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NDB4N_TITSE
ID   NDB4N_TITSE             Reviewed;          73 AA.
AC   S6D3A7;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-OCT-2013, sequence version 1.
DT   25-MAY-2022, entry version 11.
DE   RecName: Full=Antimicrobial peptide TsAP-2 {ECO:0000303|PubMed:23770440};
DE   AltName: Full=Non-disulfide-bridged peptide 4.23 {ECO:0000303|PubMed:24184590};
DE            Short=NDBP-4.23 {ECO:0000303|PubMed:24184590};
DE   Flags: Precursor;
OS   Tityus serrulatus (Brazilian scorpion).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Buthida; Buthoidea; Buthidae; Tityus.
OX   NCBI_TaxID=6887;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SYNTHESIS OF 23-39, MUTAGENESIS OF
RP   GLY-29; 32-GLY-GLY-33 AND SER-36, MASS SPECTROMETRY, AMIDATION AT LYS-39,
RP   AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom, and Venom gland;
RX   PubMed=23770440; DOI=10.1016/j.biochi.2013.06.003;
RA   Guo X., Ma C., Du Q., Wei R., Wang L., Zhou M., Chen T., Shaw C.;
RT   "Two peptides, TsAP-1 and TsAP-2, from the venom of the Brazilian yellow
RT   scorpion, Tityus serrulatus: evaluation of their antimicrobial and
RT   anticancer activities.";
RL   Biochimie 95:1784-1794(2013).
RN   [2]
RP   FUNCTION, AND SYNTHESIS OF 23-39.
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, BIOPHYSICOCHEMICAL PROPERTIES, AND BIOASSAY.
RX   PubMed=27567704; DOI=10.1016/j.toxicon.2016.08.016;
RA   Daniele-Silva A., Machado R.J., Monteiro N.K., Estrela A.B., Santos E.C.,
RA   Carvalho E., Araujo Junior R.F., Melo-Silveira R.F., Rocha H.A.,
RA   Silva-Junior A.A., Fernandes-Pedrosa M.F.;
RT   "Stigmurin and TsAP-2 from Tityus stigmurus scorpion venom: assessment of
RT   structure and therapeutic potential in experimental sepsis.";
RL   Toxicon 121:10-21(2016).
RN   [4]
RP   NOMENCLATURE.
RX   PubMed=24184590; DOI=10.1016/j.peptides.2013.10.021;
RA   Almaaytah A., Albalas Q.;
RT   "Scorpion venom peptides with no disulfide bridges: a review.";
RL   Peptides 51:35-45(2014).
CC   -!- FUNCTION: Antimicrobial peptide (PubMed:23770440, PubMed:27917162,
CC       PubMed:27567704). Has a high antibacterial activity against the Gram-
CC       positive bacterium S.aureus (MIC=5-17.30 uM), the methicillin-resistant
CC       S.aureus (MRSA) (MIC=17.30 uM), and E.faecalis (MIC=69.23 uM)
CC       (PubMed:23770440, PubMed:27567704). Has antifungal activity against
CC       Candida spp. and one Cryptococcus neoformans strains with MICs values
CC       ranging from 6.25 to 100 uM (PubMed:23770440, PubMed:27917162,
CC       PubMed:27567704). Shows also an inhibitory activity on C.albicans
CC       biofilms at high concentrations (PubMed:27917162).Has a moderate
CC       hemolytic potency (18% at 20 uM) (PubMed:23770440, PubMed:27567704).
CC       Also inhibits the growth of the five cancer cell lines tested
CC       (PubMed:23770440). In the model of polymicrobial sepsis, it exhibits an
CC       antibiotic effect, reducing the levels of microorganisms in the
CC       infectious focus and the inflammatory responses in the lung and cecum
CC       of septic animals (PubMed:27567704). {ECO:0000269|PubMed:23770440,
CC       ECO:0000269|PubMed:27567704, ECO:0000269|PubMed:27917162}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Stable to pH variation. {ECO:0000269|PubMed:27567704};
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:23770440}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:23770440}.
CC   -!- MASS SPECTROMETRY: Mass=1733.32; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:23770440};
CC   -!- MISCELLANEOUS: The primary structure of the mature peptide is identical
CC       to that of NDBP4.23-like from Tityus costatus (AC Q5G8B5).
CC       {ECO:0000305}.
CC   -!- MISCELLANEOUS: Does not inhibit the Gram-negative bacterium E.coli
CC       (PubMed:23770440). Does not show antifungal activity against Candida
CC       glabrata (ATCC90030) (MIC>400 uM) (PubMed:27917162).
CC       {ECO:0000269|PubMed:23770440, ECO:0000269|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; HF677517; CCQ98792.1; -; mRNA.
DR   AlphaFoldDB; S6D3A7; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
PE   1: Evidence at protein level;
KW   Amidation; Antibiotic; Antimicrobial; Cytolysis; Fungicide; Hemolysis;
KW   Secreted; Signal.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000305|PubMed:23770440"
FT   PEPTIDE         23..39
FT                   /note="Antimicrobial peptide TsAP-2"
FT                   /evidence="ECO:0000269|PubMed:23770440"
FT                   /id="PRO_5001155573"
FT   PROPEP          45..73
FT                   /evidence="ECO:0000305|PubMed:23770440"
FT                   /id="PRO_5001155574"
FT   MOD_RES         39
FT                   /note="Lysine amide"
FT                   /evidence="ECO:0000269|PubMed:23770440"
FT   MUTAGEN         29
FT                   /note="G->K: Important increase of antimicrobial and
FT                   hemolytic activities; when associated wiTH 32-K-K-33 AND K-
FT                   36."
FT                   /evidence="ECO:0000269|PubMed:23770440"
FT   MUTAGEN         32..33
FT                   /note="GG->KK: Important increase of antimicrobial and
FT                   hemolytic activities; when associated with K-29 AND K-36."
FT                   /evidence="ECO:0000269|PubMed:23770440"
FT   MUTAGEN         36
FT                   /note="S->K: Important increase of antimicrobial and
FT                   hemolytic activities; when associated with K-29 AND 32-K-K-
FT                   33."
FT                   /evidence="ECO:0000269|PubMed:23770440"
SQ   SEQUENCE   73 AA;  8391 MW;  8E0E39B93B61F561 CRC64;
     MQIKHLITIF FLVLIVADHC HAFLGMIPGL IGGLISAFKG RRKREITSQI EQYRNLQKRE
     AELENLLANL PVY
 
 
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