Vesicle-associated membrane protein-associated protein B/C (VAPB)
The protein contains 243 amino acids for an estimated molecular weight of 27228 Da.
Participates in the endoplasmic reticulum unfolded protein response (UPR) by inducing ERN1/IRE1 activity. Involved in cellular calcium homeostasis regulation. (updated: March 4, 2015)
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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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.
| 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.
This protein is annotated as membranous in Gene Ontology, is predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| ALS8 | |
| ALS8 and SMAPAD |
Biological Process
Cellular calcium ion homeostasis
COPII-coated vesicle budding
Endoplasmic reticulum membrane organization
Endoplasmic reticulum organization
Endoplasmic reticulum to Golgi vesicle-mediated transport
Endoplasmic reticulum unfolded protein response
Endoplasmic reticulum-plasma membrane tethering
IRE1-mediated unfolded protein response
Modulation by host of viral RNA genome replication
Modulation by virus of host process
Negative regulation by host of viral genome replication
Negative regulation by host of viral release from host cell
Negative regulation by virus of viral protein levels in host cell
Obsolete activation of signaling protein activity involved in unfolded protein response
Positive regulation by host of viral genome replication
Positive regulation by host of viral release from host cell
Positive regulation of viral genome replication
Small molecule metabolic process
Sphingolipid biosynthetic process
Sphingolipid metabolic process
The reference OMIM entry for this protein is 182980
Spinal muscular atrophy, late-onset, finkel type; smafk
Finkel late-adult type sma
Spinal muscular atrophy, proximal, adult, autosomal dominant
A number sign (#) is used with this entry because the Finkel type of late-onset autosomal dominant spinal muscular atrophy (SMAFK) is caused by heterozygous mutation in the gene encoding vesicle-associated membrane protein-associated protein B (VAPB; 605704) on chromosome 20q13.
DESCRIPTION
Spinal muscular atrophy is characterized by degeneration of the anterior horn cells in the spinal cord, leading to symmetric muscle weakness and wasting. See also autosomal recessive adult-onset proximal spinal muscular atrophy (SMA4; 271150), caused by defect in the SMN1 gene (600354), and autosomal dominant childhood-onset proximal SMA (158600).CLINICAL FEATURES
Pearn (1978) reported 13 patients from 6 kindreds with autosomal dominant proximal spinal muscular atrophy. Median age at disease onset was 37 years. The authors estimated that 30% of adult onset cases of SMA are due to an autosomal dominant gene. Pearn (1978) suggested that a separate gene was responsible for autosomal dominant SMA with childhood onset (birth to 8 years). Richieri-Costa et al. (1981) studied 2 kindreds in which 80 members were affected with an autosomal dominant, slowly progressive spinal muscular atrophy of late onset (average 48.8 years). One of the 2 kindreds was first described by Finkel (1962); the second was a black family living in the same region. The neurogenic nature of the disorder was established by electromyography and muscle biopsy. Unusual findings in this disorder were slow loss of muscle strength and progressive proximal atrophy, which started in the legs and later involved the arms; hypoactive or absent deep tendon reflexes; and generalized fasciculations. Adult spinal muscular atrophy usually begins after the third decade of life, and survival for several decades is typical. Emery (1971) cited cases by Tsukagoshi et al. (1965) and Peters et al. (1968). In a study on the classification and genetics of proximal SMA, Zerres (1989) documented the clinical course of 6 families including 20 patients suffering from an autosomal dominant form. Three families were classified as having the adult-onset form (after age 20 years). The patients showed a benign course, most of them remaining ambulatory 10 to 40 years after clinical onset (Rietschel et al., 1992). Three patients of the other 3 families suffered from the childhood-onset form, with first symptoms before the age of 12 years and walking difficulties throughout life, whereas other members of these families would have been classified as the adult-onset form. The latter had an onset between ages 17 and 28 years and were only moderately handicapped when examined at ages 38 to 60 years. Rietschel et al. (1992) suggested that the great intrafamilial variability in at least some of the families with autosomal dominant SMA is not compatible with the distinction of 2 clinically defined genetic entities.MAPPING
Kausch et al. (1991) performed linkage studies in 4 families with the autosomal dominant form of proximal spinal muscular atrophy. Three of the families met the criteria proposed by Pearn (1978). In a fourth family, affected individuals presented with an unusually mild SMA with muscle cramps (Ricker and Moxley, 1990); see 158400. For the first 3 families taken together and the fourth family taken alone, close linkage to D5S6, where the SMN1 gene is located, was excluded. The authors concluded that autosomal dominant and autosomal recessive forms of SMA are distinct genetic en ... 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 182980 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed