Rab3 GTPase-activating protein non-catalytic subunit (RAB3GAP2)
The protein contains 1393 amino acids for an estimated molecular weight of 155985 Da.
Regulatory 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. Rab3 GTPase-activating complex 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: Jan. 7, 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.
- 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.
- 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.
- 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.
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| Variant | Description |
|---|---|
| dbSNP:rs12045447 | |
| MARTS | |
| dbSNP:rs2289189 |
Biological Process
Establishment of protein localization to endoplasmic reticulum membrane
Intracellular protein transport
Positive regulation of autophagosome assembly
Positive regulation of catalytic activity
Positive regulation of endoplasmic reticulum tubular network organization
Positive regulation of GTPase activity
Positive regulation of protein lipidation
Regulation of GTPase activity
The reference OMIM entry for this protein is 212720
Martsolf syndrome
Cataract-mental retardation-hypogonadism
A number sign (#) is used with this entry because of evidence that some cases of the Martsolf syndrome are caused by mutation in the gene encoding the noncatalytic subunit of RAB3 GTPase-activating protein (RAB3GAP2; 609275). Warburg Micro syndrome-2 (WARBM2; 614225), a clinically overlapping but more severe disorder, is also caused by mutation in the RAB3GAP2 gene.
CLINICAL FEATURES
Martsolf et al. (1978) described a family in which 2 brothers had severe mental retardation, cataracts, short stature, primary hypogonadism, and minor digital and cephalic abnormalities. The parents were first cousins of Polish-Jewish descent and had 1 normal daughter. There are several mental retardation syndromes associated with cataracts, with or without short stature. These were reviewed by Cuendet et al. (1976). The association of mental retardation, cataracts, and primary hypogonadism is more rare. Sanchez et al. (1985) described this syndrome in 2 brothers of Sephardic Jewish ancestry. Strisciuglio et al. (1988) reported a non-Jewish case. Hennekam et al. (1988) described an affected brother and sister of Dutch or Belgian ancestry. Harbord et al. (1989) described a syndrome of microcephaly, mental retardation, cataracts, and hypogonadism in a brother and sister with consanguineous parents of Pakistani origin. One sib had cardiomyopathy while the other had cardiac failure. Cardiac features had not previously been described in Martsolf syndrome. Aligianis et al. (2006) described a consanguineous Pakistani family with 3 affected sibs. The first child had cataracts, microphthalmia, micropenis, and cryptorchidism at birth. Spastic diplegia was noted at the age of 3.5 years. At age 11 years, he had mild learning difficulties, was microcephalic, and walked with a walker. The sister of the proband likewise had dense bilateral cataracts, microphthalmia, and microcephaly at birth. Hypotonia was noted in infancy, and she later developed spastic diplegia. She had global developmental delay. At age 5 years, she had moderate learning difficulties and required special schooling, but she was bilingual in English and Punjabi. The third sib had congenitally corrected transposition of the great vessels with micropenis, bilateral cryptorchidism, congenital cataracts, and microphthalmia. Cardiac arrest of unknown cause occurred immediately after cataract surgery at the age of 2 months and, following resuscitation, he was found to have severe hypoxic ischemic encephalopathy with convulsions. Ehara et al. (2007) reported a Japanese brother and sister with clinical features consistent with Martsolf syndrome. They were 31 and 24 years of age, respectively, at the time of the report. As children, both showed delayed motor development, short stature, cataracts, thoracic scoliosis, and severe mental retardation. Both also developed skeletal abnormalities of the femoral neck, including metaphyseal broadening and fragmentation consistent with Legg-Calve-Perthes disease (150600). The sister was found to have Klipper-Feil malformation (118100). Laboratory evaluations showed growth hormone deficiency and lack of response to GnRH stimulation suggesting hypothalamic-pituitary insufficiency. Brain MRI showed enlarged Sylvian fissures, mildly dilated ventricles, and mild cerebral atrophy. Other features included brachycephaly, short philtrum, low posterior hairline, scoliosis, talipes valgus, flat feet, and lax finger joints. Bora et al. (2007) described a 7-year-old Turkish ... 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 212720 was added.