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

 SCX4_CENSU              Reviewed;          87 AA.
P60266; F1CGT5;
16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
22-NOV-2017, sequence version 2.
18-JUL-2018, entry version 58.
RecName: Full=Beta-mammal toxin Css4;
AltName: Full=Css IV {ECO:0000303|PubMed:2435711, ECO:0000303|PubMed:9808476};
Short=CssIV {ECO:0000305};
Flags: Precursor;
Centruroides suffusus suffusus (Mexican scorpion).
Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
Scorpiones; Buthida; Buthoidea; Buthidae; Centruroides.
NCBI_TaxID=6881;
[1]
NUCLEOTIDE SEQUENCE [MRNA], MASS SPECTROMETRY, AND LETHAL DOSE.
TISSUE=Venom, and Venom gland;
PubMed=21329715; DOI=10.1016/j.toxicon.2011.02.006;
Espino-Solis G.P., Estrada G., Olamendi-Portugal T., Villegas E.,
Zamudio F., Cestele S., Possani L.D., Corzo G.;
"Isolation and molecular cloning of beta-neurotoxins from the venom of
the scorpion Centruroides suffusus suffusus.";
Toxicon 57:739-746(2011).
[2]
PROTEIN SEQUENCE OF 20-85, 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).
[3]
FUNCTION, LETHAL DOSE, AND SUBCELLULAR LOCATION.
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).
[4]
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).
[5]
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).
[6]
MUTAGENESIS OF ASN-26; SER-27; TYR-28; LYS-32; GLU-34; PHE-36; LYS-37;
LEU-38; ASP-40; ASN-41; ASP-42; TYR-43; LEU-45; ARG-46; GLU-47;
ARG-49; GLN-50; GLN-51; LYS-54; TYR-59; TYR-61; PHE-63; THR-68;
TYR-71; GLU-72; GLN-73; VAL-75; VAL-76; TRP-77; PRO-80; ASN-81; THR-83
AND ASN-85.
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).
[7]
MUTAGENESIS OF GLU-34.
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 {ECO:0000269|PubMed:2435711}.
-!- TISSUE SPECIFICITY: Expressed by the venom gland.
{ECO:0000305|PubMed:2435711}.
-!- MASS SPECTROMETRY: Mass=7601.6; Method=Electrospray; Range=20-85;
Evidence={ECO:0000269|PubMed:21329715};
-!- 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}.
-!- TOXIC DOSE: LD(100) is 3 ug/kg by intracranial injection into
mice. {ECO:0000269|PubMed:21329715}.
-!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin
superfamily. Sodium channel inhibitor family. Beta subfamily.
{ECO:0000305}.
-!- CAUTION: Authors of PubMed:21329715 cite the nucleotide sequence
HQ262493 as coding for Css8 (AC P0DL83), but the sequence
corresponds to Css4. For this reason, the corresponding cross-
reference is indicated in this entry.
{ECO:0000305|PubMed:21329715}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution (CC BY 4.0) License
-----------------------------------------------------------------------
EMBL; HQ262493; ADY17425.1; -; mRNA.
ProteinModelPortal; P60266; -.
SMR; P60266; -.
GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
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.
PRINTS; PR00285; SCORPNTOXIN.
SMART; SM00505; Knot1; 1.
SUPFAM; SSF57095; SSF57095; 1.
PROSITE; PS51863; LCN_CSAB; 1.
1: Evidence at protein level;
Amidation; Direct protein sequencing; Disulfide bond;
Ion channel impairing toxin; Neurotoxin; Secreted; Signal; Toxin;
Voltage-gated sodium channel impairing toxin.
SIGNAL 1 18 {ECO:0000269|PubMed:21329715}.
CHAIN 19 85 Beta-mammal toxin Css4.
{ECO:0000269|PubMed:10491073}.
/FTId=PRO_0000066778.
DOMAIN 20 85 LCN-type CS-alpha/beta.
{ECO:0000255|PROSITE-ProRule:PRU01210}.
SITE 43 43 May interact with the receptor site.
{ECO:0000269|PubMed:15569679}.
SITE 46 46 May interact with the receptor site.
{ECO:0000269|PubMed:15569679}.
SITE 47 47 May interact with the receptor site.
{ECO:0000269|PubMed:15569679}.
SITE 51 51 May interact with the receptor site.
{ECO:0000269|PubMed:15569679}.
MOD_RES 85 85 Asparagine amide.
{ECO:0000250|UniProtKB:P08900}.
DISULFID 31 84 {ECO:0000255|PROSITE-ProRule:PRU01210}.
DISULFID 35 60 {ECO:0000255|PROSITE-ProRule:PRU01210}.
DISULFID 44 65 {ECO:0000255|PROSITE-ProRule:PRU01210}.
DISULFID 48 67 {ECO:0000255|PROSITE-ProRule:PRU01210}.
MUTAGEN 26 26 N->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 27 27 S->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 28 28 Y->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 32 32 K->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 34 34 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 34 34 E->Q,R: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679,
ECO:0000269|PubMed:17166514}.
MUTAGEN 36 36 F->A: 11.2-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 36 36 F->W: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 37 37 K->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 38 38 L->A: 157-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 38 38 L->I: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 40 40 D->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 41 41 N->A: 649-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 42 42 D->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 43 43 Y->A: 886-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 43 43 Y->W: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 45 45 L->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 46 46 R->A: 30.8-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 46 46 R->I: 39-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 46 46 R->Q: 14-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 47 47 E->A: 648-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 47 47 E->L: 45-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 47 47 E->Q: 394-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 47 47 E->R: 962-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 49 49 R->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 50 50 Q->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 51 51 Q->A: 10.8-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 51 51 Q->W: 35.8-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 54 54 K->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 59 59 Y->A: 1451-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 61 61 Y->A: 1533-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 63 63 F->A: 831-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 68 68 T->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 71 71 Y->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 72 72 E->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 73 73 Q->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 75 75 V->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 76 76 V->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 77 77 W->A: 87-fold decrease in binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 80 80 P->G: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 81 81 N->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 83 83 T->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
MUTAGEN 85 85 N->A: Has little effect on the binding
affinity to rat sodium channels.
{ECO:0000269|PubMed:15569679}.
SEQUENCE 87 AA; 9785 MW; 3AD30B6651C0C238 CRC64;
MNSLLMITAC LALVGTVWAK EGYLVNSYTG CKFECFKLGD NDYCLRECRQ QYGKGSGGYC
YAFGCWCTHL YEQAVVWPLP NKTCNGK


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