ID   VKT2I_HETCR             Reviewed;          85 AA.
AC   A0A6B7FBD3;
DT   02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT   17-JUN-2020, sequence version 1.
DT   25-MAY-2022, entry version 9.
DE   RecName: Full=PI-stichotoxin-Hcr2i {ECO:0000305};
DE            Short=PI-SHTX-Hcr2i {ECO:0000305};
DE   AltName: Full=Kunitz-peptide HCIQ2c1 {ECO:0000303|PubMed:32144281};
DE   Flags: Precursor;
GN   Name=iq2c1 {ECO:0000303|PubMed:32144281};
OS   Heteractis crispa (Leathery sea anemone) (Radianthus macrodactylus).
OC   Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria;
OC   Stichodactylidae; Heteractis.
OX   NCBI_TaxID=175771;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND RECOMBINANT EXPRESSION.
RX   PubMed=32144281; DOI=10.1038/s41598-020-61034-x;
RA   Kvetkina A., Leychenko E., Chausova V., Zelepuga E., Chernysheva N.,
RA   Guzev K., Pislyagin E., Yurchenko E., Menchinskaya E., Aminin D.,
RA   Kaluzhskiy L., Ivanov A., Peigneur S., Tytgat J., Kozlovskaya E.,
RA   Isaeva M.;
RT   "A new multigene HCIQ subfamily from the sea anemone Heteractis crispa
RT   encodes Kunitz-peptides exhibiting neuroprotective activity against 6-
RT   hydroxydopamine.";
RL   Sci. Rep. 10:4205-4205(2020).
CC   -!- FUNCTION: Serine protease inhibitor that also shows protective effect
CC       in a cytotoxicity model. It binds to all proteases tested (trypsin
CC       (Ki=52 nM), alpha-chymotrypsin, cathepsin G, kallikrein, and human
CC       neutrophil elastase). It significantly increases neuroblastoma cell
CC       viability in an in vitro neurotoxicity model (in which cytotoxicity is
CC       induced by 6-hydroxydopamine (6-OHDA)) being a consequence of an
CC       effective decrease of reactive oxygen species (ROS) level in the cells.
CC       {ECO:0000269|PubMed:32144281}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P31713}.
CC       Nematocyst {ECO:0000250|UniProtKB:P31713}.
CC   -!- MISCELLANEOUS: Does not show activity on all potassium channel tested
CC       (Kv1.1/KCNA1, Kv1.2/KCNA2, Kv1.3/KCNA3, Kv1.4/KCNA4, Kv1.5/KCNA5,
CC       Kv1.6/KCNA8, Shaker IR, and Kv11.1/KCNH2/ERG1).
CC       {ECO:0000269|PubMed:32144281}.
CC   -!- SIMILARITY: Belongs to the venom Kunitz-type family. Sea anemone type 2
CC       potassium channel toxin subfamily. {ECO:0000305}.
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DR   EMBL; MH249934; QBA29483.1; -; mRNA.
DR   AlphaFoldDB; A0A6B7FBD3; -.
DR   SMR; A0A6B7FBD3; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0042151; C:nematocyst; 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   3: Inferred from homology;
KW   Cleavage on pair of basic residues; Disulfide bond; Nematocyst;
KW   Protease inhibitor; Secreted; Serine protease inhibitor; Signal.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   PROPEP          23..29
FT                   /evidence="ECO:0000305|PubMed:32144281"
FT                   /id="PRO_0000453028"
FT   CHAIN           28..85
FT                   /note="PI-stichotoxin-Hcr2i"
FT                   /evidence="ECO:0000305|PubMed:32144281"
FT                   /id="PRO_5025489489"
FT   DOMAIN          33..83
FT                   /note="BPTI/Kunitz inhibitor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT   SITE            43..44
FT                   /note="Reactive bond for trypsin"
FT                   /evidence="ECO:0000250|UniProtKB:P31713"
FT   SITE            74
FT                   /note="Important for the stabilization when complexed with
FT                   trypsin"
FT                   /evidence="ECO:0000250|UniProtKB:P0DMJ5"
FT   DISULFID        33..83
FT                   /evidence="ECO:0000250|UniProtKB:P31713"
FT   DISULFID        42..66
FT                   /evidence="ECO:0000250|UniProtKB:P31713"
FT   DISULFID        58..79
FT                   /evidence="ECO:0000250|UniProtKB:P31713"
SQ   SEQUENCE   85 AA;  9552 MW;  FC0AB91100347DEC CRC64;
     MKGTFLICLI LIAGFYFRSI QGFYFKRIQG NICSEPKKVG RCRGSFPRFY FDSETGKCTP
     FIYGGCGGNG NNFETLHACR AICRA