VKT1A_CYRSC
ID VKT1A_CYRSC Reviewed; 88 AA.
AC P68425; B2ZBB7; B3FIU6;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 2.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Kunitz-type kappaPI-theraphotoxin-Hs1a;
DE Short=KappaPI-TRTX-Hs1a;
DE AltName: Full=Huwentoxin-11g8 {ECO:0000303|PubMed:18590782};
DE Short=HW11g8 {ECO:0000303|PubMed:18590782};
DE AltName: Full=Huwentoxin-XI;
DE Short=HwTx-XI;
DE AltName: Full=Kunitz-type serine protease inhibitor huwentoxin-11;
DE Flags: Precursor;
OS Cyriopagopus schmidti (Chinese bird spider) (Haplopelma schmidti).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Theraphosidae; Cyriopagopus.
OX NCBI_TaxID=29017;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=18590782; DOI=10.1016/j.peptides.2008.06.001;
RA Jiang L., Chen J., Peng L., Zhang Y., Xiong X., Liang S.;
RT "Genomic organization and cloning of novel genes encoding toxin-like
RT peptides of three superfamilies from the spider Orinithoctonus huwena.";
RL Peptides 29:1679-1684(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 34-88, MUTAGENESIS OF
RP ARG-38; LEU-39 AND LYS-47, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18923708; DOI=10.1371/journal.pone.0003414;
RA Yuan C.-H., He Q.-Y., Peng K., Diao J.-B., Jiang L.-P., Tang X.,
RA Liang S.-P.;
RT "Discovery of a distinct superfamily of Kunitz-type toxin (KTT) from
RT tarantulas.";
RL PLoS ONE 3:E3414-E3414(2008).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=18482741; DOI=10.1016/j.toxicon.2008.03.024;
RA Jiang L., Peng L., Chen J., Zhang Y., Xiong X., Liang S.;
RT "Molecular diversification based on analysis of expressed sequence tags
RT from the venom glands of the Chinese bird spider Ornithoctonus huwena.";
RL Toxicon 51:1479-1489(2008).
RN [4]
RP PROTEIN SEQUENCE OF 34-88, FUNCTION, TOXIC DOSE, MASS SPECTROMETRY, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=15066414; DOI=10.1016/j.toxicon.2004.02.005;
RA Liang S.-P.;
RT "An overview of peptide toxins from the venom of the Chinese bird spider
RT Selenocosmia huwena Wang [=Ornithoctonus huwena (Wang)].";
RL Toxicon 43:575-585(2004).
RN [5]
RP STRUCTURE BY NMR OF 34-88, DISULFIDE BOND, AND FUNCTION.
RX PubMed=16820861; DOI=10.1111/j.1745-7270.2006.00191.x;
RA Peng K., Lin Y., Liang S.-P.;
RT "Nuclear magnetic resonance studies on huwentoxin-XI from the Chinese bird
RT spider Ornithoctonus huwena: 15N labeling and sequence-specific 1H, 15N
RT nuclear magnetic resonance assignments.";
RL Acta Biochim. Biophys. Sin. 38:457-466(2006).
CC -!- FUNCTION: Dual-function toxin that inhibits both serine proteases
CC (trypsin) and voltage-gated potassium channels (Kv). The toxin is more
CC active on Kv1.1/KCNA1 (78% inhibition), than on Kv1.2/KCNA2 (10%
CC inhibition), and Kv1.3/KCNA3 (28% inhibition), although a high dose (5
CC uM) is needed. The inhibition of potassium channels is voltage-
CC dependent. {ECO:0000269|PubMed:15066414, ECO:0000269|PubMed:16820861}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15066414}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:18923708}.
CC -!- MASS SPECTROMETRY: Mass=6166.23; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:15066414};
CC -!- TOXIC DOSE: LD(50) is 256 +/- 23 ug/kg by injection into the fourth
CC ventricle of the adult mouse brain. {ECO:0000269|PubMed:15066414}.
CC -!- SIMILARITY: Belongs to the venom Kunitz-type family. 02 (native)
CC subfamily. {ECO:0000305}.
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DR EMBL; EU635745; ACD01237.1; -; Genomic_DNA.
DR EMBL; EU195290; ABY77743.1; -; mRNA.
DR PDB; 2JOT; NMR; -; A=34-88.
DR PDBsum; 2JOT; -.
DR AlphaFoldDB; P68425; -.
DR BMRB; P68425; -.
DR SMR; P68425; -.
DR MEROPS; I02.968; -.
DR ArachnoServer; AS000326; kappa-theraphotoxin-Hs1a.
DR EvolutionaryTrace; P68425; -.
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:UniProtKB-KW.
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; IEA:UniProt.
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; Potassium channel impairing toxin;
KW Protease inhibitor; Secreted; Serine protease inhibitor; Signal; Toxin;
KW Voltage-gated potassium channel impairing toxin.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT PROPEP 28..33
FT /evidence="ECO:0000269|PubMed:15066414,
FT ECO:0000269|PubMed:18923708"
FT /id="PRO_0000378335"
FT CHAIN 34..88
FT /note="Kunitz-type kappaPI-theraphotoxin-Hs1a"
FT /id="PRO_0000087671"
FT DOMAIN 37..85
FT /note="BPTI/Kunitz inhibitor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031"
FT SITE 39
FT /note="May bind Kv1.1/KCNA1"
FT SITE 47..48
FT /note="Reactive bond for trypsin"
FT DISULFID 37..85
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031,
FT ECO:0000269|PubMed:16820861"
FT DISULFID 46..68
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031,
FT ECO:0000269|PubMed:16820861"
FT DISULFID 60..81
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00031,
FT ECO:0000269|PubMed:16820861"
FT MUTAGEN 38
FT /note="R->I: 14-fold reduction in inhibitory potency toward
FT Kv1.1/KCNA1."
FT /evidence="ECO:0000269|PubMed:18923708"
FT MUTAGEN 39
FT /note="L->A,Y: 200-fold reduction in inhibitory potency
FT toward Kv1.1/KCNA1."
FT /evidence="ECO:0000269|PubMed:18923708"
FT MUTAGEN 47
FT /note="K->A: No binding to trypsin."
FT /evidence="ECO:0000269|PubMed:18923708"
FT CONFLICT 30
FT /note="H -> R (in Ref. 3; ABY77743)"
FT /evidence="ECO:0000305"
FT CONFLICT 30
FT /note="H -> S (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT STRAND 51..56
FT /evidence="ECO:0007829|PDB:2JOT"
FT STRAND 59..64
FT /evidence="ECO:0007829|PDB:2JOT"
FT STRAND 71..77
FT /evidence="ECO:0007829|PDB:2JOT"
FT HELIX 78..85
FT /evidence="ECO:0007829|PDB:2JOT"
SQ SEQUENCE 88 AA; 9721 MW; 1A99CEA6DDD4F652 CRC64;
MGIARILSAV LFLSVLFVVT FPALLSADHH DGRIDTCRLP SDRGRCKASF ERWYFNGRTC
AKFIYGGCGG NGNKFPTQEA CMKRCAKA
