Summary

7 transmembrane receptor (Secretin family)

This family is known as Family B, the secretin-receptor family or family 2 of the G-protein-coupled receptors (GCPRs).They have been described in many animal species, but not in plants, fungi or prokaryotes. Three distinct sub-families are recognised. Subfamily B1 contains classical hormone receptors, such as receptors for secretin and glucagon, that are all involved in cAMP-mediated signalling pathways. Subfamily B2 contains receptors with long extracellular N-termini, such as the leukocyte cell-surface antigen CD97 (P48960); calcium-independent receptors for latrotoxin (such as O94910), and brain-specific angiogenesis inhibitors (such as O14514) amongst others. Subfamily B3 includes Methuselah and other Drosophila proteins (e.g. P83119). Other than the typical seven-transmembrane region, characteristic structural features include an amino-terminal extracellular domain involved in ligand binding, and an intracellular loop (IC3) required for specific G-protein coupling [1].

Literature references

Harmar AJ; , Genome Biol 2001;2:REVIEWS3013.: Family-B G-protein-coupled receptors. PUBMED:11790261

InterPro entry IPR000832

G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence PUBMED:8170923. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/).

The secretin-like GPCRs include secretin PUBMED:1646711, calcitonin PUBMED:1658940, parathyroid hormone/parathyroid hormone-related peptides PUBMED:1658941 and vasoactive intestinal peptide PUBMED:1314625, all of which activate adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. These receptors contain seven transmembrane regions, in a manner reminiscent of the rhodopsins and other receptors believed to interact with G-proteins (however there is no significant sequence identity between these families, the secretin-like receptors thus bear their own unique '7TM' signature). Their N-terminus is probably located on the extracellular side of the membrane and potentially glycosylated. This N-terminal region contains a long conserved region which allow the binding of large peptidic ligand such as glucagon, secretin, VIP and PACAP; this region contains five conserved cysteines residues which could be involved in disulphide bond. The C-terminal region of these receptor is probably cytoplasmic. Every receptor gene in this family is encoded on multiple exons, and several of these genes are alternatively spliced to yield functionally distinct products.

Clan

This family is a member of clan GPCR_A (CL0192), which contains the following 34 members:

7TM-7TMR_HD 7tm_1 7tm_2 7TM_GPCR_Sra 7TM_GPCR_Srab 7TM_GPCR_Srb 7TM_GPCR_Srbc 7TM_GPCR_Srd 7TM_GPCR_Srh 7TM_GPCR_Sri 7TM_GPCR_Srj 7TM_GPCR_Srsx 7TM_GPCR_Srt 7TM_GPCR_Sru 7TM_GPCR_Srv 7TM_GPCR_Srw 7TM_GPCR_Srx 7TM_GPCR_Srz 7TM_GPCR_Str Bac_rhodopsin Dicty_CAR DUF1182 DUF621 Frizzled Git3 Git3_C GpcrRhopsn4 Lung_7-TM_R Ocular_alb Serpentine_r_xa Sre Srg TAS2R V1R

Gene Ontology

Cellular component	membrane (GO:0016020)
Molecular function	G-protein coupled receptor activity (GO:0004930)
Biological process	G-protein coupled receptor protein signaling pathway (GO:0007186)

External database links

PANDIT:	PF00002
PROSITE:	PDOC00559
SCOP:	1bl1
SYSTERS:	7tm_2

Domain organisation

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

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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 (32) Full (1317) NCBI (3349) Metagenomics (5)
Viewer:

Formatting options

Alignment:	Seed (32) Full (1317)
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 (32) Full (1317) NCBI (3349) Metagenomics (5)
Full length sequences	Full-sequences (1317)

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:

Prosite

Previous IDs:

none

Type:

Family

Author:

Sonnhammer ELL

Number in seed:

32

Number in full:

1317

Average length of the domain:

219.10 aa

Average identity of full alignment:

22 %

Average coverage of the sequence by the domain:

30.20 %

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	20.2	20.2
Trusted cut-off	20.3	20.3
Noise cut-off	20.0	20.0

Model length:

242

Family (HMM) version:

17

Download:

download the raw HMM for this family

Species distribution

Tree controls

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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

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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 7tm_2 domain has been found.

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Family: 7tm_2 (PF00002)

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