ID   MELS_APICE              Reviewed;          77 AA.
AC   Q8LW54;
DT   01-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   27-MAR-2024, entry version 80.
DE   RecName: Full=Melittin {ECO:0000303|Ref.2};
DE            Short=MEL;
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;
OC   Anthophila; Apidae; Apis.
OX   NCBI_TaxID=7461;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Le H.Q., Le B.T.;
RT   "Gene encoding melittin in honeybee Apis cerana colleted in Hanoi
RT   Vietnam.";
RL   Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   PROTEIN SEQUENCE OF 51-76, AMIDATION AT GLN-76, AND SUBCELLULAR LOCATION.
RA   Kreil G.;
RT   "Structure of melittin isolated from two species of honey bees.";
RL   FEBS Lett. 33:241-244(1973).
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:0000269|Ref.2}. Target cell
CC       membrane {ECO:0000250|UniProtKB:P01501}. Note=Alpha-helical peptides
CC       form toroidal pores in the prey. {ECO:0000250|UniProtKB:P01501}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|Ref.2}.
CC   -!- ALLERGEN: Causes an allergic reaction in human.
CC       {ECO:0000250|UniProtKB:P01501}.
CC   -!- SIMILARITY: Belongs to the melittin family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Why Pooh luvvs hunny - Issue
CC       12 of July 2001;
CC       URL="https://web.expasy.org/spotlight/back_issues/012";
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DR   EMBL; AJ489619; CAD33921.1; -; Genomic_DNA.
DR   PIR; A01762; MEHBCI.
DR   AlphaFoldDB; Q8LW54; -.
DR   BMRB; Q8LW54; -.
DR   SMR; Q8LW54; -.
DR   Proteomes; UP000694868; Unplaced.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0044218; C:other organism cell membrane; IEA:UniProtKB-KW.
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:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW.
DR   GO; GO:0006811; P:monoatomic 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; Direct protein sequencing;
KW   Formylation; Hemolysis; Ion transport; Membrane; Porin; Secreted; Signal;
KW   Target cell membrane; Target membrane; Toxin; Transmembrane; Transport.
FT   SIGNAL          1..30
FT                   /evidence="ECO:0000255"
FT   PROPEP          31..50
FT                   /note="Removed by a dipeptidylpeptidase"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000035146"
FT   PEPTIDE         51..76
FT                   /note="Melittin"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="PRO_0000035147"
FT   SITE            64
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         51
FT                   /note="N-formylglycine; partial"
FT                   /evidence="ECO:0000250|UniProtKB:P01501"
FT   MOD_RES         76
FT                   /note="Glutamine amide"
FT                   /evidence="ECO:0000269|Ref.2"
SQ   SEQUENCE   77 AA;  8515 MW;  091BEF7CE6019374 CRC64;
     MKFLVNVALV FYGRVHFLHL CVHFLHLWAP EPEPAPEAEA EADAEADPEA GIGAVLKVLT
     TGLPALISWI KRKRQQG
//