ID   ANFB_HUMAN              Reviewed;         134 AA.
AC   P16860; B0ZBE9; Q6FGY0; Q9P2Q7;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   27-MAR-2024, entry version 213.
DE   RecName: Full=Natriuretic peptides B;
DE   AltName: Full=Brain natriuretic factor prohormone {ECO:0000303|PubMed:2138890};
DE            Short=preproBNP {ECO:0000250|UniProtKB:P40753};
DE            Short=proBNP {ECO:0000303|PubMed:2138890};
DE   AltName: Full=Gamma-brain natriuretic peptide {ECO:0000250|UniProtKB:P07634};
DE   AltName: Full=Iso-ANP {ECO:0000250|UniProtKB:P13205};
DE   Contains:
DE     RecName: Full=NT-proBNP {ECO:0000303|PubMed:25339504};
DE     AltName: Full=NT-pro-BNP {ECO:0000303|PubMed:17372040};
DE     AltName: Full=NT-proBNP(1-76) {ECO:0000303|PubMed:18466803};
DE   Contains:
DE     RecName: Full=proBNP(3-108) {ECO:0000303|PubMed:17367664};
DE   Contains:
DE     RecName: Full=Brain natriuretic peptide 32 {ECO:0000305};
DE              Short=BNP(1-32) {ECO:0000305};
DE              Short=BNP-32 {ECO:0000305};
DE     AltName: Full=Brain natriuretic peptide {ECO:0000303|PubMed:2597152};
DE              Short=BNP {ECO:0000303|PubMed:2597152};
DE   Contains:
DE     RecName: Full=BNP(1-30);
DE   Contains:
DE     RecName: Full=BNP(1-29);
DE   Contains:
DE     RecName: Full=BNP(1-28);
DE   Contains:
DE     RecName: Full=BNP(2-31);
DE   Contains:
DE     RecName: Full=BNP(3-32) {ECO:0000303|PubMed:16254193};
DE     AltName: Full=des-SerPro-BNP {ECO:0000303|PubMed:16254193};
DE     AltName: Full=proBNP(79-108) {ECO:0000303|PubMed:17367664};
DE   Contains:
DE     RecName: Full=BNP(3-30);
DE   Contains:
DE     RecName: Full=BNP(3-29);
DE   Contains:
DE     RecName: Full=Brain natriuretic peptide 29 {ECO:0000250|UniProtKB:P07634};
DE              Short=BNP(4-32) {ECO:0000303|PubMed:20489134};
DE   Contains:
DE     RecName: Full=BNP(4-31);
DE   Contains:
DE     RecName: Full=BNP(4-30);
DE   Contains:
DE     RecName: Full=BNP(4-29);
DE   Contains:
DE     RecName: Full=BNP(4-27);
DE   Contains:
DE     RecName: Full=BNP(5-32);
DE   Contains:
DE     RecName: Full=BNP(5-31);
DE   Contains:
DE     RecName: Full=BNP(5-29);
DE   Flags: Precursor;
GN   Name=NPPB;
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=2597152; DOI=10.1016/s0006-291x(89)80015-4;
RA   Seilhamer J.J., Arfsten A., Miller J.A., Lundquist P., Scarborough R.M.,
RA   Lewicki J.A., Porter J.G.;
RT   "Human and canine gene homologs of porcine brain natriuretic peptide.";
RL   Biochem. Biophys. Res. Commun. 165:650-658(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2522777; DOI=10.1016/0006-291x(89)92269-9;
RA   Sudoh T., Maekawa K., Kojima M., Minamino N., Kangawa K., Matsuo H.;
RT   "Cloning and sequence analysis of cDNA encoding a precursor for human brain
RT   natriuretic peptide.";
RL   Biochem. Biophys. Res. Commun. 159:1427-1434(1989).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Kitano T., Kobayakawa H., Saitou N.;
RT   "Silver Project.";
RL   Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA   Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA   LaBaer J.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG   NHLBI resequencing and genotyping service (RS&G);
RL   Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [7]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pancreas, and Spleen;
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   [9]
RP   PROTEIN SEQUENCE OF 27-58 AND 103-134, AND TISSUE SPECIFICITY (BRAIN
RP   NATRIURETIC PEPTIDE 32).
RX   PubMed=2138890; DOI=10.1016/0006-291x(90)92081-a;
RA   Hino J., Tateyaa H., Minamino N., Kangawa K., Matsuo H.;
RT   "Isolation and identification of human brain natriuretic peptides in
RT   cardiac atrium.";
RL   Biochem. Biophys. Res. Commun. 167:693-700(1990).
RN   [10]
RP   PROTEIN SEQUENCE OF 103-134, AND TISSUE SPECIFICITY (BRAIN NATRIURETIC
RP   PEPTIDE 32).
RX   PubMed=2136732; DOI=10.1016/0014-5793(90)80043-i;
RA   Kambayashi Y., Nakao K., Mukoyama M., Saito Y., Ogawa Y., Shiono S.,
RA   Inouye K., Yoshida N., Imura H.;
RT   "Isolation and sequence determination of human brain natriuretic peptide in
RT   human atrium.";
RL   FEBS Lett. 259:341-345(1990).
RN   [11]
RP   FUNCTION (BRAIN NATRIURETIC PEPTIDE 32), AND SUBCELLULAR LOCATION (BRAIN
RP   NATRIURETIC PEPTIDE 32).
RX   PubMed=1914098; DOI=10.1161/01.cir.84.4.1581;
RA   Yoshimura M., Yasue H., Morita E., Sakaino N., Jougasaki M., Kurose M.,
RA   Mukoyama M., Saito Y., Nakao K., Imura H.;
RT   "Hemodynamic, renal, and hormonal responses to brain natriuretic peptide
RT   infusion in patients with congestive heart failure.";
RL   Circulation 84:1581-1588(1991).
RN   [12]
RP   RECEPTOR-BINDING (BRAIN NATRIURETIC PEPTIDE 32).
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   [13]
RP   FUNCTION (BRAIN NATRIURETIC PEPTIDE 32).
RX   PubMed=9458824; DOI=10.1152/ajprenal.1998.274.1.f63;
RA   Jensen K.T., Carstens J., Pedersen E.B.;
RT   "Effect of BNP on renal hemodynamics, tubular function and vasoactive
RT   hormones in humans.";
RL   Am. J. Physiol. 274:F63-F72(1998).
RN   [14]
RP   TISSUE SPECIFICITY (BRAIN NATRIURETIC PEPTIDE 32).
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   [15]
RP   PROTEOLYTIC PROCESSING BY CORIN.
RX   PubMed=10880574; DOI=10.1073/pnas.150149097;
RA   Yan W., Wu F., Morser J., Wu Q.;
RT   "Corin, a transmembrane cardiac serine protease, acts as a pro-atrial
RT   natriuretic peptide-converting enzyme.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:8525-8529(2000).
RN   [16]
RP   GLYCOSYLATION AT THR-62; SER-63; SER-70; THR-74; SER-79; THR-84 AND THR-97.
RX   PubMed=16750161; DOI=10.1016/j.abb.2006.03.028;
RA   Schellenberger U., O'Rear J., Guzzetta A., Jue R.A., Protter A.A.,
RA   Pollitt N.S.;
RT   "The precursor to B-type natriuretic peptide is an O-linked glycoprotein.";
RL   Arch. Biochem. Biophys. 451:160-166(2006).
RN   [17]
RP   PROTEOLYTIC CLEAVAGE BY DPP4 AND MME (BRAIN NATRIURETIC PEPTIDE 32).
RX   PubMed=16254193; DOI=10.1373/clinchem.2005.057638;
RA   Brandt I., Lambeir A.M., Ketelslegers J.M., Vanderheyden M., Scharpe S.,
RA   De Meester I.;
RT   "Dipeptidyl-peptidase IV converts intact B-type natriuretic peptide into
RT   its des-SerPro form.";
RL   Clin. Chem. 52:82-87(2006).
RN   [18]
RP   FUNCTION (NT-PROBNP; BRAIN NATRIURETIC PEPTIDE 32 AND BNP(3-32)).
RX   PubMed=17372040; DOI=10.1161/hypertensionaha.106.081083;
RA   Heublein D.M., Huntley B.K., Boerrigter G., Cataliotti A., Sandberg S.M.,
RA   Redfield M.M., Burnett J.C. Jr.;
RT   "Immunoreactivity and guanosine 3',5'-cyclic monophosphate activating
RT   actions of various molecular forms of human B-type natriuretic peptide.";
RL   Hypertension 49:1114-1119(2007).
RN   [19]
RP   FUNCTION (BRAIN NATRIURETIC PEPTIDE 32).
RX   PubMed=17349887; DOI=10.1016/j.jacc.2006.10.063;
RA   Liang F., O'Rear J., Schellenberger U., Tai L., Lasecki M., Schreiner G.F.,
RA   Apple F.S., Maisel A.S., Pollitt N.S., Protter A.A.;
RT   "Evidence for functional heterogeneity of circulating B-type natriuretic
RT   peptide.";
RL   J. Am. Coll. Cardiol. 49:1071-1078(2007).
RN   [20]
RP   SYNTHESIS (PROBNP(3-108); BRAIN NATRIURETIC PEPTIDE 32 AND BNP(3-32)), AND
RP   SUBCELLULAR LOCATION (PROBNP(3-108); BRAIN NATRIURETIC PEPTIDE 32 AND
RP   BNP(3-32)).
RX   PubMed=17367664; DOI=10.1016/j.jacc.2006.12.024;
RA   Lam C.S., Burnett J.C. Jr., Costello-Boerrigter L., Rodeheffer R.J.,
RA   Redfield M.M.;
RT   "Alternate circulating pro-B-type natriuretic peptide and B-type
RT   natriuretic peptide forms in the general population.";
RL   J. Am. Coll. Cardiol. 49:1193-1202(2007).
RN   [21]
RP   PROTEOLYTIC PROCESSING (BRAIN NATRIURETIC PEPTIDE 32), AND IDENTIFICATION
RP   BY MASS SPECTROMETRY.
RX   PubMed=19808300; DOI=10.1161/circheartfailure.108.790774;
RA   Niederkofler E.E., Kiernan U.A., O'Rear J., Menon S., Saghir S.,
RA   Protter A.A., Nelson R.W., Schellenberger U.;
RT   "Detection of endogenous B-type natriuretic peptide at very low
RT   concentrations in patients with heart failure.";
RL   Circ. Heart Fail. 1:258-264(2008).
RN   [22]
RP   SUBCELLULAR LOCATION (NT-PROBNP AND BRAIN NATRIURETIC PEPTIDE 32).
RX   PubMed=18466803; DOI=10.1016/j.jacc.2007.12.051;
RA   Waldo S.W., Beede J., Isakson S., Villard-Saussine S., Fareh J.,
RA   Clopton P., Fitzgerald R.L., Maisel A.S.;
RT   "Pro-B-type natriuretic peptide levels in acute decompensated heart
RT   failure.";
RL   J. Am. Coll. Cardiol. 51:1874-1882(2008).
RN   [23]
RP   PROTEOLYTIC PROCESSING BY FURIN AND CORIN, GLYCOSYLATION, AND CLEAVAGE
RP   SITE.
RX   PubMed=20489134; DOI=10.1373/clinchem.2010.143883;
RA   Semenov A.G., Tamm N.N., Seferian K.R., Postnikov A.B., Karpova N.S.,
RA   Serebryanaya D.V., Koshkina E.V., Krasnoselsky M.I., Katrukha A.G.;
RT   "Processing of pro-B-type natriuretic peptide: furin and corin as candidate
RT   convertases.";
RL   Clin. Chem. 56:1166-1176(2010).
RN   [24]
RP   PROTEOLYTIC PROCESSING BY FURIN AND CORIN, GLYCOSYLATION AT THR-97,
RP   CLEAVAGE SITE, AND MUTAGENESIS OF THR-97; ARG-99; ARG-102 AND LYS-105.
RX   PubMed=21763278; DOI=10.1016/j.bbrc.2011.06.192;
RA   Peng J., Jiang J., Wang W., Qi X., Sun X.L., Wu Q.;
RT   "Glycosylation and processing of pro-B-type natriuretic peptide in
RT   cardiomyocytes.";
RL   Biochem. Biophys. Res. Commun. 411:593-598(2011).
RN   [25]
RP   GLYCOSYLATION AT THR-97, AND MUTAGENESIS OF THR-97.
RX   PubMed=21482747; DOI=10.1373/clinchem.2010.157438;
RA   Tonne J.M., Campbell J.M., Cataliotti A., Ohmine S., Thatava T., Sakuma T.,
RA   Macheret F., Huntley B.K., Burnett J.C. Jr., Ikeda Y.;
RT   "Secretion of glycosylated pro-B-type natriuretic peptide from normal
RT   cardiomyocytes.";
RL   Clin. Chem. 57:864-873(2011).
RN   [26]
RP   PROTEOLYTIC CLEAVAGE BY FAP AND DPP4 (BRAIN NATRIURETIC PEPTIDE 32), AND
RP   CLEAVAGE SITE.
RX   PubMed=21314817; DOI=10.1111/j.1742-4658.2011.08051.x;
RA   Keane F.M., Nadvi N.A., Yao T.W., Gorrell M.D.;
RT   "Neuropeptide Y, B-type natriuretic peptide, substance P and peptide YY are
RT   novel substrates of fibroblast activation protein-alpha.";
RL   FEBS J. 278:1316-1332(2011).
RN   [27]
RP   FUNCTION (BRAIN NATRIURETIC PEPTIDE 32), SUBCELLULAR LOCATION (NT-PROBNP
RP   AND BRAIN NATRIURETIC PEPTIDE 32), AND PROTEOLYTIC PROCESSING.
RX   PubMed=25339504; DOI=10.1161/circheartfailure.114.001174;
RA   Huntley B.K., Sandberg S.M., Heublein D.M., Sangaralingham S.J.,
RA   Burnett J.C. Jr., Ichiki T.;
RT   "Pro-B-type natriuretic peptide-1-108 processing and degradation in human
RT   heart failure.";
RL   Circ. Heart Fail. 8:89-97(2015).
RN   [28]
RP   GLYCOSYLATION AT SER-41.
RX   PubMed=32337544; DOI=10.1093/glycob/cwaa039;
RA   Toledo A.G., Pihl J., Spliid C.B., Persson A., Nilsson J., Pereira M.A.,
RA   Gustavsson T., Choudhary S., Oo H.Z., Black P.C., Daugaard M., Esko J.D.,
RA   Larson G., Salanti A., Clausen T.M.;
RT   "An affinity chromatography and glycoproteomics workflow to profile the
RT   chondroitin sulfate proteoglycans that interact with malarial VAR2CSA in
RT   the placenta and in cancer.";
RL   Glycobiology 30:989-1002(2020).
RN   [29]
RP   X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 111-131 IN COMPLEX WITH NPR3,
RP   FUNCTION (BRAIN NATRIURETIC PEPTIDE 32), AND DISULFIDE BOND.
RX   PubMed=16870210; DOI=10.1016/j.jmb.2006.06.060;
RA   He X.-L., Dukkipati A., Garcia K.C.;
RT   "Structural determinants of natriuretic peptide receptor specificity and
RT   degeneracy.";
RL   J. Mol. Biol. 361:698-714(2006).
RN   [30] {ECO:0007744|PDB:3N56}
RP   X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 103-134, FUNCTION (BRAIN
RP   NATRIURETIC PEPTIDE 32), AND PROTEOLYTIC DEGRADATION BY IDE (BRAIN
RP   NATRIURETIC PEPTIDE 32).
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).
CC   -!- FUNCTION: [Brain natriuretic peptide 32]: Cardiac hormone that plays a
CC       key role in mediating cardio-renal homeostasis (PubMed:9458824,
CC       PubMed:1672777, PubMed:1914098, PubMed:17372040). May also function as
CC       a paracrine antifibrotic factor in the heart (By similarity). Acts by
CC       specifically binding and stimulating NPR1 to produce cGMP, which in
CC       turn activates effector proteins that drive various biological
CC       responses (PubMed:9458824, PubMed:1672777, PubMed:17372040,
CC       PubMed:21098034, PubMed:17349887, PubMed:25339504). Involved in
CC       regulating the extracellular fluid volume and maintaining the fluid-
CC       electrolyte balance through natriuresis, diuresis, vasorelaxation, and
CC       inhibition of renin and aldosterone secretion (PubMed:9458824,
CC       PubMed:1914098). Binds the clearance receptor NPR3 (PubMed:16870210).
CC       {ECO:0000250|UniProtKB:P40753, ECO:0000269|PubMed:1672777,
CC       ECO:0000269|PubMed:16870210, ECO:0000269|PubMed:17349887,
CC       ECO:0000269|PubMed:17372040, ECO:0000269|PubMed:1914098,
CC       ECO:0000269|PubMed:21098034, ECO:0000269|PubMed:25339504,
CC       ECO:0000269|PubMed:9458824}.
CC   -!- FUNCTION: [NT-proBNP]: May affect cardio-renal homeostasis
CC       (PubMed:17372040). Able to promote the production of cGMP although its
CC       potency is very low compared to brain natriuretic peptide 32
CC       (PubMed:17372040). {ECO:0000269|PubMed:17372040}.
CC   -!- FUNCTION: [BNP(3-32)]: May have a role in cardio-renal homeostasis
CC       (PubMed:17372040). Able to promote the production of cGMP
CC       (PubMed:17372040). {ECO:0000269|PubMed:17372040}.
CC   -!- INTERACTION:
CC       P16860; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-747044, EBI-3867333;
CC       P16860; P57678: GEMIN4; NbExp=3; IntAct=EBI-747044, EBI-356700;
CC       P16860; Q6A162: KRT40; NbExp=3; IntAct=EBI-747044, EBI-10171697;
CC       P16860; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-747044, EBI-10172052;
CC       P16860; Q7Z3S9: NOTCH2NLA; NbExp=4; IntAct=EBI-747044, EBI-945833;
CC       P16860; P25788: PSMA3; NbExp=3; IntAct=EBI-747044, EBI-348380;
CC       P16860; Q9UJW9: SERTAD3; NbExp=3; IntAct=EBI-747044, EBI-748621;
CC   -!- SUBCELLULAR LOCATION: [NT-proBNP]: Secreted
CC       {ECO:0000269|PubMed:18466803, ECO:0000269|PubMed:25339504}.
CC       Note=Detected in blood. {ECO:0000269|PubMed:18466803,
CC       ECO:0000269|PubMed:25339504}.
CC   -!- SUBCELLULAR LOCATION: [proBNP(3-108)]: Secreted
CC       {ECO:0000269|PubMed:17367664}. Note=Detected in blood.
CC       {ECO:0000269|PubMed:17367664}.
CC   -!- SUBCELLULAR LOCATION: [Brain natriuretic peptide 32]: Secreted
CC       {ECO:0000269|PubMed:17367664, ECO:0000269|PubMed:18466803,
CC       ECO:0000269|PubMed:1914098, ECO:0000269|PubMed:25339504}. Note=Detected
CC       in blood. {ECO:0000269|PubMed:17367664, ECO:0000269|PubMed:18466803,
CC       ECO:0000269|PubMed:1914098, ECO:0000269|PubMed:25339504}.
CC   -!- SUBCELLULAR LOCATION: [BNP(3-32)]: Secreted
CC       {ECO:0000269|PubMed:17367664}. Note=Detected in blood.
CC       {ECO:0000269|PubMed:17367664}.
CC   -!- TISSUE SPECIFICITY: [Brain natriuretic peptide 32]: Detected in the
CC       cardiac atria (at protein level) (PubMed:2138890, PubMed:2136732).
CC       Detected in the kidney distal tubular cells (at protein level)
CC       (PubMed:9794555). {ECO:0000269|PubMed:2136732,
CC       ECO:0000269|PubMed:2138890, ECO:0000269|PubMed:9794555}.
CC   -!- PTM: The precursor molecule is proteolytically cleaved by the
CC       endoproteases FURIN or CORIN at Arg-102 to produce brain natriuretic
CC       peptide 32 and NT-proBNP (PubMed:21314817, PubMed:10880574,
CC       PubMed:21763278, PubMed:20489134, PubMed:21482747). This likely occurs
CC       after it has been secreted into the blood, either during circulation or
CC       in the target cells (PubMed:21482747). CORIN also cleaves the precursor
CC       molecule at additional residues including Arg-99 and possibly Lys-105
CC       (PubMed:20489134, PubMed:21763278). In patients with heart failure,
CC       processing and degradation of natriuretic peptides B occurs but is
CC       delayed, possibly due to a decrease in enzyme level or activity of
CC       CORIN and DPP4 (PubMed:25339504). {ECO:0000269|PubMed:10880574,
CC       ECO:0000269|PubMed:20489134, ECO:0000269|PubMed:21314817,
CC       ECO:0000269|PubMed:21482747, ECO:0000269|PubMed:21763278,
CC       ECO:0000269|PubMed:25339504}.
CC   -!- PTM: [Brain natriuretic peptide 32]: Undergoes further proteolytic
CC       cleavage by various proteases such as DPP4, MME and possibly FAP, to
CC       give rise to a variety of shorter peptides (PubMed:16254193,
CC       PubMed:19808300, PubMed:21314817, PubMed:21098034). Cleaved at Pro-104
CC       by the prolyl endopeptidase FAP (seprase) activity (in vitro)
CC       (PubMed:21314817). Degraded by IDE (PubMed:21098034). During IDE
CC       degradation, the resulting products initially increase the activation
CC       of NPR1 and can also stimulate NPR2 to produce cGMP before the
CC       fragments are completely degraded and inactivated by IDE (in vitro)
CC       (PubMed:21098034). {ECO:0000269|PubMed:16254193,
CC       ECO:0000269|PubMed:19808300, ECO:0000269|PubMed:21098034,
CC       ECO:0000269|PubMed:21314817}.
CC   -!- PTM: O-glycosylated on at least seven residues (PubMed:20489134,
CC       PubMed:21763278, PubMed:16750161, PubMed:17349887, PubMed:21482747). In
CC       cardiomyocytes, glycosylation at Thr-97 is essential for the stability
CC       and processing of the extracellular natriuretic peptides B
CC       (PubMed:21482747). Glycosylation, especially at Thr-97, may also be
CC       important for brain natriuretic peptide 32 stability and/or
CC       extracellular distribution (PubMed:21763278). Glycosylation at Thr-97
CC       appears to inhibit FURIN- or CORIN-mediated proteolytic processing, at
CC       least in HEK293 cells (PubMed:20489134, PubMed:21763278).
CC       {ECO:0000269|PubMed:16750161, ECO:0000269|PubMed:17349887,
CC       ECO:0000269|PubMed:20489134, ECO:0000269|PubMed:21482747,
CC       ECO:0000269|PubMed:21763278}.
CC   -!- PHARMACEUTICAL: Available under the name Nesiritide (Scios). Used for
CC       the treatment of heart failure.
CC   -!- MISCELLANEOUS: Plasma levels of natriuretic peptides B, brain
CC       natriuretic peptide 32 and NT-proBNP are widely used for screening and
CC       diagnosis of heart failure (HF), as these markers are typically higher
CC       in patients with severe HF. {ECO:0000269|PubMed:17349887,
CC       ECO:0000269|PubMed:17372040, ECO:0000269|PubMed:18466803,
CC       ECO:0000269|PubMed:21482747, ECO:0000269|PubMed:25339504}.
CC   -!- SIMILARITY: Belongs to the natriuretic peptide family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA90441.1; Type=Frameshift; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Brain natriuretic peptide entry;
CC       URL="https://en.wikipedia.org/wiki/Brain_natriuretic_peptide";
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DR   EMBL; M31776; AAA35603.1; -; Genomic_DNA.
DR   EMBL; M25296; AAA36355.1; -; mRNA.
DR   EMBL; AB037521; BAA90441.1; ALT_FRAME; Genomic_DNA.
DR   EMBL; CR541976; CAG46774.1; -; mRNA.
DR   EMBL; CR542003; CAG46800.1; -; mRNA.
DR   EMBL; EU326309; ACA05917.1; -; Genomic_DNA.
DR   EMBL; AL021155; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471130; EAW71718.1; -; Genomic_DNA.
DR   EMBL; BC025785; AAH25785.1; -; mRNA.
DR   CCDS; CCDS140.1; -.
DR   PIR; A36736; AWHUB.
DR   RefSeq; NP_002512.1; NM_002521.2.
DR   PDB; 1YK1; X-ray; 2.90 A; E=111-131.
DR   PDB; 3N56; X-ray; 3.10 A; C/D=103-134.
DR   PDBsum; 1YK1; -.
DR   PDBsum; 3N56; -.
DR   AlphaFoldDB; P16860; -.
DR   SMR; P16860; -.
DR   BioGRID; 110939; 28.
DR   IntAct; P16860; 10.
DR   MINT; P16860; -.
DR   STRING; 9606.ENSP00000365651; -.
DR   DrugBank; DB01136; Carvedilol.
DR   DrugBank; DB06412; Oxymetholone.
DR   GlyCosmos; P16860; 7 sites, No reported glycans.
DR   GlyGen; P16860; 8 sites, 1 O-linked glycan (4 sites).
DR   iPTMnet; P16860; -.
DR   PhosphoSitePlus; P16860; -.
DR   BioMuta; NPPB; -.
DR   DMDM; 113836; -.
DR   MassIVE; P16860; -.
DR   PaxDb; 9606-ENSP00000365651; -.
DR   PeptideAtlas; P16860; -.
DR   ProteomicsDB; 53393; -.
DR   ABCD; P16860; 9 sequenced antibodies.
DR   Antibodypedia; 13918; 1705 antibodies from 41 providers.
DR   DNASU; 4879; -.
DR   Ensembl; ENST00000376468.4; ENSP00000365651.3; ENSG00000120937.9.
DR   GeneID; 4879; -.
DR   KEGG; hsa:4879; -.
DR   MANE-Select; ENST00000376468.4; ENSP00000365651.3; NM_002521.3; NP_002512.1.
DR   UCSC; uc001atj.4; human.
DR   AGR; HGNC:7940; -.
DR   CTD; 4879; -.
DR   DisGeNET; 4879; -.
DR   GeneCards; NPPB; -.
DR   HGNC; HGNC:7940; NPPB.
DR   HPA; ENSG00000120937; Tissue enriched (heart).
DR   MIM; 600295; gene.
DR   neXtProt; NX_P16860; -.
DR   OpenTargets; ENSG00000120937; -.
DR   PharmGKB; PA31734; -.
DR   VEuPathDB; HostDB:ENSG00000120937; -.
DR   eggNOG; ENOG502SD0X; Eukaryota.
DR   GeneTree; ENSGT00940000154513; -.
DR   HOGENOM; CLU_158067_0_0_1; -.
DR   InParanoid; P16860; -.
DR   OMA; RPTGVWK; -.
DR   OrthoDB; 4262493at2759; -.
DR   PhylomeDB; P16860; -.
DR   TreeFam; TF106304; -.
DR   PathwayCommons; P16860; -.
DR   SignaLink; P16860; -.
DR   SIGNOR; P16860; -.
DR   BioGRID-ORCS; 4879; 15 hits in 1154 CRISPR screens.
DR   EvolutionaryTrace; P16860; -.
DR   GeneWiki; Brain_natriuretic_peptide; -.
DR   GenomeRNAi; 4879; -.
DR   Pharos; P16860; Tbio.
DR   PRO; PR:P16860; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; P16860; Protein.
DR   Bgee; ENSG00000120937; Expressed in right atrium auricular region and 101 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; TAS:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0032991; C:protein-containing complex; IDA:CAFA.
DR   GO; GO:0008613; F:diuretic hormone activity; TAS:UniProtKB.
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; IDA:UniProtKB.
DR   GO; GO:0097746; P:blood vessel diameter maintenance; NAS:UniProtKB.
DR   GO; GO:0007589; P:body fluid secretion; TAS:UniProtKB.
DR   GO; GO:0003161; P:cardiac conduction system development; NAS:BHF-UCL.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; NAS:UniProtKB.
DR   GO; GO:0006182; P:cGMP biosynthetic process; IDA:GO_Central.
DR   GO; GO:0019934; P:cGMP-mediated signaling; IBA:GO_Central.
DR   GO; GO:0016525; P:negative regulation of angiogenesis; TAS:UniProtKB.
DR   GO; GO:0030308; P:negative regulation of cell growth; NAS:UniProtKB.
DR   GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; IBA:GO_Central.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR   GO; GO:0035815; P:positive regulation of renal sodium excretion; TAS:UniProtKB.
DR   GO; GO:0035810; P:positive regulation of urine volume; TAS:UniProtKB.
DR   GO; GO:0006457; P:protein folding; IDA:CAFA.
DR   GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; IDA:UniProtKB.
DR   GO; GO:0008217; P:regulation of blood pressure; NAS:UniProtKB.
DR   GO; GO:0043114; P:regulation of vascular permeability; TAS:UniProtKB.
DR   GO; GO:0042311; P:vasodilation; IEA:UniProtKB-KW.
DR   DisProt; DP00551; -.
DR   InterPro; IPR000663; Natr_peptide.
DR   InterPro; IPR030480; Natr_peptide_CS.
DR   InterPro; IPR002408; Natriuretic_peptide_brain.
DR   PANTHER; PTHR14066; ATRIAL NATRIURETIC FACTOR PRECURSOR; 1.
DR   PANTHER; PTHR14066:SF10; NATRIURETIC PEPTIDES B; 1.
DR   Pfam; PF00212; ANP; 1.
DR   PRINTS; PR00712; BNATPEPTIDE.
DR   SMART; SM00183; NAT_PEP; 1.
DR   PROSITE; PS00263; NATRIURETIC_PEPTIDE; 1.
DR   Genevisible; P16860; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW   Hormone; Pharmaceutical; Proteoglycan; Reference proteome; Secreted;
KW   Signal; Vasoactive; Vasodilator.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000269|PubMed:2138890"
FT   CHAIN           27..134
FT                   /note="Natriuretic peptides B"
FT                   /id="PRO_0000001531"
FT   PEPTIDE         27..102
FT                   /note="NT-proBNP"
FT                   /evidence="ECO:0000305|PubMed:17372040"
FT                   /id="PRO_0000451939"
FT   PEPTIDE         29..134
FT                   /note="proBNP(3-108)"
FT                   /evidence="ECO:0000305|PubMed:17367664"
FT                   /id="PRO_0000451940"
FT   PEPTIDE         103..134
FT                   /note="Brain natriuretic peptide 32"
FT                   /evidence="ECO:0000269|PubMed:2136732,
FT                   ECO:0000269|PubMed:2138890"
FT                   /id="PRO_0000001532"
FT   PEPTIDE         103..132
FT                   /note="BNP(1-30)"
FT                   /id="PRO_0000364993"
FT   PEPTIDE         103..131
FT                   /note="BNP(1-29)"
FT                   /id="PRO_0000364994"
FT   PEPTIDE         103..130
FT                   /note="BNP(1-28)"
FT                   /id="PRO_0000364995"
FT   PEPTIDE         104..133
FT                   /note="BNP(2-31)"
FT                   /id="PRO_0000364996"
FT   PEPTIDE         105..134
FT                   /note="BNP(3-32)"
FT                   /evidence="ECO:0000305|PubMed:17367664"
FT                   /id="PRO_0000364997"
FT   PEPTIDE         105..132
FT                   /note="BNP(3-30)"
FT                   /id="PRO_0000364998"
FT   PEPTIDE         105..131
FT                   /note="BNP(3-29)"
FT                   /id="PRO_0000364999"
FT   PEPTIDE         106..134
FT                   /note="Brain natriuretic peptide 29"
FT                   /id="PRO_0000365000"
FT   PEPTIDE         106..133
FT                   /note="BNP(4-31)"
FT                   /id="PRO_0000365001"
FT   PEPTIDE         106..132
FT                   /note="BNP(4-30)"
FT                   /id="PRO_0000365002"
FT   PEPTIDE         106..131
FT                   /note="BNP(4-29)"
FT                   /id="PRO_0000365003"
FT   PEPTIDE         106..129
FT                   /note="BNP(4-27)"
FT                   /id="PRO_0000365004"
FT   PEPTIDE         107..134
FT                   /note="BNP(5-32)"
FT                   /id="PRO_0000365005"
FT   PEPTIDE         107..133
FT                   /note="BNP(5-31)"
FT                   /id="PRO_0000365006"
FT   PEPTIDE         107..131
FT                   /note="BNP(5-29)"
FT                   /id="PRO_0000365007"
FT   SITE            99..100
FT                   /note="Cleavage; by CORIN"
FT                   /evidence="ECO:0000269|PubMed:21763278"
FT   SITE            102..103
FT                   /note="Cleavage; by FURIN or CORIN"
FT                   /evidence="ECO:0000269|PubMed:20489134,
FT                   ECO:0000269|PubMed:21763278"
FT   SITE            104..105
FT                   /note="Cleavage; by FAP"
FT                   /evidence="ECO:0000269|PubMed:21314817"
FT   SITE            105..106
FT                   /note="Cleavage; by CORIN"
FT                   /evidence="ECO:0000269|PubMed:20489134,
FT                   ECO:0000269|PubMed:21763278"
FT   CARBOHYD        41
FT                   /note="O-linked (Xyl...) (chondroitin sulfate) serine"
FT                   /evidence="ECO:0000269|PubMed:32337544"
FT   CARBOHYD        62
FT                   /note="O-linked (HexNAc...) threonine; Partial"
FT                   /evidence="ECO:0000269|PubMed:16750161"
FT   CARBOHYD        63
FT                   /note="O-linked (HexNAc...) serine"
FT                   /evidence="ECO:0000269|PubMed:16750161"
FT   CARBOHYD        70
FT                   /note="O-linked (HexNAc...) serine"
FT                   /evidence="ECO:0000269|PubMed:16750161"
FT   CARBOHYD        74
FT                   /note="O-linked (HexNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:16750161"
FT   CARBOHYD        79
FT                   /note="O-linked (HexNAc...) serine"
FT                   /evidence="ECO:0000269|PubMed:16750161"
FT   CARBOHYD        84
FT                   /note="O-linked (HexNAc...) threonine; Partial"
FT                   /evidence="ECO:0000269|PubMed:16750161"
FT   CARBOHYD        97
FT                   /note="O-linked (HexNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:16750161,
FT                   ECO:0000269|PubMed:21763278"
FT   DISULFID        112..128
FT                   /evidence="ECO:0000269|PubMed:16870210"
FT   VARIANT         25
FT                   /note="R -> L (in dbSNP:rs5227)"
FT                   /id="VAR_014580"
FT   VARIANT         47
FT                   /note="R -> H (in dbSNP:rs5229)"
FT                   /id="VAR_014581"
FT   VARIANT         93
FT                   /note="M -> L (in dbSNP:rs5230)"
FT                   /id="VAR_014582"
FT   MUTAGEN         97
FT                   /note="T->A: Prevents O-glycosylation at this residue.
FT                   Decreased extracellular levels of NPPB due to decreased
FT                   stability after secretion whereas extracellular levels of
FT                   brain natriuretic peptide 32 is increased. In HEK293 cells,
FT                   proteolytic processing by CORIN or FURIN is reduced but in
FT                   HL1 cells proteolytic processing is not affected."
FT                   /evidence="ECO:0000269|PubMed:21482747,
FT                   ECO:0000269|PubMed:21763278"
FT   MUTAGEN         99
FT                   /note="R->A: Loss of FURIN-mediated proteolytic processing
FT                   in HEK293 cells, however processing in HL1 cells, likely
FT                   mediated by CORIN, is only slightly reduced. Loss of
FT                   CORIN-mediated processing in HL1 cells; when associated
FT                   with A-102 and A-105."
FT                   /evidence="ECO:0000269|PubMed:21763278"
FT   MUTAGEN         102
FT                   /note="R->A: Loss of FURIN-mediated proteolytic processing
FT                   in HEK293 cells, however processing in HL1 cells, likely
FT                   mediated by CORIN, is only slightly reduced. Loss of
FT                   CORIN-mediated processing in HL1 cells; when associated
FT                   with A-99 and A-105."
FT                   /evidence="ECO:0000269|PubMed:21763278"
FT   MUTAGEN         105
FT                   /note="K->A: No effect on proteolytic processing in HEK293
FT                   or HL1 cells. Loss of CORIN-mediated processing in HL1
FT                   cells; when associated with A-99 and A-102."
FT                   /evidence="ECO:0000269|PubMed:21763278"
FT   STRAND          121..123
FT                   /evidence="ECO:0007829|PDB:1YK1"
SQ   SEQUENCE   134 AA;  14726 MW;  DC884D9408462146 CRC64;
     MDPQTAPSRA LLLLLFLHLA FLGGRSHPLG SPGSASDLET SGLQEQRNHL QGKLSELQVE
     QTSLEPLQES PRPTGVWKSR EVATEGIRGH RKMVLYTLRA PRSPKMVQGS GCFGRKMDRI
     SSSSGLGCKV LRRH
//