ID   T2G3A_AGEOR             Reviewed;          71 AA.
AC   Q5Y4V8;
DT   03-NOV-2009, integrated into UniProtKB/Swiss-Prot.
DT   23-NOV-2004, sequence version 1.
DT   25-MAY-2022, entry version 55.
DE   RecName: Full=U3-agatoxin-Ao1a {ECO:0000305};
DE            Short=U3-AGTX-Ao1a {ECO:0000305};
DE   AltName: Full=Beta/delta-agatoxin-7;
DE   AltName: Full=Mu-2Aga_01 {ECO:0000312|EMBL:AAU87886.1};
DE   Flags: Precursor;
OS   Agelena orientalis (Funnel-web spider).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC   Araneomorphae; Entelegynae; Agelenidae; Agelena.
OX   NCBI_TaxID=293813;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RX   PubMed=15688451; DOI=10.1002/prot.20390;
RA   Kozlov S.A., Malyavka A., McCutchen B., Lu A., Schepers E., Herrmann R.,
RA   Grishin E.V.;
RT   "A novel strategy for the identification of toxinlike structures in spider
RT   venom.";
RL   Proteins 59:131-140(2005).
RN   [2]
RP   PROTEIN SEQUENCE OF 34-70, FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, MASS SPECTROMETRY, AND AMIDATION AT SER-70.
RC   TISSUE=Venom;
RX   PubMed=20385552; DOI=10.1074/jbc.m110.125211;
RA   Billen B., Vassilevski A., Nikolsky A., Debaveye S., Tytgat J., Grishin E.;
RT   "Unique bell-shaped voltage-dependent modulation of Na+ channel gating by
RT   novel insect-selective toxins from the spider Agelena orientalis.";
RL   J. Biol. Chem. 285:18545-18554(2010).
CC   -!- FUNCTION: Insecticidal neurotoxin that modulates the insect Nav channel
CC       (DmNaV1/tipE (para/tipE)) in a unique manner, with both the activation
CC       and inactivation processes being affected. The voltage dependence of
CC       activation is shifted toward more hyperpolarized potentials (analogous
CC       to site 4 toxins) and a non-inactivating persistent sodium current is
CC       induced (site 3-like action). Interestingly, both effects take place in
CC       a voltage-dependent manner, producing a bell-shaped curve between -80
CC       and 0 mV. Compared to beta/delta-agatoxin-1 to -3, this toxin appears
CC       to affect the insect sodium channel only weakly.
CC       {ECO:0000269|PubMed:20385552}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20385552}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000269|PubMed:20385552}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin. {ECO:0000250}.
CC   -!- MASS SPECTROMETRY: Mass=4112.4; Mass_error=0.5; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:20385552};
CC   -!- MISCELLANEOUS: Does not affect mammalian sodium channels (Nav).
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the neurotoxin 07 (Beta/delta-agtx) family. 01
CC       (aga-2) subfamily. {ECO:0000305}.
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DR   EMBL; AY681326; AAU87886.1; -; mRNA.
DR   AlphaFoldDB; Q5Y4V8; -.
DR   SMR; Q5Y4V8; -.
DR   ArachnoServer; AS000086; U3-agatoxin-Ao1a.
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; IPR016328; Beta/delta-agatoxin_fam.
DR   PROSITE; PS60015; MU_AGATOXIN; 1.
PE   1: Evidence at protein level;
KW   Amidation; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Knottin; Neurotoxin; Secreted; Signal; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   PROPEP          21..33
FT                   /evidence="ECO:0000269|PubMed:20385552"
FT                   /id="PRO_5000093655"
FT   CHAIN           34..70
FT                   /note="U3-agatoxin-Ao1a"
FT                   /evidence="ECO:0000269|PubMed:20385552"
FT                   /id="PRO_5000093656"
FT   MOD_RES         70
FT                   /note="Serine amide"
FT                   /evidence="ECO:0000269|PubMed:20385552"
FT   DISULFID        35..51
FT                   /evidence="ECO:0000250|UniProtKB:P83257"
FT   DISULFID        42..56
FT                   /evidence="ECO:0000250|UniProtKB:P83257"
FT   DISULFID        50..66
FT                   /evidence="ECO:0000250|UniProtKB:P83257"
FT   DISULFID        58..64
FT                   /evidence="ECO:0000250|UniProtKB:P83257"
SQ   SEQUENCE   71 AA;  7789 MW;  31EBCF905E3D0DB2 CRC64;
     MKAVIFFCLL SVMVFTVIEA VKEEGTKPAE AARECAAKNK RCADWAGPWC CEGLYCSCRS
     YPGCMCRPNS G