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.
This is the Wikipedia entry entitled "RasGEF domain". More...
RasGEF domain Edit Wikipedia article
RasGEF domain | |||||||||
---|---|---|---|---|---|---|---|---|---|
![]() Structure of human H-Ras.[1]
|
|||||||||
Identifiers | |||||||||
Symbol | RasGEF | ||||||||
Pfam | PF00617 | ||||||||
InterPro | IPR001895 | ||||||||
SMART | RasGEF | ||||||||
PROSITE | PDOC00594 | ||||||||
SCOP | 1bkd | ||||||||
SUPERFAMILY | 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.
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
KNDC1; PLCE1; RALGDS; RALGPS1; RALGPS2; RAPGEF1; RAPGEF2; RAPGEF3; RAPGEF4; RAPGEF5; RAPGEF6; RAPGEFL1; RASGEF1A; RASGEF1B; RASGEF1C; RASGRF1; RASGRF2; RASGRP1; RASGRP2; RASGRP3; RASGRP4; RGL1; RGL2; RGL3; RGL4/RGR; SOS1; SOS2;
References
- ^ 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.
- ^ 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.
- ^ McCormick F, Boguski MS (1993). "Proteins regulating Ras and its relatives". Nature. 366 (6456): 643–654. doi:10.1038/366643a0. PMID 8259209.
- ^ 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 membrane protein–related article is a stub. You can help Wikipedia by expanding it. |
This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
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
-
Boguski MS, McCormick F; , Nature 1993;366:643-654.: Proteins regulating Ras and its relatives. PUBMED:8259209 EPMC:8259209
-
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
-
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
-
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
SCOOP: | RasGEF_N |
External database links
SCOP: | 1bkd |
SMART: | RasGEF |
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
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
Molecular function | guanyl-nucleotide exchange factor activity (GO:0005085) |
Biological process | small GTPase mediated signal transduction (GO:0007264) |
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 and the UniProtKB 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 (631) |
Full (19334) |
Representative proteomes | UniProt (32674) |
||||
---|---|---|---|---|---|---|---|
RP15 (3050) |
RP35 (7307) |
RP55 (15848) |
RP75 (21649) |
||||
Jalview | |||||||
HTML | |||||||
PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
available,
not generated,
— not available.
Format an alignment
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 (631) |
Full (19334) |
Representative proteomes | UniProt (32674) |
||||
---|---|---|---|---|---|---|---|
RP15 (3050) |
RP35 (7307) |
RP55 (15848) |
RP75 (21649) |
||||
Raw Stockholm | |||||||
Gzipped |
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
Seed source: | SMART |
Previous IDs: | none |
Type: | Family |
Sequence Ontology: | SO:0100021 |
Author: |
Ponting CP |
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 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
|
||||||||||||
Model details: |
|
||||||||||||
Model length: | 179 | ||||||||||||
Family (HMM) version: | 21 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
Sunburst controls
HideWeight segments by...
Change the size of the sunburst
Colour assignments
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
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...
Tree controls
HideThe 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.
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 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.
Loading structure mapping...