SFI1_SEGFL
ID SFI1_SEGFL Reviewed; 46 AA.
AC P61095;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2004, sequence version 1.
DT 25-MAY-2022, entry version 50.
DE RecName: Full=Mu-segestritoxin-Sf1a {ECO:0000303|PubMed:25559770};
DE Short=Mu-SGTX-Sf1a {ECO:0000303|PubMed:25559770};
DE AltName: Full=F5.6 {ECO:0000303|PubMed:11689233};
DE AltName: Full=Toxin SFI1 {ECO:0000303|PubMed:11689233, ECO:0000303|PubMed:15037094};
OS Segestria florentina (Tube-web spider) (Segestria gracilis).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Haplogynae; Dysderoidea; Segestriidae; Segestria.
OX NCBI_TaxID=31925;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-18, FUNCTION, SUBCELLULAR
RP LOCATION, MASS SPECTROMETRY, AND TOXIC DOSE.
RC TISSUE=Venom, and Venom gland;
RX PubMed=11689233; DOI=10.1016/s0041-0101(01)00181-7;
RA Lipkin A., Kozlov S., Nosyreva E., Blake A., Windass J.D., Grishin E.;
RT "Novel insecticidal toxins from the venom of the spider Segestria
RT florentina.";
RL Toxicon 40:125-130(2002).
RN [2]
RP BIOTECHNOLOGY, AND RECOMBINANT EXPRESSION AS A CHIMERIC VARIANT.
RX PubMed=15037094; DOI=10.1016/j.jinsphys.2003.09.010;
RA Fitches E., Edwards M.G., Mee C., Grishin E., Gatehouse A.M., Edwards J.P.,
RA Gatehouse J.A.;
RT "Fusion proteins containing insect-specific toxins as pest control agents:
RT snowdrop lectin delivers fused insecticidal spider venom toxin to insect
RT haemolymph following oral ingestion.";
RL J. Insect Physiol. 50:61-71(2004).
RN [3]
RP BIOTECHNOLOGY, AND RECOMBINANT EXPRESSION AS A CHIMERIC VARIANT.
RX PubMed=16206236; DOI=10.1002/ps.1119;
RA Down R.E., Fitches E.C., Wiles D.P., Corti P., Bell H.A., Gatehouse J.A.,
RA Edwards J.P.;
RT "Insecticidal spider venom toxin fused to snowdrop lectin is toxic to the
RT peach-potato aphid, Myzus persicae (Hemiptera: Aphididae) and the rice
RT brown planthopper, Nilaparvata lugens (Hemiptera: Delphacidae).";
RL Pest Manag. Sci. 62:77-85(2006).
RN [4]
RP STRUCTURE BY NMR, DISULFIDE BOND, FUNCTION, MUTAGENESIS OF 31-ARG--TRP-33,
RP TOXIC DOSE, AND NOMENCLATURE.
RX PubMed=25559770; DOI=10.1111/febs.13189;
RA Bende N.S., Dziemborowicz S., Herzig V., Ramanujam V., Brown G.W.,
RA Bosmans F., Nicholson G.M., King G.F., Mobli M.;
RT "The insecticidal spider toxin SFI1 is a knottin peptide that blocks the
RT pore of insect voltage-gated sodium channels via a large beta-hairpin
RT loop.";
RL FEBS J. 282:904-920(2015).
CC -!- FUNCTION: Insecticidal toxin (PubMed:11689233). It inhibits insect
CC voltage-gated sodium channels (Nav) by partially blocking the channel
CC pore (1 uM inhibits 55.7% sodium current in DUM neurons from the
CC American cockroach), not by acting as a gating modifier
CC (PubMed:25559770). The inhibition is only partially reversible (about
CC 25% recovery) after prolonged washout (PubMed:25559770). In vivo, the
CC toxin causes flaccid paralysis followed by death when injected into
CC Heliothis virescens larvae (PubMed:11689233). It also causes
CC uncoordinated movements followed by full paralysis to sheep blowflies
CC (Lucilia cuprina) (PubMed:25559770). {ECO:0000269|PubMed:11689233,
CC ECO:0000269|PubMed:25559770}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11689233}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:11689233}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:25559770}.
CC -!- MASS SPECTROMETRY: Mass=4973; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:11689233};
CC -!- TOXIC DOSE: LD(50) is 10 mg/kg on H.virescens larvae.
CC {ECO:0000269|PubMed:11689233}.
CC -!- TOXIC DOSE: PD(50) are 2.2 +-0.2 and 1.5 +-0.3 nmol/g (native and
CC recombinant toxins, respectively) when injected into sheep blowfiles
CC (L.cuprina). {ECO:0000269|PubMed:25559770}.
CC -!- BIOTECHNOLOGY: Could be considered as a biological insecticide
CC candidate, when fused to Galanthus nivalis agglutinin (GNA), a protein
CC with the potential to cross the insect gut (PubMed:15037094,
CC PubMed:16206236). This chimeric Sf1a/GNA variant shows a gain in
CC toxicity against insects when administered orally, while maintaining
CC similar effects as the wild-type toxin when injected (PubMed:15037094).
CC This variant has been found to be orally toxic against larvae of the
CC tomato moth (Laconobia oleracea), the rice brown planthopper
CC (Nilaparvata lugens), and the peach-potato aphid (Myzus persicae)
CC (PubMed:15037094, PubMed:16206236). {ECO:0000269|PubMed:15037094,
CC ECO:0000269|PubMed:16206236}.
CC -!- MISCELLANEOUS: It does not show significant effects on voltage-gated
CC calcium channel (Cav) and voltage-gated potassium channel (Kv) currents
CC in cockroach DUM neurons (PubMed:25559770). In vivo, it does not induce
CC any toxic effects when injected intravenously into adult mice at a dose
CC of 1.5 mg/kg body weight (PubMed:25559770).
CC {ECO:0000269|PubMed:25559770}.
CC -!- MISCELLANEOUS: Exists in two forms, due to cis-trans isomerization at
CC 31-Arg-Pro-32. {ECO:0000305|PubMed:25559770}.
CC -!- SIMILARITY: Belongs to the neurotoxin 16 (SFI) family. {ECO:0000305}.
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DR PDB; 2MF3; NMR; -; A=1-46.
DR PDBsum; 2MF3; -.
DR AlphaFoldDB; P61095; -.
DR BMRB; P61095; -.
DR SMR; P61095; -.
DR ArachnoServer; AS000116; mu-segestritoxin-Sf1a.
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.
DR InterPro; IPR012633; Toxin_28.
DR Pfam; PF08115; Toxin_28; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Knottin; Secreted; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT CHAIN 1..46
FT /note="Mu-segestritoxin-Sf1a"
FT /evidence="ECO:0000305|PubMed:11689233"
FT /id="PRO_0000087616"
FT REGION 31..33
FT /note="Keys region for toxin activity"
FT /evidence="ECO:0000269|PubMed:25559770"
FT DISULFID 3..19
FT /evidence="ECO:0000269|PubMed:25559770,
FT ECO:0000312|PDB:2MF3"
FT DISULFID 10..22
FT /evidence="ECO:0000269|PubMed:25559770,
FT ECO:0000312|PDB:2MF3"
FT DISULFID 18..42
FT /evidence="ECO:0000269|PubMed:25559770,
FT ECO:0000312|PDB:2MF3"
FT DISULFID 24..40
FT /evidence="ECO:0000269|PubMed:25559770,
FT ECO:0000312|PDB:2MF3"
FT MUTAGEN 31..33
FT /note="RPW->APA: Complete loss of insecticidal activity as
FT well as complete loss of inhibition of sodium current in
FT DUM neurons."
FT /evidence="ECO:0000269|PubMed:25559770"
FT CONFLICT 18
FT /note="C -> E (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT TURN 12..15
FT /evidence="ECO:0007829|PDB:2MF3"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:2MF3"
SQ SEQUENCE 46 AA; 4982 MW; BFBA4A2A738BB48F CRC64;
KECMTDGTVC YIHNHNDCCG SCLCSNGPIA RPWEMMVGNC MCGPKA
