Rho GTPase-activating protein 1 (ARHGAP1)
The protein contains 439 amino acids for an estimated molecular weight of 50436 Da.
GTPase activator for the Rho, Rac and Cdc42 proteins, converting them to the putatively inactive GDP-bound state. Cdc42 seems to be the preferred substrate. (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.
- 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.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs11822837 |
Biological Process
Endosomal transport
Endosome localization
Iron ion import across cell outer membrane
Negative regulation of endocytic recycling
Positive regulation of signal transduction
Regulation of small GTPase mediated signal transduction
Rho protein signal transduction
Small GTPase mediated signal transduction
Transferrin transport
The reference OMIM entry for this protein is 602732
Rho gtpase-activating protein 1; arhgap1
Gtpase-activating protein, rho, 1
Rhogap1
Rhogap
Cdc42gap
CLONING
The Rho family of GTP-binding proteins modulates cytoskeletal changes. Garrett et al. (1991) purified a 29-kD cytoplasmic GTPase-activating protein (GAP), called RHOGAP by them, from human spleen extracts. RHOGAP stimulated the GTPase activity of p21-Rho but not other small molecular mass GTP-binding proteins. Diekmann et al. (1991) reported a partial amino acid sequence of RHOGAP. Using PCR with primers based on the RHOGAP protein sequence, Lancaster et al. (1994) isolated a human fibrosarcoma cell line cDNA encoding RHOGAP. Northern blot analysis revealed that RHOGAP is expressed as a 3.6-kb mRNA. The RHOGAP cDNA encodes a predicted 439-amino acid protein with a calculated molecular mass of 50 kD. Since antibodies against RHOGAP detected a 50-kD protein on Western blots of cell extracts, Lancaster et al. (1994) suggested that the previously observed 29-kD protein was a C-terminal proteolytic fragment of RHOGAP that was generated during protein purification. Barfod et al. (1993) cloned human platelet-precursor cell cDNAs encoding CDC42GAP, a protein that inactivates CDC42 by stimulating GTP hydrolysis. They found that CDC42GAP contains a functional SH3-binding domain.GENE FUNCTION
Lancaster et al. (1994) found that the Rho family members Rho, RAC, and CDC42 (116952) were substrates for RHOGAP, with CDC42 the preferred substrate. Shen et al. (2008) showed that Nudel (NDEL1; 607538) colocalized with Cdc42gap at the leading edge of migrating NIH3T3 mouse fibroblasts. This localization of Nudel required its phosphorylation by Erk1 (MAPK3; 601795)/Erk2 (MAPK1; 176948). Shen et al. (2008) found that Nudel competed with Cdc42 for binding Cdc42gap. Consequently, Nudel inhibited Cdc42gap-mediated inactivation of Cdc42 in a dose-dependent manner. Depletion of Nudel by RNA interference or overexpression of a nonphosphorylatable Nudel mutant abolished Cdc42 activation and cell migration. Shen et al. (2008) concluded that NUDEL facilitates cell migration by sequestering CDC42GAP at the leading edge to stabilize active CDC42 in response to extracellular stimuli.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the RHOGAP1 gene to chromosome 11 (TMAP RH79109). ... 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 602732 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed