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106  structures 1260  species 0  interactions 19334  sequences 509  architectures

Family: RasGEF (PF00617)

Summary: RasGEF domain

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RasGEF domain Edit Wikipedia article

RasGEF domain
PDB 1bkd EBI.jpg
Structure of human H-Ras.[1]
Symbol RasGEF
Pfam PF00617
InterPro IPR001895
SCOP 1bkd
OPM protein 1xd4
CDD cd00155

RasGEF domain is domain found in the CDC25 family of guanine nucleotide exchange factors for Ras-like small GTPases.

Main article: Ras (protein)

Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP.[2] The balance between the GTP bound (active) and GDP bound (inactive) states is regulated by the opposite action of proteins activating the GTPase activity and that of proteins which promote the loss of bound GDP and the uptake of fresh GTP.[3][4] The latter proteins are known as guanine-nucleotide dissociation stimulators (GDSs) (or also as guanine-nucleotide releasing (or exchange) factors (GRFs)). Proteins that act as GDS can be classified into at least two families, on the basis of sequence similarities, the CDC24 family (see InterPro: IPR001331) and this CDC25 (RasGEF) family.

The size of the proteins of the CDC25 family range from 309 residues (LTE1) to 1596 residues (sos). The sequence similarity shared by all these proteins is limited to a region of about 250 amino acids generally located in their C-terminal section (currently the only exceptions are sos and ralGDS where this domain makes up the central part of the protein). This domain has been shown, in CDC25 an SCD25, to be essential for the activity of these proteins.

Human proteins containing this domain



  1. ^ Boriack-Sjodin PA, Margarit SM, Bar-Sagi D, Kuriyan J (July 1998). "The structural basis of the activation of Ras by Sos". Nature. 394 (6691): 337–43. doi:10.1038/28548. PMID 9690470. 
  2. ^ McCormick F, Bourne HR, Sanders DA (1991). "The GTPase superfamily: conserved structure and molecular mechanism". Nature. 349 (6305): 117–127. doi:10.1038/349117a0. PMID 1898771. 
  3. ^ McCormick F, Boguski MS (1993). "Proteins regulating Ras and its relatives". Nature. 366 (6456): 643–654. doi:10.1038/366643a0. PMID 8259209. 
  4. ^ Downward J (1992). "Ras regulation: putting back the GTP". Curr. Biol. 2 (6): 329–331. doi:10.1016/0960-9822(92)90897-J. PMID 15335949. 

Further reading

  • Boguski, MS; McCormick, F (1993). "Proteins regulating Ras and its relatives". Nature. 366 (6456): 643–54. doi:10.1038/366643a0. PMID 8259209. 
  • Quilliam, LA; Khosravi-Far, R; Huff, SY; Der, CJ (1995). "Guanine nucleotide exchange factors: Activators of the Ras superfamily of proteins". BioEssays. 17 (5): 395–404. doi:10.1002/bies.950170507. PMID 7786285. 
  • Li, N; Batzer, A; Daly, R; Yajnik, V; Skolnik, E; Chardin, P; Bar-Sagi, D; Margolis, B; Schlessinger, J (1993). "Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling". Nature. 363 (6424): 85–8. doi:10.1038/363085a0. PMID 8479541. 
  • Skolnik, EY; Batzer, A; Li, N; Lee, CH; Lowenstein, E; Mohammadi, M; Margolis, B; Schlessinger, J (1993). "The function of GRB2 in linking the insulin receptor to Ras signaling pathways". Science. 260 (5116): 1953–5. doi:10.1126/science.8316835. PMID 8316835. 

This article incorporates text from the public domain Pfam and InterPro IPR001895

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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RasGEF domain Provide feedback

Guanine nucleotide exchange factor for Ras-like small GTPases.

Literature references

  1. Boguski MS, McCormick F; , Nature 1993;366:643-654.: Proteins regulating Ras and its relatives. PUBMED:8259209 EPMC:8259209

  2. Quilliam LA, Khosravi-Far R, Huff SY, Der CJ; , Bioessays 1995;17:395-404.: Guanine nucleotide exchange factors: activators of the Ras superfamily of proteins. PUBMED:7786285 EPMC:7786285

  3. Li N, Batzer A, Daly R, Yajnik V, Skolnik E, Chardin P, Bar-Sagi D, Margolis B, Schlessinger J; , Nature 1993;363:85-88.: Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling. PUBMED:8479541 EPMC:8479541

  4. Skolnik EY, Batzer A, Li N, Lee CH, Lowenstein E, Mohammadi M, Margolis B, Schlessinger J; , Science 1993;260:1953-1955.: The function of GRB2 in linking the insulin receptor to Ras signaling pathways. PUBMED:8316835 EPMC:8316835

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001895

Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP [ PUBMED:1898771 ] in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. The balance between the GTP bound (active) and GDP bound (inactive) states is regulated by the opposite action of proteins activating the GTPase activity and that of proteins which promote the loss of bound GDP and the uptake of fresh GTP [ PUBMED:8259209 , PUBMED:15335949 ]. The latter proteins are known as guanine-nucleotide exchange (or releasing) factors (GEFs or GRFs) (or also as guanine-nucleotide dissociation stimulators (GDSs)). GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors [ PUBMED:9438849 , PUBMED:7786285 ].

The crystal structure of the GEF region of human Sos1 complexes with Ras has been solved [ PUBMED:8094051 ]. The structure consists of two distinct alpha helical structural domains: the N-terminal domain which seems to have a purely structural role and the C-terminal domain which is sufficient for catalytic activity and contains all residues that interact with Ras. A main feature of the catalytic domain is the protrusion of a helical hairpin important for the nucleotide-exchange mechanism. The N-terminal domain is likely to be important for the stability and correct placement of the hairpin structure.

Some proteins known to contain a Ras-GEF domain are listed below:

  • Cdc25 from yeast.
  • Scd25 from yeast.
  • Ste6 from fission yeast.
  • Son of sevenless (gene sos) from Drosophila and mammals.
  • p140-RAS GRF (cdc25Mm) from mammals. This protein possesses both a domain belonging to the CDC25 family and one belonging to the CDC24 family.
  • Bud5 from yeast, that may interact with the ras-like protein RSR1/BUD1.
  • Lte1 from yeast, whose target protein is not yet known.
  • ralGDS from mammals, which interacts with the ras-like proteins ralA and ralB [ PUBMED:8094051 ].

This entry represents the catalytic domain of the Ras guanine-nucleotide exchange factors.

Gene Ontology

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Domain organisation

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We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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Curation and family details

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Seed source: SMART
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Ponting CP , Schultz J, Bork P
Number in seed: 631
Number in full: 19334
Average length of the domain: 182.10 aa
Average identity of full alignment: 26 %
Average coverage of the sequence by the domain: 18.58 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.1 23.1
Trusted cut-off 23.1 23.1
Noise cut-off 23.0 23.0
Model length: 179
Family (HMM) version: 21
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Species distribution

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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the RasGEF domain has been found. There are 106 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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