Glycogen [starch] synthase, muscle (GYS1)

The protein contains 737 amino acids for an estimated molecular weight of 83786 Da.

 

Transfers the glycosyl residue from UDP-Glc to the non-reducing end of alpha-1,4-glucan. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  5. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 94%
Model score: 55

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VariantDescription
dbSNP:rs5455
dbSNP:rs5456
dbSNP:rs5461
dbSNP:rs5465
dbSNP:rs5447
NIDDM
dbSNP:rs5450
dbSNP:rs5453

The reference OMIM entry for this protein is 138570

Glycogen synthase 1; gys1
Glycogen synthase, muscle
Gys

DESCRIPTION

Glycogen is a high molecular mass polysaccharide that serves as a repository of glucose for use in times of metabolic need. Glycogen synthase (EC 2.4.1.11) catalyzes the addition of glucose monomers to the growing glycogen molecule through the formation of alpha-1,4-glycoside linkages (Pederson et al., 2004).

CLONING

Browner et al. (1989) cloned and sequenced a cDNA for human muscle glycogen synthase. They found that it encodes a protein of 737 amino acids. Its primary structure is not related either to bacterial glycogen synthase or to any glycogen phosphorylase. They concluded that the glycogen synthase mRNA expressed in both fetal and adult heart and skeletal muscle tissue are the same, based on the size of mRNA species that were hybridized. Liver glycogen synthase is distinct (see GYS2, 138571).

MAPPING

By Southern blot analysis of somatic cell hybrid DNAs, Groop et al. (1993) determined that the GYS1 gene is located on chromosome 19. Lehto et al. (1993) regionalized the GYS gene to 19q13.3 by fluorescence in situ hybridization.

GENE FUNCTION

To examine whether defective muscle GYS1 expression is associated with impaired glycogen synthesis in type 2 diabetes (see 125853) and whether the defect is inherited or acquired, Huang et al. (2000) measured GYS1 gene expression and enzyme activity in muscle biopsies taken before and after an insulin clamp in 12 monozygotic twin pairs discordant for type 2 diabetes and in 12 matched control subjects. The effect of insulin on GYS1 fractional activity, when expressed as the increment over the basal values, was significantly impaired in diabetic, but not in nondiabetic, twins compared with that in control subjects. Insulin increased GYS1 mRNA expression in control subjects and in nondiabetic and diabetic twins. The effect of insulin on GYS1 expression was, however, significantly reduced in the diabetic (P less than 0.003), but not in the nondiabetic, twins, compared with that in control subjects. The postclamp GYS1 mRNA levels correlated strongly with the hemoglobin A1c levels (r = -0.61; P less than 0.001). The authors concluded that insulin stimulates GYS1 mRNA expression and that impaired stimulation of GYS1 gene expression by insulin in patients with type 2 diabetes is acquired and most likely is secondary to chronic hyperglycemia. Kollberg et al. (2007) summarized the functions of muscle glycogen synthase and liver glycogen synthase, the key enzymes of glycogen synthesis, encoded by the GYS1 and GYS2 (138571) genes, respectively. The liver enzyme expression is restricted to the liver, whereas the muscle enzyme is ubiquitously expressed. Liver glycogen serves as a pool to maintain the blood glucose level during fasting, whereas muscle glycogen synthesis accounts for disposal of up to 90% of ingested glucose. The role of muscle and heart glycogen is to provide critical energy during bursts of activity and sustained muscle work. Deficiency of either muscle or liver glycogen synthase leads to distinct phenotypes; see 240600 for a description of liver glycogen synthase deficiency.

MOLECULAR GENETICS

- Muscle Glycogen Storage Disease Kollberg et al. (2007) described 3 sibs with profound muscle and heart glycogen deficiency (GSD0B; 611556) caused by homozygosity for a stop codon mutation in the GYS1 gene (R462X; 138570.0001). Several findings in the patients were in accordance with the findings in muscle glycogen synthase knockout m ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 138570 was added.