BNP_GLOBL
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 25-MAY-2022, entry version 79.
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 (1.99 ANGSTROMS) OF 85-95 AND 103-113 (BPP-B) IN
RP COMPLEX WITH DROSOPHILA 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 (2.6 ANGSTROMS) OF 85-95 AND 103-113 IN COMPLEX WITH
RP HUMAN 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]: 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: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=104-113.
DR PDB; 4APJ; X-ray; 2.60 A; P=104-113.
DR PDBsum; 4AA2; -.
DR PDBsum; 4APJ; -.
DR AlphaFoldDB; P01021; -.
DR SMR; P01021; -.
DR IntAct; P01021; 1.
DR MINT; P01021; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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 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:0000255"
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:0000255"
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:0000255"
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:0000255"
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:0000255"
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:0000255"
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..239
FT /evidence="ECO:0000255"
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 PEPTIDE 242..263
FT /note="C-type natriuretic peptide"
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 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"
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
