TXC1_CUPSA
ID TXC1_CUPSA Reviewed; 122 AA.
AC P81694; A0A4Y5UH50;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2013, sequence version 2.
DT 25-MAY-2022, entry version 72.
DE RecName: Full=Toxin CSTX-1 {ECO:0000303|PubMed:22613721, ECO:0000303|PubMed:8016851};
DE AltName: Full=Omega-ctenitoxin-Cs1a {ECO:0000303|PubMed:22613721};
DE Short=Omega-CNTX-Cs1a {ECO:0000305};
DE Contains:
DE RecName: Full=Toxin CSTX-2a {ECO:0000303|PubMed:22613721};
DE AltName: Full=ctenitoxin-Cs2a {ECO:0000303|PubMed:22613721};
DE Contains:
DE RecName: Full=Toxin CSTX-2b {ECO:0000303|PubMed:22613721};
DE AltName: Full=Ctenitoxin-Cs2b {ECO:0000303|PubMed:22613721};
DE Flags: Precursor;
OS Cupiennius salei (American wandering spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Entelegynae; Lycosoidea; Ctenidae; Cupiennius.
OX NCBI_TaxID=6928;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION AS A CYTOLYTIC TOXIN, AMIDATION AT
RP LYS-121, CIRCULAR DICHROISM ANALYSIS, AND ALPHA-HELICAL REGION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=22613721; DOI=10.1074/jbc.m112.339051;
RA Kuhn-Nentwig L., Fedorova I.M., Luscher B.P., Kopp L.S., Trachsel C.,
RA Schaller J., Vu X.L., Seebeck T., Streitberger K., Nentwig W., Sigel E.,
RA Magazanik L.G.;
RT "A venom-derived neurotoxin, CsTx-1, from the spider Cupiennius salei
RT exhibits cytolytic activities.";
RL J. Biol. Chem. 287:25640-25649(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=30893800; DOI=10.3390/toxins11030167;
RA Kuhn-Nentwig L., Langenegger N., Heller M., Koua D., Nentwig W.;
RT "The dual prey-inactivation strategy of spiders-in-depth venomic analysis
RT of Cupiennius salei.";
RL Toxins 11:0-0(2019).
RN [3]
RP PROTEIN SEQUENCE OF 48-121, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=8016851; DOI=10.1016/0041-0101(94)90082-5;
RA Kuhn-Nentwig L., Schaller J., Nentwig W.;
RT "Purification of toxic peptides and the amino acid sequence of CSTX-1 from
RT the multicomponent venom of Cupiennius salei (Araneae:Ctenidae).";
RL Toxicon 32:287-302(1994).
RN [4]
RP PROTEIN SEQUENCE OF 48-108, FUNCTION, AND MASS SPECTROMETRY.
RA Nentwig W., Kuhn-Nentwig L., Schaller J., Kaempfer U.;
RT "Amino acid sequence of the toxic spider peptide CSTX-2 and its structural
RT and physiological differences to CSTX-1.";
RL Toxicon 36:1276-1276(1998).
RN [5]
RP PROTEIN SEQUENCE OF 48-108, FUNCTION, TOXIC DOSE, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=10897091;
RX DOI=10.1002/1520-6327(200007)44:3<101::aid-arch1>3.0.co;2-s;
RA Kuhn-Nentwig L., Schaller J., Kaempfer U., Imboden H., Malli H.,
RA Nentwig W.;
RT "A lysine rich C-terminal tail is directly involved in the toxicity of
RT CSTX-1, a neurotoxic peptide from the venom of the spider Cupiennius
RT salei.";
RL Arch. Insect Biochem. Physiol. 44:101-111(2000).
RN [6]
RP PARTIAL PROTEIN SEQUENCE, AND FUNCTION.
RC TISSUE=Venom;
RX PubMed=17517422; DOI=10.1016/j.neuropharm.2007.03.012;
RA Kubista H., Mafra R.A., Chong Y., Nicholson G.M., Beirao P.S.L., Cruz J.S.,
RA Boehm S., Nentwig W., Kuhn-Nentwig L.;
RT "CSTX-1, a toxin from the venom of the hunting spider Cupiennius salei, is
RT a selective blocker of L-type calcium channels in mammalian neurons.";
RL Neuropharmacology 52:1650-1662(2007).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=10772256; DOI=10.1007/s004419900141;
RA Malli H., Kuhn-Nentwig L., Imboden H., Moon M.J., Wyler T.;
RT "Immunocytochemical localization and secretion process of the toxin CSTX-1
RT in the venom gland of the wandering spider Cupiennius salei (Araneae:
RT Ctenidae).";
RL Cell Tissue Res. 299:417-426(2000).
RN [8]
RP FUNCTION IN SYNERGY WITH OTHER TOXINS, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=15914655; DOI=10.1242/jeb.01594;
RA Wullschleger B., Nentwig W., Kuhn-Nentwig L.;
RT "Spider venom: enhancement of venom efficacy mediated by different
RT synergistic strategies in Cupiennius salei.";
RL J. Exp. Biol. 208:2115-2121(2005).
RN [9]
RP REVIEW, AND AMIDATION AT ARG-108.
RX PubMed=15066412; DOI=10.1016/j.toxicon.2004.02.009;
RA Kuhn-Nentwig L., Schaller J., Nentwig W.;
RT "Biochemistry, toxicology and ecology of the venom of the spider Cupiennius
RT salei (Ctenidae).";
RL Toxicon 43:543-553(2004).
RN [10]
RP FUNCTION, TOXIC DOSE, SUBUNIT, AND 3D-STRUCTURE MODELING.
RC TISSUE=Venom;
RX PubMed=32290562; DOI=10.3390/toxins12040250;
RA Clemencon B., Kuhn-Nentwig L., Langenegger N., Kopp L., Peigneur S.,
RA Tytgat J., Nentwig W., Luescher B.P.;
RT "Neurotoxin merging: a strategy deployed by the venom of the spider
RT cupiennius salei to potentiate toxicity on insects.";
RL Toxins 12:0-0(2020).
CC -!- FUNCTION: [Toxin CSTX-1]: Spider venom toxin that shows calcium channel
CC blocking activity and exhibits cytolytic activity by affecting the
CC outer leaflet curvature and/or pore formation across the membrane
CC (PubMed:22613721, PubMed:32290562). It blocks L-type calcium channels
CC (Cav1/CACNA1) in mammalian neurons at nanomolar concentrations.
CC Furthermore, it produces a slow voltage-independent block of mid/low
CC and high voltage-activated calcium channels in cockroach neurons
CC (PubMed:17517422). Potassium ions, histamine, M-ctenitoxin-Cs1a (AC
CC P83619), CSTX-9 (AC P58604), and CSTX-13 (AC P83919) synergistically
CC increase the insecticidal activity of this toxin (PubMed:15914655,
CC PubMed:32290562). In vivo, it causes paralysis in blow flies and
CC provokes death in drosophila (PubMed:32290562).
CC {ECO:0000269|PubMed:17517422, ECO:0000269|PubMed:22613721,
CC ECO:0000269|PubMed:32290562}.
CC -!- FUNCTION: [Toxin CSTX-2a]: Blocks voltage-activated calcium channels
CC (Cav) (By similarity). Does not induce cell membrane permeability
CC increase when tested on Xenopus oocytes. No alpha-helical structures
CC are detectable. Is 7-fold less neurotoxic than omega-ctenitoxin-Cs1a on
CC drosophila flies. {ECO:0000250}.
CC -!- FUNCTION: [Toxin CSTX-2b]: Blocks voltage-activated calcium channels
CC (Cav) (By similarity). Is 190-fold less neurotoxic than omega-
CC ctenitoxin-Cs1a on drosophila flies. {ECO:0000250}.
CC -!- SUBUNIT: Monomer (Probable). Interacts with CSTX-13 (AC P83919) (Kd=430
CC nM), but does not interact with CSTX-9 (AC P58604) (PubMed:32290562).
CC {ECO:0000269|PubMed:32290562, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8016851}. Target
CC cell membrane {ECO:0000305|PubMed:32290562}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000269|PubMed:10772256}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin. {ECO:0000250}.
CC -!- MASS SPECTROMETRY: [Toxin CSTX-1]: Mass=8352.62; Method=Electrospray;
CC Evidence={ECO:0000269|Ref.4};
CC -!- MASS SPECTROMETRY: [Toxin CSTX-2a]: Mass=6865.75; Method=Electrospray;
CC Evidence={ECO:0000269|Ref.4};
CC -!- MASS SPECTROMETRY: [Toxin CSTX-2b]: Mass=6709.57; Method=Electrospray;
CC Evidence={ECO:0000269|Ref.4};
CC -!- TOXIC DOSE: [Toxin CSTX-1]: LD(50) is 0.535 pmol/mg when
CC intrathoracically injected into drosophila.
CC {ECO:0000269|PubMed:10897091}.
CC -!- TOXIC DOSE: [Toxin CSTX-1]: LD(50) is 0.432 pmol/mg when
CC intrathoracically co-injected with CSTX-9 (AC P58604) into drosophila.
CC {ECO:0000269|PubMed:32290562}.
CC -!- TOXIC DOSE: [Toxin CSTX-1]: LD(50) is 0.075 pmol/mg when
CC intrathoracically co-injected with CSTX-13 (AC P83919) into drosophila.
CC {ECO:0000269|PubMed:32290562}.
CC -!- TOXIC DOSE: [Toxin CSTX-2a]: LD(50) is 2.58 pmol/mg on Drosophila.
CC {ECO:0000269|PubMed:10897091}.
CC -!- TOXIC DOSE: [Toxin CSTX-2b]: LD(50) is 66.51 pmol/mg on Drosophila.
CC {ECO:0000269|PubMed:10897091}.
CC -!- MISCELLANEOUS: Omega-ctenitoxin-Cs1a is the most abundant neurotoxin in
CC the venom of C.salei.
CC -!- MISCELLANEOUS: Omega-ctenitoxin-Cs1a has no antimicrobial activity
CC against E.coli (ATCC 25922) and S.aureus (ATCC29213). Surprisingly, it
CC destroys the E.coli mutant (SBS363) in a concentration of 31.25 uM
CC (PubMed:22613721). {ECO:0000305|PubMed:22613721}.
CC -!- SIMILARITY: Belongs to the neurotoxin 19 (CSTX) family. 04 (U1-Lctx)
CC subfamily. {ECO:0000305}.
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DR EMBL; MH754547; QDC23082.1; -; mRNA.
DR EMBL; MH754548; QDC23083.1; -; mRNA.
DR PIR; A53356; A53356.
DR AlphaFoldDB; P81694; -.
DR SMR; P81694; -.
DR TCDB; 8.B.19.2.2; the sea anemone k+ channel blocker toxin, bcstx3 (bcstx3) family.
DR ArachnoServer; AS000292; omega-ctenitoxin-Cs1a.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR InterPro; IPR019553; Spider_toxin_CSTX_knottin.
DR InterPro; IPR011142; Spider_toxin_CSTX_Knottin_CS.
DR Pfam; PF10530; Toxin_35; 1.
DR PROSITE; PS60029; SPIDER_CSTX; 1.
PE 1: Evidence at protein level;
KW Amidation; Calcium channel impairing toxin; Cytolysis;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Knottin; Membrane; Neurotoxin; Secreted; Signal; Target cell membrane;
KW Target membrane; Toxin; Voltage-gated calcium channel impairing toxin.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..47
FT /evidence="ECO:0000269|PubMed:10897091,
FT ECO:0000269|PubMed:8016851, ECO:0000269|Ref.4"
FT /id="PRO_0000421161"
FT CHAIN 48..121
FT /note="Toxin CSTX-1"
FT /evidence="ECO:0000269|PubMed:8016851"
FT /id="PRO_0000035572"
FT CHAIN 48..108
FT /note="Toxin CSTX-2a"
FT /evidence="ECO:0000269|PubMed:10897091, ECO:0000269|Ref.4"
FT /id="PRO_0000035573"
FT CHAIN 48..107
FT /note="Toxin CSTX-2b"
FT /evidence="ECO:0000269|PubMed:10897091, ECO:0000269|Ref.4"
FT /id="PRO_0000035574"
FT REGION 99..112
FT /note="Predicted alpha-helix"
FT MOD_RES 108
FT /note="Arginine amide; in CSTX-2a"
FT /evidence="ECO:0000269|PubMed:15066412"
FT MOD_RES 121
FT /note="Lysine amide; in omega-ctenitoxin-Cs1a"
FT /evidence="ECO:0000269|PubMed:22613721"
FT DISULFID 49..64
FT /evidence="ECO:0000250|UniProtKB:P58604"
FT DISULFID 56..73
FT /evidence="ECO:0000250|UniProtKB:P58604"
FT DISULFID 63..91
FT /evidence="ECO:0000250|UniProtKB:P58604"
FT DISULFID 75..89
FT /evidence="ECO:0000250|UniProtKB:P58604"
SQ SEQUENCE 122 AA; 13840 MW; 82AD3C97168F4AC5 CRC64;
MKVLIISAVL FITIFSNISA EIEDDFLEDE SFEAEDIIPF FENEQARSCI PKHEECTNDK
HNCCRKGLFK LKCQCSTFDD ESGQPTERCA CGRPMGHQAI ETGLNIFRGL FKGKKKNKKT
KG
