1,4-alpha-glucan-branching enzyme (GBE1)
The protein contains 702 amino acids for an estimated molecular weight of 80474 Da.
Required for normal glycogen accumulation (PubMed:8463281, PubMed:26199317, PubMed:8613547). The alpha 1-6 branches of glycogen play an important role in increasing the solubility of the molecule (Probable). (updated: Dec. 20, 2017)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
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| Variant | Description |
|---|---|
| dbSNP:rs2229519 | |
| GSD4 | |
| GSD4 | |
| dbSNP:rs17856389 | |
| GSD4 | |
| dbSNP:rs2172397 | |
| dbSNP:rs2228389 | |
| GSD4 | |
| APBN | |
| GSD4 and APBN | |
| GSD4 | |
| GSD4 |
The reference OMIM entry for this protein is 232500
Glycogen storage disease iv; gsd4
Gsd iv
Glycogen branching enzyme deficiency
Gbe1 deficiency
Andersen disease
Brancher deficiency
Glycogenosis iv
Amylopectinosis
Cirrhosis, familial, with deposition of abnormal glycogen gsd iv, class
A number sign (#) is used with this entry because glycogen storage disease type IV (GSD4) is caused by homozygous or compound heterozygous mutation in the GBE1 gene (607839), which encodes the glycogen branching enzyme, on chromosome 3p12. Mutation in the GBE1 gene causes an allelic disorder, adult polyglucosan body neuropathy (APBN; 263570).
CLINICAL FEATURES
Glycogen storage disease type IV is a clinically heterogeneous disorder. The typical 'classic' hepatic presentation is liver disease of childhood, progressing to lethal cirrhosis. The neuromuscular presentation of GSD IV is distinguished by age at onset into 4 groups: perinatal, presenting as fetal akinesia deformation sequence (FADS) and perinatal death; congenital, with hypotonia, neuronal involvement, and death in early infancy; childhood, with myopathy or cardiomyopathy; and adult, with isolated myopathy or adult polyglucosan body disease (Bruno et al., 2004). The enzyme deficiency results in tissue accumulation of abnormal glycogen with fewer branching points and longer outer branches, resembling an amylopectin-like structure, also known as polyglucosan (Tay et al., 2004). Bruno et al. (2007) provided a review of the neuromuscular forms of glycogen branching enzyme deficiency. - Classic Hepatic Form Andersen (1956) originally reported GSD IV as 'familial cirrhosis of the liver with storage of abnormal glycogen.' Brown and Brown (1966) determined that the defect in GSD IV was a deficiency of the alpha-1,4-glucan branching enzyme. Bao et al. (1996) noted that the most common form of GSD IV presents in the first 18 months of life with failure to thrive, hepatosplenomegaly, and liver cirrhosis. There is progression to portal hypertension, ascites, and liver failure, leading to death by age 5 years. A simple iodine test shows formation of a blue colored complex of glycogen and iodine. The liver shows the main involvement, resulting from a defect of amylo(1,4 to 1,6) transglucosidase (brancher enzyme). - Nonprogressive Hepatic Form Less frequently, patients may have liver dysfunction without liver failure, referred to as 'nonprogressive hepatic GSD IV.' Greene et al. (1988) reported a 5-year-old boy who was first noted to have elevated serum transaminase levels and hepatomegaly at age 2 years following an acute febrile illness. Successive liver biopsies showed hepatocellular periodic-acid Schiff-positive diastase-resistant inclusions and hepatic fibrosis that was nonprogressive over 3 years. Enzymatic assays showed deficient branching enzyme in liver, skeletal muscle, and skin fibroblasts. The child showed normal growth and development. McConkie-Rosell et al. (1996) found that 6 patients with nonprogressive hepatic GSD IV did not develop progressive liver cirrhosis, cardiac, or neurologic involvement, despite residual branching enzyme activity in skin fibroblasts that was indistinguishable from patients with more severe forms of GSD IV. The authors concluded that residual enzyme activity could not be used to predict the clinical course in GSD IV, that not all patients require liver transplant, and that caution should be used in genetic counseling. - Fatal Perinatal Neuromuscular Form Alegria et al. (1999) reported hydrops fetalis as a presenting manifestation of glycogen storage disease type IV. The infant, delivered by cesarean section at 34 weeks, had generalized edema, severe hypotonia, and arthrogryposis of the lower limbs at birth. There were no signs of cirrhosis o ... More on the omim web site
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
March 15, 2016: Protein entry updated
Automatic update: OMIM entry 232500 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed