ID   CLIT_CLINE              Reviewed;         150 AA.
AC   Q9P4A2; P82314;
DT   27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 2.
DT   25-MAY-2022, entry version 53.
DE   RecName: Full=Clitocypin;
DE   AltName: Full=Cysteine protease inhibitor;
GN   Name=Cnc1;
OS   Clitocybe nebularis (Clouded agaric) (Lepista nebularis).
OC   Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC   Agaricomycetidae; Agaricales; Tricholomataceae; Clitocybe.
OX   NCBI_TaxID=117024;
RN   [1]
RP   PROTEIN SEQUENCE, NUCLEOTIDE SEQUENCE [MRNA] OF 18-146, FUNCTION, SUBUNIT,
RP   AND MASS SPECTROMETRY.
RC   TISSUE=Fruiting body;
RX   PubMed=10748021; DOI=10.1074/jbc.m001392200;
RA   Brzin J., Rogelj B., Popovic T., Strukelj B., Ritonja A.;
RT   "Clitocypin, a new type of cysteine proteinase inhibitor from fruit bodies
RT   of mushroom Clitocybe nebularis.";
RL   J. Biol. Chem. 275:20104-20109(2000).
RN   [2]
RP   PROTEIN SEQUENCE OF 1-8, FUNCTION, SUBUNIT, AND MASS SPECTROMETRY.
RX   PubMed=17223361; DOI=10.1016/j.pep.2006.11.015;
RA   Sabotic J., Galesa K., Popovic T., Leonardi A., Brzin J.;
RT   "Comparison of natural and recombinant clitocypins, the fungal cysteine
RT   protease inhibitors.";
RL   Protein Expr. Purif. 53:104-111(2007).
RN   [3]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=17132101; DOI=10.1515/bc.2006.194;
RA   Sabotic J., Gaser D., Rogelj B., Gruden K., Strukelj B., Brzin J.;
RT   "Heterogeneity in the cysteine protease inhibitor clitocypin gene family.";
RL   Biol. Chem. 387:1559-1566(2006).
RN   [4]
RP   TISSUE SPECIFICITY.
RX   PubMed=21672601; DOI=10.1016/j.biochi.2011.05.034;
RA   Sabotic J., Kilaru S., Budic M., Gasparic M.B., Gruden K., Bailey A.M.,
RA   Foster G.D., Kos J.;
RT   "Protease inhibitors clitocypin and macrocypin are differentially expressed
RT   within basidiomycete fruiting bodies.";
RL   Biochimie 93:1685-1693(2011).
RN   [5]
RP   BIOTECHNOLOGY.
RX   PubMed=26071808; DOI=10.1016/j.pestbp.2014.12.022;
RA   Smid I., Rotter A., Gruden K., Brzin J., Buh Gasparic M., Kos J., Zel J.,
RA   Sabotic J.;
RT   "Clitocypin, a fungal cysteine protease inhibitor, exerts its insecticidal
RT   effect on Colorado potato beetle larvae by inhibiting their digestive
RT   cysteine proteases.";
RL   Pestic. Biochem. Physiol. 122:59-66(2015).
CC   -!- FUNCTION: Binds and inhibits cysteine proteinases. Inhibits most
CC       strongly papain and cathepsin L, more weakly bromelain and cathepsin B
CC       while it is completely ineffective against cathepsin H.
CC       {ECO:0000269|PubMed:10748021}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10748021,
CC       ECO:0000269|PubMed:17223361}.
CC   -!- SUBCELLULAR LOCATION: Note=Not secreted. {ECO:0000269|PubMed:17132101}.
CC   -!- TISSUE SPECIFICITY: Uniformly expressed throughout the mature fruiting
CC       body (at mRNA and protein level). {ECO:0000269|PubMed:17132101,
CC       ECO:0000269|PubMed:21672601}.
CC   -!- MASS SPECTROMETRY: Mass=16863; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:10748021, ECO:0000269|PubMed:17223361};
CC   -!- BIOTECHNOLOGY: Promising candidate for a biopesticide. Slows growth and
CC       reduces survival of Colorado potato beetle (Leptinotarsa decemlineata)
CC       larvae in a concentration dependent manner. Younger larvae are more
CC       susceptible to the action of clitocypin. Expressed at low levels by
CC       transgenic potato reduced larval weight gain and delayed development.
CC       The inhibition of digestive cysteine proteases, intestains, by
CC       clitocypin was shown to be the underlying mode of action.
CC       {ECO:0000269|PubMed:26071808}.
CC   -!- SIMILARITY: Belongs to the protease inhibitor I48 family.
CC       {ECO:0000305}.
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DR   EMBL; AF230360; AAF81409.1; -; mRNA.
DR   AlphaFoldDB; Q9P4A2; -.
DR   SMR; Q9P4A2; -.
DR   MEROPS; I48.001; -.
DR   GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR   InterPro; IPR019508; Prot_inh_I48_clitocypin.
DR   Pfam; PF10467; Inhibitor_I48; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Protease inhibitor; Thiol protease inhibitor.
FT   CHAIN           1..150
FT                   /note="Clitocypin"
FT                   /id="PRO_0000195902"
FT   CONFLICT        119..124
FT                   /note="EEGGQQ -> VVGVQG (in Ref. 1; AAF81409)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        128
FT                   /note="T -> V (in Ref. 1; AAF81409)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        138
FT                   /note="G -> S (in Ref. 1; AAF81409)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        145
FT                   /note="R -> S (in Ref. 1; AAF81409)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   150 AA;  16854 MW;  3FB34C773CF71270 CRC64;
     LEDGIYRLRA VTTHNPDPGV GGEYATVEGA RRPVKAEPNT PPFFEQQIWQ VTRNADGQYT
     IKYQGLNTPF EYGFSYDELE PNAPVIAGDP KEYILQLVPS TADVYIIRAP IQRIGVDVEE
     GGQQNTLTYK FFPVDGSGGD RPAWRFTREE