TXP3_APOSC
ID TXP3_APOSC Reviewed; 37 AA.
AC P49268;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 25-MAY-2022, entry version 79.
DE RecName: Full=Mu-cyrtautoxin-As1a;
DE Short=Mu-CUTX-As1a;
DE AltName: Full=Aptotoxin III {ECO:0000303|PubMed:23473802};
DE Short=Aps III {ECO:0000303|PubMed:23473802};
DE AltName: Full=Aptotoxin-3;
DE Short=Aps-3;
DE AltName: Full=Paralytic peptide III;
DE Short=PP III;
OS Apomastus schlingeri (Trap-door spider) (Aptostichus schlingeri).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Mygalomorphae; Euctenizidae; Apomastus.
OX NCBI_TaxID=12944;
RN [1]
RP PROTEIN SEQUENCE, SUBCELLULAR LOCATION, BIOASSAY, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=1440641; DOI=10.1016/0041-0101(92)90049-b;
RA Skinner W.S., Dennis P.A., Li J.P., Quistad G.B.;
RT "Identification of insecticidal peptides from venom of the trap-door
RT spider, Aptostichus schlingeri (Ctenizidae).";
RL Toxicon 30:1043-1050(1992).
RN [2]
RP FUNCTION, STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=23473802; DOI=10.1016/j.bcp.2013.02.030;
RA Bende N.S., Kang E., Herzig V., Bosmans F., Nicholson G.M., Mobli M.,
RA King G.F.;
RT "The insecticidal neurotoxin Aps III is an atypical knottin peptide that
RT potently blocks insect voltage-gated sodium channels.";
RL Biochem. Pharmacol. 85:1542-1554(2013).
CC -!- FUNCTION: The recombinant mu-cyrtautoxin-As1a potently and voltage-
CC independently blocks voltage-gated sodium channels (Nav) of insects. It
CC acts by pluging the outer vestibule of the channel. It acts in
CC combination with a weak (30%) voltage-independent block of insect
CC voltage-gated calcium (Cav) channels (low-voltage and high-voltage
CC channels). Tested on DUM neurons, it inhibits sodium currents with an
CC IC(50) of 540 nM (and a Hill coefficient >1, reflecting an incomplete
CC block at higher concentrations). In vivo, it induces flaccid paralysis
CC in adult Australian sheep blowfly Lucilia cuprina (PubMed:23473802). It
CC is both paralytic and lethal, when injected into lepidopteran larvae.
CC It is a slower acting toxin, being lethal at 24 hours, but not
CC paralytic at 1 hour post-injection (PubMed:1440641).
CC {ECO:0000269|PubMed:1440641, ECO:0000269|PubMed:23473802}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1440641}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:1440641}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:23473802}.
CC -!- TOXIC DOSE: LD(50) is 133 pmol/g in the tobacco hornworm Manduca sexta
CC (PubMed:1440641). {ECO:0000269|PubMed:1440641}.
CC -!- TOXIC DOSE: LD(50) is more than 2.66 pmol/g against the beet armyworm
CC Spodoptera exigua (PubMed:1440641). {ECO:0000269|PubMed:1440641}.
CC -!- TOXIC DOSE: PD(50) is 700 +- 35 pmol/g in adult Australian sheep
CC blowfly (Lucilia cuprina) (at 24 hours post-injection).
CC {ECO:0000269|PubMed:1440641, ECO:0000269|PubMed:23473802}.
CC -!- MISCELLANEOUS: Does not modulate the activity of delayed-rectifier, 'A-
CC type' or BKCa potassium channels. {ECO:0000305|PubMed:23473802}.
CC -!- SIMILARITY: Belongs to the neurotoxin 13 (insecticidal toxin ABC)
CC family. 01 (Aps III) subfamily. {ECO:0000305}.
CC -!- CAUTION: No comparison between the natural toxin and the recombinant
CC one has been done to attest that the results can be also attributed to
CC the natural toxin (mode of action and disulfide bonds).
CC {ECO:0000305|PubMed:23473802}.
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DR PIR; E44007; E44007.
DR PDB; 2M36; NMR; -; A=1-37.
DR PDBsum; 2M36; -.
DR AlphaFoldDB; P49268; -.
DR BMRB; P49268; -.
DR SMR; P49268; -.
DR TCDB; 8.B.21.1.1; the spider insecticidal neurotoxin cyrtautoxin (cyrautoxin) family.
DR ArachnoServer; AS000403; mu-cyrtautoxin-As1a.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005246; F:calcium channel regulator activity; 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 GO; GO:0044487; P:envenomation resulting in modulation of transmission of nerve impulse in another organism; IDA:UniProtKB.
DR GO; GO:0044475; P:envenomation resulting in negative regulation of high voltage-gated calcium channel activity in another organism; IDA:UniProtKB.
DR GO; GO:0044476; P:envenomation resulting in negative regulation of low voltage-gated calcium channel activity in another organism; IDA:UniProtKB.
DR GO; GO:0044493; P:envenomation resulting in negative regulation of voltage-gated sodium channel activity in another organism; IDA:UniProtKB.
DR InterPro; IPR012626; Spider_insecticidal_peptide.
DR Pfam; PF08091; Toxin_21; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium channel impairing toxin; Direct protein sequencing;
KW Disulfide bond; Ion channel impairing toxin; Knottin; Neurotoxin; Secreted;
KW Toxin; Voltage-gated calcium channel impairing toxin;
KW Voltage-gated sodium channel impairing toxin.
FT PEPTIDE 1..37
FT /note="Mu-cyrtautoxin-As1a"
FT /evidence="ECO:0000269|PubMed:1440641"
FT /id="PRO_0000044986"
FT DISULFID 1..15
FT /evidence="ECO:0000269|PubMed:23473802,
FT ECO:0000312|PDB:2M36"
FT DISULFID 8..19
FT /evidence="ECO:0000269|PubMed:23473802,
FT ECO:0000312|PDB:2M36"
FT DISULFID 14..35
FT /evidence="ECO:0000269|PubMed:23473802,
FT ECO:0000312|PDB:2M36"
FT DISULFID 26..31
FT /evidence="ECO:0000269|PubMed:23473802,
FT ECO:0000312|PDB:2M36"
FT STRAND 7..10
FT /evidence="ECO:0007829|PDB:2M36"
FT HELIX 11..13
FT /evidence="ECO:0007829|PDB:2M36"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:2M36"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:2M36"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:2M36"
SQ SEQUENCE 37 AA; 3769 MW; CBD01091694E1908 CRC64;
CNSKGTPCTN ADECCGGKCA YNVWNCIGGG CSKTCGY
