ID APJ_MOUSE Reviewed; 377 AA.
AC Q9WV08; Q3TZS9;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 27-MAR-2024, entry version 172.
DE RecName: Full=Apelin receptor;
DE AltName: Full=Angiotensin receptor-like 1;
DE AltName: Full=G-protein coupled receptor APJ;
DE AltName: Full=MSR;
GN Name=Aplnr; Synonyms=Agtrl1, Apj;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=10473142; DOI=10.1016/s0925-4773(99)00081-7;
RA Devic E., Rizzoti K., Bodin S., Knibiehler B., Audigier Y.;
RT "Amino acid sequence and embryonic expression of msr/apj, the mouse homolog
RT of Xenopus X-msr and human APJ.";
RL Mech. Dev. 84:199-203(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Lung, Pituitary, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=28854362; DOI=10.1016/j.celrep.2017.08.014;
RA Freyer L., Hsu C.W., Nowotschin S., Pauli A., Ishida J., Kuba K.,
RA Fukamizu A., Schier A.F., Hoodless P.A., Dickinson M.E.,
RA Hadjantonakis A.K.;
RT "Loss of Apela peptide in mice causes low penetrance embryonic lethality
RT and defects in early mesodermal derivatives.";
RL Cell Rep. 20:2116-2130(2017).
RN [5]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=26611206; DOI=10.1007/s00395-015-0521-6;
RA Perjes A., Kilpioe T., Ulvila J., Magga J., Alakoski T., Szabo Z.,
RA Vainio L., Halmetoja E., Vuolteenaho O., Petaejae-Repo U., Szokodi I.,
RA Kerkelae R.;
RT "Characterization of apela, a novel endogenous ligand of apelin receptor,
RT in the adult heart.";
RL Basic Res. Cardiol. 111:2-2(2016).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28371822; DOI=10.1093/cvr/cvx061;
RA Sato T., Sato C., Kadowaki A., Watanabe H., Ho L., Ishida J., Yamaguchi T.,
RA Kimura A., Fukamizu A., Penninger J.M., Reversade B., Ito H., Imai Y.,
RA Kuba K.;
RT "ELABELA-APJ axis protects from pressure overload heart failure and
RT angiotensin II-induced cardiac damage.";
RL Cardiovasc. Res. 113:760-769(2017).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=28890073; DOI=10.1016/j.devcel.2017.08.008;
RA Sharma B., Ho L., Ford G.H., Chen H.I., Goldstone A.B., Woo Y.J.,
RA Quertermous T., Reversade B., Red-Horse K.;
RT "Alternative progenitor cells compensate to rebuild the coronary
RT vasculature in Elabela- and Apj-deficient hearts.";
RL Dev. Cell 42:655-666(2017).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=28663440; DOI=10.1126/science.aam6607;
RA Ho L., van Dijk M., Chye S.T.J., Messerschmidt D.M., Chng S.C., Ong S.,
RA Yi L.K., Boussata S., Goh G.H., Afink G.B., Lim C.Y., Dunn N.R., Solter D.,
RA Knowles B.B., Reversade B.;
RT "ELABELA deficiency promotes preeclampsia and cardiovascular malformations
RT in mice.";
RL Science 357:707-713(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. Plays a key role in early development such as
CC gastrulation, blood vessels formation and heart morphogenesis by acting
CC as a receptor for APELA hormone (PubMed:28854362, PubMed:28890073,
CC PubMed:28663440). May promote angioblast migration toward the embryonic
CC midline, i.e. the position of the future vessel formation, during
CC vasculogenesis (By similarity). Promotes sinus venosus (SV)-derived
CC endothelial cells migration into the developing heart to promote
CC coronary blood vessel development (PubMed:28890073). Also plays a role
CC in various processes in adults such as regulation of blood vessel
CC formation, blood pressure, heart contractility and heart failure
CC (PubMed:28371822). {ECO:0000250|UniProtKB:P79960,
CC ECO:0000250|UniProtKB:Q7SZP9, ECO:0000269|PubMed:28371822,
CC ECO:0000269|PubMed:28663440, ECO:0000269|PubMed:28854362,
CC ECO:0000269|PubMed:28890073}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P35414};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P79960}. Note=After
CC exposure to apelin (APLN) or apelin receptor early endogenous ligand
CC (APELA), internalized from the cell surface into an endosomal recycling
CC compartment, from where it is recycled to the cell membrane.
CC {ECO:0000250|UniProtKB:P35414, ECO:0000250|UniProtKB:Q9JHG3}.
CC -!- TISSUE SPECIFICITY: Expressed in coronary endothelial cells (at protein
CC level) (PubMed:28890073). Expressed in the embryo, allantoic and
CC endothelial precursor cells of the yolk sac at 8 days post-coitum (dpc)
CC (PubMed:28663440). Expressed in the secondary heart field and somite at
CC 8.25 dpc (PubMed:28854362). Expressed in fetal allantoic endothelial
CC cells at 9 dpc (PubMed:28663440). Expressed in the allantoid and the
CC invading fetal vasculature of the placenta at 9.5 dpc
CC (PubMed:28854362). Expressed in endothelial cells adjacent to
CC syncytiotrophoblast cells at 10.5 dpc (PubMed:28663440). Expressed
CC weakly in the embryonic heart at 11.5 dpc (PubMed:26611206). Expressed
CC in the adult heart (PubMed:26611206). Expressed in endothelial cells
CC and cardiomyocytes and weakly expressed in fibroblasts
CC (PubMed:10473142, PubMed:26611206). {ECO:0000269|PubMed:10473142,
CC ECO:0000269|PubMed:26611206, ECO:0000269|PubMed:28663440,
CC ECO:0000269|PubMed:28854362, ECO:0000269|PubMed:28890073}.
CC -!- DEVELOPMENTAL STAGE: Expressed from embryonic 8 days post-coitum (dpc)
CC throughout the subsequent stages of formation of the cardiovascular
CC system (PubMed:10473142). {ECO:0000269|PubMed:10473142}.
CC -!- INDUCTION: Up-regulated following myocardial infarction (MI) (at
CC protein level) (PubMed:26611206). {ECO:0000269|PubMed:26611206}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking APLNR are not represented at
CC Mendelian ratios. Mutant embryos exhibit incomplete penetrance of
CC embryonic lethality (PubMed:28854362, PubMed:28663440). Mutant embryos
CC display improper establishment of the fetal-maternal circulation, such
CC as underdeveloped yolk sac vasculature, embryonic vascular
CC malformations and impaired cardiac tube looping at 10.5 dpc
CC (PubMed:28854362, PubMed:28663440). Mice heart of embryos show reduced
CC coronary vessel growth at 13.5 dpc (PubMed:28890073). The heart of
CC mutant adult mice induced by pressure overload display no improvement
CC in cardiac dysfunction, hypertrophy and fibrosis in response to peptide
CC hormone APELA treatment (PubMed:28371822). Conditional knockout in
CC heart endothelial cells leads to delayed progression of vessel growth
CC onto the heart and reduced branching of the developing coronary plexus
CC in both the subepicardial and intramyocardial layers at 13.5 and 15.5
CC dpc (PubMed:28890073). Conditional endothelial-specific knockout adult
CC mice, despite severe embryonic coronary vessel defects recover normal
CC cardiac functions; endocardial-derived coronary vessels expand to
CC rescue defective sinus venosus development in a APELA-APLNR-independent
CC manner (PubMed:28890073). Double knockout mice of APLNR and APELA genes
CC exhibited the same penetrance and embryonic lethality as single APELA
CC knockout mice (PubMed:28854362). {ECO:0000269|PubMed:28371822,
CC ECO:0000269|PubMed:28663440, ECO:0000269|PubMed:28854362,
CC ECO:0000269|PubMed:28890073}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AJ007612; CAB50696.1; -; mRNA.
DR EMBL; AK075706; BAC35901.1; -; mRNA.
DR EMBL; AK133580; BAE21731.1; -; mRNA.
DR EMBL; AK157582; BAE34128.1; -; mRNA.
DR EMBL; BC039224; AAH39224.1; -; mRNA.
DR CCDS; CCDS16201.1; -.
DR RefSeq; NP_035914.1; NM_011784.3.
DR AlphaFoldDB; Q9WV08; -.
DR SMR; Q9WV08; -.
DR STRING; 10090.ENSMUSP00000053638; -.
DR BindingDB; Q9WV08; -.
DR ChEMBL; CHEMBL4879524; -.
DR GlyCosmos; Q9WV08; 2 sites, No reported glycans.
DR GlyGen; Q9WV08; 2 sites.
DR iPTMnet; Q9WV08; -.
DR PhosphoSitePlus; Q9WV08; -.
DR SwissPalm; Q9WV08; -.
DR MaxQB; Q9WV08; -.
DR PaxDb; 10090-ENSMUSP00000053638; -.
DR ProteomicsDB; 296374; -.
DR Antibodypedia; 14066; 642 antibodies from 36 providers.
DR DNASU; 23796; -.
DR Ensembl; ENSMUST00000057019.9; ENSMUSP00000053638.8; ENSMUSG00000044338.10.
DR GeneID; 23796; -.
DR KEGG; mmu:23796; -.
DR UCSC; uc008kkb.2; mouse.
DR AGR; MGI:1346086; -.
DR CTD; 187; -.
DR MGI; MGI:1346086; Aplnr.
DR VEuPathDB; HostDB:ENSMUSG00000044338; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244888; -.
DR HOGENOM; CLU_009579_8_1_1; -.
DR InParanoid; Q9WV08; -.
DR OMA; TVMLTCY; -.
DR OrthoDB; 5317155at2759; -.
DR PhylomeDB; Q9WV08; -.
DR TreeFam; TF330024; -.
DR Reactome; R-MMU-375276; Peptide ligand-binding receptors.
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR BioGRID-ORCS; 23796; 2 hits in 78 CRISPR screens.
DR PRO; PR:Q9WV08; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9WV08; Protein.
DR Bgee; ENSMUSG00000044338; Expressed in renal medulla interstitium and 213 other cell types or tissues.
DR ExpressionAtlas; Q9WV08; baseline and differential.
DR Genevisible; Q9WV08; MM.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0060182; F:apelin receptor activity; IBA:GO_Central.
DR GO; GO:0007512; P:adult heart development; IMP:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0035904; P:aorta development; IMP:BHF-UCL.
DR GO; GO:0060183; P:apelin receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0003171; P:atrioventricular valve development; IMP:BHF-UCL.
DR GO; GO:0001568; P:blood vessel development; IBA:GO_Central.
DR GO; GO:0060976; P:coronary vasculature development; IMP:UniProtKB.
DR GO; GO:0003272; P:endocardial cushion formation; IMP:BHF-UCL.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISS: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; IMP:BHF-UCL.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:1903589; P:positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IMP:UniProtKB.
DR GO; GO:1904325; P:positive regulation of inhibitory G protein-coupled receptor phosphorylation; ISS:UniProtKB.
DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; ISS:UniProtKB.
DR GO; GO:0050878; P:regulation of body fluid levels; ISO:MGI.
DR GO; GO:1903596; P:regulation of gap junction assembly; IMP:BHF-UCL.
DR GO; GO:0010468; P:regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0035886; P:vascular associated smooth muscle cell differentiation; IMP:BHF-UCL.
DR GO; GO:0001944; P:vasculature development; IMP:BHF-UCL.
DR GO; GO:0001570; P:vasculogenesis; IMP:UniProtKB.
DR GO; GO:0060841; P:venous blood vessel development; IMP:BHF-UCL.
DR GO; GO:0060412; P:ventricular septum morphogenesis; IMP: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; 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 Angiogenesis; Cell membrane; Developmental protein;
KW G-protein coupled receptor; Gastrulation; Glycoprotein; Membrane; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..377
FT /note="Apelin receptor"
FT /id="PRO_0000069175"
FT TOPO_DOM 1..24
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 25..49
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 50..64
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 65..89
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 90..98
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 99..123
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 124..142
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 143..164
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 165..198
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 199..219
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 220..242
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 243..269
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 270..282
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 283..306
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 307..377
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 334..377
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 334..352
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 13
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 377 AA; 42266 MW; AA443A7800A24E0B CRC64;
MEDDGYNYYG ADNQSECDYA DWKPSGALIP AIYMLVFLLG TTGNGLVLWT VFRTSREKRR
SADIFIASLA VADLTFVVTL PLWATYTYRE FDWPFGTFSC KLSSYLIFVN MYASVFCLTG
LSFDRYLAIV RPVANARLRL RVSGAVATAV LWVLAALLAV PVMVFRSTDA SENGTKIQCY
MDYSMVATSN SEWAWEVGLG VSSTAVGFVV PFTIMLTCYF FIAQTIAGHF RKERIEGLRK
RRRLLSIIVV LVVTFALCWM PYHLVKTLYM LGSLLHWPCD FDIFLMNVFP YCTCISYVNS
CLNPFLYAFF DPRFRQACTS MLCCDQSGCK GTPHSSSAEK SASYSSGHSQ GPGPNMGKGG
EQMHEKSIPY SQETLVD
//
