VKT2F_HETCR
ID VKT2F_HETCR Reviewed; 56 AA.
AC C0HJU6;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 09-DEC-2015, sequence version 1.
DT 25-MAY-2022, entry version 13.
DE RecName: Full=PI-stichotoxin-Hcr2f {ECO:0000305};
DE Short=PI-SHTX-Hcr2f {ECO:0000305};
DE AltName: Full=Kunitz-type serine protease inhibitor HCRG1 {ECO:0000303|PubMed:26404319, ECO:0000303|PubMed:33158163};
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 PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND
RP DISULFIDE BONDS.
RX PubMed=26404319; DOI=10.3390/md13106038;
RA Gladkikh I., Monastyrnaya M., Zelepuga E., Sintsova O., Tabakmakher V.,
RA Gnedenko O., Ivanov A., Hua K.F., Kozlovskaya E.;
RT "New Kunitz-type HCRG polypeptides from the sea anemone Heteractis
RT crispa.";
RL Mar. Drugs 13:6038-6063(2015).
RN [2]
RP FUNCTION, MASS SPECTROMETRY, AND 3D-STRUCTURE MODELING.
RX PubMed=33158163; DOI=10.3390/biomedicines8110473;
RA Gladkikh I., Peigneur S., Sintsova O., Lopes Pinheiro-Junior E.,
RA Klimovich A., Menshov A., Kalinovsky A., Isaeva M., Monastyrnaya M.,
RA Kozlovskaya E., Tytgat J., Leychenko E.;
RT "Kunitz-type peptides from the sea anemone Heteractis crispa demonstrate
RT potassium channel blocking and anti-inflammatory activities.";
RL Biomedicines 8:0-0(2020).
RN [3]
RP FUNCTION.
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: Dual-function toxin that inhibits both serine proteases and
CC voltage-gated potassium channels (PubMed:26404319, PubMed:33158163).
CC Has potent activity on both trypsin (Ki=28 nM) and chymotrypsin (Kd=1.8
CC nM) (PubMed:26404319). Shows inhibitory activity against 4 of the 7
CC potassium channels tested (rKv1.1/KCNA1; IC(50)=142.6 nM, hKv1.3/KCNA3;
CC IC(50)=40.7 nM, rKv1.6/KCNA6; IC(50)=154.9 nM and drosophila Shaker;
CC IC(50)=433.1 nM) (PubMed:33158163). Has an anti-inflammatory effect in
CC LPS-activated macrophages in vitro, specifically reducing release of
CC TNF and IL6 but not nitric oxide and reducing expression of IL1B
CC precursor (PubMed:26404319). In contrast to some paralogs, this protein
CC decreases reactive oxygen species (ROS) level in the oxidative stress
CC agent 6-hydroxydopamine (6-OHDA)-induced neurotoxicity model, but does
CC not show cytoprotective activity on neuroblastoma cells
CC (PubMed:33802055). This protein also shows a weak free-radical
CC scavenging activity (PubMed:33802055). In vivo, when tested in a mice
CC model of acute local inflammation, it reduces paw edema during 24
CC hours. In addition, it also reduces the synthesis of TNF in this model
CC (PubMed:33158163). {ECO:0000269|PubMed:26404319,
CC ECO:0000269|PubMed:33158163}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:26404319}.
CC Nematocyst {ECO:0000269|PubMed:26404319}.
CC -!- PTM: Contains 3 disulfide bonds. {ECO:0000269|PubMed:26404319}.
CC -!- MASS SPECTROMETRY: Mass=6196; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:26404319, ECO:0000269|PubMed:33158163};
CC -!- MISCELLANEOUS: Does not bind to and, hence, probably does not inhibit
CC serine proteases plasmin, kallikrein and thrombin (PubMed:26404319).
CC Has no or weak activity on hKv1.2/KCNA2 (IC(50)=52 uM), rKv1.4/KCNA4
CC and rKv1.5/KCNA5 (PubMed:33158163). {ECO:0000269|PubMed:26404319,
CC ECO:0000269|PubMed:33158163}.
CC -!- SIMILARITY: Belongs to the venom Kunitz-type family. Sea anemone type 2
CC potassium channel toxin subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR AlphaFoldDB; C0HJU6; -.
DR SMR; C0HJU6; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0042151; C:nematocyst; IEA:UniProtKB-SubCell.
DR GO; GO:0015459; F:potassium 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 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Nematocyst; Potassium channel impairing toxin; Protease inhibitor;
KW Secreted; Serine protease inhibitor; Toxin;
KW Voltage-gated potassium channel impairing toxin.
FT CHAIN 1..56
FT /note="PI-stichotoxin-Hcr2f"
FT /evidence="ECO:0000269|PubMed:26404319"
FT /id="PRO_0000434949"
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; 6202 MW; 4B522F66F1027CB1 CRC64;
RGICSEPKVV GPCKAGLRRF YYDSETGECK PFIYGGCKGN KNNFETLHAC RGICRA
