Family

APJ receptor (IPR003904)

Short name: APJ_rcpt

Overlapping homologous superfamilies

None.

Family relationships

Description

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 [PMID: 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 [PMID: 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) [PMID: 8170923, PMID: 8081729, PMID: 15914470, PMID: 18948278, PMID: 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 [PMID: 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 [PMID: 23020293].

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [PMID: 2111655, PMID: 2830256, PMID: 8386361].

The human APJ gene was originally cloned in 1993 using a set of primers based on the 7 conserved TM domains. The putative sequence is closest in terms of identity (40-50% in the TM regions) to the angiotensin receptor (AT1); however, angiotensin II shows no affinity for the receptor [PMID: 8294032]. The endogenous ligand has recently been isolated from bovine stomach and characterised as a 77 amino acid peptide, which was named apelin [PMID: 9792798]. The mature transcript encodes a preproprotein that yields a 13 amino acid active peptide from the C-terminal end. Apelin has a similar mRNA distribution to angiotensin II and the active peptides share some similarity. In vivo administration of apelin to rats results in acute hypotensive and thirst promoting effects [PMID: 10617103].

GO terms

Biological Process

GO:0007186 G-protein coupled receptor signaling pathway

Molecular Function

GO:0004930 G-protein coupled receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PRINTS