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 02-OCT-2024, entry version 201. 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; O43613: HCRTR1; NbExp=6; IntAct=EBI-2875891, EBI-21914411; CC P35414; P41145: OPRK1; NbExp=4; 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:25639753, PubMed:8294032). 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="https://atlasgeneticsoncology.org/gene/44364/APLNR"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7SUS; X-ray; 2.70 A; A=7-229, A=243-330. DR PDB; 7W0L; EM; 3.57 A; Q/R=2-330. DR PDB; 7W0M; EM; 3.71 A; R=2-330. DR PDB; 7W0N; EM; 4.21 A; Q/R=2-330. DR PDB; 7W0O; EM; 3.78 A; R=2-330. DR PDB; 7W0P; EM; 3.16 A; R=2-330. DR PDB; 8XZF; EM; 3.00 A; R=1-380. DR PDB; 8XZG; EM; 3.20 A; R=1-380. DR PDB; 8XZH; EM; 2.60 A; R=1-380. DR PDB; 8XZI; EM; 2.70 A; R=1-380. DR PDB; 8XZJ; EM; 3.00 A; R=1-380. DR PDBsum; 2LOT; -. DR PDBsum; 2LOU; -. DR PDBsum; 2LOV; -. DR PDBsum; 2LOW; -. DR PDBsum; 5VBL; -. DR PDBsum; 6KNM; -. DR PDBsum; 7SUS; -. DR PDBsum; 7W0L; -. DR PDBsum; 7W0M; -. DR PDBsum; 7W0N; -. DR PDBsum; 7W0O; -. DR PDBsum; 7W0P; -. DR PDBsum; 8XZF; -. DR PDBsum; 8XZG; -. DR PDBsum; 8XZH; -. DR PDBsum; 8XZI; -. DR PDBsum; 8XZJ; -. DR AlphaFoldDB; P35414; -. DR BMRB; P35414; -. DR EMDB; EMD-38794; -. DR EMDB; EMD-38795; -. DR EMDB; EMD-38796; -. DR EMDB; EMD-38797; -. DR EMDB; EMD-38798; -. DR SMR; P35414; -. DR BioGRID; 106693; 233. DR IntAct; P35414; 215. 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 GlyCosmos; P35414; 2 sites, No reported glycans. 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; 9606-ENSP00000475344; -. DR PeptideAtlas; P35414; -. DR ProteomicsDB; 55061; -. DR ABCD; P35414; 2 sequenced antibodies. DR Antibodypedia; 14066; 638 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 AGR; HGNC:339; -. DR CTD; 187; -. DR DisGeNET; 187; -. DR GeneCards; APLNR; -. DR HGNC; HGNC:339; APLNR. DR HPA; ENSG00000134817; Tissue enhanced (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; ENSGT01120000271849; -. DR HOGENOM; CLU_009579_8_1_1; -. DR InParanoid; P35414; -. DR OMA; TVMLTCY; -. DR OrthoDB; 5317155at2759; -. 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 1156 CRISPR screens. DR ChiTaRS; APLNR; human. DR EvolutionaryTrace; P35414; -. 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 cell types or tissues. 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; TAS:ProtInc. 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:1904022; P:positive regulation of G protein-coupled receptor internalization; 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 CDD; cd15190; 7tmA_Apelin_R; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR003904; Apelin_rcpt. DR InterPro; IPR050119; GPCR1. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR PANTHER; PTHR10489:SF951; APELIN RECEPTOR; 1. DR PANTHER; PTHR10489; CELL ADHESION MOLECULE; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR01416; APJRECEPTOR. DR PRINTS; PR00237; GPCRRHODOPSN. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. 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; Proteomics identification; Receptor; KW Reference proteome; Transducer; 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 TURN 134..136 FT /evidence="ECO:0007829|PDB:7W0P" 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 TURN 174..176 FT /evidence="ECO:0007829|PDB:8XZH" FT STRAND 180..183 FT /evidence="ECO:0007829|PDB:5VBL" FT TURN 186..188 FT /evidence="ECO:0007829|PDB:5VBL" FT HELIX 191..193 FT /evidence="ECO:0007829|PDB:8XZH" FT HELIX 194..209 FT /evidence="ECO:0007829|PDB:5VBL" FT HELIX 211..228 FT /evidence="ECO:0007829|PDB:5VBL" FT STRAND 234..236 FT /evidence="ECO:0007829|PDB:8XZH" 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 //