Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

APLNR (apelin receptor)

Identity

Other namesAGTRL1
APJ
APJR
FLJ90771
HG11
MGC45246
HGNC (Hugo) APLNR
LocusID (NCBI) 187
Location 11q12.1
Location_base_pair Starts at 57001052 and ends at 57004927 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

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

Protein

 
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).

Mutations

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).
  

External links

Nomenclature
HGNC (Hugo)APLNR   339
Cards
AtlasAPLNRID44364ch11q12
Entrez_Gene (NCBI)APLNR  187  apelin receptor
GeneCards (Weizmann)APLNR
Ensembl (Hinxton)ENSG00000134817 [Gene_View]  chr11:57001052-57004927 [Contig_View]  APLNR [Vega]
ICGC DataPortalENSG00000134817
AceView (NCBI)APLNR
Genatlas (Paris)APLNR
WikiGenes187
SOURCE (Princeton)NM_005161
Genomic and cartography
GoldenPath (UCSC)APLNR  -  11q12.1   chr11:57001052-57004927 -  11q12.1   [Description]    (hg19-Feb_2009)
EnsemblAPLNR - 11q12.1 [CytoView]
Mapping of homologs : NCBIAPLNR [Mapview]
OMIM600052   
Gene and transcription
Genbank (Entrez)AK074514 AK075252 AK097232 AK315542 AL548962
RefSeq transcript (Entrez)NM_005161
RefSeq genomic (Entrez)AC_000143 NC_000011 NC_018922 NT_167190 NW_001838023 NW_004929380
Consensus coding sequences : CCDS (NCBI)APLNR
Cluster EST : UnigeneHs.438311 [ NCBI ]
CGAP (NCI)Hs.438311
Alternative Splicing : Fast-db (Paris)GSHG0005773
Alternative Splicing GalleryENSG00000134817
Gene ExpressionAPLNR [ NCBI-GEO ]     APLNR [ SEEK ]   APLNR [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP35414 (Uniprot)
NextProtP35414  [Medical]
With graphics : InterProP35414
Splice isoforms : SwissVarP35414 (Swissvar)
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   
Related proteins : CluSTrP35414
Domain families : Pfam (Sanger)7tm_1 (PF00001)   
Domain families : Pfam (NCBI)pfam00001   
Domain structure : Prodom (Prabi Lyon)Apelin_receptor_C (PD061381)   
DMDM Disease mutations187
Blocks (Seattle)P35414
PDB (SRS)2LOT    2LOU    2LOV    2LOW   
PDB (PDBSum)2LOT    2LOU    2LOV    2LOW   
PDB (IMB)2LOT    2LOU    2LOV    2LOW   
PDB (RSDB)2LOT    2LOU    2LOV    2LOW   
Human Protein AtlasENSG00000134817
Peptide AtlasP35414
HPRD02503
IPIIPI00018672   IPI00903039   IPI00180692   
Protein Interaction databases
DIP (DOE-UCLA)P35414
IntAct (EBI)P35414
FunCoupENSG00000134817
BioGRIDAPLNR
IntegromeDBAPLNR
STRING (EMBL)APLNR
Ontologies - Pathways
QuickGOP35414
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 PathwaysREACT_111102 Signal Transduction [pathway]
Protein Interaction DatabaseAPLNR
Wikipedia pathwaysAPLNR
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)APLNR
SNP (GeneSNP Utah)APLNR
SNP : HGBaseAPLNR
Genetic variants : HAPMAPAPLNR
1000_GenomesAPLNR 
ICGC programENSG00000134817 
CONAN: Copy Number AnalysisAPLNR 
Somatic Mutations in Cancer : COSMICAPLNR 
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
DECIPHER (Syndromes)11:57001052-57004927
Mutations and Diseases : HGMDAPLNR
OMIM600052   
MedgenAPLNR
GENETestsAPLNR
Disease Genetic AssociationAPLNR
Huge Navigator APLNR [HugePedia]  APLNR [HugeCancerGEM]
Genomic VariantsAPLNR  APLNR [DGVbeta]
Exome VariantAPLNR
dbVarAPLNR
ClinVarAPLNR
snp3D : Map Gene to Disease187
General knowledge
Homologs : HomoloGeneAPLNR
Homology/Alignments : Family Browser (UCSC)APLNR
Phylogenetic Trees/Animal Genes : TreeFamAPLNR
Chemical/Protein Interactions : CTD187
Chemical/Pharm GKB GenePA162376687
Clinical trialAPLNR
Cancer Resource (Charite)ENSG00000134817
Other databases
Probes
Litterature
PubMed55 Pubmed reference(s) in Entrez
CoreMineAPLNR
GoPubMedAPLNR
iHOPAPLNR

Bibliography

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
 
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, 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
 
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
 
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
 
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
 
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
 
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, 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
 
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
 
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
 
Apelin (65-77) activates p70 S6 kinase and is mitogenic for umbilical endothelial cells.
Masri B, Morin N, Cornu M, Knibiehler B, Audigier Y.
FASEB J. 2004 Dec;18(15):1909-11. Epub 2004 Sep 22.
PMID 15385434
 
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 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
 
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
 
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
 
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
 
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
 
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
 
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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written08-2009Yves Audigier
Unite INSERM U-858, I2MR, equipe 13, CHU Rangueil, Bat. L3, BP 84225, 1 avenue Jean-Poulhes, 31432-Toulouse Cedex 4, France

Citation

This paper should be referenced as such :
Audigier, Y
APLNR (apelin receptor)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(7):-.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/APLNRID44364ch11q12.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Nov 8 16:29:32 CET 2014

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.