Rab GTPase-binding effector protein 1 (RABEP1)
The protein contains 862 amino acids for an estimated molecular weight of 99290 Da.
Rab effector protein acting as linker between gamma-adaptin, RAB4A and RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Involved in KCNH1 channels trafficking to and from the cell membrane (PubMed:22841712). Stimulates RABGEF1 mediated nucleotide exchange on RAB5A. Mediates the traffic of PKD1:PKD2 complex from the endoplasmic reticulum through the Golgi to the cilium (By similarity). (updated: Dec. 5, 2018)
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.
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| Variant | Description |
|---|---|
| dbSNP:rs3026099 |
Biological Process
Apoptotic process
Endocytosis
Golgi to plasma membrane transport
Membrane fusion
Positive regulation of GTPase activity
Protein localization to ciliary membrane
Protein transport
Vesicle-mediated transport
The reference OMIM entry for this protein is 603616
Rab gtpase-binding effector protein 1; rabep1
Rabaptin 5; rabpt5 rabep1/pdgfrb fusion gene, included
CLONING
The small GTPase RAB5 (179512) is a rate-limiting component in membrane docking or fusion in the early endocytic pathway. The GTP-bound form of RAB5 is the active conformation. Using a yeast 2-hybrid screen, Stenmark et al. (1995) identified HeLa cell cDNAs encoding a protein that interacted with the GTP-bound form of RAB5. The predicted 862-amino acid protein was designated rabaptin-5, a name combining the Greek word 'apto,' meaning 'touch', with RAB5. Both the N- and C-terminal regions of rabaptin-5 are predicted to be mainly alpha-helical and contain heptad repeats characteristic of coiled-coil domains. Western blot analysis of mammalian cell extracts indicated that the 115-kD protein is ubiquitously expressed and is present in a major cytosolic and minor endosome-bound pool.GENE FUNCTION
Stenmark et al. (1995) demonstrated that rabaptin-5 binds directly to RAB5 and preferentially to its GTP-bound form. RAB5 recruits rabaptin-5 to early endosomes in a GTP-dependent manner. Overexpression of rabaptin-5 leads to morphologic alterations of the early endosome compartment similar to those induced by overexpression of RAB5. The authors concluded that rabaptin-5 is an effector of RAB5 that transmits the signal of the active GTP-bound RAB5 conformation to the membrane docking and/or fusion apparatus. They proposed a model in which RAB5-GDP is converted by a membrane-bound GDP/GTP exchange factor into the active GTP-bound conformation. Once activated, GTP-bound RAB5 then recruits rabaptin-5 from the cytosol, thereby positioning rabaptin-5 to exert its function in membrane docking or fusion. Xiao et al. (1997) reported that tuberin (191092) exhibits substantial GTPase-activating protein activity towards RAB5, and that rabaptin-5 mediates the tuberin association with RAB5. Using immunodepletion experiments, Horiuchi et al. (1997) found that the RABGEF1 (609700)-RABPT5 complex was essential for both homotypic and heterotypic endosome fusions. Both RABGEF1 and RABPT5 bound RAB5 preferentially in the presence of GTP rather than GDP. RABGEF1 displayed specific GDP/GTP exchange activity on RAB5 upon delivery of RAB5 to the membrane. Mattera et al. (2003) found that the GGAs (e.g., GGA1; 606004), a family of ARF (see 103180)-dependent clathrin adaptors involved in selection of trans-Golgi network cargo, interacted with the RABGEF1-RABPT5 complex in vitro and in vivo. Omori et al. (2008) identified elipsa, the zebrafish ortholog of TRAF3IP1 (607380), as a component of intraflagellar transport particles, which are involved in the formation and function of cilia. Elipsa interacted with rabaptin-5, which in turn interacted with Rab8 (RAB8A; 165040), a small GTPase localized to cilia. Omori et al. (2008) concluded that elipsa, rabaptin-5, and Rab8 provide a bridge between the intraflagellar transport particle and protein complexes that assemble at the ciliary membrane. Endocytosis plays a major role in the deactivation of receptors localized to the plasma membrane. Wang et al. (2009) found that hypoxia, via the VHL (608537)-HIF2A (EPAS1; 603349) signaling pathway, downregulated rabaptin-5 expression, leading to decelerated endocytosis and prolonged activation of ligand-bound EGFR (131550). Primary kidney and breast tumors with strong hypoxic signatures showed significantly lower expression of rabaptin-5 RNA and protein. Wang et al. (2009) identified a conserved hypoxia-responsive element (HRE) in the rabaptin-5 promoter that ... More on the omim web site
Dec. 10, 2018: Protein entry updated
Automatic update: model status changed
Dec. 9, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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 603616 was added.