ID   TOAP4_TITOB             Reviewed;          74 AA.
AC   A0A1E1WVR9;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   18-JAN-2017, sequence version 1.
DT   03-AUG-2022, entry version 7.
DE   RecName: Full=Peptide ToAP4 {ECO:0000303|PubMed:27917162, ECO:0000303|PubMed:31376652};
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:JAT91119.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Telson;
RX   PubMed=29561852; DOI=10.1371/journal.pone.0193739;
RA   de Oliveira U.C., Nishiyama M.Y. Jr., Dos Santos M.B.V.,
RA   Santos-da-Silva A.P., Chalkidis H.M., Souza-Imberg A., Candido D.M.,
RA   Yamanouye N., Dorce V.A.C., Junqueira-de-Azevedo I.L.M.;
RT   "Proteomic endorsed transcriptomic profiles of venom glands from Tityus
RT   obscurus and T. serrulatus scorpions.";
RL   PLoS ONE 13:e0193739-e0193739(2018).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS OF 23-39, AND PROBABLE AMIDATION AT
RP   LYS-39.
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   [3]
RP   FUNCTION, AND SYNTHESIS OF 23-39.
RX   PubMed=31376652; DOI=10.1016/j.biopha.2019.109152;
RA   Veloso Junior P.H.H., Simon K.S., de Castro R.J.A., Coelho L.C.,
RA   Erazo F.A.H., de Souza A.C.B., das Neves R.C., Lozano V.F., Schwartz E.F.,
RA   Tavares A.H., Mortari M.R., Junqueira-Kipnis A.P., Silva-Pereira I.,
RA   Bocca A.L.;
RT   "Peptides ToAP3 and ToAP4 decrease release of inflammatory cytokines
RT   through TLR-4 blocking.";
RL   Biomed. Pharmacother. 118:109152-109152(2019).
CC   -!- FUNCTION: Shows anti-inflammatory activities, since it decreases
CC       release of pro-inflammatory cytokines, and increases release of anti-
CC       inflammatory cytokines (PubMed:31376652). Acts by blocking the Toll-
CC       like receptor 4 (TLR4) (PubMed:31376652). Also increases MHC-II
CC       expression in LPS-stimulated cells (PubMed:31376652). Does not show
CC       antibacterial activity on Mycobacterium abscessus subsp. massiliense
CC       (PubMed:31376652). Does not show antifungal activity (PubMed:27917162).
CC       Has low hemolytic activity on human erythrocyte and low monocyte
CC       cytotoxicity (PubMed:31376652). In vivo, does not induce immune cell
CC       migration (PubMed:31376652). Helical wheel projections predict an
CC       amphipathic peptide with distinct hydrophobic and hydrophilic faces
CC       (Probable). {ECO:0000269|PubMed:27917162, ECO:0000269|PubMed:31376652,
CC       ECO:0000305|PubMed:27917162}.
CC   -!- SUBCELLULAR LOCATION: Secreted {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. Short antimicrobial peptide (group 4) family.
CC       {ECO:0000305}.
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DR   EMBL; GEMQ01000070; JAT91119.1; -; Transcribed_RNA.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
PE   1: Evidence at protein level;
KW   Amidation; Immunity; Secreted; Signal.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   PEPTIDE         23..39
FT                   /note="Peptide ToAP4"
FT                   /evidence="ECO:0000269|PubMed:31376652"
FT                   /id="PRO_5009115649"
FT   PROPEP          40..74
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000454903"
FT   MOD_RES         39
FT                   /note="Lysine amide"
FT                   /evidence="ECO:0000305|PubMed:27917162"
SQ   SEQUENCE   74 AA;  8489 MW;  686EC283F5E238F9 CRC64;
     MQIKHLITLF FLVLIVADQC SAFFSLIPSL IGGLVSAIKG GRRKREIAAQ IEQYRDLQKR
     EAELEELLDR LPMF