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117  structures 511  species 3  interactions 2902  sequences 23  architectures

Family: G-alpha (PF00503)

Summary: G-protein alpha subunit

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "G alpha subunit". More...

G alpha subunit Edit Wikipedia article

G-alpha
PDB 1got EBI.jpg
heterotrimeric complex of a gt-alpha/gi-alpha chimera and the gt-beta-gamma subunits
Identifiers
Symbol G-alpha
Pfam PF00503
Pfam clan CL0023
InterPro IPR001019
SCOP 1gia
SUPERFAMILY 1gia
CDD cd00066

Guanine nucleotide binding proteins (G proteins) are membrane-associated, heterotrimeric proteins composed of three subunits: alpha (INTERPRO), beta (INTERPRO) and gamma (INTERPRO).[1] G proteins and their receptors (GPCRs) form one of the most prevalent signalling systems in mammalian cells, regulating systems as diverse as sensory perception, cell growth and hormonal regulation.[2] At the cell surface, the binding of ligands such as hormones and neurotransmitters to a GPCR activates the receptor by causing a conformational change, which in turn activates the bound G protein on the intracellular-side of the membrane. The activated receptor promotes the exchange of bound GDP for GTP on the G protein alpha subunit. GTP binding changes the conformation of switch regions within the alpha subunit, which allows the bound trimeric G protein (inactive) to be released from the receptor, and to dissociate into active alpha subunit (GTP-bound) and beta/gamma dimer. The alpha subunit and the beta/gamma dimer go on to activate distinct downstream effectors, such as adenylyl cyclase, phosphodiesterases, phospholipase C, and ion channels. These effectors in turn regulate the intracellular concentrations of secondary messengers, such as cAMP, diacylglycerol, sodium or calcium cations, which ultimately lead to a physiological response, usually via the downstream regulation of gene transcription. The cycle is completed by the hydrolysis of alpha subunit-bound GTP to GDP, resulting in the re-association of the alpha and beta/gamma subunits and their binding to the receptor, which terminates the signal.[3] The length of the G protein signal is controlled by the duration of the GTP-bound alpha subunit, which can be regulated by RGS (regulator of G protein signalling) proteins (INTERPRO) or by covalent modifications.[4]

There are several isoforms of each subunit, many of which have splice variants, which together can make up hundreds of combinations of G proteins. The specific combination of subunits in heterotrimeric G proteins affects not only which receptor it can bind to, but also which downstream target is affected, providing the means to target specific physiological processes in response to specific external stimuli.[5][6] G proteins carry lipid modifications on one or more of their subunits to target them to the plasma membrane and to contribute to protein interactions.

This family consists of the G protein alpha subunit, which acts as a weak GTPase. G protein classes are defined based on the sequence and function of their alpha subunits, which in mammals fall into several sub-types: G(S)alpha, G(Q)alpha, G(I)alpha, transducin and G(12)alpha; there are also fungal and plant classes of alpha subunits. The alpha subunit consists of two domains: a GTP-binding domain and a helical insertion domain (INTERPRO). The GTP-binding domain is homologous to Ras-like small GTPases, and includes switch regions I and II, which change conformation during activation. The switch regions are loops of alpha-helices with conformations sensitive to guanine nucleotides. The helical insertion domain is inserted into the GTP-binding domain before switch region I and is unique to heterotrimeric G proteins. This helical insertion domain functions to sequester the guanine nucleotide at the interface with the GTP-binding domain and must be displaced to enable nucleotide dissociation.

References[edit]

  1. ^ Preininger AM, Hamm HE (February 2004). "G protein signaling: insights from new structures". Sci. STKE 2004 (218): re3. doi:10.1126/stke.2182004re3. PMID 14762218. 
  2. ^ Roberts DJ, Waelbroeck M (September 2004). "G protein activation by G protein coupled receptors: ternary complex formation or catalyzed reaction?". Biochem. Pharmacol. 68 (5): 799–806. doi:10.1016/j.bcp.2004.05.044. PMID 15294442. 
  3. ^ Svoboda P, Teisinger J, Novotný J, Bourová L, Drmota T, Hejnová L, Moravcová Z, Lisý V, Rudajev V, Stöhr J, Vokurková A, Svandová I, Durchánková D. (2004). "Biochemistry of transmembrane signaling mediated by trimeric G proteins". Physiol Res. 53 Suppl 1: S141–52. PMID 15119945. 
  4. ^ Chen CA, Manning DR (March 2001). "Regulation of G proteins by covalent modification". Oncogene 20 (13): 1643–52. doi:10.1038/sj.onc.1204185. PMID 11313912. 
  5. ^ Hildebrandt JD (August 1997). "Role of subunit diversity in signaling by heterotrimeric G proteins". Biochem. Pharmacol. 54 (3): 325–39. doi:10.1016/S0006-2952(97)00269-4. PMID 9278091. 
  6. ^ Albert PR, Robillard L (May 2002). "G protein specificity: traffic direction required". Cell. Signal. 14 (5): 407–18. doi:10.1016/S0898-6568(01)00259-5. PMID 11882385. 

This article incorporates text from the public domain Pfam and InterPro IPR001019

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.

G-protein alpha subunit Provide feedback

G proteins couple receptors of extracellular signals to intracellular signaling pathways. The G protein alpha subunit binds guanyl nucleotide and is a weak GTPase. A set of residues that are unique to G-alpha as compared to its ancestor the Arf-like family form a ring of residues centered on the nucleotide binding site [3]. A Ggamma is found fused to an inactive Galpha in the Dictyostelium protein gbqA [3].

Literature references

  1. Coleman DE, Berghuis AM, Lee E, Linder ME, Gilman AG, Sprang SR; , Science 1994;265:1405-1412.: Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis. PUBMED:8073283 EPMC:8073283

  2. Coleman DE, Sprang SR; , Trends Biochem Sci 1996;21:41-44.: How G proteins work: a continuing story. PUBMED:8851656 EPMC:8851656

  3. 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 IPR001019

Guanine nucleotide binding proteins (G proteins) are membrane-associated, heterotrimeric proteins composed of three subunits: alpha (INTERPRO), beta (INTERPRO) and gamma (INTERPRO) [PUBMED:14762218]. G proteins and their receptors (GPCRs) form one of the most prevalent signalling systems in mammalian cells, regulating systems as diverse as sensory perception, cell growth and hormonal regulation [PUBMED:15294442]. At the cell surface, the binding of ligands such as hormones and neurotransmitters to a GPCR activates the receptor by causing a conformational change, which in turn activates the bound G protein on the intracellular-side of the membrane. The activated receptor promotes the exchange of bound GDP for GTP on the G protein alpha subunit. GTP binding changes the conformation of switch regions within the alpha subunit, which allows the bound trimeric G protein (inactive) to be released from the receptor, and to dissociate into active alpha subunit (GTP-bound) and beta/gamma dimer. The alpha subunit and the beta/gamma dimer go on to activate distinct downstream effectors, such as adenylyl cyclase, phosphodiesterases, phospholipase C, and ion channels. These effectors in turn regulate the intracellular concentrations of secondary messengers, such as cAMP, diacylglycerol, sodium or calcium cations, which ultimately lead to a physiological response, usually via the downstream regulation of gene transcription. The cycle is completed by the hydrolysis of alpha subunit-bound GTP to GDP, resulting in the re-association of the alpha and beta/gamma subunits and their binding to the receptor, which terminates the signal [PUBMED:15119945]. The length of the G protein signal is controlled by the duration of the GTP-bound alpha subunit, which can be regulated by RGS (regulator of G protein signalling) proteins (INTERPRO) or by covalent modifications [PUBMED:11313912].

There are several isoforms of each subunit, many of which have splice variants, which together can make up hundreds of combinations of G proteins. The specific combination of subunits in heterotrimeric G proteins affects not only which receptor it can bind to, but also which downstream target is affected, providing the means to target specific physiological processes in response to specific external stimuli [PUBMED:9278091, PUBMED:11882385]. G proteins carry lipid modifications on one or more of their subunits to target them to the plasma membrane and to contribute to protein interactions.

This family consists of the G protein alpha subunit, which acts as a weak GTPase. G protein classes are defined based on the sequence and function of their alpha subunits, which in mammals fall into four main categories: G(S)alpha, G(Q)alpha, G(I)alpha and G(12)alpha; there are also fungal and plant classes of alpha subunits. The alpha subunit consists of two domains: a GTP-binding domain and a helical insertion domain (INTERPRO). The GTP-binding domain is homologous to Ras-like small GTPases, and includes switch regions I and II, which change conformation during activation. The switch regions are loops of alpha-helices with conformations sensitive to guanine nucleotides. The helical insertion domain is inserted into the GTP-binding domain before switch region I and is unique to heterotrimeric G proteins. This helical insertion domain functions to sequester the guanine nucleotide at the interface with the GTP-binding domain and must be displaced to enable nucleotide dissociation.

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 P-loop_NTPase (CL0023), which has the following description:

AAA family proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes [2].

The clan contains the following 198 members:

6PF2K AAA AAA-ATPase_like AAA_10 AAA_11 AAA_12 AAA_13 AAA_14 AAA_15 AAA_16 AAA_17 AAA_18 AAA_19 AAA_2 AAA_21 AAA_22 AAA_23 AAA_24 AAA_25 AAA_26 AAA_27 AAA_28 AAA_29 AAA_3 AAA_30 AAA_31 AAA_32 AAA_33 AAA_34 AAA_35 AAA_4 AAA_5 AAA_6 AAA_7 AAA_8 AAA_9 AAA_PrkA ABC_ATPase ABC_tran ABC_tran_2 Adeno_IVa2 Adenylsucc_synt ADK AFG1_ATPase AIG1 APS_kinase Arch_ATPase Arf ArgK ArsA_ATPase ATP-synt_ab ATP_bind_1 ATP_bind_2 Bac_DnaA CbiA CMS1 CoaE CobA_CobO_BtuR CobU cobW CPT CTP_synth_N Cytidylate_kin Cytidylate_kin2 DAP3 DEAD DEAD_2 DLIC DNA_pack_C DNA_pack_N DNA_pol3_delta DNA_pol3_delta2 DnaB_C dNK DUF1253 DUF1611 DUF2075 DUF2478 DUF258 DUF2791 DUF2813 DUF3584 DUF463 DUF815 DUF853 DUF87 DUF927 Dynamin_N Exonuc_V_gamma FeoB_N Fer4_NifH Flavi_DEAD FTHFS FtsK_SpoIIIE G-alpha Gal-3-0_sulfotr GBP GTP_EFTU GTP_EFTU_D2 GTP_EFTU_D4 Gtr1_RagA Guanylate_kin GvpD HDA2-3 Helicase_C Helicase_C_2 Helicase_C_4 Helicase_RecD Herpes_Helicase Herpes_ori_bp Herpes_TK IIGP IPPT IPT IstB_IS21 KaiC KAP_NTPase Kinesin Kinesin-relat_1 Kinesin-related KTI12 LpxK MCM MEDS Mg_chelatase Mg_chelatase_2 MipZ Miro MMR_HSR1 MobB MukB MutS_V Myosin_head NACHT NB-ARC NOG1 NTPase_1 ParA Parvo_NS1 PAXNEB PduV-EutP PhoH PIF1 Podovirus_Gp16 Polyoma_lg_T_C Pox_A32 PPK2 PPV_E1_C PRK Rad17 Rad51 Ras RecA ResIII RHD3 RHSP RNA12 RNA_helicase RuvB_N SbcCD_C SecA_DEAD Septin Sigma54_activ_2 Sigma54_activat SKI SMC_N SNF2_N Spore_IV_A SRP54 SRPRB Sulfotransfer_1 Sulfotransfer_2 Sulfotransfer_3 Sulphotransf T2SE T4SS-DNA_transf Terminase_1 Terminase_3 Terminase_6 Terminase_GpA Thymidylate_kin TIP49 TK TniB Torsin TraG-D_C tRNA_lig_kinase TrwB_AAD_bind UPF0079 UvrD-helicase UvrD_C UvrD_C_2 Viral_helicase1 VirC1 VirE YhjQ Zeta_toxin Zot

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
(134)
Full
(2902)
Representative proteomes NCBI
(2617)
Meta
(11)
RP15
(558)
RP35
(822)
RP55
(1230)
RP75
(1599)
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  Seed
(134)
Full
(2902)
Representative proteomes NCBI
(2617)
Meta
(11)
RP15
(558)
RP35
(822)
RP55
(1230)
RP75
(1599)
Alignment:
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Sequence:
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  Seed
(134)
Full
(2902)
Representative proteomes NCBI
(2617)
Meta
(11)
RP15
(558)
RP35
(822)
RP55
(1230)
RP75
(1599)
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: Anantharaman V
Previous IDs: none
Type: Domain
Author: Finn RD, Anantharaman V
Number in seed: 134
Number in full: 2902
Average length of the domain: 305.60 aa
Average identity of full alignment: 39 %
Average coverage of the sequence by the domain: 89.11 %

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 48.8 48.8
Trusted cut-off 48.8 48.9
Noise cut-off 48.7 48.5
Model length: 389
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 3 interactions for this family. More...

G-alpha WD40 Guanylate_cyc

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 G-alpha domain has been found. There are 117 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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