TX34_PHONI
ID TX34_PHONI Reviewed; 116 AA.
AC P81790;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 3.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=Omega-ctenitoxin-Pn3a;
DE Short=Omega-CNTX-Pn3a;
DE AltName: Full=Neurotoxin Tx3-4;
DE AltName: Full=Omega-phonetoxin-2A;
DE AltName: Full=Omega-phonetoxin-IIA;
DE Short=Omega-Ptx-IIA;
DE AltName: Full=PF3;
DE AltName: Full=Phoneutriatoxin 3-4;
DE AltName: Full=Pn3-4A;
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=12782075; DOI=10.1016/s0041-0101(03)00011-4;
RA Cardoso F.C., Pacifico L.G., Carvalho D.C., Victoria J.M.N., Neves A.L.G.,
RA Chavez-Olortegui C., Gomez M.V., Kalapothakis E.;
RT "Molecular cloning and characterization of Phoneutria nigriventer toxins
RT active on calcium channels.";
RL Toxicon 41:755-763(2003).
RN [2]
RP PROTEIN SEQUENCE OF 40-115, MASS SPECTROMETRY, FUNCTION, AND AMIDATION AT
RP HIS-115.
RC TISSUE=Venom;
RX PubMed=9683727; DOI=10.1007/s004240050670;
RA Cassola A.C., Jaffe H., Fales H.M., Castro-Afeche S., Magnoli F.,
RA Cipolla-Neto J.;
RT "Omega-phonetoxin-IIA: a calcium channel blocker from the spider Phoneutria
RT nigriventer.";
RL Pflugers Arch. 436:545-552(1998).
RN [3]
RP PROTEIN SEQUENCE OF 40-115, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP MASS SPECTROMETRY.
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 PROTEIN SEQUENCE OF 40-79, AND FUNCTION.
RC TISSUE=Venom;
RX PubMed=8446961; DOI=10.1016/0041-0101(93)90354-l;
RA Cordeiro M.N., De Figueiredo S.G., Valentim A.D.C., Diniz C.R.,
RA von Eickstedt V.R.D., Gilroy J., Richardson M.;
RT "Purification and amino acid sequences of six Tx3 type neurotoxins from the
RT venom of the Brazilian 'armed' spider Phoneutria nigriventer (Keys).";
RL Toxicon 31:35-42(1993).
RN [5]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=9631431; DOI=10.1097/00001756-199805110-00022;
RA Miranda D.M., Romano-Silva M.A., Kalapothakis E., Diniz C.R.,
RA Cordeiro M.N., Santos T.M., Prado M.A.M., Gomez M.V.;
RT "Phoneutria nigriventer toxins block tityustoxin-induced calcium influx in
RT synaptosomes.";
RL NeuroReport 9:1371-1373(1998).
RN [6]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=10510308; DOI=10.1042/bj3430413;
RA Reis H.J., Prado M.A.M., Kalapothakis E., Cordeiro M.N., Diniz C.R.,
RA De Marco L.A., Gomez M.V., Romano-Silva M.A.;
RT "Inhibition of glutamate uptake by a polypeptide toxin (phoneutriatoxin 3-
RT 4) from the spider Phoneutria nigriventer.";
RL Biochem. J. 343:413-418(1999).
RN [7]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=10923668; DOI=10.1097/00001756-200007140-00025;
RA Reis H.J., Gomez M.V., Kalapothakis E., Diniz C.R., Cordeiro M.N.,
RA Prado M.A.M., Romano-Silva M.A.;
RT "Inhibition of glutamate uptake by Tx3-4 is dependent on the redox state of
RT cysteine residues.";
RL NeuroReport 11:2191-2194(2000).
RN [8]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=11397544; DOI=10.1016/s0361-9230(01)00443-9;
RA Miranda D.M., Romano-Silva M.A., Kalapothakis E., Diniz C.R.,
RA Cordeiro M.N., Moraes-Santos T., De Marco L.A., Prado M.A.M., Gomez M.V.;
RT "Spider neurotoxins block the beta scorpion toxin-induced calcium uptake in
RT rat brain cortical synaptosomes.";
RL Brain Res. Bull. 54:533-536(2001).
RN [9]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=11827974; DOI=10.1074/jbc.m112348200;
RA Dos Santos R.G., Van Renterghem C., Martin-Moutot N., Mansuelle P.,
RA Cordeiro M.N., Diniz C.R., Mori Y., De Lima M.E., Seagar M.;
RT "Phoneutria nigriventer omega-phonetoxin IIA blocks the Cav2 family of
RT calcium channels and interacts with omega-conotoxin-binding sites.";
RL J. Biol. Chem. 277:13856-13862(2002).
RN [10]
RP BIOTECHNOLOGY.
RX PubMed=16289869; DOI=10.1016/j.nbd.2005.10.003;
RA Martin-Moutot N., Haro L., Santos R.G., Mori Y., Seagar M.;
RT "Phoneutria nigriventer omega-Phonetoxin IIA: a new tool for anti-calcium
RT channel autoantibody assays in Lambert-Eaton myasthenic syndrome.";
RL Neurobiol. Dis. 22:57-63(2006).
RN [11]
RP FUNCTION.
RX PubMed=18524484; DOI=10.1016/j.neulet.2008.05.019;
RA de Castro Junior C.J., Pinheiro A.C., Guatimosim C., Cordeiro M.N.,
RA Souza A.H., Richardson M., Romano-Silva M.A., Prado M.A., Gomez M.V.;
RT "Tx3-4 a toxin from the venom of spider Phoneutria nigriventer blocks
RT calcium channels associated with exocytosis.";
RL Neurosci. Lett. 439:170-172(2008).
RN [12]
RP FUNCTION.
RX PubMed=19370546; DOI=10.1002/hipo.20580;
RA Pinheiro A.C., da Silva A.J., Prado M.A., Cordeiro M.D., Richardson M.,
RA Batista M.C., de Castro Junior C.J., Massensini A.R., Guatimosim C.,
RA Romano-Silva M.A., Kushmerick C., Gomez M.V.;
RT "Phoneutria spider toxins block ischemia-induced glutamate release,
RT neuronal death, and loss of neurotransmission in hippocampus.";
RL Hippocampus 19:1123-1129(2009).
CC -!- FUNCTION: This toxin is a potent and practically irreversible
CC antagonist of both Cav2.1/CACNA1A and Cav2.2/CACNA1B calcium channels,
CC while it displays a partial and rapidly reversible block of
CC Cav2.3/CACNA1E calcium channels and no effect on Cav3/CACNA1 calcium
CC channels. Inhibits glutamate uptake from rat brain synaptosomes by an
CC interaction between cysteines from both glutamate transporter and
CC toxin. Blocks potassium-induced exocytosis of synaptic vesicles in
CC brain cortical synaptosomes with an IC(50) of 1.1 nM. In mice, induces
CC rapid general flaccid paralysis followed by death in 10-30 minutes at
CC dose levels of 5 ug per mouse. In rat brain, inhibits glutamate
CC release, neuronal death and loss of neurotransmission in the
CC hippocampus resulting from ischemia. {ECO:0000269|PubMed:10510308,
CC ECO:0000269|PubMed:10923668, ECO:0000269|PubMed:11397544,
CC ECO:0000269|PubMed:11827974, ECO:0000269|PubMed:18524484,
CC ECO:0000269|PubMed:19370546, ECO:0000269|PubMed:8446961,
CC ECO:0000269|PubMed:9631431, ECO:0000269|PubMed:9683727}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16278100}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000269|PubMed:16278100}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin. {ECO:0000305}.
CC -!- MASS SPECTROMETRY: Mass=8362.7; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:9683727};
CC -!- MASS SPECTROMETRY: Mass=8449.6; Method=Unknown;
CC Evidence={ECO:0000269|PubMed:16278100};
CC -!- BIOTECHNOLOGY: Could be used as a diagnostic tool for the autoimmune
CC disease Lambert-Eaton myasthenic syndrome.
CC {ECO:0000269|PubMed:16289869}.
CC -!- SIMILARITY: Belongs to the neurotoxin 04 (omega-agtx) family. 03 (type
CC II/III omega-agtx) subfamily. {ECO:0000305}.
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DR PIR; D44336; D44336.
DR AlphaFoldDB; P81790; -.
DR SMR; P81790; -.
DR TCDB; 8.B.19.2.8; the sea anemone k+ channel blocker toxin, bcstx3 (bcstx3) family.
DR ArachnoServer; AS000262; omega-ctenitoxin-Pn3a.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR005853; Omega-agatoxin_II/III_CS.
DR InterPro; IPR013605; Toxin_34.
DR Pfam; PF08396; Toxin_34; 1.
DR PROSITE; PS60023; OMEGA_AGA_II_III; 1.
PE 1: Evidence at protein level;
KW Amidation; Calcium channel impairing toxin; Direct protein sequencing;
KW Disulfide bond; Ion channel impairing toxin; Knottin; Neurotoxin; Secreted;
KW Signal; Toxin; Voltage-gated calcium channel impairing toxin.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..38
FT /id="PRO_0000285663"
FT CHAIN 40..115
FT /note="Omega-ctenitoxin-Pn3a"
FT /id="PRO_0000087613"
FT MOD_RES 115
FT /note="Histidine amide"
FT /evidence="ECO:0000269|PubMed:9683727"
FT DISULFID 41..58
FT /evidence="ECO:0000305"
FT DISULFID 48..64
FT /evidence="ECO:0000305"
FT DISULFID 55..90
FT /evidence="ECO:0000305"
FT DISULFID 57..78
FT /evidence="ECO:0000305"
FT DISULFID 66..76
FT /evidence="ECO:0000305"
FT DISULFID 96..102
FT /evidence="ECO:0000255"
FT DISULFID 106..111
FT /evidence="ECO:0000255"
FT CONFLICT 54
FT /note="D -> C (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 58
FT /note="C -> D (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 116 AA; 12678 MW; 020D4FD17978C8F0 CRC64;
MKMKLLGIIL LVSFPFVLGF AGIPIEEGEN SVEVGEVERS CINVGDFCDG KKDDCQCCRD
NAFCSCSVIF GYKTNCRCEV GTTATSYGIC MAKHKCGRQT TCTKPCLSKR CKKNHG
