ID   MEL_POLHE               Reviewed;          70 AA.
AC   P59261;
DT   01-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-2003, sequence version 1.
DT   25-MAY-2022, entry version 69.
DE   RecName: Full=Melittin {ECO:0000303|PubMed:12939801};
DE            Short=MEL;
DE            Short=MLT;
DE   Flags: Precursor;
GN   Name=MELT;
OS   Polistes hebraeus (Paper wasp).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Hymenoptera; Apocrita; Aculeata; Vespoidea;
OC   Vespidae; Polistinae; Polistini; Polistes.
OX   NCBI_TaxID=202806;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RX   PubMed=12939801;
RA   Shi W.J., Zhang S.F., Zhang C.-X., Cheng J.A.;
RT   "Cloning and comparative analysis of the venom prepromelittin genes from
RT   four wasp species.";
RL   Yi Chuan Xue Bao 30:555-559(2003).
CC   -!- FUNCTION: Main toxin of bee venom with strong hemolytic activity and
CC       antimicrobial activity. It has enhancing effects on bee venom
CC       phospholipase A2 activity. This amphipathic toxin binds to negatively
CC       charged membrane surface and forms pore by inserting into lipid
CC       bilayers inducing the leakage of ions and molecules and the enhancement
CC       of permeability that ultimately leads to cell lysis. It acts as a
CC       voltage-gated pore with higher selectivity for anions over cations. The
CC       ion conductance has been shown to be voltage-dependent. Self-
CC       association of melittin in membranes is promoted by high ionic
CC       strength, but not by the presence of negatively charged lipids. In
CC       vivo, intradermal injection into healthy human volunteers produce sharp
CC       pain sensation and an inflammatory response. It produces pain by
CC       activating primary nociceptor cells directly and indirectly due to its
CC       ability to activate plasma membrane phospholipase A2 and its pore-
CC       forming activity. {ECO:0000250|UniProtKB:P01501}.
CC   -!- SUBUNIT: Monomer (in solution and for integration into membranes),
CC       homotetramer (in solution and potentially as a toroidal pore in
CC       membranes), and potenially homomultimer (as a toroidal pore in
CC       membranes). {ECO:0000250|UniProtKB:P01501}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:12939801}. Target
CC       cell membrane {ECO:0000250|UniProtKB:P01501}. Note=Alpha-helical
CC       peptides form toroidal pores in the prey.
CC       {ECO:0000250|UniProtKB:P01501}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:12939801}.
CC   -!- SIMILARITY: Belongs to the melittin family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AF487909; AAO12203.1; -; mRNA.
DR   AlphaFoldDB; P59261; -.
DR   SMR; P59261; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0046930; C:pore complex; IEA:UniProtKB-KW.
DR   GO; GO:0015288; F:porin activity; IEA:UniProtKB-KW.
DR   GO; GO:0004860; F:protein kinase inhibitor activity; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   GO; GO:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
DR   GO; GO:0006811; P:ion transport; IEA:UniProtKB-KW.
DR   InterPro; IPR002116; Melittin/Api_allergen.
DR   Pfam; PF01372; Melittin; 1.
PE   3: Inferred from homology;
KW   Amidation; Antimicrobial; Cytolysis; Formylation; Hemolysis; Ion transport;
KW   Membrane; Porin; Secreted; Signal; Target cell membrane; Target membrane;
KW   Toxin; Transmembrane; Transport.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000250"
FT   PROPEP          22..43
FT                   /note="Removed by a dipeptidylpeptidase"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000035150"
FT   PEPTIDE         44..69
FT                   /note="Melittin"
FT                   /evidence="ECO:0000250|UniProtKB:P01501"
FT                   /id="PRO_0000035151"
FT   SITE            57
FT                   /note="Important for the flexibility at the center of the
FT                   helix, flexibility that is important for the stability of
FT                   the voltage-gated pore"
FT                   /evidence="ECO:0000250|UniProtKB:P01501"
FT   MOD_RES         44
FT                   /note="N-formylglycine; partial"
FT                   /evidence="ECO:0000250|UniProtKB:P01501"
FT   MOD_RES         69
FT                   /note="Glutamine amide"
FT                   /evidence="ECO:0000250|UniProtKB:P01501"
SQ   SEQUENCE   70 AA;  7513 MW;  DA70167086C9560C CRC64;
     MKFLVNVALV FMVVYISFIY AAPEPEPAPE AEAEADAEAD PEAGIGAVLK VLATGLPALI
     SWIKRKRQQG