VKT2E_HETCR
ID VKT2E_HETCR Reviewed; 78 AA.
AC P0DMJ5;
DT 11-JUN-2014, integrated into UniProtKB/Swiss-Prot.
DT 11-JUN-2014, sequence version 1.
DT 25-MAY-2022, entry version 17.
DE RecName: Full=PI-stichotoxin-Hcr2e {ECO:0000305};
DE Short=PI-SHTX-Hcr2e {ECO:0000305};
DE AltName: Full=Kunitz-type serine protease inhibitor InhVJ {ECO:0000303|PubMed:17886436, ECO:0000303|PubMed:22851925};
DE Flags: Precursor;
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], PROTEIN SEQUENCE OF 23-78, MASS SPECTROMETRY,
RP AND 3D-STRUCTURE MODELING.
RX PubMed=22851925; DOI=10.3390/md10071545;
RA Gladkikh I., Monastyrnaya M., Leychenko E., Zelepuga E., Chausova V.,
RA Isaeva M., Anastyuk S., Andreev Y., Peigneur S., Tytgat J., Kozlovkaya E.;
RT "Atypical reactive center Kunitz-type inhibitor from the sea anemone
RT Heteractis crispa.";
RL Mar. Drugs 10:1545-1565(2012).
RN [2]
RP PROTEIN SEQUENCE OF 23-41, AND MASS SPECTROMETRY.
RX PubMed=17886436; DOI=10.1134/s1068162007040073;
RA Sokotun I.N., Leichenko E.V., Vakorina T.I., Es'kov A.A., Il'ina A.P.,
RA Monastyrnaia M.M., Kozlovskaia E.P.;
RT "A serine protease inhibitor from the anemone Radianthus macrodactylus:
RT isolation and physicochemical characteristics.";
RL Bioorg. Khim. 33:448-455(2007).
RN [3]
RP FUNCTION.
RX PubMed=17288251;
RA Sokotun I.N., Gnedenko O.V., Leichenko E.V., Monastyrnaia M.M.,
RA Kozlovskaia E.P., Mol'nar A.A., Ivanov A.C.;
RT "Interaction investigation of trypsin inhibitor from sea anemone Radianthus
RT macrodactylus with proteases.";
RL Biomed. Khim. 52:595-600(2006).
RN [4]
RP FUNCTION, AND MASS SPECTROMETRY.
RX PubMed=33802055; DOI=10.3390/biomedicines9030283;
RA Sintsova O., Gladkikh I., Monastyrnaya M., Tabakmakher V., Yurchenko E.,
RA Menchinskaya E., Pislyagin E., Andreev Y., Kozlov S., Peigneur S.,
RA Tytgat J., Aminin D., Kozlovskaya E., Leychenko E.;
RT "Sea anemone kunitz-type peptides demonstrate neuroprotective activity in
RT the 6-hydroxydopamine induced neurotoxicity model.";
RL Biomedicines 9:0-0(2021).
CC -!- FUNCTION: Serine protease inhibitor that specifically inhibits trypsin
CC (Ki=73.8-78 nM) and chymotrypsin (Ki=993 nM) (PubMed:17886436,
CC PubMed:17288251, PubMed:33802055). In vitro, it shows cytoprotective
CC activity in the oxidative stress agent 6-hydroxydopamine (6-OHDA)-
CC induced neurotoxicity model (PubMed:33802055). In this model, it
CC decreases reactive oxygen species (ROS) level, and increases cell
CC viability in a correlated manner (PubMed:33802055). It is possible that
CC the observed effect is due to the ability of this peptides to act as
CC free-radical scavenger (PubMed:33802055). {ECO:0000269|PubMed:17288251,
CC ECO:0000269|PubMed:17886436, ECO:0000269|PubMed:33802055}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:22851925}.
CC Nematocyst {ECO:0000305}.
CC -!- MASS SPECTROMETRY: Mass=6106; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:17886436, ECO:0000269|PubMed:22851925};
CC -!- MASS SPECTROMETRY: Mass=6107.9; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:33802055};
CC -!- MISCELLANEOUS: Does not inhibit potassium channels (Kv1.1/KCNA1,
CC Kv1.2/KCNA2, Kv1.3/KCNA3, Kv1.4/KCNA4, Kv1.5/KCNA5, Kv1.6/KCNA6,
CC Shaker, Kv2.1/KCNB1, Kv3.1/KCNC1, Kv4.2/KCND2, Kv4.3/KCND3, hERG/KCNH2)
CC and TRPV1, the capsaicin receptors (PubMed:22851925). Does not inhibit
CC the serine proteases plasmin, thrombin, kallikrein, the cysteine
CC proteinase papain, and the aspartic protease pepsin (PubMed:22851925,
CC PubMed:17886436). {ECO:0000269|PubMed:22851925}.
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 AlphaFoldDB; P0DMJ5; -.
DR SMR; P0DMJ5; -.
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 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Nematocyst; Protease inhibitor;
KW Secreted; Serine protease inhibitor; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:22851925"
FT CHAIN 23..78
FT /note="PI-stichotoxin-Hcr2e"
FT /evidence="ECO:0000269|PubMed:22851925"
FT /id="PRO_0000429352"
FT DOMAIN 26..76
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT SITE 36..37
FT /note="Reactive bond for trypsin"
FT /evidence="ECO:0000250|UniProtKB:P31713"
FT SITE 67
FT /note="Important for the stabilization when complexed with
FT trypsin"
FT DISULFID 26..76
FT /evidence="ECO:0000250|UniProtKB:P31713"
FT DISULFID 35..59
FT /evidence="ECO:0000250|UniProtKB:P31713"
FT DISULFID 51..72
FT /evidence="ECO:0000250|UniProtKB:P31713"
FT CONFLICT 36
FT /note="T -> G (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 78 AA; 8485 MW; A95F4F682471CB17 CRC64;
MKGTFLICLI LIAGFSFKST QAGSICLEPK VVGPCTAYFP RFYFDSETGK CTPFIYGGCE
GNGNNFETLH ACRAICRA
