Rab GDP dissociation inhibitor alpha (GDI1)
The protein contains 447 amino acids for an estimated molecular weight of 50583 Da.
Regulates the GDP/GTP exchange reaction of most Rab proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Promotes the dissociation of GDP-bound Rab proteins from the membrane and inhibits their activation. Promotes the dissociation of RAB1A, RAB3A, RAB5A and RAB10 from membranes. (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.
Biological Process
Negative regulation of axonogenesis
Negative regulation of protein targeting to membrane
Positive regulation of axon extension
Positive regulation of GTPase activity
Protein transport
Rab protein signal transduction
Regulation of small GTPase mediated signal transduction
Response to calcium ion
Signal transduction
Small GTPase mediated signal transduction
Vesicle-mediated transport
The reference OMIM entry for this protein is 300104
Gdp dissociation inhibitor 1; gdi1
Rab gdp-dissociation inhibitor, alpha; rabgdia
Rab gdi-alpha
Rhogdi
Oligophrenin 2; ophn2
DESCRIPTION
The GDP dissociation inhibitor-1 gene (GDI1) regulates the GDP-GTP exchange reaction of members of the rab family, small GTP-binding proteins of the ras superfamily, that are involved in vesicular trafficking of molecules between cellular organelles. The rab proteins undergo activation upon GTP binding, and GTP hydrolysis to GDP inactivates the protein. GDI proteins slow the rate of dissociation of GDP from rab proteins and release GDP from membrane-bound rabs (Bachner et al., 1995). Chelly (1999) referred to the protein as oligophrenin-2 (OPHN2).CLONING
Matsui et al. (1990) cloned a bovine GDI gene, designated smg p25A, using an oligomer probe based on partial amino acid sequence. The 447-amino acid protein was expressed in E. coli and shown to have GDI activity. Sedlacek et al. (1994) noted 2 rat rab GDI sequences, designated alpha and beta, in the EMBL database (accession nos. X74401 and X74402). Sedlacek et al. (1993) characterized a human rab GDI1 locus, which they called XAP-4. The predicted amino acid sequence of the protein is 98.4% identical to the bovine and rat GDI-alphas and 86.5% identical to human rab GDI-beta (GDI2; 600767). The rab GDI-alpha gene was expressed at highest levels as a 2.5-kb mRNA in brain, with lesser amounts in the muscle and kidney. Subsequent work by Bachner et al. (1995) showed expression predominantly in neural and sensory tissues. D'Adamo et al. (1997) noted that GDI is expressed in all parts of the adult brain and, by in situ hybridization analysis, it is detectable in post-mitotic neural cells during mouse development, with the same timing and in the same cell types as Rab3a. Shisheva et al. (1994) cloned and characterized the mouse gene.GENE FUNCTION
Rab GTPases regulate vesicle trafficking in eukaryotic cells by reversibly associating with lipid membranes. Inactive Rab GTPases are maintained in the cytosol by binding to GDP-dissociation inhibitor. It is believed that specialized proteins are required to displace GDI from Rab GTPases before Rab activation by GDP-GTP exchange factors (GEFs). Machner and Isberg (2007) found that SidM from Legionella pneumophila could act as both GEF and GDI-displacement factor (GDF) for Rab1 (179508). Rab1 released from GDI was inserted into liposomal membranes and was used as a substrate for SidM-mediated nucleotide exchange. During host cell infection, recruitment of Rab1 to Legionella-containing vacuoles depended on the GDF activity of SidM. Thus, Machner and Isberg (2007) concluded that GDF and GEF activity can be promoted by a single protein, and GDF activity can coordinate Rab1 recruitment from the GDI-bound pool.GENE STRUCTURE
Sedlacek et al. (1994) characterized the human RABGDIA gene, which has 11 exons in a span of about 7 kb.BIOCHEMICAL FEATURES
Hoffman et al. (2000) determined the 2.6-angstrom x-ray crystallographic structure of the GTP-binding protein CDC42 (116952) in complex with GDI1. The structure revealed 2 important sites of interaction between GDI1 and CDC42. First, the N-terminal regulatory arm of GDI1 binds to the switch I and II domains of CDC42, leading to inhibition of both GDP dissociation and GTP hydrolysis. Second, the geranylgeranyl moiety of CDC42 inserts into a hydrophobic pocket within the immunoglobulin-like domain of the GDI1 molecule, leading to membrane release. The structural data demonstrated how GDIs serve as negative regulators of small GTP-binding proteins ... 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300104 was added.