ANPRB_HUMAN
ID ANPRB_HUMAN Reviewed; 1047 AA.
AC P20594; B0ZBF2; B0ZBF3; D3DRP3; D3DRP4; O60871; Q4VAK7; Q5TCV2; Q8TA93;
AC Q9UQ50;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 225.
DE RecName: Full=Atrial natriuretic peptide receptor 2;
DE EC=4.6.1.2 {ECO:0000269|PubMed:26980729};
DE AltName: Full=Atrial natriuretic peptide receptor type B;
DE Short=ANP-B;
DE Short=ANPR-B;
DE Short=NPR-B;
DE AltName: Full=Guanylate cyclase B;
DE Short=GC-B;
DE Flags: Precursor;
GN Name=NPR2; Synonyms=ANPRB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE (ISOFORM LONG).
RC TISSUE=Brain;
RX PubMed=2570358; DOI=10.1038/341068a0;
RA Chang M.S., Lowe D.G., Lewis M., Hellmiss R., Chen E., Goeddel D.V.;
RT "Differential activation by atrial and brain natriuretic peptides of two
RT different receptor guanylate cyclases.";
RL Nature 341:68-72(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Blood;
RX PubMed=10082481; DOI=10.1161/01.res.84.5.605;
RA Rehemudula D., Nakayama T., Soma M., Takahashi Y., Uwabo J., Sato M.,
RA Izumi Y., Kanmatsuse K., Ozawa Y.;
RT "Structure of the type B human natriuretic peptide receptor gene and
RT association of a novel microsatellite polymorphism with essential
RT hypertension.";
RL Circ. Res. 84:605-610(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RC TISSUE=Kidney;
RX PubMed=10073597; DOI=10.1681/asn.v103472;
RA Hirsch J.R., Meyer M., Maegert H.-J., Forssmann W.-G., Mollerup S.,
RA Herter P., Weber G., Cermak R., Ankorina-Stark I., Schlatter E.,
RA Kruhoffer M.;
RT "cGMP-dependent and -independent inhibition of a K+ conductance by
RT natriuretic peptides: molecular and functional studies in human proximal
RT tubule cells.";
RL J. Am. Soc. Nephrol. 10:472-480(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC TISSUE=Brain;
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 [8]
RP LIGAND-BINDING.
RX PubMed=1660465; DOI=10.1016/s0021-9258(18)54463-x;
RA Bennett B.D., Bennett G.L., Vitangcol R.V., Jewett J.R., Burnier J.,
RA Henzel W., Lowe D.G.;
RT "Extracellular domain-IgG fusion proteins for three human natriuretic
RT peptide receptors. Hormone pharmacology and application to solid phase
RT screening of synthetic peptide antisera.";
RL J. Biol. Chem. 266:23060-23067(1991).
RN [9]
RP FUNCTION.
RX PubMed=1672777; DOI=10.1126/science.1672777;
RA Koller K.J., Lowe D.G., Bennett G.L., Minamino N., Kangawa K., Matsuo H.,
RA Goeddel D.V.;
RT "Selective activation of the B natriuretic peptide receptor by C-type
RT natriuretic peptide (CNP).";
RL Science 252:120-123(1991).
RN [10]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [11]
RP FUNCTION, VARIANTS AMD1 THR-32; GLY-115; GLU-176; MET-297; CYS-338;
RP THR-409; GLU-413; CYS-708; TRP-776; CYS-957 AND ALA-959, AND
RP CHARACTERIZATION OF VARIANTS AMD1 GLY-115; MET-297 AND GLU-413.
RX PubMed=15146390; DOI=10.1086/422013;
RA Bartels C.F., Buekuelmez H., Padayatti P., Rhee D.K.,
RA van Ravenswaaij-Arts C., Pauli R.M., Mundlos S., Chitayat D., Shih L.-Y.,
RA Al-Gazali L.I., Kant S., Cole T., Morton J., Cormier-Daire V., Faivre L.,
RA Lees M., Kirk J., Mortier G.R., Leroy J., Zabel B., Kim C.A., Crow Y.,
RA Braverman N.E., van den Akker F., Warman M.L.;
RT "Mutations in the transmembrane natriuretic peptide receptor NPR-B impair
RT skeletal growth and cause acromesomelic dysplasia, type Maroteaux.";
RL Am. J. Hum. Genet. 75:27-34(2004).
RN [12]
RP PHOSPHORYLATION AT SER-513; THR-516; SER-518; SER-523; SER-526 AND THR-529.
RX PubMed=20977274; DOI=10.1021/bi101700e;
RA Yoder A.R., Stone M.D., Griffin T.J., Potter L.R.;
RT "Mass spectrometric identification of phosphorylation sites in guanylyl
RT cyclase A and B.";
RL Biochemistry 49:10137-10145(2010).
RN [13]
RP VARIANTS [LARGE SCALE ANALYSIS] ILE-232 AND ILE-882.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [14]
RP INVOLVEMENT IN ECDM, VARIANT ECDM MET-882, AND CHARACTERIZATION OF VARIANT
RP ECDM MET-882.
RX PubMed=22870295; DOI=10.1371/journal.pone.0042180;
RA Miura K., Namba N., Fujiwara M., Ohata Y., Ishida H., Kitaoka T.,
RA Kubota T., Hirai H., Higuchi C., Tsumaki N., Yoshikawa H., Sakai N.,
RA Michigami T., Ozono K.;
RT "An overgrowth disorder associated with excessive production of cGMP due to
RT a gain-of-function mutation of the natriuretic peptide receptor 2 gene.";
RL PLoS ONE 7:E42180-E42180(2012).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN SNSK, VARIANTS SNSK PRO-76;
RP PRO-263 AND CYS-819, AND CHARACTERIZATION OF VARIANTS SNSK PRO-76; PRO-263
RP AND CYS-819.
RX PubMed=24001744; DOI=10.1210/jc.2013-2142;
RA Vasques G.A., Amano N., Docko A.J., Funari M.F., Quedas E.P., Nishi M.Y.,
RA Arnhold I.J., Hasegawa T., Jorge A.A.;
RT "Heterozygous mutations in natriuretic peptide receptor-B (NPR2) gene as a
RT cause of short stature in patients initially classified as idiopathic short
RT stature.";
RL J. Clin. Endocrinol. Metab. 98:E1636-E1644(2013).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN SNSK, VARIANTS SNSK CYS-110
RP AND GLU-417, VARIANT ILE-187, CHARACTERIZATION OF VARIANTS SNSK CYS-110 AND
RP GLU-417, AND CHARACTERIZATION OF VARIANT ILE-187.
RX PubMed=24471569; DOI=10.1210/jc.2013-3525;
RA Amano N., Mukai T., Ito Y., Narumi S., Tanaka T., Yokoya S., Ogata T.,
RA Hasegawa T.;
RT "Identification and functional characterization of two novel NPR2 mutations
RT in Japanese patients with short stature.";
RL J. Clin. Endocrinol. Metab. 99:E713-E718(2014).
RN [17]
RP CHARACTERIZATION OF VARIANT ECDM MET-882.
RX PubMed=23827346; DOI=10.1016/j.bone.2013.06.024;
RA Robinson J.W., Dickey D.M., Miura K., Michigami T., Ozono K., Potter L.R.;
RT "A human skeletal overgrowth mutation increases maximal velocity and blocks
RT desensitization of guanylyl cyclase-B.";
RL Bone 56:375-382(2013).
RN [18]
RP CHARACTERIZATION OF VARIANTS AMD1 PHE-658; CYS-708; TRP-776 AND ALA-959,
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TOPOLOGY,
RP GLYCOSYLATION, PHOSPHORYLATION, AND MUTAGENESIS OF ASN-24.
RX PubMed=26980729; DOI=10.1074/jbc.m115.704015;
RA Dickey D.M., Edmund A.B., Otto N.M., Chaffee T.S., Robinson J.W.,
RA Potter L.R.;
RT "Catalytically active guanylyl cyclase b requires endoplasmic reticulum-
RT mediated glycosylation, and mutations that inhibit this process cause
RT dwarfism.";
RL J. Biol. Chem. 291:11385-11393(2016).
RN [19]
RP VARIANT AMD1 PHE-658, AND CHARACTERIZATION OF VARIANT AMD1 PHE-658.
RX PubMed=17652215; DOI=10.1210/jc.2007-1101;
RA Hachiya R., Ohashi Y., Kamei Y., Suganami T., Mochizuki H., Mitsui N.,
RA Saitoh M., Sakuragi M., Nishimura G., Ohashi H., Hasegawa T., Ogawa Y.;
RT "Intact kinase homology domain of natriuretic peptide receptor-B is
RT essential for skeletal development.";
RL J. Clin. Endocrinol. Metab. 92:4009-4014(2007).
RN [20]
RP VARIANT ECDM CYS-655, AND CHARACTERIZATION OF VARIANT ECDM CYS-655.
RX PubMed=24057292; DOI=10.1210/jc.2013-2358;
RA Hannema S.E., van Duyvenvoorde H.A., Premsler T., Yang R.B., Mueller T.D.,
RA Gassner B., Oberwinkler H., Roelfsema F., Santen G.W., Prickett T.,
RA Kant S.G., Verkerk A.J., Uitterlinden A.G., Espiner E., Ruivenkamp C.A.,
RA Oostdijk W., Pereira A.M., Losekoot M., Kuhn M., Wit J.M.;
RT "An activating mutation in the kinase homology domain of the natriuretic
RT peptide receptor-2 causes extremely tall stature without skeletal
RT deformities.";
RL J. Clin. Endocrinol. Metab. 98:E1988-E1998(2013).
RN [21]
RP VARIANT ECDM PRO-488, AND CHARACTERIZATION OF VARIANT ECDM PRO-488.
RX PubMed=24259409; DOI=10.1002/ajmg.a.36218;
RA Miura K., Kim O.H., Lee H.R., Namba N., Michigami T., Yoo W.J., Choi I.H.,
RA Ozono K., Cho T.J.;
RT "Overgrowth syndrome associated with a gain-of-function mutation of the
RT natriuretic peptide receptor 2 (NPR2) gene.";
RL Am. J. Med. Genet. A 164A:156-163(2014).
CC -!- FUNCTION: Receptor for the C-type natriuretic peptide NPPC/CNP hormone.
CC Has guanylate cyclase activity upon binding of its ligand. May play a
CC role in the regulation of skeletal growth.
CC {ECO:0000269|PubMed:15146390, ECO:0000269|PubMed:1672777,
CC ECO:0000269|PubMed:24001744, ECO:0000269|PubMed:24471569,
CC ECO:0000269|PubMed:26980729}.
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 Evidence={ECO:0000269|PubMed:26980729};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24001744,
CC ECO:0000269|PubMed:26980729}; Single-pass type I membrane protein
CC {ECO:0000305|PubMed:26980729}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P20594-1; Sequence=Displayed;
CC Name=Short; Synonyms=NPR-BI;
CC IsoId=P20594-2; Sequence=VSP_001810;
CC -!- PTM: Phosphorylated (PubMed:26980729). Phosphorylation of the protein
CC kinase-like domain is required for full activation by CNP (By
CC similarity). {ECO:0000250|UniProtKB:P16067,
CC ECO:0000269|PubMed:26980729}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:26980729}.
CC -!- DISEASE: Acromesomelic dysplasia 1 (AMD1) [MIM:602875]: A form of
CC acromesomelic dysplasia, a skeletal disorder characterized by short
CC stature, very short limbs and hand/foot malformations. The severity of
CC limb abnormalities increases from proximal to distal with profoundly
CC affected hands and feet showing brachydactyly and/or rudimentary
CC fingers (knob-like fingers). AMD1 is an autosomal recessive form
CC characterized by axial skeletal involvement with wedging of vertebral
CC bodies. All skeletal elements are present but show abnormal rates of
CC linear growth. {ECO:0000269|PubMed:15146390,
CC ECO:0000269|PubMed:17652215, ECO:0000269|PubMed:26980729}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Epiphyseal chondrodysplasia, Miura type (ECDM) [MIM:615923]:
CC An overgrowth syndrome characterized by tall stature, long hands and
CC feet with arachnodactyly, macrodactyly of the great toes, scoliosis,
CC coxa valga and slipped capital femoral epiphysis.
CC {ECO:0000269|PubMed:22870295, ECO:0000269|PubMed:23827346,
CC ECO:0000269|PubMed:24057292, ECO:0000269|PubMed:24259409}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Short stature with non-specific skeletal abnormalities (SNSK)
CC [MIM:616255]: A condition characterized by short stature, defined as a
CC height less than 2 SD below normal, and no endocrine abnormalities.
CC {ECO:0000269|PubMed:24001744, ECO:0000269|PubMed:24471569}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: [Isoform Short]: May be produced at very low levels due
CC to a premature stop codon in the mRNA, leading to nonsense-mediated
CC mRNA decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR EMBL; AB005647; BAA81737.1; -; Genomic_DNA.
DR EMBL; AJ005282; CAA06466.1; -; mRNA.
DR EMBL; AL133410; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; EU326311; ACA05920.1; -; Genomic_DNA.
DR EMBL; EU326311; ACA05921.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58338.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58337.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58339.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58340.1; -; Genomic_DNA.
DR EMBL; BC023017; AAH23017.1; -; mRNA.
DR CCDS; CCDS6590.1; -. [P20594-1]
DR PIR; S05514; OYHUBR.
DR RefSeq; NP_003986.2; NM_003995.3. [P20594-1]
DR AlphaFoldDB; P20594; -.
DR SMR; P20594; -.
DR BioGRID; 110942; 12.
DR IntAct; P20594; 3.
DR STRING; 9606.ENSP00000341083; -.
DR BindingDB; P20594; -.
DR ChEMBL; CHEMBL1795; -.
DR DrugBank; DB01613; Erythrityl tetranitrate.
DR DrugBank; DB04899; Nesiritide.
DR DrugBank; DB11928; Vosoritide.
DR GuidetoPHARMACOLOGY; 1748; -.
DR TCDB; 8.A.85.1.2; the guanylate cyclase (gc) family.
DR GlyGen; P20594; 7 sites.
DR iPTMnet; P20594; -.
DR PhosphoSitePlus; P20594; -.
DR BioMuta; NPR2; -.
DR DMDM; 113916; -.
DR EPD; P20594; -.
DR jPOST; P20594; -.
DR MassIVE; P20594; -.
DR MaxQB; P20594; -.
DR PaxDb; P20594; -.
DR PeptideAtlas; P20594; -.
DR PRIDE; P20594; -.
DR ProteomicsDB; 53766; -. [P20594-1]
DR ProteomicsDB; 53767; -. [P20594-2]
DR Antibodypedia; 1647; 243 antibodies from 32 providers.
DR DNASU; 4882; -.
DR Ensembl; ENST00000342694.7; ENSP00000341083.2; ENSG00000159899.16. [P20594-1]
DR GeneID; 4882; -.
DR KEGG; hsa:4882; -.
DR MANE-Select; ENST00000342694.7; ENSP00000341083.2; NM_003995.4; NP_003986.2.
DR UCSC; uc003zyd.4; human. [P20594-1]
DR CTD; 4882; -.
DR DisGeNET; 4882; -.
DR GeneCards; NPR2; -.
DR HGNC; HGNC:7944; NPR2.
DR HPA; ENSG00000159899; Low tissue specificity.
DR MalaCards; NPR2; -.
DR MIM; 108961; gene.
DR MIM; 602875; phenotype.
DR MIM; 615923; phenotype.
DR MIM; 616255; phenotype.
DR neXtProt; NX_P20594; -.
DR OpenTargets; ENSG00000159899; -.
DR Orphanet; 40; Acromesomelic dysplasia, Maroteaux type.
DR Orphanet; 329191; Tall stature-scoliosis-macrodactyly of the great toes syndrome.
DR PharmGKB; PA257; -.
DR VEuPathDB; HostDB:ENSG00000159899; -.
DR eggNOG; KOG1023; Eukaryota.
DR GeneTree; ENSGT00940000156985; -.
DR HOGENOM; CLU_001072_1_3_1; -.
DR InParanoid; P20594; -.
DR OMA; AAKSEHY; -.
DR OrthoDB; 229634at2759; -.
DR PhylomeDB; P20594; -.
DR TreeFam; TF106338; -.
DR BRENDA; 4.6.1.2; 2681.
DR PathwayCommons; P20594; -.
DR Reactome; R-HSA-5578768; Physiological factors.
DR SignaLink; P20594; -.
DR BioGRID-ORCS; 4882; 9 hits in 1104 CRISPR screens.
DR ChiTaRS; NPR2; human.
DR GeneWiki; NPR2; -.
DR GenomeRNAi; 4882; -.
DR Pharos; P20594; Tbio.
DR PRO; PR:P20594; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P20594; protein.
DR Bgee; ENSG00000159899; Expressed in right uterine tube and 184 other tissues.
DR ExpressionAtlas; P20594; baseline and differential.
DR Genevisible; P20594; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
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:UniProtKB.
DR GO; GO:0042562; F:hormone binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0016941; F:natriuretic peptide receptor activity; IDA:UniProtKB.
DR GO; GO:0017046; F:peptide hormone binding; IPI:UniProtKB.
DR GO; GO:0001653; F:peptide receptor activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
DR GO; GO:0060348; P:bone development; IEA:Ensembl.
DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; IEP:UniProtKB.
DR GO; GO:0006182; P:cGMP biosynthetic process; IDA:GO_Central.
DR GO; GO:0019934; P:cGMP-mediated signaling; IEA:Ensembl.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:Ensembl.
DR GO; GO:0051447; P:negative regulation of meiotic cell cycle; IEA:Ensembl.
DR GO; GO:1900194; P:negative regulation of oocyte maturation; IEA:Ensembl.
DR GO; GO:0001503; P:ossification; IEA:UniProtKB-KW.
DR GO; GO:0010753; P:positive regulation of cGMP-mediated signaling; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; IDA:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd07302; CHD; 1.
DR Gene3D; 3.30.70.1230; -; 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 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; SSF53822; SSF53822; 1.
DR SUPFAM; SSF55073; SSF55073; 1.
DR SUPFAM; SSF56112; SSF56112; 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 Alternative splicing; Cell membrane; cGMP biosynthesis; Disease variant;
KW Disulfide bond; Dwarfism; Glycoprotein; GTP-binding; Lyase; Membrane;
KW Nucleotide-binding; Osteogenesis; Phosphoprotein; Receptor;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..1047
FT /note="Atrial natriuretic peptide receptor 2"
FT /id="PRO_0000012364"
FT TOPO_DOM 23..458
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 459..478
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 479..1047
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 513..786
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 861..991
FT /note="Guanylate cyclase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT MOD_RES 513
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20977274"
FT MOD_RES 516
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:20977274"
FT MOD_RES 518
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20977274"
FT MOD_RES 522
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16066"
FT MOD_RES 523
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20977274"
FT MOD_RES 526
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20977274"
FT MOD_RES 529
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:20977274"
FT CARBOHYD 24
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 35
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 244
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 277
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 349
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 75..101
FT /evidence="ECO:0000250"
FT DISULFID 439
FT /note="Interchain"
FT /evidence="ECO:0000305"
FT DISULFID 448
FT /note="Interchain"
FT /evidence="ECO:0000305"
FT VAR_SEQ 964..1047
FT /note="PVCAGVVGLKMPRYCLFGDTVNTASRMESNGQALKIHVSSTTKDALDELGCF
FT QLELRGDVEMKGKGKMRTYWLLGERKGPPGLL -> KADSHSSPSLHLSQTLPTCFFSK
FT GQSVLGLLA (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:10073597"
FT /id="VSP_001810"
FT VARIANT 32
FT /note="P -> T (in AMD1; dbSNP:rs28931581)"
FT /evidence="ECO:0000269|PubMed:15146390"
FT /id="VAR_022583"
FT VARIANT 76
FT /note="S -> P (in SNSK; loss of C-type natriuretic peptide-
FT induced signaling; dominant negative effect; loss of
FT localization to the plasma membrane; dbSNP:rs796065355)"
FT /evidence="ECO:0000269|PubMed:24001744"
FT /id="VAR_074678"
FT VARIANT 110
FT /note="R -> C (in SNSK; loss of C-type natriuretic peptide-
FT induced signaling; dominant negative effect; retained in
FT the endoplasmic reticulum; dbSNP:rs758478717)"
FT /evidence="ECO:0000269|PubMed:24471569"
FT /id="VAR_074679"
FT VARIANT 115
FT /note="W -> G (in AMD1; markedly deficient activity;
FT dbSNP:rs28931582)"
FT /evidence="ECO:0000269|PubMed:15146390"
FT /id="VAR_022584"
FT VARIANT 176
FT /note="D -> E (in AMD1; dbSNP:rs28929479)"
FT /evidence="ECO:0000269|PubMed:15146390"
FT /id="VAR_022585"
FT VARIANT 187
FT /note="V -> I (does not affect C-type natriuretic peptide-
FT induced signaling; dbSNP:rs768423636)"
FT /evidence="ECO:0000269|PubMed:24471569"
FT /id="VAR_074680"
FT VARIANT 232
FT /note="M -> I (in dbSNP:rs55747238)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042219"
FT VARIANT 263
FT /note="R -> P (in SNSK; loss of C-type natriuretic peptide-
FT induced signaling; dominant negative effect; loss of
FT localization to the plasma membrane; dbSNP:rs139036657)"
FT /evidence="ECO:0000269|PubMed:24001744"
FT /id="VAR_074681"
FT VARIANT 297
FT /note="T -> M (in AMD1; markedly deficient activity;
FT dbSNP:rs1313765432)"
FT /evidence="ECO:0000269|PubMed:15146390"
FT /id="VAR_022586"
FT VARIANT 338
FT /note="Y -> C (in AMD1)"
FT /evidence="ECO:0000269|PubMed:15146390"
FT /id="VAR_022587"
FT VARIANT 409
FT /note="A -> T (in AMD1)"
FT /evidence="ECO:0000269|PubMed:15146390"
FT /id="VAR_022588"
FT VARIANT 413
FT /note="G -> E (in AMD1; markedly deficient activity)"
FT /evidence="ECO:0000269|PubMed:15146390"
FT /id="VAR_022589"
FT VARIANT 417
FT /note="Q -> E (in SNSK; loss of C-type natriuretic peptide-
FT induced signaling; dominant negative effect; no effect on
FT cell surface expression; dbSNP:rs796065356)"
FT /evidence="ECO:0000269|PubMed:24471569"
FT /id="VAR_074682"
FT VARIANT 488
FT /note="A -> P (in ECDM; mutant and wild-type alleles have
FT similar expression levels; the mutation results in
FT increased guanylate cyclase activity; dbSNP:rs587777597)"
FT /evidence="ECO:0000269|PubMed:24259409"
FT /id="VAR_071875"
FT VARIANT 655
FT /note="R -> C (in ECDM; the mutation results in increased
FT guanylate cyclase activity; dbSNP:rs587777596)"
FT /evidence="ECO:0000269|PubMed:24057292"
FT /id="VAR_071876"
FT VARIANT 658
FT /note="L -> F (in AMD1; no effect on subcellular location;
FT changed glycosylation; no effect on C-type natriuretic
FT peptide binding; decreased guanylate cyclase activity; loss
FT of natriuretic peptide receptor activity; dominant negative
FT effect; dbSNP:rs1314542724)"
FT /evidence="ECO:0000269|PubMed:17652215,
FT ECO:0000269|PubMed:26980729"
FT /id="VAR_076481"
FT VARIANT 708
FT /note="Y -> C (in AMD1; no effect on subcellular location;
FT changed glycosylation; no effect on C-type natriuretic
FT peptide binding; decreased guanylate cyclase activity;
FT dbSNP:rs1305337032)"
FT /evidence="ECO:0000269|PubMed:15146390,
FT ECO:0000269|PubMed:26980729"
FT /id="VAR_022590"
FT VARIANT 771
FT /note="Q -> E (in dbSNP:rs5816)"
FT /id="VAR_011968"
FT VARIANT 776
FT /note="R -> W (in AMD1; no effect on subcellular location;
FT changed glycosylation; no effect on C-type natriuretic
FT peptide binding; decreased guanylate cyclase activity;
FT dbSNP:rs1303913631)"
FT /evidence="ECO:0000269|PubMed:15146390,
FT ECO:0000269|PubMed:26980729"
FT /id="VAR_022591"
FT VARIANT 819
FT /note="R -> C (in SNSK; loss of C-type natriuretic peptide-
FT induced signaling; dominant negative effect; no effect on
FT cell surface expression; dbSNP:rs766256429)"
FT /evidence="ECO:0000269|PubMed:24001744"
FT /id="VAR_074683"
FT VARIANT 882
FT /note="V -> I (in dbSNP:rs55700371)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042220"
FT VARIANT 882
FT /note="V -> M (in ECDM; the mutation results in higher
FT guanylate cyclase activity; causes a 15-fold increase in
FT basal Vmax; has higher affinity for GTP than wild-type in
FT the presence of NPPC; might lead to a structural change
FT that locks the enzyme in a conformation mimicking the ATP-
FT bound state)"
FT /evidence="ECO:0000269|PubMed:22870295,
FT ECO:0000269|PubMed:23827346"
FT /id="VAR_071877"
FT VARIANT 957
FT /note="R -> C (in AMD1; dbSNP:rs370158184)"
FT /evidence="ECO:0000269|PubMed:15146390"
FT /id="VAR_022592"
FT VARIANT 959
FT /note="G -> A (in AMD1; no effect on subcellular location;
FT changed glycosylation; no effect on C-type natriuretic
FT peptide binding; decreased guanylate cyclase activity)"
FT /evidence="ECO:0000269|PubMed:15146390,
FT ECO:0000269|PubMed:26980729"
FT /id="VAR_022593"
FT MUTAGEN 24
FT /note="N->D,Q: Decreased glycosylation. Decreased guanylate
FT cyclase activity."
FT /evidence="ECO:0000269|PubMed:26980729"
FT CONFLICT 755
FT /note="T -> S (in Ref. 2; BAA81737)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1047 AA; 117022 MW; 817FB74D6B31F7EF CRC64;
MALPSLLLLV AALAGGVRPP GARNLTLAVV LPEHNLSYAW AWPRVGPAVA LAVEALGRAL
PVDLRFVSSE LEGACSEYLA PLSAVDLKLY HDPDLLLGPG CVYPAASVAR FASHWRLPLL
TAGAVASGFS AKNDHYRTLV RTGPSAPKLG EFVVTLHGHF NWTARAALLY LDARTDDRPH
YFTIEGVFEA LQGSNLSVQH QVYAREPGGP EQATHFIRAN GRIVYICGPL EMLHEILLQA
QRENLTNGDY VFFYLDVFGE SLRAGPTRAT GRPWQDNRTR EQAQALREAF QTVLVITYRE
PPNPEYQEFQ NRLLIRARED FGVELGPSLM NLIAGCFYDG ILLYAEVLNE TIQEGGTRED
GLRIVEKMQG RRYHGVTGLV VMDKNNDRET DFVLWAMGDL DSGDFQPAAH YSGAEKQIWW
TGRPIPWVKG APPSDNPPCA FDLDDPSCDK TPLSTLAIVA LGTGITFIMF GVSSFLIFRK
LMLEKELASM LWRIRWEELQ FGNSERYHKG AGSRLTLSLR GSSYGSLMTA HGKYQIFANT
GHFKGNVVAI KHVNKKRIEL TRQVLFELKH MRDVQFNHLT RFIGACIDPP NICIVTEYCP
RGSLQDILEN DSINLDWMFR YSLINDLVKG MAFLHNSIIS SHGSLKSSNC VVDSRFVLKI
TDYGLASFRS TAEPDDSHAL YAKKLWTAPE LLSGNPLPTT GMQKADVYSF GIILQEIALR
SGPFYLEGLD LSPKEIVQKV RNGQRPYFRP SIDRTQLNEE LVLLMERCWA QDPAERPDFG
QIKGFIRRFN KEGGTSILDN LLLRMEQYAN NLEKLVEERT QAYLEEKRKA EALLYQILPH
SVAEQLKRGE TVQAEAFDSV TIYFSDIVGF TALSAESTPM QVVTLLNDLY TCFDAIIDNF
DVYKVETIGD AYMVVSGLPG RNGQRHAPEI ARMALALLDA VSSFRIRHRP HDQLRLRIGV
HTGPVCAGVV GLKMPRYCLF GDTVNTASRM ESNGQALKIH VSSTTKDALD ELGCFQLELR
GDVEMKGKGK MRTYWLLGER KGPPGLL
