CA1D_CONGE
ID CA1D_CONGE Reviewed; 66 AA.
AC P60274; X5IH33;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2017, sequence version 2.
DT 25-MAY-2022, entry version 74.
DE RecName: Full=Alpha-conotoxin GID {ECO:0000303|PubMed:12419800};
DE Flags: Precursor;
OS Conus geographus (Geography cone) (Nubecula geographus).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Gastridium.
OX NCBI_TaxID=6491;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom duct;
RX PubMed=24662800; DOI=10.1038/ncomms4521;
RA Dutertre S., Jin A.-H., Vetter I., Hamilton B., Sunagar K., Lavergne V.,
RA Dutertre V., Fry B.G., Antunes A., Venter D.J., Alewood P.F., Lewis R.J.;
RT "Evolution of separate predation- and defence-evoked venoms in carnivorous
RT cone snails.";
RL Nat. Commun. 5:3521-3521(2014).
RN [2]
RP PROTEIN SEQUENCE OF 45-63, FUNCTION, HYDROXYLATION AT PRO-60,
RP GAMMA-CARBOXYGLUTAMATION AT GLU-48, STRUCTURE BY NMR OF 45-63, DISULFIDE
RP BONDS, SYNTHESIS, MASS SPECTROMETRY, MUTAGENESIS OF ARG-56 AND
RP 1-ILE--GLU-4, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=12419800; DOI=10.1074/jbc.m210280200;
RA Nicke A., Loughnan M.L., Millard E.L., Alewood P.F., Adams D.J., Daly N.L.,
RA Craik D.J., Lewis R.J.;
RT "Isolation, structure, and activity of GID, a novel alpha 4/7-conotoxin
RT with an extended N-terminal sequence.";
RL J. Biol. Chem. 278:3137-3144(2003).
RN [3]
RP FUNCTION ON ALPHA-3-BETA-2 AND ALPHA-4-BETA-2 NACHR.
RX PubMed=15929983; DOI=10.1074/jbc.m504229200;
RA Dutertre S., Nicke A., Lewis R.J.;
RT "Beta2 subunit contribution to 4/7 alpha-conotoxin binding to the nicotinic
RT acetylcholine receptor.";
RL J. Biol. Chem. 280:30460-30468(2005).
RN [4]
RP FUNCTION, MUTAGENESIS OF 45-ILE--ASP-47; 45-ILE-ARG-46; ILE-45; ARG-46;
RP ASP-47; GLU-48; SER-51; ASN-52; PRO-53; ARG-56; VAL-57; ASN-58; ASN-59;
RP PRO-60; HIS-61 AND VAL-62, AND STRUCTURE BY NMR OF [45-ILE--GLU-48 DEL]GID
RP AND [ARG-56]GID MUTANTS.
RX PubMed=19098004; DOI=10.1074/jbc.m804950200;
RA Millard E.L., Nevin S.T., Loughnan M.L., Nicke A., Clark R.J.,
RA Alewood P.F., Lewis R.J., Adams D.J., Craik D.J., Daly N.L.;
RT "Inhibition of neuronal nicotinic acetylcholine receptor subtypes by alpha-
RT Conotoxin GID and analogues.";
RL J. Biol. Chem. 284:4944-4951(2009).
RN [5]
RP FUNCTION, MUTAGENESIS OF ILE-45; ARG-46; ASP-47; GLU-48; ALA-54; VAL-57;
RP ASN-59 AND VAL-62, AND SYNTHESIS OF 45-63.
RX PubMed=24122487; DOI=10.1002/bip.22413;
RA Banerjee J., Yongye A.B., Chang Y.P., Gyanda R., Medina-Franco J.L.,
RA Armishaw C.J.;
RT "Design and synthesis of alpha-conotoxin GID analogues as selective
RT alpha4beta2 nicotinic acetylcholine receptor antagonists.";
RL Biopolymers 102:78-87(2014).
RN [6]
RP STRUCTURE BY NMR OF 45-63 OF MUTANTS ALA-54 AND TYR-57, MUTAGENESIS OF
RP ALA-54 AND VAL-57, AND SYNTHESIS OF 45-63.
RX PubMed=28874590; DOI=10.1073/pnas.1703952114;
RA Leffler A.E., Kuryatov A., Zebroski H.A., Powell S.R., Filipenko P.,
RA Hussein A.K., Gorson J., Heizmann A., Lyskov S., Tsien R.W., Poget S.F.,
RA Nicke A., Lindstrom J., Rudy B., Bonneau R., Holford M.;
RT "Discovery of peptide ligands through docking and virtual screening at
RT nicotinic acetylcholine receptor homology models.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E8100-E8109(2017).
CC -!- FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to
CC the nicotinic acetylcholine receptors (nAChR) and thus inhibit them.
CC This toxin reversibly blocks alpha-3-beta-2/CHRNA3-CHRNB2 (IC(50)=3.1-
CC 5.1 nM), alpha-7/CHRNA7 (IC(50)=4.5-5.1 nM), and alpha-4-beta-2/CHRNA4-
CC CHRNB2 (IC(50)=128.6-390 nM) nAChRs. {ECO:0000269|PubMed:12419800,
CC ECO:0000269|PubMed:15929983, ECO:0000269|PubMed:19098004,
CC ECO:0000269|PubMed:24122487}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12419800}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:12419800}.
CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC {ECO:0000305}.
CC -!- PTM: Gamma-carboxyglutamation of Glu-48 seems to be not important for
CC nAChR inhibition, since synthetic peptides without this modification do
CC not show change in inhibition of alpha-7/CHRNA7 and alpha-3-beta-
CC 2/CHRNA3-CHRNB2 nAChR and show a 2.3-fold increase in inhibition of
CC alpha-4-beta-2/CHRNA4-CHRNB2 nAChR. {ECO:0000269|PubMed:19098004}.
CC -!- PTM: Hydroxylation of Pro-60 seems to be important for nAChR
CC inhibition, since synthetic peptides without this modification show a
CC small decrease in inhibition of alpha-7/CHRNA7 and alpha-3-beta-
CC 2/CHRNA3-CHRNB2 nAChR and a very important decrease in inhibition of
CC alpha-4-beta-2/CHRNA4-CHRNB2 nAChR. {ECO:0000269|PubMed:19098004}.
CC -!- PTM: An amidation of Cys-63 increases potency against alpha-7/CHRNA7
CC (2.6-fold) and alpha-3-beta-2/CHRNA3-CHRNB2 (2-fold) nAChR. On the
CC other hand, the peptide has no more activity on alpha-4-beta-2/CHRNA4-
CC CHRNB2 nAChR with an amidated Cys-63. {ECO:0000269|PubMed:19098004}.
CC -!- MASS SPECTROMETRY: Mass=2184.9; Method=Unknown;
CC Evidence={ECO:0000269|PubMed:12419800};
CC -!- MISCELLANEOUS: The mutant [V62N] (V18N) shows a very important
CC selectivity for alpha-4-beta-2/CHRNA4-CHRNB2 over alpha-3-beta-
CC 2/CHRNA3-CHRNB2 nAChR. {ECO:0000269|PubMed:24122487}.
CC -!- MISCELLANEOUS: This toxin does not inhibit neuronal alpha-3-beta-
CC 4/CHRNA3-CHRNB4 and alpha-4-beta-4/CHRNA4-CHRNB4 nAChR, and muscle
CC alpha-1-beta-1-gamma-delta/CHRNA1-CHRNB1-CHRND nAChR.
CC {ECO:0000269|PubMed:12419800, ECO:0000269|PubMed:15929983}.
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
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DR EMBL; AB910812; BAO65580.1; -; mRNA.
DR EMBL; AB910893; BAO65661.1; -; mRNA.
DR PDB; 1MTQ; NMR; -; A=45-63.
DR PDB; 5UG3; NMR; -; A=45-63.
DR PDB; 5UG5; NMR; -; A=45-63.
DR PDBsum; 1MTQ; -.
DR PDBsum; 5UG3; -.
DR PDBsum; 5UG5; -.
DR AlphaFoldDB; P60274; -.
DR SMR; P60274; -.
DR ConoServer; 98; GID.
DR EvolutionaryTrace; P60274; -.
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:0099106; F:ion channel regulator 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 1: Evidence at protein level;
KW 3D-structure; Acetylcholine receptor inhibiting toxin;
KW Direct protein sequencing; Disulfide bond; Gamma-carboxyglutamic acid;
KW Hydroxylation; Ion channel impairing toxin; Neurotoxin;
KW Postsynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..44
FT /evidence="ECO:0000269|PubMed:12419800"
FT /id="PRO_0000439929"
FT PEPTIDE 45..63
FT /note="Alpha-conotoxin GID"
FT /evidence="ECO:0000269|PubMed:12419800"
FT /id="PRO_0000044459"
FT REGION 45..48
FT /note="N-terminal tail important for activity on alpha-3-
FT beta-2/CHRNA3-CHRNB2 and alpha-4-beta-2/CHRNA4-CHRNB2
FT nAChR"
FT /evidence="ECO:0000269|PubMed:12419800,
FT ECO:0000269|PubMed:19098004, ECO:0000269|PubMed:24122487"
FT REGION 51..53
FT /note="Ser-Xaa-Pro motif, crucial for potent interaction
FT with nAChR"
FT /evidence="ECO:0000250|UniProtKB:P56636"
FT SITE 47
FT /note="Key residue for activity on alpha-7/CHRNA7, alpha-3-
FT beta-2/CHRNA3-CHRNB2 and alpha-4-beta-2/CHRNA4-CHRNB2
FT nAChR"
FT /evidence="ECO:0000269|PubMed:19098004,
FT ECO:0000269|PubMed:24122487"
FT SITE 53
FT /note="Key residue for activity on alpha-7/CHRNA7, alpha-3-
FT beta-2/CHRNA3-CHRNB2 and alpha-4-beta-2/CHRNA4-CHRNB2
FT nAChR"
FT /evidence="ECO:0000269|PubMed:19098004"
FT SITE 54
FT /note="Important for determining subtype selectivity"
FT /evidence="ECO:0000269|PubMed:24122487"
FT SITE 56
FT /note="Key residue for activity on alpha-7/CHRNA7 and
FT alpha-4-beta-2/CHRNA4-CHRNB2 nAChR"
FT /evidence="ECO:0000269|PubMed:12419800,
FT ECO:0000269|PubMed:19098004"
FT SITE 57
FT /note="Important for determining subtype selectivity"
FT /evidence="ECO:0000269|PubMed:24122487"
FT SITE 58
FT /note="Key residue for activity on alpha-7/CHRNA7 and
FT alpha-4-beta-2/CHRNA4-CHRNB2 nAChR"
FT /evidence="ECO:0000269|PubMed:19098004"
FT MOD_RES 48
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000269|PubMed:12419800"
FT MOD_RES 60
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000269|PubMed:12419800"
FT DISULFID 49..55
FT /evidence="ECO:0000269|PubMed:12419800,
FT ECO:0000312|PDB:1MTQ"
FT DISULFID 50..63
FT /evidence="ECO:0000269|PubMed:12419800,
FT ECO:0000312|PDB:1MTQ"
FT MUTAGEN 45..48
FT /note="Missing: No change or small decrease in inhibitory
FT potency on alpha-3-beta-2/CHRNA3-CHRNB2 and alpha-7/CHRNA7
FT nAChRs, 4.4-fold decrease in inhibitory potency on alpha-4-
FT beta-2/CHRNA4-CHRNB2 nAChR."
FT /evidence="ECO:0000269|PubMed:12419800"
FT MUTAGEN 45..47
FT /note="IRD->A: 3.4-fold and 9.6-fold decrease in inhibitory
FT potency on alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2
FT nAChR, respectively, and complete loss of activity on
FT alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with
FT lack of gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:19098004"
FT MUTAGEN 45..47
FT /note="Missing: 19.7-fold and 22.9-fold decrease in
FT inhibitory potency on alpha-7/CHRNA7 and alpha-3-beta-
FT 2/CHRNA3-CHRNB2 nAChR, respectively, and complete loss of
FT activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when
FT associated with A-48. 2.5-fold and 18-fold decrease in
FT inhibitory potency on alpha-7/CHRNA7 and alpha-3-beta-
FT 2/CHRNA3-CHRNB2 nAChR, respectively, and complete loss of
FT activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when
FT associated with lack of gamma-carboxyglutamation at Glu-
FT 48."
FT /evidence="ECO:0000269|PubMed:19098004"
FT MUTAGEN 45..46
FT /note="IR->A: 2.8-fold and 5.8-fold decrease in inhibitory
FT potency on alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2
FT nAChR, respectively, and complete loss of activity on
FT alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with
FT lack of gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:19098004"
FT MUTAGEN 45..46
FT /note="Missing: 2.5-fold decrease in inhibitory potency on
FT alpha-7/CHRNA7 nAChR; when associated with lack of gamma-
FT carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:19098004"
FT MUTAGEN 45
FT /note="I->A: No change in inhibitory potency on alpha-
FT 7/CHRNA7, 4.6-fold decrease or small increase in inhibitory
FT potency on alpha-3-beta-2/CHRNA3-CHRNB2 (depending on
FT experiments), 2-fold decrease or no change in inhibitory
FT potency on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR (depending on
FT experiments); when associated with lack of gamma-
FT carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:19098004,
FT ECO:0000269|PubMed:24122487"
FT MUTAGEN 46
FT /note="R->A: 2.5-fold decrease in inhibitory potency on
FT alpha-7/CHRNA7, very important decrease in inhibitory
FT potency on alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, and loss of
FT activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when
FT associated with lack of gamma-carboxyglutamation at Glu-
FT 48."
FT /evidence="ECO:0000269|PubMed:19098004,
FT ECO:0000269|PubMed:24122487"
FT MUTAGEN 46
FT /note="R->K: Loss in inhibitory potency on alpha-4-beta-
FT 2/CHRNA4-CHRNB2 and loss in inhibitory potency on alpha-3-
FT beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-
FT carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:24122487"
FT MUTAGEN 47
FT /note="D->A: 8.3-fold decrease in inhibitory potency on
FT alpha-7/CHRNA7, important decrease in inhibitory potency on
FT alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, and loss of activity on
FT alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with
FT lack of gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:19098004,
FT ECO:0000269|PubMed:24122487"
FT MUTAGEN 47
FT /note="D->N: Loss in inhibitory potency on alpha-4-beta-
FT 2/CHRNA4-CHRNB2 and loss in inhibitory potency on alpha-3-
FT beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-
FT carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:24122487"
FT MUTAGEN 48
FT /note="E->A: No change in inhibitory potency on alpha-
FT 7/CHRNA7, no change or small increase in inhibitory potency
FT on alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, and small increase
FT in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2
FT nAChR; when associated with lack of gamma-
FT carboxyglutamation at Glu-48. 19.7-fold decrease in
FT inhibitory potency on alpha-7/CHRNA7, 22.9-fold decrease in
FT inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2 nAChR,
FT and loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR;
FT when associated with 45-I--D-47 DEL."
FT /evidence="ECO:0000269|PubMed:19098004,
FT ECO:0000269|PubMed:24122487"
FT MUTAGEN 48
FT /note="E->Q: Loss in inhibitory potency on alpha-4-beta-
FT 2/CHRNA4-CHRNB2 and loss in inhibitory potency on alpha-3-
FT beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-
FT carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:24122487"
FT MUTAGEN 51
FT /note="S->A: 2.5-fold and 3.3-fold decrease in inhibitory
FT potency on alpha-7/CHRNA7 and alpha-4-beta-2/CHRNA4-CHRNB2
FT nAChR, and 1.4-fold increase in inhibitory potency on
FT alpha-3-beta-2/CHRNA3-CHRNB2 nAChR; when associated with
FT lack of gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:19098004"
FT MUTAGEN 52
FT /note="N->A: Important decrease in inhibitory potency on
FT alpha-7/CHRNA7 nAChR, no change in inhibitory potency on
FT alpha-3-beta-2/CHRNA3-CHRNB2 nAChR and complete loss of
FT activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when
FT associated with lack of gamma-carboxyglutamation at Glu-
FT 48."
FT /evidence="ECO:0000269|PubMed:19098004"
FT MUTAGEN 53
FT /note="P->A: 17.7-fold and 50-fold decrease in inhibitory
FT potency on alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2
FT nAChR, respectively, and complete loss of activity on
FT alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with
FT lack of gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:19098004"
FT MUTAGEN 54
FT /note="A->Q: Loss of inhibitory potency on all receptors
FT tested (alpha-4-beta-2/CHRNA4-CHRNB2, alpha-7/CHRNA7, and
FT alpha-3-beta-2/CHRNA3-CHRNB2); when associated with lack of
FT gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:28874590"
FT MUTAGEN 54
FT /note="A->S: No change in inhibitory potency on alpha-4-
FT beta-2/CHRNA4-CHRNB2 and important decrease in inhibitory
FT potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated
FT with lack of gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:24122487"
FT MUTAGEN 54
FT /note="A->T: Loss in inhibitory potency on alpha-4-beta-
FT 2/CHRNA4-CHRNB2 and loss in inhibitory potency on alpha-3-
FT beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-
FT carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:24122487"
FT MUTAGEN 54
FT /note="A->V: >10-fold increase in selectivity on alpha-4-
FT beta-2/CHRNA4-CHRNB2 over alpha-7/CHRNA7; when associated
FT with lack of gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:28874590"
FT MUTAGEN 56
FT /note="R->A: 3.2-fold decrease in inhibitory potency on
FT alpha3-beta-2/CHRNA3-CHRNB2, 13.2-fold decrease in
FT inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2, and
FT 10.7-fold decrease in inhibitory potency on alpha-7/CHRNA7
FT nAChRs. 9.6-fold decrease in inhibitory potency on alpha-
FT 7/CHRNA7, 3.1-fold decrease in inhibitory potency on alpha-
FT 3-beta-2/CHRNA3-CHRNB2 nAChR, and complete loss of activity
FT on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with
FT lack of gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:12419800,
FT ECO:0000269|PubMed:19098004"
FT MUTAGEN 57
FT /note="V->A: 2.2-fold decrease in inhibitory potency on
FT alpha-7/CHRNA7 nAChR, 5.7-fold increase in inhibitory
FT potency on alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, and no
FT change in activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR;
FT when associated with lack of gamma-carboxyglutamation at
FT Glu-48."
FT /evidence="ECO:0000269|PubMed:19098004"
FT MUTAGEN 57
FT /note="V->F: Loss in inhibitory potency on alpha-4-beta-
FT 2/CHRNA4-CHRNB2 and very important decrease in inhibitory
FT potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated
FT with lack of gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:24122487"
FT MUTAGEN 57
FT /note="V->I: 2-3-fold decrease in inhibitory activity on
FT alpha-4-beta-2/CHRNA4-CHRNB2 and alpha-7/CHRNA7, and 10-
FT fold increase in inhibitory activity on alpha-3-beta-
FT 2/CHRNA3-CHRNB2; when associated with lack of gamma-
FT carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:28874590"
FT MUTAGEN 57
FT /note="V->I: No change in inhibitory potency on alpha-4-
FT beta-2/CHRNA4-CHRNB2 and important decrease in inhibitory
FT potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated
FT with lack of gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:24122487"
FT MUTAGEN 57
FT /note="V->L,W: Loss in inhibitory potency on alpha-4-beta-
FT 2/CHRNA4-CHRNB2 and loss in inhibitory potency on alpha-3-
FT beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-
FT carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:24122487"
FT MUTAGEN 57
FT /note="V->S: No change in inhibitory potency on alpha-4-
FT beta-2/CHRNA4-CHRNB2 and small increase in inhibitory
FT potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated
FT with lack of gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:24122487"
FT MUTAGEN 57
FT /note="V->T: No change in inhibitory potency on alpha-4-
FT beta-2/CHRNA4-CHRNB2 and no change in inhibitory potency on
FT alpha-4-beta-2/CHRNA4-CHRNB2; when associated with lack of
FT gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:24122487"
FT MUTAGEN 57
FT /note="V->Y: 40-fold increase in selectivity on alpha-4-
FT beta-2/CHRNA4-CHRNB2 over alpha-7/CHRNA7; when associated
FT with lack of gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:28874590"
FT MUTAGEN 58
FT /note="N->A: 10.1-fold decrease in inhibitory potency on
FT alpha-7/CHRNA7 nAChR, 2.6-fold increase in inhibitory
FT potency on alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, and complete
FT loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR;
FT when associated with lack of gamma-carboxyglutamation at
FT Glu-48."
FT /evidence="ECO:0000269|PubMed:19098004"
FT MUTAGEN 59
FT /note="N->A: No change in inhibitory potency on alpha-
FT 7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2 nAChR and
FT complete loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2
FT nAChR; when associated with lack of gamma-
FT carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:19098004"
FT MUTAGEN 59
FT /note="N->H: Loss in inhibitory potency on alpha-4-beta-
FT 2/CHRNA4-CHRNB2 and very important decrease in inhibitory
FT potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated
FT with lack of gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:24122487"
FT MUTAGEN 59
FT /note="N->K: Loss in inhibitory potency on alpha-4-beta-
FT 2/CHRNA4-CHRNB2 and loss in inhibitory potency on alpha-3-
FT beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-
FT carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:24122487"
FT MUTAGEN 60
FT /note="P->A: 2.5-fold and 4-fold decrease in inhibitory
FT potency on alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2
FT nAChR, respectively, and complete loss of activity on
FT alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with
FT lack of gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:19098004"
FT MUTAGEN 61
FT /note="H->A: No change in inhibitory potency on alpha-
FT 7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, and 4.7-
FT fold decrease in inhibitory potency on alpha-4-beta-
FT 2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-
FT carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:19098004"
FT MUTAGEN 62
FT /note="V->A: 1.5-fold and 12-fold decrease in inhibitory
FT potency on alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2
FT nAChR, and complete loss of activity on alpha-4-beta-
FT 2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-
FT carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:19098004"
FT MUTAGEN 62
FT /note="V->N: Small increase in inhibitory potency on alpha-
FT 4-beta-2/CHRNA4-CHRNB2 and loss in inhibitory potency on
FT alpha-3-beta-2/CHRNA3-CHRNB2; when associated with lack of
FT gamma-carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:24122487"
FT MUTAGEN 62
FT /note="V->Y,Q: Loss in inhibitory potency on alpha-4-beta-
FT 2/CHRNA4-CHRNB2 and loss in inhibitory potency on alpha-3-
FT beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-
FT carboxyglutamation at Glu-48."
FT /evidence="ECO:0000269|PubMed:24122487"
FT TURN 49..51
FT /evidence="ECO:0007829|PDB:1MTQ"
FT HELIX 53..58
FT /evidence="ECO:0007829|PDB:1MTQ"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:5UG3"
SQ SEQUENCE 66 AA; 7428 MW; A366397F42F3A876 CRC64;
MGMRMMFTVF LLVVLAATIV SFTSDRASDG RNVAAKAFHR IGRTIRDECC SNPACRVNNP
HVCRRR
