HORDB

General Information

ID: hor005987
Uniprot ID: P68515
Protein name: Bradykinin-potentiating peptide S3
Gene name: NA
Organism: Bothrops insularis (Golden lancehead) (Lachesis insularis)
Family: Bradykinin-potentiating peptide family; Natriuretic peptide family
Source: animal
Expression: Expressed by the venom gland.
Disease: NA
Comments: NA
Taxonomy: Bothrops (genus), Crotalinae (subfamily), Viperidae (family), Colubroidea (superfamily), Serpentes (infraorder), Toxicofera , Episquamata , Unidentata , Bifurcata , Squamata (order), Lepidosauria (class), Sauria , Sauropsida , Amniota , Tetrapoda , Dipnotetrapodomorpha , Sarcopterygii (superclass), Euteleostomi , Teleostomi , Gnathostomata , Vertebrata , Craniata (subphylum), Chordata (phylum), Deuterostomia , Bilateria , Eumetazoa , Metazoa (kingdom), Opisthokonta , Eukaryota (superkingdom),cellular organisms
GO MF: GO:0004857 enzyme inhibitor activity; GO:0005179 hormone activity; GO:0008191 metalloendopeptidase inhibitor activity; GO:0030414 peptidase inhibitor activity; GO:0090729 toxin activity
GO BP: GO:0007165 signal transduction; GO:0008217 regulation of blood pressure; GO:0035821 modulation of process of another organism; GO:0042311 vasodilation; GO:0097746 blood vessel diameter maintenance
GO CC: GO:0005576 extracellular region; GO:0005737 cytoplasm; GO:0005829 cytosol

Sequence Information

Sequence: QGGWPRPGPEIPP
Length: 13
Propeptide: MVLSRLAASGLLLLALLALSVDGKPVQQWAQGGWPRPGPEIPPLKVQQWAQGGWPRPGPEIPPLTVQQWAQNWPHPQIPPLTVQQWAQLGPPPRPQIPPLEVQQWAQGRAPHPPIPPAPLQKWAPVQKWAPLLQPHESPASGTTALREELSLGPEAASGVPSAGAEVGRSGSKAPAAPHRLSKSKGAAATSAASRPMRDLRPDGKQARQNWGRMVHHDHHAAVGGGGGGGGGGARRLKGLAKKGAAKGCFGLKLDRIGTMSGLGC
Signal peptide: MVLSRLAASGLLLLALLALSVDG
Modification: T1 Pyrrolidone carboxylic acid
Glycosylation: NA
Mutagenesis: NA

Activity

Function: [Bradykinin-potentiating peptide 5a]: Modestly inhibits ACE (with highest affinity for the N-site) and reveals strong bradykinin-potentiating activity. Induces nitric oxide (NO) production depended on muscarinic acetylcholine receptor M1 subtype (CHRM1) and bradykinin B2 receptor (BDKRB2) activation. Both these receptors contribute to the vasodilation induced by this peptide that may have an indirect action on BDKRB2 and a direct agonistic action on CHRM1.; [Bradykinin-potentiating peptide 10c]: Peptide with several activities. It inhibits the activity of the angiotensin-converting enzyme (ACE) by a preferential interaction with its C-domain (PubMed:11994001). It evokes transient hypotension (-14 mmHg) similar to that evoked by 0,5 ug of bradykinin, when injected alone into rats. It has a high bradykinin-potentiating effect (120%), when 60 nmol of BPP-10c are coinjected with 0.5 ug of bradykinin into rats (PubMed:22869554). Does not affect angiotensin-1 pressor effects. Shows potent and long-lasting antihypertensive activity as well as a reduction of the heart rate (PubMed:17475904). It also binds and dose-dependently promotes the activation of cytosolic argininosuccinate synthase (ASS1), an enzyme that catalyzes the conversion of citrulline, L-aspartate and ATP to argininosuccinate, AMP and pyrophosphate. It also enhances ASS1-dependent arginine production in HEK 293 cells, as well as in spontaneous hypertensive rat (SHR) and Wistar rat plasma. In addition, it induces the production of nitric-oxide (NO) by HUVEC cells via the endothelial nitric-oxide synthase (NOS3), which use arginine as a substrate and produce NO. It has been shown to be internalized by ASS1-expressing endothelial (HUVEC) and kidney (HEK 293) cells, and is detected homogenously distributed within the cell cytoplasm for up to 2 hours (PubMed:19491403).
Mechanism: NA
Cross BBB: NA
Target: NA
Target Unid: NA
IC50: NA
EC50: NA
ED50: NA
kd: NA
Half life: NA

Structure

Disulfide bond: NA
Structure ID: AF-P68515-F1(AlphaFold_DB_ID)

Structure: (PDB_ID-from https://www.rcsb.org/; AlphaFold_DB_ID-from https://alphafold.ebi.ac.uk/; hordbxxxxxx_AF2.pdb was predicted structure by AlphaFold2; hordbxxxxxx_ESM.pdb was predicted structure by ESMFold)

hor005987_AF2.pdb

hor005987_ESM.pdb

Physical Information

Mass:	160177	Formula:	C64H94N18O17
Absent amino acids:	ACDFHKLMNSTVY	Common amino acids:	P
pI:	6.41	Basic residues:	1
Polar residues:	3	Hydrophobic residues:	2
Hydrophobicity:	-131.54	Boman Index:	-1720
Half-Life:	0.8 hour	Half-Life Yeast:	10 min
Half-Life E.Coli:	>10 hour	Aliphatic Index	30
Instability Index:	7801.54	Extinction Coefficient cystines:	5500
Absorbance 280nm:	458.33

Literature

PubMed ID: 12459276
Title: A survey of gene expression and diversity in the venom glands of the pitviper snake Bothrops insularis through the generation of expressed sequence tags (ESTs).
PubMed ID: 2386615
Title: Primary structure and biological activity of bradykinin potentiating peptides from Bothrops insularis snake venom.
PubMed ID: 15912471
Title: Fast analysis of low molecular mass compounds present in snake venom: identification of ten new pyroglutamate-containing peptides.
PubMed ID: 18200607
Title: Peptide fingerprinting of snake venoms by direct infusion nano-electrospray ionization mass spectrometry: potential use in venom identification and taxonomy.
PubMed ID: 11994001
Title: Selective inhibition of the C-domain of angiotensin I converting enzyme by bradykinin potentiating peptides.
PubMed ID: 17475904
Title: Do the cardiovascular effects of angiotensin-converting enzyme (ACE) I involve ACE-independent mechanisms? new insights from proline-rich peptides of Bothrops jararaca.
PubMed ID: 19491403
Title: Argininosuccinate synthetase is a functional target for a snake venom anti-hypertensive peptide: role in arginine and nitric oxide production.
PubMed ID: 21185808
Title: Bj-PRO-5a, a natural angiotensin-converting enzyme inhibitor, promotes vasodilatation mediated by both bradykinin B₂and M1 muscarinic acetylcholine receptors.
PubMed ID: 22869554
Title: Peptidomics of three Bothrops snake venoms: insights into the molecular diversification of proteomes and peptidomes.