ID ANPRA_MOUSE Reviewed; 1057 AA.
AC P18293;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 2.
DT 27-MAR-2024, entry version 205.
DE RecName: Full=Atrial natriuretic peptide receptor 1;
DE EC=4.6.1.2;
DE AltName: Full=Atrial natriuretic peptide receptor type A;
DE Short=ANP-A;
DE Short=ANPR-A;
DE Short=NPR-A;
DE AltName: Full=Guanylate cyclase A;
DE Short=GC-A;
DE Flags: Precursor;
GN Name=Npr1; Synonyms=Npra;
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=C57BL/6J;
RX PubMed=1973687; DOI=10.1016/s0021-9258(19)38352-8;
RA Pandey K.N., Singh S.;
RT "Molecular cloning and expression of murine guanylate cyclase/atrial
RT natriuretic factor receptor cDNA.";
RL J. Biol. Chem. 265:12342-12348(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7838126;
RA Schoenfeld J.R., Sehl P., Quan C., Burnier J.P., Lowe D.G.;
RT "Agonist selectivity for three species of natriuretic peptide receptor-A.";
RL Mol. Pharmacol. 47:172-180(1995).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=9405681; DOI=10.1073/pnas.94.26.14730;
RA Oliver P.M., Fox J.E., Kim R., Rockman H.A., Kim H.S., Reddick R.L.,
RA Pandey K.N., Milgram S.L., Smithies O., Maeda N.;
RT "Hypertension, cardiac hypertrophy, and sudden death in mice lacking
RT natriuretic peptide receptor A.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:14730-14735(1997).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Liver, Lung, and Testis;
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 atrial natriuretic peptide NPPA/ANP and the
CC brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones
CC playing a key role in cardiovascular homeostasis. Has guanylate cyclase
CC activity upon binding of the ligand.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP = 3',5'-cyclic GMP + diphosphate; Xref=Rhea:RHEA:13665,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:57746; EC=4.6.1.2;
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- PTM: Phosphorylation of the protein kinase-like domain is required for
CC full activation by ANP. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice display systemic hypertension associated
CC with cardiac hypertrophy and ventricular enlargement.
CC {ECO:0000269|PubMed:9405681}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR EMBL; J05504; AAA37670.1; -; mRNA.
DR EMBL; L31932; AAA66945.1; -; mRNA.
DR CCDS; CCDS17529.1; -.
DR PIR; A36568; OYMSAR.
DR PIR; I57963; I57963.
DR RefSeq; NP_032753.5; NM_008727.5.
DR AlphaFoldDB; P18293; -.
DR SMR; P18293; -.
DR BioGRID; 201830; 4.
DR ComplexPortal; CPX-34; ANPR-A receptor complex.
DR STRING; 10090.ENSMUSP00000029540; -.
DR GlyCosmos; P18293; 6 sites, No reported glycans.
DR GlyGen; P18293; 6 sites.
DR iPTMnet; P18293; -.
DR PhosphoSitePlus; P18293; -.
DR CPTAC; non-CPTAC-3386; -.
DR PaxDb; 10090-ENSMUSP00000029540; -.
DR ProteomicsDB; 281996; -.
DR Pumba; P18293; -.
DR Antibodypedia; 20386; 369 antibodies from 32 providers.
DR DNASU; 18160; -.
DR Ensembl; ENSMUST00000029540.13; ENSMUSP00000029540.7; ENSMUSG00000027931.13.
DR GeneID; 18160; -.
DR KEGG; mmu:18160; -.
DR UCSC; uc008qcg.1; mouse.
DR AGR; MGI:97371; -.
DR CTD; 4881; -.
DR MGI; MGI:97371; Npr1.
DR VEuPathDB; HostDB:ENSMUSG00000027931; -.
DR eggNOG; KOG1023; Eukaryota.
DR GeneTree; ENSGT00940000156223; -.
DR HOGENOM; CLU_001072_1_3_1; -.
DR InParanoid; P18293; -.
DR OMA; KCAYEKS; -.
DR OrthoDB; 3683909at2759; -.
DR PhylomeDB; P18293; -.
DR TreeFam; TF106338; -.
DR BRENDA; 4.6.1.2; 3474.
DR Reactome; R-MMU-5578768; Physiological factors.
DR BioGRID-ORCS; 18160; 2 hits in 80 CRISPR screens.
DR ChiTaRS; Npr1; mouse.
DR PRO; PR:P18293; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P18293; Protein.
DR Bgee; ENSMUSG00000027931; Expressed in yolk sac and 78 other cell types or tissues.
DR ExpressionAtlas; P18293; baseline and differential.
DR Genevisible; P18293; MM.
DR GO; GO:1990620; C:ANPR-A receptor complex; ISS:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0004016; F:adenylate cyclase activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0004383; F:guanylate cyclase activity; IDA:MGI.
DR GO; GO:0042562; F:hormone binding; ISO:MGI.
DR GO; GO:0016941; F:natriuretic peptide receptor activity; ISS:UniProtKB.
DR GO; GO:0017046; F:peptide hormone binding; ISO:MGI.
DR GO; GO:0001653; F:peptide receptor activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
DR GO; GO:0097746; P:blood vessel diameter maintenance; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISO:MGI.
DR GO; GO:0006182; P:cGMP biosynthetic process; ISO:MGI.
DR GO; GO:0019934; P:cGMP-mediated signaling; ISO:MGI.
DR GO; GO:0042417; P:dopamine metabolic process; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0010753; P:positive regulation of cGMP-mediated signaling; ISO:MGI.
DR GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; ISO:MGI.
DR GO; GO:0008217; P:regulation of blood pressure; IDA:ComplexPortal.
DR CDD; cd07302; CHD; 1.
DR CDD; cd06385; PBP1_NPR_A; 1.
DR CDD; cd14042; PK_GC-A_B; 1.
DR Gene3D; 3.40.50.2300; -; 2.
DR Gene3D; 3.30.70.1230; Nucleotide cyclase; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR001054; A/G_cyclase.
DR InterPro; IPR018297; A/G_cyclase_CS.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR001170; ANPR/GUC.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR InterPro; IPR028082; Peripla_BP_I.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR PANTHER; PTHR11920:SF300; ATRIAL NATRIURETIC PEPTIDE RECEPTOR 1; 1.
DR PANTHER; PTHR11920; GUANYLYL CYCLASE; 1.
DR Pfam; PF01094; ANF_receptor; 1.
DR Pfam; PF00211; Guanylate_cyc; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00255; NATPEPTIDER.
DR SMART; SM00044; CYCc; 1.
DR SUPFAM; SSF55073; Nucleotide cyclase; 1.
DR SUPFAM; SSF53822; Periplasmic binding protein-like I; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS00458; ANF_RECEPTORS; 1.
DR PROSITE; PS00452; GUANYLATE_CYCLASE_1; 1.
DR PROSITE; PS50125; GUANYLATE_CYCLASE_2; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW cGMP biosynthesis; Chloride; Disulfide bond; Glycoprotein; GTP-binding;
KW Lyase; Membrane; Nucleotide-binding; Phosphoprotein; Receptor;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix; Vasoactive.
FT SIGNAL 1..28
FT CHAIN 29..1057
FT /note="Atrial natriuretic peptide receptor 1"
FT /id="PRO_0000012361"
FT TOPO_DOM 29..469
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 470..490
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 491..1057
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 524..801
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 872..1002
FT /note="Guanylate cyclase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 81
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 113
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 114
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT MOD_RES 515
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16066"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16066"
FT MOD_RES 528
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P16066"
FT MOD_RES 530
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16066"
FT MOD_RES 534
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16066"
FT MOD_RES 538
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P18910"
FT MOD_RES 541
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P18910"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 208
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 375
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 382
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 423
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 88..114
FT /evidence="ECO:0000250"
FT DISULFID 192..241
FT /evidence="ECO:0000250"
FT DISULFID 451..460
FT /evidence="ECO:0000250"
FT CONFLICT 3
FT /note="G -> R (in Ref. 1; AAA37670)"
FT /evidence="ECO:0000305"
FT CONFLICT 39
FT /note="L -> V (in Ref. 1; AAA37670)"
FT /evidence="ECO:0000305"
FT CONFLICT 122
FT /note="G -> D (in Ref. 1; AAA37670)"
FT /evidence="ECO:0000305"
FT CONFLICT 130
FT /note="V -> L (in Ref. 1; AAA37670)"
FT /evidence="ECO:0000305"
FT CONFLICT 285
FT /note="R -> E (in Ref. 1; AAA37670)"
FT /evidence="ECO:0000305"
FT CONFLICT 301
FT /note="A -> R (in Ref. 1; AAA37670)"
FT /evidence="ECO:0000305"
FT CONFLICT 404..405
FT /note="FS -> SP (in Ref. 1; AAA37670)"
FT /evidence="ECO:0000305"
FT CONFLICT 590
FT /note="H -> Q (in Ref. 1; AAA37670)"
FT /evidence="ECO:0000305"
FT CONFLICT 652
FT /note="G -> C (in Ref. 1; AAA37670)"
FT /evidence="ECO:0000305"
FT CONFLICT 833
FT /note="A -> P (in Ref. 1; AAA37670)"
FT /evidence="ECO:0000305"
FT CONFLICT 958
FT /note="R -> G (in Ref. 1; AAA37670)"
FT /evidence="ECO:0000305"
FT CONFLICT 1044
FT /note="T -> S (in Ref. 1; AAA37670)"
FT /evidence="ECO:0000305"
FT CONFLICT 1050
FT /note="E -> D (in Ref. 1; AAA37670)"
FT /evidence="ECO:0000305"
FT CONFLICT 1055..1057
FT /note="TRG -> SRA (in Ref. 1; AAA37670)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1057 AA; 119109 MW; 53A544FB2C8EF253 CRC64;
MPGSRRVRPR LRALLLLPPL LLLRSGHASD LTVAVVLPLT NTSYPWSWAR VGPAVELALG
RVKARPDLLP GWTVRMVLGS SENAAGVCSD TAAPLAAVDL KWEHSPAVFL GPGCVYSAAP
VGRFTAHWRV PLLTAGAPAL GIGVKDEYAL TTRTGPSHVK LGDFVTALHR RLGWEHQALV
LYADRLGDDR PCFFIVEGLY MRVRERLNIT VNHQEFVEGD PDHYTKLLRT VQRKGRVIYI
CSSPDAFRNL MLLALDAGLT GEDYVFFHLD VFGQSLQGAQ GPVPRKPWER DDGQDRRARQ
AFQAAKIITY KEPDNPEYLE FLKQLKLLAD KKFNFTMEDG LKNIIPASFH DGLLLYVQAV
TETLAQGGTV TDGENITQRM WNRSFQGVTG YLKIDRNGDR DTDFSLWDMD PETGAFRVVL
NFNGTSQELM AVSEHRLYWP LGYPPPDIPK CGFDNEDPAC NQDHFSTLEV LALVGSLSLV
SFLIVSFFIY RKMQLEKELV SELWRVRWED LQPSSLERHL RSAGSRLTLS GRGSNYGSLL
TTEGQFQVFA KTAYYKGNLV AVKRVNRKRI ELTRKVLFEL KHMRDVQNEH LTRFVGACTD
PPNICILTEY CPRGSLQDIL ENESITLDWM FRYSLTNDIV KGMLFLHNGA IGSHGNLKSS
NCVVDGRFVL KITDYGLESF RDPEPEQGHT LFAKKLWTAP ELLRMASPPA RGSQAGDVYS
FGIILQEIAL RSGVFYVEGL DLSPKEIIER VTRGEQPPFR PSMDLQSHLE ELGQLMQRCW
AEDPQERPPF QQIRLALRKF NKENSSNILD NLLSRMEQYA NNLEELVEER TQAYLEEKRK
AEALLYQILP HSVAEQLKRG ETVQAEAFDS VTIYFSDIVG FTALSAESTP MQVVTLLNDL
YTCFDAVIDN FDVYKVETIG DAYMVVSGLP VRNGQLHARE VARMALALLD AVRSFRIRHR
PQEQLRLRIG IHTGPVCAGV VGLKMPRYCL FGDTVNTASR MESNGEALRI HLSSETKAVL
EEFDGFELEL RGDVEMKGKG KVRTYWLLGE RGCSTRG
//
