Ras-related protein Rab-11A (RAB11A)
The protein contains 216 amino acids for an estimated molecular weight of 24394 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 set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. The small Rab GTPase RAB11A regulates endocytic recycling. Acts as a major regulator of membrane delivery during cytokinesis. Together with MYO5B and RAB8A participates in epithelial cell polarization. Together with RAB3IP, RAB8A, 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. Together with MYO5B participates in CFTR trafficking to the plasma membrane and TF (Transferrin) recycling in nonpolarized cells. Required in a complex with MYO5B and RAB11FIP2 for the transport of NPC1L1 to the plasma membrane. Participates in the sorting and basolateral transport of CDH1 from the Golgi apparatus to the plasma membrane. Regulates the recycling of FCGRT (receptor of Fc region of monomeric Ig G) to basolateral membranes. May also play a role in melanosome transport and release from melanocytes. (updated: May 8, 2019)
Protein identification was indicated in the following studies:
- 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.
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 UniProt.
(right-click above to access to more options from the contextual menu)
Biological Process
Amyloid-beta clearance by transcytosis
Astral microtubule organization
Ciliary basal body-plasma membrane docking
Cilium assembly
Establishment of protein localization to membrane
Establishment of protein localization to organelle
Establishment of vesicle localization
Exocytosis
Exosomal secretion
Intracellular protein transport
Melanosome transport
Mitotic metaphase plate congression
Mitotic spindle assembly
Multivesicular body assembly
Neuron projection development
Neurotransmitter receptor transport, endosome to postsynaptic membrane
Plasma membrane to endosome transport
Positive regulation of axon extension
Positive regulation of epithelial cell migration
Positive regulation of G2/M transition of mitotic cell cycle
Positive regulation of protein localization to plasma membrane
Post-translational protein modification
Protein localization to cell surface
Protein localization to plasma membrane
Rab protein signal transduction
Regulation of cytokinesis
Regulation of long-term neuronal synaptic plasticity
Regulation of multivesicular body size
Regulation of protein transport
Regulation of vesicle-mediated transport
Renal water homeostasis
Vesicle-mediated transport
Vesicle-mediated transport in synapse
Cellular Component
Axon
Centriolar satellite
Centrosome
Cleavage furrow
Cytoplasmic vesicle
Cytoplasmic vesicle membrane
Cytosol
Endomembrane system
Endosome
Extracellular exosome
Glutamatergic synapse
Golgi apparatus
Intracellular membrane-bounded organelle
Microtubule organizing center
Multivesicular body
Obsolete cell
Perinuclear region of cytoplasm
Phagocytic vesicle
Postsynaptic recycling endosome
Protein-containing complex
Recycling endosome
Recycling endosome membrane
Schaffer collateral - CA1 synapse
Spindle pole
Trans-Golgi network
Transport vesicle
Vesicle
Molecular Function
GTP binding
GTPase activity
Microtubule binding
Myosin V binding
Syntaxin binding
The reference OMIM entry for this protein is 605570
Ras-associated protein rab11a; rab11a
DESCRIPTION
Small GTP-binding proteins of the RAB family, such as RAB11A, play essential roles in vesicle and granule targeting (Bao et al., 2002).CLONING
Using PCR to amplify Ras and Ras-like sequences from carcinoma and T-cell cDNA libraries, Drivas et al. (1991) obtained a cDNA encoding RAB11A, which they termed YL8. RAB11A shares 69% homology with yeast Ypt3. The deduced 651-amino acid protein has many conserved features of Ras and Rab proteins, except that its C terminus lacks the cys-cys found in other Rab family members. Northern blot analysis detected expression in 4 tumor cell lines. By screening lambda libraries for small GTP-binding proteins, Gromov et al. (1998) identified 2 cDNAs, arising from alternative splicing, that encode RAB11A. Northern blot analysis revealed ubiquitous expression of 1.0- and 2.3-kb RAB11A transcripts, with highest levels in heart and lowest levels in liver. The larger transcript was more abundant in brain and lung, whereas the smaller transcript was more abundant in placenta and heart. Using RT-PCR, Bao et al. (2002) cloned RAB11A from human platelets. Western blot analysis detected RAB11A at an apparent molecular mass of 26 kD in human platelets and leukemia cell lines. Western blot analysis of rat tissues detected high Rab11a expression in platelets and much lower expression in kidney, liver, heart, lung, and brain. Differential centrifugation of human platelets showed enrichment of RAB11A in the granule/mitochondrion and membrane fractions, with a small amount in the cytosolic fraction.GENE FUNCTION
Bao et al. (2002) noted that mutation of a conserved glutamine (Q70) to leucine within the GTP-binding motif of RAB11A does not inhibit its GTPase activity (Casanova et al., 1999), in contrast to the effect of similar mutations in most small GTPases. Bao et al. (2002) found that mutation of the conserved glutamines in RAB31 (605694) and RAB32 (612906) also had no effect on their GTPase activities, suggesting that these proteins form a subfamily of small GTPases. Shirane and Nakayama (2006) identified protrudin (ZFYVE27; 610243) as a mammalian protein that promoted neurite formation through interaction with the guanosine diphosphate (GDP)-bound form of Rab11. Phosphorylation of protrudin by extracellular signal-regulated kinase (ERK; 600997) in response to nerve growth factor (NGFB; 162030) promoted protrudin association with Rab11-GDP. Downregulation of protrudin by RNA interference induced membrane extension in all directions and inhibited neurite formation. Thus, Shirane and Nakayama (2006) concluded that protrudin regulates Rab11-dependent membrane recycling to promote the directional membrane trafficking required for neurite formation. In muscle and fat cells, insulin (INS; 176730) stimulation activates a signaling cascade that causes intracellular vesicles containing glucose transporter-4 (GLUT4, or SLC2A4; 138190) to translocate to and fuse with the plasma membrane. Using mass spectrometry, Larance et al. (2005) identified Rab10 (612672), Rab11, and Rab14 (612673) on Glut4 vesicles from cultured mouse adipocytes. These vesicles also contained the RAB GTPase-activating protein As160 (TBC1D4; 612465), suggesting that the RAB proteins may be AS160 substrates. In lethal systemic anthrax, proliferating bacilli secrete large quantities of the toxins lethal factor (LF) and edema factor (EF), leading to widespread vascular leakage and shock. Host targets of LF (mitogen ... More on the omim web site
June 7, 2019: Protein entry updated
Automatic update: OMIM entry 605570 was added.
May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).