ID   ANFC_HUMAN              Reviewed;         126 AA.
AC   P23582; Q4ZG41;
DT   01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1991, sequence version 1.
DT   27-MAR-2024, entry version 191.
DE   RecName: Full=C-type natriuretic peptide;
DE   Contains:
DE     RecName: Full=CNP-22;
DE   Contains:
DE     RecName: Full=CNP-29;
DE   Contains:
DE     RecName: Full=CNP-53;
DE   Flags: Precursor;
GN   Name=NPPC; Synonyms=CNP2;
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 [GENOMIC DNA].
RX   PubMed=2018508; DOI=10.1016/0006-291x(91)91614-i;
RA   Tawaragi Y., Fuchimura K., Tanaka S., Minamino N., Kangawa K., Matsuo H.;
RT   "Gene and precursor structures of human C-type natriuretic peptide.";
RL   Biochem. Biophys. Res. Commun. 175:645-651(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1339402; DOI=10.1161/01.hyp.19.6.809;
RA   Ogawa Y., Nakao K., Nakagawa O., Komatsu Y., Hosoda K., Suga S., Arai H.,
RA   Nagata K., Yoshida N., Imura H.;
RT   "Human C-type natriuretic peptide. Characterization of the gene and
RT   peptide.";
RL   Hypertension 19:809-813(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [5]
RP   PROTEIN SEQUENCE OF 98-126.
RX   PubMed=1472040; DOI=10.1016/0006-291x(92)92257-x;
RA   Ishizaka Y., Kangawa K., Minamino N., Ishii K., Takano S., Eto T.,
RA   Matsuo H.;
RT   "Isolation and identification of C-type natriuretic peptide in human
RT   monocytic cell line, THP-1.";
RL   Biochem. Biophys. Res. Commun. 189:697-704(1992).
RN   [6]
RP   FUNCTION (CNP-22).
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   [7]
RP   TISSUE SPECIFICITY (CNP-22).
RX   PubMed=9794555; DOI=10.1093/ndt/13.10.2529;
RA   Herten M., Lenz W., Gerzer R., Drummer C.;
RT   "The renal natriuretic peptide urodilatin is present in human kidney.";
RL   Nephrol. Dial. Transplant. 13:2529-2535(1998).
RN   [8]
RP   FUNCTION (CNP-22), AND PROTEOLYTIC DEGRADATION BY IDE (CNP-22).
RX   PubMed=21098034; DOI=10.1074/jbc.m110.173252;
RA   Ralat L.A., Guo Q., Ren M., Funke T., Dickey D.M., Potter L.R., Tang W.J.;
RT   "Insulin-degrading enzyme modulates the natriuretic peptide-mediated
RT   signaling response.";
RL   J. Biol. Chem. 286:4670-4679(2011).
RN   [9]
RP   PHARMACEUTICAL, AND REVIEW.
RX   PubMed=29941213; DOI=10.1016/j.ijcard.2018.06.002;
RA   Ichiki T., Dzhoyashvili N., Burnett J.C. Jr.;
RT   "Natriuretic peptide based therapeutics for heart failure: cenderitide: a
RT   novel first-in-class designer natriuretic peptide.";
RL   Int. J. Cardiol. 281:166-171(2019).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 105-126 IN COMPLEX WITH NPR3, AND
RP   DISULFIDE BOND.
RX   PubMed=11533490; DOI=10.1126/science.1062246;
RA   He X.-L., Chow D.-C., Martick M.M., Garcia K.C.;
RT   "Allosteric activation of a spring-loaded natriuretic peptide receptor
RT   dimer by hormone.";
RL   Science 293:1657-1662(2001).
CC   -!- FUNCTION: [CNP-22]: Hormone which plays a role in endochondral
CC       ossification through regulation of cartilaginous growth plate
CC       chondrocytes proliferation and differentiation (By similarity). May
CC       also be vasoactive and natriuretic (PubMed:1672777). Acts by
CC       specifically binding and stimulating NPR2 to produce cGMP
CC       (PubMed:1672777, PubMed:21098034). Binds the clearance receptor NPR3
CC       (PubMed:11533490). {ECO:0000250|UniProtKB:Q61839,
CC       ECO:0000269|PubMed:11533490, ECO:0000269|PubMed:1672777,
CC       ECO:0000269|PubMed:21098034}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: [CNP-22]: In the kidney, predominantly expressed in
CC       the distal tubular cells (at protein level).
CC       {ECO:0000269|PubMed:9794555}.
CC   -!- PTM: [CNP-22]: Degraded by IDE (in vitro).
CC       {ECO:0000269|PubMed:21098034}.
CC   -!- PHARMACEUTICAL: Cenderitide, a chimeric peptide consisting of C-type
CC       natriuretic peptide (NPPC) fused to the C-terminal tail of Dendroaspis
CC       natriuretic peptide (DNP) is under phase II clinical trial to treat
CC       heart failure (HF) with reduced ejection fraction (HFrEF) and HF with
CC       preserved ejection fraction (HFpEF). unlike the 2 peptides from which
CC       it is derived, Cenderitide activates both NPR1 and NPR2.
CC       {ECO:0000305|PubMed:29941213}.
CC   -!- SIMILARITY: Belongs to the natriuretic peptide family. {ECO:0000305}.
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DR   EMBL; M64710; AAA35703.1; -; Genomic_DNA.
DR   EMBL; D90337; BAA14351.1; -; Genomic_DNA.
DR   EMBL; AC013435; AAX88912.1; -; Genomic_DNA.
DR   EMBL; BC069120; AAH69120.1; -; mRNA.
DR   EMBL; BC105065; AAI05066.1; -; mRNA.
DR   EMBL; BC105067; AAI05068.1; -; mRNA.
DR   CCDS; CCDS2489.1; -.
DR   PIR; JT0567; AWHUC.
DR   RefSeq; NP_077720.1; NM_024409.3.
DR   RefSeq; XP_011509547.1; XM_011511245.2.
DR   PDB; 1JDP; X-ray; 2.00 A; H=105-126.
DR   PDBsum; 1JDP; -.
DR   AlphaFoldDB; P23582; -.
DR   SMR; P23582; -.
DR   BioGRID; 110940; 10.
DR   STRING; 9606.ENSP00000387159; -.
DR   TCDB; 1.C.46.1.1; the c-type natriuretic peptide (cnp) family.
DR   GlyGen; P23582; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; P23582; -.
DR   PhosphoSitePlus; P23582; -.
DR   BioMuta; NPPC; -.
DR   DMDM; 113850; -.
DR   jPOST; P23582; -.
DR   MassIVE; P23582; -.
DR   PaxDb; 9606-ENSP00000387159; -.
DR   PeptideAtlas; P23582; -.
DR   ProteomicsDB; 54134; -.
DR   Antibodypedia; 50954; 313 antibodies from 31 providers.
DR   DNASU; 4880; -.
DR   Ensembl; ENST00000295440.2; ENSP00000295440.2; ENSG00000163273.4.
DR   Ensembl; ENST00000409852.2; ENSP00000387159.1; ENSG00000163273.4.
DR   GeneID; 4880; -.
DR   KEGG; hsa:4880; -.
DR   MANE-Select; ENST00000409852.2; ENSP00000387159.1; NM_024409.4; NP_077720.1.
DR   UCSC; uc002vsl.3; human.
DR   AGR; HGNC:7941; -.
DR   CTD; 4880; -.
DR   DisGeNET; 4880; -.
DR   GeneCards; NPPC; -.
DR   HGNC; HGNC:7941; NPPC.
DR   HPA; ENSG00000163273; Tissue enhanced (brain).
DR   MIM; 600296; gene.
DR   neXtProt; NX_P23582; -.
DR   OpenTargets; ENSG00000163273; -.
DR   PharmGKB; PA31735; -.
DR   VEuPathDB; HostDB:ENSG00000163273; -.
DR   eggNOG; ENOG502S2QY; Eukaryota.
DR   GeneTree; ENSGT00390000015492; -.
DR   HOGENOM; CLU_160791_0_0_1; -.
DR   InParanoid; P23582; -.
DR   OMA; HDYPNAR; -.
DR   OrthoDB; 4269066at2759; -.
DR   PhylomeDB; P23582; -.
DR   TreeFam; TF106305; -.
DR   PathwayCommons; P23582; -.
DR   Reactome; R-HSA-5578768; Physiological factors.
DR   SignaLink; P23582; -.
DR   SIGNOR; P23582; -.
DR   BioGRID-ORCS; 4880; 11 hits in 1134 CRISPR screens.
DR   EvolutionaryTrace; P23582; -.
DR   GenomeRNAi; 4880; -.
DR   Pharos; P23582; Tbio.
DR   PRO; PR:P23582; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; P23582; Protein.
DR   Bgee; ENSG00000163273; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 85 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR   GO; GO:0032991; C:protein-containing complex; IDA:CAFA.
DR   GO; GO:0030141; C:secretory granule; IEA:Ensembl.
DR   GO; GO:0005179; F:hormone activity; IBA:GO_Central.
DR   GO; GO:0051427; F:hormone receptor binding; IPI:UniProtKB.
DR   GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB.
DR   GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
DR   GO; GO:0097746; P:blood vessel diameter maintenance; IEA:UniProtKB-KW.
DR   GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl.
DR   GO; GO:0061939; P:c-di-GMP signaling; IEA:Ensembl.
DR   GO; GO:1904588; P:cellular response to glycoprotein; IEA:Ensembl.
DR   GO; GO:0006182; P:cGMP biosynthetic process; IDA:GO_Central.
DR   GO; GO:0019934; P:cGMP-mediated signaling; IEA:Ensembl.
DR   GO; GO:0051276; P:chromosome organization; IEA:Ensembl.
DR   GO; GO:0001549; P:cumulus cell differentiation; IEA:Ensembl.
DR   GO; GO:0035483; P:gastric emptying; IEA:Ensembl.
DR   GO; GO:0003418; P:growth plate cartilage chondrocyte differentiation; ISS:UniProtKB.
DR   GO; GO:0003419; P:growth plate cartilage chondrocyte proliferation; ISS:UniProtKB.
DR   GO; GO:0006874; P:intracellular calcium ion homeostasis; IEA:Ensembl.
DR   GO; GO:1903537; P:meiotic cell cycle process involved in oocyte maturation; IEA:Ensembl.
DR   GO; GO:0071965; P:multicellular organismal locomotion; IEA:Ensembl.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR   GO; GO:0032966; P:negative regulation of collagen biosynthetic process; IEA:Ensembl.
DR   GO; GO:2000279; P:negative regulation of DNA biosynthetic process; IEA:Ensembl.
DR   GO; GO:0051447; P:negative regulation of meiotic cell cycle; IDA:MGI.
DR   GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR   GO; GO:1900194; P:negative regulation of oocyte maturation; IDA:MGI.
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:0045669; P:positive regulation of osteoblast differentiation; IEA:Ensembl.
DR   GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR   GO; GO:0006457; P:protein folding; IDA:CAFA.
DR   GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; IDA:UniProtKB.
DR   GO; GO:0040014; P:regulation of multicellular organism growth; IEA:Ensembl.
DR   GO; GO:0048660; P:regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR   GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR   GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR   GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR   GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR   GO; GO:0090649; P:response to oxygen-glucose deprivation; IEA:Ensembl.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR   InterPro; IPR002406; C_natriurtcpep.
DR   InterPro; IPR000663; Natr_peptide.
DR   InterPro; IPR030480; Natr_peptide_CS.
DR   PANTHER; PTHR12167; C-TYPE NATRIURETIC PEPTIDE; 1.
DR   PANTHER; PTHR12167:SF2; C-TYPE NATRIURETIC PEPTIDE; 1.
DR   Pfam; PF00212; ANP; 1.
DR   PRINTS; PR00713; CNATPEPTIDE.
DR   PRINTS; PR00710; NATPEPTIDES.
DR   SMART; SM00183; NAT_PEP; 1.
DR   PROSITE; PS00263; NATRIURETIC_PEPTIDE; 1.
DR   Genevisible; P23582; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cleavage on pair of basic residues;
KW   Direct protein sequencing; Disulfide bond; Hormone; Osteogenesis;
KW   Pharmaceutical; Reference proteome; Secreted; Signal; Vasoactive.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   PROPEP          24..73
FT                   /id="PRO_0000001553"
FT   PEPTIDE         74..126
FT                   /note="CNP-53"
FT                   /id="PRO_0000001554"
FT   PEPTIDE         98..126
FT                   /note="CNP-29"
FT                   /evidence="ECO:0000269|PubMed:1472040"
FT                   /id="PRO_0000001555"
FT   PEPTIDE         105..126
FT                   /note="CNP-22"
FT                   /id="PRO_0000001556"
FT   REGION          20..71
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   DISULFID        110..126
FT                   /evidence="ECO:0000269|PubMed:11533490"
FT   VARIANT         82
FT                   /note="R -> Q (in dbSNP:rs5267)"
FT                   /id="VAR_014583"
SQ   SEQUENCE   126 AA;  13246 MW;  58F6E657868F9A2D CRC64;
     MHLSQLLACA LLLTLLSLRP SEAKPGAPPK VPRTPPAEEL AEPQAAGGGQ KKGDKAPGGG
     GANLKGDRSR LLRDLRVDTK SRAAWARLLQ EHPNARKYKG ANKKGLSKGC FGLKLDRIGS
     MSGLGC
//