ID   TX4A_PARAW              Reviewed;         122 AA.
AC   P0DV62;
DT   25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT   25-MAY-2022, sequence version 1.
DT   03-AUG-2022, entry version 2.
DE   RecName: Full=Lycotoxin-Pa4a {ECO:0000303|PubMed:32707636};
DE            Short=LCTX-Pa4a {ECO:0000305};
DE   Flags: Precursor;
OS   Pardosa astrigera (Wolf spider).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Araneomorphae; Entelegynae; Lycosoidea; Lycosidae; Pardosa.
OX   NCBI_TaxID=317848;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SYNTHESIS OF 48-122.
RC   TISSUE=Venom gland;
RX   PubMed=32707636; DOI=10.3390/antibiotics9070422;
RA   Shin M.K., Hwang I.W., Kim Y., Kim S.T., Jang W., Lee S., Bang W.Y.,
RA   Bae C.H., Sung J.S.;
RT   "Antibacterial and anti-inflammatory effects of novel peptide toxin from
RT   the spider Pardosa astrigera.";
RL   Antibiotics 9:0-0(2020).
CC   -!- FUNCTION: Potent antibacterial peptide with anti-inflammatory
CC       properties. Inhibits both Gram-negative and Gram-positive bacteria by
CC       disrupting both the outer membrane and the cytosolic membrane of
CC       bacteria. Also downregulates the expression of pro-inflammatory
CC       mediators (cyclooxygenase-2 (PTGS2/COX2), nitric oxide-induced synthase
CC       (NOS2), IL-1 beta (IL1B), TNF-alpha (TNF)) and upregulates the level of
CC       anti-inflammatory cytokine (IL10) by inactivating mitogen-activated
CC       protein kinase signaling in a lipopolysaccharide-stimulated murine
CC       macrophage cell line. {ECO:0000269|PubMed:32707636}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:32707636}. Target
CC       cell membrane {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:32707636}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the neurotoxin 19 (CSTX) family. {ECO:0000305}.
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DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   InterPro; IPR019553; Spider_toxin_CSTX_knottin.
DR   InterPro; IPR011142; Spider_toxin_CSTX_Knottin_CS.
DR   Pfam; PF10530; Toxin_35; 1.
DR   PROSITE; PS60029; SPIDER_CSTX; 1.
PE   2: Evidence at transcript level;
KW   Antibiotic; Antimicrobial; Disulfide bond; Immunity; Innate immunity;
KW   Knottin; Membrane; Secreted; Signal; Target cell membrane; Target membrane.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   PROPEP          21..47
FT                   /evidence="ECO:0000305|PubMed:32707636"
FT                   /id="PRO_0000455162"
FT   CHAIN           48..122
FT                   /note="Lycotoxin-Pa4a"
FT                   /evidence="ECO:0000305|PubMed:32707636"
FT                   /id="PRO_0000455163"
FT   DISULFID        58..73
FT                   /evidence="ECO:0000250|UniProtKB:P58604,
FT                   ECO:0000305|PubMed:32707636"
FT   DISULFID        65..82
FT                   /evidence="ECO:0000250|UniProtKB:P58604,
FT                   ECO:0000305|PubMed:32707636"
FT   DISULFID        72..100
FT                   /evidence="ECO:0000250|UniProtKB:P58604,
FT                   ECO:0000305|PubMed:32707636"
FT   DISULFID        84..98
FT                   /evidence="ECO:0000250|UniProtKB:P58604,
FT                   ECO:0000305|PubMed:32707636"
SQ   SEQUENCE   122 AA;  14037 MW;  2FAE4905E91EA05C CRC64;
     MKLGIFFSVF FLAMIHSCLS ETNEDKNLES YFREDDLKAL SFGEYARAMM AESRKDNCIP
     KHHECTSRPK DCCKQNLMQF KCSCMTIIDK NNKETERCKC DNSIFQKVAK TSVNIGKAVV
     TK