InterPro : IPR020849

Name  Small GTPase superfamily, Ras type Short Name  Small_GTPase_Ras
Type  Family Description  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 [, ]. 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 [].Crystallographic analysis of various small G proteins revealed the presence of a 20 kDa catalytic domain that is unique for the whole superfamily [, ]. 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 [].The small GTPase superfamily can be divided into at least 8 different families, including:Arf small GTPases. GTP-binding proteins involved in protein trafficking by modulating vesicle budding and uncoating within the Golgi apparatus.Ran small GTPases. GTP-binding proteins involved in nucleocytoplasmic transport. Required for the import of proteins into the nucleus and also for RNA export.Rab small GTPases. GTP-binding proteins involved in vesicular traffic.Rho small GTPases. GTP-binding proteins that control cytoskeleton reorganisation.Ras small GTPases. GTP-binding proteins involved in signalling pathways.Sar1 small GTPases. Small GTPase component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER).Mitochondrial Rho (Miro). Small GTPase domain found in mitochondrial proteins involved in mitochondrial trafficking.Roc small GTPases domain. Small GTPase domain always found associated with the COR domain.Ras proteins are small GTPases that regulate cell growth, proliferation anddifferentiation. The different Ras isoforms: H-ras, N-ras and K-ras, generate distinct signaloutputs, despite interacting with a common set of activators and effectors. Ras is activated by guanine nucleotide exchange factors (GEFs) thatrelease GDP and allow GTP binding. Many RasGEFs have been identified.These are sequestered in the cytosol until activation by growth factorstriggers recruitment to the plasma membrane or Golgi, where the GEFcolocalizes with Ras. Active GTP-bound Ras interacts with severaleffector proteins: among the best characterised are the Raf kinases,phosphatidylinositol 3-kinase (PI3K), RalGEFs and NORE/MST1. Ras proteins are synthesized ascytosolic precursors that undergo post-translational processing to be ableto associate with cell membranes []. First, protein farnesyl transferase, a cytosolicenzyme, attaches a farnesyl group to the cysteine residue of the CAAXmotif. Second, the farnesylated CAAX sequence targets Ras to thecytosolic surface of the ER where an endopeptidase removes the AAX tripeptide. Third, the alpha-carboxyl group on the now carboxy-terminal farnesylcysteine ismethylated by isoprenylcysteine carboxyl methyltransferase. Finally, after methylation, Ras proteins take one oftwo routes to the cell surface, which is dictated by a second targetingsignal that is located immediately amino-terminal to the farnesylatedcysteine. N-ras and H-ras are expressedstably on the plasma membrane, on Golgi in transfected cells, and at least transiently on the ER. Ras has also been visualized on endosomes.

Sequence Features

GO Displayer


InterPro protein domain ID --> Contigs



2 Child Features

Id Name Short Name Type
IPR028412 Ras-related protein Ral Ral Family
IPR017358 Small GTPase superfamily, GEM/REM/Rad Small_GTPase_GEM/REM/Rad Family

0 Contains

0 Found In

1 Parent Features

Id Name Short Name Type
IPR001806 Small GTPase superfamily Small_GTPase Family

6 Publications

First Author Title Year Journal Volume Pages
Bourne HR The GTPase superfamily: conserved structure and molecular mechanism. 1991 Nature 349 117-27
Valencia A The ras protein family: evolutionary tree and role of conserved amino acids. 1991 Biochemistry 30 4637-48
Paduch M Structure of small G proteins and their regulators. 2001 Acta Biochim Pol 48 829-50
Pai EF Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35 A resolution: implications for the mechanism of GTP hydrolysis. 1990 EMBO J 9 2351-9
Bourne HR The GTPase superfamily: a conserved switch for diverse cell functions. 1990 Nature 348 125-32
Hancock JF Ras proteins: different signals from different locations. 2003 Nat Rev Mol Cell Biol 4 373-84

To cite PlanMine, please refer to the following publication:

Rozanski, A., Moon, H., Brandl, H., Martín-Durán, J. M., Grohme, M., Hüttner, K., Bartscherer, K., Henry, I., & Rink, J. C.
PlanMine 3.0—improvements to a mineable resource of flatworm biology and biodiversity
Nucleic Acids Research, gky1070. doi:10.1093/nar/gky1070 (2018)