VKT21_LYCMC
ID VKT21_LYCMC Reviewed; 80 AA.
AC P0DJ46; P0CJ20;
DT 11-JUL-2012, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2012, sequence version 1.
DT 25-MAY-2022, entry version 28.
DE RecName: Full=Kunitz-type serine protease inhibitor LmKTT-1a;
DE AltName: Full=Delta-KTx 2.1;
DE AltName: Full=SdPII;
DE Flags: Precursor;
OS Lychas mucronatus (Chinese swimming scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Lychas.
OX NCBI_TaxID=172552;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Yunnan; TISSUE=Venom gland;
RX PubMed=20663230; DOI=10.1186/1471-2164-11-452;
RA Zhao R., Ma Y., He Y., Di Z., Wu Y.-L., Cao Z.-J., Li W.-X.;
RT "Comparative venom gland transcriptome analysis of the scorpion Lychas
RT mucronatus reveals intraspecific toxic gene diversity and new venomous
RT components.";
RL BMC Genomics 11:452-452(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], STRUCTURE BY NMR OF 22-80, DISULFIDE
RP BOND, MUTAGENESIS OF CYS-72 AND CYS-80, AND NOMENCLATURE.
RX PubMed=23573241; DOI=10.1371/journal.pone.0060201;
RA Chen Z., Luo F., Feng J., Yang W., Zeng D., Zhao R., Cao Z., Liu M., Li W.,
RA Jiang L., Wu Y.;
RT "Genomic and structural characterization of Kunitz-type peptide LmKTT-1a
RT highlights diversity and evolution of scorpion potassium channel toxins.";
RL PLoS ONE 8:E60201-E60201(2013).
RN [3]
RP FUNCTION.
RX PubMed=22087336; DOI=10.1371/journal.pone.0027548;
RA Zhao R.M., Dai H., Qiu S., Li T., He Y., Ma Y., Chen Z.-Y., Wu Y.-L.,
RA Li W.-X., Cao Z.-J.;
RT "SdPI, the first functionally characterized Kunitz-type trypsin inhibitor
RT from scorpion venom.";
RL PLoS ONE 6:E27548-E27548(2011).
RN [4]
RP FUNCTION.
RX PubMed=22354971; DOI=10.1074/jbc.m112.343996;
RA Chen Z.-Y., Hu Y.T., Yang W.S., He Y.W., Feng J., Wang B., Zhao R.M.,
RA Ding J.P., Cao Z.-J., Li W.-X., Wu Y.-L.;
RT "Hg1, novel peptide inhibitor specific for Kv1.3 channels from first
RT scorpion Kunitz-type potassium channel toxin family.";
RL J. Biol. Chem. 287:13813-13821(2012).
CC -!- FUNCTION: Dual-function toxin that completely inhibits trypsin activity
CC at a molar ratio of 1:1 (Ki=140 nM) and that inhibits mKv1.3/KCNA3
CC potassium channel currents (1 uM inhibits 50% of currents) (IC(50)=1.58
CC uM). Shows also weak inhibition on Kv1.1/KCNA1 (1 uM inhibits 25% of
CC currents) and Kv1.2/KCNA2 (1 uM inhibits 25% of currents).
CC {ECO:0000269|PubMed:22087336, ECO:0000269|PubMed:22354971}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- PTM: Lacks the conserved CysII-CysIV disulfide bond but contains 2
CC cysteine residues at the C-terminus that generate a new disulfide bond.
CC -!- MISCELLANEOUS: Has no effect on chymotrypsin and elastase.
CC {ECO:0000305|PubMed:22354971}.
CC -!- SIMILARITY: Belongs to the venom Kunitz-type family. Scorpion delta-Ktx
CC subfamily. Delta-Ktx 2 sub-subfamily. {ECO:0000305}.
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DR EMBL; GT028614; -; NOT_ANNOTATED_CDS; mRNA.
DR PDB; 2M01; NMR; -; A=22-80.
DR PDBsum; 2M01; -.
DR AlphaFoldDB; P0DJ46; -.
DR SMR; P0DJ46; -.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0033644; C:host cell membrane; NAS:UniProtKB.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
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:0044562; P:envenomation resulting in negative regulation of voltage-gated potassium channel activity 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 Pfam; PF00014; Kunitz_BPTI; 1.
DR PRINTS; PR00759; BASICPTASE.
DR SMART; SM00131; KU; 1.
DR SUPFAM; SSF57362; SSF57362; 1.
DR PROSITE; PS50279; BPTI_KUNITZ_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Ion channel impairing toxin;
KW Potassium channel impairing toxin; Protease inhibitor; Secreted;
KW Serine protease inhibitor; Signal; Toxin;
KW Voltage-gated potassium channel impairing toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..80
FT /note="Kunitz-type serine protease inhibitor LmKTT-1a"
FT /id="PRO_0000418102"
FT DOMAIN 25..75
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT SITE 35
FT /note="Key residue that directly interacts with the S1
FT pocket of trypsin"
FT /evidence="ECO:0000250"
FT DISULFID 25..75
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031,
FT ECO:0000269|PubMed:23573241"
FT DISULFID 50..71
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031,
FT ECO:0000269|PubMed:23573241"
FT DISULFID 72..80
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031,
FT ECO:0000269|PubMed:23573241"
FT MUTAGEN 72
FT /note="C->A: 5-fold decrease in trypsin inhibition, and no
FT change in Kv1.3/KCNA3 inhibition; when associated with A-
FT 80."
FT /evidence="ECO:0000269|PubMed:23573241"
FT MUTAGEN 80
FT /note="C->A: 5-fold decrease in trypsin inhibition, and no
FT change in Kv1.3/KCNA3 inhibition; when associated with A-
FT 72."
FT /evidence="ECO:0000269|PubMed:23573241"
FT STRAND 38..44
FT /evidence="ECO:0007829|PDB:2M01"
FT TURN 45..48
FT /evidence="ECO:0007829|PDB:2M01"
FT STRAND 49..55
FT /evidence="ECO:0007829|PDB:2M01"
FT HELIX 70..76
FT /evidence="ECO:0007829|PDB:2M01"
SQ SEQUENCE 80 AA; 8864 MW; D83664064E8A8CBC CRC64;
MKSFLLIALV LFFLFVSYAS AKKKCQLPSD VGKGKASFTR YYYNEESGKC ETFIYGGVGG
NSNNFLTKED CCRECAQGSC
