CA1B_CONTE
ID CA1B_CONTE Reviewed; 41 AA.
AC K4RNX9; L7MTK0;
DT 19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2013, sequence version 1.
DT 25-MAY-2022, entry version 32.
DE RecName: Full=Alpha-conotoxin TxIB {ECO:0000303|PubMed:23184959};
DE Flags: Precursor; Fragment;
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], FUNCTION, SYNTHESIS OF 22-37, AMIDATION
RP AT CYS-37, STRUCTURE BY NMR 22-37, DISULFIDE BONDS, AND MUTAGENESIS OF
RP CYS-37.
RX PubMed=23184959; DOI=10.1074/jbc.m112.427898;
RA Luo S., Zhangsun D., Wu Y., Zhu X., Hu Y., McIntyre M., Christensen S.,
RA Akcan M., Craik D.J., McIntosh J.M.;
RT "Characterization of a novel alpha-conotoxin from conus textile that
RT selectively targets alpha6/alpha3beta2beta3 nicotinic acetylcholine
RT receptors.";
RL J. Biol. Chem. 288:894-902(2013).
RN [2]
RP MUTAGENESIS OF LYS-32, AND 3D-STRUCTURE MODELING OF MUTANT.
RX PubMed=30025921; DOI=10.1016/j.neuropharm.2018.07.019;
RA Yu J., Zhu X., Zhang L., Kudryavtsev D., Kasheverov I., Lei Y.,
RA Zhangsun D., Tsetlin V., Luo S.;
RT "Species specificity of rat and human alpha7 nicotinic acetylcholine
RT receptors towards different classes of peptide and protein antagonists.";
RL Neuropharmacology 139:226-237(2018).
RN [3]
RP FUNCTION, SYNTHESIS OF CYCLIC PEPTIDE, AND MUTAGENESIS OF CYS-37.
RX PubMed=32235388; DOI=10.3390/md18040180;
RA Li X., Wang S., Zhu X., Zhangsun D., Wu Y., Luo S.;
RT "Effects of cyclization on activity and stability of alpha-conotoxin
RT TxIB.";
RL Mar. Drugs 18:0-0(2020).
CC -!- FUNCTION: [Alpha-conotoxin TxIB]: Alpha-conotoxins act on postsynaptic
CC membranes, they bind to the nicotinic acetylcholine receptors (nAChR)
CC and thus inhibit them. This conotoxin is a subtype-specific blocker of
CC alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3) nAChRs
CC nicotinic acetylcholine receptors (nAChRs) (IC(50)=28.4 nM).
CC {ECO:0000269|PubMed:23184959, ECO:0000269|PubMed:32235388}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:23184959}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:23184959}.
CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: Does not affect the following neuronal AChR: alpha-
CC 6/alpha-3 beta-4 (CHRNA6/CHRNA3 CHRNB4), rat alpha-7 (CHRNA7), alpha-9
CC alpha-10 (CHRNA9 CHRNA10), alpha-2 beta-2 (CHRNA2 CHRNB2), alpha-2
CC beta-4 (CHRNA2 CHRNB4), alpha-3 beta-2 (CHRNA3 CHRNB2), alpha-3 beta-4
CC (CHRNA3 CHRNB4), alpha-4 beta-2 (CHRNA4 CHRNB2), alpha-4 beta-4 (CHRNA4
CC CHRNB4), nor the muscle receptor alpha-1 beta-1 delta epsilon (CHRNA1
CC CHRNB1 CHRNE CHRND). {ECO:0000269|PubMed:23184959}.
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
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DR EMBL; HE995411; CCM73829.1; -; Genomic_DNA.
DR PDB; 2LZ5; NMR; -; A=22-37.
DR PDBsum; 2LZ5; -.
DR AlphaFoldDB; K4RNX9; -.
DR BMRB; K4RNX9; -.
DR SMR; K4RNX9; -.
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 InterPro; IPR018072; Conotoxin_a-typ_CS.
DR Pfam; PF07365; Toxin_8; 1.
DR PROSITE; PS60014; ALPHA_CONOTOXIN; 1.
PE 3: Inferred from homology;
KW 3D-structure; Acetylcholine receptor inhibiting toxin; Amidation;
KW Disulfide bond; Neurotoxin; Postsynaptic neurotoxin; Secreted; Toxin.
FT PROPEP 1..20
FT /evidence="ECO:0000305|PubMed:23184959"
FT /id="PRO_0000425962"
FT PEPTIDE 22..37
FT /note="Alpha-conotoxin TxIB"
FT /evidence="ECO:0000305|PubMed:23184959"
FT /id="PRO_0000425964"
FT PROPEP 39..41
FT /evidence="ECO:0000305|PubMed:23184959"
FT /id="PRO_0000425965"
FT REGION 25..27
FT /note="Ser-Xaa-Pro motif, crucial for potent interaction
FT with nAChR"
FT /evidence="ECO:0000250|UniProtKB:P56636"
FT MOD_RES 37
FT /note="Cysteine amide; in Alpha-conotoxin TxIB"
FT /evidence="ECO:0000305|PubMed:23184959"
FT DISULFID 23..29
FT /evidence="ECO:0000305|PubMed:23184959"
FT DISULFID 24..37
FT /evidence="ECO:0000305|PubMed:23184959"
FT MUTAGEN 32
FT /note="K->A: Increase in inhibition potency of rat alpha-
FT 7/CHRNA7 nAChR. Does not show activity on human alpha-
FT 7/CHRNA7 nAChR."
FT /evidence="ECO:0000269|PubMed:30025921"
FT MUTAGEN 37
FT /note="C->CG: Amidated TxIB(G); 9-fold decrease in activity
FT on alpha-6/alpha-3-beta-2-beta-3 nAChRs."
FT /evidence="ECO:0000269|PubMed:23184959"
FT MUTAGEN 37
FT /note="C->CGAAG: Cyclic cTxIB-4; no change in activity and
FT potency."
FT /evidence="ECO:0000269|PubMed:32235388"
FT MUTAGEN 37
FT /note="C->CGAGAAG: Cyclic cTxIB-6; no change in activity
FT and potency."
FT /evidence="ECO:0000269|PubMed:32235388"
FT MUTAGEN 37
FT /note="C->CGGAAG: Cyclic cTxIB-5; no change in activity and
FT potency."
FT /evidence="ECO:0000269|PubMed:32235388"
FT MUTAGEN 37
FT /note="C->CGGAAGAG: Cyclic cTxIB-7; no change in activity
FT and potency."
FT /evidence="ECO:0000269|PubMed:32235388"
FT NON_TER 1
FT HELIX 23..25
FT /evidence="ECO:0007829|PDB:2LZ5"
FT HELIX 27..29
FT /evidence="ECO:0007829|PDB:2LZ5"
FT TURN 30..32
FT /evidence="ECO:0007829|PDB:2LZ5"
FT TURN 34..36
FT /evidence="ECO:0007829|PDB:2LZ5"
SQ SEQUENCE 41 AA; 4445 MW; 85F2BDD62A31A281 CRC64;
FDGRNTSANN KATDLMALPV RGCCSDPPCR NKHPDLCGGR R
