TX23A_AGEAP
ID TX23A_AGEAP Reviewed; 48 AA.
AC P30288;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 25-MAY-2022, entry version 105.
DE RecName: Full=Omega-agatoxin-Aa4a {ECO:0000305};
DE Short=Omega-AGTX-Aa4a {ECO:0000305};
DE AltName: Full=Omega-agatoxin IVA;
DE Short=Omega-Aga-IVA;
DE AltName: Full=Omega-agatoxin-4A;
OS Agelenopsis aperta (North American funnel-web spider) (Agelenopsis
OS gertschi).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Entelegynae; Agelenidae; Agelenopsis.
OX NCBI_TaxID=6908;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=1311418; DOI=10.1038/355827a0;
RA Mintz I.M., Venema V.J., Swiderek K.M., Lee T.D., Bean B.P., Adams M.E.;
RT "P-type calcium channels blocked by the spider toxin omega-Aga-IVA.";
RL Nature 355:827-829(1992).
RN [2]
RP SYNTHESIS, FUNCTION, AND DISULFIDE BONDS.
RX PubMed=8250902; DOI=10.1006/bbrc.1993.2414;
RA Nishio H., Kumagaye K.Y., Kubo S., Chen Y.N., Momiyama A., Takahashi T.,
RA Kimura T., Sakakibara S.;
RT "Synthesis of omega-agatoxin IVA and its related peptides.";
RL Biochem. Biophys. Res. Commun. 196:1447-1453(1993).
RN [3]
RP FUNCTION.
RX PubMed=7898748; DOI=10.1016/0304-3940(94)90572-x;
RA Bickmeyer U., Rossler W., Wiegand H.;
RT "Omega AGA toxin IVA blocks high-voltage-activated calcium channel currents
RT in cultured pars intercerebralis neurosecretory cells of adult locusta
RT migratoria.";
RL Neurosci. Lett. 181:113-116(1994).
RN [4]
RP FUNCTION.
RX PubMed=9129813; DOI=10.1016/s0006-3495(97)78854-4;
RA McDonough S.I., Mintz I.M., Bean B.P.;
RT "Alteration of P-type calcium channel gating by the spider toxin omega-Aga-
RT IVA.";
RL Biophys. J. 72:2117-2128(1997).
RN [5]
RP FUNCTION.
RX PubMed=9120560; DOI=10.1152/jn.1997.77.1.186;
RA Wicher D., Penzlin H.;
RT "Ca2+ currents in central insect neurons: electrophysiological and
RT pharmacological properties.";
RL J. Neurophysiol. 77:186-199(1997).
RN [6]
RP FUNCTION.
RX PubMed=11055992; DOI=10.1085/jgp.116.5.637;
RA Winterfield J.R., Swartz K.J.;
RT "A hot spot for the interaction of gating modifier toxins with voltage-
RT dependent ion channels.";
RL J. Gen. Physiol. 116:637-644(2000).
RN [7]
RP FUNCTION.
RX PubMed=11522785; DOI=10.1074/jbc.m105206200;
RA Wang X.-H., Connor M., Wilson D., Wilson H.I., Nicholson G.M., Smith R.,
RA Shaw D., Mackay J.P., Alewood P.F., Christie M.J., King G.F.;
RT "Discovery and structure of a potent and highly specific blocker of insect
RT calcium channels.";
RL J. Biol. Chem. 276:40306-40312(2001).
RN [8]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=7623383; DOI=10.1006/jmbi.1995.0406;
RA Kim J.I., Konishi S., Iwai H., Kohno T., Gouda H., Shimada I., Sato K.,
RA Arata Y.;
RT "Three-dimensional solution structure of the calcium channel antagonist
RT omega-agatoxin IVA: consensus molecular folding of calcium channel
RT blockers.";
RL J. Mol. Biol. 250:659-671(1995).
RN [9]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=7773772; DOI=10.1038/nsb1294-853;
RA Reily M.D., Holub K.E., Gray W.R., Norris T.M., Adams M.E.;
RT "Structure-activity relationships for P-type calcium channel-selective
RT omega-agatoxins.";
RL Nat. Struct. Biol. 1:853-856(1994).
CC -!- FUNCTION: Omega-agatoxins inhibit neuronal voltage-gated calcium
CC channels. This toxin acts by modifying the gating of the high voltage
CC activated P-type Cav2.1/CACNA1A channel. Is a potent blocker in both
CC insect and mammalian central neurons. {ECO:0000269|PubMed:11055992,
CC ECO:0000269|PubMed:11522785, ECO:0000269|PubMed:1311418,
CC ECO:0000269|PubMed:7898748, ECO:0000269|PubMed:8250902,
CC ECO:0000269|PubMed:9120560, ECO:0000269|PubMed:9129813}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1311418}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:1311418}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:7623383, ECO:0000269|PubMed:7773772}.
CC -!- MISCELLANEOUS: This toxin is a diagnostic ligand for P-type channels
CC Ca2.1/CACNA1A in the mammalian brain.
CC -!- MISCELLANEOUS: The binding site for this toxin has been localized in
CC part to the extracellular S3-S4 loop in repeat IV of the alpha1 subunit
CC of mammalian Cav2.1/CACNA1A channels, which is proximal to the S4
CC sensor domain.
CC -!- SIMILARITY: Belongs to the neurotoxin 02 (plectoxin) family. 03 (omega-
CC agtx) subfamily. {ECO:0000305}.
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DR PIR; S20256; S20256.
DR PDB; 1IVA; NMR; -; A=1-48.
DR PDB; 1OAV; NMR; -; A=1-48.
DR PDB; 1OAW; NMR; -; A=1-48.
DR PDB; 2NDB; NMR; -; A=1-48.
DR PDBsum; 1IVA; -.
DR PDBsum; 1OAV; -.
DR PDBsum; 1OAW; -.
DR PDBsum; 2NDB; -.
DR AlphaFoldDB; P30288; -.
DR BMRB; P30288; -.
DR SMR; P30288; -.
DR TCDB; 8.B.6.1.1; the ca(2+) channel-targeting spider toxin (cst) family.
DR ArachnoServer; AS000182; omega-agatoxin-Aa4a.
DR EvolutionaryTrace; P30288; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0019855; F:calcium channel inhibitor activity; IDA:CACAO.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR CDD; cd12960; Spider_toxin; 1.
DR InterPro; IPR004169; Spidertoxin.
DR Pfam; PF02819; Toxin_9; 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;
KW Presynaptic neurotoxin; Secreted; Toxin;
KW Voltage-gated calcium channel impairing toxin.
FT CHAIN 1..48
FT /note="Omega-agatoxin-Aa4a"
FT /evidence="ECO:0000269|PubMed:1311418"
FT /id="PRO_0000087610"
FT DISULFID 4..20
FT /evidence="ECO:0000269|PubMed:7623383,
FT ECO:0000269|PubMed:7773772, ECO:0007744|PDB:1IVA,
FT ECO:0007744|PDB:1OAV, ECO:0007744|PDB:1OAW,
FT ECO:0007744|PDB:2NDB"
FT DISULFID 12..25
FT /evidence="ECO:0000269|PubMed:7623383,
FT ECO:0000269|PubMed:7773772, ECO:0007744|PDB:1IVA,
FT ECO:0007744|PDB:1OAV, ECO:0007744|PDB:1OAW,
FT ECO:0007744|PDB:2NDB"
FT DISULFID 19..36
FT /evidence="ECO:0000269|PubMed:7623383,
FT ECO:0000269|PubMed:7773772, ECO:0007744|PDB:1IVA,
FT ECO:0007744|PDB:1OAV, ECO:0007744|PDB:1OAW,
FT ECO:0007744|PDB:2NDB"
FT DISULFID 27..34
FT /evidence="ECO:0000269|PubMed:7623383,
FT ECO:0000269|PubMed:7773772, ECO:0007744|PDB:1IVA,
FT ECO:0007744|PDB:1OAV, ECO:0007744|PDB:1OAW,
FT ECO:0007744|PDB:2NDB"
FT STRAND 3..5
FT /evidence="ECO:0007829|PDB:1OAV"
FT STRAND 7..11
FT /evidence="ECO:0007829|PDB:1OAW"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:1IVA"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:1OAV"
FT STRAND 29..33
FT /evidence="ECO:0007829|PDB:1IVA"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:1OAV"
FT TURN 41..44
FT /evidence="ECO:0007829|PDB:1IVA"
FT TURN 45..47
FT /evidence="ECO:0007829|PDB:1OAV"
SQ SEQUENCE 48 AA; 5210 MW; 945054B55EAE81FD CRC64;
KKKCIAKDYG RCKWGGTPCC RGRGCICSIM GTNCECKPRL IMEGLGLA
