TX35C_PHONI
ID TX35C_PHONI Reviewed; 81 AA.
AC P59367;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 2.
DT 25-MAY-2022, entry version 64.
DE RecName: Full=GAMMA-ctenitoxin-Pn1a {ECO:0000303|PubMed:31467512};
DE Short=GAMMA-CNTX-Pn1a {ECO:0000303|PubMed:31467512};
DE AltName: Full=Insecticidal neurotoxin Tx4(5-5) {ECO:0000303|PubMed:10978749};
DE Short=PnTx4(5-5) {ECO:0000303|PubMed:16278100};
DE Short=PnTx4-5-5 {ECO:0000303|PubMed:26802625};
DE AltName: Full=Toxin Pn4A {ECO:0000303|PubMed:10758278};
DE Flags: Precursor;
OS Phoneutria nigriventer (Brazilian armed spider) (Ctenus nigriventer).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Entelegynae; Lycosoidea; Ctenidae; Phoneutria.
OX NCBI_TaxID=6918;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=10758278; DOI=10.1016/s0041-0101(99)00237-8;
RA Penaforte C.L., Prado V.F., Prado M.A.M., Romano-Silva M.A.,
RA Guimaraes P.E.M., De Marco L., Gomez M.V., Kalapothakis E.;
RT "Molecular cloning of cDNAs encoding insecticidal neurotoxic peptides from
RT the spider Phoneutria nigriventer.";
RL Toxicon 38:1443-1449(2000).
RN [2]
RP PROTEIN SEQUENCE OF 35-81, FUNCTION, SUBCELLULAR LOCATION, MASS
RP SPECTROMETRY, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=10978749; DOI=10.1016/s0041-0101(00)00129-x;
RA de Figueiredo S.G., de Lima M.E., Nascimento Cordeiro M., Diniz C.R.,
RA Patten D., Halliwell R.F., Gilroy J., Richardson M.;
RT "Purification and amino acid sequence of a highly insecticidal toxin from
RT the venom of the Brazilian spider Phoneutria nigriventer which inhibits
RT NMDA-evoked currents in rat hippocampal neurones.";
RL Toxicon 39:309-317(2001).
RN [3]
RP PROTEIN SEQUENCE OF 35-81.
RC TISSUE=Venom;
RX PubMed=16278100; DOI=10.1016/j.cbpc.2005.09.010;
RA Richardson M., Pimenta A.M., Bemquerer M.P., Santoro M.M., Beirao P.S.,
RA Lima M.E., Figueiredo S.G., Bloch C. Jr., Vasconcelos E.A., Campos F.A.,
RA Gomes P.C., Cordeiro M.N.;
RT "Comparison of the partial proteomes of the venoms of Brazilian spiders of
RT the genus Phoneutria.";
RL Comp. Biochem. Physiol. 142:173-187(2006).
RN [4]
RP FUNCTION.
RX PubMed=26747232; DOI=10.1016/j.biochi.2015.12.019;
RA Paiva A.L., Matavel A., Peigneur S., Cordeiro M.N., Tytgat J., Diniz M.R.,
RA de Lima M.E.;
RT "Differential effects of the recombinant toxin PnTx4(5-5) from the spider
RT Phoneutria nigriventer on mammalian and insect sodium channels.";
RL Biochimie 121:326-335(2016).
RN [5]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=26802625; DOI=10.1016/j.toxicon.2016.01.056;
RA Silva F.R., Batista E.M., Gomez M.V., Kushmerick C., Da Silva J.F.,
RA Cordeiro M.N., Vieira L.B., Ribeiro F.M.;
RT "The Phoneutria nigriventer spider toxin, PnTx4-5-5, promotes neuronal
RT survival by blocking NMDA receptors.";
RL Toxicon 112:16-21(2016).
RN [6]
RP FUNCTION.
RX PubMed=31467512; DOI=10.1590/1678-9199-jvatitd-2019-0022;
RA Oliveira C.F.B., Alves D.P., Emerich B.L., de Figueiredo S.G.,
RA Cordeiro M.D.N., Borges M.H., Richardson M., Pimenta A.M.C., Duarte I.D.G.,
RA de Lima M.E.;
RT "Antinociceptive effect of PnTx4(5-5), a peptide from Phoneutria
RT nigriventer spider venom, in rat models and the involvement of
RT glutamatergic system.";
RL J. Venom. Anim. Toxins Incl. Trop. Dis. 25:e20190022-e20190022(2019).
CC -!- FUNCTION: This insecticidal neurotoxin targets two types of
CC channels/receptors. It reversibly inhibits the N-methyl-D-aspartate
CC (NMDA)-subtype of ionotropic glutamate receptor (GRIN)
CC (PubMed:10978749). It inhibits glutamate uptake from rat brain
CC synaptosomes, and blocks GRIN in hippocampal slices (PubMed:10978749,
CC PubMed:26802625). It also acts on sodium channels of both insects and
CC mammals (PubMed:26747232). On sodium channel insects, it strongly slows
CC down channel inactivation (EC(50)=212.5 nM) and causes an increase
CC (105%) in peak amplitude (at 1 uM) of B.germanica sodium channel (Nav),
CC whereas it inhibits all mammalien sodium channels tested with the
CC following order of potency: Nav1.3/SCN3A (IC(50)=1.5 uM) > Nav1.6/SCN8A
CC > Nav1.5/SCN5A > Nav1.4/SCN4A >= Nav1.2/SCN2A (PubMed:26747232). In
CC vivo, it is highly toxic to house fly (Musca domestica), cockroach
CC (Periplaneta americana), and cricket (Acheta domesticus)
CC (PubMed:10978749). In different rat pain models (induced by PGE2,
CC carrageenan or glutamate), it shows antinociceptive effect that may be
CC related to an inhibitory activity on the glutamatergic system
CC (PubMed:31467512). {ECO:0000269|PubMed:10978749,
CC ECO:0000269|PubMed:26747232, ECO:0000269|PubMed:26802625,
CC ECO:0000269|PubMed:31467512}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10978749}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:10978749}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin. {ECO:0000305}.
CC -!- MASS SPECTROMETRY: Mass=5170; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:10978749};
CC -!- TOXIC DOSE: LD(50) is 9.3 ng/house fly. {ECO:0000269|PubMed:10978749}.
CC -!- MISCELLANEOUS: This toxin protects against glutamate-induced neuronal
CC cell death in corticostriatal neurons from both wild-type mice and the
CC Huntingtons disease mice model (BACHD) (PubMed:26802625). In addition,
CC it also protects neurons from Abeta peptides, which are the main
CC components of Alzheimer's disease amyloid plaques and are very toxic to
CC neurons (PubMed:26802625). {ECO:0000269|PubMed:26802625}.
CC -!- MISCELLANEOUS: This toxin has little or no effect on kainate-, alpha-
CC amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)- or gamma-
CC aminobutyric acid (GABA)-activated currents. In addition, it has no
CC effect when intracerebroventricularly injected into mice.
CC {ECO:0000305|PubMed:10978749}.
CC -!- SIMILARITY: Belongs to the neurotoxin 03 (Tx2) family. 05 subfamily.
CC {ECO:0000305}.
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DR AlphaFoldDB; P59367; -.
DR SMR; P59367; -.
DR ArachnoServer; AS000279; GAMMA-ctenitoxin-Pn1a.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0035792; C:host cell postsynaptic membrane; IEA:UniProtKB-KW.
DR GO; GO:0017080; F:sodium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR035285; CNTX.
DR Pfam; PF17492; D_CNTX; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Ionotropic glutamate receptor inhibitor; Knottin; Neurotoxin;
KW Postsynaptic neurotoxin; Secreted; Signal; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT PROPEP 17..34
FT /evidence="ECO:0000269|PubMed:10978749,
FT ECO:0000269|PubMed:16278100"
FT /id="PRO_0000035507"
FT CHAIN 35..81
FT /note="GAMMA-ctenitoxin-Pn1a"
FT /evidence="ECO:0000269|PubMed:10978749,
FT ECO:0000269|PubMed:16278100"
FT /id="PRO_0000035508"
FT DISULFID 35..49
FT /evidence="ECO:0000305"
FT DISULFID 42..55
FT /evidence="ECO:0000305"
FT DISULFID 46..81
FT /evidence="ECO:0000305"
FT DISULFID 48..65
FT /evidence="ECO:0000305"
FT DISULFID 57..63
FT /evidence="ECO:0000305"
SQ SEQUENCE 81 AA; 9021 MW; 7DB856AFC5651B60 CRC64;
MKVAIVFLSL LVLAFASESI EENREEFPVE ESARCADING ACKSDCDCCG DSVTCDCYWS
DSCKCRESNF KIGMAIRKKF C
