 [ dbSNP | Ensembl ].		VAR_014730
	Natural variant	464	1	G → S in NIDDM. Ref.2		VAR_007859
	Natural variant	619	1	E → Q. Corresponds to variant rs5450 [ dbSNP | Ensembl ].		VAR_014731
	Natural variant	691	1	P → A. Corresponds to variant rs5453 [ dbSNP | Ensembl ].		VAR_014732
Experimental info
	Mutagenesis	641	1	S → A: Abolishes PASK-mediated phosphorylation. Ref.7
	Mutagenesis	645	1	S → A: Does not affect PASK-mediated phosphorylation. Ref.7
	Sequence conflict	136	1	T → I in AAA88046. Ref.1
	Sequence conflict	136	1	T → I in AAB60385. Ref.3
	Sequence conflict	462	1	Missing in AAB60385. Ref.3
	Sequence conflict	608	1	A → D in AAB60385. Ref.3
	Sequence conflict	706	1	S → R in AAA88046. Ref.1
	Sequence conflict	706	1	S → R in AAB60385. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: 0E321BBFDEB0BD7F	FASTA	737	83,786
	10 20 30 40 50 60 MPLNRTLSMS SLPGLEDWED EFDLENAVLF EVAWEVANKV GGIYTVLQTK AKVTGDEWGD 70 80 90 100 110 120 NYFLVGPYTE QGVRTQVELL EAPTPALKRT LDSMNSKGCK VYFGRWLIEG GPLVVLLDVG 130 140 150 160 170 180 ASAWALERWK GELWDTCNIG VPWYDREAND AVLFGFLTTW FLGEFLAQSE EKPHVVAHFH 190 200 210 220 230 240 EWLAGVGLCL CRARRLPVAT IFTTHATLLG RYLCAGAVDF YNNLENFNVD KEAGERQIYH 250 260 270 280 290 300 RYCMERAAAH CAHVFTTVSQ ITAIEAQHLL KRKPDIVTPN GLNVKKFSAM HEFQNLHAQS 310 320 330 340 350 360 KARIQEFVRG HFYGHLDFNL DKTLYFFIAG RYEFSNKGAD VFLEALARLN YLLRVNGSEQ 370 380 390 400 410 420 TVVAFFIMPA RTNNFNVETL KGQAVRKQLW DTANTVKEKF GRKLYESLLV GSLPDMNKML 430 440 450 460 470 480 DKEDFTMMKR AIFATQRQSF PPVCTHNMLD DSSDPILTTI RRIGLFNSSA DRVKVIFHPE 490 500 510 520 530 540 FLSSTSPLLP VDYEEFVRGC HLGVFPSYYE PWGYTPAECT VMGIPSISTN LSGFGCFMEE 550 560 570 580 590 600 HIADPSAYGI YILDRRFRSL DDSCSQLTSF LYSFCQQSRR QRIIQRNRTE RLSDLLDWKY 610 620 630 640 650 660 LGRYYMSARH MALSKAFPEH FTYEPNEADA AQGYRYPRPA SVPPSPSLSR HSSPHQSEDE 670 680 690 700 710 720 EDPRNGPLEE DGERYDEDEE AAKDRRNIRA PEWPRRASCT SSTSGSKRNS VDTATSSSLS 730 TPSEPLSPTS SLGEERN
	Isoform 2 [UniParc]. Checksum: 8C059070E0D075FC	FASTA	673	76,483
	10 20 30 40 50 60 MPLNRTLSMS SLPGLEDWED EFDLENAVLF EVAWEVANKV GGIYTVLQTK AKVTGDEWGD 70 80 90 100 110 120 NYFLVGPYTE QGVRTQVELL EAPTPALKRT LDSMNSKGCK FLAQSEEKPH VVAHFHEWLA 130 140 150 160 170 180 GVGLCLCRAR RLPVATIFTT HATLLGRYLC AGAVDFYNNL ENFNVDKEAG ERQIYHRYCM 190 200 210 220 230 240 ERAAAHCAHV FTTVSQITAI EAQHLLKRKP DIVTPNGLNV KKFSAMHEFQ NLHAQSKARI 250 260 270 280 290 300 QEFVRGHFYG HLDFNLDKTL YFFIAGRYEF SNKGADVFLE ALARLNYLLR VNGSEQTVVA 310 320 330 340 350 360 FFIMPARTNN FNVETLKGQA VRKQLWDTAN TVKEKFGRKL YESLLVGSLP DMNKMLDKED 370 380 390 400 410 420 FTMMKRAIFA TQRQSFPPVC THNMLDDSSD PILTTIRRIG LFNSSADRVK VIFHPEFLSS 430 440 450 460 470 480 TSPLLPVDYE EFVRGCHLGV FPSYYEPWGY TPAECTVMGI PSISTNLSGF GCFMEEHIAD 490 500 510 520 530 540 PSAYGIYILD RRFRSLDDSC SQLTSFLYSF CQQSRRQRII QRNRTERLSD LLDWKYLGRY 550 560 570 580 590 600 YMSARHMALS KAFPEHFTYE PNEADAAQGY RYPRPASVPP SPSLSRHSSP HQSEDEEDPR 610 620 630 640 650 660 NGPLEEDGER YDEDEEAAKD RRNIRAPEWP RRASCTSSTS GSKRNSVDTA TSSSLSTPSE 670 PLSPTSSLGE ERN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human muscle glycogen synthase cDNA sequence: a negatively charged protein with an asymmetric charge distribution." Browner M.F., Nakano K., Bang A.G., Fletterick R.J. Proc. Natl. Acad. Sci. U.S.A. 86:1443-1447(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Muscle.
[2]	"Isolation and characterization of the human muscle glycogen synthase gene." Orho M., Nikula-Ijas P., Schalin-Jantti C., Permutt M.A., Groop L.C. Diabetes 44:1099-1105(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT NIDDM SER-464.
[3]	"Cloning and characterization of a glycogen synthase cDNA from human endometrium." Su X., Schuler L., Shapiro S.S. J. Steroid Biochem. Mol. Biol. 59:459-465(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Endometrium.
[4]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORMS 1 AND 2). Tissue: Kidney, Lymph and Skin.
[7]	"Control of mammalian glycogen synthase by PAS kinase." Wilson W.A., Skurat A.V., Probst B., de Paoli-Roach A., Roach P.J., Rutter J. Proc. Natl. Acad. Sci. U.S.A. 102:16596-16601(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-641, MUTAGENESIS OF SER-641 AND SER-645.
[8]	"Interaction between glycogenin and glycogen synthase." Skurat A.V., Dietrich A.D., Roach P.J. Arch. Biochem. Biophys. 456:93-97(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GYG1.
[9]	"Cardiomyopathy and exercise intolerance in muscle glycogen storage disease 0." Kollberg G., Tulinius M., Gilljam T., Oestman-Smith I., Forsander G., Jotorp P., Oldfors A., Holme E. N. Engl. J. Med. 357:1507-1514(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN GSD0B.
[10]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641; SER-645 AND SER-649, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"R3F, a novel membrane-associated glycogen targeting subunit of protein phosphatase 1 regulates glycogen synthase in astrocytoma cells in response to glucose and extracellular signals." Kelsall I.R., Voss M., Munro S., Cuthbertson D.J., Cohen P.T. J. Neurochem. 118:596-610(2011) [PubMed] [Europe PMC] [Abstract] Cited for: DEPHOSPHORYLATION AT SER-641 AND SER-645 BY PP1.
[15]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J04501 mRNA. Translation: AAA88046.1. Z33622 , Z33623, Z33609, Z33624, Z33625, Z33626, Z33610, Z33627, Z33628, Z33629, Z33630, Z33631, Z33633 Genomic DNA. Translation: CAA83916.1. U32573 mRNA. Translation: AAB60385.1. AC008687 Genomic DNA. No translation available. AC026803 Genomic DNA. No translation available. AC098792 Genomic DNA. No translation available. CH471177 Genomic DNA. Translation: EAW52424.1. BC002617 mRNA. Translation: AAH02617.1. BC003182 mRNA. Translation: AAH03182.1. BC007688 mRNA. Translation: AAH07688.1.
IPI	IPI00157144. IPI00303868.
PIR	A32156.
RefSeq	NP_001155059.1. NM_001161587.1. NP_002094.2. NM_002103.4.
UniGene	Hs.386225.
3D structure databases
ProteinModelPortal	P13807.
ModBase	Search...
Protein-protein interaction databases
IntAct	P13807. 16 interactions.
STRING	9606.ENSP00000317904.
Protein family/group databases
CAZy	GT3. Glycosyltransferase Family 3.
PTM databases
PhosphoSite	P13807.
Polymorphism databases
DMDM	1351366.
Proteomic databases
PaxDb	P13807.
PRIDE	P13807.
Protocols and materials databases
DNASU	2997.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000263276; ENSP00000263276; ENSG00000104812. ENST00000323798; ENSP00000317904; ENSG00000104812.
GeneID	2997.
KEGG	hsa:2997.
UCSC	uc002plp.3. human.
Organism-specific databases
CTD	2997.
GeneCards	GC19M049471.
HGNC	HGNC:4706. GYS1.
HPA	CAB007793.
MIM	138570. gene. 611556. phenotype.
neXtProt	NX_P13807.
Orphanet	137625. Cardiomyopathy-exercise intolerance due to muscle and heart glycogen deficiency.
PharmGKB	PA29084.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0438.
HOGENOM	HOG000160890.
HOVERGEN	HBG001960.
InParanoid	P13807.
KO	K00693.
OMA	HEWLAGL.
OrthoDB	EOG4C2H91.
PhylomeDB	P13807.
Enzyme and pathway databases
BioCyc	MetaCyc:HS02622-MONOMER.
Pathway_Interaction_DB	insulin_glucose_pathway. Insulin-mediated glucose transport.
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00164.
Gene expression databases
ArrayExpress	P13807.
Bgee	P13807.
CleanEx	HS_GYS1.
Genevestigator	P13807.
GermOnline	ENSG00000104812. Homo sapiens.
Family and domain databases
InterPro	IPR008631. Glycogen_synth. [Graphical view]
PANTHER	PTHR10176. PTHR10176. 1 hit.
Pfam	PF05693. Glycogen_syn. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P13807.
ChEMBL	CHEMBL4000.
ChiTaRS	GYS1. human.
GenomeRNAi	2997.
NextBio	11884.
SOURCE	Search...

Entry information

Entry name

GYS1_HUMAN

Accession

Primary (citable) accession number: P13807
Secondary accession number(s): Q9BTT9

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	February 1, 1996
Last modified:	May 1, 2013
This is version 134 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.