Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
46  structures 478  species 7  interactions 4986  sequences 239  architectures

Family: RasGEF (PF00617)

Summary: RasGEF domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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]. 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)).

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

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Alignments

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, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(729)
Full
(4986)
Representative proteomes UniProt
(9010)
NCBI
(18857)
Meta
(4)
RP15
(1337)
RP35
(2387)
RP55
(3505)
RP75
(4480)
Jalview View  View  View  View  View  View  View  View  View 
HTML View  View               
PP/heatmap 1 View               

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(729)
Full
(4986)
Representative proteomes UniProt
(9010)
NCBI
(18857)
Meta
(4)
RP15
(1337)
RP35
(2387)
RP55
(3505)
RP75
(4480)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(729)
Full
(4986)
Representative proteomes UniProt
(9010)
NCBI
(18857)
Meta
(4)
RP15
(1337)
RP35
(2387)
RP55
(3505)
RP75
(4480)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: SMART
Previous IDs: none
Type: Family
Author: Ponting C, Schultz J, Bork P
Number in seed: 729
Number in full: 4986
Average length of the domain: 182.80 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 18.71 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.2 22.2
Trusted cut-off 22.2 22.3
Noise cut-off 22.1 22.1
Model length: 172
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Hide

Weight segments by...


Change the size of the sunburst

Small
Large

Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There are 7 interactions for this family. More...

DEP Ras RasGEF Ras RA RasGEF_N DUF3513

Structures

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 46 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 seqence.

Loading structure mapping...