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69  structures 775  species 0  interactions 23336  sequences 1017  architectures

Family: 7tm_2 (PF00002)

Summary: 7 transmembrane receptor (Secretin family)

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This is the Wikipedia entry entitled "Secretin receptor family". More...

Secretin receptor family Edit Wikipedia article

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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.

7 transmembrane receptor (Secretin family) Provide feedback

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

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

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000832

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-terminal is probably located on the extracellular side of the membrane and potentially glycosylated. This N-terminal region contains a long conserved region which allows 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.

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 [ PUBMED:12679517 ]. The term clan can be used 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 rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [ PUBMED:8170923 , PUBMED:8081729 , PUBMED:15914470 , PUBMED:18948278 , PUBMED:16753280 ]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice [ PUBMED:12679517 ]. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [ PUBMED:23020293 ].

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 GPCR_A (CL0192), which has the following description:

This clan contains various seven-transmembrane receptors and related proteins. A major member is Pfam:PF00001, members of which have been considered to be typical members of the rhodopsin superfamily. Many members of this clan are Caenorhabditis proteins, suggesting great expansion of the relevant families in these nematode worms.

The clan contains the following 45 members:

7TM-7TMR_HD 7tm_1 7tm_2 7tm_3 7tm_4 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 7TMR-DISM_7TM Bac_rhodopsin Ceramidase Dicty_CAR DUF1182 DUF3522 DUF621 Frizzled Git3 GpcrRhopsn4 GPR_Gpa2_C Heliorhodopsin HisKA_7TM HlyIII Lung_7-TM_R Ocular_alb Per1 Pombe_5TM Serpentine_r_xa SID-1_RNA_chan Sre Srg TAS2R V1R


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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB 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.

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

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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...


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.

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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: Prosite
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Sonnhammer ELL
Number in seed: 28
Number in full: 23336
Average length of the domain: 226.40 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 25.39 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.6 20.6
Trusted cut-off 20.6 20.6
Noise cut-off 20.5 20.5
Model length: 246
Family (HMM) version: 26
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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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. There are 69 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 sequence.

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