ANPRC_MOUSE
ID ANPRC_MOUSE Reviewed; 536 AA.
AC P70180; G3X9E5; P97804; Q9R025; Q9R027; Q9R028;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 3.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Atrial natriuretic peptide receptor 3;
DE AltName: Full=Atrial natriuretic peptide clearance receptor;
DE AltName: Full=Atrial natriuretic peptide receptor type C;
DE Short=ANP-C;
DE Short=ANPR-C;
DE Short=NPR-C;
DE AltName: Full=EF-2;
DE Flags: Precursor;
GN Name=Npr3;
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].
RC STRAIN=BALB/cJ; TISSUE=Lung;
RX PubMed=8620881; DOI=10.1111/j.1432-1033.1996.0025n.x;
RA Yanaka N., Kotera J., Taguchi I., Sugiura M., Kawashima K., Omori K.;
RT "Structure of the 5'-flanking regulatory region of the mouse gene encoding
RT the clearance receptor for atrial natriuretic peptide.";
RL Eur. J. Biochem. 237:25-34(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LGJ ASN-168, VARIANT LGJ-2J
RP 66-ARG--SER-77 DEL, AND POSSIBLE INVOLVEMENT IN SKELETAL-OVERGROWTH
RP SYNDROME.
RC STRAIN=129/Sv, and BALB/cJ;
RX PubMed=10468599; DOI=10.1073/pnas.96.18.10278;
RA Jaubert J., Jaubert F., Martin N., Washburn L.L., Lee B.K., Eicher E.M.,
RA Guenet J.-L.;
RT "Three new allelic mouse mutations that cause skeletal overgrowth involve
RT the natriuretic peptide receptor C gene (Npr3).";
RL Proc. Natl. Acad. Sci. U.S.A. 96:10278-10283(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 255-439.
RX PubMed=9032278; DOI=10.1128/mcb.17.3.1503;
RA Fu X., Kamps M.P.;
RT "E2a-Pbx1 induces aberrant expression of tissue-specific and
RT developmentally regulated genes when expressed in NIH 3T3 fibroblasts.";
RL Mol. Cell. Biol. 17:1503-1512(1997).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10377427; DOI=10.1073/pnas.96.13.7403;
RA Matsukawa N., Grzesik W.J., Takahashi N., Pandey K.N., Pang S.,
RA Yamauchi M., Smithies O.;
RT "The natriuretic peptide clearance receptor locally modulates the
RT physiological effects of the natriuretic peptide system.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:7403-7408(1999).
RN [7]
RP FUNCTION, AND INTERACTION WITH OSTN.
RX PubMed=17951249; DOI=10.1074/jbc.m708596200;
RA Moffatt P., Thomas G., Sellin K., Bessette M.C., Lafreniere F.,
RA Akhouayri O., St-Arnaud R., Lanctot C.;
RT "Osteocrin is a specific ligand of the natriuretic Peptide clearance
RT receptor that modulates bone growth.";
RL J. Biol. Chem. 282:36454-36462(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Receptor for the natriuretic peptide hormones, binding with
CC similar affinities atrial natriuretic peptide NPPA/ANP, brain
CC natriuretic peptide NPPB/BNP, and C-type natriuretic peptide NPPC/CNP
CC (PubMed:10377427, PubMed:17951249). May function as a clearance
CC receptor for NPPA, NPPB and NPPC, regulating their local concentrations
CC and effects (PubMed:10377427, PubMed:17951249). May regulate diuresis,
CC blood pressure and skeletal development (PubMed:10377427). Does not
CC have guanylate cyclase activity (PubMed:10377427).
CC {ECO:0000269|PubMed:10377427, ECO:0000269|PubMed:17951249}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts with
CC OSTN (PubMed:17951249). {ECO:0000250|UniProtKB:P17342,
CC ECO:0000269|PubMed:17951249}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P17342};
CC Single-pass type I membrane protein.
CC -!- DISEASE: Note=Defects in Npr3 are the cause of a number of skeletal-
CC overgrowth phenotypes, Longjohn (Lgj), Longjohn-2J (Lgj-2J) and
CC Strigosus (Stri). These are all recessive conditions characterized by
CC an elongated body, thoracic kyphosis, arachnodactyly, and sacral and/or
CC tail kinks, but no significant changes in craniofacial structures
CC (PubMed:10468599). {ECO:0000269|PubMed:10468599}.
CC -!- DISRUPTION PHENOTYPE: Half of the mice dies before weaning. They
CC display reduced ability to concentrate urine, a lower blood pressure,
CC and skeletal abnormalities. Despite a reduced half-life of NPPA in the
CC circulation, the plasma levels of NPPA AND NPPB are not affected.
CC {ECO:0000269|PubMed:10377427}.
CC -!- MISCELLANEOUS: Has low affinity for peptide hormones in the absence of
CC bound chloride. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ANF receptor family. {ECO:0000305}.
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DR EMBL; D78175; BAA11241.1; -; mRNA.
DR EMBL; AF131861; AAF00104.1; -; Genomic_DNA.
DR EMBL; AF131862; AAF00105.1; -; Genomic_DNA.
DR EMBL; AF131864; AAF00107.1; -; Genomic_DNA.
DR EMBL; AC134793; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466581; EDL03281.1; -; Genomic_DNA.
DR EMBL; U72676; AAB51036.1; -; mRNA.
DR CCDS; CCDS27386.1; -.
DR PIR; S71332; S71332.
DR RefSeq; NP_032754.2; NM_008728.2.
DR AlphaFoldDB; P70180; -.
DR SMR; P70180; -.
DR DIP; DIP-46248N; -.
DR IntAct; P70180; 2.
DR STRING; 10090.ENSMUSP00000066737; -.
DR BindingDB; P70180; -.
DR ChEMBL; CHEMBL4711; -.
DR GlyGen; P70180; 3 sites.
DR iPTMnet; P70180; -.
DR PhosphoSitePlus; P70180; -.
DR MaxQB; P70180; -.
DR PaxDb; P70180; -.
DR PRIDE; P70180; -.
DR ProteomicsDB; 296047; -.
DR Antibodypedia; 5387; 481 antibodies from 35 providers.
DR DNASU; 18162; -.
DR Ensembl; ENSMUST00000066529; ENSMUSP00000066737; ENSMUSG00000022206.
DR GeneID; 18162; -.
DR KEGG; mmu:18162; -.
DR UCSC; uc007vhf.2; mouse.
DR CTD; 4883; -.
DR MGI; MGI:97373; Npr3.
DR VEuPathDB; HostDB:ENSMUSG00000022206; -.
DR eggNOG; KOG1023; Eukaryota.
DR GeneTree; ENSGT00440000033872; -.
DR HOGENOM; CLU_013995_1_0_1; -.
DR InParanoid; P70180; -.
DR OMA; ENNIGKH; -.
DR OrthoDB; 1423201at2759; -.
DR PhylomeDB; P70180; -.
DR TreeFam; TF106339; -.
DR BioGRID-ORCS; 18162; 5 hits in 72 CRISPR screens.
DR ChiTaRS; Npr3; mouse.
DR PRO; PR:P70180; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; P70180; protein.
DR Bgee; ENSMUSG00000022206; Expressed in epididymal fat pad and 235 other tissues.
DR ExpressionAtlas; P70180; baseline and differential.
DR Genevisible; P70180; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0031404; F:chloride ion binding; ISO:MGI.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; ISO:MGI.
DR GO; GO:0042562; F:hormone binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0016941; F:natriuretic peptide receptor activity; ISS:UniProtKB.
DR GO; GO:0042277; F:peptide binding; ISO:MGI.
DR GO; GO:0017046; F:peptide hormone binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0007194; P:negative regulation of adenylate cyclase activity; ISO:MGI.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0002158; P:osteoclast proliferation; IMP:UniProtKB.
DR GO; GO:0030157; P:pancreatic juice secretion; ISO:MGI.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; ISO:MGI.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; ISO:MGI.
DR GO; GO:0035810; P:positive regulation of urine volume; IMP:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; IMP:UniProtKB.
DR GO; GO:0033688; P:regulation of osteoblast proliferation; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0001501; P:skeletal system development; IDA:HGNC.
DR GO; GO:0042311; P:vasodilation; ISO:MGI.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR001170; ANPR/GUC.
DR InterPro; IPR028082; Peripla_BP_I.
DR Pfam; PF01094; ANF_receptor; 1.
DR PRINTS; PR00255; NATPEPTIDER.
DR SUPFAM; SSF53822; SSF53822; 1.
DR PROSITE; PS00458; ANF_RECEPTORS; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Chloride; Disease variant; Disulfide bond; Glycoprotein;
KW Membrane; Receptor; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT PROPEP 27..40
FT /evidence="ECO:0000255"
FT /id="PRO_0000012371"
FT CHAIN 41..536
FT /note="Atrial natriuretic peptide receptor 3"
FT /id="PRO_0000012372"
FT TOPO_DOM 41..478
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 479..499
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 500..536
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT BINDING 101
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 130
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 131
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 103..131
FT /evidence="ECO:0000250|UniProtKB:P10730"
FT DISULFID 208..256
FT /evidence="ECO:0000250|UniProtKB:P10730"
FT DISULFID 468
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P10730"
FT VARIANT 66..77
FT /note="Missing (in Lgj-2J)"
FT /evidence="ECO:0000269|PubMed:10468599"
FT VARIANT 168
FT /note="H -> N (in Lgj)"
FT /evidence="ECO:0000269|PubMed:10468599"
FT CONFLICT 4
FT /note="L -> F (in Ref. 1; BAA11241 and 2; AAF00104/
FT AAF00105/AAF00107)"
FT /evidence="ECO:0000305"
FT CONFLICT 58..59
FT /note="DS -> IT (in Ref. 1; BAA11241)"
FT /evidence="ECO:0000305"
FT CONFLICT 132
FT /note="E -> G (in Ref. 1; BAA11241)"
FT /evidence="ECO:0000305"
FT CONFLICT 293
FT /note="G -> V (in Ref. 5; AAB51036)"
FT /evidence="ECO:0000305"
FT CONFLICT 348
FT /note="Y -> C (in Ref. 5; AAB51036)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 536 AA; 59808 MW; 78E14B5C4711411E CRC64;
MRSLLLFTFS ACVLLARVLL AGGASSGAGD TRPGSRRRAR EALAAQKIEV LVLLPRDDSY
LFSLARVRPA IEYALRSVEG NGTGRKLLPP GTRFQVAYED SDCGNRALFS LVDRVAAARG
AKPDLILGPV CEYAAAPVAR LASHWDLPML SAGALAAGFQ HKDTEYSHLT RVAPAYAKMG
EMMLALFRHH HWSRAALVYS DDKLERNCYF TLEGVHEVFQ EEGLHTSAYN FDETKDLDLD
DIVRYIQGSE RVVIMCASGD TIRRIMLAVH RHGMTSGDYA FFNIELFNSS SYGDGSWRRG
DKHDSEAKQA YSSLQTVTLL RTVKPEFEKF SMEVKSSVEK QGLNEEDYVN MFVEGFHDAI
LLYVLALHEV LRAGYSKKDG GKIIQQTWNR TFEGIAGQVS IDANGDRYGD FSVVAMTDTE
AGTQEVIGDY FGKEGRFQMR SNVKYPWGPL KLRLDETRIV EHTNSSPCKS SGGLEESAVT
GIVVGALLGA GLLMAFYFFR KKYRITIERR NQQEESNIGK HRELREDSIR SHFSVA
