SCX9_MESEU
ID SCX9_MESEU Reviewed; 66 AA.
AC P09981;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Alpha-like toxin BeM9 {ECO:0000303|PubMed:30007037};
DE AltName: Full=Neurotoxin M9 {ECO:0000303|PubMed:6497916};
OS Mesobuthus eupeus (Lesser Asian scorpion) (Buthus eupeus).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Mesobuthus.
OX NCBI_TaxID=34648;
RN [1]
RP PROTEIN SEQUENCE, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=6497916;
RA Volkova T.M., Garsia A.F., Telezhinskaya I.N., Potapenko N.A.,
RA Grishin E.V.;
RT "Amino acid sequence of 2 neurotoxins from the scorpion Buthus eupeus
RT venom.";
RL Bioorg. Khim. 10:979-982(1984).
RN [2]
RP PROTEIN SEQUENCE, AND BIOASSAY.
RC TISSUE=Venom;
RX PubMed=4091860;
RA Volkova T.M., Garsia A.F., Telezhinskaia I.N., Potapenko N.A.,
RA Grishin E.V.;
RT "Neurotoxins from the venom of the Central Asian scorpion Buthus eupeus.";
RL Bioorg. Khim. 11:1445-1456(1985).
RN [3]
RP FUNCTION.
RX PubMed=23637230; DOI=10.1074/jbc.m112.431650;
RA Chugunov A.O., Koromyslova A.D., Berkut A.A., Peigneur S., Tytgat J.,
RA Polyansky A.A., Pentkovsky V.M., Vassilevski A.A., Grishin E.V.,
RA Efremov R.G.;
RT "Modular organization of alpha-toxins from scorpion venom mirrors domain
RT structure of their targets, sodium channels.";
RL J. Biol. Chem. 288:19014-19027(2013).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF ALA-4; 8-LYS--HIS-10; VAL-13; GLU-15;
RP 17-TYR--SER-22; 40-ILE--LYS-43; ASN-56; 58-PRO--ILE-61 AND LYS-64.
RX PubMed=28889641; DOI=10.1002/1873-3468.12839;
RA Kuldyushev N.A., Berkut A.A., Peigneur S., Tytgat J., Grishin E.V.,
RA Vassilevski A.A.;
RT "Design of sodium channel ligands with defined selectivity - a case study
RT in scorpion alpha-toxins.";
RL FEBS Lett. 591:3414-3420(2017).
RN [5]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=3814183;
RA Pashkov V.S., Hoang A.N., Maiorov V.N., Bystrov V.F.;
RT "The structure of Buthus eupeus neurotoxin M9 in a solution studied by 1H-
RT NMR spectroscopy.";
RL Bioorg. Khim. 12:1306-1316(1986).
RN [6]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=3233282; DOI=10.1016/0301-4622(88)80016-4;
RA Pashkov V.S., Maiorov V.N., Bystrov V.F., Hoang A.N., Volkova T.M.,
RA Grishin E.V.;
RT "Solution spatial structure of 'long' neurotoxin M9 from the scorpion
RT Buthus eupeus by 1H-NMR spectroscopy.";
RL Biophys. Chem. 31:121-131(1988).
RN [7]
RP STRUCTURE BY NMR, DISULFIDE BOND, AND MUTAGENESIS OF ARG-60.
RX PubMed=30007037; DOI=10.1002/prot.25583;
RA Kuldyushev N.A., Mineev K.S., Berkut A.A., Peigneur S., Arseniev A.S.,
RA Tytgat J., Grishin E.V., Vassilevski A.A.;
RT "Refined structure of BeM9 reveals arginine hand, an overlooked structural
RT motif in scorpion toxins affecting sodium channels.";
RL Proteins 86:1117-1122(2018).
CC -!- FUNCTION: Alpha toxins bind voltage-independently at site-3 of sodium
CC channels (Nav) and inhibit the inactivation of the activated channels,
CC thereby blocking neuronal transmission. This toxin is active on both
CC mammals and insects, since it inhibits inactivation of rNav1.4/SCN4A,
CC hNav1.5/SCN5A, mNav1.6/SCN8A and insect BgNav1 and DmNav1 channels
CC (PubMed:23637230). In vivo, it shows paralytic activity in mice
CC (PubMed:4091860). {ECO:0000269|PubMed:23637230,
CC ECO:0000269|PubMed:4091860}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:6497916}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:6497916}.
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|PubMed:23637230}.
CC -!- MISCELLANEOUS: Does not show activity on rNav1.2/SCN2A (neither peak
CC current reduction, nor inhibition of inactivation) (PubMed:23637230).
CC {ECO:0000269|PubMed:23637230}.
CC -!- MISCELLANEOUS: Adopts a cis conformation at 9-Pro-His-10.
CC {ECO:0000269|PubMed:30007037}.
CC -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC Sodium channel inhibitor family. Alpha subfamily. {ECO:0000305}.
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DR PIR; JT0014; NTSR9E.
DR PDB; 5MOU; NMR; -; A=1-66.
DR PDBsum; 5MOU; -.
DR AlphaFoldDB; P09981; -.
DR BMRB; P09981; -.
DR SMR; P09981; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IEA:InterPro.
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; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Secreted; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT CHAIN 1..66
FT /note="Alpha-like toxin BeM9"
FT /evidence="ECO:0000269|PubMed:4091860,
FT ECO:0000269|PubMed:6497916"
FT /id="PRO_0000066729"
FT DOMAIN 2..66
FT /note="LCN-type CS-alpha/beta"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT SITE 60
FT /note="Key residue for activity on mammalian channels, it
FT controls twisting and flexibility of active residues at the
FT C-terminus"
FT /evidence="ECO:0000305|PubMed:30007037"
FT DISULFID 12..65
FT /evidence="ECO:0000269|PubMed:30007037,
FT ECO:0000269|PubMed:3233282, ECO:0000269|PubMed:3814183,
FT ECO:0000312|PDB:5MOU"
FT DISULFID 16..38
FT /evidence="ECO:0000269|PubMed:30007037,
FT ECO:0000269|PubMed:3233282, ECO:0000269|PubMed:3814183,
FT ECO:0000312|PDB:5MOU"
FT DISULFID 24..48
FT /evidence="ECO:0000269|PubMed:30007037,
FT ECO:0000269|PubMed:3233282, ECO:0000269|PubMed:3814183,
FT ECO:0000312|PDB:5MOU"
FT DISULFID 28..50
FT /evidence="ECO:0000269|PubMed:30007037,
FT ECO:0000269|PubMed:3233282, ECO:0000269|PubMed:3814183,
FT ECO:0000312|PDB:5MOU"
FT MUTAGEN 4
FT /note="A->G: In msBeM9; gain of activity on rNav1.2/SCN2A
FT (reduces peak current and inhibits inactivation), important
FT decrease or loss in activity on rNav1.4/SCN4A,
FT hNav1.5/SCN5A and BgNav1, and no change in activity on
FT mNav1.6/SCN8A."
FT /evidence="ECO:0000269|PubMed:28889641"
FT MUTAGEN 8..10
FT /note="KPH->DDV: In msBeM9; gain of activity on
FT rNav1.2/SCN2A (reduces peak current and inhibits
FT inactivation), important decrease or loss in activity on
FT rNav1.4/SCN4A, hNav1.5/SCN5A and BgNav1, and no change in
FT activity on mNav1.6/SCN8A."
FT /evidence="ECO:0000269|PubMed:28889641"
FT MUTAGEN 13
FT /note="V->T: In msBeM9; gain of activity on rNav1.2/SCN2A
FT (reduces peak current and inhibits inactivation), important
FT decrease or loss in activity on rNav1.4/SCN4A,
FT hNav1.5/SCN5A and BgNav1, and no change in activity on
FT mNav1.6/SCN8A."
FT /evidence="ECO:0000269|PubMed:28889641"
FT MUTAGEN 15
FT /note="E->F: In msBeM9; gain of activity on rNav1.2/SCN2A
FT (reduces peak current and inhibits inactivation), important
FT decrease or loss in activity on rNav1.4/SCN4A,
FT hNav1.5/SCN5A and BgNav1, and no change in activity on
FT mNav1.6/SCN8A."
FT /evidence="ECO:0000269|PubMed:28889641"
FT MUTAGEN 17..22
FT /note="YNPKGS->GRNA: In msBeM9; gain of activity on
FT rNav1.2/SCN2A (reduces peak current and inhibits
FT inactivation), important decrease or loss in activity on
FT rNav1.4/SCN4A, hNav1.5/SCN5A and BgNav1, and no change in
FT activity on mNav1.6/SCN8A."
FT /evidence="ECO:0000269|PubMed:28889641"
FT MUTAGEN 40..43
FT /note="ILGK->WASP: In msBeM9; gain of activity on
FT rNav1.2/SCN2A (reduces peak current and inhibits
FT inactivation), important decrease or loss in activity on
FT rNav1.4/SCN4A, hNav1.5/SCN5A and BgNav1, and no change in
FT activity on mNav1.6/SCN8A."
FT /evidence="ECO:0000269|PubMed:28889641"
FT MUTAGEN 56
FT /note="N->H: In msBeM9; gain of activity on rNav1.2/SCN2A
FT (reduces peak current and inhibits inactivation), important
FT decrease or loss in activity on rNav1.4/SCN4A,
FT hNav1.5/SCN5A and BgNav1, and no change in activity on
FT mNav1.6/SCN8A."
FT /evidence="ECO:0000269|PubMed:28889641"
FT MUTAGEN 58..61
FT /note="PIRI->RTKG: In msBeM9; gain of activity on
FT rNav1.2/SCN2A (reduces peak current and inhibits
FT inactivation), important decrease or loss in activity on
FT rNav1.4/SCN4A, hNav1.5/SCN5A and BgNav1, and no change in
FT activity on mNav1.6/SCN8A."
FT /evidence="ECO:0000269|PubMed:28889641"
FT MUTAGEN 60
FT /note="R->K: Loss of activity on mammalian channels and
FT increase in activity on insect channels, since there is a
FT complete loss of activity on rNav1.4/SCN4A, hNav1.5/SCN5A,
FT mNav1.6/SCN8A, no change on rNav1.2/SCN2A and increase in
FT activity on B.germanica BgNav1."
FT /evidence="ECO:0000269|PubMed:30007037"
FT MUTAGEN 64
FT /note="K->R: In msBeM9; gain of activity on rNav1.2/SCN2A
FT (reduces peak current and inhibits inactivation), important
FT decrease or loss in activity on rNav1.4/SCN4A,
FT hNav1.5/SCN5A and BgNav1, and no change in activity on
FT mNav1.6/SCN8A."
FT /evidence="ECO:0000269|PubMed:28889641"
FT STRAND 2..8
FT /evidence="ECO:0007829|PDB:5MOU"
FT TURN 9..11
FT /evidence="ECO:0007829|PDB:5MOU"
FT TURN 19..22
FT /evidence="ECO:0007829|PDB:5MOU"
FT HELIX 23..29
FT /evidence="ECO:0007829|PDB:5MOU"
FT TURN 30..32
FT /evidence="ECO:0007829|PDB:5MOU"
FT STRAND 34..42
FT /evidence="ECO:0007829|PDB:5MOU"
FT STRAND 45..53
FT /evidence="ECO:0007829|PDB:5MOU"
SQ SEQUENCE 66 AA; 7343 MW; B8ADBD5FE47AE263 CRC64;
ARDAYIAKPH NCVYECYNPK GSYCNDLCTE NGAESGYCQI LGKYGNACWC IQLPDNVPIR
IPGKCH
