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Protein

Alpha-conotoxin GID

Gene
N/A
Organism
Conus geographus (Geography cone) (Nubecula geographus)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin reversibly blocks alpha-3-beta-2/CHRNA3-CHRNB2 (IC50=3.1-5.1 nM), alpha-7/CHRNA7 (IC50=4.5-5.1 nM), and alpha-4-beta-2/CHRNA4-CHRNB2 (IC50=128.6-390 nM) nAChRs.4 Publications

Miscellaneous

The mutant [V62N] (V18N) shows a very important selectivity for alpha-4-beta-2/CHRNA4-CHRNB2 over alpha-3-beta-2/CHRNA3-CHRNB2 nAChR.1 Publication
This toxin does not inhibit neuronal alpha-3-beta-4/CHRNA3-CHRNB4 and alpha-4-beta-4/CHRNA4-CHRNB4 nAChR, and muscle alpha-1-beta-1-gamma-delta/CHRNA1-CHRNB1-CHRND nAChR.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei47Key residue for activity on alpha-7/CHRNA7, alpha-3-beta-2/CHRNA3-CHRNB2 and alpha-4-beta-2/CHRNA4-CHRNB2 nAChR2 Publications1
Sitei53Key residue for activity on alpha-7/CHRNA7, alpha-3-beta-2/CHRNA3-CHRNB2 and alpha-4-beta-2/CHRNA4-CHRNB2 nAChR1 Publication1
Sitei54Important for determining subtype selectivity1 Publication1
Sitei56Key residue for activity on alpha-7/CHRNA7 and alpha-4-beta-2/CHRNA4-CHRNB2 nAChR2 Publications1
Sitei57Important for determining subtype selectivity1 Publication1
Sitei58Key residue for activity on alpha-7/CHRNA7 and alpha-4-beta-2/CHRNA4-CHRNB2 nAChR1 Publication1

GO - Molecular functioni

Keywordsi

Molecular functionAcetylcholine receptor inhibiting toxin, Ion channel impairing toxin, Neurotoxin, Postsynaptic neurotoxin, Toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-conotoxin GID1 Publication
OrganismiConus geographus (Geography cone) (Nubecula geographus)
Taxonomic identifieri6491 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaNeogastropodaConoideaConidaeConusGastridium

Organism-specific databases

ConoServeri98 GID

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi45 – 48Missing : No change or small decrease in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2 and alpha-7/CHRNA7 nAChRs, 4.4-fold decrease in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR. 1 Publication4
Mutagenesisi45 – 47IRD → A: 3.4-fold and 9.6-fold decrease in inhibitory potency on alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, respectively, and complete loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication3
Mutagenesisi45 – 47Missing : 19.7-fold and 22.9-fold decrease in inhibitory potency on alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, respectively, and complete loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with A-48. 1 Publication3
Mutagenesisi45 – 47Missing : 2.5-fold and 18-fold decrease in inhibitory potency on of alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, respectively, and complete loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication3
Mutagenesisi45 – 46IR → A: 2.8-fold and 5.8-fold decrease in inhibitory potency on alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, respectively, and complete loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication2
Mutagenesisi45 – 46Missing : 2.5-fold decrease in inhibitory potency on alpha-7/CHRNA7 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication2
Mutagenesisi45I → A: No change in inhibitory potency on alpha-7/CHRNA7, 4.6-fold decrease or small increase in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2 (depending on experiments), 2-fold decrease or no change in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR (depending on experiments); when associated with lack of gamma-carboxyglutamation at Glu-48. 2 Publications1
Mutagenesisi46R → A: 2.5-fold decrease in inhibitory potency on alpha-7/CHRNA7, very important decrease in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, and loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 2 Publications1
Mutagenesisi46R → K: Loss in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 and loss in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi47D → A: 8.3-fold decrease in inhibitory potency on alpha-7/CHRNA7, important decrease in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, and loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 2 Publications1
Mutagenesisi47D → N: Loss in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 and loss in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi48E → A: No change in inhibitory potency on alpha-7/CHRNA7, no change or small increase in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, and small increase in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 19.7-fold decrease in inhibitory potency on alpha-7/CHRNA7, 22.9-fold decrease in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, and loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with 45-I--D-47 DEL. 2 Publications1
Mutagenesisi48E → Q: Loss in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 and loss in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi51S → A: 2.5-fold and 3.3-fold decrease in inhibitory potency on alpha-7/CHRNA7 and alpha-4-beta-2/CHRNA4-CHRNB2 nAChR, and 1.4-fold increase in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi52N → A: Important decrease in inhibitory potency on alpha-7/CHRNA7 nAChR, no change in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2 nAChR and complete loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi53P → A: 17.7-fold and 50-fold decrease in inhibitory potency on alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, respectively, and complete loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi54A → Q: Loss of inhibitory potency on all receptors tested (alpha-4-beta-2/CHRNA4-CHRNB2, alpha-7/CHRNA7, and alpha-3-beta-2/CHRNA3-CHRNB2); when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi54A → S: No change in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 and important decrease in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi54A → T: Loss in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 and loss in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi54A → V: >10-fold increase in selectivity on alpha-4-beta-2/CHRNA4-CHRNB2 over alpha-7/CHRNA7; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi56R → A: 3.2-fold decrease in inhibitory potency on alpha3-beta-2/CHRNA3-CHRNB2, 13.2-fold decrease in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2, and 10.7-fold decrease in inhibitory potency on alpha-7/CHRNA7 nAChRs. 9.6-fold decrease in inhibitory potency on alpha-7/CHRNA7, 3.1-fold decrease in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, and complete loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 2 Publications1
Mutagenesisi57V → A: 2.2-fold decrease in inhibitory potency on alpha-7/CHRNA7 nAChR, 5.7-fold increase in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, and no change in activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi57V → F: Loss in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 and very important decrease in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi57V → I: 2-3-fold decrease in inhibitory activity on alpha-4-beta-2/CHRNA4-CHRNB2 and alpha-7/CHRNA7, and 10-fold increase in inhibitory activity on alpha-3-beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi57V → I: No change in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 and important decrease in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi57V → L or W: Loss in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 and loss in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi57V → S: No change in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 and small increase in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi57V → T: No change in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 and no change in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi57V → Y: 40-fold increase in selectivity on alpha-4-beta-2/CHRNA4-CHRNB2 over alpha-7/CHRNA7; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi58N → A: 10.1-fold decrease in inhibitory potency on alpha-7/CHRNA7 nAChR, 2.6-fold increase in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, and complete loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi59N → A: No change in inhibitory potency on alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2 nAChR and complete loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi59N → H: Loss in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 and very important decrease in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi59N → K: Loss in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 and loss in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi60P → A: 2.5-fold and 4-fold decrease in inhibitory potency on alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, respectively, and complete loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi61H → A: No change in inhibitory potency on alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, and 4.7-fold decrease in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi62V → A: 1.5-fold and 12-fold decrease in inhibitory potency on alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2 nAChR, and complete loss of activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi62V → N: Small increase in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 and loss in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi62V → Y or Q: Loss in inhibitory potency on alpha-4-beta-2/CHRNA4-CHRNB2 and loss in inhibitory potency on alpha-3-beta-2/CHRNA3-CHRNB2; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
PropeptideiPRO_000043992922 – 441 PublicationAdd BLAST23
PeptideiPRO_000004445945 – 63Alpha-conotoxin GID1 PublicationAdd BLAST19

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei484-carboxyglutamate1 Publication1
Disulfide bondi49 ↔ 551 PublicationImported
Disulfide bondi50 ↔ 631 PublicationImported
Modified residuei604-hydroxyproline1 Publication1

Post-translational modificationi

Gamma-carboxyglutamation of Glu-48 seems to be not important for nAChR inhibition, since synthetic peptides without this modification do not show change in inhibition of alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2 nAChR and show a 2.3-fold increase in inhibition of alpha-4-beta-2/CHRNA4-CHRNB2 nAChR.1 Publication
Hydroxylation of Pro-60 seems to be important for nAChR inhibition, since synthetic peptides without this modification show a small decrease in inhibition of alpha-7/CHRNA7 and alpha-3-beta-2/CHRNA3-CHRNB2 nAChR and a very important decrease in inhibition of alpha-4-beta-2/CHRNA4-CHRNB2 nAChR.1 Publication
An amidation of Cys-63 increases potency against alpha-7/CHRNA7 (2.6-fold) and alpha-3-beta-2/CHRNA3-CHRNB2 (2-fold) nAChR. On the other hand, the peptide has no more activity on alpha-4-beta-2/CHRNA4-CHRNB2 nAChR with an amidated Cys-63.1 Publication

Keywords - PTMi

Disulfide bond, Gamma-carboxyglutamic acid, Hydroxylation

Expressioni

Tissue specificityi

Expressed by the venom duct.1 Publication

Structurei

Secondary structure

166
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SMRiP60274
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP60274

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni45 – 48N-terminal tail important for activity on alpha-3-beta-2/CHRNA3-CHRNB2 and alpha-4-beta-2/CHRNA4-CHRNB2 nAChR3 Publications4

Domaini

The cysteine framework is I (CC-C-C). Alpha4/7 pattern.Curated

Sequence similaritiesi

Belongs to the conotoxin A superfamily.Curated

Keywords - Domaini

Signal

Family and domain databases

InterProiView protein in InterPro
IPR009958 Conotoxin_a-typ
IPR018072 Conotoxin_a-typ_CS
PfamiView protein in Pfam
PF07365 Toxin_8, 1 hit
PROSITEiView protein in PROSITE
PS60014 ALPHA_CONOTOXIN, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P60274-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGMRMMFTVF LLVVLAATIV SFTSDRASDG RNVAAKAFHR IGRTIRDECC
60
SNPACRVNNP HVCRRR
Length:66
Mass (Da):7,428
Last modified:May 10, 2017 - v2
Checksum:iA366397F42F3A876
GO

Mass spectrometryi

Molecular mass is 2184.9 Da from positions 45 - 63. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB910812 mRNA Translation: BAO65580.1
AB910893 mRNA Translation: BAO65661.1

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB910812 mRNA Translation: BAO65580.1
AB910893 mRNA Translation: BAO65661.1

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1MTQNMR-A45-63[»]
5UG3NMR-A45-63[»]
5UG5NMR-A45-63[»]
SMRiP60274
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ConoServeri98 GID

Miscellaneous databases

EvolutionaryTraceiP60274

Family and domain databases

InterProiView protein in InterPro
IPR009958 Conotoxin_a-typ
IPR018072 Conotoxin_a-typ_CS
PfamiView protein in Pfam
PF07365 Toxin_8, 1 hit
PROSITEiView protein in PROSITE
PS60014 ALPHA_CONOTOXIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCA1D_CONGE
AccessioniPrimary (citable) accession number: P60274
Secondary accession number(s): X5IH33
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 16, 2004
Last sequence update: May 10, 2017
Last modified: September 12, 2018
This is version 65 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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