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68  structures 301  species 5  interactions 7395  sequences 583  architectures

Family: RhoGEF (PF00621)

Summary: RhoGEF domain

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This is the Wikipedia entry entitled "RhoGEF domain". More...

RhoGEF domain Edit Wikipedia article

RhoGEF domain
PDB 1dbh EBI.jpg
Structure of the Dbl and pleckstrin homology domains from the human Son of sevenless protein.[1]
Identifiers
Symbol RhoGEF
Pfam PF00621
InterPro IPR000219
SMART RhoGEF
SCOP 1dbh
SUPERFAMILY 1dbh
OPM protein 1xd4

RhoGEF domain is a structural domain of guanine nucleotide exchange factors for Rho/Rac/Cdc42-like GTPases. It is also called "Dbl-homologous" (DH) domain.

Subfamilies[edit]

Human proteins containing this domain[edit]

ABR; AKAP13; ARHGEF1; ARHGEF10; ARHGEF10L; ARHGEF11; ARHGEF12; ARHGEF15; ARHGEF16; ARHGEF17; ARHGEF18; ARHGEF19; ARHGEF2; ARHGEF3; ARHGEF4; ARHGEF5; ARHGEF6; ARHGEF7; ARHGEF9; ASEF2; BCR; C9orf100; DEPDC2; DNMBP; ECT2; FARP1; FARP2; FGD1; FGD2; FGD3; FGD4; FGD5; FGD6; GEFT; ITSN1; ITSN2; KALRN; LFDH; MCF2; MCF2L; MCF2L2; NET1; NGEF; OBSCN; PLEKHG1; PLEKHG2; PLEKHG3; PLEKHG4; PLEKHG5; PLEKHG6; PREX1; RASGRF1; SGEF; SOS1; SOS2; SPATA13; TIAM1; TIAM2; TRIO; VAV1; VAV2; VAV3;

Notes[edit]

  1. ^ Soisson, S.; Nimnual, A.; Uy, M.; Bar-Sagi, D.; Kuriyan, J. (1998). "Crystal Structure of the Dbl and Pleckstrin Homology Domains from the Human Son of Sevenless Protein". Cell 95 (2): 259–268. doi:10.1016/S0092-8674(00)81756-0. PMID 9790532.  edit

References[edit]

  • Cerione, R. A.; Zheng, Y. (1996). "The Dbl family of oncogenes". Current opinion in cell biology 8 (2): 216–222. PMID 8791419.  edit
  • Hart, M. J.; Eva, A.; Evans, T.; Aaronson, S. A.; Cerione, R. A. (1991). "Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbloncogene product". Nature 354 (6351): 311–314. doi:10.1038/354311a0. PMID 1956381.  edit
  • Tan, E. C.; Leung, T.; Manser, E.; Lim, L. (1993). "The human active breakpoint cluster region-related gene encodes a brain protein with homology to guanine nucleotide exchange proteins and GTPase-activating proteins". The Journal of biological chemistry 268 (36): 27291–27298. PMID 8262969.  edit
  • Soisson, S.; Nimnual, A.; Uy, M.; Bar-Sagi, D.; Kuriyan, J. (1998). "Crystal Structure of the Dbl and Pleckstrin Homology Domains from the Human Son of Sevenless Protein". Cell 95 (2): 259–268. doi:10.1016/S0092-8674(00)81756-0. PMID 9790532.  edit

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RhoGEF domain Provide feedback

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PF00169 domains invariably occur C-terminal to RhoGEF/DH domains.

Literature references

  1. Cerione RA, Zheng Y; , Curr Opin Cell Biol 1996;8:216-222.: The Dbl family of oncogenes. PUBMED:8791419 EPMC:8791419

  2. Hart MJ, Eva A, Evans T, Aaronson SA, Cerione RA; , Nature 1991;354:311-314.: Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbl oncogene product. PUBMED:1956381 EPMC:1956381

  3. Tan EC, Leung T, Manser E, Lim L; , J Biol Chem 1993;268:27291-27298.: The human active breakpoint cluster region-related gene encodes a brain protein with homology to guanine nucleotide exchange proteins and GTPase-activating proteins. PUBMED:8262969 EPMC:8262969

  4. Soisson SM, Nimnual AS, Uy M, Bar-Sagi D, Kuriyan J; , Cell 1998;95:259-268.: Crystal structure of the Dbl and pleckstrin homology domains from the human Son of sevenless protein. PUBMED:9790532 EPMC:9790532


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000219

The Rho family GTPases Rho, Rac and CDC42 regulate a diverse array of cellular processes. Like all members of the Ras superfamily, the Rho proteins cycle between active GTP-bound and inactive GDP-bound conformational states. Activation of Rho proteins through release of bound GDP and subsequent binding of GTP, is catalysed by guanine nucleotide exchange factors (GEFs) in the Dbl family. The proteins encoded by members of the Dbl family share a common domain, presented in this entry, of about 200 residues (designated the Dbl homology or DH domain) that has been shown to encode a GEF activity specific for a number of Rho family members. In addition, all family members possess a second, shared domain designated the pleckstrin homology (PH) domain (INTERPRO). Trio and its homologue UNC-73 are unique within the Dbl family insomuch as they encode two distinct DH/PH domain modules. The PH domain is invariably located immediately C-terminal to the DH domain and this invariant topography suggests a functional interdependence between these two structural modules. Biochemical data have established the role of the conserved DH domain in Rho GTPase interaction and activation, and the role of the tandem PH domain in intracellular targeting and/or regulation of DH domain function. The DH domain of Dbl has been shown to mediate oligomerisation that is mostly homophilic in nature. In addition to the tandem DH/PH domains Dbl family GEFs contain diverse structural motifs like serine/threonine kinase, RBD, PDZ, RGS, IQ, REM, Cdc25, RasGEF, CH, SH2, SH3, EF, spectrin or Ig.

The DH domain is composed of three structurally conserved regions separated by more variable regions. It does not share significant sequence homology with other subtypes of small G-protein GEF motifs such as the Cdc25 domain and the Sec7 domain, which specifically interact with Ras and ARF family small GTPases, respectively, nor with other Rho protein interactive motifs, indicating that the Dbl family proteins are evolutionarily unique. The DH domain is composed of 11 alpha helices that are folded into a flattened, elongated alpha-helix bundle in which two of the three conserved regions, conserved region 1 (CR1) and conserved region 3 (CR3), are exposed near the centre of one surface. CR1 and CR3, together with a part of alpha-6 and the DH/PH junction site, constitute the Rho GTPase interacting pocket.

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
(192)
Full
(7395)
Representative proteomes NCBI
(6705)
Meta
(27)
RP15
(1275)
RP35
(1737)
RP55
(2801)
RP75
(4161)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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Format an alignment

  Seed
(192)
Full
(7395)
Representative proteomes NCBI
(6705)
Meta
(27)
RP15
(1275)
RP35
(1737)
RP55
(2801)
RP75
(4161)
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
(192)
Full
(7395)
Representative proteomes NCBI
(6705)
Meta
(27)
RP15
(1275)
RP35
(1737)
RP55
(2801)
RP75
(4161)
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: Alignment kindly provided by SMART
Previous IDs: none
Type: Domain
Author: SMART
Number in seed: 192
Number in full: 7395
Average length of the domain: 174.70 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 17.10 %

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 20.9 20.9
Trusted cut-off 21.0 21.0
Noise cut-off 20.8 20.8
Model length: 180
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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Interactions

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

PH SH3_1 Ras RhoGEF RasGEF_N

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 RhoGEF domain has been found. There are 68 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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