SCX1_ODODO
ID SCX1_ODODO Reviewed; 65 AA.
AC P84646;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=Alpha-toxin OD1 {ECO:0000303|PubMed:16038905};
OS Odontobuthus doriae (Yellow Iranian scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Odontobuthus.
OX NCBI_TaxID=342590;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND
RP AMIDATION AT ARG-65.
RC TISSUE=Venom;
RX PubMed=16038905; DOI=10.1016/j.febslet.2005.06.052;
RA Jalali A., Bosmans F., Amininasab M., Clynen E., Cuypers E.,
RA Zaremirakabadi A., Sarbolouki M.N., Schoofs L., Vatanpour H., Tytgat J.;
RT "OD1, the first toxin isolated from the venom of the scorpion Odonthobuthus
RT doriae active on voltage-gated Na+ channels.";
RL FEBS Lett. 579:4181-4186(2005).
RN [2]
RP FUNCTION.
RX PubMed=16641312; DOI=10.1124/mol.106.022970;
RA Maertens C., Cuypers E., Amininasab M., Jalali A., Vatanpour H., Tytgat J.;
RT "Potent modulation of the voltage-gated sodium channel Nav1.7 by OD1, a
RT toxin from the scorpion Odonthobuthus doriae.";
RL Mol. Pharmacol. 70:405-414(2006).
RN [3]
RP FUNCTION, AND MODEL OF NAV1.7/SCN9A-MEDIATED PAIN.
RX PubMed=26999206; DOI=10.3390/toxins8030078;
RA Deuis J.R., Wingerd J.S., Winter Z., Durek T., Dekan Z., Sousa S.R.,
RA Zimmermann K., Hoffmann T., Weidner C., Nassar M.A., Alewood P.F.,
RA Lewis R.J., Vetter I.;
RT "Analgesic effects of GpTx-1, PF-04856264 and CNV1014802 in a mouse model
RT of Nav1.7-mediated pain.";
RL Toxins 8:1-19(2016).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS), SYNTHESIS, FUNCTION, DISULFIDE
RP BONDS, AND MUTAGENESIS OF TYR-6; 9-ASP--LYS-11; LYS-11; LYS-51; GLU-55 AND
RP ILE-60.
RX PubMed=23527544; DOI=10.1021/cb400012k;
RA Durek T., Vetter I., Wang C.I., Motin L., Knapp O., Adams D.J., Lewis R.J.,
RA Alewood P.F.;
RT "Chemical engineering and structural and pharmacological characterization
RT of the alpha-scorpion toxin OD1.";
RL ACS Chem. Biol. 8:1215-1222(2013).
CC -!- FUNCTION: Alpha toxins bind voltage-independently at site-3 of sodium
CC channels and inhibit the inactivation of the activated channels. The
CC toxin affect mammalian sodium channels Nav1.7/SCN9A (EC(50)=4.5 nM),
CC Nav1.4/SCN4A (EC(50)=9.6 nM), Nav1.6/SCN8A (EC(50)=30 nM), Nav1.5/SCN5A
CC (only at micromolar concentrations), and insect sodium channel
CC para/tipE (EC(50)=80 nM) (PubMed:16038905, PubMed:16641312,
CC PubMed:23527544). In vivo, intraplantar administration of this toxin
CC elicits pain behaviors, including licking and flinching of the hind paw
CC (PubMed:26999206). {ECO:0000269|PubMed:16038905,
CC ECO:0000269|PubMed:16641312, ECO:0000269|PubMed:23527544}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16038905}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000269|PubMed:16038905}.
CC -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to
CC antiparallel beta-sheets by disulfide bonds (CS-alpha/beta).
CC {ECO:0000305}.
CC -!- MASS SPECTROMETRY: Mass=7204.8; Method=MALDI; Note=With amidation.;
CC Evidence={ECO:0000269|PubMed:16038905};
CC -!- BIOTECHNOLOGY: Intraplantal administration of this protein is used as a
CC pharmacological tool to establish a Nav1.7/SCN9A-mediated mouse model
CC of pain. {ECO:0000269|PubMed:26999206}.
CC -!- MISCELLANEOUS: Has no effect on mammalian sodium channels Nav1.2/SCN2A,
CC Nav1.3/SCN3A, and Nav1.8/SCN10A (PubMed:16038905, PubMed:16641312).
CC {ECO:0000269|PubMed:16038905, ECO:0000269|PubMed:16641312}.
CC -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC Sodium channel inhibitor family. Alpha subfamily. {ECO:0000255}.
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DR PDB; 4HHF; X-ray; 1.80 A; A=1-65.
DR PDBsum; 4HHF; -.
DR AlphaFoldDB; P84646; -.
DR SMR; P84646; -.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006952; P:defense response; IEA:InterPro.
DR CDD; cd00107; Knot1; 1.
DR Gene3D; 3.30.30.10; -; 1.
DR InterPro; IPR044062; LCN-type_CS_alpha_beta_dom.
DR InterPro; IPR003614; Scorpion_toxin-like.
DR InterPro; IPR036574; Scorpion_toxin-like_sf.
DR InterPro; IPR018218; Scorpion_toxinL.
DR InterPro; IPR002061; Scorpion_toxinL/defensin.
DR Pfam; PF00537; Toxin_3; 1.
DR PRINTS; PR00285; SCORPNTOXIN.
DR SMART; SM00505; Knot1; 1.
DR SUPFAM; SSF57095; SSF57095; 1.
DR PROSITE; PS51863; LCN_CSAB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Secreted; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT CHAIN 1..65
FT /note="Alpha-toxin OD1"
FT /evidence="ECO:0000269|PubMed:16038905"
FT /id="PRO_0000066788"
FT DOMAIN 3..65
FT /note="LCN-type CS-alpha/beta"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT MOTIF 9..11
FT /note="Important for toxin selectivity for individual Nav
FT channel subtype (Nav1.6/SCN8A and Nav1.7/SCN9A), but not
FT for toxin potency"
FT /evidence="ECO:0000269|PubMed:23527544"
FT SITE 6
FT /note="Important for toxin potency but not for selectivity
FT for individual Nav channel subtype (Nav1.6/SCN8A and
FT Nav1.7/SCN9A)"
FT /evidence="ECO:0000269|PubMed:23527544"
FT MOD_RES 65
FT /note="Arginine amide"
FT /evidence="ECO:0000269|PubMed:16038905"
FT DISULFID 13..64
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210,
FT ECO:0000269|PubMed:23527544, ECO:0000312|PDB:4HHF"
FT DISULFID 17..37
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210,
FT ECO:0000269|PubMed:23527544, ECO:0000312|PDB:4HHF"
FT DISULFID 23..47
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210,
FT ECO:0000269|PubMed:23527544, ECO:0000312|PDB:4HHF"
FT DISULFID 27..49
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210,
FT ECO:0000269|PubMed:23527544, ECO:0000312|PDB:4HHF"
FT MUTAGEN 6
FT /note="Y->F: Decrease in potency for Nav1.4/SCN4A (17-
FT fold), Nav1.6/SCN8A (8-fold), and Nav1.7/SCN9A (17-fold)."
FT /evidence="ECO:0000269|PubMed:23527544"
FT MUTAGEN 9..11
FT /note="DDK->KPH: Increase in potency for Nav1.4/SCN4A (1.6-
FT fold) and Nav1.7/SCN9A (2.3-fold) and decrease in potency
FT for Nav1.6/SCN8A (3-fold), resulting in a 40-fold increase
FT of selectivity for Nav1.7/SCN9A over Nav1.6/SCN8A. No
FT change in potency for Nav1.4/SCN4A and Nav1.6/SCN8A, and
FT important increase in potency for Nav1.7/SCN9A (11.7-fold);
FT when associated with A-55."
FT /evidence="ECO:0000269|PubMed:23527544"
FT MUTAGEN 11
FT /note="K->V: Increase in potency for Nav1.4/SCN4A (5-fold)
FT and Nav1.6/SCN8A (7.8-fold) and decrease in potency for
FT Nav1.7/SCN9A (4.3-fold), resulting in a 5-fold increase of
FT selectivity for Nav1.6/SCN8A over Nav1.7/SCN9A. Increase in
FT potency for Nav1.6/SCN8A (16-fold), no change in potency
FT for Nav1.7/SCN9A, and decrease in potency for Nav1.4/SCN4A
FT (1.6-fold); when associated with A-55."
FT /evidence="ECO:0000269|PubMed:23527544"
FT MUTAGEN 51
FT /note="K->A: No change in potency for Nav1.4/SCN4A,
FT Nav1.6/SCN8A and Nav1.7/SCN9A."
FT /evidence="ECO:0000269|PubMed:23527544"
FT MUTAGEN 55
FT /note="E->A: No change in potency for Nav1.4/SCN4A and
FT Nav1.7/SCN9A, and important decrease in potency for
FT Nav1.6/SCN8A (2.3-fold), resulting in a 13-fold increase of
FT selectivity for Nav1.4/SCN4A and Nav1.7/SCN9A over
FT Nav1.6/SCN8A. No change in potency for Nav1.4/SCN4A;
FT Nav1.6/SCN8A, and important increase in potency for
FT Nav1.7/SCN9A (11.7-fold); when associated with 9-K--H-11.
FT Increase in potency for Nav1.6/SCN8A (16-fold), no change
FT in potency for Nav1.7/SCN9A, and decrease in potency for
FT Nav1.4/SCN4A (1.6-fold); when associated with V-11."
FT /evidence="ECO:0000269|PubMed:23527544"
FT MUTAGEN 55
FT /note="E->H: No change in potency for Nav1.4/SCN4A and
FT Nav1.7/SCN9A, and decrease in potency for Nav1.6/SCN8A
FT (1.7-fold)."
FT /evidence="ECO:0000269|PubMed:23527544"
FT MUTAGEN 60
FT /note="I->G: No change in potency for Nav1.4/SCN4A, and
FT decrease in potency for Nav1.6/SCN8A (1.6-fold) and
FT Nav1.7/SCN9A (2.6-fold)."
FT /evidence="ECO:0000269|PubMed:23527544"
FT STRAND 2..8
FT /evidence="ECO:0007829|PDB:4HHF"
FT HELIX 20..29
FT /evidence="ECO:0007829|PDB:4HHF"
FT STRAND 33..39
FT /evidence="ECO:0007829|PDB:4HHF"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:4HHF"
FT STRAND 45..53
FT /evidence="ECO:0007829|PDB:4HHF"
SQ SEQUENCE 65 AA; 7215 MW; FF76362F0C7ACCE7 CRC64;
GVRDAYIADD KNCVYTCASN GYCNTECTKN GAESGYCQWI GRYGNACWCI KLPDEVPIRI
PGKCR
