CA1A_CONTE
ID CA1A_CONTE Reviewed; 56 AA.
AC P0DM21;
DT 12-SEP-2018, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 1.
DT 25-MAY-2022, entry version 13.
DE RecName: Full=Alpha-conotoxin TxIA {ECO:0000303|PubMed:17660751};
DE AltName: Full=Conotoxin tx1a {ECO:0000303|PubMed:23031820};
DE Flags: Precursor;
OS Conus textile (Cloth-of-gold cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Cylinder.
OX NCBI_TaxID=6494;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Watkins M., Olivera B.M., Hillyard D.R., Mcintosh M.J., Jones R.M.;
RT "Alpha-conotoxin peptides.";
RL Patent number US6797808, 22-OCT-2002.
RN [2]
RP PROTEIN SEQUENCE OF 40-55, FUNCTION, MASS SPECTROMETRY, SUBCELLULAR
RP LOCATION, AMIDATION AT CYS-55, X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF
RP [A10L]-TXIA IN COMPLEX WITH SOLUBLE ACETYLCHOLINE RECEPTOR, AND MUTAGENESIS
RP OF ALA-49.
RX PubMed=17660751; DOI=10.1038/sj.emboj.7601785;
RA Dutertre S., Ulens C., Buettner R., Fish A., van Elk R., Kendel Y.,
RA Hopping G., Alewood P.F., Schroeder C., Nicke A., Smit A.B., Sixma T.K.,
RA Lewis R.J.;
RT "AChBP-targeted alpha-conotoxin correlates distinct binding orientations
RT with nAChR subtype selectivity.";
RL EMBO J. 26:3858-3867(2007).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY, POSITION IN VENOM
RP DUCT, HYDROXYLATION AT PRO-45 AND PRO-46, AND AMIDATION AT CYS-55.
RC TISSUE=Venom;
RX PubMed=23031820; DOI=10.1016/j.toxicon.2012.09.013;
RA Dobson R., Collodoro M., Gilles N., Turtoi A., De Pauw E., Quinton L.;
RT "Secretion and maturation of conotoxins in the venom ducts of Conus
RT textile.";
RL Toxicon 60:1370-1379(2012).
CC -!- FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to
CC the nicotinic acetylcholine receptors (nAChR) and thus inhibit them.
CC This toxin inhibits rat alpha-3-beta-2/CHRNA3-CHRNB2 (IC(50)=3.5 nM),
CC rat alpha-7/CHRNA7 (IC(50)=392 nM) nAChR, and the L.stagnalis soluble
CC acetylcholine receptor (all tested without hydroxyproline).
CC {ECO:0000269|PubMed:17660751}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17660751}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct (PubMed:17660751,
CC PubMed:23031820). Tx1a that containing 1 or 2 non-hydroxylated prolines
CC are mostly present in part 5 of the venom duct (distal part near the
CC pharynx), whereas tx1a-OO (with 2 hydroxyprolines) is mostly present in
CC part 4 of the venom duct (follewed by part 3) (PubMed:23031820).
CC {ECO:0000305|PubMed:17660751, ECO:0000305|PubMed:23031820}.
CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC {ECO:0000305}.
CC -!- PTM: Exists in 4 different forms, depending on hydroxylations. Tx1a-PP
CC does not contain hydroxyproline, tx1a-OP has one hydroxyproline at
CC position 45, tx1a-PO has one hydroxyproline at position 46, and tx1a-PP
CC has two hydroxyprolines at positions 45 and 46.
CC {ECO:0000269|PubMed:23031820}.
CC -!- MASS SPECTROMETRY: Mass=1656.68; Method=Electrospray; Note=Monoisotopic
CC mass.; Evidence={ECO:0000269|PubMed:17660751};
CC -!- MISCELLANEOUS: Shows no inhibition on alpha-4-beta-2/CHRNA4-CHRNB2 and
CC on alpha-1-beta-1-delta-epsilon/CHRNA1-CHRNB1-CHRND-CHRNE up to 10 uM.
CC {ECO:0000269|PubMed:17660751}.
CC -!- MISCELLANEOUS: The toxin with a different disulfide pairing [C1-C4; C2-
CC C3] shows an important loss of activity on L.stagnalis soluble
CC acetylcholine receptor and a complete loss of activity on alpha-
CC 7/CHRNA7 nAChR, respectively. {ECO:0000269|PubMed:17660751}.
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
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DR EMBL; BD261399; -; NOT_ANNOTATED_CDS; Unassigned_DNA.
DR EMBL; AR584806; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PDB; 2UZ6; X-ray; 2.40 A; K/L/M/N/O/P/Q/R/S/T=40-55.
DR PDB; 6OTA; NMR; -; A=40-55.
DR PDBsum; 2UZ6; -.
DR PDBsum; 6OTA; -.
DR AlphaFoldDB; P0DM21; -.
DR BMRB; P0DM21; -.
DR SMR; P0DM21; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0035792; C:host cell postsynaptic membrane; IEA:UniProtKB-KW.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR009958; Conotoxin_a-typ.
DR Pfam; PF07365; Toxin_8; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylcholine receptor inhibiting toxin; Amidation;
KW Direct protein sequencing; Disulfide bond; Hydroxylation; Neurotoxin;
KW Postsynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT PROPEP 17..39
FT /evidence="ECO:0000269|PubMed:17660751"
FT /id="PRO_0000445008"
FT PEPTIDE 40..55
FT /note="Alpha-conotoxin TxIA"
FT /evidence="ECO:0000269|PubMed:17660751"
FT /id="PRO_0000445009"
FT REGION 43..45
FT /note="Ser-Xaa-Pro motif, crucial for potent interaction
FT with nAChR"
FT /evidence="ECO:0000250|UniProtKB:P56636"
FT SITE 44
FT /note="Important for binding with soluble acetylcholine
FT receptor"
FT /evidence="ECO:0000305|PubMed:17660751"
FT SITE 46
FT /note="Important for binding with soluble acetylcholine
FT receptor"
FT /evidence="ECO:0000305|PubMed:17660751"
FT MOD_RES 45
FT /note="4-hydroxyproline; partial"
FT /evidence="ECO:0000269|PubMed:23031820"
FT MOD_RES 46
FT /note="4-hydroxyproline; partial"
FT /evidence="ECO:0000269|PubMed:23031820"
FT MOD_RES 55
FT /note="Cysteine amide"
FT /evidence="ECO:0000269|PubMed:17660751,
FT ECO:0000269|PubMed:23031820"
FT DISULFID 41..47
FT /evidence="ECO:0000305|PubMed:17660751"
FT DISULFID 42..55
FT /evidence="ECO:0000305|PubMed:17660751"
FT MUTAGEN 49
FT /note="A->L: 10-fold increase in ability to inhibit rat
FT alpha-7/CHRNA7, and no change in ability to inhibit
FT L.stagnalis soluble acetylcholine receptor (tested without
FT hydroxyproline)."
FT /evidence="ECO:0000269|PubMed:17660751"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:6OTA"
FT TURN 45..48
FT /evidence="ECO:0007829|PDB:6OTA"
SQ SEQUENCE 56 AA; 5791 MW; FA270015287C3237 CRC64;
MFTVFLLVVL ATAVVSFTSD RASDDGKAAA SDLITLTIKG CCSRPPCIAN NPDLCG
