Summary

G-protein alpha subunit

G proteins couple receptors of extracellular signals to intracellular signaling pathways. The G protein alpha subunit binds guanyl nucleotide and is a weak GTPase.

Literature references

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

InterPro entry IPR001019

Guanine nucleotide binding proteins (G proteins) are membrane-associated, heterotrimeric proteins composed of three subunits: alpha (), beta () and gamma () 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 () 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 (). 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.

Clan

This family is a member of clan AAA (CL0023), which contains the following 142 members:

6PF2K AAA AAA-ATPase_like AAA_2 AAA_3 AAA_5 AAA_PrkA ABC_ATPase ABC_tran 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 CoaE CobA_CobO_BtuR CobU cobW CPT CTP_synth_N Cytidylate_kin DAP3 DEAD DEAD_2 DLIC DNA_pack_C DNA_pack_N DNA_pol3_delta DnaB_C dNK DUF1253 DUF1611 DUF2075 DUF2478 DUF258 DUF265 DUF699 DUF815 DUF853 DUF87 DUF889 Dynamin_N Exonuc_V_gamma FeoB_N Fer4_NifH Flavi_DEAD FTHFS FtsK_SpoIIIE G-alpha Gal-3-0_sulfotr GBP GSPII_E GTP_EFTU Gtr1_RagA Guanylate_kin GvpD HDA2-3 Helicase_C Herpes_Helicase Herpes_ori_bp Herpes_TK IIGP IPPT IPT IstB KaiC KAP_NTPase Kinesin KTI12 LpxK MCM Mg_chelatase MipZ Miro MMR_HSR1 MobB MutS_V Myosin_head NACHT NB-ARC NOG1 ParA Parvo_NS1 PAXNEB PduV-EutP PhoH Podovirus_Gp16 Polyoma_lg_T_C Pox_A32 PPK2 PPV_E1_C PRK Rad17 Rad51 Ras RecA Rep_fac_C ResIII RHD3 RNA12 RNA_helicase RuvB_N SecA_DEAD Septin Sigma54_activat SKI SMC_N SNF2_N Spore_IV_A SRP54 SRPRB Sulfotransfer_1 Sulfotransfer_2 Sulphotransf Terminase_1 Terminase_3 Terminase_6 Terminase_GpA Thymidylate_kin TIP49 TK TniB Torsin TraG TrwB_AAD_bind UPF0079 UvrD-helicase Viral_helicase1 VirC1 YhjQ Zeta_toxin Zot

Gene Ontology

Molecular function	guanyl nucleotide binding (GO:0019001)
Molecular function	signal transducer activity (GO:0004871)
Biological process	G-protein coupled receptor protein signaling pathway (GO:0007186)

Internal database links

SCOOP:	DUF320 Gtr1_RagA Ras TniB SRPRB
Similarity to PfamA using HHSearch:	Arf

External database links

HOMSTRAD:	galpha
PANDIT:	PF00503
PRINTS:	PR00318
SCOP:	1gia
SYSTERS:	G-alpha

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Alignments

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

View options

Alignment:	Seed (25) Full (1506) NCBI (5220) Metagenomics (45)
Viewer:

Formatting options

Alignment:	Seed (25) Full (1506)
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (25) Full (1506) NCBI (5220) Metagenomics (45)
Full length sequences	Full-sequences (1506)

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 HMMER2.

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. 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 or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

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:

Pfam-B_11 (release 1.0)

Previous IDs:

none

Type:

Domain

Author:

Finn RD

Number in seed:

25

Number in full:

1506

Average length of the domain:

265.50 aa

Average identity of full alignment:

35 %

Average coverage of the sequence by the domain:

78.29 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 9421015 -E 1000 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	20.1	20.1
Trusted cut-off	20.1	20.1
Noise cut-off	20.0	20.0

Model length:

351

Family (HMM) version:

13

Download:

download the raw HMM for this family

Species distribution

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

Loading...

Interactions

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

WD40 G-alpha 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.

Loading structure mapping...

Family: G-alpha (PF00503)

Jump to...