VKT2B_HETCR
ID VKT2B_HETCR Reviewed; 78 AA.
AC B2G331;
DT 10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 25-MAY-2022, entry version 56.
DE RecName: Full=TauPI-stichotoxin-Hcr2b {ECO:0000305};
DE Short=TauPI-SHTX-Hcr2b {ECO:0000303|PubMed:22683676};
DE AltName: Full=Analgesic polypeptide HC1 {ECO:0000303|PubMed:18579526};
DE Short=APHC1 {ECO:0000303|PubMed:18579526};
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 23-37, FUNCTION, MASS
RP SPECTROMETRY, SUBCELLULAR LOCATION, AND 3D-STRUCTURE MODELING.
RC TISSUE=Nematoblast;
RX PubMed=18579526; DOI=10.1074/jbc.m800776200;
RA Andreev Y.A., Kozlov S.A., Koshelev S.G., Ivanova E.A., Monastyrnaya M.M.,
RA Kozlovskaya E.P., Grishin E.V.;
RT "Analgesic compound from sea anemone Heteractis crispa is the first
RT polypeptide inhibitor of vanilloid receptor 1 (TRPV1).";
RL J. Biol. Chem. 283:23914-23921(2008).
RN [2]
RP 3D-STRUCTURE MODELING IN COMPLEX WITH TRPV1 RECEPTOR.
RX PubMed=22792722; DOI=10.1134/s106816201202015x;
RA Zelepuga E.A., Tabakmakher V.M., Chausova V.E., Monastyrnaia M.M.,
RA Isaeva M.P., Kozlovskaia E.P.;
RT "Interaction of sea amemone Heteractis crispa Kunitz type polypeptides with
RT pain vanilloid receptor TRPV1: in silico investigation.";
RL Bioorg. Khim. 38:185-198(2012).
RN [3]
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 [4]
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 [5]
RP NOMENCLATURE.
RX PubMed=22683676; DOI=10.1016/j.toxicon.2012.05.020;
RA Oliveira J.S., Fuentes-Silva D., King G.F.;
RT "Development of a rational nomenclature for naming peptide and protein
RT toxins from sea anemones.";
RL Toxicon 60:539-550(2012).
CC -!- FUNCTION: This protease inhibitor shows two different activities, it
CC inhibits both the capsaicin receptor TRPV1 and serine proteases. It
CC partially (max 50%) and reversibly inhibits capsaicin-induced response
CC of TRPV1 (IC(50)=54 nM), a receptor of the pain pathway
CC (PubMed:18579526, PubMed:24351908). The second activity is a weak
CC inhibition of trypsin and chymotrypsin activity (Ki=1 uM and Ki=5 uM,
CC respectively) (PubMed:18579526). In vivo, it shows antinociceptive and
CC analgesic activities (PubMed:24351908). It significantly prolongs tail-
CC flick latency and reduces capsaicin-induced acute pain
CC (PubMed:18579526, PubMed:24351908). In vivo, unlike other TRPV1
CC antagonists whose activity is associated with hyperthermia, this
CC protein has the remarkable feature of dropping core body temperature
CC (PubMed:24351908). {ECO:0000269|PubMed:18579526,
CC ECO:0000269|PubMed:22982418, ECO:0000269|PubMed:24351908}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18579526}.
CC Nematocyst {ECO:0000269|PubMed:18579526}.
CC -!- MASS SPECTROMETRY: Mass=6187.0; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:18579526};
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; AM933240; CAP69846.1; -; mRNA.
DR AlphaFoldDB; B2G331; -.
DR SMR; B2G331; -.
DR MEROPS; I02.061; -.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0042151; C:nematocyst; IDA:UniProtKB.
DR GO; GO:0008200; F:ion channel inhibitor activity; IDA:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0044465; P:modulation of sensory perception of pain in another organism; IDA:UniProtKB.
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; Signal; Toxin.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:18579526"
FT CHAIN 23..78
FT /note="TauPI-stichotoxin-Hcr2b"
FT /evidence="ECO:0000305|PubMed:18579526"
FT /id="PRO_5000342888"
FT DOMAIN 26..76
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT SITE 23
FT /note="May bind to TRPV1 subunit B"
FT /evidence="ECO:0000305|PubMed:22792722"
FT SITE 28
FT /note="May bind to TRPV1 subunit B"
FT /evidence="ECO:0000305|PubMed:22792722"
FT SITE 36..37
FT /note="Reactive bond for trypsin"
FT /evidence="ECO:0000250|UniProtKB:P31713"
FT SITE 53
FT /note="May bind to TRPV1 subunit D"
FT /evidence="ECO:0000305|PubMed:18579526,
FT ECO:0000305|PubMed:22792722"
FT SITE 60
FT /note="May bind to TRPV1 subunit B"
FT /evidence="ECO:0000305|PubMed:22792722"
FT SITE 70
FT /note="Important for modulatory effect on TRPV1"
FT /evidence="ECO:0000305|PubMed:18579526,
FT ECO:0000305|PubMed:22792722"
FT SITE 73
FT /note="Has role in the stabilization of the complex by
FT binding to different residues of TRPV1 subunit D"
FT /evidence="ECO:0000305|PubMed:22792722"
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"
SQ SEQUENCE 78 AA; 8565 MW; 9F812F0E2471C841 CRC64;
MKGTFLICLI LIAGFSFKST QAGSICLEPK VVGPCTAYFR RFYFDSETGK CTVFIYGGCE
GNGNNFETLR ACRAICRA
