BNP_BOTIN
ID BNP_BOTIN Reviewed; 265 AA.
AC P68515; P01020; P30421; P30422; P30423; P30425; Q8QG91;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 20-MAY-2008, sequence version 2.
DT 25-MAY-2022, entry version 54.
DE RecName: Full=Bradykinin-potentiating and C-type natriuretic peptides;
DE AltName: Full=Angiotensin-converting enzyme inhibitor;
DE AltName: Full=BPP-CNP homolog;
DE Contains:
DE RecName: Full=Bradykinin-potentiating peptide 13a {ECO:0000303|PubMed:2386615};
DE Short=BPP-13a {ECO:0000303|PubMed:2386615};
DE AltName: Full=Bradykinin-potentiating peptide S3,1 {ECO:0000303|PubMed:2386615};
DE Contains:
DE RecName: Full=Bradykinin-potentiating peptide 10c {ECO:0000303|PubMed:2386615};
DE Short=BPP-10c {ECO:0000303|PubMed:2386615};
DE Short=BPP-2 {ECO:0000303|PubMed:11994001};
DE AltName: Full=Bradykinin-potentiating peptide S4,3,1 {ECO:0000303|PubMed:2386615};
DE Contains:
DE RecName: Full=Bradykinin-potentiating peptide 12b {ECO:0000250|UniProtKB:Q9PW56};
DE Short=BPP-12b {ECO:0000250|UniProtKB:Q9PW56};
DE AltName: Full=Bradykinin-potentiating peptide S4,3,2 {ECO:0000303|PubMed:2386615};
DE Contains:
DE RecName: Full=Bradykinin-potentiating peptide 11e {ECO:0000250|UniProtKB:Q9PW56};
DE Short=BPP-11e {ECO:0000250|UniProtKB:Q9PW56};
DE Contains:
DE RecName: Full=Bradykinin-potentiating peptide 5a {ECO:0000303|PubMed:2386615};
DE Short=BPP-5a {ECO:0000303|PubMed:2386615};
DE AltName: Full=Bradykinin-potentiating peptide S5,2 {ECO:0000303|PubMed:2386615};
DE AltName: Full=Bradykinin-potentiating peptide Va {ECO:0000250|UniProtKB:Q6LEM5};
DE Short=BPPVa {ECO:0000250|UniProtKB:Q6LEM5};
DE AltName: Full=Proline-rich peptide 5a {ECO:0000303|PubMed:21185808};
DE Short=PRO-5a {ECO:0000303|PubMed:21185808};
DE Contains:
DE RecName: Full=C-type natriuretic peptide;
DE Short=CNP;
DE Flags: Precursor;
OS Bothrops insularis (Golden lancehead) (Lachesis insularis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=8723;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=12459276; DOI=10.1016/s0378-1119(02)01080-6;
RA Junqueira-de-Azevedo I.L.M., Ho P.L.;
RT "A survey of gene expression and diversity in the venom glands of the
RT pitviper snake Bothrops insularis through the generation of expressed
RT sequence tags (ESTs).";
RL Gene 299:279-291(2002).
RN [2]
RP PROTEIN SEQUENCE OF 31-43; 51-63; 71-80; 88-99; 121-125 AND 127-131
RP (BPP-13A; BPP-10C; BPP-12B AND BPP-5A), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND PYROGLUTAMATE FORMATION AT GLN-31; GLN-51; GLN-71; GLN-88;
RP GLN-121 AND GLN-127.
RC TISSUE=Venom;
RX PubMed=2386615; DOI=10.1007/bf01025312;
RA Cintra A.C.O., Vieira C.A., Giglio J.R.;
RT "Primary structure and biological activity of bradykinin potentiating
RT peptides from Bothrops insularis snake venom.";
RL J. Protein Chem. 9:221-227(1990).
RN [3]
RP PROTEIN SEQUENCE OF 31-43; 51-63; 71-80 AND 88-99 (BPP-13A; BPP-10C AND
RP BPP-12B), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MASS SPECTROMETRY, AND
RP PYROGLUTAMATE FORMATION AT GLN-31; GLN-51; GLN-71 AND GLN-88.
RC TISSUE=Venom;
RX PubMed=15912471; DOI=10.1002/rcm.1973;
RA Wermelinger L.S., Dutra D.L., Oliveira-Carvalho A.L., Soares M.R.,
RA Bloch C. Jr., Zingali R.B.;
RT "Fast analysis of low molecular mass compounds present in snake venom:
RT identification of ten new pyroglutamate-containing peptides.";
RL Rapid Commun. Mass Spectrom. 19:1703-1708(2005).
RN [4]
RP PROTEIN SEQUENCE OF 31-43 AND 51-63 (BPP-13A), IDENTIFICATION BY MASS
RP SPECTROMETRY, SUBCELLULAR LOCATION, AND PYROGLUTAMATE FORMATION AT GLN-31
RP AND GLN-51.
RC TISSUE=Venom;
RX PubMed=18200607; DOI=10.1002/jms.1351;
RA Souza G.H.M.F., Catharino R.R., Ifa D.R., Eberlin M.N., Hyslop S.;
RT "Peptide fingerprinting of snake venoms by direct infusion nano-
RT electrospray ionization mass spectrometry: potential use in venom
RT identification and taxonomy.";
RL J. Mass Spectrom. 43:594-599(2008).
RN [5]
RP SYNTHESIS OF 71-80 (BPP-10C), AND FUNCTION.
RX PubMed=11994001; DOI=10.1021/bi012121x;
RA Cotton J., Hayashi M.A., Cuniasse P., Vazeux G., Ianzer D.,
RA De Camargo A.C., Dive V.;
RT "Selective inhibition of the C-domain of angiotensin I converting enzyme by
RT bradykinin potentiating peptides.";
RL Biochemistry 41:6065-6071(2002).
RN [6]
RP FUNCTION (BPP-10C).
RX PubMed=17475904; DOI=10.1124/jpet.107.120873;
RA Ianzer D., Santos R.A., Etelvino G.M., Xavier C.H., de Almeida Santos J.,
RA Mendes E.P., Machado L.T., Prezoto B.C., Dive V., de Camargo A.C.;
RT "Do the cardiovascular effects of angiotensin-converting enzyme (ACE) I
RT involve ACE-independent mechanisms? new insights from proline-rich peptides
RT of Bothrops jararaca.";
RL J. Pharmacol. Exp. Ther. 322:795-805(2007).
RN [7]
RP FUNCTION, BIOASSAY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF PRO-74;
RP PRO-76; ILE-78; PRO-79 AND PRO-80.
RX PubMed=19491403; DOI=10.1074/jbc.m109.021089;
RA Guerreiro J.R., Lameu C., Oliveira E.F., Klitzke C.F., Melo R.L.,
RA Linares E., Augusto O., Fox J.W., Lebrun I., Serrano S.M., Camargo A.C.;
RT "Argininosuccinate synthetase is a functional target for a snake venom
RT anti-hypertensive peptide: role in arginine and nitric oxide production.";
RL J. Biol. Chem. 284:20022-20033(2009).
RN [8]
RP SYNTHESIS OF 121-125 AND 127-131 (BPP-5A), AND FUNCTION.
RX PubMed=21185808; DOI=10.1016/j.bcp.2010.12.016;
RA Morais K.L., Hayashi M.A., Bruni F.M., Lopes-Ferreira M., Camargo A.C.,
RA Ulrich H., Lameu C.;
RT "Bj-PRO-5a, a natural angiotensin-converting enzyme inhibitor, promotes
RT vasodilatation mediated by both bradykinin B(2)and M1 muscarinic
RT acetylcholine receptors.";
RL Biochem. Pharmacol. 81:736-742(2011).
RN [9]
RP SYNTHESIS OF 71-80 (BPP-10C), AND FUNCTION.
RX PubMed=22869554; DOI=10.1074/mcp.m112.019331;
RA Tashima A.K., Zelanis A., Kitano E.S., Ianzer D., Melo R.L., Rioli V.,
RA Sant'anna S.S., Schenberg A.C., Camargo A.C., Serrano S.M.T.;
RT "Peptidomics of three Bothrops snake venoms: insights into the molecular
RT diversification of proteomes and peptidomes.";
RL Mol. Cell. Proteomics 11:1245-1262(2012).
CC -!- FUNCTION: [Bradykinin-potentiating peptide 5a]: Modestly inhibits ACE
CC (with highest affinity for the N-site) and reveals strong bradykinin-
CC potentiating activity. Induces nitric oxide (NO) production depended on
CC muscarinic acetylcholine receptor M1 subtype (CHRM1) and bradykinin B2
CC receptor (BDKRB2) activation. Both these receptors contribute to the
CC vasodilation induced by this peptide that may have an indirect action
CC on BDKRB2 and a direct agonistic action on CHRM1.
CC -!- FUNCTION: [Bradykinin-potentiating peptide 10c]: Peptide with several
CC activities. It inhibits the activity of the angiotensin-converting
CC enzyme (ACE) by a preferential interaction with its C-domain
CC (PubMed:11994001). It evokes transient hypotension (-14 mmHg) similar
CC to that evoked by 0,5 ug of bradykinin, when injected alone into rats.
CC It has a high bradykinin-potentiating effect (120%), when 60 nmol of
CC BPP-10c are coinjected with 0.5 ug of bradykinin into rats
CC (PubMed:22869554). Does not affect angiotensin-1 pressor effects. Shows
CC potent and long-lasting antihypertensive activity as well as a
CC reduction of the heart rate (PubMed:17475904). It also binds and dose-
CC dependently promotes the activation of cytosolic argininosuccinate
CC synthase (ASS1), an enzyme that catalyzes the conversion of citrulline,
CC L-aspartate and ATP to argininosuccinate, AMP and pyrophosphate. It
CC also enhances ASS1-dependent arginine production in HEK 293 cells, as
CC well as in spontaneous hypertensive rat (SHR) and Wistar rat plasma. In
CC addition, it induces the production of nitric-oxide (NO) by HUVEC cells
CC via the endothelial nitric-oxide synthase (NOS3), which use arginine as
CC a substrate and produce NO. It has been shown to be internalized by
CC ASS1-expressing endothelial (HUVEC) and kidney (HEK 293) cells, and is
CC detected homogenously distributed within the cell cytoplasm for up to 2
CC hours (PubMed:19491403). {ECO:0000269|PubMed:11994001,
CC ECO:0000269|PubMed:17475904, ECO:0000269|PubMed:19491403,
CC ECO:0000269|PubMed:22869554}.
CC -!- FUNCTION: [C-type natriuretic peptide]: Exhibits hypotensive and
CC vasodepressor activity. Acts by activating natriuretic receptors (NPR1
CC and/or NPR2 and/or NPR3) (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18200607}.
CC Cytoplasm, cytosol. Note=BPP-10c is internalized in the cytosol of prey
CC cells.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000269|PubMed:15912471, ECO:0000269|PubMed:2386615}.
CC -!- MASS SPECTROMETRY: [Bradykinin-potentiating peptide 13a]: Mass=1370.81;
CC Method=MALDI; Evidence={ECO:0000269|PubMed:15912471};
CC -!- MASS SPECTROMETRY: [Bradykinin-potentiating peptide 10c]: Mass=1196.41;
CC Method=MALDI; Evidence={ECO:0000269|PubMed:15912471};
CC -!- MASS SPECTROMETRY: [Bradykinin-potentiating peptide 12b]: Mass=1279.50;
CC Method=MALDI; Evidence={ECO:0000269|PubMed:15912471};
CC -!- SIMILARITY: In the N-terminal section; belongs to the bradykinin-
CC potentiating peptide family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the natriuretic
CC peptide family. {ECO:0000305}.
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DR EMBL; AF490531; AAM09690.1; -; mRNA.
DR PIR; B37196; B37196.
DR PIR; C37196; C37196.
DR PIR; G37196; G37196.
DR AlphaFoldDB; P68515; -.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005179; F:hormone activity; IEA:InterPro.
DR GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0008217; P:regulation of blood pressure; IEA:UniProtKB-KW.
DR GO; GO:0042311; P:vasodilation; IEA:UniProtKB-KW.
DR InterPro; IPR000663; Natr_peptide.
DR InterPro; IPR030480; Natr_peptide_CS.
DR Pfam; PF00212; ANP; 1.
DR PRINTS; PR00710; NATPEPTIDES.
DR SMART; SM00183; NAT_PEP; 1.
DR PROSITE; PS00263; NATRIURETIC_PEPTIDE; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; G-protein coupled acetylcholine receptor impairing toxin;
KW G-protein coupled receptor impairing toxin; Hypotensive agent;
KW Metalloenzyme inhibitor; Metalloprotease inhibitor; Protease inhibitor;
KW Pyrrolidone carboxylic acid; Repeat; Secreted; Signal; Toxin; Vasoactive;
KW Vasodilator.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT PROPEP 24..30
FT /evidence="ECO:0000305"
FT /id="PRO_0000334179"
FT PEPTIDE 31..43
FT /note="Bradykinin-potentiating peptide 13a"
FT /evidence="ECO:0000269|PubMed:15912471,
FT ECO:0000269|PubMed:18200607, ECO:0000269|PubMed:2386615"
FT /id="PRO_0000043507"
FT PROPEP 44..50
FT /evidence="ECO:0000305"
FT /id="PRO_0000334180"
FT PEPTIDE 51..63
FT /note="Bradykinin-potentiating peptide 13a"
FT /evidence="ECO:0000269|PubMed:15912471,
FT ECO:0000269|PubMed:18200607, ECO:0000269|PubMed:2386615"
FT /id="PRO_0000334181"
FT PROPEP 64..70
FT /evidence="ECO:0000305"
FT /id="PRO_0000334182"
FT PEPTIDE 71..80
FT /note="Bradykinin-potentiating peptide 10c"
FT /evidence="ECO:0000269|PubMed:15912471,
FT ECO:0000269|PubMed:2386615"
FT /id="PRO_0000043508"
FT PROPEP 81..87
FT /evidence="ECO:0000305"
FT /id="PRO_0000334183"
FT PEPTIDE 88..99
FT /note="Bradykinin-potentiating peptide 12b"
FT /evidence="ECO:0000269|PubMed:15912471,
FT ECO:0000269|PubMed:2386615"
FT /id="PRO_0000043509"
FT PROPEP 100..106
FT /evidence="ECO:0000305"
FT /id="PRO_0000334184"
FT PEPTIDE 107..117
FT /note="Bradykinin-potentiating peptide 11e"
FT /evidence="ECO:0000250|UniProtKB:Q9PW56"
FT /id="PRO_0000334185"
FT PROPEP 118..120
FT /evidence="ECO:0000305"
FT /id="PRO_0000334186"
FT PEPTIDE 121..125
FT /note="Bradykinin-potentiating peptide 5a"
FT /evidence="ECO:0000269|PubMed:2386615"
FT /id="PRO_0000043511"
FT PROPEP 126
FT /evidence="ECO:0000305"
FT /id="PRO_0000334187"
FT PEPTIDE 127..131
FT /note="Bradykinin-potentiating peptide 5a"
FT /evidence="ECO:0000269|PubMed:2386615"
FT /id="PRO_0000334188"
FT PROPEP 132..241
FT /evidence="ECO:0000305"
FT /id="PRO_0000334189"
FT PEPTIDE 244..265
FT /note="C-type natriuretic peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000334190"
FT REGION 153..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 31
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:15912471,
FT ECO:0000269|PubMed:18200607, ECO:0000269|PubMed:2386615"
FT MOD_RES 51
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:15912471,
FT ECO:0000269|PubMed:18200607, ECO:0000269|PubMed:2386615"
FT MOD_RES 71
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:15912471,
FT ECO:0000269|PubMed:2386615"
FT MOD_RES 88
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:15912471,
FT ECO:0000269|PubMed:2386615"
FT MOD_RES 107
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250|UniProtKB:Q9PW56"
FT MOD_RES 121
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:2386615"
FT MOD_RES 127
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:2386615"
FT DISULFID 249..265
FT /evidence="ECO:0000250|UniProtKB:P23582"
FT MUTAGEN 74
FT /note="P->A: Low decrease in ability to enhance AsS
FT activity."
FT /evidence="ECO:0000269|PubMed:19491403"
FT MUTAGEN 76
FT /note="P->A: Low decrease in ability to enhance AsS
FT activity."
FT /evidence="ECO:0000269|PubMed:19491403"
FT MUTAGEN 78
FT /note="I->A: Low decrease in ability to enhance AsS
FT activity."
FT /evidence="ECO:0000269|PubMed:19491403"
FT MUTAGEN 79
FT /note="P->A: Important decrease in ability to enhance AsS
FT activity."
FT /evidence="ECO:0000269|PubMed:19491403"
FT MUTAGEN 80
FT /note="P->A: Important decrease in ability to enhance AsS
FT activity."
FT /evidence="ECO:0000269|PubMed:19491403"
FT CONFLICT 92
FT /note="Missing (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 265 AA; 27763 MW; 0EAE1408B42358BE CRC64;
MVLSRLAASG LLLLALLALS VDGKPVQQWA QGGWPRPGPE IPPLKVQQWA QGGWPRPGPE
IPPLTVQQWA QNWPHPQIPP LTVQQWAQLG PPPRPQIPPL EVQQWAQGRA PHPPIPPAPL
QKWAPVQKWA PLLQPHESPA SGTTALREEL SLGPEAASGV PSAGAEVGRS GSKAPAAPHR
LSKSKGAAAT SAASRPMRDL RPDGKQARQN WGRMVHHDHH AAVGGGGGGG GGGARRLKGL
AKKGAAKGCF GLKLDRIGTM SGLGC
