ID   VKT_MACLN               Reviewed;          95 AA.
AC   I2G9B4;
DT   01-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT   11-JUL-2012, sequence version 1.
DT   25-MAY-2022, entry version 22.
DE   RecName: Full=Kunitz-type serine protease inhibitor PIVL;
DE   Flags: Precursor;
OS   Macrovipera lebetina transmediterranea (Blunt-nosed viper) (Vipera lebetina
OS   transmediterranea).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Viperidae; Viperinae; Macrovipera.
OX   NCBI_TaxID=384075;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, PYROGLUTAMATE FORMATION AT
RP   GLN-25, AND MASS SPECTROMETRY.
RC   TISSUE=Venom, and Venom gland;
RX   PubMed=23262217; DOI=10.1016/j.matbio.2012.11.015;
RA   Morjen M., Kallech-Ziri O., Bazaa A., Othman H., Mabrouk K.,
RA   Zouari-Kessentini R., Sanz L., Calvete J.J., Srairi-Abid N., El Ayeb M.,
RA   Luis J., Marrakchi N.;
RT   "PIVL, a new serine protease inhibitor from Macrovipera lebetina
RT   transmediterranea venom, impairs motility of human glioblastoma cells.";
RL   Matrix Biol. 32:52-62(2013).
CC   -!- FUNCTION: Serine protease inhibitor that inhibits trypsin. Exhibits an
CC       anti-tumor effect and displays integrin inhibitory activity without
CC       being cytotoxic. Is able to dose-dependently inhibit the adhesion,
CC       migration and invasion of human glioblastoma U87 cells. Also impairs
CC       the function of alphavbeta3 and to a lesser extent, the activity of
CC       alphavbeta6, alphavbeta5, alpha1beta1 and alpha5beta1 integrins.
CC       {ECO:0000269|PubMed:23262217}.
CC   -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:23262217}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC   -!- MASS SPECTROMETRY: Mass=7691.7; Method=MALDI; Note=Average mass.;
CC       Evidence={ECO:0000269|PubMed:23262217};
CC   -!- MISCELLANEOUS: Does not inhibit chymotrypsin.
CC       {ECO:0000305|PubMed:23262217}.
CC   -!- MISCELLANEOUS: When intracerebroventricularly injected into mice, does
CC       not cause any toxic symptoms until a dose of 2 ug.
CC       {ECO:0000305|PubMed:23262217}.
CC   -!- SIMILARITY: Belongs to the venom Kunitz-type family. {ECO:0000305}.
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DR   EMBL; HE800183; CCH15044.1; -; mRNA.
DR   AlphaFoldDB; I2G9B4; -.
DR   SMR; I2G9B4; -.
DR   MEROPS; I02.062; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR   CDD; cd00109; KU; 1.
DR   Gene3D; 4.10.410.10; -; 1.
DR   InterPro; IPR002223; Kunitz_BPTI.
DR   InterPro; IPR036880; Kunitz_BPTI_sf.
DR   InterPro; IPR020901; Prtase_inh_Kunz-CS.
DR   Pfam; PF00014; Kunitz_BPTI; 1.
DR   PRINTS; PR00759; BASICPTASE.
DR   SMART; SM00131; KU; 1.
DR   SUPFAM; SSF57362; SSF57362; 1.
DR   PROSITE; PS00280; BPTI_KUNITZ_1; 1.
DR   PROSITE; PS50279; BPTI_KUNITZ_2; 1.
PE   1: Evidence at protein level;
KW   Disulfide bond; Protease inhibitor; Pyrrolidone carboxylic acid; Secreted;
KW   Serine protease inhibitor; Signal.
FT   SIGNAL          1..24
FT   CHAIN           25..91
FT                   /note="Kunitz-type serine protease inhibitor PIVL"
FT                   /id="PRO_0000422086"
FT   PROPEP          92..95
FT                   /id="PRO_0000422087"
FT   DOMAIN          31..81
FT                   /note="BPTI/Kunitz inhibitor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   REGION          65..67
FT                   /note="Responsible for the anti-cancer effect"
FT   SITE            41..42
FT                   /note="Reactive bond"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         25
FT                   /note="Pyrrolidone carboxylic acid"
FT                   /evidence="ECO:0000269|PubMed:23262217"
FT   DISULFID        31..81
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   DISULFID        40..64
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   DISULFID        56..77
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   VARIANT         67
FT                   /note="N -> S"
SQ   SEQUENCE   95 AA;  10569 MW;  CF3FE5D9C82B97F7 CRC64;
     MSSGGLLLLL GLLTLWAELT PVSSQDRPKF CYLPADPAEC NAYMPRFYYD SASNKCKEFI
     YGGCRGNANN FKNRAECRHT CVASRKGIQP RIASN