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3  structures 246  species 0  interactions 4718  sequences 348  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

Secretin family of 7 transmembrane receptors
PDB 1bl1 EBI.jpg
Structure of a 31 amino acid fragment of the extracellular N-terminus of the human parathyroid hormone receptor.[1]
Identifiers
Symbol 7tm_2
Pfam PF00002
InterPro IPR000832
PROSITE PDOC00559
SCOP 1bl1
SUPERFAMILY 1bl1
OPM superfamily 6
OPM protein 1fjr

Secretin family of 7 transmembrane receptors is a family of evolutionarily related proteins.[2]

This family is known as Family B, the secretin-receptor family or family 2 of the G-protein-coupled receptors (GPCR). Many secretin receptors are regulated by peptide hormones from the glucagon hormone family.

The secretin-receptor family GPCRs include vasoactive intestinal peptide receptors and receptors for secretin, calcitonin and parathyroid hormone/parathyroid hormone-related peptides. These receptors activate adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. The receptors in this family have 7 transmembrane helices [3], like rhodopsin-like GPCRs. However, there is no significant sequence identity between these two GPCR families and the secretin-receptor family has its own characteristic 7TM signature.[4]

The secretin-receptor family GPCRs exist in many animal species, but have not been found in plants, fungi or prokaryotes. Three distinct sub-families (B1-B3) are recognized.

Subfamily B1[edit]

Subfamily B1 contains classical hormone receptors, such as receptors for secretin and glucagon, that are all involved in cAMP-mediated signalling pathways.

Subfamily B2[edit]

Subfamily B2 contains receptors with long extracellular N-termini, such as the leukocyte cell-surface antigen CD97; calcium-independent receptors for latrotoxin (such as O94910, and brain-specific angiogenesis inhibitor receptors (such as O14514) amongst others.

Subfamily B3[edit]

Subfamily B3 includes Methuselah and other Drosophila proteins. 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.

Unclassified subfamilies[edit]

Unclassified members[edit]

HCTR-5; HCTR-6; KPG_006; KPG_008

References[edit]

  1. ^ PDB 1BL1; Pellegrini M, Bisello A, Rosenblatt M, Chorev M, Mierke DF (September 1998). "Binding domain of human parathyroid hormone receptor: from conformation to function". Biochemistry 37 (37): 12737–43. doi:10.1021/bi981265h. PMID 9737850. 
  2. ^ Harmar AJ (2001). "Family-B G-protein-coupled receptors". Genome Biol. 2 (12): REVIEWS3013. doi:10.1186/gb-2001-2-12-reviews3013. PMC 138994. PMID 11790261. 
  3. ^ PDB 4L6R; Siu FY, He M, de Graaf C, Han GW, Yang D, Zhang Z, Zhou C, Xu Q, Wacker D, Joseph JS, Liu W, Lau J, Cherezov V, Katritch V, Wang M-W, Stevens RC (July 2013). "Structure of the human glucagon class B G-protein-coupled receptor". Nature 499 (7459): 444–449. doi:10.1038/nature12393. PMID 23863937. 
  4. ^ Hollenstein K, de Graaf C, Bortolato A, Wang MW, Marshall FH, Stevens RC (2014). "Insights into the structure of class B GPCRs". Trends Pharmacol Sci 35 (1): 12–22. doi:10.1016/j.tips.2013.11.001. PMID 24359917. 

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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


External database links

This tab holds annotation information from the InterPro database.

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.

Gene Ontology

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Domain organisation

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Alignments

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(31)
Full
(4718)
Representative proteomes NCBI
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Meta
(5)
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(852)
RP35
(1057)
RP55
(1672)
RP75
(2544)
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  Seed
(31)
Full
(4718)
Representative proteomes NCBI
(4248)
Meta
(5)
RP15
(852)
RP35
(1057)
RP55
(1672)
RP75
(2544)
Alignment:
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  Seed
(31)
Full
(4718)
Representative proteomes NCBI
(4248)
Meta
(5)
RP15
(852)
RP35
(1057)
RP55
(1672)
RP75
(2544)
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.

Pfam alignments:

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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.

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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.

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Seed source: Prosite
Previous IDs: none
Type: Family
Author: Sonnhammer ELL
Number in seed: 31
Number in full: 4718
Average length of the domain: 225.10 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 28.73 %

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 20.6 20.6
Trusted cut-off 20.6 20.6
Noise cut-off 20.5 20.5
Model length: 243
Family (HMM) version: 19
Download: download the raw HMM for this family

Species distribution

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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. There are 3 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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