Ras-related protein Rab-18 (RAB18)
The protein contains 206 amino acids for an estimated molecular weight of 22977 Da.
Required for the localization of ZFYVE1 to lipid droplets and for its function in mediating the formation of endoplasmic reticulum-lipid droplets (ER-LD) contacts (PubMed:30970241). Plays a role in apical endocytosis/recycling (By similarity). Plays a key role in eye and brain development and neurodegeneration (PubMed:21473985). (updated: June 17, 2020)
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, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| WARBM3 | |
| dbSNP:rs12268932 | |
| dbSNP:rs11015859 |
Biological Process
Brain development
Endoplasmic reticulum tubular network organization
Eye development
Import into nucleus
Intracellular protein transport
Lipid droplet organization
Metabolic process
Neutrophil degranulation
Protein transport
Rab protein signal transduction
Small GTPase mediated signal transduction
Viral process
The reference OMIM entry for this protein is 602207
Ras-associated protein rab18; rab18
DESCRIPTION
Rab proteins comprise a complex family of small GTPases involved in the regulation of intracellular membrane trafficking and reorganization. Rab18 inhibits secretory activity in vertebrate neuroendocrine cells (Vazquez-Martinez et al., 2007).CLONING
By stimulating umbilical vein endothelial cells (HUVEC) with histamine and differential display gene expression analysis, Schafer et al. (2000) isolated a cDNA encoding RAB18. The deduced 206-amino acid protein shares 98%, 92%, and 85% identity with the mouse, snail, and worm sequences, respectively. RAB18 contains totally conserved phosphate/Mg(2+)-binding motifs and guanine-binding motifs as well as somewhat variable organelle-targeting regions. Northern blot analysis detected 2.5- and 1.0-kb transcripts in endothelial cells but not in smooth muscle cells or leukocytes. RT-PCR analysis suggested ubiquitous expression, which HPLC analysis determined to be strongest in heart, kidney, pancreas, lung, and liver, with weak expression in brain, placenta, and skeletal muscle.GENE FUNCTION
Schafer et al. (2000) reported that stimulation of polarized HUVEC or nonpolarized mononuclear cells with histamine showed a significant time- and dose-dependent increase of RAB18 transcript in both cell types, suggesting a possible role for Rab proteins in inflammation. Vazquez-Martinez et al. (2007) found that Rab18 localized to the cytosol in rat PC12 adrenal chromaffin cells and AtT20 mouse pituitary corticotropes. However, Rab18 associated with a subpopulation of secretory granules after stimulation of the regulated secretory pathway and subsequently relocalized to the cell surface. A dominant-inactive rat Rab18 mutant distributed diffusely in the cytosol, whereas a dominant-active rat Rab18 mutant predominantly associated with secretory granules. Interaction with Rab18 slowed secretory granule movement and inhibited secretory activity of PC12 and AtT20 cells in response to stimulatory challenges. Immunoelectron microscopy of normal frog pituitary melanotropes showed an inverse correlation between Rab18 protein content and secretory activity. Vazquez-Martinez et al. (2007) concluded that RAB18 acts as a negative regulator of secretory activity by impairing secretory granule transport.MAPPING
McMurtrie et al. (1997) mapped the mouse Rab18 gene to chromosome 18. Hartz (2009) mapped the RAB18 gene to chromosome 10p12.1 based on an alignment of the RAB18 sequence (GenBank GENBANK AA216667) with the genomic sequence (GRCh37).MOLECULAR GENETICS
In affected members of 5 large consanguineous families, 4 Pakistani and 1 Turkish, segregating Warburg Micro syndrome (WARBM3; 614222), Bem et al. (2011) identified homozygous loss-of-function mutations in the RAB18 gene (602207.0001 and 602207.0002, respectively). Direct sequencing for RAB18 mutations in 58 additional families segregating Warburg Micro syndrome detected compound heterozygous mutations (602207.0003-602207.0004) in affected sibs of 1 family. Bem et al. (2011) performed nucleotide-binding assays and showed that although RAB18 bound GDP and GTP comparably to other RABs (RAB5A, 179512; RAB35, 604199), the RAB18 L24Q (602207.0001) and R93del (602207.0003) mutant proteins did not bind detectable levels of either GDP or GTP and are therefore functionally null. Bem et al. (2011) noted that the pathogenicity of these mutations could be explained by their lack of guanosine nucleotide binding beca ... More on the omim web site
June 29, 2020: 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 602207 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed