Ras-related protein Rab-8A (RAB8A)
The protein contains 207 amino acids for an estimated molecular weight of 23668 Da.
The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in polarized vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis (PubMed:20890297). Together with MYO5B and RAB11A participates in epithelial cell polarization (PubMed:21282656). May be involved in ciliogenesis (PubMed:21844891, PubMed:30398148). Together with MICALL2, may also regulate adherens junction assembly (By similarity). May play a role in insulin-induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore play a role in glucose homeostasis (By similarity). Involved in autophagy (PubMed:27103069). (updated: July 31, 2019)
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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
(right-click above to access to more options from the contextual menu)
Biological Process
Autophagy
Axonogenesis
Cellular response to insulin stimulus
Ciliary basal body-plasma membrane docking
Cilium assembly
Cilium assembly
G2/M transition of mitotic cell cycle
Golgi vesicle fusion to target membrane
Intracellular protein transport
Membrane organization
Metabolic process
Mitotic cell cycle
Neurotransmitter receptor transport to postsynaptic membrane
Neurotransmitter receptor transport, endosome to postsynaptic membrane
Organelle organization
Post-translational protein modification
Protein localization to plasma membrane
Protein secretion
Rab protein signal transduction
Regulation of autophagy
Regulation of exocytosis
Regulation of long-term neuronal synaptic plasticity
Regulation of protein transport
Synaptic vesicle exocytosis
Vesicle docking involved in exocytosis
Vesicle-mediated transport in synapse
Cellular Component
Centriole
Centrosome
Ciliary basal body
Ciliary base
Cilium
Cytoplasmic vesicle membrane
Cytosol
Dendrite
Dendritic spine
Endomembrane system
Endosome
Extracellular exosome
Extracellular matrix
Glutamatergic synapse
Golgi membrane
Midbody
Neuronal cell body
Non-motile cilium
Nonmotile primary cilium
Nucleolus
Nucleoplasm
Nucleus
Phagocytic vesicle
Phagocytic vesicle membrane
Plasma membrane
Postsynaptic density
Primary cilium
Recycling endosome membrane
Secretory granule membrane
Synaptic vesicle
Trans-Golgi network membrane
Trans-Golgi network transport vesicle
The reference OMIM entry for this protein is 165040
Ras-associated protein rab8a; rab8a
Ras-associated protein rab8; rab8
Oncogene mel; mel
DESCRIPTION
Members of the RAS superfamily, such as RAB8A, are small GTP/GDP-binding proteins with an average size of 200 amino acids. The RAS-related proteins of the RAB/YPT family may play a role in the transport of proteins from the endoplasmic reticulum to the Golgi and the plasma membrane (Nimmo et al., 1991).CLONING
Using DNA transfection into NIH 3T3 cells, Padua et al. (1984) demonstrated that the human malignant melanoma cell line NK14 contains a novel transforming gene. Nimmo et al. (1991) isolated human MEL genomic clones and cDNAs, as well as a cDNA encoding the mouse MEL homolog. The predicted 206-amino acid human MEL protein shares 97%, 96%, and 51% identity with the dog RAB8, mouse MEL, and mouse YPT1 (RAB1; 179508) proteins, respectively. MEL contains the 4 GTP/GDP-binding sites that are present in all the RAS proteins. The putative effector-binding site of MEL is similar to that of the RAB/YPT proteins. However, MEL contains a C-terminal CAAX motif that is characteristic of many RAS superfamily members but which is not found in YPT1 and the majority of RAB proteins.GENE FUNCTION
Sato et al. (2007) showed that Rab8 is responsible for the localization of apical proteins in intestinal epithelial cells. The authors found that apical peptidases and transporters localized to lysosomes in the small intestine of Rab8-deficient mice. Their mislocalization and degradation in lysosomes led to a marked reduction in the absorption rate of nutrients in the small intestine, and ultimately to death. Ultrastructurally, a shortening of apical microvilli, an increased number of enlarged lysosomes, and microvillus inclusions in the enterocytes were also observed. One patient with microvillus inclusion disease (251850) who showed an identical phenotype to that of Rab8-deficient mice expressed a reduced amount of Rab8. Sato et al. (2007) concluded that RAB8 is necessary for the proper localization of apical proteins and the absorption and digestion of various nutrients in the small intestine. 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 (RABEP1; 603616), a regulator of endocytosis, and rabaptin-5 in turn interacted with Rab8. 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. RAB8A regulates cilia assembly by targeting and promoting fusion of vesicles near the ciliary membrane. Tsang et al. (2008) found that RAB8A localized to the centrosome in growing human RPE1 retinal pigment epithelial cells and to the ciliary membrane in quiescent cells. RAB8A bound a central domain of CEP290 (610142) and interacted with CEP290 in both growing and quiescent cells. Both RAB8A and CEP290 interacted with CP110 (609544) in growing cells. Knockdown of CEP290 prevented ciliogenesis in differentiating RPE1 cells and reduced the number of RAB8A foci. Tsang et al. (2008) concluded that RAB8A requires CEP290 for centrosome localization and that CEP290 regulates entry of RAB8A into the cilium during assembly of this organelle. Hsiao et al. (2009) showed that AHI1 (608894), which is mutated in Joubert syndrome type 3 (JBTS3; 608629), regulated formation of the primary nonmotile cilium via its interaction with RAB8 ... More on the omim web site
Aug. 20, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 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 165040 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed