ANFB_HUMAN
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 03-AUG-2022, entry version 204.
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 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 [29] {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";
CC ---------------------------------------------------------------------------
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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 GlyGen; P16860; 7 sites.
DR iPTMnet; P16860; -.
DR PhosphoSitePlus; P16860; -.
DR BioMuta; NPPB; -.
DR DMDM; 113836; -.
DR MassIVE; P16860; -.
DR PaxDb; P16860; -.
DR PeptideAtlas; P16860; -.
DR PRIDE; P16860; -.
DR ProteomicsDB; 53393; -.
DR ABCD; P16860; 9 sequenced antibodies.
DR Antibodypedia; 13918; 1550 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 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; PTGVWKA; -.
DR OrthoDB; 1493586at2759; -.
DR PhylomeDB; P16860; -.
DR TreeFam; TF106304; -.
DR PathwayCommons; P16860; -.
DR SignaLink; P16860; -.
DR SIGNOR; P16860; -.
DR BioGRID-ORCS; 4879; 15 hits in 1076 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 tissues.
DR Genevisible; P16860; HS.
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:0005634; C:nucleus; 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:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; 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:0031640; P:killing of cells of another organism; IDA:UniProtKB.
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 Pfam; PF00212; ANP; 1.
DR PRINTS; PR00712; BNATPEPTIDE.
DR SMART; SM00183; NAT_PEP; 1.
DR PROSITE; PS00263; NATRIURETIC_PEPTIDE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hormone; Pharmaceutical; Reference proteome; Secreted; Signal; Vasoactive;
KW 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 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 CORIN-
FT mediated processing in HL1 cells; when associated with A-
FT 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 CORIN-
FT mediated processing in HL1 cells; when associated with A-99
FT 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
