VKTH1_DENPO
ID VKTH1_DENPO Reviewed; 60 AA.
AC P00979;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 2.
DT 25-MAY-2022, entry version 112.
DE RecName: Full=Kunitz-type serine protease inhibitor homolog dendrotoxin I;
DE Short=DTX-I;
DE AltName: Full=Dendrotoxin-1;
DE AltName: Full=Venom basic protease inhibitor 1;
OS Dendroaspis polylepis polylepis (Black mamba).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Dendroaspis.
OX NCBI_TaxID=8620;
RN [1]
RP PROTEIN SEQUENCE.
RC TISSUE=Venom;
RX PubMed=4512962;
RA Strydom D.J.;
RT "Protease inhibitors as snake venom toxins.";
RL Nature New Biol. 243:88-89(1973).
RN [2]
RP REVIEW.
RX PubMed=10936620; DOI=10.1016/s0041-0101(00)00162-8;
RA Harvey A.L.;
RT "Twenty years of dendrotoxins.";
RL Toxicon 39:15-26(2001).
RN [3]
RP REVIEW, AND SITE LYS-5; LEU-9 AND LYS-19.
RX PubMed=23771044; DOI=10.3390/md11062069;
RA Mourao C.B., Schwartz E.F.;
RT "Protease inhibitors from marine venomous animals and their counterparts in
RT terrestrial venomous animals.";
RL Mar. Drugs 11:2069-2112(2013).
RN [4]
RP FUNCTION.
RX PubMed=8612784; DOI=10.1016/0014-5793(96)00211-6;
RA Robertson B., Owen D., Stow J., Butler C., Newland C.;
RT "Novel effects of dendrotoxin homologues on subtypes of mammalian Kv1
RT potassium channels expressed in Xenopus oocytes.";
RL FEBS Lett. 383:26-30(1996).
RN [5]
RP STRUCTURE BY NMR.
RX PubMed=7679640; DOI=10.1111/j.1432-1033.1993.tb17613.x;
RA Foray M.-F., Lancelin J.-M., Hollecker M., Marion D.;
RT "Sequence-specific 1H-NMR assignment and secondary structure of black mamba
RT dendrotoxin I, a highly selective blocker of voltage-gated potassium
RT channels.";
RL Eur. J. Biochem. 211:813-820(1993).
RN [6]
RP STRUCTURE BY NMR.
RX PubMed=7544683; DOI=10.1038/nsb0494-246;
RA Lancelin J.-M., Foray M.-F., Poncin M.-F., Hollecker M., Marion D.;
RT "Proteinase inhibitor homologues as potassium channel blockers.";
RL Nat. Struct. Biol. 1:246-250(1994).
CC -!- FUNCTION: Serine protease inhibitor homolog that blocks voltage-gated
CC potassium channels (Kv1.1/KCNA1, Kv1.2/KCNA2, and Kv1.6/KCNA6)
CC (IC(50)=0.13-50 nM). {ECO:0000269|PubMed:8612784}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- TOXIC DOSE: LD(50) is 38 mg/kg by intravenous injection.
CC -!- MISCELLANEOUS: Does not inhibit serine proteases.
CC -!- SIMILARITY: Belongs to the venom Kunitz-type family. {ECO:0000305}.
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DR PIR; A01211; TIEPVI.
DR PDB; 1DEM; NMR; -; A=1-60.
DR PDB; 1DEN; NMR; -; A=1-60.
DR PDBsum; 1DEM; -.
DR PDBsum; 1DEN; -.
DR AlphaFoldDB; P00979; -.
DR SMR; P00979; -.
DR EvolutionaryTrace; P00979; -.
DR GO; GO:0005576; C:extracellular region; 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:InterPro.
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 3D-structure; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Potassium channel impairing toxin;
KW Secreted; Toxin; Voltage-gated potassium channel impairing toxin.
FT CHAIN 1..60
FT /note="Kunitz-type serine protease inhibitor homolog
FT dendrotoxin I"
FT /id="PRO_0000155434"
FT DOMAIN 7..57
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT SITE 5
FT /note="May be the major determinant of the binding affinity
FT for potassium channels"
FT SITE 9
FT /note="Important for binding to potassium channels"
FT SITE 19
FT /note="Not important for inhibition of potassium channels"
FT DISULFID 7..57
FT DISULFID 16..40
FT DISULFID 32..53
FT HELIX 5..7
FT /evidence="ECO:0007829|PDB:1DEM"
FT STRAND 20..25
FT /evidence="ECO:0007829|PDB:1DEM"
FT STRAND 29..37
FT /evidence="ECO:0007829|PDB:1DEM"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:1DEM"
FT HELIX 50..57
FT /evidence="ECO:0007829|PDB:1DEM"
SQ SEQUENCE 60 AA; 7155 MW; 94E5CD5609E7AD81 CRC64;
QPLRKLCILH RNPGRCYQKI PAFYYNQKKK QCEGFTWSGC GGNSNRFKTI EECRRTCIRK
