APJ_HUMAN
ID APJ_HUMAN Reviewed; 380 AA.
AC P35414;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Apelin receptor;
DE AltName: Full=Angiotensin receptor-like 1;
DE AltName: Full=G-protein coupled receptor APJ;
DE AltName: Full=G-protein coupled receptor HG11;
GN Name=APLNR; Synonyms=AGTRL1, APJ;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=8294032; DOI=10.1016/0378-1119(93)90495-o;
RA O'Dowd B.F., Heiber M., Chan A., Heng H.H.Q., Tsui L.-C., Kennedy J.L.,
RA Shi X., Petronis A., George S.R., Nguyen T.;
RT "A human gene that shows identity with the gene encoding the angiotensin
RT receptor is located on chromosome 11.";
RL Gene 136:355-360(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Eggerickx D., Schurmans S., Vassart G., Parmentier M.;
RT "Molecular cloning and tissue distribution of a human orphan receptor
RT belonging to the G protein coupled receptors family.";
RL Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AND FUNCTION (MICROBIAL INFECTION).
RX PubMed=11090199; DOI=10.1128/jvi.74.24.11972-11976.2000;
RA Cayabyab M., Hinuma S., Farzan M., Choe H., Fukusumi S., Kitada C.,
RA Nishizawa N., Hosoya M., Nishimura O., Messele T., Pollakis G.,
RA Goudsmit J., Fujino M., Sodroski J.;
RT "Apelin, the natural ligand of the orphan seven-transmembrane receptor APJ,
RT inhibits human immunodeficiency virus type 1 entry.";
RL J. Virol. 74:11972-11976(2000).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=25639753; DOI=10.1038/srep08170;
RA Wang Z., Yu D., Wang M., Wang Q., Kouznetsova J., Yang R., Qian K., Wu W.,
RA Shuldiner A., Sztalryd C., Zou M., Zheng W., Gong D.W.;
RT "Elabela-apelin receptor signaling pathway is functional in mammalian
RT systems.";
RL Sci. Rep. 5:8170-8170(2015).
RN [6]
RP FUNCTION.
RX PubMed=28137936; DOI=10.1161/circulationaha.116.023218;
RA Yang P., Read C., Kuc R.E., Buonincontri G., Southwood M., Torella R.,
RA Upton P.D., Crosby A., Sawiak S.J., Carpenter T.A., Glen R.C.,
RA Morrell N.W., Maguire J.J., Davenport A.P.;
RT "Elabela/Toddler is an endogenous agonist of the apelin APJ receptor in the
RT adult cardiovascular system, and exogenous administration of the peptide
RT compensates for the downregulation of its expression in pulmonary arterial
RT hypertension.";
RL Circulation 135:1160-1173(2017).
CC -!- FUNCTION: Receptor for apelin receptor early endogenous ligand (APELA)
CC and apelin (APLN) hormones coupled to G proteins that inhibit adenylate
CC cyclase activity (PubMed:11090199, PubMed:25639753, PubMed:28137936).
CC Plays a key role in early development such as gastrulation, blood
CC vessels formation and heart morphogenesis by acting as a receptor for
CC APELA hormone (By similarity). May promote angioblast migration toward
CC the embryonic midline, i.e. the position of the future vessel
CC formation, during vasculogenesis (By similarity). Promotes sinus
CC venosus (SV)-derived endothelial cells migration into the developing
CC heart to promote coronary blood vessel development (By similarity).
CC Also plays a role in various processes in adults such as regulation of
CC blood vessel formation, blood pressure, heart contractility and heart
CC failure (PubMed:25639753, PubMed:28137936).
CC {ECO:0000250|UniProtKB:P79960, ECO:0000250|UniProtKB:Q7SZP9,
CC ECO:0000250|UniProtKB:Q9WV08, ECO:0000269|PubMed:11090199,
CC ECO:0000269|PubMed:25639753, ECO:0000269|PubMed:28137936}.
CC -!- FUNCTION: (Microbial infection) Alternative coreceptor with CD4 for
CC HIV-1 infection; may be involved in the development of AIDS dementia
CC (PubMed:11090199). {ECO:0000269|PubMed:11090199}.
CC -!- INTERACTION:
CC P35414; P30556: AGTR1; NbExp=14; IntAct=EBI-2875891, EBI-6623016;
CC P35414; P29033: GJB2; NbExp=3; IntAct=EBI-2875891, EBI-3905204;
CC P35414; P41145: OPRK1; NbExp=3; IntAct=EBI-2875891, EBI-925028;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25639753}.
CC Note=After exposure to apelin (APLN), internalized from the cell
CC surface into an endosomal recycling compartment, from where it is
CC recycled to the cell membrane (By similarity). After exposure to apelin
CC receptor early endogenous ligand (APELA), internalized from the cell
CC surface into an endosomal recycling compartment, from where it is
CC recycled to the cell membrane (PubMed:25639753).
CC {ECO:0000250|UniProtKB:Q9JHG3, ECO:0000269|PubMed:25639753}.
CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, kidney, stomach, spleen,
CC thymus, lung, ovary, small intestine and colon, adipose tissues and
CC pancreas (PubMed:8294032, PubMed:25639753). Expressed in glial cells,
CC astrocytes and neuronal subpopulations (PubMed:8294032). Expressed in
CC embryonic (ESCs) and induced (iPSCs) pluripotent stem cells
CC (PubMed:25639753). {ECO:0000269|PubMed:25639753,
CC ECO:0000269|PubMed:8294032}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/APLNRID44364ch11q12.html";
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DR EMBL; U03642; AAA18954.1; -; Genomic_DNA.
DR EMBL; X89271; CAA61546.1; -; mRNA.
DR EMBL; BC032688; AAH32688.1; -; mRNA.
DR CCDS; CCDS7950.1; -.
DR PIR; I38435; I38435.
DR RefSeq; NP_005152.1; NM_005161.4.
DR PDB; 2LOT; NMR; -; A=1-55.
DR PDB; 2LOU; NMR; -; A=1-55.
DR PDB; 2LOV; NMR; -; A=1-55.
DR PDB; 2LOW; NMR; -; A=1-55.
DR PDB; 5VBL; X-ray; 2.60 A; B=7-229, B=243-330.
DR PDB; 6KNM; X-ray; 3.20 A; B=7-229, B=243-330.
DR PDBsum; 2LOT; -.
DR PDBsum; 2LOU; -.
DR PDBsum; 2LOV; -.
DR PDBsum; 2LOW; -.
DR PDBsum; 5VBL; -.
DR PDBsum; 6KNM; -.
DR AlphaFoldDB; P35414; -.
DR BMRB; P35414; -.
DR SMR; P35414; -.
DR BioGRID; 106693; 233.
DR IntAct; P35414; 109.
DR MINT; P35414; -.
DR STRING; 9606.ENSP00000475344; -.
DR BindingDB; P35414; -.
DR ChEMBL; CHEMBL1628481; -.
DR GuidetoPHARMACOLOGY; 36; -.
DR TCDB; 9.A.14.13.10; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P35414; 2 sites.
DR iPTMnet; P35414; -.
DR PhosphoSitePlus; P35414; -.
DR BioMuta; APLNR; -.
DR DMDM; 543823; -.
DR jPOST; P35414; -.
DR MassIVE; P35414; -.
DR PaxDb; P35414; -.
DR PeptideAtlas; P35414; -.
DR PRIDE; P35414; -.
DR ProteomicsDB; 55061; -.
DR ABCD; P35414; 2 sequenced antibodies.
DR Antibodypedia; 14066; 539 antibodies from 36 providers.
DR DNASU; 187; -.
DR Ensembl; ENST00000257254.3; ENSP00000257254.3; ENSG00000134817.12.
DR Ensembl; ENST00000606794.2; ENSP00000475344.1; ENSG00000134817.12.
DR GeneID; 187; -.
DR KEGG; hsa:187; -.
DR MANE-Select; ENST00000606794.2; ENSP00000475344.1; NM_005161.6; NP_005152.1.
DR UCSC; uc001njo.4; human.
DR CTD; 187; -.
DR DisGeNET; 187; -.
DR GeneCards; APLNR; -.
DR HGNC; HGNC:339; APLNR.
DR HPA; ENSG00000134817; Group enriched (brain, lymphoid tissue, placenta).
DR MIM; 600052; gene.
DR neXtProt; NX_P35414; -.
DR OpenTargets; ENSG00000134817; -.
DR PharmGKB; PA162376687; -.
DR VEuPathDB; HostDB:ENSG00000134817; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244888; -.
DR HOGENOM; CLU_009579_8_1_1; -.
DR InParanoid; P35414; -.
DR OMA; TVMLTCY; -.
DR OrthoDB; 788659at2759; -.
DR PhylomeDB; P35414; -.
DR TreeFam; TF330024; -.
DR PathwayCommons; P35414; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P35414; -.
DR SIGNOR; P35414; -.
DR BioGRID-ORCS; 187; 13 hits in 1078 CRISPR screens.
DR ChiTaRS; APLNR; human.
DR GeneWiki; Apelin_receptor; -.
DR GenomeRNAi; 187; -.
DR Pharos; P35414; Tchem.
DR PRO; PR:P35414; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P35414; protein.
DR Bgee; ENSG00000134817; Expressed in cranial nerve II and 171 other tissues.
DR Genevisible; P35414; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0060182; F:apelin receptor activity; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc.
DR GO; GO:0007512; P:adult heart development; IEA:Ensembl.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0035904; P:aorta development; ISS:BHF-UCL.
DR GO; GO:0060183; P:apelin receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0003171; P:atrioventricular valve development; ISS:BHF-UCL.
DR GO; GO:0001568; P:blood vessel development; IBA:GO_Central.
DR GO; GO:0060976; P:coronary vasculature development; ISS:UniProtKB.
DR GO; GO:0003272; P:endocardial cushion formation; ISS:BHF-UCL.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0007369; P:gastrulation; IEA:UniProtKB-KW.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0001947; P:heart looping; ISS:BHF-UCL.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; IMP:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:BHF-UCL.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:1903589; P:positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; ISS:BHF-UCL.
DR GO; GO:1904325; P:positive regulation of inhibitory G protein-coupled receptor phosphorylation; IMP:UniProtKB.
DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IMP:UniProtKB.
DR GO; GO:0050878; P:regulation of body fluid levels; IEA:Ensembl.
DR GO; GO:1903596; P:regulation of gap junction assembly; ISS:BHF-UCL.
DR GO; GO:0010468; P:regulation of gene expression; ISS:BHF-UCL.
DR GO; GO:0035886; P:vascular associated smooth muscle cell differentiation; ISS:BHF-UCL.
DR GO; GO:0001944; P:vasculature development; ISS:BHF-UCL.
DR GO; GO:0001570; P:vasculogenesis; ISS:UniProtKB.
DR GO; GO:0060841; P:venous blood vessel development; ISS:BHF-UCL.
DR GO; GO:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL.
DR InterPro; IPR003904; Apelin_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR24228:SF31; PTHR24228:SF31; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR01416; APJRECEPTOR.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Angiogenesis; Cell membrane; Developmental protein;
KW G-protein coupled receptor; Gastrulation; Glycoprotein;
KW Host-virus interaction; Membrane; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..380
FT /note="Apelin receptor"
FT /id="PRO_0000069173"
FT TOPO_DOM 1..26
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 27..51
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 52..66
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 67..91
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 92..100
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 101..125
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 126..144
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 145..166
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 167..200
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..221
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 222..244
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..271
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 272..284
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 285..308
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 309..380
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 342..380
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 15
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 175
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 300
FT /note="V -> I (in dbSNP:rs7943508)"
FT /id="VAR_049375"
FT STRAND 9..12
FT /evidence="ECO:0007829|PDB:2LOV"
FT HELIX 13..16
FT /evidence="ECO:0007829|PDB:2LOU"
FT STRAND 18..20
FT /evidence="ECO:0007829|PDB:2LOT"
FT TURN 21..23
FT /evidence="ECO:0007829|PDB:2LOT"
FT HELIX 24..27
FT /evidence="ECO:0007829|PDB:2LOT"
FT HELIX 30..55
FT /evidence="ECO:0007829|PDB:5VBL"
FT HELIX 58..60
FT /evidence="ECO:0007829|PDB:5VBL"
FT HELIX 65..79
FT /evidence="ECO:0007829|PDB:5VBL"
FT HELIX 82..90
FT /evidence="ECO:0007829|PDB:5VBL"
FT HELIX 98..131
FT /evidence="ECO:0007829|PDB:5VBL"
FT HELIX 137..140
FT /evidence="ECO:0007829|PDB:5VBL"
FT HELIX 142..160
FT /evidence="ECO:0007829|PDB:5VBL"
FT HELIX 162..167
FT /evidence="ECO:0007829|PDB:5VBL"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:5VBL"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:6KNM"
FT STRAND 180..183
FT /evidence="ECO:0007829|PDB:5VBL"
FT TURN 186..188
FT /evidence="ECO:0007829|PDB:5VBL"
FT TURN 191..193
FT /evidence="ECO:0007829|PDB:6KNM"
FT HELIX 194..209
FT /evidence="ECO:0007829|PDB:5VBL"
FT HELIX 211..228
FT /evidence="ECO:0007829|PDB:5VBL"
FT HELIX 245..275
FT /evidence="ECO:0007829|PDB:5VBL"
FT TURN 276..278
FT /evidence="ECO:0007829|PDB:5VBL"
FT HELIX 281..312
FT /evidence="ECO:0007829|PDB:5VBL"
FT HELIX 314..325
FT /evidence="ECO:0007829|PDB:5VBL"
FT TURN 326..329
FT /evidence="ECO:0007829|PDB:5VBL"
SQ SEQUENCE 380 AA; 42660 MW; 78DB18BEA6D2B2E4 CRC64;
MEEGGDFDNY YGADNQSECE YTDWKSSGAL IPAIYMLVFL LGTTGNGLVL WTVFRSSREK
RRSADIFIAS LAVADLTFVV TLPLWATYTY RDYDWPFGTF FCKLSSYLIF VNMYASVFCL
TGLSFDRYLA IVRPVANARL RLRVSGAVAT AVLWVLAALL AMPVMVLRTT GDLENTTKVQ
CYMDYSMVAT VSSEWAWEVG LGVSSTTVGF VVPFTIMLTC YFFIAQTIAG HFRKERIEGL
RKRRRLLSII VVLVVTFALC WMPYHLVKTL YMLGSLLHWP CDFDLFLMNI FPYCTCISYV
NSCLNPFLYA FFDPRFRQAC TSMLCCGQSR CAGTSHSSSG EKSASYSSGH SQGPGPNMGK
GGEQMHEKSI PYSQETLVVD
