VKT2D_HETCR
ID VKT2D_HETCR Reviewed; 56 AA.
AC C0HJF3;
DT 11-DEC-2013, integrated into UniProtKB/Swiss-Prot.
DT 11-DEC-2013, sequence version 1.
DT 25-MAY-2022, entry version 23.
DE RecName: Full=TauPI-stichotoxin-Hcr2d {ECO:0000305};
DE Short=TauPI-SHTX-Hcr2d {ECO:0000305};
DE AltName: Full=Analgesic polypeptide HC3 {ECO:0000303|PubMed:20208578};
DE Short=APHC3 {ECO:0000303|PubMed:20208578};
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, AND MASS SPECTROMETRY.
RC TISSUE=Nematoblast;
RX PubMed=20208578; DOI=10.1134/s1068162009060065;
RA Kozlov S.A., Andreev Y.A., Murashev A.N., Skobtsov D.I., D'iachenko I.A.,
RA Grishin E.V.;
RT "New polypeptide components from the Heteractis crispa sea anemone with
RT analgesic activity.";
RL Bioorg. Khim. 35:789-798(2009).
RN [2]
RP FUNCTION.
RX PubMed=22982418; DOI=10.1016/j.lfs.2012.09.001;
RA Philyppov I.B., Paduraru O.N., Andreev Y.A., Grishin E.V., Shuba Y.M.;
RT "Modulation of TRPV1-dependent contractility of normal and diabetic bladder
RT smooth muscle by analgesic toxins from sea anemone Heteractis crispa.";
RL Life Sci. 91:912-920(2012).
RN [3]
RP FUNCTION.
RX PubMed=24351908; DOI=10.3390/md11125100;
RA Andreev Y.A., Kozlov S.A., Korolkova Y.V., Dyachenko I.A., Bondarenko D.A.,
RA Skobtsov D.I., Murashev A.N., Kotova P.D., Rogachevskaja O.A.,
RA Kabanova N.V., Kolesnikov S.S., Grishin E.V.;
RT "Polypeptide modulators of TRPV1 produce analgesia without hyperthermia.";
RL Mar. Drugs 11:5100-5115(2013).
RN [4]
RP FUNCTION.
RX PubMed=33477357; DOI=10.3390/md19010039;
RA Logashina Y.A., Palikova Y.A., Palikov V.A., Kazakov V.A., Smolskaya S.V.,
RA Dyachenko I.A., Tarasova N.V., Andreev Y.A.;
RT "Anti-inflammatory and analgesic effects of TRPV1 polypeptide modulator
RT APHC3 in models of osteo- and rheumatoid arthritis.";
RL Mar. Drugs 19:0-0(2021).
CC -!- FUNCTION: This protease inhibitor shows two different activities, it
CC inhibits both the capsaicin receptor TRPV1 and serine proteases. It
CC partially blocks the capsaicin- and acid-induced response of TRPV1, a
CC receptor of the pain pathway (PubMed:20208578, PubMed:24351908). It
CC also weakly inhibits trypsin and chymotrypsin activity (Ki=0.5 uM and
CC Ki=7 uM, respectively) (PubMed:20208578). In addition, it may also
CC alter tachykinin levels by suppressing endogenous proteases
CC (PubMed:22982418). In vivo, it shows antinociceptive and analgesic
CC activities (PubMed:24351908). It significantly prolongs paw withdrawal
CC latency and blocks heat-induced and chemical-induced acute pain
CC (PubMed:20208578). In addition, it also shows anti-inflammatory and
CC analgesic effects in models of osteoarthritis and rheumatoid arthritis
CC (PubMed:33477357). In vivo, unlike other TRPV1 antagonists whose
CC activity is associated with hyperthermia, this protein has the
CC remarkable feature of dropping core body temperature (PubMed:24351908).
CC {ECO:0000269|PubMed:20208578, ECO:0000269|PubMed:22982418,
CC ECO:0000269|PubMed:24351908, ECO:0000269|PubMed:33477357}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20208578}.
CC Nematocyst {ECO:0000269|PubMed:20208578}.
CC -!- MASS SPECTROMETRY: Mass=6111; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:20208578};
CC -!- MISCELLANEOUS: Intravenous dose (up to 1mg/kg) has no toxic effect and
CC generates no behavioral disorders in mice.
CC {ECO:0000269|PubMed:20208578}.
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; C0HJF3; -.
DR SMR; C0HJF3; -.
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 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Nematocyst; Neurotoxin; Protease inhibitor; Secreted;
KW Serine protease inhibitor; Toxin.
FT CHAIN 1..56
FT /note="TauPI-stichotoxin-Hcr2d"
FT /evidence="ECO:0000269|PubMed:20208578"
FT /id="PRO_0000424700"
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:P31713"
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; 6117 MW; 1E0B5B63C28C2B5A CRC64;
GSICLEPKVV GPCTAYFPRF YFNSETGKCT PFIYGGCEGN GNNFETLRAC RGICRA
