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23  structures 292  species 5  interactions 3434  sequences 184  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]
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 a 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 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[edit]

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[edit]

  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[edit]

  • 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 : news and reviews in molecular, cellular and developmental biology 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. PMID 8316835. 

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


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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


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 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) and the CDC25 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.

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...

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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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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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
(148)
Full
(3434)
Representative proteomes NCBI
(3165)
Meta
(4)
RP15
(658)
RP35
(907)
RP55
(1382)
RP75
(1986)
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Format an alignment

  Seed
(148)
Full
(3434)
Representative proteomes NCBI
(3165)
Meta
(4)
RP15
(658)
RP35
(907)
RP55
(1382)
RP75
(1986)
Alignment:
Format:
Order:
Sequence:
Gaps:
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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
(148)
Full
(3434)
Representative proteomes NCBI
(3165)
Meta
(4)
RP15
(658)
RP35
(907)
RP55
(1382)
RP75
(1986)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped 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.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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: 148
Number in full: 3434
Average length of the domain: 186.00 aa
Average identity of full alignment: 25 %
Average coverage of the sequence by the domain: 19.95 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.8 20.8
Trusted cut-off 20.8 20.8
Noise cut-off 20.6 20.7
Model length: 188
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 5 interactions for this family. More...

RA DEP RasGEF_N RasGEF Ras

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 23 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.

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