RAB11B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2F9L, 2F9M, 4OJK
Identifiers
Aliases	RAB11B, H-YPT3, member RAS oncogene family, NDAGSCW
External IDs	OMIM: 604198 MGI: 99425 HomoloGene: 68691 GeneCards: RAB11B
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.2 Start 8,389,981 bp[1] End 8,404,434 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17 B1|17 17.98 cM Start 33,961,458 bp[2] End 33,979,504 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of thyroid gland left lobe of thyroid gland right uterine tube popliteal artery ganglionic eminence anterior pituitary right coronary artery body of stomach gastric mucosa thoracic aorta Top expressed in superior frontal gyrus lip esophagus otolith organ utricle yolk sac neural tube thymus ciliary body morula More reference expression data BioGPS n/a
Gene ontology Molecular function nucleotide binding GDP binding GTP binding myosin V binding protein binding GTPase activity cadherin binding Cellular component cytoplasm recycling endosome endosome phagocytic vesicle membrane membrane synaptic vesicle synapse synaptic vesicle membrane phagocytic vesicle mitochondrion extracellular exosome cytoplasmic vesicle cytosol cell junction recycling endosome membrane anchored component of synaptic vesicle membrane Biological process regulation of protein localization to cell surface transferrin transport regulation of endocytic recycling establishment of protein localization to membrane cellular response to acidic pH constitutive secretory pathway receptor recycling melanosome transport transport protein transport regulated exocytosis regulation of anion transport insulin secretion involved in cellular response to glucose stimulus membrane organization post-translational protein modification intracellular protein transport exocytosis Rab protein signal transduction amyloid-beta clearance by transcytosis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9230 19326 Ensembl ENSG00000185236 ENSMUSG00000077450 UniProt Q15907 P46638 RefSeq (mRNA) NM_004218 NM_008997 RefSeq (protein) NP_004209 NP_033023 Location (UCSC) Chr 19: 8.39 – 8.4 Mb Chr 17: 33.96 – 33.98 Mb PubMed search [3] [4]
Wikidata
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Ras-related protein Rab-11B is a protein that in humans is encoded by the RAB11B gene.^[5][6] Rab11b is reported as most abundantly expressed in brain, heart and testes.

Rab (Ras-related in brain) proteins form the largest section of the Ras superfamily of small GTPases. The Rab family proteins regulate intracellular membrane trafficking processes including vesicle budding, tethering, and fusion. The isoforms Rab11a, Rab11b, and Rab11c/Rab25 constitute the Rab11 subfamily based on specific sequence motifs.^[7] While RAB11A is located on chromosome 15^[8] and RAB11C on chromosome 1, RAB11B is placed on chromosome 19. Rab11 proteins are implicated in endocytosis and exocytosis.^[9] Rab11b is reported as most abundantly expressed in brain, heart and testes.^[10] Early studies with deletions of RAB11 homologs in Saccharomyces cerevisiae proved their importance in cell survival.^[11][12] Despite sharing high sequence homology, Rab11a and Rab11b appear to reside within distinct vesicle compartments.^[13] Majority of Rab11b neither colocalize with transferrin receptor nor with the polymeric IgA receptor. This protein also exhibits a dependence on the microtubule cytoskeleton that is different from Rab11a.^[13] High sequence diversity in the C-terminal hypervariable region is responsible for variable membrane targeting between these proteins.

Function

Members of the Rab11 subfamily act in recycling of proteins from the endosomes to the plasma membrane, in transport of molecules from the trans-Golgi network to the plasma membrane and in phagocytosis. This subfamily also acts in polarized transport in epithelial cells.^{[14][15][16][17][18]} Whereas most studies refer to the Rab11a isoform, little is known about Rab11b so far. Rab11b localizes predominantly in the pericentriolar recycling compartment and serves as an important component of the vesicular machinery.^[19] It is required for the transfer of internalized transferrin from the recycling compartment to the plasma membrane for which active Rab11b as well as GTP hydrolysis is necessary.^[19]

Structure

All Ras GTPases consist of a similar core structure and highly conserved P-loop, switch 1 and switch 2 regions. The Rab11b monomer exhibits a typical Ras-like, small GTPase fold with a six stranded β-sheet core (β1-β6) surrounded by five major α-helices (α1-α5)^[16] and one minor α-helix (α6). According to the sequence similarity to other Rab GTPases can be assumed that they show closely resembling characteristics in nucleotide binding and hydrolysis. However, Rab11 isoforms could differ in hydrolysis kinetics owing to the differences in conformation, since Rab11a and Rab11b do not show an α-helical switch 2 region like other Rab GTPases. Rab11b shares 90% amino acid identity to Rab11a.^[16] Kinetic experiments with Rab11a/b and Rab11-interacting proteins (FIPs) indicate that FIPs cannot differentiate between GTP-bound Rab11a and Rab11b in vitro.^[20] The major divergence reveals in the inactive state. While Pasqualato et al. crystallized inactive Rab11a as a dimer in the asymmetric unit, Scapin et al. observed single crystallographically independent monomers of both the GDP- and the GppNHp-bound Rab11b structures.^[16][21]

Cartoon model of active Rab11b-GppNP complex (PDB-ID: 2F9M^[16]). This model includes amino acids 8–188. The model shows classic Ras-like structure with a six stranded beta sheet core encircled by 5 major and one minor α-helix. GppNp and Mg2+ form polar bonds with the residues S20, K24, S25, N27, S40/S42/T43 (switch1), N124, K125, D127, S154, and with some parts of the backbone highlighted in olive green. Hydrogen-bonds are drawn as black dots. Atoms of GppNP, Mg2+, and sidechains are colored corresponding to their element. O = red, N = blue, P = orange, and Mg = green. The purple sequence represents the Rab-typical α310 helix region.

Alignment of inactive and active Rab11b (PDB-IDs: 2F9L/2F9M^[16]). The alignment shows slight conformational differences between the GDP- and the GppNP-bound form. Major divergences are displayed in red. The Rab11b-GDP structure shows the α310 helix in the switch 2 region whereas Rab11b-GppNP does not. Rab11b-GDP model lacks in the switch 1 section 39–41. These amino acids could not be modeled from the electron density map. Due to the lack in switch 1 structure, the two states are not comparable from these models. Furthermore, the inactive state shows a truncated α-6 helix.

Clinical significance

Due to their crucial importance in vesicle transport and recycling, Rab11 proteins are linked to various non-pathogen or pathogen induced diseases. Most of the published data do not specify whether it is the a- or the b-isoform. Rab11 proteins have been implicated in Alzheimer's disease,^[22][23] Arthrogryposis-renal dysfunction-cholestasis (ARC),^[24] Batten disease,^[25] and Charcot-Marie-Tooth Neuropathy Type 4C (CMT4C).^[26] Intracellular bacteria Chlamydia pneumoniae and Chlamydia trachomatis that replicate in membrane bound compartments hijack the trafficking machinery recruiting Rab GTPases to promote their replication within the host cell. Knock down of Rab11 decreased the formation of infectious particles.^[27][28][29] Recent studies report a similar use of intracellular trafficking by Hantavirus and Influenza A virus. Replicated viruses benefit from Rab11 mediated recycling endosome pathway to exit the cell and infect surrounding tissue.^{[30][31][32][33]}

References

Further reading