ID   BNP_GLOBL               Reviewed;         263 AA.
AC   P01021; Q9PT52;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   20-MAY-2008, sequence version 4.
DT   04-NOV-2026, entry version 92.
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=Blomhotin {ECO:0000303|PubMed:10519653, ECO:0000303|PubMed:10866809};
DE   Contains:
DE     RecName: Full=Bradykinin-potentiating peptide A;
DE              Short=BPP-a;
DE     AltName: Full=Potentiator A {ECO:0000303|PubMed:4323853, ECO:0000303|PubMed:4730295};
DE   Contains:
DE     RecName: Full=Leu3-blomhotin {ECO:0000303|PubMed:10866809};
DE     AltName: Full=Potentiator D {ECO:0000303|PubMed:4323853};
DE   Contains:
DE     RecName: Full=Bradykinin-potentiating peptide B {ECO:0000303|Ref.5};
DE              Short=BPP-b;
DE     AltName: Full=Potentiator B {ECO:0000303|PubMed:4323853};
DE   Contains:
DE     RecName: Full=Bradykinin-potentiating peptide C;
DE              Short=BPP-c;
DE     AltName: Full=Potentiator C {ECO:0000303|PubMed:4323853};
DE   Contains:
DE     RecName: Full=Bradykinin-potentiating peptide E;
DE              Short=BPP-e;
DE     AltName: Full=Potentiator E {ECO:0000303|PubMed:4323853};
DE   Contains:
DE     RecName: Full=Bradykinin-potentiating peptide Ahb1 {ECO:0000303|PubMed:11994001};
DE              Short=BPP-Ahb1 {ECO:0000303|PubMed:11994001};
DE   Contains:
DE     RecName: Full=Bradykinin-potentiating peptide Ahb2 {ECO:0000303|PubMed:11994001};
DE              Short=BPP-Ahb2 {ECO:0000303|PubMed:11994001};
DE   Contains:
DE     RecName: Full=C-type natriuretic peptide;
DE   Flags: Precursor;
OS   Gloydius blomhoffii (Mamushi) (Agkistrodon halys blomhoffi).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Viperidae; Crotalinae; Gloydius.
OX   NCBI_TaxID=242054;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RX   PubMed=10604536; DOI=10.1016/s0162-3109(99)00119-8;
RA   Higuchi S., Murayama N., Saguchi K., Ohi H., Fujita Y., de Camargo A.C.M.,
RA   Ogawa T., Deshimaru M., Ohno M.;
RT   "Bradykinin-potentiating peptides and C-type natriuretic peptides from
RT   snake venom.";
RL   Immunopharmacology 44:129-135(1999).
RN   [2]
RP   PROTEIN SEQUENCE OF 31-41, PYROGLUTAMATE FORMATION AT GLN-31, FUNCTION, AND
RP   SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=10519653; DOI=10.1016/s0041-0101(99)00117-8;
RA   Yanoshita R., Kasuga A., Inoue S., Ikeda K., Samejima Y.;
RT   "Blomhotin: a novel peptide with smooth muscle contractile activity
RT   identified in the venom of Agkistrodon halys blomhoffii.";
RL   Toxicon 37:1761-1770(1999).
RN   [3]
RP   PROTEIN SEQUENCE OF 31-40, PYROGLUTAMATE FORMATION AT GLN-31, AND
RP   SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=4730295; DOI=10.1007/bf01926673;
RA   Kato H., Suzuki T., Okada K., Kimura T., Sakakibara S.;
RT   "Structure of potentiator A, one of the five bradykinin potentiating
RT   peptides from the venom of Agkistrodon halys blomhoffii.";
RL   Experientia 29:574-575(1973).
RN   [4]
RP   PROTEIN SEQUENCE OF 67-77, PYROGLUTAMATE FORMATION AT GLN-67, FUNCTION, AND
RP   SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=4323853; DOI=10.1021/bi00782a007;
RA   Kato H., Suzuki T.;
RT   "Bradykinin-potentiating peptides from the venom of Agkistrodon halys
RT   blomhoffi. Isolation of five bradykinin potentiators and the amino acid
RT   sequences of two of them, potentiators B and C.";
RL   Biochemistry 10:972-980(1971).
RN   [5]
RP   PROTEIN SEQUENCE OF 85-95 AND 103-113, PYROGLUTAMATE FORMATION AT GLN-85
RP   AND GLN-103, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RA   Kato H., Suzuki T.;
RT   "Amino acid sequence of bradykinin-potentiating peptide isolated from the
RT   venom of Agkistrodon halys blomhoffii.";
RL   Proc. Jpn. Acad., B, Phys. Biol. Sci. 46:176-181(1970).
RN   [6]
RP   PROTEIN SEQUENCE OF 49-59, SYNTHESIS OF 31-40 AND 49-59 (BPP-A AND
RP   LEU3-BLOMHOTIN), FUNCTION, PYROGLUTAMATE FORMATION AT GLN-49, MASS
RP   SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=10866809; DOI=10.1046/j.1432-1327.2000.01443.x;
RA   Murayama N., Michel G.H., Yanoshita R., Samejima Y., Saguchi K., Ohi H.,
RA   Fujita Y., Higuchi S.;
RT   "cDNA cloning of bradykinin-potentiating peptides-C-type natriuretic
RT   peptide precursor, and characterization of the novel peptide Leu3-blomhotin
RT   from the venom of Agkistrodon blomhoffi.";
RL   Eur. J. Biochem. 267:4075-4080(2000).
RN   [7]
RP   SYNTHESIS OF 67-77; 85-95 AND 103-113 (BPP-B AND BPP-C), 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   [8]
RP   SYNTHESIS OF 117-121 AND 131-136 (BPP-AHB1 AND BPP-AHB2), FUNCTION, AND
RP   PYROGLUTAMATE FORMATION AT GLN-117 AND GLN-131.
RX   PubMed=17714693; DOI=10.1016/j.bcp.2007.07.014;
RA   Gomes C.L., Konno K., Conceicao I.M., Ianzer D., Yamanouye N.,
RA   Prezoto B.C., Assakura M.T., Radis-Baptista G., Yamane T., Santos R.A.,
RA   de Camargo A.C.M., Hayashi M.A.F.;
RT   "Identification of novel bradykinin-potentiating peptides (BPPs) in the
RT   venom gland of a rattlesnake allowed the evaluation of the structure-
RT   function relationship of BPPs.";
RL   Biochem. Pharmacol. 74:1350-1360(2007).
RN   [9] {ECO:0000312|PDB:4AA2}
RP   X-RAY CRYSTALLOGRAPHY AND 103-113 (BPP-B) IN COMPLEX WITH DROSOPHILA
RP   ANGIOTENSIN-CONVERTING ENZYME, AND FUNCTION.
RX   PubMed=23082758; DOI=10.1111/febs.12038;
RA   Akif M., Masuyer G., Bingham R.J., Sturrock E.D., Isaac R.E., Acharya K.R.;
RT   "Structural basis of peptide recognition by the angiotensin-1 converting
RT   enzyme homologue AnCE from Drosophila melanogaster.";
RL   FEBS J. 279:4525-4534(2012).
RN   [10] {ECO:0000312|PDB:4APJ}
RP   X-RAY CRYSTALLOGRAPHY AND 103-113 IN COMPLEX WITH HUMAN
RP   ANGIOTENSIN-CONVERTING ENZYME.
RX   PubMed=23056909; DOI=10.1038/srep00717;
RA   Masuyer G., Schwager S.L., Sturrock E.D., Isaac R.E., Acharya K.R.;
RT   "Molecular recognition and regulation of human angiotensin-I converting
RT   enzyme (ACE) activity by natural inhibitory peptides.";
RL   Sci. Rep. 2:717-717(2012).
CC   -!- FUNCTION: [Blomhotin]: Inhibits the rabbit lung angiotensin-converting
CC       enzyme (ACE) (IC(50)=15 uM) (PubMed:10866809). Contracts the rat
CC       gastric fundus smooth muscle in a rapid and transient manner
CC       (PubMed:10519653, PubMed:10866809). {ECO:0000269|PubMed:10519653,
CC       ECO:0000269|PubMed:10866809}.
CC   -!- FUNCTION: [Bradykinin-potentiating peptide A]: Causes no contraction of
CC       the rat gastric fundus smooth muscle even at high concentrations.
CC       Causes very weak contraction of the isolated guinea pig ileum
CC       (PubMed:4323853). Causes weak contraction on rat uterus
CC       (PubMed:4323853). {ECO:0000269|PubMed:4323853}.
CC   -!- FUNCTION: [Bradykinin-potentiating peptide B]: Inhibits the activity of
CC       the angiotensin-converting enzyme (ACE) by a preferential interaction
CC       with its C-domain (Ki=30 nM, IC(50)=1.1 uM) (PubMed:10866809,
CC       PubMed:11994001, PubMed:23082758). It binds ACE in a zinc-independent
CC       manner (PubMed:23056909). Also potentiates the hypotensive effects of
CC       bradykinin. Causes high contraction of the isolated guinea pig ileum
CC       and weak contraction on rat uterus (PubMed:4323853).
CC       {ECO:0000269|PubMed:10866809, ECO:0000269|PubMed:11994001,
CC       ECO:0000269|PubMed:23082758, ECO:0000269|PubMed:4323853}.
CC   -!- FUNCTION: [Bradykinin-potentiating peptide C]: Inhibits the activity of
CC       the angiotensin-converting enzyme (ACE) by interacting with the same
CC       potency to its C- and N-domains (PubMed:11994001). Inhibits the rabbit
CC       lung angiotensin-converting enzyme (ACE) (IC(50)=7.1 uM)
CC       (PubMed:10866809). Causes weak contraction of the isolated guinea pig
CC       ileum (PubMed:4323853). Causes weak contraction on rat uterus
CC       (PubMed:4323853). {ECO:0000269|PubMed:10866809,
CC       ECO:0000269|PubMed:11994001, ECO:0000269|PubMed:4323853}.
CC   -!- FUNCTION: [Leu3-blomhotin]: Inhibits the rabbit lung angiotensin-
CC       converting enzyme (ACE) (IC(50)=46 uM) (PubMed:10866809). Synthetic
CC       Leu3-blomhotin contracts the rat gastric fundus smooth muscle in a
CC       rapid and transient manner (PubMed:10866809). Causes moderate
CC       contraction of the isolated guinea pig ileum (PubMed:4323853). Causes
CC       weak contraction on rat uterus (PubMed:4323853).
CC       {ECO:0000269|PubMed:10866809, ECO:0000269|PubMed:4323853}.
CC   -!- FUNCTION: [Bradykinin-potentiating peptide E]: Causes weak contraction
CC       of the isolated guinea pig ileum (PubMed:4323853). Causes about 50-fold
CC       more potentiating activity on rat uterus than on guinea pig ileum
CC       (PubMed:4323853). {ECO:0000269|PubMed:4323853}.
CC   -!- FUNCTION: [Bradykinin-potentiating peptide Ahb1]: Synthetic peptide
CC       potentiates the bradykinin in vivo. {ECO:0000269|PubMed:11994001}.
CC   -!- FUNCTION: [Bradykinin-potentiating peptide Ahb2]: Synthetic peptide
CC       does not show any bradykinin-potentiating effects.
CC       {ECO:0000269|PubMed:11994001}.
CC   -!- FUNCTION: [C-type natriuretic peptide]: has a vasorelaxant activity in
CC       rat aortic strips and a diuretic potency in anesthetized rats (By
CC       similarity). May act by activating natriuretic receptors (NPR1 and/or
CC       NPR2). {ECO:0000250|UniProtKB:P0C7P5}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10519653,
CC       ECO:0000269|PubMed:10866809, ECO:0000269|PubMed:4323853,
CC       ECO:0000269|PubMed:4730295, ECO:0000269|Ref.5}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:10604536}.
CC   -!- MASS SPECTROMETRY: [Leu3-blomhotin]: Mass=1073.3; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:10866809};
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; AB020810; BAA36953.1; -; mRNA.
DR   PIR; A01254; XASNBA.
DR   PDB; 4AA2; X-ray; 1.99 A; P=103-113.
DR   PDB; 4APJ; X-ray; 2.60 A; P=103-113.
DR   AlphaFoldDB; P01021; -.
DR   MDRepo; P01021; -.
DR   SMR; P01021; -.
DR   IntAct; P01021; 1.
DR   EvolutionaryTrace; P01021; -.
DR   GO; GO:0005576; C:extracellular region; EXP:UniProtKB.
DR   GO; GO:0005179; F:hormone activity; IEA:InterPro.
DR   GO; GO:0006182; P:cGMP biosynthetic process; IEA:TreeGrafter.
DR   GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; IEA:TreeGrafter.
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; 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; 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_0000334172"
FT   PEPTIDE         31..41
FT                   /note="Blomhotin"
FT                   /evidence="ECO:0000269|PubMed:10519653"
FT                   /id="PRO_5000049304"
FT   PEPTIDE         31..40
FT                   /note="Bradykinin-potentiating peptide A"
FT                   /evidence="ECO:0000269|PubMed:4730295"
FT                   /id="PRO_5000049303"
FT   PROPEP          42..48
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000334173"
FT   PEPTIDE         49..59
FT                   /note="Leu3-blomhotin"
FT                   /evidence="ECO:0000269|PubMed:10866809"
FT                   /id="PRO_5000049305"
FT   PROPEP          60..66
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000334174"
FT   PEPTIDE         67..77
FT                   /note="Bradykinin-potentiating peptide C"
FT                   /evidence="ECO:0000269|PubMed:4323853"
FT                   /id="PRO_5000049306"
FT   PROPEP          78..84
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000334175"
FT   PEPTIDE         85..95
FT                   /note="Bradykinin-potentiating peptide B"
FT                   /evidence="ECO:0000269|Ref.5"
FT                   /id="PRO_5000049307"
FT   PROPEP          96..102
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000334176"
FT   PEPTIDE         103..113
FT                   /note="Bradykinin-potentiating peptide B"
FT                   /evidence="ECO:0000269|Ref.5"
FT                   /id="PRO_5000049308"
FT   PROPEP          114..116
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000334177"
FT   PEPTIDE         117..127
FT                   /note="Bradykinin-potentiating peptide E"
FT                   /evidence="ECO:0000305|PubMed:4323853"
FT                   /id="PRO_5000049309"
FT   PEPTIDE         117..121
FT                   /note="Bradykinin-potentiating peptide Ahb1"
FT                   /evidence="ECO:0000305|PubMed:17714693"
FT                   /id="PRO_0000342453"
FT   PROPEP          128..130
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000334178"
FT   PEPTIDE         131..136
FT                   /note="Bradykinin-potentiating peptide Ahb2"
FT                   /evidence="ECO:0000305|PubMed:17714693"
FT                   /id="PRO_0000342454"
FT   PROPEP          137..241
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000459644"
FT   PEPTIDE         242..263
FT                   /note="C-type natriuretic peptide"
FT                   /evidence="ECO:0000250|UniProtKB:Q27J49"
FT                   /id="PRO_5000049310"
FT   REGION          89..95
FT                   /note="Angiotensin-converting enzyme active site binding"
FT                   /evidence="ECO:0000269|PubMed:23056909,
FT                   ECO:0000269|PubMed:23082758"
FT   REGION          107..113
FT                   /note="Angiotensin-converting enzyme active site binding"
FT                   /evidence="ECO:0000269|PubMed:23056909,
FT                   ECO:0000269|PubMed:23082758"
FT   REGION          152..171
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          177..205
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        181..192
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        194..204
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            86
FT                   /note="Angiotensin-converting enzyme active site binding;
FT                   via amide nitrogen"
FT                   /evidence="ECO:0000269|PubMed:23056909"
FT   SITE            104
FT                   /note="Angiotensin-converting enzyme active site binding;
FT                   via amide nitrogen"
FT                   /evidence="ECO:0000269|PubMed:23056909"
FT   MOD_RES         31
FT                   /note="Pyrrolidone carboxylic acid"
FT                   /evidence="ECO:0000269|PubMed:10519653,
FT                   ECO:0000269|PubMed:4730295"
FT   MOD_RES         49
FT                   /note="Pyrrolidone carboxylic acid"
FT                   /evidence="ECO:0000269|PubMed:10866809"
FT   MOD_RES         67
FT                   /note="Pyrrolidone carboxylic acid"
FT                   /evidence="ECO:0000269|PubMed:4323853"
FT   MOD_RES         85
FT                   /note="Pyrrolidone carboxylic acid"
FT                   /evidence="ECO:0000269|Ref.5"
FT   MOD_RES         103
FT                   /note="Pyrrolidone carboxylic acid"
FT                   /evidence="ECO:0000269|Ref.5"
FT   MOD_RES         117
FT                   /note="Pyrrolidone carboxylic acid"
FT                   /evidence="ECO:0000303|PubMed:17714693"
FT   MOD_RES         131
FT                   /note="Pyrrolidone carboxylic acid"
FT                   /evidence="ECO:0000303|PubMed:17714693"
FT   DISULFID        247..263
FT                   /evidence="ECO:0000250|UniProtKB:P0DMD6"
FT   HELIX           106..109
FT                   /evidence="ECO:0007829|PDB:4APJ"
SQ   SEQUENCE   263 AA;  27339 MW;  407BA9A572BF5FC8 CRC64;
     MFVSRLAASG LLLLALMALS LDGKPVQQWS QGRPPGPPIP RLVVQQWSQG LPPGPPIPRL
     VVQQWSQGLP PGPPIPPLVV QQWSQGLPPR PKIPPLVVQQ WSQGLPPRPK IPPLVVQKWD
     PPPVSPPLLL QPHESPAGGT TALREELSLG PEAASGPAAA GADGGRSGSK APAALHRLSK
     SKGASATSAS ASRPMRDLRT DGKQARQNWA RMVNPDHHAV GGCCCGGGGG GARRLKGLVK
     KGVAKGCFGL KLDRIGTMSG LGC
//