VKT2M_HETCR
ID VKT2M_HETCR Reviewed; 56 AA.
AC P0DV03;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 1.
DT 03-AUG-2022, entry version 3.
DE RecName: Full=PI-stichotoxin-Hcr2m {ECO:0000305};
DE Short=PI-SHTX-Hcr2m {ECO:0000305};
DE AltName: Full=Kunitz-type serine protease inhibitor HCGS1.10 {ECO:0000303|Ref.3};
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 3D-STRUCTURE MODELING.
RX PubMed=22001835; DOI=10.1016/j.peptides.2011.09.022;
RA Isaeva M.P., Chausova V.E., Zelepuga E.A., Guzev K.V., Tabakmakher V.M.,
RA Monastyrnaya M.M., Kozlovskaya E.P.;
RT "A new multigene superfamily of Kunitz-type protease inhibitors from sea
RT anemone Heteractis crispa.";
RL Peptides 34:88-97(2012).
RN [2]
RP FUNCTION.
RX PubMed=25937220; DOI=10.1134/s1607672915020052;
RA Tabakmakher V.M., Sintsova O.V., Krivoshapko O.N., Zelepuga E.A.,
RA Monastyrnaya M.M., Kozlovskaya E.P.;
RT "Analgesic effect of novel Kunitz-type polypeptides of the sea anemone
RT Heteractis crispa.";
RL Dokl. Biochem. Biophys. 461:80-83(2015).
RN [3]
RP FUNCTION, AND RECOMBINANT EXPRESSION.
RA Sintsovaa O.V., Pislyagina E.A., Gladkikha I.N., Monastyrnayaa M.M.,
RA Menchinskayaa E.S., Leychenkoa E.V., Aminina D.L., Kozlovskaya E.P.;
RT "Kunitz-type peptides of the sea anemone Heteractis crispa: potential anti-
RT inflammatory compounds.";
RL Russ. J. Bioorg. Chem. 43:91-97(2017).
RN [4]
RP FUNCTION, AND RECOMBINANT EXPRESSION.
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: This recombinant serine protease inhibitor inhibits trypsin
CC (Ki=210 nM) (Ref.3). In contrast to other sea anemone serine protease
CC inhibitors, it does not significantly blocks histamine influence on
CC intracellular calcium concentration in murine bone marrow-derived
CC macrophages (tested at 1 and 10 uM) (Ref.3). In vitro, it shows
CC cytoprotective activity in the oxidative stress agent 6-hydroxydopamine
CC (6-OHDA)-induced neurotoxicity model (PubMed:33802055). In this model,
CC it decreases reactive oxygen species (ROS) levels, 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). In vivo, it shows analgesic
CC activity, since it increases hot plate and tail flick withdrawal
CC latencies, when using a mice thermal pain stimulation model
CC (PubMed:25937220). {ECO:0000269|PubMed:25937220, ECO:0000269|Ref.3}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. Nematocyst {ECO:0000305}.
CC -!- MISCELLANEOUS: Has no activity on Kv1.1/KCNA1, Kv1.2/KCNA2,
CC Kv1.3/KCNA3, Kv1.4/KCNA4, Kv1.5/KCNA5, Kv1.6/KCNA6, Shaker,
CC Kv11.1/KCNH2/ERG1 potassium channels and on TRPV1, the capsaicin
CC receptors. {ECO:0000269|PubMed:33802055}.
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 GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0042151; C:nematocyst; IEA:UniProtKB-SubCell.
DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin 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 Disulfide bond; Ion channel impairing toxin; Nematocyst;
KW Protease inhibitor; Secreted; Serine protease inhibitor; Toxin.
FT CHAIN 1..56
FT /note="PI-stichotoxin-Hcr2m"
FT /evidence="ECO:0000305"
FT /id="PRO_0000454104"
FT DOMAIN 4..54
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT SITE 14..15
FT /note="Reactive bond for trypsin"
FT /evidence="ECO:0000250|UniProtKB:P00974"
FT DISULFID 4..54
FT /evidence="ECO:0000250|UniProtKB:P31713"
FT DISULFID 13..37
FT /evidence="ECO:0000250|UniProtKB:P31713"
FT DISULFID 29..50
FT /evidence="ECO:0000250|UniProtKB:P31713"
SQ SEQUENCE 56 AA; 6157 MW; 3C8DD783272C2802 CRC64;
GSICLEPKVV GPCTAYLRRF YFDSETGKCT PFIYGGCEGN GNNFETLRAC RAICRA
