RABRab subfamily of small GTPases
|SMART accession number:||SM00175|
|Description:||Rab GTPases are implicated in vesicle trafficking.|
|Interpro abstract (IPR003579):|
Small GTPases form an independent superfamily within the larger class of regulatory GTP hydrolases. This superfamily contains proteins that control a vast number of important processes and possess a common, structurally preserved GTP-binding domain [(PUBMED:2122258), (PUBMED:1898771)]. Sequence comparisons of small G proteins from various species have revealed that they are conserved in primary structures at the level of 30-55% similarity [(PUBMED:2029511)].
Crystallographic analysis of various small G proteins revealed the presence of a 20 kDa catalytic domain that is unique for the whole superfamily [(PUBMED:1898771), (PUBMED:2196171)]. The domain is built of five alpha helices (A1-A5), six beta-strands (B1-B6) and five polypeptide loops (G1-G5). A structural comparison of the GTP- and GDP-bound form, allows one to distinguish two functional loop regions: switch I and switch II that surround the gamma-phosphate group of the nucleotide. The G1 loop (also called the P-loop) that connects the B1 strand and the A1 helix is responsible for the binding of the phosphate groups. The G3 loop provides residues for Mg(2+) and phosphate binding and is located at the N terminus of the A2 helix. The G1 and G3 loops are sequentially similar to Walker A and Walker B boxes that are found in other nucleotide binding motifs. The G2 loop connects the A1 helix and the B2 strand and contains a conserved Thr residue responsible for Mg(2+) binding. The guanine base is recognised by the G4 and G5 loops. The consensus sequence NKXD of the G4 loop contains Lys and Asp residues directly interacting with the nucleotide. Part of the G5 loop located between B6 and A5 acts as a recognition site for the guanine base [(PUBMED:11995995)].
The small GTPase superfamily can be divided into at least 8 different families, including:
Rab-like GTPases are key regulators of most if not all vesicular trafficking events between the various subcellular compartments within the eukaryotic cell. Rab-related proteins have been implicated in regulating the formation of vesicles at the donor membrane, as well as the movement, tethering and docking of vesicles, and their fusion with the acceptor membrane [(PUBMED:15561774)]. The regulatory capacity of Rab-like proteins is dependent on their ability to cycle between GTP-bound active and GDP-bound inactive states. Activation of a Rab is coupled to its association with intracellular membranes, allowing it to recruit downstream effector proteins to the cytoplasmic surface of a subcellular compartment [(PUBMED:15153432)].
The crystal structures of a number of Rab GTPases have been determined:
|GO process:||protein transport (GO:0015031), small GTPase mediated signal transduction (GO:0007264)|
|GO function:||GTP binding (GO:0005525)|
Click on the following links for more information.
- Evolution (species in which this domain is found)
- Cellular role (predicted cellular role)
- Literature (relevant references for this domain)
- Disease (disease genes where sequence variants are found in this domain)
- Metabolism (metabolic pathways involving proteins which contain this domain)
- Structure (3D structures containing this domain)
- Links (links to other resources describing this domain)