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Protein Domain : 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.

Publication Counts Displayer

2 Child Features

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

0 Contains

3 Cross References

Identifier
Source . Name

Subject . Primary Identifier
PTHR24070 PANTHER IPR020849
PS51421 PROFILE IPR020849
SM00173 SMART IPR020849

3 Data Sets

Name URL
Swiss-Prot data set http://ca.expasy.org/sprot
InterPro data set  
InterPro GO Annotation data set  

0 Found In

4 GO Annotation


Subject . Secondary Identifier

Subject . Name

Subject . Symbol

Ontology Term . Identifier

Ontology Term . Name
Small GTPase superfamily, Ras type   GO:0005525 GTP binding
Small GTPase superfamily, Ras type   GO:0006184 GTP catabolic process
Small GTPase superfamily, Ras type   GO:0007165 signal transduction
Small GTPase superfamily, Ras type   GO:0016020 membrane

4 Ontology Annotations


Subject . Secondary Identifier

Subject . Name

Subject . Symbol

Ontology Term . Identifier

Ontology Term . Name
Small GTPase superfamily, Ras type   GO:0005525 GTP binding
Small GTPase superfamily, Ras type   GO:0006184 GTP catabolic process
Small GTPase superfamily, Ras type   GO:0007165 signal transduction
Small GTPase superfamily, Ras type   GO:0016020 membrane

1 Parent Features

DB identifier Name Short Name Type
IPR001806 Small GTPase superfamily Small_GTPase Family

214 Proteins

DB identifier Primary Accession
Organism . Name
FBpp0086392 Q7JMZ0 Drosophila melanogaster
FBpp0072086 O96692 Drosophila melanogaster
FBpp0070098 Q9W5G7 Drosophila melanogaster
FBpp0081617 Q9VH66 Drosophila melanogaster
FBpp0088074 Q9V4L4 Drosophila melanogaster
FBpp0085498 A1Z6R7 Drosophila melanogaster
FBpp0309684 A8DYK6 Drosophila melanogaster
FBpp0076640 Q9VS10 Drosophila melanogaster
FBpp0073068 P04388 Drosophila melanogaster
FBpp0079092 Q9VM20 Drosophila melanogaster
FBpp0081600 P08646 Drosophila melanogaster
FBpp0070559 P48555 Drosophila melanogaster
FBpp0070557 Q962I2 Drosophila melanogaster
FBpp0111545 Q6NN22 Drosophila melanogaster
FBpp0304663 M9PJ04 Drosophila melanogaster
FBpp0072746 P08645 Drosophila melanogaster
FBpp0078342 Q9VND8 Drosophila melanogaster
FBpp0076651 Q9VRY2 Drosophila melanogaster
FBpp0078328 Q9VNB7 Drosophila melanogaster
FBpp0306397 Q6NR39 Drosophila melanogaster
FBpp0290321 Q7KVX6 Drosophila melanogaster
FBpp0290322 Q2PE29 Drosophila melanogaster
FBpp0297125 D0IQG6 Drosophila melanogaster
FBpp0305285 D5A7K3 Drosophila melanogaster
FBpp0304662 M9PGL8 Drosophila melanogaster
FBpp0276552 Q28ZU5 Drosophila pseudoobscura
FBpp0285105 B5DUR5 Drosophila pseudoobscura
FBpp0277516 B5DZ13 Drosophila pseudoobscura
FBpp0273775 Q29GN2 Drosophila pseudoobscura
FBpp0274968 Q2M0S8 Drosophila pseudoobscura