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83  structures 303  species 4  interactions 4150  sequences 139  architectures

Family: RGS (PF00615)

Summary: Regulator of G protein signaling domain

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This is the Wikipedia entry entitled "Regulator of G protein signalling". More...

Regulator of G protein signalling Edit Wikipedia article

Regulator of G-Protein Signaling Domain
PDB 1gia EBI.jpg
Structures of active conformations of Gi alpha 1.[1]
Identifiers
Symbol RGS
Pfam PF00615
InterPro IPR000342
SMART RGS
PROSITE PDOC50132
SCOP 1gia
SUPERFAMILY 1gia
OPM protein 2bcj

Regulators of G protein signaling (or RGS) are protein structural domains that activate GTPases for heterotrimeric G-protein alpha-subunits.

RGS 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 signaling pathways.[2] 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 (IPR001019), which can then bind the beta-gamma dimer (IPR001632 IPR001770) 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 little more than an RGS domain, while others also contain additional domains that confer further functionality.[3]

RGS domains can be found within the same protein in combination with a variety of other domains, including: DEP for membrane targeting (IPR000591), PDZ for binding to GPCRs (IPR001478), PTB for phosphotyrosine-binding (IPR006020), RBD for Ras-binding (IPR003116), GoLoco for guanine nucleotide inhibitor activity (IPR003109), PX for phosphoinositide-binding (IPR001683), PXA that is associated with PX (IPR003114), PH for phosphatidylinositol-binding (IPR001849), and GGL (G protein gamma subunit-like) for binding G protein beta subunits (IPR001770 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.

Examples

Human proteins containing this domain include:

See also

GTP-binding protein regulators:

References

  1. ^ Coleman DE, Berghuis AM, Lee E, Linder ME, Gilman AG, Sprang SR (September 1994). "Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis". Science 265 (5177): 1405–12. doi:10.1126/science.8073283. PMID 8073283. 
  2. ^ De Vries L, Farquhar MG, Zheng B, Fischer T, Elenko E (2000). "The regulator of G protein signaling family". Annu. Rev. Pharmacol. Toxicol. 40: 235–271. doi:10.1146/annurev.pharmtox.40.1.235. PMID 10836135. 
  3. ^ Burchett SA (2000). "Regulators of G protein signaling: a bestiary of modular protein binding domains". J. Neurochem. 75 (4): 1335–1351. doi:10.1046/j.1471-4159.2000.0751335.x. PMID 10987813. 

Further reading

External links

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.

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RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.

Literature references

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000342

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 [PUBMED:10836135]. 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 [PUBMED:10987813]. 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) [PUBMED:15090201]. 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.

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 RGS (CL0272), which has the following description:

This clan includes RGS domains that possess an alpha helical fold.

The clan contains the following 2 members:

RGS RGS-like

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
(74)
Full
(4150)
Representative proteomes NCBI
(3808)
Meta
(11)
RP15
(835)
RP35
(1141)
RP55
(1805)
RP75
(2509)
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Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(74)
Full
(4150)
Representative proteomes NCBI
(3808)
Meta
(11)
RP15
(835)
RP35
(1141)
RP55
(1805)
RP75
(2509)
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
(74)
Full
(4150)
Representative proteomes NCBI
(3808)
Meta
(11)
RP15
(835)
RP35
(1141)
RP55
(1805)
RP75
(2509)
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: Domain
Author: Ponting C, Schultz J, Bork P
Number in seed: 74
Number in full: 4150
Average length of the domain: 120.60 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 22.88 %

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 21.0 21.0
Trusted cut-off 21.0 21.0
Noise cut-off 20.9 20.9
Model length: 118
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 4 interactions for this family. More...

G-gamma RGS WD40 Pkinase

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 83 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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