iVenomDB

Basic info

Organism	Apis mellifera
Taxonomy	Insecta > Hymenoptera > Apidae > Apis > Apis mellifera
Protein Description	Melittin precursor
Mass Weight	7584.76 Da
Isoelectric Point	4.69
Expression	Highly expressed in venom gland

Annotation

Function

Melittin: Main toxin of bee venom with strong hemolytic activity and antimicrobial activity. It has enhancing effects on bee venom phospholipase A2 activity. This amphipathic toxin binds to negatively charged membrane surface and forms pore by inserting into lipid bilayers inducing the leakage of ions and molecules and the enhancement of permeability that ultimately leads to cell lysis. It acts as a voltage-gated pore with higher selectivity for anions over cations. The ion conductance has been shown to be voltage- dependent. Self-association of melittin in membranes is promoted by high ionic strength, but not by the presence of negatively charged lipids. In vivo, intradermal injection into healthy human volunteers produce sharp pain sensation and an inflammatory response. It produces pain by activating primary nociceptor cells directly and indirectly due to its ability to activate plasma membrane phospholipase A2 and its pore- forming activity.

Pfam

PF01372

Melittin

Features

Feature key	Position	Length
Signal Peptide	1..21	21
Propeptide	22..43	22
Peptide	44..69	26

Cross-Reference

NCBI Nucleotide	NM_001011607.2
NCBI Protein	NP_001011607.1
UniProt	P01501

Sequence

CDS[Download]

ATGAAATTCTTAGTCAACGTTGCCCTTGTTTTTATGGTCGTGTACATTTCTTACATCTATGCGGCCCCTGAACCGGAACCGGCACCAGAGCCAGAGGCGGAGGCAGACGCGGAGGCAGATCCGGAAGCGGGAATTGGAGCAGTTCTGAAGGTATTAACCACAGGATTGCCCGCCCTCATAAGTTGGATTAAACGTAAGAGGCAACAGGGTTAG

Protein[Download]

MKFLVNVALVFMVVYISYIYAAPEPEPAPEPEAEADAEADPEAGIGAVLKVLTTGLPALISWIKRKRQQG

3D Structure

Alphafold Prediction

Publication

1.	Vlasak R., Unger-Ullmann C., Kreil G., Frischauf A.-M.; "Nucleotide sequence of cloned cDNA coding for honeybee prepromelittin."; Eur. J. Biochem. 135:123-126(1983).
2.	Hou C.-S., Guo L.-Q., Wang J.-R., You L.-F., Lin J.-F., Wu W.-H., Wang C.-S., Wang T.; Submitted (APR-2012) to the EMBL/GenBank/DDBJ databases.
3.	Habermann E., Jentsch J.; "Sequence analysis of melittin from tryptic and peptic degradation products."; Hoppe-Seyler's Z. Physiol. Chem. 348:37-50(1967).
4.	Sciani J.M., Marques-Porto R., Lourenco A. Jr., Orsi R.D., Junior R.S., Barraviera B., Pimenta D.C.; "Identification of a novel melittin isoform from Africanized Apis mellifera venom."; Peptides 31:1473-1479(2010).
5.	Ferreira Junior R.S., Sciani J.M., Marques-Porto R., Junior A.L., Orsi R.D., Barraviera B., Pimenta D.C.; "Africanized honey bee (Apis mellifera) venom profiling: Seasonal variation of melittin and phospholipase A(2) levels."; Toxicon 56:355-362(2010).
6.	Mollay C., Kreil G.; "Enhancement of bee venom phospholipase A2 activity by melittin, direct lytic factor from cobra venom and polymyxin B."; FEBS Lett. 46:141-144(1974).
7.	Sessa G., Freer J.H., Colacicco G., Weissmann G.; "Interaction of a lytic polypeptide, melittin, with lipid membrane systems."; J. Biol. Chem. 244:3575-3582(1969).
8.	Schroeder E., Luebke K., Lehmann M., Beetz I.; "Haemolytic activity and action on the surface tension of aqueous solutions of synthetic melittins and their derivatives."; Experientia 27:764-765(1971).
9.	Luebke K., Matthes S., Kloss G.; "Isolation and structure of N 1-formyl melittin."; Experientia 27:765-767(1971).
10.	Paull B.R., Yunginger J.W., Gleich G.J.; "Melittin: an allergen of honeybee venom."; J. Allergy Clin. Immunol. 59:334-338(1977).
11.	Faucon J.F., Dufourcq J., Lussan C.; "The self-association of melittin and its binding to lipids: an intrinsic fluorescence polarization study."; FEBS Lett. 102:187-190(1979).
12.	Lauterwein J., Brown L.R., Wuethrich K.; "High-resolution 1H-NMR studies of monomeric melittin in aqueous solution."; Biochim. Biophys. Acta 622:219-230(1980).
13.	Tosteson M.T., Tosteson D.C.; "The sting. Melittin forms channels in lipid bilayers."; Biophys. J. 36:109-116(1981).
14.	Kempf C., Klausner R.D., Weinstein J.N., Van Renswoude J., Pincus M., Blumenthal R.; "Voltage-dependent trans-bilayer orientation of melittin."; J. Biol. Chem. 257:2469-2476(1982).
15.	Hider R.C., Khader F., Tatham A.S.; "Lytic activity of monomeric and oligomeric melittin."; Biochim. Biophys. Acta 728:206-214(1983).
16.	Tosteson M.T., Holmes S.J., Razin M., Tosteson D.C.; "Melittin lysis of red cells."; J. Membr. Biol. 87:35-44(1985).
17.	Talbot J.C., Faucon J.F., Dufourcq J.; "Different states of self-association of melittin in phospholipid bilayers. A resonance energy transfer approach."; Eur. Biophys. J. 15:147-157(1987).
18.	Batenburg A.M., van Esch J.H., Leunissen-Bijvelt J., Verkleij A.J., de Kruijff B.; "Interaction of melittin with negatively charged phospholipids: consequences for lipid organization."; FEBS Lett. 223:148-154(1987).
19.	Shiomi K., Igarashi T., Yokota H., Nagashima Y., Ishida M.; "Isolation and structures of grammistins, peptide toxins from the skin secretion of the soapfish Grammistes sexlineatus."; Toxicon 38:91-103(2000).
20.	Yang L., Harroun T.A., Weiss T.M., Ding L., Huang H.W.; "Barrel-stave model or toroidal model? A case study on melittin pores."; Biophys. J. 81:1475-1485(2001).
21.	Park D., Jung J.W., Lee M.O., Lee S.Y., Kim B., Jin H.J., Kim J., Ahn Y.J., Lee K.W., Song Y.S., Hong S., Womack J.E., Kwon H.W.; "Functional characterization of naturally occurring melittin peptide isoforms in two honey bee species, Apis mellifera and Apis cerana."; Peptides 53:185-193(2014).
22.	Fennouri A., Mayer S.F., Schroeder T.B.H., Mayer M.; "Single channel planar lipid bilayer recordings of the melittin variant MelP5."; Biochim. Biophys. Acta 1859:2051-2057(2017).
23.	Dempsey C.E.; "The actions of melittin on membranes."; Biochim. Biophys. Acta 1031:143-161(1990).
24.	Chen J., Guan S.M., Sun W., Fu H.; "Melittin, the major pain-producing substance of bee venom."; Neurosci. Bull. 32:265-272(2016).
25.	Rady I., Siddiqui I.A., Rady M., Mukhtar H.; "Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy."; Cancer Lett. 402:16-31(2017).
26.	Terwilliger T.C., Eisenberg D.; "The structure of melittin. II. Interpretation of the structure."; J. Biol. Chem. 257:6016-6022(1982).
27.	Barnham K.J., Hewish D., Werkmeister J., Curtain C., Kirkpatrick A., Bartone N., Norton R., Rivett D.; Submitted (JUN-1998) to the PDB data bank.

Venom Protein Card