VKT11_HOFGE
ID VKT11_HOFGE Reviewed; 88 AA.
AC P0C8W3;
DT 03-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 25-MAY-2022, entry version 35.
DE RecName: Full=Kunitz-type serine protease inhibitor Hg1;
DE AltName: Full=Delta-KTx 1.1;
DE Flags: Precursor;
OS Hoffmannihadrurus gertschi (Scorpion) (Hadrurus gertschi).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Iurida; Iuroidea; Hadrurus.
OX NCBI_TaxID=380989;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Venom gland;
RX PubMed=17506894; DOI=10.1186/1471-2164-8-119;
RA Schwartz E.F., Diego-Garcia E., Rodriguez de la Vega R.C., Possani L.D.;
RT "Transcriptome analysis of the venom gland of the Mexican scorpion Hadrurus
RT gertschi (Arachnida: Scorpiones).";
RL BMC Genomics 8:119-119(2007).
RN [2]
RP FUNCTION, AND MUTAGENESIS OF LYS-77; ARG-78; PHE-82 AND LYS-84.
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 the activity of
CC trypsin at a molar ratio of 1:1 (dissociation constant of 107 nM) and
CC that inhibits mKv1.3/KCNA3 potassium channel currents with an IC(50) of
CC 6.2 nM (where 1 uM inhibits 80% of currents). Also has weak inhibitory
CC activity against mKv1.1/KCNA1 (where 1 uM inhibits less than 50% of
CC currents), hKv1.2/KCNA2 (where 1 uM inhibits less than 50% of
CC currents), and hKCa2.3/KCNN3. {ECO:0000269|PubMed:22354971}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- MISCELLANEOUS: Has no effect on chymotrypsin, nor elastase, nor the
CC KCa1.1/KCNMA1 potassium channel. {ECO:0000305|PubMed:22354971}.
CC -!- SIMILARITY: Belongs to the venom Kunitz-type family. Scorpion delta-Ktx
CC subfamily. Delta-Ktx 1 sub-subfamily. {ECO:0000305}.
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DR EMBL; EL698904; -; NOT_ANNOTATED_CDS; mRNA.
DR AlphaFoldDB; P0C8W3; -.
DR SMR; P0C8W3; -.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0043655; C:host extracellular space; 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 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 Disulfide bond; Glycoprotein; 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..88
FT /note="Kunitz-type serine protease inhibitor Hg1"
FT /id="PRO_0000366101"
FT DOMAIN 29..79
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT SITE 39..40
FT /note="Reactive bond for trypsin"
FT /evidence="ECO:0000250"
FT SITE 77
FT /note="Pore-blocking residue"
FT /evidence="ECO:0000305"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..79
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 38..62
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT DISULFID 54..75
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT MUTAGEN 77
FT /note="K->A: 94-fold reduction in KCNA3 inhibition."
FT /evidence="ECO:0000269|PubMed:22354971"
FT MUTAGEN 78
FT /note="R->A: 49-fold reduction in KCNA3 inhibition."
FT /evidence="ECO:0000269|PubMed:22354971"
FT MUTAGEN 82
FT /note="F->A: 58-fold reduction in KCNA3 inhibition."
FT /evidence="ECO:0000269|PubMed:22354971"
FT MUTAGEN 84
FT /note="K->A: 74-fold reduction in KCNA3 inhibition."
FT /evidence="ECO:0000269|PubMed:22354971"
SQ SEQUENCE 88 AA; 9855 MW; 03698FA348984FE9 CRC64;
MIIFYGLFSI LVLTSINIAE AGHHNRVNCL LPPKTGPCKG SFARYYFDIE TGSCKAFIYG
GCEGNSNNFS EKHHCEKRCR GFRKFGGK
