Summary: Regulator of G protein signaling domain
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RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.
Literature references
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Tesmer JJ, Berman DM, Gilman AG, Sprang SR; , Cell 1997;89:251-261.: Structure of RGS4 bound to AlF4--activated G(i alpha1): stabilization of the transition state for GTP hydrolysis. PUBMED:9108480 EPMC:9108480
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Dohlman HG, Apaniesk D, Chen Y, Song J, Nusskern D; , Mol Cell Biol 1995;15:3635-3643.: Inhibition of G-protein signaling by dominant gain-of-function mutations in Sst2p, a pheromone desensitization factor in Saccharomyces cerevisiae. PUBMED:7791771 EPMC:7791771
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Watson N, Linder ME, Druey KM, Kehrl JH, Blumer KJ; , Nature 1996;383:172-175.: RGS family members: GTPase-activating proteins for heterotrimeric G-protein alpha-subunits. PUBMED:8774882 EPMC:8774882
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Berman DM, Wilkie TM, Gilman AG; , Cell 1996;86:445-452.: GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein alpha subunits. PUBMED:8756726 EPMC:8756726
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De Vries L, Mousli M, Wurmser A, Farquhar MG; , Proc Natl Acad Sci U S A 1995;92:11916-11920.: GAIP, a protein that specifically interacts with the trimeric G protein G alpha i3, is a member of a protein family with a highly conserved core domain. PUBMED:8524874 EPMC:8524874
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Anantharaman V, Abhiman S, de Souza RF, Aravind L;, Gene. 2011;475:63-78.: Comparative genomics uncovers novel structural and functional features of the heterotrimeric GTPase signaling system. PUBMED:21182906 EPMC:21182906
Internal database links
SCOOP: | Pkinase_fungal RGS-like |
Similarity to PfamA using HHSearch: | RGS-like |
External database links
HOMSTRAD: | RGS |
SCOP: | 1gia |
SMART: | RGS |
This tab holds annotation information from the InterPro database.
InterPro entry IPR016137
This entry represents a structural domain with a multi-helical fold consisting of a 4-helical bundle with a left-handed twist and an up-and-down topology. This domain can be divided into two all-alpha subdomains. This domain is found in regulation of G-protein signalling (RGS) proteins, as well as other related proteins, including:
- RGS4 [PUBMED:9108480].
- RGS9 [PUBMED:11234020].
- G-alpha interacting protein GaIP [PUBMED:10452897].
- Axin [PUBMED:10811618].
- p115RhoGEF [PUBMED:11524686].
- Pdz-RhoGEF [PUBMED:11470431].
- G-protein coupled receptor kinase 2 N-terminal domain [PUBMED:12764189].
RGS (Regulator of G Protein Signalling) proteins are multi-functional, GTPase-accelerating proteins that promote GTP hydrolysis by the alpha subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signalling pathways. Upon activation by GPCRs, heterotrimeric G proteins exchange GDP for GTP, are released from the receptor, and dissociate into free, active GTP-bound alpha subunit and beta-gamma dimer, both of which activate downstream effectors. The response is terminated upon GTP hydrolysis by the alpha subunit (INTERPRO), which can then bind the beta-gamma dimer (INTERPRO, INTERPRO) and the receptor. RGS proteins markedly reduce the lifespan of GTP-bound alpha subunits by stabilising the G protein transition state.
All RGS proteins contain an 'RGS-box' (or RGS domain), which is required for activity. Some small RGS proteins such as RGS1 and RGS4 are comprised of little more than an RGS domain, while others also contain additional domains that confer further functionality. RGS domains can be found in conjunction with a variety of domains, including: DEP for membrane targeting (INTERPRO), PDZ for binding to GPCRs (INTERPRO), PTB for phosphotyrosine-binding (INTERPRO), RBD for Ras-binding (INTERPRO), GoLoco for guanine nucleotide inhibitor activity (INTERPRO), PX for phosphatidylinositol-binding (INTERPRO), PXA that is associated with PX (INTERPRO), PH for stimulating guanine nucleotide exchange (INTERPRO), and GGL (G protein gamma subunit-like) for binding G protein beta subunits (INTERPRO). Those RGS proteins that contain GGL domains can interact with G protein beta subunits to form novel dimers that prevent G protein gamma subunit binding and G protein alpha subunit association, thereby preventing heterotrimer formation.
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
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...
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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 (60) |
Full (16156) |
Representative proteomes | UniProt (25591) |
NCBI (40984) |
Meta (11) |
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RP15 (2509) |
RP35 (5429) |
RP55 (10603) |
RP75 (16253) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
available,
not generated,
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Seed (60) |
Full (16156) |
Representative proteomes | UniProt (25591) |
NCBI (40984) |
Meta (11) |
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RP15 (2509) |
RP35 (5429) |
RP55 (10603) |
RP75 (16253) |
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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: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
Ponting CP |
Number in seed: | 60 |
Number in full: | 16156 |
Average length of the domain: | 121.70 aa |
Average identity of full alignment: | 22 % |
Average coverage of the sequence by the domain: | 22.59 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 118 | ||||||||||||
Family (HMM) version: | 20 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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Interactions
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 RGS domain has been found. There are 126 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.
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