ANFC_HUMAN
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 03-AUG-2022, entry version 182.
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 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 -!- 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 iPTMnet; P23582; -.
DR PhosphoSitePlus; P23582; -.
DR BioMuta; NPPC; -.
DR DMDM; 113850; -.
DR jPOST; P23582; -.
DR MassIVE; P23582; -.
DR PaxDb; P23582; -.
DR PeptideAtlas; P23582; -.
DR PRIDE; P23582; -.
DR ProteomicsDB; 54134; -.
DR Antibodypedia; 50954; 291 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 CTD; 4880; -.
DR DisGeNET; 4880; -.
DR GeneCards; NPPC; -.
DR HGNC; HGNC:7941; NPPC.
DR HPA; ENSG00000163273; Tissue enriched (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; 1491136at2759; -.
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; 9 hits in 1057 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 C1 segment of cervical spinal cord and 85 other tissues.
DR Genevisible; P23582; HS.
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:0006182; P:cGMP biosynthetic process; IDA:GO_Central.
DR GO; GO:0019934; P:cGMP-mediated signaling; 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:0051321; P:meiotic cell cycle; 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: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:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; 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 Pfam; PF00212; ANP; 1.
DR PRINTS; PR00713; CNATPEPTIDE.
DR PRINTS; PR00710; NATPEPTIDES.
DR SMART; SM00183; NAT_PEP; 1.
DR PROSITE; PS00263; NATRIURETIC_PEPTIDE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Hormone; Osteogenesis;
KW 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 /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
