TK1C_HADVE
ID TK1C_HADVE Reviewed; 37 AA.
AC P82228;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 1.
DT 25-MAY-2022, entry version 86.
DE RecName: Full=Lambda-hexatoxin-Hv1c {ECO:0000305};
DE Short=Lambda-HXTX-Hv1c {ECO:0000305};
DE AltName: Full=Janus-atracotoxin-Hv1c {ECO:0000303|PubMed:10881200, ECO:0000303|PubMed:11937509, ECO:0000303|PubMed:12220722};
DE Short=Janus-AcTx-Hv1c {ECO:0000303|PubMed:10881200, ECO:0000303|PubMed:11937509, ECO:0000303|PubMed:12220722};
DE AltName: Full=Kappa-atracotoxin-Hv1c;
DE Short=Kappa-AcTx-Hv1c;
DE AltName: Full=Kappa-hexatoxin-Hv1c {ECO:0000305};
DE Short=Kappa-HXTX-Hv1c {ECO:0000305};
OS Hadronyche versuta (Blue mountains funnel-web spider) (Atrax versutus).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Hexathelidae; Hadronyche.
OX NCBI_TaxID=6904;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, STRUCTURE BY NMR, AND
RP DISULFIDE BOND.
RC TISSUE=Venom;
RX PubMed=10881200; DOI=10.1038/75921;
RA Wang X.-H., Connor M., Smith R., Maciejewski M.W., Howden M.E.H.,
RA Nicholson G.M., Christie M.J., King G.F.;
RT "Discovery and characterization of a family of insecticidal neurotoxins
RT with a rare vicinal disulfide bridge.";
RL Nat. Struct. Biol. 7:505-513(2000).
RN [2]
RP MUTAGENESIS OF ILE-2; ARG-8; PRO-9; 13-CYS-CYS-14; VAL-29 AND TYR-31, AND
RP TOXIC DOSE.
RX PubMed=11937509; DOI=10.1074/jbc.m202297200;
RA Maggio F., King G.F.;
RT "Scanning mutagenesis of a Janus-faced atracotoxin reveals a bipartite
RT surface patch that is essential for neurotoxic function.";
RL J. Biol. Chem. 277:22806-22813(2002).
RN [3]
RP MUTAGENESIS OF ALA-1; 1-ALA-ILE-2 AND 36-GLU-PRO-37, AND TOXIC DOSE.
RX PubMed=12220722; DOI=10.1016/s0041-0101(02)00154-x;
RA Maggio F., King G.F.;
RT "Role of the structurally disordered N- and C-terminal residues in the
RT Janus-faced atracotoxins.";
RL Toxicon 40:1355-1361(2002).
RN [4]
RP FUNCTION.
RX PubMed=17141372; DOI=10.1016/j.peptides.2006.08.026;
RA Tedford H.W., Maggio F., Reenan R.A., King G.;
RT "A model genetic system for testing the in vivo function of peptide
RT toxins.";
RL Peptides 28:51-56(2007).
RN [5]
RP FUNCTION.
RX PubMed=18986214; DOI=10.1371/journal.pbio.0060273;
RA Wu Y., Cao G., Pavlicek B., Luo X., Nitabach M.N.;
RT "Phase coupling of a circadian neuropeptide with rest/activity rhythms
RT detected using a membrane-tethered spider toxin.";
RL PLoS Biol. 6:E273-E273(2008).
RN [6]
RP FUNCTION.
RX PubMed=18625007; DOI=10.1111/j.1742-4658.2008.06545.x;
RA Gunning S.J., Maggio F., Windley M.J., Valenzuela S.M., King G.F.,
RA Nicholson G.M.;
RT "The Janus-faced atracotoxins are specific blockers of invertebrate K(Ca)
RT channels.";
RL FEBS J. 275:4045-4059(2008).
CC -!- FUNCTION: This excitatory toxin inhibits insect calcium-activated
CC potassium (KCa) channels (Slo-type). Pan-neuronal expression in
CC Drosophila is lethal but flies engineered to express the toxin only in
CC clock neurons have defects in circadian rhythm but a normal lifespan.
CC {ECO:0000269|PubMed:10881200, ECO:0000269|PubMed:17141372,
CC ECO:0000269|PubMed:18625007, ECO:0000269|PubMed:18986214}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10881200}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:10881200}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:10881200}.
CC -!- TOXIC DOSE: LD(50) of recombinant toxin is 320 +-20 pmol/g in house
CC flies (Musca domestica). {ECO:0000269|PubMed:11937509}.
CC -!- TOXIC DOSE: LD(50) of recombinant toxin is 91 +-5 pmol/g in house flies
CC (Musca domestica). {ECO:0000269|PubMed:12220722}.
CC -!- MISCELLANEOUS: Does not affect a wide range of potassium, calcium and
CC sodium voltage-gated channels. {ECO:0000269|PubMed:18625007}.
CC -!- SIMILARITY: Belongs to the neurotoxin 11 (kappa toxin) family.
CC {ECO:0000305}.
CC -!- CAUTION: This toxin has the prefix lambda in its name (instead of
CC kappa), since lambda is the Greek letter attributed to calcium-
CC activated potassium (KCa) channel impairing toxins (according to the
CC nomenclature of King et al., 2008). {ECO:0000305}.
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DR PDB; 1DL0; NMR; -; A=1-37.
DR PDBsum; 1DL0; -.
DR AlphaFoldDB; P82228; -.
DR BMRB; P82228; -.
DR SMR; P82228; -.
DR ArachnoServer; AS000174; kappa-hexatoxin-Hv1c.
DR EvolutionaryTrace; P82228; -.
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:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR012499; Toxin_16.
DR Pfam; PF07945; Toxin_16; 1.
DR PROSITE; PS60020; J_ACTX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium-activated potassium channel impairing toxin;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Knottin; Neurotoxin; Potassium channel impairing toxin; Secreted; Toxin.
FT PEPTIDE 1..37
FT /note="Lambda-hexatoxin-Hv1c"
FT /evidence="ECO:0000269|PubMed:10881200"
FT /id="PRO_0000044998"
FT SITE 2
FT /note="Important for the neurotoxic activity"
FT SITE 8
FT /note="Critical for the neurotoxic activity"
FT SITE 9
FT /note="Critical for the neurotoxic activity"
FT SITE 13
FT /note="Critical for the neurotoxic activity"
FT SITE 14
FT /note="Critical for the neurotoxic activity"
FT SITE 29
FT /note="Important for the neurotoxic activity"
FT SITE 31
FT /note="Critical for the neurotoxic activity"
FT DISULFID 3..17
FT /evidence="ECO:0000269|PubMed:10881200,
FT ECO:0000312|PDB:1DL0"
FT DISULFID 10..22
FT /evidence="ECO:0000269|PubMed:10881200,
FT ECO:0000312|PDB:1DL0"
FT DISULFID 13..14
FT /evidence="ECO:0000269|PubMed:10881200,
FT ECO:0000312|PDB:1DL0"
FT DISULFID 16..32
FT /evidence="ECO:0000269|PubMed:10881200,
FT ECO:0000312|PDB:1DL0"
FT MUTAGEN 1..2
FT /note="Missing: 73-fold decrease in toxicity to flies."
FT /evidence="ECO:0000269|PubMed:12220722"
FT MUTAGEN 1
FT /note="Missing: No change in toxicity."
FT /evidence="ECO:0000269|PubMed:12220722"
FT MUTAGEN 2
FT /note="I->A: 7-fold decrease in toxicity to flies."
FT /evidence="ECO:0000269|PubMed:11937509"
FT MUTAGEN 8
FT /note="R->A: 98-fold decrease in toxicity to flies."
FT /evidence="ECO:0000269|PubMed:11937509"
FT MUTAGEN 8
FT /note="R->E: 270-fold decrease in toxicity to flies."
FT /evidence="ECO:0000269|PubMed:11937509"
FT MUTAGEN 9
FT /note="P->A: 269-fold decrease in toxicity to flies."
FT /evidence="ECO:0000269|PubMed:11937509"
FT MUTAGEN 13..14
FT /note="CC->SS: 423-fold decrease in toxicity to flies."
FT /evidence="ECO:0000269|PubMed:11937509"
FT MUTAGEN 29
FT /note="V->A: 13-fold decrease in toxicity to flies."
FT /evidence="ECO:0000269|PubMed:11937509"
FT MUTAGEN 31
FT /note="Y->A: 162-fold decrease in toxicity to flies."
FT /evidence="ECO:0000269|PubMed:11937509"
FT MUTAGEN 31
FT /note="Y->F: 1.8-fold decrease in toxicity to flies."
FT /evidence="ECO:0000269|PubMed:11937509"
FT MUTAGEN 35..37
FT /note="Missing: No change in toxicity to flies."
FT MUTAGEN 36..37
FT /note="Missing: No change in toxicity."
FT /evidence="ECO:0000269|PubMed:12220722"
FT STRAND 20..24
FT /evidence="ECO:0007829|PDB:1DL0"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:1DL0"
SQ SEQUENCE 37 AA; 3768 MW; E4DDF046CC750FFC CRC64;
AICTGADRPC AACCPCCPGT SCKAESNGVS YCRKDEP
