PMTXA_ANOSM
ID PMTXA_ANOSM Reviewed; 56 AA.
AC P69391; A6P330;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2014, sequence version 2.
DT 25-MAY-2022, entry version 39.
DE RecName: Full=Alpha-pompilidotoxin {ECO:0000303|PubMed:9464629, ECO:0000303|PubMed:9784394};
DE Short=Alpha-PMTX {ECO:0000303|PubMed:9464629, ECO:0000303|PubMed:9784394};
DE Flags: Precursor;
OS Anoplius samariensis (Solitary wasp).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Hymenoptera; Apocrita; Aculeata; Pompiloidea;
OC Pompilidae; Pompilinae; Anoplius.
OX NCBI_TaxID=200614;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hisada M., Kanda A., Kuroda K., Minakata H., Nakajima T.;
RT "Cloning of alpha-pompilidotoxin and As126 cDNA in Anoplius samariensis.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 43-55, MASS SPECTROMETRY, AMIDATION AT LEU-55, AND
RP SYNTHESIS OF 43-55.
RC TISSUE=Venom;
RX PubMed=9784394; DOI=10.1006/bbrc.1998.9299;
RA Konno K., Hisada M., Itagaki Y., Naoki H., Kawai N., Miwa A., Yasuhara T.,
RA Takayama H.;
RT "Isolation and structure of pompilidotoxins, novel peptide neurotoxins in
RT solitary wasp venoms.";
RL Biochem. Biophys. Res. Commun. 250:612-616(1998).
RN [3]
RP CHARACTERIZATION.
RC TISSUE=Venom;
RX PubMed=9464629; DOI=10.1016/s0304-3940(97)00849-5;
RA Konno K., Miwa A., Takayama H., Hisada M., Itagaki Y., Naoki H.,
RA Yasuhara T., Kawai N.;
RT "Alpha-pompilidotoxin (alpha-PMTX), a novel neurotoxin from the venom of a
RT solitary wasp, facilitates transmission in the crustacean neuromuscular
RT synapse.";
RL Neurosci. Lett. 238:99-102(1997).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=9756356; DOI=10.1016/s0304-3940(98)00555-2;
RA Harsch A., Konno K., Takayama H., Kawai N., Robinson H.;
RT "Effects of alpha-pompilidotoxin on synchronized firing in networks of rat
RT cortical neurons.";
RL Neurosci. Lett. 252:49-52(1998).
RN [5]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=10886337; DOI=10.1046/j.1460-9568.2000.00084.x;
RA Sahara Y., Gotoh M., Konno K., Miwa A., Tsubokawa H., Robinson H.P.,
RA Kawai N.;
RT "A new class of neurotoxin from wasp venom slows inactivation of sodium
RT current.";
RL Eur. J. Neurosci. 12:1961-1970(2000).
RN [6]
RP MUTAGENESIS OF ARG-43; ILE-44; LYS-45; ILE-46; GLY-47; LEU-48; PHE-49;
RP ASP-50; GLN-51; LEU-52; SER-53; LYS-54 AND LEU-55, AND SYNTHESIS OF 43-55.
RX PubMed=10788700; DOI=10.1016/s0304-3940(00)01017-x;
RA Konno K., Hisada M., Naoki H., Itagaki Y., Yasuhara T., Nakata Y., Miwa A.,
RA Kawai N.;
RT "Molecular determinants of binding of a wasp toxin (PMTXs) and its analogs
RT in the Na+ channels proteins.";
RL Neurosci. Lett. 285:29-32(2000).
RN [7]
RP FUNCTION, SYNTHESIS OF 43-55, AND MUTAGENESIS OF ARG-43.
RX PubMed=20059541; DOI=10.1111/j.1742-4658.2009.07533.x;
RA Schiavon E., Stevens M., Zaharenko A.J., Konno K., Tytgat J., Wanke E.;
RT "Voltage-gated sodium channel isoform-specific effects of
RT pompilidotoxins.";
RL FEBS J. 277:918-930(2010).
RN [8]
RP REVIEW.
RX PubMed=27096870; DOI=10.3390/toxins8040114;
RA Konno K., Kazuma K., Nihei K.;
RT "Peptide toxins in solitary wasp venoms.";
RL Toxins 8:114-114(2016).
CC -!- FUNCTION: Inhibits sodium channels (Nav) inactivation. Shows two types
CC of inhibitory activities on channels. Inhibition of hNav1.6/SCN8A shows
CC a large increase in the steady-state current component without any
CC increase in the slow component, whereas inhibition of hNav1.1/SCN1A,
CC hNav1.2/SCN2A, hNav1.3/SCN3A and hNav1.7/SCN9A shows a large increase
CC in the slow component with only a small steady-state component
CC (PubMed:20059541). Is 5-fold less potent than beta-PMTX for inducing
CC repetitive action potentials in lobster neuromuscular junctions.
CC {ECO:0000269|PubMed:10886337, ECO:0000269|PubMed:20059541,
CC ECO:0000269|PubMed:9756356}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9756356}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC -!- MASS SPECTROMETRY: Mass=1530; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:9784394};
CC -!- MISCELLANEOUS: Does not or very slightly inactivate hNav1.4/SCN4A and
CC hNav1.5/SCN5A sodium channels. {ECO:0000269|PubMed:20059541}.
CC -!- MISCELLANEOUS: Potency in mutagenesis experiments is measured by the
CC concentration of these mutant toxins for inducing repetitive action
CC potentials. {ECO:0000305|PubMed:10788700}.
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DR EMBL; AB087726; BAF65254.1; -; mRNA.
DR AlphaFoldDB; P69391; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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 Amidation; Direct protein sequencing; Ion channel impairing toxin;
KW Neurotoxin; Presynaptic neurotoxin; Secreted; Signal; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..42
FT /evidence="ECO:0000269|PubMed:9784394"
FT /id="PRO_0000430343"
FT PEPTIDE 43..55
FT /note="Alpha-pompilidotoxin"
FT /evidence="ECO:0000269|PubMed:9784394"
FT /id="PRO_0000044536"
FT MOD_RES 55
FT /note="Leucine amide"
FT /evidence="ECO:0000305|PubMed:9784394"
FT MUTAGEN 43
FT /note="R->K: 5-fold increase in potency and similar order
FT of inhibition potency on different Nav isoforms. No change
FT in potency; when associated with R-342. 3-fold increase in
FT potency; when associated with R-12. 3-fold increase in
FT potency; when associated with R-342 and R-144."
FT /evidence="ECO:0000269|PubMed:10788700,
FT ECO:0000269|PubMed:20059541"
FT MUTAGEN 44
FT /note="I->F: Complete loss of potency."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 44
FT /note="I->T: Complete loss of potency."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 45
FT /note="K->G: Complete loss of potency; when associated with
FT K-542."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 45
FT /note="K->I: Complete loss of potency; when associated with
FT K-442."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 45
FT /note="K->L: Complete loss of potency."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 45
FT /note="K->R: 5-fold increase in potency. No change in
FT potency; when associated with K-142. 3-fold increase in
FT potency; when associated with K-142 and R-12. 5-fold
FT increase in potency; when associated with R-144."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 46
FT /note="I->K: Complete loss of potency; when associated with
FT I-342."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 46
FT /note="I->T: Complete loss of potency."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 47
FT /note="G->K: Complete loss of potency; when associated with
FT G-342."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 47
FT /note="G->L: Complete loss of potency."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 47
FT /note="G->P: Complete loss of potency."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 48
FT /note="L->S: Complete loss of potency."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 49
FT /note="F->Y: Complete loss of potency."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 50
FT /note="D->A: 2-fold decrease in potency."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 50
FT /note="D->N: Complete loss of potency."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 51
FT /note="Q->L: 1.25-fold decrease in potency."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 51
FT /note="Q->N: 2-fold decrease in potency."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 52
FT /note="L->T: Complete loss of potency."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 53
FT /note="S->A: Complete loss of potency."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 54
FT /note="K->R: 5-fold increase in potency (This mutant
FT corresponds to beta-PMTX). 5-fold increase in potency; when
FT associated with R-342. 3-fold increase in potency; when
FT associated with K-1. 3-fold increase in potency; when
FT associated with K-142 and R-342."
FT /evidence="ECO:0000269|PubMed:10788700"
FT MUTAGEN 55
FT /note="L->S: 10-fold decrease in potency."
FT /evidence="ECO:0000269|PubMed:10788700"
SQ SEQUENCE 56 AA; 5920 MW; 12FEF411CBB5991F CRC64;
MFKQLILLAL AAVFLLINIS SAEPAAEPNA NAEPLAEASA EPRIKIGLFD QLSKLG
