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TX35D_PHONI
ID   TX35D_PHONI             Reviewed;          82 AA.
AC   P59368;
DT   28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT   10-MAY-2004, sequence version 2.
DT   25-MAY-2022, entry version 60.
DE   RecName: Full=Delta-ctenitoxin-Pn1a {ECO:0000303|PubMed:27077886};
DE            Short=Delta-CNTX-Pn1a {ECO:0000303|PubMed:27077886};
DE   AltName: Full=Insecticidal neurotoxin Tx4(6-1) {ECO:0000303|PubMed:7778132};
DE            Short=PnTx4(6-1) {ECO:0000303|PubMed:10758278, ECO:0000303|PubMed:16278100, ECO:0000303|PubMed:7778132};
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 35-82, FUNCTION, MASS SPECTROMETRY, TOXIC DOSE, AND
RP   SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=7778132; DOI=10.1016/0041-0101(94)00130-z;
RA   Figueiredo S.G., Lima-Perez Garcia M.E., Valentim A.D.C., Cordeiro M.N.,
RA   Diniz C.R., Richardson M.;
RT   "Purification and amino acid sequence of the insecticidal neurotoxin Tx4(6-
RT   1) from the venom of the 'armed' spider Phoneutria nigriventer (Keys).";
RL   Toxicon 33:83-93(1995).
RN   [3]
RP   PROTEIN SEQUENCE OF 35-82.
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.
RC   TISSUE=Venom;
RX   PubMed=12770132; DOI=10.1016/s0022-1910(01)00143-3;
RA   de Lima M.E., Stankiewicz M., Hamon A., de Figueiredo S.G., Cordeiro M.N.,
RA   Diniz C.R., Martin-Eauclaire M.-F., Pelhate M.;
RT   "The toxin Tx4(6-1) from the spider Phoneutria nigriventer slows down Na(+)
RT   current inactivation in insect CNS via binding to receptor site 3.";
RL   J. Insect Physiol. 48:53-61(2002).
RN   [5]
RP   FUNCTION.
RX   PubMed=14757211; DOI=10.1016/j.toxicon.2003.10.009;
RA   Oliveira L.C., De Lima M.E., Pimenta A.M.C., Mansuelle P., Rochat H.,
RA   Cordeiro M.N., Richardson M., Figueiredo S.G.;
RT   "PnTx4-3, a new insect toxin from Phoneutria nigriventer venom elicits the
RT   glutamate uptake inhibition exhibited by PhTx4 toxic fraction.";
RL   Toxicon 42:793-800(2003).
RN   [6]
RP   FUNCTION.
RX   PubMed=27077886; DOI=10.3390/toxins8040106;
RA   Emerich B.L., Ferreira R.C., Cordeiro M.N., Borges M.H., Pimenta A.M.,
RA   Figueiredo S.G., Duarte I.D., de Lima M.E.;
RT   "Delta-ctenitoxin-Pn1a, a peptide from Phoneutria nigriventer spider venom,
RT   shows antinociceptive effect involving opioid and cannabinoid systems, in
RT   rats.";
RL   Toxins 8:106-106(2016).
CC   -!- FUNCTION: This neurotoxin binds at site 3 of insect voltage-activated
CC       sodium channels (Nav) and prolongs evoked axonal action potentials by a
CC       slowing down of sodium current inactivation (PubMed:12770132). The
CC       toxin also inhibits glutamate uptake from rat brain synaptosomes
CC       (PubMed:14757211). It reversibly inhibits the N-methyl-D-aspartate
CC       (NMDA)-subtype of ionotropic glutamate receptor (GRIN) (By similarity).
CC       In addition, the toxin shows antinociceptive effect in all rat pain
CC       models tested (inflammatory, neuropathic and nociceptive)
CC       (PubMed:27077886). The antinociceptive effect is partially blocked when
CC       selective antagonists of both mu- and delta-opioid receptors are
CC       administered, revealing that the antinociceptive effect of the toxin
CC       involves both opiod and cannabinoid endogenous systems
CC       (PubMed:27077886). In vivo, it is highly toxic to house fly (Musca
CC       domestica), toxic to cockroach, but has no effect when
CC       intracerebroventricularly injected into mice (PubMed:7778132,
CC       PubMed:12770132). {ECO:0000250|UniProtKB:P59367,
CC       ECO:0000269|PubMed:12770132, ECO:0000269|PubMed:14757211,
CC       ECO:0000269|PubMed:27077886, ECO:0000269|PubMed:7778132}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7778132}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:7778132}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin. {ECO:0000305}.
CC   -!- MASS SPECTROMETRY: Mass=5244.6; Method=Plasma desorption;
CC       Evidence={ECO:0000269|PubMed:7778132};
CC   -!- TOXIC DOSE: LD(50) is 3.8 ng/house fly. {ECO:0000269|PubMed:7778132}.
CC   -!- MISCELLANEOUS: Does not affect the currents in rat brain Nav1.2/SCN2A
CC       or skeletal muscle Nav1.4/SCN4A sodium channels.
CC       {ECO:0000269|PubMed:12770132}.
CC   -!- SIMILARITY: Belongs to the neurotoxin 03 (Tx2) family. 05 subfamily.
CC       {ECO:0000305}.
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DR   AlphaFoldDB; P59368; -.
DR   SMR; P59368; -.
DR   ArachnoServer; AS000280; delta-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.
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:16278100,
FT                   ECO:0000269|PubMed:7778132"
FT                   /id="PRO_0000035509"
FT   CHAIN           35..82
FT                   /note="Delta-ctenitoxin-Pn1a"
FT                   /evidence="ECO:0000269|PubMed:7778132"
FT                   /id="PRO_0000035510"
FT   DISULFID        35..49
FT                   /evidence="ECO:0000305"
FT   DISULFID        42..55
FT                   /evidence="ECO:0000305"
FT   DISULFID        46..82
FT                   /evidence="ECO:0000305"
FT   DISULFID        48..65
FT                   /evidence="ECO:0000305"
FT   DISULFID        57..63
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   82 AA;  9088 MW;  94CF974B000B06C3 CRC64;
     MKVAIVFLSL LVLAFASESI EENREEFPVE ESARCGDINA ACKEDCDCCG YTTACDCYWS
     KSCKCREAAI VIYTAPKKKL TC
 
 
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