Ras-related protein Rab-21 (RAB21)
The protein contains 225 amino acids for an estimated molecular weight of 24348 Da.
Small GTPase involved in membrane trafficking control (PubMed:18804435, PubMed:25648148). During the mitosis of adherent cells, controls the endosomal trafficking of integrins which is required for the successful completion of cytokinesis (PubMed:18804435). Regulates integrin internalization and recycling, but does not influence the traffic of endosomally translocated receptors in general (By similarity). As a result, may regulate cell adhesion and migration (By similarity). Involved in neurite growth (By similarity). Following SBF2/MTMT13-mediated activation in response to starvation-induced autophagy, binds to and regulates SNARE protein VAMP8 endolysosomal transport required for SNARE-mediated autophagosome-lysosome fusion (PubMed:25648148). Modulates protein levels of the cargo receptors TMED2 and TMED10, and required for appropriate Golgi localization of TMED10 (PubMed:31455601). (updated: Oct. 7, 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.
- 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.
- 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.
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Biological Process
Anterograde axonal transport
Intracellular protein transport
Metabolic process
Positive regulation of dendrite morphogenesis
Positive regulation of early endosome to late endosome transport
Positive regulation of receptor-mediated endocytosis
Protein stabilization
Protein transport
Rab protein signal transduction
Regulation of axon extension
Regulation of endocytosis
Regulation of exocytosis
Cellular Component
Axon cytoplasm
Cleavage furrow
Cytoplasmic side of early endosome membrane
Cytoplasmic side of plasma membrane
Cytoplasmic vesicle membrane
Cytosol
Early endosome
Early endosome membrane
Endomembrane system
Endoplasmic reticulum membrane
Endosome
Extracellular exosome
Focal adhesion
Golgi cisterna membrane
Synapse
Trans-Golgi network
Vesicle membrane
The reference OMIM entry for this protein is 612398
Rab-associated protein rab21; rab21
Kiaa0118
DESCRIPTION
RAB21 belongs to the RAB family of small GTP-binding proteins that regulate intracellular vesicle targeting (Opdam et al., 2000).CLONING
By sequencing clones obtained from a human immature myeloid cell line cDNA library, Nagase et al. (1995) cloned RAB21, which they designated KIAA0118. The transcript contains a repetitive element in its 3-prime end, and the deduced protein shares significant similarity with slime mold Rab-B. Northern blot analysis detected expression of RAB21 in all human tissues and cell lines examined, with highest expression in heart and skeletal muscle. By RT-PCR of Caco2 human colon cancer cell RNA using degenerate primers based on conserved regions of RAB family members, followed by screening a Caco2 cDNA library, Opdam et al. (2000) obtained 2 RAB21 clones that appeared to differ in their polyadenylation sites. The deduced 225-amino acid RAB21 protein has a calculated molecular mass of 24.5 kD. Like other RAB proteins, RAB21 contains 6 GTP-binding domains and C-terminal cysteines required for prenylation. Northern blot analysis detected transcripts of 1.8, 2.5, and 4.0 kb in lung, kidney, liver, esophagus, stomach, jejunum, rectum, and all human cell lines examined. Immunofluorescence analysis showed RAB21 associated with the endoplasmic reticulum in nonpolarized Caco2 cells and with apical membranes and late endosomes or lysosomes in differentiated, polarized Caco2 cells. Immunohistochemical analysis of human jejunum revealed strongest RAB21 staining in the apical cytoplasmic region of epithelial cells. RAB21 was also detected in capillary endothelial cells and in some cells of the lamina propria.GENE FUNCTION
Opdam et al. (2000) showed that recombinant human RAB21 bound radiolabeled GTP. Using human and rodent cell lines, Pellinen et al. (2008) showed that integrins (see ITGB1; 135630) anchored the cleavage furrow to the matrix during cytokinesis and that targeting of integrins to and from the cleavage furrow was regulated by RAB21. RAB21 activity, integrin-RAB21 association, and integrin endocytosis were all necessary for normal cytokinesis. Pellinen et al. (2008) found a deletion of the RAB21 gene in 2 ovarian cancer cell lines and a prostate cancer tumor sample. Cells harboring this deletion were multinucleated, and reintroduction of RAB21 into the ovarian cancer cell lines rescued the phenotype. Pellinen et al. (2008) concluded that RAB21-regulated integrin trafficking is essential for normal cell division and that defects in this trafficking may contribute to multinucleation and genomic instability.MAPPING
By radiation hybrid analysis, Nagase et al. (1995) mapped the RAB21 gene to chromosome 12. ... More on the omim web site
Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 612398 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed