APJA_DANRE
ID APJA_DANRE Reviewed; 362 AA.
AC Q7SZP9; Q002B2; Q08CP6;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Apelin receptor A;
DE AltName: Full=Angiotensin II receptor-like 1a;
DE AltName: Full=Angiotensin receptor-like 1a;
DE AltName: Full=G-protein coupled receptor APJ A;
GN Name=aplnra; Synonyms=agtrl1 {ECO:0000312|EMBL:ABI99470.1}, agtrl1a;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1] {ECO:0000305, ECO:0000312|EMBL:ABI99470.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Embryo {ECO:0000269|PubMed:17085078};
RX PubMed=17085078; DOI=10.1016/j.modgep.2006.09.006;
RA Tucker B., Hepperle C., Kortschak D., Rainbird B., Wells S., Oates A.C.,
RA Lardelli M.;
RT "Zebrafish angiotensin II receptor-like 1a (agtrl1a) is expressed in
RT migrating hypoblast, vasculature, and in multiple embryonic epithelia.";
RL Gene Expr. Patterns 7:258-265(2007).
RN [2] {ECO:0000312|EMBL:AAI24151.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo {ECO:0000312|EMBL:AAI24151.1}, and
RC Kidney {ECO:0000312|EMBL:AAH56308.2};
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP FUNCTION.
RX PubMed=17336906; DOI=10.1016/j.devcel.2007.01.012;
RA Scott I.C., Masri B., D'Amico L.A., Jin S.-W., Jungblut B., Wehman A.M.,
RA Baier H., Audigier Y., Stainier D.Y.R.;
RT "The G protein-coupled receptor Agtrl1b regulates early development of
RT myocardial progenitors.";
RL Dev. Cell 12:403-413(2007).
RN [4]
RP FUNCTION, INTERACTION WITH APELA, AND DISRUPTION PHENOTYPE.
RX PubMed=24316148; DOI=10.1016/j.devcel.2013.11.002;
RA Chng S.C., Ho L., Tian J., Reversade B.;
RT "ELABELA: a hormone essential for heart development signals via the apelin
RT receptor.";
RL Dev. Cell 27:672-680(2013).
RN [5]
RP FUNCTION, INTERACTION WITH APELA, AND DISRUPTION PHENOTYPE.
RX PubMed=24407481; DOI=10.1126/science.1248636;
RA Pauli A., Norris M.L., Valen E., Chew G.L., Gagnon J.A., Zimmerman S.,
RA Mitchell A., Ma J., Dubrulle J., Reyon D., Tsai S.Q., Joung J.K.,
RA Saghatelian A., Schier A.F.;
RT "Toddler: an embryonic signal that promotes cell movement via apelin
RT receptors.";
RL Science 343:1248636-1248636(2014).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26017639; DOI=10.7554/elife.06726;
RA Helker C.S., Schuermann A., Pollmann C., Chng S.C., Kiefer F.,
RA Reversade B., Herzog W.;
RT "The hormonal peptide Elabela guides angioblasts to the midline during
RT vasculogenesis.";
RL Elife 4:0-0(2015).
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:17336906, PubMed:24316148, PubMed:24407481).
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, promoting endoderm and mesendoderm cell migration and
CC regulating the migration of cells fated to become myocardial
CC progenitors, respectively (PubMed:17336906, PubMed:24316148,
CC PubMed:24407481, PubMed:26017639). Positively regulates angioblast
CC migration toward the embryonic midline, i.e. the position of the future
CC vessel formation, during vasculogenesis (PubMed:26017639). May promote
CC sinus venosus (SV)-derived endothelial cells migration into the
CC developing heart to promote coronary blood vessel development (By
CC similarity). Required for cardiovascular development, particularly for
CC intersomitic vein angiogenesis by acting as a receptor for apln hormone
CC (By similarity). Also plays a role in various processes in adults such
CC as regulation of blood vessel formation, blood pressure, heart
CC contractility, and heart failure (By similarity). Acts redundantly with
CC agtrl1b in heart development (PubMed:17336906).
CC {ECO:0000250|UniProtKB:P35414, ECO:0000250|UniProtKB:P79960,
CC ECO:0000250|UniProtKB:Q4VA82, ECO:0000250|UniProtKB:Q9WV08,
CC ECO:0000269|PubMed:17336906, ECO:0000269|PubMed:24316148,
CC ECO:0000269|PubMed:24407481, ECO:0000269|PubMed:26017639}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P79960};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P79960}.
CC Note=Internalized to the cytoplasm after exposure to apelin (apln).
CC After exposure to apelin receptor early endogenous ligand (apela),
CC 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:P79960}.
CC -!- TISSUE SPECIFICITY: First expressed before epiboly in dorsal
CC precursors. During epiboly, expressed in the enveloping layer, yolk
CC syncytial layer and migrating mesendoderm. During segmentation stages,
CC expressed in epithelial structures such as adaxial cells, border cells
CC of the newly formed somites, developing lens, otic vesicles and venous
CC vasculature. {ECO:0000269|PubMed:17085078}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein induces
CC embryonic lethality due to cardiac dysplasia with little to no blood
CC circulation around 6 days post-fertilization (dpf) (PubMed:24316148).
CC Mutant embryos show pericardial edema and accumulation of erythrocytes
CC in the intermediate cell mass (ICM) at 30 hours post-fertilization
CC (hpf) (PubMed:24316148). Display decreased angioblast migration to the
CC embryonic midline during late gastrulation (PubMed:24316148,
CC PubMed:24407481, PubMed:26017639). {ECO:0000269|PubMed:24316148,
CC ECO:0000269|PubMed:24407481, ECO:0000269|PubMed:26017639}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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; DQ983235; ABI99470.1; -; mRNA.
DR EMBL; BC056308; AAH56308.2; -; mRNA.
DR EMBL; BC124150; AAI24151.1; -; mRNA.
DR RefSeq; NP_001068573.1; NM_001075105.1.
DR AlphaFoldDB; Q7SZP9; -.
DR SMR; Q7SZP9; -.
DR STRING; 7955.ENSDARP00000068614; -.
DR PaxDb; Q7SZP9; -.
DR Ensembl; ENSDART00000074125; ENSDARP00000068614; ENSDARG00000002172.
DR GeneID; 561935; -.
DR KEGG; dre:561935; -.
DR CTD; 561935; -.
DR ZFIN; ZDB-GENE-060929-512; aplnra.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244888; -.
DR HOGENOM; CLU_009579_8_1_1; -.
DR InParanoid; Q7SZP9; -.
DR OMA; NSCGFLR; -.
DR OrthoDB; 788659at2759; -.
DR PhylomeDB; Q7SZP9; -.
DR TreeFam; TF330024; -.
DR Reactome; R-DRE-375276; Peptide ligand-binding receptors.
DR Reactome; R-DRE-418594; G alpha (i) signalling events.
DR PRO; PR:Q7SZP9; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 8.
DR Bgee; ENSDARG00000002172; Expressed in gastrula and 52 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0060182; F:apelin receptor activity; IDA:ZFIN.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0035479; P:angioblast cell migration from lateral mesoderm to midline; IMP:ZFIN.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0001568; P:blood vessel development; IBA:GO_Central.
DR GO; GO:0048738; P:cardiac muscle tissue development; ISS:UniProtKB.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0042074; P:cell migration involved in gastrulation; IMP:ZFIN.
DR GO; GO:0060976; P:coronary vasculature development; ISS:UniProtKB.
DR GO; GO:0061371; P:determination of heart left/right asymmetry; IMP:ZFIN.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:ZFIN.
DR GO; GO:0071910; P:determination of liver left/right asymmetry; IMP:ZFIN.
DR GO; GO:0035987; P:endodermal cell differentiation; IGI:ZFIN.
DR GO; GO:0055113; P:epiboly involved in gastrulation with mouth forming second; IMP:ZFIN.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0001702; P:gastrulation with mouth forming second; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; IGI:UniProtKB.
DR GO; GO:0070121; P:Kupffer's vesicle development; IMP:ZFIN.
DR GO; GO:0001945; P:lymph vessel development; IMP:ZFIN.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; ISS:UniProtKB.
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; ISS: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:1900107; P:regulation of nodal signaling pathway; IGI:ZFIN.
DR GO; GO:0001570; P:vasculogenesis; ISS:UniProtKB.
DR InterPro; IPR000248; ATII_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00241; ANGIOTENSINR.
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 Angiogenesis; Cell membrane; Developmental protein;
KW G-protein coupled receptor; Gastrulation; Glycoprotein; Membrane; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..362
FT /note="Apelin receptor A"
FT /id="PRO_0000312593"
FT TOPO_DOM 1..34
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 35..55
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 56..73
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 74..94
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 95..106
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 107..127
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 128..149
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 150..170
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 171..211
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..232
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 233..248
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 249..269
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 270..284
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 285..305
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 306..362
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255, ECO:0000312|EMBL:ABI99470.1"
FT CARBOHYD 19
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 5
FT /note="S -> P (in Ref. 2; AAI24151)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="F -> FL (in Ref. 1; ABI99470)"
FT /evidence="ECO:0000305"
FT CONFLICT 305
FT /note="V -> A (in Ref. 2; AAI24151)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 362 AA; 40649 MW; 81422A572D2B33A0 CRC64;
MEPTSEYTET YDYYDTGYND SGCDYSEWEP SYSLIPVLYM LIFILGLSGN GVVIFTVWRA
KSKRRAADVY IGNLALADLT FVITLPLWAV YTALGYHWPF GVALCKISSY VVLVNMYASV
FCLTCLSFDR YLAIVHSLSS GRLRSRATML ASLGAIWFLS CLLAVPTLLF RTTVDDTGSN
RTTCAMDFSL VTLNQDHESL WIAGLSLSSS ALGFLLPFLA MTVCYCFIGC TVTRHFSHLR
KEDQKKRRLL KIITTLVVVF AFCWTPFHVL KSMDALSYLD LAPNSCGFLH FLLLAHPYAT
CLAYVNSCLN PFLYAFFDLR FRSQCLCLLN LKKAMHGHMS SMSSTLSAQT QKSEVQSLAT
KV
