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Beta-mammal toxin Css4 (Css IV) (CssIV)

 SCX4_CENSU              Reviewed;          66 AA.
P60266;
16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
16-JAN-2004, sequence version 1.
25-OCT-2017, entry version 53.
RecName: Full=Beta-mammal toxin Css4;
AltName: Full=Css IV;
Short=CssIV;
Centruroides suffusus suffusus (Mexican scorpion).
Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
Scorpiones; Buthida; Buthoidea; Buthidae; Centruroides.
NCBI_TaxID=6881;
[1]
PROTEIN SEQUENCE, AND REVIEW.
PubMed=10491073; DOI=10.1046/j.1432-1327.1999.00625.x;
Possani L.D., Becerril B., Delepierre M., Tytgat J.;
"Scorpion toxins specific for Na+-channels.";
Eur. J. Biochem. 264:287-300(1999).
[2]
FUNCTION, AND LETHAL DOSE.
TISSUE=Venom;
PubMed=2435711;
Martin M.-F., Garcia Y., Perez L.G., el Ayeb M., Kopeyan C.,
Bechis G., Jover E., Rochat H.;
"Purification and chemical and biological characterizations of seven
toxins from the Mexican scorpion, Centruroides suffusus suffusus.";
J. Biol. Chem. 262:4452-4459(1987).
[3]
FUNCTION.
PubMed=9808476; DOI=10.1016/S0896-6273(00)80606-6;
Cestele S., Qu Y., Rogers J.C., Rochat H., Scheuer T., Catterall W.A.;
"Voltage sensor-trapping: enhanced activation of sodium channels by
beta-scorpion toxin bound to the S3-S4 loop in domain II.";
Neuron 21:919-931(1998).
[4]
FUNCTION.
PubMed=11524459; DOI=10.1085/jgp.118.3.291;
Cestele S., Scheuer T., Mantegazza M., Rochat H., Catterall W.A.;
"Neutralization of gating charges in domain II of the sodium channel
alpha subunit enhances voltage-sensor trapping by a beta-scorpion
toxin.";
J. Gen. Physiol. 118:291-302(2001).
[5]
MUTAGENESIS OF ASN-7; SER-8; TYR-9; LYS-13; GLU-15; PHE-17; LYS-18;
LEU-19; ASP-21; ASN-22; ASP-23; TYR-24; LEU-26; ARG-27; GLU-28;
ARG-30; GLN-31; GLN-32; LYS-35; TYR-40; TYR-42; PHE-44; THR-49;
TYR-52; GLU-53; GLN-54; VAL-56; VAL-57; TRP-58; PRO-61; ASN-62; THR-64
AND ASN-66.
PubMed=15569679; DOI=10.1074/jbc.M408427200;
Cohen L., Karbat I., Gilles N., Ilan N., Benveniste M., Gordon D.,
Gurevitz M.;
"Common features in the functional surface of scorpion beta-toxins and
elements that confer specificity for insect and mammalian voltage-
gated sodium channels.";
J. Biol. Chem. 280:5045-5053(2005).
[6]
MUTAGENESIS OF GLU-15.
PubMed=17166514; DOI=10.1016/j.jmb.2006.10.085;
Karbat I., Turkov M., Cohen L., Kahn R., Gordon D., Gurevitz M.,
Frolow F.;
"X-ray structure and mutagenesis of the scorpion depressant toxin
LqhIT2 reveals key determinants crucial for activity and anti-insect
selectivity.";
J. Mol. Biol. 366:586-601(2007).
-!- FUNCTION: Beta toxins bind voltage-independently at site-4 of
sodium channels (Nav) and shift the voltage of activation toward
more negative potentials thereby affecting sodium channel
activation and promoting spontaneous and repetitive firing. This
toxin is active only on mammals. {ECO:0000269|PubMed:11524459,
ECO:0000269|PubMed:2435711, ECO:0000269|PubMed:9808476}.
-!- SUBCELLULAR LOCATION: Secreted.
-!- TISSUE SPECIFICITY: Expressed by the venom gland.
-!- TOXIC DOSE: LD(50) is 0.12 ug/kg in mouse by
intracerebroventricular injection and LD(50) is 115 ug/kg in mouse
by subcutaneous injection. {ECO:0000269|PubMed:2435711}.
-!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin
superfamily. Sodium channel inhibitor family. Beta subfamily.
{ECO:0000305}.
-----------------------------------------------------------------------
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-----------------------------------------------------------------------
ProteinModelPortal; P60266; -.
SMR; P60266; -.
GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
GO; GO:0006952; P:defense response; IEA:InterPro.
Gene3D; 3.30.30.10; -; 1.
InterPro; IPR003614; Scorpion_toxin-like.
InterPro; IPR036574; Scorpion_toxin-like_sf.
InterPro; IPR018218; Scorpion_toxinL.
InterPro; IPR002061; Scorpion_toxinL/defensin.
Pfam; PF00537; Toxin_3; 1.
PRINTS; PR00285; SCORPNTOXIN.
SMART; SM00505; Knot1; 1.
SUPFAM; SSF57095; SSF57095; 1.
1: Evidence at protein level;
Amidation; Direct protein sequencing; Disulfide bond;
Ion channel impairing toxin; Neurotoxin; Secreted; Toxin;
Voltage-gated sodium channel impairing toxin.
CHAIN 1 66 Beta-mammal toxin Css4.
/FTId=PRO_0000066778.
SITE 24 24 May interact with the receptor site.
SITE 27 27 May interact with the receptor site.
SITE 28 28 May interact with the receptor site.
SITE 32 32 May interact with the receptor site.
MOD_RES 66 66 Asparagine amide. {ECO:0000250}.
DISULFID 12 65 {ECO:0000250}.
DISULFID 16 41 {ECO:0000250}.
DISULFID 25 46 {ECO:0000250}.
DISULFID 29 48 {ECO:0000250}.
MUTAGEN 7 7 N->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 8 8 S->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 9 9 Y->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 13 13 K->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 15 15 E->A: Induces a marked shift in the
voltage dependence of activation of
Drosophila DmNav1 (para) channels and a
contraction paralysis in blowfly larvae.
However, it retains its high affinity for
rat brain neuronal membranes and is
highly active on the SCN2A (Nav1.2)
channel. {ECO:0000269|PubMed:15569679,
ECO:0000269|PubMed:17166514}.
MUTAGEN 15 15 E->Q,R: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679,
ECO:0000269|PubMed:17166514}.
MUTAGEN 17 17 F->A: 11.2-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 17 17 F->W: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 18 18 K->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 19 19 L->A: 157-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 19 19 L->I: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 21 21 D->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 22 22 N->A: 649-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 23 23 D->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 24 24 Y->A: 886-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 24 24 Y->W: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 26 26 L->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 27 27 R->A: 30.8-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 27 27 R->I: 39-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 27 27 R->Q: 14-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 28 28 E->A: 648-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 28 28 E->L: 45-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 28 28 E->Q: 394-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 28 28 E->R: 962-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 30 30 R->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 31 31 Q->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 32 32 Q->A: 10.8-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 32 32 Q->W: 35.8-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 35 35 K->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 40 40 Y->A: 1451-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 42 42 Y->A: 1533-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 44 44 F->A: 831-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 49 49 T->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 52 52 Y->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 53 53 E->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 54 54 Q->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 56 56 V->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 57 57 V->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 58 58 W->A: 87-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 61 61 P->G: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 62 62 N->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 64 64 T->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 66 66 N->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
SEQUENCE 66 AA; 7611 MW; 700F57377D4E8361 CRC64;
KEGYLVNSYT GCKFECFKLG DNDYCLRECR QQYGKGSGGY CYAFGCWCTH LYEQAVVWPL
PNKTCN


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