The domain within your query sequence starts at position 7 and ends at position 68; the E-value for the GGL domain shown below is 2.79e-28.

VAAMKKVVQQLRLEAGLNRVKVSQAAADLKQFCLQNAQHDPLLTGVSSSTNPFRPQKVCS
FL

GGL

G protein gamma subunit-like motifs

• SMART accession number: SM00224
• Description: -
• Interpro abstract (IPR015898):

  This entry represents the G protein gamma subunit and the GGL (G protein gamma-like) domain, which are related in sequence and are comprised of an extended alpha-helical polypeptide. The G protein gamma subunit forms a stable dimer with the beta subunit, but it does not make any contact with the alpha subunit, which contacts the opposite face of the beta subunit. The GGL domain is found in several RGS (regulators of G protein signaling) proteins. GGL domains can interact with beta subunits to form novel dimers that prevent gamma subunit binding, and may prevent heterotrimer formation by inhibiting alpha subunit binding. The interaction between G protein beta-5 neuro-specific isoforms and RGS GGL domains may represent a general mode of binding between beta-propeller proteins and their partners [ (PUBMED:11331068) ].

• GO process: G protein-coupled receptor signaling pathway (GO:0007186)

There are 4851 GGL domains in 4845 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: signalling

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Snow BE et al.
• A G protein gamma subunit-like domain shared between RGS11 and other RGS proteins specifies binding to Gbeta5 subunits.
• Proc Natl Acad Sci U S A. 1998; 95: 13307-12

Regulators of G protein signaling (RGS) proteins act as GTPase-activating proteins (GAPs) toward the alpha subunits of heterotrimeric, signal-transducing G proteins. RGS11 contains a G protein gamma subunit-like (GGL) domain between its Dishevelled/Egl-10/Pleckstrin and RGS domains. GGL domains are also found in RGS6, RGS7, RGS9, and the Caenorhabditis elegans protein EGL-10. Coexpression of RGS11 with different Gbeta subunits reveals specific interaction between RGS11 and Gbeta5. The expression of mRNA for RGS11 and Gbeta5 in human tissues overlaps. The Gbeta5/RGS11 heterodimer acts as a GAP on Galphao, apparently selectively. RGS proteins that contain GGL domains appear to act as GAPs for Galpha proteins and form complexes with specific Gbeta subunits, adding to the combinatorial complexity of G protein-mediated signaling pathways.

• Garcia-Higuera I et al.
• Folding of proteins with WD-repeats: comparison of six members of the WD-repeat superfamily to the G protein beta subunit.
• Biochemistry. 1996; 35: 13985-94

The family of WD-repeat proteins comprises over 30 different proteins that share a highly conserved repeating motif [Neer, E. J., Schmidt, C. J., Nambudripad, R., & Smith, T. F. (1994) Nature 371, 297-300]. Members of this family include the signal-transducing G protein beta subunit, as well as other proteins that regulate signal transduction, transcription, pre-mRNA splicing, cytoskeletal organization, and vesicular fusion. The crystal structure of one WD-repeat protein (G beta) has now been solved (Wall et al., 1995; Sondek et al, 1996) and reveals that the seven repeating units form a circular, propeller-like structure with seven blades each made up of four beta strands. It is very likely that all WD-repeat proteins form a similar structure. If so, it will be possible to use information about important surface regions of one family member to predict properties of another. If WD proteins form structures similar to G beta, their hydrodynamic properties should be those of compact, globular proteins, and they should be resistant to cleavage by trypsin. However, the only studied example of a WD-repeat protein, G beta, synthesized in vitro in a rabbit reticulocyte lysate, is unable to fold into a native structure without its partner protein G gamma. The non-WD-repeat amino terminal alpha helix of G beta does not inhibit folding because G beta does not fold even when this region is removed. It is not known whether all WD-repeat proteins are unable to fold when synthesized in an in vitro system. We synthesized seven members of the family in a rabbit reticulocyte lysate, determined their Stokes radius, sedimentation coefficient, and frictional ratio, and assayed their stability to trypsin. Our working definition of folding was that the proteins from globular, trypsin-resistant structures because, except for G beta gamma, their functions are not known or cannot be assayed in reticulocyte lysates. We chose proteins that include amino and carboxyl extensions as well as proteins that are made up entirely of WD-repeats. We show that unlike G beta, several proteins with WD-repeats are able to fold into globular proteins in a rabbit reticulocyte lysate. One protein, beta Trcp, formed large aggregates like G beta, suggesting that it may also require a partner protein. Despite the presence of many potential tryptic cleavage sites, all of the proteins that did fold gave stable large products on tryptic proteolysis, as predicted on the basis of the structure of G beta. These studies suggest that other WD-repeat proteins are likely to form propeller structures similar to G beta.

• Sondek J, Bohm A, Lambright DG, Hamm HE, Sigler PB
• Crystal structure of a G-protein beta gamma dimer at 2.1A resolution.
• Nature. 1996; 379: 369-74

Many signalling cascades use seven-helical transmembrane receptors coupled to heterotrimeric G proteins (G alpha beta gamma) to convert extracellular signals into intracellular responses. Upon nucleotide exchange catalysed by activated receptors, heterotrimers dissociate into GTP-bound G alpha subunits and G beta gamma dimers, either of which can modulate many downstream effectors. Here we use multiwavelength anomalous diffraction data to solve the crystal structure of the beta gamma dimer of the G protein transducin. The beta-subunit is primarily a seven-bladed beta-propeller that is partially encircled by an extended gamma-subunit. The beta-propeller, which contains seven structurally similar WD repeats, defines the stereochemistry of the WD repeat and the probable architecture of all WD-repeat-containing domains. The structure details interactions between G protein beta- and gamma-subunits and highlights regions implicated in effector modulation for the conserved family of G protein beta gamma dimers.

• Hurley JB, Fong HK, Teplow DB, Dreyer WJ, Simon MI
• Isolation and characterization of a cDNA clone for the gamma subunit of bovine retinal transducin.
• Proc Natl Acad Sci U S A. 1984; 81: 6948-52

We have isolated and characterized a cDNA clone that encodes the gamma subunit of transducin, the guanine nucleotide binding regulatory protein found in vertebrate photoreceptors. The gamma subunit was separated from the alpha and beta subunits of transducin and purified to homogeneity by reversed-phase high performance liquid chromatography. The sequence of the first 45 amino acids at the amino terminus of this polypeptide was then determined by automated Edman degradation. Oligodeoxynucleotide probes corresponding to two nonoverlapping regions of this sequence were synthesized and then used to screen a bovine retinal cDNA library. One probe, T gamma 1, was a mixture of 32 different heptadecamers complementary to all possible mRNA sequences that could encode a portion of the T gamma sequence; the other probe, T gamma 2, was a mixture of 128 different heptadecamers. Thirteen clones that hybridized with T gamma 1 were selected. Only one of these had an insert that also hybridized with T gamma 2. The DNA sequence of this insert encodes a 73-amino acid polypeptide that corresponds to the transducin gamma subunit on the basis of amino-terminal sequence, amino acid composition, and carboxyl-terminal sequence. The molecular weight of the mature gamma subunit is 8400. It appears to be synthesized as a discrete polypeptide and not as a domain of a larger precursor polyprotein. The transducin gamma subunit is very hydrophilic and acidic; it has 19 acidic and 11 basic amino acids as well as three cysteine residues. Furthermore, significant homology was found in comparisons of the nucleic acid sequence corresponding to the carboxyl terminus of the gamma transducin transcript with the sequences corresponding to the carboxyl terminus of ras oncogene products, suggesting a possible ancestral relationship between these genes.

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
33.33	map04810	Regulation of actin cytoskeleton
33.33	map04742	Taste transduction
33.33	map04010	MAPK signaling pathway

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with GGL domain which could be assigned to a KEGG orthologous group, and not all proteins containing GGL domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of GGL domains in PDB

PDB code	Title
1a0r	HETEROTRIMERIC COMPLEX OF PHOSDUCIN/TRANSDUCIN BETA-GAMMA
1b9x	STRUCTURAL ANALYSIS OF PHOSDUCIN AND ITS PHOSPHORYLATION-REGULATED INTERACTION WITH TRANSDUCIN
1b9y	STRUCTURAL ANALYSIS OF PHOSDUCIN AND ITS PHOSPHORYLATION-REGULATED INTERACTION WITH TRANSDUCIN BETA-GAMMA
1gg2	G PROTEIN HETEROTRIMER MUTANT GI_ALPHA_1(G203A) BETA_1 GAMMA_2 WITH GDP BOUND
1got	HETEROTRIMERIC COMPLEX OF A GT-ALPHA/GI-ALPHA CHIMERA AND THE GT-BETA-GAMMA SUBUNITS
1gp2	G PROTEIN HETEROTRIMER GI_ALPHA_1 BETA_1 GAMMA_2 WITH GDP BOUND
1omw	Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and gamma 2 subunits
1tbg	BETA-GAMMA DIMER OF THE HETEROTRIMERIC G-PROTEIN TRANSDUCIN
1xhm	The Crystal Structure of a Biologically Active Peptide (SIGK) Bound to a G Protein Beta:Gamma Heterodimer
2bcj	Crystal Structure of G Protein-Coupled Receptor Kinase 2 in Complex with Galpha-q and Gbetagamma Subunits
2pbi	The multifunctional nature of Gbeta5/RGS9 revealed from its crystal structure
2trc	PHOSDUCIN/TRANSDUCIN BETA-GAMMA COMPLEX
3ah8	Structure of heterotrimeric G protein Galpha-q beta gamma in complex with an inhibitor YM-254890
3cik	Human GRK2 in Complex with Gbetagamma subunits
3krw	Human GRK2 in complex with Gbetgamma subunits and balanol (soak)
3krx	Human GRK2 in complex with Gbetgamma subunits and balanol (co-crystal)
3psc	Bovine GRK2 in complex with Gbetagamma subunits
3pvu	Bovine GRK2 in complex with Gbetagamma subunits and a selective kinase inhibitor (CMPD101)
3pvw	Bovine GRK2 in complex with Gbetagamma subunits and a selective kinase inhibitor (CMPD103A)
3sn6	Crystal structure of the beta2 adrenergic receptor-Gs protein complex
3uzs	Structure of the C13.28 RNA Aptamer Bound to the G Protein-Coupled Receptor Kinase 2-Heterotrimeric G Protein Beta 1 and Gamma 2 Subunit Complex
3v5w	Human G Protein-Coupled Receptor Kinase 2 in Complex with Soluble Gbetagamma Subunits and Paroxetine
4kfm	Crystal structure of the G protein-gated inward rectifier K+ channel GIRK2 (Kir3.2) in complex with the beta-gamma G protein subunits
4mk0	Crystal structure of G protein-coupled receptor kinase 2 in complex with a a rationally designed paroxetine derivative
4pnk	4PNK
5he0	5HE0
5he1	5HE1
5he2	5HE2
5he3	5HE3
5kdo	5KDO
5tdh	5TDH

Links (links to other resources describing this domain)

• PROSITE: G_PROTEIN_GAMMA
• PFAM: G_protein_gamma
• INTERPRO: IPR015898