3SX1_OPHHA
ID 3SX1_OPHHA Reviewed; 57 AA.
AC P83302;
DT 27-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-MAY-2002, sequence version 1.
DT 25-MAY-2022, entry version 73.
DE RecName: Full=Neurotoxin Oh9-1 {ECO:0000303|PubMed:12056805, ECO:0000303|PubMed:26448325};
DE AltName: Full=OMEGA-neurotoxin Oh9-1 {ECO:0000303|PubMed:26448325};
DE AltName: Full=Three-finger toxin;
DE Short=3FTx;
OS Ophiophagus hannah (King cobra) (Naja hannah).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Ophiophagus.
OX NCBI_TaxID=8665;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, TOXIC DOSE, MASS
RP SPECTROMETRY, AND CIRCULAR DICHROISM ANALYSIS.
RC TISSUE=Venom;
RX PubMed=12056805; DOI=10.1016/s0006-291x(02)00518-1;
RA Chang L.-S., Liou J.-C., Lin S.-R., Huang H.-B.;
RT "Purification and characterization of a neurotoxin from the venom of
RT Ophiophagus hannah (king cobra).";
RL Biochem. Biophys. Res. Commun. 294:574-578(2002).
RN [2]
RP FUNCTION, AND MUTAGENESIS OF HIS-7; LYS-22; THR-23; THR-24; MET-25; PHE-26;
RP PHE-27; ASN-29; HIS-30; VAL-32; LYS-45 AND TYR-46.
RX PubMed=26448325; DOI=10.1021/acschembio.5b00492;
RA Hassan-Puttaswamy V., Adams D.J., Kini R.M.;
RT "A distinct functional site in OMEGA-neurotoxins: novel antagonists of
RT nicotinic acetylcholine receptors from snake venom.";
RL ACS Chem. Biol. 10:2805-2815(2015).
CC -!- FUNCTION: This toxin binds and inhibits rat muscle adult alpha-1-beta-
CC 1-delta-epsilon/CHRNA1-CHRNB1-CHRND-CHRNE (IC(50)=3.1 uM) and fetal
CC alpha-1-beta-1-gamma-delta/CHRNA1-CHRNB1-CHRNG-CHRND (IC(50)=5.6 uM)
CC nicotinic acetylcholine receptors (nAChR) (PubMed:26448325). It shows a
CC very low inhibition on rat neuronal alpha-3-beta-2/CHRNA3-CHRNB2 nAChR
CC (IC(50)=50.2 uM) nAChR (PubMed:26448325). It does not inhibit human
CC glycine receptor (homopentamer composed of alpha-1 subunits), but seems
CC to potentiate it (about 2-fold increased activity). It binds to the
CC acetylcholine-binding pocket and acts as a competitive antagonist
CC (PubMed:26448325). {ECO:0000269|PubMed:12056805,
CC ECO:0000269|PubMed:26448325}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12056805}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:12056805}.
CC -!- MASS SPECTROMETRY: Mass=6508; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:12056805};
CC -!- TOXIC DOSE: LD(50) is 2 mg/kg by intravenous injection into mouse.
CC {ECO:0000269|PubMed:12056805}.
CC -!- MISCELLANEOUS: Does not inhibit human alpha-7/CHRNA7, alpha-9-alpha-
CC 10/CHRNA9-CHRNA10, alpha-3-beta-2/CHRNA3-CHRNB2, alpha-4-beta-4/CHRNA4-
CC CHRNB4, alpha-4-beta-2/CHRNA4-CHRNB2 and rat alpha-3-beta-4/CHRNA3-
CC CHRNB4 nAChR. Does not inhibit human GABA(A) receptor (heteropentamer
CC composed of alpha-1-beta-2-gamma-2 subunits and homopentamer composed
CC of rho-1 subunits). {ECO:0000269|PubMed:26448325}.
CC -!- MISCELLANEOUS: Hassan-Puttaswamy et al., 2015 propose to call this
CC novel class of nAChR competitive inhibitors 'OMEGA toxins'.
CC {ECO:0000305|PubMed:26448325}.
CC -!- MISCELLANEOUS: Is classified as a P-type cytotoxin, since a proline
CC residue stands at position 28 (Pro-31 in standard classification).
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the snake three-finger toxin family. Short-chain
CC subfamily. {ECO:0000305}.
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DR AlphaFoldDB; P83302; -.
DR SMR; P83302; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR SUPFAM; SSF57302; SSF57302; 1.
PE 1: Evidence at protein level;
KW Acetylcholine receptor inhibiting toxin; Direct protein sequencing;
KW Disulfide bond; Ion channel impairing toxin; Neurotoxin;
KW Postsynaptic neurotoxin; Secreted; Toxin.
FT CHAIN 1..57
FT /note="Neurotoxin Oh9-1"
FT /evidence="ECO:0000269|PubMed:12056805"
FT /id="PRO_0000093630"
FT SITE 7
FT /note="Important residue for inhibition of muscle alpha-1-
FT beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) and
FT neuronal alpha-3-beta-2/CHRNA3-CHRNB2 nAChR"
FT /evidence="ECO:0000269|PubMed:26448325"
FT SITE 22
FT /note="Important residue for inhibition of muscle alpha-1-
FT beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) and
FT neuronal alpha-3-beta-2/CHRNA3-CHRNB2 nAChR"
FT /evidence="ECO:0000269|PubMed:26448325"
FT SITE 23
FT /note="Key residue for inhibition of muscle alpha-1-beta-1-
FT delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) nAChR"
FT /evidence="ECO:0000269|PubMed:26448325"
FT SITE 24
FT /note="Important residue for inhibition of muscle alpha-1-
FT beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) nAChR"
FT /evidence="ECO:0000269|PubMed:26448325"
FT SITE 25
FT /note="Key residue for inhibition of muscle alpha-1-beta-1-
FT delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) and important for
FT inhibition of neuronal alpha-3-beta-2/CHRNA3-CHRNB2 nAChR"
FT /evidence="ECO:0000269|PubMed:26448325"
FT SITE 26
FT /note="Important residue for inhibition of muscle alpha-1-
FT beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) nAChR"
FT /evidence="ECO:0000269|PubMed:26448325"
FT SITE 27
FT /note="Key residue for inhibition of muscle alpha-1-beta-1-
FT delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) and important
FT residue for inhibition of neuronal alpha-3-beta-2/CHRNA3-
FT CHRNB2 nAChR"
FT /evidence="ECO:0000269|PubMed:26448325"
FT SITE 30
FT /note="Important residue for inhibition of muscle alpha-1-
FT beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) and
FT neuronal alpha-3-beta-2/CHRNA3-CHRNB2 nAChR"
FT /evidence="ECO:0000269|PubMed:26448325"
FT SITE 45
FT /note="Important residue for inhibition of muscle alpha-1-
FT beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) and
FT neuronal alpha-3-beta-2/CHRNA3-CHRNB2 nAChR"
FT /evidence="ECO:0000269|PubMed:26448325"
FT SITE 46
FT /note="Important residue for interaction with muscle alpha-
FT 1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) and
FT neuronal alpha-3-beta-2/CHRNA3-CHRNB2 nAChR"
FT /evidence="ECO:0000269|PubMed:26448325"
FT DISULFID 3..19
FT /evidence="ECO:0000250|UniProtKB:P0DKR6"
FT DISULFID 12..37
FT /evidence="ECO:0000250|UniProtKB:P0DKR6"
FT DISULFID 41..49
FT /evidence="ECO:0000250|UniProtKB:P0DKR6"
FT DISULFID 50..55
FT /evidence="ECO:0000250|UniProtKB:P0DKR6"
FT MUTAGEN 7
FT /note="H->A: Small decrease in inhibition of rat muscle
FT alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE)
FT and neuronal alpha-3-beta-2/CHRNA3-CHRNB2 nAChR."
FT /evidence="ECO:0000269|PubMed:26448325"
FT MUTAGEN 22
FT /note="K->A: Small decrease in inhibition of rat muscle
FT alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE)
FT and neuronal alpha-3-beta-2/CHRNA3-CHRNB2 nAChR."
FT /evidence="ECO:0000269|PubMed:26448325"
FT MUTAGEN 23
FT /note="T->A: Complete loss of inhibition of rat muscle
FT alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE)
FT and no change in inhibition of neuronal alpha-3-beta-
FT 2/CHRNA3-CHRNB2 nAChR."
FT /evidence="ECO:0000269|PubMed:26448325"
FT MUTAGEN 24
FT /note="T->A: Small decrease in inhibition of rat muscle
FT alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE)
FT and small increase in inhibition of neuronal alpha-3-beta-
FT 2/CHRNA3-CHRNB2 nAChR."
FT /evidence="ECO:0000269|PubMed:26448325"
FT MUTAGEN 25
FT /note="M->A: Complete loss of inhibition of rat muscle
FT alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE)
FT and small decrease in inhibition of neuronal alpha-3-beta-
FT 2/CHRNA3-CHRNB2 nAChR."
FT /evidence="ECO:0000269|PubMed:26448325"
FT MUTAGEN 26
FT /note="F->A: Important decrease in inhibition of rat muscle
FT alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE)
FT and no change in inhibition of neuronal alpha-3-beta-
FT 2/CHRNA3-CHRNB2 nAChR."
FT /evidence="ECO:0000269|PubMed:26448325"
FT MUTAGEN 27
FT /note="F->A: Important decrease in inhibition of rat muscle
FT alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE)
FT and small decrease in inhibition of neuronal alpha-3-beta-
FT 2/CHRNA3-CHRNB2 nAChR."
FT /evidence="ECO:0000269|PubMed:26448325"
FT MUTAGEN 29
FT /note="N->A: No change in inhibition of rat muscle alpha-1-
FT beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) and small
FT increase in inhibition of neuronal alpha-3-beta-2/CHRNA3-
FT CHRNB2 nAChR."
FT /evidence="ECO:0000269|PubMed:26448325"
FT MUTAGEN 30
FT /note="H->A: Small decrease in inhibition of rat muscle
FT alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE)
FT and important decrease in inhibition of neuronal alpha-3-
FT beta-2/CHRNA3-CHRNB2 nAChR."
FT /evidence="ECO:0000269|PubMed:26448325"
FT MUTAGEN 32
FT /note="V->A: No change in inhibition of rat muscle alpha-1-
FT beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) and small
FT increase in inhibition of neuronal alpha-3-beta-2/CHRNA3-
FT CHRNB2 nAChR."
FT /evidence="ECO:0000269|PubMed:26448325"
FT MUTAGEN 45
FT /note="K->A: Small decrease in inhibition of rat muscle
FT alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE)
FT and neuronal alpha-3-beta-2/CHRNA3-CHRNB2 nAChR."
FT /evidence="ECO:0000269|PubMed:26448325"
FT MUTAGEN 46
FT /note="Y->A: Small increase in inhibition of rat muscle
FT alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE)
FT and neuronal alpha-3-beta-2/CHRNA3-CHRNB2 nAChR."
FT /evidence="ECO:0000269|PubMed:26448325"
SQ SEQUENCE 57 AA; 6516 MW; B2AE91DEA942F1BB CRC64;
LICHRVHGLQ TCEPDQKFCF RKTTMFFPNH PVLLMGCTSS CPTEKYSVCC STDKCNK
