ID   MELN_APICE              Reviewed;          70 AA.
AC   P0DPR9;
DT   16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT   16-JAN-2019, sequence version 1.
DT   25-MAY-2022, entry version 10.
DE   RecName: Full=Melittin-N {ECO:0000303|PubMed:24512991};
DE            Short=MEL-N {ECO:0000303|PubMed:24512991};
DE            Short=MLT;
DE   Flags: Precursor;
GN   Name=MELT;
OS   Apis cerana (Indian honeybee).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Hymenoptera; Apocrita; Aculeata; Apoidea; Apidae;
OC   Apis.
OX   NCBI_TaxID=7461;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], SYNTHESIS OF 44-69, FUNCTION, AND
RP   MUTAGENESIS OF ASN-61.
RX   PubMed=24512991; DOI=10.1016/j.peptides.2014.01.026;
RA   Park D., Jung J.W., Lee M.O., Lee S.Y., Kim B., Jin H.J., Kim J., Ahn Y.J.,
RA   Lee K.W., Song Y.S., Hong S., Womack J.E., Kwon H.W.;
RT   "Functional characterization of naturally occurring melittin peptide
RT   isoforms in two honey bee species, Apis mellifera and Apis cerana.";
RL   Peptides 53:185-193(2014).
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 (By similarity). Shows lower cytotoxicity when tested
CC       on E.coli and cancer cell lines than melittin, as well as lower anti-
CC       inflammatory properties and lower properties to interact to small
CC       unilamellar liposomes (PubMed:24512991). {ECO:0000250|UniProtKB:P01501,
CC       ECO:0000269|PubMed:24512991}.
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:0000250|UniProtKB:P01501}. 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. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the melittin family. {ECO:0000305}.
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DR   AlphaFoldDB; P0DPR9; -.
DR   SMR; P0DPR9; -.
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   1: Evidence at protein level;
KW   Allergen; Amidation; Antimicrobial; Cytolysis; Formylation; Hemolysis;
KW   Ion transport; Membrane; Porin; Secreted; Signal; Target cell membrane;
KW   Target membrane; Toxin; Transmembrane; Transport.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   PROPEP          22..43
FT                   /note="Removed by a dipeptidylpeptidase"
FT                   /evidence="ECO:0000250|UniProtKB:P01501"
FT                   /id="PRO_0000446007"
FT   PEPTIDE         44..69
FT                   /note="Melittin-N"
FT                   /evidence="ECO:0000250|UniProtKB:P01501"
FT                   /id="PRO_0000446008"
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"
FT   MUTAGEN         61
FT                   /note="N->S: Increase in cytotoxicity when tested on E.coli
FT                   and cancer cell lines, increase in anti-inflammatory
FT                   properties since it inhibits more potently IL-6 and TNF-
FT                   alpha (but not IL-1 beta) production in melittin-treated
FT                   cells, and increase in interaction to small unilamellar
FT                   liposomes."
FT                   /evidence="ECO:0000269|PubMed:24512991"
SQ   SEQUENCE   70 AA;  7612 MW;  60657BC091C23BB6 CRC64;
     MKFLVNVALV FMVVYISYIY AAPEPEPAPE PEAEADAEAD PEAGIGAVLK VLTTGLPALI
     NWIKRKRQQG