VKTHK_DENPO
ID VKTHK_DENPO Reviewed; 79 AA.
AC P00981; Q91351;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2004, sequence version 2.
DT 25-MAY-2022, entry version 121.
DE RecName: Full=Kunitz-type serine protease inhibitor homolog dendrotoxin K;
DE Short=DTX-K;
DE AltName: Full=Venom basic protease inhibitor K;
DE Flags: Precursor; Fragment;
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 NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 23-39.
RX PubMed=8504088; DOI=10.1021/bi00072a026;
RA Smith L.A., Lafaye P.J., LaPenotiere H.F., Spain T., Dolly J.O.;
RT "Cloning and functional expression of dendrotoxin K from black mamba, a K+
RT channel blocker.";
RL Biochemistry 32:5692-5697(1993).
RN [2]
RP PROTEIN SEQUENCE OF 23-79.
RC TISSUE=Venom;
RX PubMed=857902; DOI=10.1016/0005-2795(77)90279-3;
RA Strydom D.J.;
RT "Snake venom toxins. The amino acid sequence of toxin Vi2, a homologue of
RT pancreatic trypsin inhibitor, from Dendroaspis polylepis polylepis (black
RT mamba) venom.";
RL Biochim. Biophys. Acta 491:361-369(1977).
RN [3]
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 [4]
RP MUTAGENESIS OF LYS-25; LYS-28; LYS-46; TRP-47; LYS-48; ALA-49; LYS-50;
RP ARG-74 AND ARG-75, AND SITES LYS-25; LYS-28; TRP-47 AND LYS-48.
RX PubMed=9201909; DOI=10.1021/bi963105g;
RA Smith L.A., Reid P.F., Wang F.C., Parcej D.N., Schmidt J.J., Olson M.A.,
RA Dolly J.O.;
RT "Site-directed mutagenesis of dendrotoxin K reveals amino acids critical
RT for its interaction with neuronal K+ channels.";
RL Biochemistry 36:7690-7696(1997).
RN [5]
RP FUNCTION.
RX PubMed=9134213; DOI=10.1038/sj.bjp.0701004;
RA Owen D.G., Hall A., Stephens G., Stow J., Robertson B.;
RT "The relative potencies of dendrotoxins as blockers of the cloned voltage-
RT gated K+ channel, mKv1.1 (MK-1), when stably expressed in Chinese hamster
RT ovary cells.";
RL Br. J. Pharmacol. 120:1029-1034(1997).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF PRO-35; LYS-37; ARG-38; LYS-39; TRP-47;
RP LYS-48; ALA-49; LYS-50; ARG-74 AND ARG-75.
RX PubMed=10429207; DOI=10.1046/j.1432-1327.1999.00494.x;
RA Wang F.C., Bell N., Reid P., Smith L.A., McIntosh P., Robertson B.,
RA Dolly J.O.;
RT "Identification of residues in dendrotoxin K responsible for its
RT discrimination between neuronal K+ channels containing Kv1.1 and 1.2 alpha
RT subunits.";
RL Eur. J. Biochem. 263:222-229(1999).
RN [7]
RP STRUCTURE BY NMR OF 23-79.
RX PubMed=8254670; DOI=10.1006/jmbi.1993.1623;
RA Berndt K.D., Guentert P., Wuethrich K.;
RT "Nuclear magnetic resonance solution structure of dendrotoxin K from the
RT venom of Dendroaspis polylepis polylepis.";
RL J. Mol. Biol. 234:735-750(1993).
CC -!- FUNCTION: Serine protease inhibitor homolog that selectively blocks
CC voltage-gated potassium channels homooligomer Kv1.1/KCNA1 (EC(50)=0.6
CC nM) and Kv1.1-containing heterooligomer. {ECO:0000269|PubMed:10429207,
CC ECO:0000269|PubMed:8612784, ECO:0000269|PubMed:9134213}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- TOXIC DOSE: LD(50) is 30 mg/kg by intravenous injection.
CC -!- MISCELLANEOUS: Does not inhibit serine proteases and voltage-gated
CC potassium channels Kv1.2/KCNA2 and Kv1.6/KCNA6.
CC {ECO:0000305|PubMed:8612784}.
CC -!- SIMILARITY: Belongs to the venom Kunitz-type family. {ECO:0000305}.
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DR EMBL; S61886; AAB26998.1; -; mRNA.
DR PIR; A49291; TIEPVK.
DR PDB; 1DTK; NMR; -; A=23-79.
DR PDBsum; 1DTK; -.
DR AlphaFoldDB; P00981; -.
DR BMRB; P00981; -.
DR SMR; P00981; -.
DR MEROPS; I02.056; -.
DR EvolutionaryTrace; P00981; -.
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; Signal; Toxin; Voltage-gated potassium channel impairing toxin.
FT SIGNAL <1..?
FT PROPEP ?..22
FT /evidence="ECO:0000269|PubMed:8504088,
FT ECO:0000269|PubMed:857902"
FT /id="PRO_0000016869"
FT CHAIN 23..79
FT /note="Kunitz-type serine protease inhibitor homolog
FT dendrotoxin K"
FT /id="PRO_0000016870"
FT DOMAIN 27..77
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT SITE 25
FT /note="Important for binding to potassium channels"
FT SITE 28
FT /note="Important for binding to potassium channels"
FT SITE 47
FT /note="Important for binding to potassium channels"
FT SITE 48
FT /note="Important for binding to potassium channels"
FT DISULFID 27..77
FT DISULFID 36..60
FT DISULFID 52..73
FT MUTAGEN 25
FT /note="K->A: Important decrease in binding affinity for
FT Kv."
FT /evidence="ECO:0000269|PubMed:9201909"
FT MUTAGEN 28
FT /note="K->A: Decrease in binding affinity for Kv."
FT /evidence="ECO:0000269|PubMed:9201909"
FT MUTAGEN 35
FT /note="P->Q: Important decrease in binding affinity for Kv;
FT when associated with A-48 and A-50."
FT /evidence="ECO:0000269|PubMed:10429207"
FT MUTAGEN 37
FT /note="K->Y: Slight decrease in binding affinity for Kv."
FT /evidence="ECO:0000269|PubMed:10429207"
FT MUTAGEN 38
FT /note="R->A: Slight decrease in binding affinity for Kv."
FT /evidence="ECO:0000269|PubMed:10429207"
FT MUTAGEN 39
FT /note="K->A: Slight decrease in binding affinity for Kv.
FT Important decrease in binding affinity for Kv; when
FT associated with A-48."
FT /evidence="ECO:0000269|PubMed:10429207"
FT MUTAGEN 46
FT /note="K->A: Slight decrease in binding affinity for Kv."
FT /evidence="ECO:0000269|PubMed:9201909"
FT MUTAGEN 47
FT /note="W->A: Decrease in binding affinity for Kv."
FT /evidence="ECO:0000269|PubMed:10429207,
FT ECO:0000269|PubMed:9201909"
FT MUTAGEN 47
FT /note="W->Q: Decrease in binding affinity for Kv; when
FT associated with K-49."
FT /evidence="ECO:0000269|PubMed:10429207,
FT ECO:0000269|PubMed:9201909"
FT MUTAGEN 48
FT /note="K->A: Important decrease in binding affinity for Kv.
FT Important decrease in binding affinity for Kv; when
FT associated with Q-35 and A-50. Important decrease in
FT binding affinity for Kv; when associated with A-39."
FT /evidence="ECO:0000269|PubMed:10429207,
FT ECO:0000269|PubMed:9201909"
FT MUTAGEN 49
FT /note="A->K: Decrease in binding affinity for Kv; when
FT associated with Q-47."
FT /evidence="ECO:0000269|PubMed:10429207,
FT ECO:0000269|PubMed:9201909"
FT MUTAGEN 49
FT /note="A->K: Slight increase in binding affinity for Kv."
FT /evidence="ECO:0000269|PubMed:10429207,
FT ECO:0000269|PubMed:9201909"
FT MUTAGEN 50
FT /note="K->A: Slight decrease in binding affinity for Kv.
FT Important decrease in binding affinity for Kv; when
FT associated with Q-35 and A-48."
FT /evidence="ECO:0000269|PubMed:10429207,
FT ECO:0000269|PubMed:9201909"
FT MUTAGEN 74
FT /note="R->A: No change in binding affinity for Kv."
FT /evidence="ECO:0000269|PubMed:10429207,
FT ECO:0000269|PubMed:9201909"
FT MUTAGEN 74
FT /note="R->A: Slight decrease in binding affinity for Kv."
FT /evidence="ECO:0000269|PubMed:10429207,
FT ECO:0000269|PubMed:9201909"
FT MUTAGEN 75
FT /note="R->A: No change in binding affinity for Kv."
FT /evidence="ECO:0000269|PubMed:10429207,
FT ECO:0000269|PubMed:9201909"
FT MUTAGEN 75
FT /note="R->A: Slight decrease in binding affinity for Kv."
FT /evidence="ECO:0000269|PubMed:10429207,
FT ECO:0000269|PubMed:9201909"
FT NON_TER 1
FT HELIX 25..28
FT /evidence="ECO:0007829|PDB:1DTK"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:1DTK"
FT STRAND 40..45
FT /evidence="ECO:0007829|PDB:1DTK"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:1DTK"
FT STRAND 50..57
FT /evidence="ECO:0007829|PDB:1DTK"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:1DTK"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:1DTK"
FT HELIX 70..77
FT /evidence="ECO:0007829|PDB:1DTK"
SQ SEQUENCE 79 AA; 8852 MW; DCDFB9AFA07D7D46 CRC64;
SGHLLLLLGL LTLWAELTPV SGAAKYCKLP LRIGPCKRKI PSFYYKWKAK QCLPFDYSGC
GGNANRFKTI EECRRTCVG
