APLNR (apelin receptor)

2009-08-01   Yves Audigier 

Unite INSERM U-858, I2MR, equipe 13, CHU Rangueil, Bat. L3, BP 84225, 1 avenue Jean-Poulhes, 31432-Toulouse Cedex 4, France





1 exon.


3.8 kb mRNA; 1140 bp open reading frame.


Atlas Image


380 amino acids.


Blood vessels, hypothalamus, heart, stomach, colon, endocrine pancreas, bone, skeletic muscle, spleen.


Plasma membrane.


The apelin receptor APJ belongs to the family of G protein-coupled receptors (ODowd et al., 1993; Devic et al., 1996; Devic et al., 1999; Scott et al., 2007) and is coupled to a Gi/o protein (Masri et al., 2006). Its activation leads to the regulation of various intracellular effectors with the following consequences: adenylylcyclase inhibition (Masri et al., 2006; Habata et al., 1999), increase of intracellular calcium (Choe et al., 2000) and activation of extracellular signal-regulated kinases (ERKs), PI-3K, Akt or p70S6 kinase (S6K1) (Masri et al., 2006; Masri et al., 2004 ).
Expression of apelin receptors by the endothelial cell (Devic et al., 1996; Devic et al., 1999) is associated with two effects :
1) NO release leading to vessel vasodilatation (Tatemoto et al., 2001) and peripheral hypotension (Lee et al., 2000);
2) cell proliferation and migration (Masri et al., 2004; Kasai et al., 2004) linked to angiogenesis (Cox et al., 2006).
The expression in the central nervous system is high in hypothalamus (De Mota et al., 2000; OCarroll et al., 2000) where receptor activation leads to the decrease of vasopressin release (De Mota et al., 2004). Activation of apelin receptors expressed by cardiomyocytes results in a strong inotropic effect (Szokodi et al., 2002). In stomach, apelin receptors are expressed by enterochromaffin-like cells where their stimulation decreases gastrin-induced acid secretion (Lambrecht et al., 2006). Apelin receptors may regulate epithelial proliferation in the colon (Han et al., 2007). Expression of apelin receptors both in endocrine pancreas and skeletic muscle contributes to the regulation of insulin plasma levels and glucose uptake (Sorhede Winzell et al., 2005; Dray et al., 2008). Apelin signalling also increases osteoblast proliferation (Xie et al., 2007) and cytokine expression by T lymphocytes (Habata et al., 1999).



No mutation has been presently described.

Implicated in

Entity name
Malignant glioma
On a quantitative point of view, APLNR gene expression is highly upregulated in microvascular proliferations of malignant gliomas (Kalin et al., 2007)
Entity name
Various diseases
On a qualitative point of view, two single nucleotide polymorphisms (SNP) have been reported. A functional SNP in an Sp1-binding site of APLNR gene is associated with susceptibility to brain infarction (Hata et al., 2007). The 212A variant of the APJ receptor gene is associated with slower heart failure progression in idiopathic dilated cardiomyopathy (Sarzani et al., 2007).


Pubmed IDLast YearTitleAuthors
108717672000Functional expression of the seven-transmembrane HIV-1 co-receptor APJ in neural cells.Choe W et al
167508222006Apelin, the ligand for the endothelial G-protein-coupled receptor, APJ, is a potent angiogenic factor required for normal vascular development of the frog embryo.Cox CM et al
111464232000Cloning, pharmacological characterization and brain distribution of the rat apelin receptor.De Mota N et al
152319962004Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release.De Mota N et al
89517911996Expression of a new G protein-coupled receptor X-msr is associated with an endothelial lineage in Xenopus laevis.Devic E et al
104731421999Amino acid sequence and embryonic expression of msr/apj, the mouse homolog of Xenopus X-msr and human APJ.Devic E et al
190465742008Apelin stimulates glucose utilization in normal and obese insulin-resistant mice.Dray C et al
105251571999Apelin, the natural ligand of the orphan receptor APJ, is abundantly secreted in the colostrum.Habata Y et al
173917792007Increased colonic apelin production in rodents with experimental colitis and in humans with IBD.Han S et al
173098822007Functional SNP in an Sp1-binding site of AGTRL1 gene is associated with susceptibility to brain infarction.Hata J et al
174123182007Paracrine and autocrine mechanisms of apelin signaling govern embryonic and tumor angiogenesis.Kälin RE et al
155304052004Apelin is a novel angiogenic factor in retinal endothelial cells.Kasai A et al
164038402006Transcriptomes of purified gastric ECL and parietal cells: identification of a novel pathway regulating acid secretion.Lambrecht NW et al
106171032000Characterization of apelin, the ligand for the APJ receptor.Lee DK et al
166793202006The apelin receptor is coupled to Gi1 or Gi2 protein and is differentially desensitized by apelin fragments.Masri B et al
110044812000Distribution of mRNA encoding B78/apj, the rat homologue of the human APJ receptor, and its endogenous ligand apelin in brain and peripheral tissues.O'Carroll AM et al
82940321993A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11.O'Dowd BF et al
178266422007The 212A variant of the APJ receptor gene for the endogenous inotrope apelin is associated with slower heart failure progression in idiopathic dilated cardiomyopathy.Sarzani R et al
173369062007The g protein-coupled receptor agtrl1b regulates early development of myocardial progenitors.Scott IC et al
159703382005The apj receptor is expressed in pancreatic islets and its ligand, apelin, inhibits insulin secretion in mice.Sörhede Winzell M et al
122154932002Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility.Szokodi I et al
113847692001The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism.Tatemoto K et al
165635312006Apelin and its receptor are expressed in human osteoblasts.Xie H et al

Other Information

Locus ID:

NCBI: 187
MIM: 600052
HGNC: 339
Ensembl: ENSG00000134817


dbSNP: 187
ClinVar: 187
TCGA: ENSG00000134817


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Neuroactive ligand-receptor interactionKEGGko04080
Neuroactive ligand-receptor interactionKEGGhsa04080
Signal TransductionREACTOMER-HSA-162582
Signaling by GPCRREACTOMER-HSA-372790
GPCR ligand bindingREACTOMER-HSA-500792
Class A/1 (Rhodopsin-like receptors)REACTOMER-HSA-373076
Peptide ligand-binding receptorsREACTOMER-HSA-375276
GPCR downstream signalingREACTOMER-HSA-388396
G alpha (i) signalling eventsREACTOMER-HSA-418594
Apelin signaling pathwayKEGGhsa04371

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
150874582004Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo.88
156646712005Immunocytochemical localisation of the apelin receptor, APJ, to human cardiomyocytes, vascular smooth muscle and endothelial cells.72
146452362004Agonist-independent nuclear localization of the Apelin, angiotensin AT1, and bradykinin B2 receptors.66
212334492011Disruption of the apelin-APJ system worsens hypoxia-induced pulmonary hypertension.61
174123182007Paracrine and autocrine mechanisms of apelin signaling govern embryonic and tumor angiogenesis.54
173098822007Functional SNP in an Sp1-binding site of AGTRL1 gene is associated with susceptibility to brain infarction.31
173098822007Functional SNP in an Sp1-binding site of AGTRL1 gene is associated with susceptibility to brain infarction.31
252755592014The apelin receptor: physiology, pathology, cell signalling, and ligand modulation of a peptide-activated class A GPCR.26
191237782009Structural insight into G-protein coupled receptor binding by apelin.24
214506942011Hypoxia and proinflammatory factors upregulate apelin receptor expression in human stellate cells and hepatocytes.24


Yves Audigier

APLNR (apelin receptor)

Atlas Genet Cytogenet Oncol Haematol. 2009-08-01

Online version: http://atlasgeneticsoncology.org/gene/44364/aplnr