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6  structures 254  species 1  interaction 1769  sequences 106  architectures

Family: RasGAP (PF00616)

Summary: GTPase-activator protein for Ras-like GTPase

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This is the Wikipedia entry entitled "GTPase-activator protein for Ras-like GTPase". More...

GTPase-activator protein for Ras-like GTPase Edit Wikipedia article

GTPase-activator protein for Ras-like GTPase
Identifiers
Symbol RasGAP
Pfam PF00616
InterPro IPR001936
SMART RasGAP
SCOP 1wer
SUPERFAMILY 1wer
CDD cd04519

GTPase-activator protein for Ras-like GTPase is a family of evolutionarily related proteins.

Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP.[1] This intrinsic GTPase activity of ras is stimulated by a family of proteins collectively known as 'GAP' or GTPase-activating proteins.[2][3] As it is the GTP bound form of ras which is active, these proteins are said to be down-regulators of ras.

The Ras GTPase-activating proteins are quite large (from 765 residues for sar1 to 3079 residues for IRA2) but share only a limited (about 250 residues) region of sequence similarity, referred to as the 'catalytic domain' or rasGAP domain.

Note: There are distinctly different GAPs for the rap and rho/rac subfamilies of ras-like proteins (reviewed in reference[4]) that do not share sequence similarity with ras GAPs.

Examples

Human genes encoding proteins containing this domain include:

References

  1. ^ 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. 
  2. ^ Wang Y, Riggs M, Rodgers L, Wigler M, Boguski M (1991). "sar1, a gene from Schizosaccharomyces pombe encoding a protein that regulates ras1". Cell Regul. 2 (6): 453–465. doi:10.1091/mbc.2.6.453. PMC 361829. PMID 1883874. 
  3. ^ Maruta H, Burgess AW (1994). "Regulation of the Ras signalling network". BioEssays 16 (7): 489–496. doi:10.1002/bies.950160708. PMID 7945277. 
  4. ^ McCormick F, Boguski MS (1993). "Proteins regulating Ras and its relatives". Nature 366 (6456): 643–654. doi:10.1038/366643a0. PMID 8259209. 


This article incorporates text from the public domain Pfam and InterPro IPR001936


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.

GTPase-activator protein for Ras-like GTPase Provide feedback

All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position.

Literature references

  1. Scheffzek K, Lautwein A, Kabsch W, Ahmadian MR, Wittinghofer A; , Nature 1996;384:591-596.: Crystal structure of the GTPase-activating domain of human p120GAP and implications for the interaction with Ras. PUBMED:8955277 EPMC:8955277

  2. Wittinghofer A, Scheffzek K, Ahmadian MR; , FEBS Lett 1997;410:63-67.: The interaction of Ras with GTPase-activating proteins. PUBMED:9247124 EPMC:9247124

  3. Xu GF, O'Connell P, Viskochil D, Cawthon R, Robertson M, Culver M, Dunn D, Stevens J, Gesteland R, White R, et al; , Cell 1990;62:599-608.: The neurofibromatosis type 1 gene encodes a protein related to GAP. PUBMED:2116237 EPMC:2116237


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001936

Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP [PUBMED:1898771]. This intrinsic GTPase activity of ras is stimulated by a family of proteins collectively known as 'GAP' or GTPase-activating proteins [PUBMED:1883874, PUBMED:7945277]. As it is the GTP bound form of ras which is active, these proteins are said to be down-regulators of ras.

The Ras GTPase-activating proteins are quite large (from 765 residues for sar1 to 3079 residues for IRA2) but share only a limited (about 250 residues) region of sequence similarity, referred to as the 'catalytic domain' or rasGAP domain.

Note: There are distinctly different GAPs for the rap and rho/rac subfamilies of ras-like proteins (reviewed in reference [PUBMED:8259209]) that do not share sequence similarity with ras GAPs.

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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Pfam Clan

This family is a member of clan GAP (CL0409), which has the following description:

Superfamily contains BCR-homology GTPase activation domain (BH-domain) and p120GAP domain-like, including the GAP related domain of neurofibromin, families.

The clan contains the following 3 members:

DUF1708 RasGAP RhoGAP

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
(115)
Full
(1769)
Representative proteomes NCBI
(1705)
Meta
(9)
RP15
(379)
RP35
(541)
RP55
(819)
RP75
(1114)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

Format an alignment

  Seed
(115)
Full
(1769)
Representative proteomes NCBI
(1705)
Meta
(9)
RP15
(379)
RP35
(541)
RP55
(819)
RP75
(1114)
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
(115)
Full
(1769)
Representative proteomes NCBI
(1705)
Meta
(9)
RP15
(379)
RP35
(541)
RP55
(819)
RP75
(1114)
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: 115
Number in full: 1769
Average length of the domain: 183.90 aa
Average identity of full alignment: 26 %
Average coverage of the sequence by the domain: 14.50 %

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 28.1 28.1
Trusted cut-off 28.1 28.1
Noise cut-off 28.0 28.0
Model length: 197
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

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 RasGAP domain has been found. There are 6 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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