ID   TOAP2_TITOB             Reviewed;          79 AA.
AC   A0A1D3IXJ5;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   30-NOV-2016, sequence version 1.
DT   03-AUG-2022, entry version 5.
DE   RecName: Full=Antimicrobial peptide ToAP2 {ECO:0000303|PubMed:27917162};
DE   Flags: Precursor;
OS   Tityus obscurus (Amazonian scorpion) (Tityus cambridgei).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Buthida; Buthoidea; Buthidae; Tityus.
OX   NCBI_TaxID=1221240;
RN   [1] {ECO:0000312|EMBL:SBQ16531.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS OF 24-49, AND MUTAGENESIS OF GLY-32;
RP   VAL-39 AND 46-LYS-LYS-47.
RC   TISSUE=Venom gland;
RX   PubMed=27917162; DOI=10.3389/fmicb.2016.01844;
RA   Guilhelmelli F., Vilela N., Smidt K.S., de Oliveira M.A.,
RA   da Cunha Morales Alvares A., Rigonatto M.C., da Silva Costa P.H.,
RA   Tavares A.H., de Freitas S.M., Nicola A.M., Franco O.L., Derengowski L.D.,
RA   Schwartz E.F., Mortari M.R., Bocca A.L., Albuquerque P., Silva-Pereira I.;
RT   "Activity of scorpion venom-derived antifungal peptides against planktonic
RT   cells of Candida spp. and Cryptococcus neoformans and Candida albicans
RT   biofilms.";
RL   Front. Microbiol. 7:1844-1844(2016).
RN   [2]
RP   FUNCTION.
RX   PubMed=29848960; DOI=10.3390/toxins10060219;
RA   Marques-Neto L.M., Trentini M.M., das Neves R.C., Resende D.P.,
RA   Procopio V.O., da Costa A.C., Kipnis A., Mortari M.R., Schwartz E.F.,
RA   Junqueira-Kipnis A.P.;
RT   "Antimicrobial and chemotactic activity of scorpion-derived peptide, ToAP2,
RT   against Mycobacterium massiliensis.";
RL   Toxins 10:0-0(2018).
CC   -!- FUNCTION: Antimicrobial peptide (PubMed:27917162, PubMed:29848960).
CC       Shows antibacterial activity against all M.massiliense bacterial
CC       strains tested (PubMed:29848960). Has antifungal activity against
CC       Candida spp. and two Cryptococcus neoformans strains with MICs values
CC       ranging from 6.25 to 200 uM (PubMed:27917162). Also shows an inhibitory
CC       activity on C.albicans biofilms at high concentrations
CC       (PubMed:27917162). Exhibits chemotactic activity for monocytes,
CC       neutrophils, and eosinophils (PubMed:29848960). Shows low cytotoxic
CC       activity and has weak hemolytic activity on human erythrocytes
CC       (PubMed:27917162, PubMed:29848960). In vivo, treatment of infected mice
CC       with M.massiliense reduces the bacterial load in the liver, lung, and
CC       spleen (PubMed:29848960). {ECO:0000269|PubMed:27917162,
CC       ECO:0000269|PubMed:29848960}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:27917162}. Target
CC       cell membrane {ECO:0000305}. Note=Has an amphipathic alpha-helical
CC       conformation. {ECO:0000305|PubMed:27917162}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:27917162}.
CC   -!- SIMILARITY: Belongs to the non-disulfide-bridged peptide (NDBP)
CC       superfamily. Medium-length antimicrobial peptide (group 3) family.
CC       {ECO:0000305}.
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DR   EMBL; LT576030; SBQ16531.1; -; mRNA.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR   GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR   GO; GO:0050832; P:defense response to fungus; IEA:UniProtKB-KW.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW.
PE   1: Evidence at protein level;
KW   Antibiotic; Antimicrobial; Chemotaxis; Cleavage on pair of basic residues;
KW   Fungicide; Immunity; Innate immunity; Membrane; Secreted; Signal;
KW   Target cell membrane; Target membrane.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   PEPTIDE         24..49
FT                   /note="Antimicrobial peptide ToAP2"
FT                   /evidence="ECO:0000305|PubMed:27917162"
FT                   /id="PRO_5008915665"
FT   PROPEP          50..79
FT                   /evidence="ECO:0000305|PubMed:27917162"
FT                   /id="PRO_0000454901"
FT   MUTAGEN         32
FT                   /note="G->L: In ToAP2S1; Loss of antifungal activity and
FT                   increase in hemolytic activity against human erythrocytes."
FT                   /evidence="ECO:0000269|PubMed:27917162"
FT   MUTAGEN         39
FT                   /note="V->L: In ToAP2S1; Loss of antifungal activity and
FT                   increase in hemolytic activity against human erythrocytes."
FT                   /evidence="ECO:0000269|PubMed:27917162"
FT   MUTAGEN         46..47
FT                   /note="KK->LL: In ToAP2S1; Loss of antifungal activity and
FT                   increase in hemolytic activity against human erythrocytes."
FT                   /evidence="ECO:0000269|PubMed:27917162"
SQ   SEQUENCE   79 AA;  9486 MW;  48A1338D758F321C CRC64;
     MQFKKQLLVI FFAYFLVVNE SEAFFGTLFK LGSKLIPGVM KLFSKKKERS LMKRELKNLY
     DPYQRSVEME RLLKELPLY