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 02-SEP-2026, entry version 243. 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 SNSK1, VARIANTS SNSK1 RP PRO-76; PRO-263 AND CYS-819, AND CHARACTERIZATION OF VARIANTS SNSK1 PRO-76; RP PRO-263 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 SNSK1, VARIANTS SNSK1 RP CYS-110 AND GLU-417, VARIANT ILE-187, CHARACTERIZATION OF VARIANTS SNSK1 RP CYS-110 AND 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 1 CC (SNSK1) [MIM:616255]: An autosomal dominant condition characterized by CC short stature, defined as a height less than 2 SD below normal, and no CC endocrine abnormalities. Some SNSK1 patients show delayed bone age. 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}. 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; 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_003995.4. [P20594-1] DR AlphaFoldDB; P20594; -. DR SMR; P20594; -. DR BioGRID; 110942; 16. DR CORUM; P20594; -. DR FunCoup; P20594; 928. DR IntAct; P20594; 24. DR NDEx; IQUERY-CP-NPR2; 1 NDEx IQuery Curated Pathway. DR STRING; 9606.ENSP00000341083; -. DR BindingDB; P20594; -. DR ChEMBL; CHEMBL1795; -. DR DrugBank; DB01613; Erythrityl tetranitrate. DR DrugBank; DB17824; Navepegritide. DR DrugBank; DB04899; Nesiritide. DR DrugBank; DB11928; Vosoritide. DR DrugCentral; P20594; -. DR GuidetoPHARMACOLOGY; 1748; -. DR TCDB; 8.A.85.1.2; the guanylate cyclase (gc) family. DR GlyCosmos; P20594; 7 sites, No reported glycans. DR GlyGen; P20594; 9 sites. DR iPTMnet; P20594; -. DR PhosphoSitePlus; P20594; -. DR BioMuta; NPR2; -. DR DMDM; 113916; -. DR jPOST; P20594; -. DR MassIVE; P20594; -. DR PaxDb; 9606-ENSP00000341083; -. DR PeptideAtlas; P20594; -. DR ProteomicsDB; 53766; -. [P20594-1] DR ProteomicsDB; 53767; -. [P20594-2] DR Pumba; P20594; -. DR Antibodypedia; 1647; 259 antibodies from 34 providers. DR DNASU; 4882; -. DR Ensembl; ENST00000342694.7; ENSP00000341083.2; ENSG00000159899.17. [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 AGR; HGNC:7944; -. DR ClinPGx; PA257; -. 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 OpenTargets; ENSG00000159899; -. DR Orphanet; 40; Acromesomelic dysplasia, Maroteaux type. DR Orphanet; 329191; Tall stature-long halluces-multiple extra-epiphyses syndrome. DR VEuPathDB; HostDB:ENSG00000159899; -. DR eggNOG; KOG1023; Eukaryota. DR GeneTree; ENSGT00940000156985; -. DR HOGENOM; CLU_001072_1_3_1; -. DR InParanoid; P20594; -. DR OMA; SEMDGAC; -. DR OrthoDB; 1890790at2759; -. DR PAN-GO; P20594; 6 GO annotations based on evolutionary models. DR PhylomeDB; P20594; -. DR BRENDA; 4.6.1.2; 2681. DR PathwayCommons; P20594; -. DR Reactome; R-HSA-5578768; Physiological factors. DR SignaLink; P20594; -. DR Agora; ENSG00000159899; -. DR BioGRID-ORCS; 4882; 10 hits in 1191 CRISPR screens. DR ChiTaRS; NPR2; human. DR GeneWiki; NPR2; -. DR GenomeRNAi; 4882; -. DR Pharos; P20594; Tclin. DR PRO; PR:P20594; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; P20594; protein. DR Bgee; ENSG00000159899; Expressed in right uterine tube and 186 other cell types or tissues. DR ExpressionAtlas; P20594; baseline and differential. DR GO; GO:0005929; C:cilium; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0043005; C:neuron projection; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0045202; C:synapse; IEA:GOC. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. 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:0004672; F:protein kinase activity; IEA:InterPro. DR GO; GO:0060466; P:activation of meiosis involved in egg activation; IEA:Ensembl. DR GO; GO:0060385; P:axonogenesis involved in innervation; IEA:Ensembl. DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl. DR GO; GO:0098868; P:bone growth; ISS:UniProt. DR GO; GO:0061939; P:c-di-GMP signaling; IEA:Ensembl. DR GO; GO:0071321; P:cellular response to cGMP; IEA:Ensembl. DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; IEP:UniProtKB. DR GO; GO:1901653; P:cellular response to peptide; IEA:Ensembl. DR GO; GO:0006182; P:cGMP biosynthetic process; IDA:GO_Central. DR GO; GO:0007268; P:chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0002062; P:chondrocyte differentiation; IEA:Ensembl. DR GO; GO:0035988; P:chondrocyte proliferation; IEA:Ensembl. DR GO; GO:0051276; P:chromosome organization; IEA:Ensembl. DR GO; GO:0048668; P:collateral sprouting; IEA:Ensembl. DR GO; GO:0001549; P:cumulus cell differentiation; IEA:Ensembl. DR GO; GO:0048546; P:digestive tract morphogenesis; IEA:Ensembl. DR GO; GO:0001958; P:endochondral ossification; IEA:Ensembl. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IEA:Ensembl. DR GO; GO:0097194; P:execution phase of apoptosis; IEA:Ensembl. DR GO; GO:0030540; P:female genitalia development; IEA:Ensembl. DR GO; GO:0035483; P:gastric emptying; IEA:Ensembl. DR GO; GO:0035112; P:genitalia morphogenesis; IEA:Ensembl. DR GO; GO:0003417; P:growth plate cartilage development; IEA:Ensembl. DR GO; GO:0035108; P:limb morphogenesis; IEA:Ensembl. DR GO; GO:0001945; P:lymph vessel development; IEA:Ensembl. DR GO; GO:0000165; P:MAPK cascade; IEA:Ensembl. DR GO; GO:1903537; P:meiotic cell cycle process involved in oocyte maturation; IEA:Ensembl. DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl. DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl. DR GO; GO:0019228; P:neuronal action potential; IEA:Ensembl. DR GO; GO:0036342; P:post-anal tail morphogenesis; IEA:Ensembl. 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:0071774; P:response to fibroblast growth factor; IEA:Ensembl. DR GO; GO:0034699; P:response to luteinizing hormone; IEA:Ensembl. DR GO; GO:1902074; P:response to salt; IEA:Ensembl. DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl. DR GO; GO:0048745; P:smooth muscle tissue development; IEA:Ensembl. DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl. DR GO; GO:0001964; P:startle response; IEA:Ensembl. DR GO; GO:0007033; P:vacuole organization; IEA:Ensembl. DR GO; GO:0061042; P:vascular wound healing; IEA:Ensembl. DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl. DR GO; GO:0021647; P:vestibulocochlear nerve maturation; IEA:Ensembl. DR GO; GO:0050872; P:white fat cell differentiation; IEA:Ensembl. DR CDD; cd07302; CHD; 1. DR CDD; cd06384; PBP1_NPR_B; 1. DR CDD; cd14042; PK_GC-A_B; 1. DR FunFam; 1.10.510.10:FF:000270; Guanylate cyclase; 1. DR FunFam; 3.30.200.20:FF:001106; Guanylate cyclase; 1. DR FunFam; 3.30.70.1230:FF:000004; Guanylate cyclase; 1. DR FunFam; 3.40.50.2300:FF:000101; Guanylate cyclase; 1. DR FunFam; 3.40.50.2300:FF:000245; Guanylate cyclase; 1. DR Gene3D; 3.40.50.2300; -; 3. 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; IPR050401; Cyclic_nucleotide_synthase. 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:SF494; ATRIAL NATRIURETIC PEPTIDE RECEPTOR 2; 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 Alternative splicing; Cell membrane; cGMP biosynthesis; Disease variant; KW Disulfide bond; Dwarfism; Glycoprotein; GTP-binding; Lyase; Membrane; KW Nucleotide-binding; Osteogenesis; Phosphoprotein; KW Proteomics identification; Receptor; Reference proteome; Signal; KW 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 SNSK1; loss of C-type natriuretic FT peptide-induced signaling; dominant negative effect; loss FT of 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 SNSK1; loss of C-type natriuretic FT peptide-induced signaling; dominant negative effect; FT retained in 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 FT peptide-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 SNSK1; loss of C-type natriuretic FT peptide-induced signaling; dominant negative effect; loss FT of 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; dbSNP:rs1828087195)" FT /evidence="ECO:0000269|PubMed:15146390" FT /id="VAR_022587" FT VARIANT 409 FT /note="A -> T (in AMD1; dbSNP:rs1828117923)" 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 SNSK1; loss of C-type natriuretic FT peptide-induced signaling; dominant negative effect; no FT effect on 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 SNSK1; loss of C-type natriuretic FT peptide-induced signaling; dominant negative effect; no FT effect on 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 FT ATP-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 //