APJA_XENLA
ID APJA_XENLA Reviewed; 362 AA.
AC P79960; A1XP42; A4QNR6; P70058;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Apelin receptor A;
DE AltName: Full=Angiotensin receptor-like 1a;
DE Short=xAngio1;
DE AltName: Full=Angiotensin receptor-related protein A;
DE AltName: Full=G-protein coupled receptor APJ-A;
DE Short=APJa;
DE AltName: Full=Mesenchyme-associated serpentine receptor;
DE Short=x-MSR;
GN Name=aplnr-a; Synonyms=agtrl1, agtrl1-a, agtrl1a, angio1, msr;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP MUTAGENESIS OF ASP-81.
RC TISSUE=Gastrula;
RX PubMed=8951791; DOI=10.1016/0925-4773(96)00585-0;
RA Devic E., Paquereau L., Vernier P., Knibiehler B., Audigier Y.;
RT "Expression of a new G protein-coupled receptor X-msr is associated with an
RT endothelial lineage in Xenopus laevis.";
RL Mech. Dev. 59:129-140(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Saha M.S., Oakes J.A., Miles R.R.;
RT "XAngio1, a novel Xenopus gene, is expressed in vascular precursor cells.";
RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Embryo;
RX PubMed=17412318; DOI=10.1016/j.ydbio.2007.03.004;
RA Kaelin R.E., Kretz M.P., Meyer A.M., Kispert A., Heppner F.L.,
RA Braendli A.W.;
RT "Paracrine and autocrine mechanisms of apelin signaling govern embryonic
RT and tumor angiogenesis.";
RL Dev. Biol. 305:599-614(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Neurula;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16750822; DOI=10.1016/j.ydbio.2006.04.452;
RA Cox C.M., D'Agostino S.L., Miller M.K., Heimark R.L., Krieg P.A.;
RT "Apelin, the ligand for the endothelial G-protein-coupled receptor, APJ, is
RT a potent angiogenic factor required for normal vascular development of the
RT frog embryo.";
RL Dev. Biol. 296:177-189(2006).
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16876154; DOI=10.1016/j.ydbio.2006.06.028;
RA Inui M., Fukui A., Ito Y., Asashima M.;
RT "Xapelin and Xmsr are required for cardiovascular development in Xenopus
RT laevis.";
RL Dev. Biol. 298:188-200(2006).
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:17412318, PubMed:16750822, PubMed:16876154).
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 (By similarity). Promotes angioblast
CC migration toward the embryonic midline, i.e. the position of the future
CC vessel formation, during vasculogenesis (By similarity). 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 (PubMed:17412318, PubMed:16750822, PubMed:16876154). 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 (By
CC similarity). Acts upstream of the i/o type of G-alpha proteins in the
CC differentiation of endothelium, erythroid cells, myeloid cells and
CC cardiomyocytes (PubMed:16876154). {ECO:0000250|UniProtKB:P35414,
CC ECO:0000250|UniProtKB:Q7SZP9, ECO:0000250|UniProtKB:Q9WV08,
CC ECO:0000269|PubMed:16750822, ECO:0000269|PubMed:16876154,
CC ECO:0000269|PubMed:17412318}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17412318};
CC Multi-pass membrane protein {ECO:0000269|PubMed:17412318}.
CC Note=Internalized to the cytoplasm after exposure to apelin (apln)
CC (PubMed:17412318). After exposure to apelin receptor early endogenous
CC ligand (apela), internalized from the cell surface into an endosomal
CC recycling compartment, from where it is recycled to the cell membrane
CC (By similarity). {ECO:0000250|UniProtKB:P35414,
CC ECO:0000269|PubMed:17412318}.
CC -!- TISSUE SPECIFICITY: Expressed in all blood vessels including the
CC posterior cardinal vein, intersomitic veins and the vitelline vein
CC network. At the gastrula stage, exclusively expressed in the mesodermal
CC layer and at the neurula stage in the lateral plate mesoderm. Larval
CC expression is observed in the endothelium of the primary blood vessels
CC and the forming heart. {ECO:0000269|PubMed:16750822,
CC ECO:0000269|PubMed:16876154, ECO:0000269|PubMed:17412318,
CC ECO:0000269|PubMed:8951791}.
CC -!- DEVELOPMENTAL STAGE: Expression starts in the late blastula (stage 8),
CC increases during gastrulation and remains constant between neurula and
CC larva stages. {ECO:0000269|PubMed:8951791}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB17004.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI39487.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA63612.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X93045; CAA63612.1; ALT_FRAME; mRNA.
DR EMBL; U72029; AAB17004.1; ALT_SEQ; mRNA.
DR EMBL; DQ473441; ABF19731.1; -; mRNA.
DR EMBL; BC139486; AAI39487.1; ALT_FRAME; mRNA.
DR RefSeq; NP_001084106.1; NM_001090637.1.
DR AlphaFoldDB; P79960; -.
DR SMR; P79960; -.
DR DNASU; 399306; -.
DR GeneID; 399306; -.
DR KEGG; xla:399306; -.
DR CTD; 399306; -.
DR Xenbase; XB-GENE-6254056; aplnr.L.
DR OMA; NQTICAM; -.
DR OrthoDB; 788659at2759; -.
DR Proteomes; UP000186698; Chromosome 1L.
DR Bgee; 399306; Expressed in gastrula and 18 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0060182; F:apelin receptor activity; IDA:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IMP:UniProtKB.
DR GO; GO:0060183; P:apelin receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0001568; P:blood vessel development; IMP:UniProtKB.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IMP:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007369; P:gastrulation; IEA:UniProtKB-KW.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
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: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 InterPro; IPR003904; Apelin_rcpt.
DR InterPro; IPR000248; ATII_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; 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; Differentiation;
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_0000069177"
FT TOPO_DOM 1..37
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 38..58
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 59..76
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..97
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 98..110
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 111..131
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 132..151
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 152..172
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 173..199
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 200..220
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 221..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..296
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 297..317
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 318..362
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 19
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 81
FT /note="D->N: No phenotype when overexpressed."
FT /evidence="ECO:0000269|PubMed:8951791"
FT CONFLICT 150
FT /note="S -> P (in Ref. 1; CAA63612)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 362 AA; 40858 MW; 33B80895612B3B5D CRC64;
METEGLSPML YEDDYYYGNE TGLQPCDETD WDFSYSLLPV FYMIVFVLGL SGNGVVIFTV
WKSKPKRRSA DTYIGNLALA DLAFVVTLPL WATYTALGFH WPFGSALCKL SSYLVLLNMF
ASVFCLTCLS FDRYLAIVHS LSSAKLRSRS SIIVSLAVIW LFSGLLALPS LILRDTRVEG
NNTICDLDFS GVSSKENENF WIGGLSILTT VPGFLLPLLL MTIFYCFIGG KVTMHFQNLK
KEEQKKKRLL KIIITLVVVF AICWLPFHIL KTIHFLDLMG FLELSCSTQN IIVSLHPYAT
CLAYVNSCLN PFLYAFFDLR FRSQCFFFFG FKKVLQGHLS NTSSSLSAQT QKSEIHSLAT
KV
