TX23B_AGEAP
ID TX23B_AGEAP Reviewed; 83 AA.
AC P37045;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 25-MAY-2022, entry version 106.
DE RecName: Full=Omega-agatoxin-Aa4b {ECO:0000305};
DE Short=Omega-AGTX-Aa4b {ECO:0000305};
DE AltName: Full=Omega-agatoxin IVB;
DE Short=Omega-Aga-IVB;
DE AltName: Full=Omega-agatoxin IVC;
DE Short=Omega-Aga-IVC;
DE AltName: Full=Omega-agatoxin tsukuba;
DE Short=Omega-Aga-TK;
DE Short=Omega-agatoxin-TK;
DE AltName: Full=Omega-agatoxin-4B;
DE Flags: Precursor;
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 NUCLEOTIDE SEQUENCE [MRNA].
RA Heck S.D., Siok C.J., Krapcho K.J.;
RL Submitted (OCT-1994) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 36-83, FUNCTION, STRUCTURE BY NMR OF 36-83, DISULFIDE
RP BONDS, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=8232218;
RA Adams M.E., Mintz I.M., Reily M.D., Thanabal V., Bean B.P.;
RT "Structure and properties of omega-agatoxin IVB, a new antagonist of P-type
RT calcium channels.";
RL Mol. Pharmacol. 44:681-688(1993).
RN [3]
RP PROTEIN SEQUENCE OF 36-83, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=8216284; DOI=10.1006/bbrc.1993.2225;
RA Teramoto T., Kuwada M., Niidome T., Sawada K., Nishizawa Y., Katayama K.;
RT "A novel peptide from funnel web spider venom, omega-Aga-TK, selectively
RT blocks, P-type calcium channels.";
RL Biochem. Biophys. Res. Commun. 196:134-140(1993).
RN [4]
RP DISULFIDE BONDS, AND D-AMINO ACID AT SER-81.
RX DOI=10.1021/ja00102a009;
RA Heck S.D., Kelbaugh P.R., Kelly M.E., Thadeio P.F., Saccomano N.A.,
RA Stroh J.G., Volkmann R.A.;
RT "Disulfide bond assignment of omega-agatoxins IVB and IVC: discovery of a
RT D-serine residue in omega-agatoxin IVB.";
RL J. Am. Chem. Soc. 116:10426-10436(1994).
RN [5]
RP D-AMINO ACID AT SER-81, AND CHARACTERIZATION OF D- AND L- FORMS.
RX PubMed=7973665; DOI=10.1126/science.7973665;
RA Heck S.D., Siok C.J., Krapcho K.J., Kelbaugh P.R., Thadeio P.F.,
RA Welch M.J., Williams R.D., Ganong A.H., Kelly M.E., Lanzetti A.J.;
RT "Functional consequences of posttranslational isomerization of Ser46 in a
RT calcium channel toxin.";
RL Science 266:1065-1068(1994).
RN [6]
RP D-AMINO ACID AT SER-81, AND CHARACTERIZATION OF D- AND L- FORMS.
RX PubMed=7969037;
RA Kuwada M., Teramoto T., Kumagaye K.Y., Nakajima K., Watanabe T., Kawai T.,
RA Kawakami Y., Niidome T., Sawada K., Nishizawa Y.;
RT "Omega-agatoxin-TK containing D-serine at position 46, but not synthetic
RT omega-[L-Ser46]agatoxin-TK, exerts blockade of P-type calcium channels in
RT cerebellar Purkinje neurons.";
RL Mol. Pharmacol. 46:587-593(1994).
RN [7]
RP STRUCTURE BY NMR OF 36-83, AND DISULFIDE BONDS.
RX PubMed=8241166; DOI=10.1021/bi00211a022;
RA Yu H., Rosen M.K., Saccomano N.A., Phillips D., Volkmann R.A.,
RA Schreiber S.L.;
RT "Sequential assignment and structure determination of spider toxin omega-
RT Aga-IVB.";
RL Biochemistry 32:13123-13129(1993).
RN [8]
RP STRUCTURE BY NMR OF 36-83, AND DISULFIDE BONDS.
RX PubMed=7703698; DOI=10.1007/bf00208803;
RA Reily M.D., Thanabal V., Adams M.E.;
RT "The solution structure of omega-Aga-IVB, a P-type calcium channel
RT antagonist from venom of the funnel web spider, Agelenopsis aperta.";
RL J. Biomol. NMR 5:122-132(1995).
CC -!- FUNCTION: Antagonist of voltage-gated Cav2.1/CACNA1A (P-type) calcium
CC channels. Paralyzes insect by blocking neuromuscular transmission.
CC {ECO:0000269|PubMed:8232218}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8216284,
CC ECO:0000269|PubMed:8232218}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:8216284, ECO:0000305|PubMed:8232218}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000250|UniProtKB:P30288}.
CC -!- PTM: The toxin with D-Ser (named omega-aga IVC) is 80-90 fold more
CC potent than that with L-Ser (omega-aga IVB) against Cav2.1/CACNA1A (P-
CC type) channels in rat cerebellar Purkinje neurons and is more resistant
CC to proteases. The epimerization is done by the venom peptide isomerase
CC heterodimer.
CC -!- SIMILARITY: Belongs to the neurotoxin 02 (plectoxin) family. 03 (omega-
CC agtx) subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U15925; AAA57116.1; -; mRNA.
DR PIR; A44664; A44664.
DR PDB; 1AGG; NMR; -; A=36-83.
DR PDB; 1OMA; NMR; -; A=36-83.
DR PDB; 1OMB; NMR; -; A=36-83.
DR PDBsum; 1AGG; -.
DR PDBsum; 1OMA; -.
DR PDBsum; 1OMB; -.
DR AlphaFoldDB; P37045; -.
DR SMR; P37045; -.
DR ArachnoServer; AS000183; omega-agatoxin-Aa4b.
DR EvolutionaryTrace; P37045; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
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; D-amino acid;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Knottin; Neurotoxin; Presynaptic neurotoxin; Secreted; Signal; Toxin;
KW Voltage-gated calcium channel impairing toxin.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..35
FT /evidence="ECO:0000250"
FT /id="PRO_0000035490"
FT CHAIN 36..83
FT /note="Omega-agatoxin-Aa4b"
FT /id="PRO_0000035491"
FT MOD_RES 81
FT /note="D-serine (Ser)"
FT /evidence="ECO:0000269|PubMed:7969037,
FT ECO:0000269|PubMed:7973665, ECO:0000269|Ref.4"
FT DISULFID 39..55
FT DISULFID 47..60
FT DISULFID 54..71
FT DISULFID 62..69
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:1AGG"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:1AGG"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:1AGG"
FT STRAND 64..71
FT /evidence="ECO:0007829|PDB:1AGG"
FT TURN 76..79
FT /evidence="ECO:0007829|PDB:1AGG"
SQ SEQUENCE 83 AA; 9167 MW; 826F5C7E2FDD3CDE CRC64;
MKLCMTLLIT AIAVVTFVVA TQEESAEFNE VEESREDNCI AEDYGKCTWG GTKCCRGRPC
RCSMIGTNCE CTPRLIMEGL SFA
