TP1B_HADIN
ID TP1B_HADIN Reviewed; 75 AA.
AC P0DP46;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2017, sequence version 1.
DT 25-MAY-2022, entry version 9.
DE RecName: Full=Pi-hexatoxin-Hi1b {ECO:0000303|PubMed:28320941};
DE Short=Pi-HXTX-Hi1b {ECO:0000303|PubMed:28320941};
DE AltName: Full=Double-knot toxin {ECO:0000305};
DE Short=DkTx {ECO:0000305};
OS Hadronyche infensa (Fraser island funnel-web spider) (Atrax infensus).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Hexathelidae; Hadronyche.
OX NCBI_TaxID=153481;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=28320941; DOI=10.1073/pnas.1614728114;
RA Chassagnon I.R., McCarthy C.A., Chin Y.K., Pineda S.S., Keramidas A.,
RA Mobli M., Pham V., De Silva T.M., Lynch J.W., Widdop R.E., Rash L.D.,
RA King G.F.;
RT "Potent neuroprotection after stroke afforded by a double-knot spider-venom
RT peptide that inhibits acid-sensing ion channel 1a.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:3750-3755(2017).
CC -!- FUNCTION: This toxin potently and selectively inhibits ASIC1a, an
CC isoform of the gene ASIC1. It incompletely inhibits ASIC1a activation
CC in a pH-independent and slowly reversible manner. This toxin acts by
CC binding to and stabilizing the closed state of the channel, thereby
CC impeding the transition into a conducting state. This toxin may bind to
CC the acidic pocket of ASIC1a, since mutation of a key residue of this
CC pocket (Arg-350) abolishes the ability of the toxin to inhibit ASIC1a.
CC In vivo, this toxin protects the brain from neuronal injury when
CC administered up to 8 hours after stroke onset.
CC {ECO:0000250|UniProtKB:A0A1L1QJU3}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P60514}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:28320941}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin. This toxin contains 2
CC 'disulfide through disulfide knots' that are separated by a short
CC linker. {ECO:0000250|UniProtKB:A0A1L1QJU3}.
CC -!- SIMILARITY: Belongs to the psalmotoxin-1 family. Double-knot toxin
CC subfamily. {ECO:0000305}.
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DR AlphaFoldDB; P0DP46; -.
DR SMR; P0DP46; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
PE 3: Inferred from homology;
KW Disulfide bond; Ion channel impairing toxin;
KW Proton-gated sodium channel impairing toxin; Secreted; Toxin.
FT CHAIN 1..75
FT /note="Pi-hexatoxin-Hi1b"
FT /evidence="ECO:0000305|PubMed:28320941"
FT /id="PRO_0000440132"
FT DISULFID 3..18
FT /evidence="ECO:0000250|UniProtKB:A0A1L1QJU3"
FT DISULFID 10..23
FT /evidence="ECO:0000250|UniProtKB:A0A1L1QJU3"
FT DISULFID 17..33
FT /evidence="ECO:0000250|UniProtKB:A0A1L1QJU3"
FT DISULFID 40..55
FT /evidence="ECO:0000250|UniProtKB:A0A1L1QJU3"
FT DISULFID 47..60
FT /evidence="ECO:0000250|UniProtKB:A0A1L1QJU3"
FT DISULFID 54..71
FT /evidence="ECO:0000250|UniProtKB:A0A1L1QJU3"
SQ SEQUENCE 75 AA; 8674 MW; 15256C77BDC68328 CRC64;
NECIRKWLSC VDRKNDCCEG LECYKRRHSF EVCVPIPGFC LVKWKQCDGR ERDCCPGLEC
WKRSGNKSSV CAPIT