SCX4_CENSU
ID SCX4_CENSU Reviewed; 87 AA.
AC P60266; F1CGT5;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2017, sequence version 2.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Beta-mammal toxin Css4;
DE AltName: Full=Css IV {ECO:0000303|PubMed:2435711, ECO:0000303|PubMed:9808476};
DE Short=CssIV {ECO:0000305};
DE Flags: Precursor;
OS Centruroides suffusus (Durango bark scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Centruroides.
OX NCBI_TaxID=6880;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], MASS SPECTROMETRY, AND TOXIC DOSE.
RC TISSUE=Venom, and Venom gland;
RX PubMed=21329715; DOI=10.1016/j.toxicon.2011.02.006;
RA Espino-Solis G.P., Estrada G., Olamendi-Portugal T., Villegas E.,
RA Zamudio F., Cestele S., Possani L.D., Corzo G.;
RT "Isolation and molecular cloning of beta-neurotoxins from the venom of the
RT scorpion Centruroides suffusus suffusus.";
RL Toxicon 57:739-746(2011).
RN [2]
RP PROTEIN SEQUENCE OF 20-85, AND REVIEW.
RX PubMed=10491073; DOI=10.1046/j.1432-1327.1999.00625.x;
RA Possani L.D., Becerril B., Delepierre M., Tytgat J.;
RT "Scorpion toxins specific for Na+-channels.";
RL Eur. J. Biochem. 264:287-300(1999).
RN [3]
RP FUNCTION, TOXIC DOSE, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=2435711; DOI=10.1016/s0021-9258(18)61214-1;
RA Martin M.-F., Garcia Y., Perez L.G., el Ayeb M., Kopeyan C., Bechis G.,
RA Jover E., Rochat H.;
RT "Purification and chemical and biological characterizations of seven toxins
RT from the Mexican scorpion, Centruroides suffusus suffusus.";
RL J. Biol. Chem. 262:4452-4459(1987).
RN [4]
RP FUNCTION.
RX PubMed=9808476; DOI=10.1016/s0896-6273(00)80606-6;
RA Cestele S., Qu Y., Rogers J.C., Rochat H., Scheuer T., Catterall W.A.;
RT "Voltage sensor-trapping: enhanced activation of sodium channels by beta-
RT scorpion toxin bound to the S3-S4 loop in domain II.";
RL Neuron 21:919-931(1998).
RN [5]
RP FUNCTION.
RX PubMed=11524459; DOI=10.1085/jgp.118.3.291;
RA Cestele S., Scheuer T., Mantegazza M., Rochat H., Catterall W.A.;
RT "Neutralization of gating charges in domain II of the sodium channel alpha
RT subunit enhances voltage-sensor trapping by a beta-scorpion toxin.";
RL J. Gen. Physiol. 118:291-302(2001).
RN [6]
RP MUTAGENESIS OF ASN-26; SER-27; TYR-28; LYS-32; GLU-34; PHE-36; LYS-37;
RP LEU-38; ASP-40; ASN-41; ASP-42; TYR-43; LEU-45; ARG-46; GLU-47; ARG-49;
RP GLN-50; GLN-51; LYS-54; TYR-59; TYR-61; PHE-63; THR-68; TYR-71; GLU-72;
RP GLN-73; VAL-75; VAL-76; TRP-77; PRO-80; ASN-81; THR-83 AND ASN-85.
RX PubMed=15569679; DOI=10.1074/jbc.m408427200;
RA Cohen L., Karbat I., Gilles N., Ilan N., Benveniste M., Gordon D.,
RA Gurevitz M.;
RT "Common features in the functional surface of scorpion beta-toxins and
RT elements that confer specificity for insect and mammalian voltage-gated
RT sodium channels.";
RL J. Biol. Chem. 280:5045-5053(2005).
RN [7]
RP MUTAGENESIS OF GLU-34.
RX PubMed=17166514; DOI=10.1016/j.jmb.2006.10.085;
RA Karbat I., Turkov M., Cohen L., Kahn R., Gordon D., Gurevitz M., Frolow F.;
RT "X-ray structure and mutagenesis of the scorpion depressant toxin LqhIT2
RT reveals key determinants crucial for activity and anti-insect
RT selectivity.";
RL J. Mol. Biol. 366:586-601(2007).
CC -!- FUNCTION: Beta toxins bind voltage-independently at site-4 of sodium
CC channels (Nav) and shift the voltage of activation toward more negative
CC potentials thereby affecting sodium channel activation and promoting
CC spontaneous and repetitive firing. This toxin is active only on
CC mammals. {ECO:0000269|PubMed:11524459, ECO:0000269|PubMed:2435711,
CC ECO:0000269|PubMed:9808476}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2435711}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:2435711}.
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=7601.6; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:21329715};
CC -!- TOXIC DOSE: LD(50) is 0.12 ug/kg in mouse by intracerebroventricular
CC injection and LD(50) is 115 ug/kg in mouse by subcutaneous injection.
CC {ECO:0000269|PubMed:2435711}.
CC -!- TOXIC DOSE: LD(100) is 3 ug/kg by intracranial injection into mice.
CC {ECO:0000269|PubMed:21329715}.
CC -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC Sodium channel inhibitor family. Beta subfamily. {ECO:0000305}.
CC -!- CAUTION: Authors of PubMed:21329715 cite the nucleotide sequence
CC HQ262493 as coding for Css8 (AC P0DL83), but the sequence corresponds
CC to Css4. For this reason, the corresponding cross-reference is
CC indicated in this entry. {ECO:0000305|PubMed:21329715}.
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DR EMBL; HQ262493; ADY17425.1; -; mRNA.
DR AlphaFoldDB; P60266; -.
DR SMR; P60266; -.
DR TCDB; 8.B.1.2.2; the long (4c-c) scorpion toxin (l-st) superfamily.
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 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 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 Amidation; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Secreted; Signal; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:21329715"
FT CHAIN 20..85
FT /note="Beta-mammal toxin Css4"
FT /evidence="ECO:0000269|PubMed:10491073"
FT /id="PRO_0000066778"
FT DOMAIN 20..85
FT /note="LCN-type CS-alpha/beta"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT SITE 43
FT /note="May interact with the receptor site"
FT /evidence="ECO:0000269|PubMed:15569679"
FT SITE 46
FT /note="May interact with the receptor site"
FT /evidence="ECO:0000269|PubMed:15569679"
FT SITE 47
FT /note="May interact with the receptor site"
FT /evidence="ECO:0000269|PubMed:15569679"
FT SITE 51
FT /note="May interact with the receptor site"
FT /evidence="ECO:0000269|PubMed:15569679"
FT MOD_RES 85
FT /note="Asparagine amide"
FT /evidence="ECO:0000250|UniProtKB:P08900"
FT DISULFID 31..84
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 35..60
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 44..65
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 48..67
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT MUTAGEN 26
FT /note="N->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 27
FT /note="S->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 28
FT /note="Y->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 32
FT /note="K->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 34
FT /note="E->A: Induces a marked shift in the voltage
FT dependence of activation of Drosophila DmNav1 (para)
FT channels and a contraction paralysis in blowfly larvae.
FT However, it retains its high affinity for rat brain
FT neuronal membranes and is highly active on the SCN2A
FT (Nav1.2) channel."
FT /evidence="ECO:0000269|PubMed:15569679,
FT ECO:0000269|PubMed:17166514"
FT MUTAGEN 34
FT /note="E->Q,R: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679,
FT ECO:0000269|PubMed:17166514"
FT MUTAGEN 36
FT /note="F->A: 11.2-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 36
FT /note="F->W: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 37
FT /note="K->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 38
FT /note="L->A: 157-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 38
FT /note="L->I: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 40
FT /note="D->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 41
FT /note="N->A: 649-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 42
FT /note="D->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 43
FT /note="Y->A: 886-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 43
FT /note="Y->W: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 45
FT /note="L->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 46
FT /note="R->A: 30.8-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 46
FT /note="R->I: 39-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 46
FT /note="R->Q: 14-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 47
FT /note="E->A: 648-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 47
FT /note="E->L: 45-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 47
FT /note="E->Q: 394-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 47
FT /note="E->R: 962-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 49
FT /note="R->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 50
FT /note="Q->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 51
FT /note="Q->A: 10.8-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 51
FT /note="Q->W: 35.8-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 54
FT /note="K->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 59
FT /note="Y->A: 1451-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 61
FT /note="Y->A: 1533-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 63
FT /note="F->A: 831-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 68
FT /note="T->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 71
FT /note="Y->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 72
FT /note="E->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 73
FT /note="Q->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 75
FT /note="V->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 76
FT /note="V->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 77
FT /note="W->A: 87-fold decrease in binding affinity to rat
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 80
FT /note="P->G: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 81
FT /note="N->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 83
FT /note="T->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
FT MUTAGEN 85
FT /note="N->A: Has little effect on the binding affinity to
FT rat sodium channels."
FT /evidence="ECO:0000269|PubMed:15569679"
SQ SEQUENCE 87 AA; 9785 MW; 3AD30B6651C0C238 CRC64;
MNSLLMITAC LALVGTVWAK EGYLVNSYTG CKFECFKLGD NDYCLRECRQ QYGKGSGGYC
YAFGCWCTHL YEQAVVWPLP NKTCNGK
