LOCUS       NP_003986               1047 aa            linear   PRI 07-APR-2024
DEFINITION  atrial natriuretic peptide receptor 2 isoform 1 precursor [Homo
            sapiens].
ACCESSION   NP_003986
VERSION     NP_003986.2
DBSOURCE    REFSEQ: accession NM_003995.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 1047)
  AUTHORS   Chen,H., Zhang,S., Sun,Y., Chen,J., Yuan,K., Zhang,Y., Yang,X.,
            Lin,X. and Chen,R.
  TITLE     Novel pathogenic NPR2 variants in short stature patients and the
            therapeutic response to rhGH
  JOURNAL   Orphanet J Rare Dis 18 (1), 221 (2023)
   PUBMED   37501190
  REMARK    GeneRIF: Novel pathogenic NPR2 variants in short stature patients
            and the therapeutic response to rhGH.
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 1047)
  AUTHORS   Zhu,J., Meng,R., Zhao,H., Cai,L., Wen,X., Zeng,W., Luo,Y. and Qi,H.
  TITLE     Identification of Diagnostic Variants in FGFR2 and NPR2 Genes in a
            Chinese Family Affected by Crouzon Syndrome and Acromesomelic
            Dysplasia, Type Maroteaux
  JOURNAL   DNA Cell Biol 41 (11), 996-1006 (2022)
   PUBMED   36322898
  REMARK    GeneRIF: Identification of Diagnostic Variants in FGFR2 and NPR2
            Genes in a Chinese Family Affected by Crouzon Syndrome and
            Acromesomelic Dysplasia, Type Maroteaux.
REFERENCE   3  (residues 1 to 1047)
  AUTHORS   Stavber,L., Gaia,M.J., Hovnik,T., Jenko Bizjan,B., Debeljak,M.,
            Kovac,J., Omladic,J.S., Battelino,T., Kotnik,P. and Dovc,K.
  TITLE     Heterozygous NPR2 Variants in Idiopathic Short Stature
  JOURNAL   Genes (Basel) 13 (6), 1065 (2022)
   PUBMED   35741827
  REMARK    GeneRIF: Heterozygous NPR2 Variants in Idiopathic Short Stature.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 1047)
  AUTHORS   Li,Q., Fan,X., Lu,W., Sun,C., Pei,Z., Zhang,M., Ni,J., Wu,J.,
            Yu,F.X. and Luo,F.
  TITLE     Novel NPR2 Gene Mutations Affect Chondrocytes Function via ER
            Stress in Short Stature
  JOURNAL   Cells 11 (8), 1265 (2022)
   PUBMED   35455946
  REMARK    GeneRIF: Novel NPR2 Gene Mutations Affect Chondrocytes Function via
            ER Stress in Short Stature.
            Publication Status: Online-Only
REFERENCE   5  (residues 1 to 1047)
  AUTHORS   Yuan,K., Chen,J., Chen,Q., Chen,H., Zhu,J., Fang,Y. and Wang,C.
  TITLE     NPR2 gene variants in familial short stature: a single-center study
  JOURNAL   J Pediatr Endocrinol Metab 35 (2), 185-190 (2021)
   PUBMED   34565054
  REMARK    GeneRIF: NPR2 gene variants in familial short stature: a
            single-center study.
            Publication Status: Online-Only
REFERENCE   6  (residues 1 to 1047)
  AUTHORS   Koller,K.J. and Goeddel,D.V.
  TITLE     Molecular biology of the natriuretic peptides and their receptors
  JOURNAL   Circulation 86 (4), 1081-1088 (1992)
   PUBMED   1327579
  REMARK    Review article
REFERENCE   7  (residues 1 to 1047)
  AUTHORS   Bennett,B.D., Bennett,G.L., Vitangcol,R.V., Jewett,J.R.,
            Burnier,J., Henzel,W. and Lowe,D.G.
  TITLE     Extracellular domain-IgG fusion proteins for three human
            natriuretic peptide receptors. Hormone pharmacology and application
            to solid phase screening of synthetic peptide antisera
  JOURNAL   J Biol Chem 266 (34), 23060-23067 (1991)
   PUBMED   1660465
REFERENCE   8  (residues 1 to 1047)
  AUTHORS   Koller,K.J., Lowe,D.G., Bennett,G.L., Minamino,N., Kangawa,K.,
            Matsuo,H. and Goeddel,D.V.
  TITLE     Selective activation of the B natriuretic peptide receptor by
            C-type natriuretic peptide (CNP)
  JOURNAL   Science 252 (5002), 120-123 (1991)
   PUBMED   1672777
REFERENCE   9  (residues 1 to 1047)
  AUTHORS   Lowe,D.G., Klisak,I., Sparkes,R.S., Mohandas,T. and Goeddel,D.V.
  TITLE     Chromosomal distribution of three members of the human natriuretic
            peptide receptor/guanylyl cyclase gene family
  JOURNAL   Genomics 8 (2), 304-312 (1990)
   PUBMED   1979052
REFERENCE   10 (residues 1 to 1047)
  AUTHORS   Chang,M.S., Lowe,D.G., Lewis,M., Hellmiss,R., Chen,E. and
            Goeddel,D.V.
  TITLE     Differential activation by atrial and brain natriuretic peptides of
            two different receptor guanylate cyclases
  JOURNAL   Nature 341 (6237), 68-72 (1989)
   PUBMED   2570358
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL133410.32.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Apr 9, 1999 this sequence version replaced NP_003986.1.
            
            Summary: This gene encodes natriuretic peptide receptor B, one of
            two integral membrane receptors for natriuretic peptides. Both NPR1
            and NPR2 contain five functional domains: an extracellular
            ligand-binding domain, a single membrane-spanning region, and
            intracellularly a protein kinase homology domain, a helical hinge
            region involved in oligomerization, and a carboxyl-terminal
            guanylyl cyclase catalytic domain. The protein is the primary
            receptor for C-type natriuretic peptide (CNP), which upon ligand
            binding exhibits greatly increased guanylyl cyclase activity.
            Mutations in this gene are the cause of acromesomelic dysplasia
            Maroteaux type. [provided by RefSeq, Jul 2008].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: L13436.1, SRR18074969.1661216.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000342694.7/ ENSP00000341083.2
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..1047
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="9"
                     /map="9p13.3"
     Protein         1..1047
                     /product="atrial natriuretic peptide receptor 2 isoform 1
                     precursor"
                     /EC_number="4.6.1.2"
                     /note="atrial natriuretic peptide receptor 2; natriuretic
                     peptide receptor B/guanylate cyclase B (atrionatriuretic
                     peptide receptor B); atrial natriuretic peptide B-type
                     receptor; atrial natriuretic peptide receptor type B;
                     guanylate cyclase 2B; guanylyl cyclase B"
                     /calculated_mol_wt=114953
     sig_peptide     1..22
                     /note="/evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (P20594.1)"
                     /calculated_mol_wt=2088
     mat_peptide     23..1047
                     /product="atrial natriuretic peptide receptor 2 isoform 1"
                     /calculated_mol_wt=114953
     Site            24
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (P20594.1)"
     Region          26..421
                     /region_name="PBP1_NPR_B"
                     /note="ligand-binding domain of type B natriuretic peptide
                     receptor; cd06384"
                     /db_xref="CDD:380607"
     Site            35
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (P20594.1)"
     Site            order(69,100..101)
                     /site_type="other"
                     /note="Cl binding site [ion binding]"
                     /db_xref="CDD:380607"
     Site            order(82,86,102..103,106,110,114..115,181..182,185,188)
                     /site_type="other"
                     /note="dimer interface (closed form) [polypeptide
                     binding]"
                     /db_xref="CDD:380607"
     Site            order(102..103,106,110,128..129,174,181..182,185,188..189,
                     200)
                     /site_type="other"
                     /note="ligand binding site [chemical binding]"
                     /db_xref="CDD:380607"
     Site            161
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (P20594.1)"
     Site            195
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (P20594.1)"
     Site            order(214..215,235,242)
                     /site_type="other"
                     /note="dimer interface (open form) [polypeptide binding]"
                     /db_xref="CDD:380607"
     Site            244
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (P20594.1)"
     Site            277
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (P20594.1)"
     Site            349
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (P20594.1)"
     Site            459..478
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (P20594.1)"
     Site            513
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000269|PubMed:20977274; propagated from
                     UniProtKB/Swiss-Prot (P20594.1)"
     Site            516
                     /site_type="phosphorylation"
                     /note="Phosphothreonine.
                     /evidence=ECO:0000269|PubMed:20977274; propagated from
                     UniProtKB/Swiss-Prot (P20594.1)"
     Region          518..792
                     /region_name="PK_GC-A_B"
                     /note="Pseudokinase domain of the membrane Guanylate
                     Cyclase receptors, GC-A and GC-B; cd14042"
                     /db_xref="CDD:270944"
     Site            518
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000269|PubMed:20977274; propagated from
                     UniProtKB/Swiss-Prot (P20594.1)"
     Site            522
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:P16066; propagated from
                     UniProtKB/Swiss-Prot (P20594.1)"
     Site            523
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000269|PubMed:20977274; propagated from
                     UniProtKB/Swiss-Prot (P20594.1)"
     Site            526
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000269|PubMed:20977274; propagated from
                     UniProtKB/Swiss-Prot (P20594.1)"
     Site            529
                     /site_type="phosphorylation"
                     /note="Phosphothreonine.
                     /evidence=ECO:0000269|PubMed:20977274; propagated from
                     UniProtKB/Swiss-Prot (P20594.1)"
     Region          <798..846
                     /region_name="HNOBA"
                     /note="Heme NO binding associated; pfam07701"
                     /db_xref="CDD:462234"
     Region          825..1009
                     /region_name="CYCc"
                     /note="Adenylyl- / guanylyl cyclase, catalytic domain;
                     smart00044"
                     /db_xref="CDD:214485"
     Site            order(864,866..871,906,908..910,913,978..980,984..985,
                     988..989,1026)
                     /site_type="active"
                     /note="nucleotidyl binding site [active]"
                     /db_xref="CDD:143636"
     Site            order(866,910)
                     /site_type="metal-binding"
                     /note="metal binding site [ion binding]"
                     /db_xref="CDD:143636"
     Site            order(871,883,886..887,890,894,906..907,966,969,979..982,
                     985,1026)
                     /site_type="other"
                     /note="dimer interface [polypeptide binding]"
                     /db_xref="CDD:143636"
     CDS             1..1047
                     /gene="NPR2"
                     /gene_synonym="AMD1; AMDM; ANPb; ANPRB; ECDM; GC-B; GCB;
                     GUC2B; GUCY2B; NPRB; NPRBi; SNSK"
                     /coded_by="NM_003995.4:819..3962"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1"
                     /db_xref="CCDS:CCDS6590.1"
                     /db_xref="GeneID:4882"
                     /db_xref="HGNC:HGNC:7944"
                     /db_xref="MIM:108961"
ORIGIN      
        1 malpsllllv aalaggvrpp garnltlavv lpehnlsyaw awprvgpava lavealgral
       61 pvdlrfvsse legacseyla plsavdlkly hdpdlllgpg cvypaasvar fashwrlpll
      121 tagavasgfs akndhyrtlv rtgpsapklg efvvtlhghf nwtaraally ldartddrph
      181 yftiegvfea lqgsnlsvqh qvyarepggp eqathfiran grivyicgpl emlheillqa
      241 qrenltngdy vffyldvfge slragptrat grpwqdnrtr eqaqalreaf qtvlvityre
      301 ppnpeyqefq nrllirared fgvelgpslm nliagcfydg illyaevlne tiqeggtred
      361 glrivekmqg rryhgvtglv vmdknndret dfvlwamgdl dsgdfqpaah ysgaekqiww
      421 tgrpipwvkg appsdnppca fdlddpscdk tplstlaiva lgtgitfimf gvssflifrk
      481 lmlekelasm lwrirweelq fgnseryhkg agsrltlslr gssygslmta hgkyqifant
      541 ghfkgnvvai khvnkkriel trqvlfelkh mrdvqfnhlt rfigacidpp nicivteycp
      601 rgslqdilen dsinldwmfr yslindlvkg maflhnsiis shgslkssnc vvdsrfvlki
      661 tdyglasfrs taepddshal yakklwtape llsgnplptt gmqkadvysf giilqeialr
      721 sgpfylegld lspkeivqkv rngqrpyfrp sidrtqlnee lvllmercwa qdpaerpdfg
      781 qikgfirrfn keggtsildn lllrmeqyan nleklveert qayleekrka eallyqilph
      841 svaeqlkrge tvqaeafdsv tiyfsdivgf talsaestpm qvvtllndly tcfdaiidnf
      901 dvykvetigd aymvvsglpg rngqrhapei armalallda vssfrirhrp hdqlrlrigv
      961 htgpvcagvv glkmpryclf gdtvntasrm esngqalkih vssttkdald elgcfqlelr
     1021 gdvemkgkgk mrtywllger kgppgll
//
