Rab3 GTPase-activating protein catalytic subunit (RAB3GAP1)
The protein contains 981 amino acids for an estimated molecular weight of 110524 Da.
Probable catalytic subunit of a GTPase activating protein that has specificity for Rab3 subfamily (RAB3A, RAB3B, RAB3C and RAB3D). Rab3 proteins are involved in regulated exocytosis of neurotransmitters and hormones. Specifically converts active Rab3-GTP to the inactive form Rab3-GDP. Required for normal eye and brain development. May participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters. (updated: April 1, 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.
- 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.
- 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.
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| Variant | Description |
|---|---|
| dbSNP:rs10445686 |
Biological Process
Brain development
Camera-type eye development
Establishment of protein localization to endoplasmic reticulum membrane
Excitatory postsynaptic potential
Face morphogenesis
Hypothalamus development
Lipid droplet organization
Positive regulation of autophagosome assembly
Positive regulation of endoplasmic reticulum tubular network organization
Positive regulation of gene expression
Positive regulation of glutamate neurotransmitter secretion in response to membrane depolarization
Positive regulation of GTPase activity
Positive regulation of protein lipidation
Regulation of calcium ion-dependent exocytosis of neurotransmitter
Regulation of GTPase activity
Regulation of short-term neuronal synaptic plasticity
The reference OMIM entry for this protein is 600118
Warburg micro syndrome 1; warbm1
Micro syndrome
A number sign (#) is used with this entry because Warburg Micro syndrome-1 (WARBM1) can be caused by homozygous mutation in the RAB3GAP1 gene (602536) on chromosome 2q21.3.
DESCRIPTION
Warburg Micro syndrome is a rare autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism (summary by Morris-Rosendahl et al., 2010). - Genetic Heterogeneity of Warburg Micro Syndrome Warburg Micro syndrome-2 (WARBM2; 614225) is caused by mutation in the RAB3GAP2 gene (609275) on chromosome 1q41. WARBM3 (614222) is caused by mutation in the RAB18 gene (602207) on chromosome 10p12.1. WARBM4 (615663) is caused by mutation in the TBC1D20 gene (611663) on chromosome 20p13. See also Martsolf syndrome (212720), a clinically overlapping but milder autosomal recessive disorder caused by autosomal recessive mutation in the RAB3GAP2 gene. Handley et al. (2013) provided an overview of the disease variants identified in the RAB3GAP1, RAB3GAP2, and RAB18 genes, noting that a total of 144 families with WARBM and 9 families with Martsolf syndrome had been investigated. Mutations were identified in RAB3GAP1 in 41% of cases, in RAB3GAP2 in 7% of cases, and in RAB18 in 5% of cases. Although RAB18 had not been linked to RAB3 pathways, Handley et al. (2013) stated that mutations in all 3 genes cause an indistinguishable phenotype, making it likely that there is some functional overlap.CLINICAL FEATURES
Warburg et al. (1993) used the designation Micro syndrome for an autosomal recessive syndrome comprising microcephaly, microcornea, congenital cataract, mental retardation, optic atrophy, and hypogenitalism. They described an affected brother and sister and their male cousin. The sibs were offspring of a consanguineous Pakistani marriage; the parents of the cousin denied consanguinity. Agenesis of the corpus callosum, prominent root of the nose, large anteverted ears, facial hypertrichosis, small pupils with posterior synechiae, hypotonia, mild to moderate spastic palsy with hip dislocations, and hormonal dysfunction, presumably of hypothalamic origin, were other features. The children were almost blind, whether or not the cataracts had been operated on. The electroretinographic responses indicated dysfunction of both retinal rods and cones, and the visual evoked potentials confirmed optic nerve atrophy. The children were late walkers and were incontinent of urine and stools. In the differential diagnosis, Warburg et al. (1993) considered COFS syndrome (214150), CAMAK/CAMFAK syndromes (212540), Martsolf syndrome (212720), lethal Rutledge syndrome (270400), and lethal Neu-Laxova syndrome (256520). Cases similar in nature to the phenotype designated 'Micro syndrome' by Warburg et al. (1993) had previously been described. Sjogren and Larsson (1949) reported 5 unrelated patients, 2 males and 3 females, with microphthalmia, mental retardation, and spastic diplegia. Additional ocular features included cataract in 2 patients, retino-choroiditis in 1, and degeneration of the retina in 1. Three of the patients also had epilepsy. Pinsky et al. (1965) described 3 sisters with microcephaly, microphthalmia, corneal opacity, severe mental retardation, spastic cerebral palsy, and seizures. None had cataract or coloboma, although 2 had pupillary abnormalities. Their mother had uni ... 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 600118 was added.