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APLNR (apelin receptor)

Written2009-08Yves Audigier
Unite INSERM U-858, I2MR, equipe 13, CHU Rangueil, Bat. L3, BP 84225, 1 avenue Jean-Poulhes, 31432-Toulouse Cedex 4, France

(Note : for Links provided by Atlas : click)


angiotensin II receptor-like 1
Alias_symbol (synonym)FLJ90771
Other aliasHG11
LocusID (NCBI) 187
Atlas_Id 44364
Location 11q12.1  [Link to chromosome band 11q12]
Location_base_pair Starts at 57233578 and ends at 57237453 bp from pter ( according to hg19-Feb_2009)  [Mapping APLNR.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
MCL1 (1q21.3) / APLNR (11q12.1)


Description 1 exon.
Transcription 3.8 kb mRNA; 1140 bp open reading frame.


Description 380 amino acids.
Expression Blood vessels, hypothalamus, heart, stomach, colon, endocrine pancreas, bone, skeletic muscle, spleen.
Localisation Plasma membrane.
Function The apelin receptor APJ belongs to the family of G protein-coupled receptors (O'Dowd 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; O'Carroll 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).


Note No mutation has been presently described.

Implicated in

Entity Malignant glioma
Note On a quantitative point of view, APLNR gene expression is highly upregulated in microvascular proliferations of malignant gliomas (Kalin et al., 2007)
Entity Various diseases
Note 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).


Functional expression of the seven-transmembrane HIV-1 co-receptor APJ in neural cells.
Choe W, Albright A, Sulcove J, Jaffer S, Hesselgesser J, Lavi E, Crino P, Kolson DL.
J Neurovirol. 2000 May;6 Suppl 1:S61-9.
PMID 10871767
Apelin, 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, D'Agostino SL, Miller MK, Heimark RL, Krieg PA.
Dev Biol. 2006 Aug 1;296(1):177-89. Epub 2006 Apr 27.
PMID 16750822
Cloning, pharmacological characterization and brain distribution of the rat apelin receptor.
De Mota N, Lenkei Z, Llorens-Cortes C.
Neuroendocrinology. 2000 Dec;72(6):400-7.
PMID 11146423
Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release.
De Mota N, Reaux-Le Goazigo A, El Messari S, Chartrel N, Roesch D, Dujardin C, Kordon C, Vaudry H, Moos F, Llorens-Cortes C.
Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10464-9. Epub 2004 Jul 1.
PMID 15231996
Expression of a new G protein-coupled receptor X-msr is associated with an endothelial lineage in Xenopus laevis.
Devic E, Paquereau L, Vernier P, Knibiehler B, Audigier Y.
Mech Dev. 1996 Oct;59(2):129-40.
PMID 8951791
Amino acid sequence and embryonic expression of msr/apj, the mouse homolog of Xenopus X-msr and human APJ.
Devic E, Rizzoti K, Bodin S, Knibiehler B, Audigier Y.
Mech Dev. 1999 Jun;84(1-2):199-203.
PMID 10473142
Apelin stimulates glucose utilization in normal and obese insulin-resistant mice.
Dray C, Knauf C, Daviaud D, Waget A, Boucher J, Buleon M, Cani PD, Attane C, Guigne C, Carpene C, Burcelin R, Castan-Laurell I, Valet P.
Cell Metab. 2008 Nov;8(5):437-45.
PMID 19046574
Apelin, the natural ligand of the orphan receptor APJ, is abundantly secreted in the colostrum.
Habata Y, Fujii R, Hosoya M, Fukusumi S, Kawamata Y, Hinuma S, Kitada C, Nishizawa N, Murosaki S, Kurokawa T, Onda H, Tatemoto K, Fujino M.
Biochim Biophys Acta. 1999 Oct 13;1452(1):25-35.
PMID 10525157
Increased colonic apelin production in rodents with experimental colitis and in humans with IBD.
Han S, Wang G, Qiu S, de la Motte C, Wang HQ, Gomez G, Englander EW, Greeley GH Jr.
Regul Pept. 2007 Aug 16;142(3):131-7. Epub 2007 Feb 22.
PMID 17391779
Functional SNP in an Sp1-binding site of AGTRL1 gene is associated with susceptibility to brain infarction.
Hata J, Matsuda K, Ninomiya T, Yonemoto K, Matsushita T, Ohnishi Y, Saito S, Kitazono T, Ibayashi S, Iida M, Kiyohara Y, Nakamura Y, Kubo M.
Hum Mol Genet. 2007 Mar 15;16(6):630-9. Epub 2007 Feb 19.
PMID 17309882
Paracrine and autocrine mechanisms of apelin signaling govern embryonic and tumor angiogenesis.
Kalin RE, Kretz MP, Meyer AM, Kispert A, Heppner FL, Brandli AW.
Dev Biol. 2007 May 15;305(2):599-614. Epub 2007 Mar 12.
PMID 17412318
Apelin is a novel angiogenic factor in retinal endothelial cells.
Kasai A, Shintani N, Oda M, Kakuda M, Hashimoto H, Matsuda T, Hinuma S, Baba A.
Biochem Biophys Res Commun. 2004 Dec 10;325(2):395-400.
PMID 15530405
Transcriptomes of purified gastric ECL and parietal cells: identification of a novel pathway regulating acid secretion.
Lambrecht NW, Yakubov I, Zer C, Sachs G.
Physiol Genomics. 2006 Mar 13;25(1):153-65. Epub 2006 Jan 10.
PMID 16403840
Characterization of apelin, the ligand for the APJ receptor.
Lee DK, Cheng R, Nguyen T, Fan T, Kariyawasam AP, Liu Y, Osmond DH, George SR, O'Dowd BF.
J Neurochem. 2000 Jan;74(1):34-41.
PMID 10617103
The apelin receptor is coupled to Gi1 or Gi2 protein and is differentially desensitized by apelin fragments.
Masri B, Morin N, Pedebernade L, Knibiehler B, Audigier Y.
J Biol Chem. 2006 Jul 7;281(27):18317-26. Epub 2006 May 5.
PMID 16679320
Distribution 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, Selby TL, Palkovits M, Lolait SJ.
Biochim Biophys Acta. 2000 Jun 21;1492(1):72-80.
PMID 11004481
A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11.
O'Dowd BF, Heiber M, Chan A, Heng HH, Tsui LC, Kennedy JL, Shi X, Petronis A, George SR, Nguyen T.
Gene. 1993 Dec 22;136(1-2):355-60.
PMID 8294032
The 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, Forleo C, Pietrucci F, Capestro A, Soura E, Guida P, Sorrentino S, Iacoviello M, Romito R, Dessi-Fulgheri P, Pitzalis M, Rappelli A.
J Card Fail. 2007 Sep;13(7):521-9.
PMID 17826642
The g protein-coupled receptor agtrl1b regulates early development of myocardial progenitors.
Scott IC, Masri B, D'Amico LA, Jin SW, Jungblut B, Wehman AM, Baier H, Audigier Y, Stainier DY.
Dev Cell. 2007 Mar;12(3):403-13.
PMID 17336906
The apj receptor is expressed in pancreatic islets and its ligand, apelin, inhibits insulin secretion in mice.
Sorhede Winzell M, Magnusson C, Ahren B.
Regul Pept. 2005 Nov;131(1-3):12-7.
PMID 15970338
Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility.
Szokodi I, Tavi P, Foldes G, Voutilainen-Myllyla S, Ilves M, Tokola H, Pikkarainen S, Piuhola J, Rysa J, Toth M, Ruskoaho H.
Circ Res. 2002 Sep 6;91(5):434-40.
PMID 12215493
The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism.
Tatemoto K, Takayama K, Zou MX, Kumaki I, Zhang W, Kumano K, Fujimiya M.
Regul Pept. 2001 Jun 15;99(2-3):87-92.
PMID 11384769
Apelin and its receptor are expressed in human osteoblasts.
Xie H, Tang SY, Cui RR, Huang J, Ren XH, Yuan LQ, Lu Y, Yang M, Zhou HD, Wu XP, Luo XH, Liao EY.
Regul Pept. 2006 May 15;134(2-3):118-25. Epub 2006 Mar 6.
PMID 16563531


This paper should be referenced as such :
Audigier, Y
APLNR (apelin receptor)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(7):627-629.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)APLNR   339
Entrez_Gene (NCBI)APLNR  187  apelin receptor
AliasesAGTRL1; APJ; APJR; HG11
GeneCards (Weizmann)APLNR
Ensembl hg19 (Hinxton)ENSG00000134817 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000134817 [Gene_View]  chr11:57233578-57237453 [Contig_View]  APLNR [Vega]
ICGC DataPortalENSG00000134817
Genatlas (Paris)APLNR
Genetics Home Reference (NIH)APLNR
Genomic and cartography
GoldenPath hg38 (UCSC)APLNR  -     chr11:57233578-57237453 -  11q12.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)APLNR  -     11q12.1   [Description]    (hg19-Feb_2009)
EnsemblAPLNR - 11q12.1 [CytoView hg19]  APLNR - 11q12.1 [CytoView hg38]
Mapping of homologs : NCBIAPLNR [Mapview hg19]  APLNR [Mapview hg38]
Gene and transcription
Genbank (Entrez)AK074514 AK075252 AK097232 AK315542 AL548962
RefSeq transcript (Entrez)NM_005161
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)APLNR
Cluster EST : UnigeneHs.438311 [ NCBI ]
CGAP (NCI)Hs.438311
Alternative Splicing GalleryENSG00000134817
Gene Expression Viewer (FireBrowse)APLNR [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)187
GTEX Portal (Tissue expression)APLNR
Human Protein AtlasENSG00000134817-APLNR [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP35414   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP35414  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP35414
Splice isoforms : SwissVarP35414
Domaine pattern : Prosite (Expaxy)G_PROTEIN_RECEP_F1_1 (PS00237)    G_PROTEIN_RECEP_F1_2 (PS50262)   
Domains : Interpro (EBI)Apelin_receptor_C    APJ_rcpt    GPCR_Rhodpsn    GPCR_Rhodpsn_7TM   
Domain families : Pfam (Sanger)7tm_1 (PF00001)   
Domain families : Pfam (NCBI)pfam00001   
Domain structure : Prodom (Prabi Lyon)Apelin_receptor_C (PD061381)   
Conserved Domain (NCBI)APLNR
DMDM Disease mutations187
Blocks (Seattle)APLNR
PDB (SRS)2LOT    2LOU    2LOV    2LOW   
PDB (PDBSum)2LOT    2LOU    2LOV    2LOW   
PDB (IMB)2LOT    2LOU    2LOV    2LOW   
PDB (RSDB)2LOT    2LOU    2LOV    2LOW   
Structural Biology KnowledgeBase2LOT    2LOU    2LOV    2LOW   
SCOP (Structural Classification of Proteins)2LOT    2LOU    2LOV    2LOW   
CATH (Classification of proteins structures)2LOT    2LOU    2LOV    2LOW   
Human Protein Atlas [tissue]ENSG00000134817-APLNR [tissue]
Peptide AtlasP35414
IPIIPI00018672   IPI00903039   IPI00180692   
Protein Interaction databases
IntAct (EBI)P35414
Ontologies - Pathways
Ontology : AmiGOreceptor activity  G-protein coupled receptor activity  plasma membrane  integral component of plasma membrane  G-protein coupled receptor signaling pathway  gastrulation  heart development  regulation of body fluid levels  
Ontology : EGO-EBIreceptor activity  G-protein coupled receptor activity  plasma membrane  integral component of plasma membrane  G-protein coupled receptor signaling pathway  gastrulation  heart development  regulation of body fluid levels  
Pathways : KEGGNeuroactive ligand-receptor interaction   
REACTOMEP35414 [protein]
REACTOME PathwaysR-HSA-418594 [pathway]   
Atlas of Cancer Signalling NetworkAPLNR
Wikipedia pathwaysAPLNR
Orthology - Evolution
GeneTree (enSembl)ENSG00000134817
Phylogenetic Trees/Animal Genes : TreeFamAPLNR
Homologs : HomoloGeneAPLNR
Homology/Alignments : Family Browser (UCSC)APLNR
Gene fusions - Rearrangements
Tumor Fusion PortalAPLNR
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerAPLNR [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)APLNR
Exome Variant ServerAPLNR
ExAC (Exome Aggregation Consortium)ENSG00000134817
GNOMAD BrowserENSG00000134817
Genetic variants : HAPMAP187
Genomic Variants (DGV)APLNR [DGVbeta]
DECIPHERAPLNR [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisAPLNR 
ICGC Data PortalAPLNR 
TCGA Data PortalAPLNR 
Broad Tumor PortalAPLNR
OASIS PortalAPLNR [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICAPLNR  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDAPLNR
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch APLNR
DgiDB (Drug Gene Interaction Database)APLNR
DoCM (Curated mutations)APLNR (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)APLNR (select a term)
NCG5 (London)APLNR
Cancer3DAPLNR(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry APLNR
NextProtP35414 [Medical]
Target ValidationAPLNR
Huge Navigator APLNR [HugePedia]
snp3D : Map Gene to Disease187
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD187
Chemical/Pharm GKB GenePA162376687
Clinical trialAPLNR
canSAR (ICR)APLNR (select the gene name)
PubMed72 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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