Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Alpha-conotoxin GID

Gene
N/A
Organism
Conus geographus (Geography cone) (Nubecula geographus)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 (IC50=3.1-5.1 nM), alpha-7 (IC50=4.5-5.1 nM), and alpha-4-beta-2 (IC50=128.6-390 nM) nAChRs.3 Publications

Miscellaneous

This toxin does not inhibit neuronal alpha-3-beta-4 and alpha-4-beta-4 nAChR, and muscle alpha-1-beta-1-gamma-delta nAChR.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei47Key residue for activity on alpha-7, alpha-3-beta-2 and alpha-4-beta-2 nAChR1 Publication1
Sitei53Key residue for activity on alpha-7, alpha-3-beta-2 and alpha-4-beta-2 nAChR1 Publication1
Sitei56Key residue for activity on alpha-7 and alpha-4-beta-2 nAChR2 Publications1
Sitei58Key residue for activity on alpha-7 and alpha-4-beta-2 nAChR1 Publication1

GO - Molecular functioni

GO - Biological processi

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 lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

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 inhibition of alpha-3-beta-2 and alpha-7 nAChRs, 4.4-fold decrease in inhibition of alpha-4-beta-2 nAChR. 1 Publication4
Mutagenesisi45 – 47IRD → A: 3.4-fold and 9.6-fold decrease in inhibition of alpha-7 and alpha-3-beta-2 nAChR, respectively, and complete loss of activity on alpha-4-beta-2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication3
Mutagenesisi45 – 47Missing : 19.7-fold and 22.9-fold decrease in inhibition of alpha-7 and alpha-3-beta-2 nAChR, respectively, and complete loss of activity on alpha-4-beta-2 nAChR; when associated with A-48. 1 Publication3
Mutagenesisi45 – 47Missing : 2.5-fold and 18-fold decrease in inhibition of alpha-7 and alpha-3-beta-2 nAChR, respectively, and complete loss of activity on alpha-4-beta-2 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 inhibition of alpha-7 and alpha-3-beta-2 nAChR, respectively, and complete loss of activity on alpha-4-beta-2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication2
Mutagenesisi45 – 46Missing : 2.5-fold decrease in inhibition of alpha-7 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication2
Mutagenesisi45I → A: No change in inhibition of alpha-7, 4.6-fold and 2-fold decrease in inhibition of alpha-3-beta-2 and alpha-4-beta-2 nAChR, respectively; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi46R → A: 2.5-fold and 28.7-fold decrease in inhibition of alpha-7 and alpha-3-beta-2 nAChR, respectively, and complete loss of activity on alpha-4-beta-2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi47D → A: 8.3-fold and 20.5-fold decrease in inhibition of alpha-7 and alpha-3-beta-2 nAChR, respectively, and complete loss of activity on alpha-4-beta-2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi48E → A: No change in inhibition of alpha-7, alpha-3-beta-2 nAChR and 2.5-fold increase in inhibition of alpha-4-beta-2 nAChR. 19.7-fold and 22.9-fold decrease in inhibition of alpha-7 and alpha-3-beta-2 nAChR, respectively, and complete loss of activity on alpha-4-beta-2 nAChR; when associated with 45-I--D-47 DEL. 1 Publication1
Mutagenesisi51S → A: 2.5-fold and 3.3-fold decrease in inhibition of alpha-7 and alpha-4-beta-2 nAChR, and 1.4-fold increase in inhibition of alpha-3-beta-2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi52N → A: Important decrease in inhibition of alpha-7 nAChR, no change in inhibition of alpha-3-beta-2 nAChR and complete loss of activity on alpha-4-beta-2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi53P → A: 17.7-fold and 50-fold decrease in inhibition of alpha-7 and alpha-3-beta-2 nAChR, respectively, and complete loss of activity on alpha-4-beta-2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi56R → A: 3.2-fold, 13.2-fold and 10.7-fold decrease in inhibition of alpha3-beta-2, alpha-4-beta-2 and alpha-7 nAChRs, respectively. 1 Publication1
Mutagenesisi56R → A: 9.6-fold and 3.1-fold decrease in inhibition of alpha-7 and alpha-3-beta-2 nAChR, respectively, and complete loss of activity on alpha-4-beta-2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi57V → A: 2.2-fold decrease in inhibition of alpha-7 nAChR, 5.7-fold increase in inhibition of alpha-3-beta-2 nAChR, and no change in activity on alpha-4-beta-2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi58N → A: 10.1-fold decrease in inhibition of alpha-7 nAChR, 2.6-fold increase in inhibition of alpha-3-beta-2 nAChR, and complete loss of activity on alpha-4-beta-2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi59N → A: No change in inhibition of alpha-7 and alpha-3-beta-2 nAChR and complete loss of activity on alpha-4-beta-2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi60P → A: 2.5-fold and 4-fold decrease in inhibition of alpha-7 and alpha-3-beta-2 nAChR, respectively, and complete loss of activity on alpha-4-beta-2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi61H → A: No change in inhibition of alpha-7 and alpha-3-beta-2 nAChR, and 4.7-fold decrease in inhibition of alpha-4-beta-2 nAChR; when associated with lack of gamma-carboxyglutamation at Glu-48. 1 Publication1
Mutagenesisi62V → A: 1.5-fold and 12-fold decrease in inhibition of alpha-7 and alpha-3-beta-2 nAChR, and complete loss of activity on alpha-4-beta-2 nAChR; 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. Synthetic peptides without this modification do not show change in inhibition of alpha-7 and alpha-3-beta-2 nAChR and show a 2.3-fold increase in inhbition of alpha-4-beta-2 nAChR.1 Publication
Hydroxylation of Pro-60 seems to be important for nAChR inhibition. Synthetic peptides without this modification show a small decrease in inhibition of alpha-7 and alpha-3-beta-2 nAChR and a very important decrease in inhibition of alpha-4-beta-2 nAChR.1 Publication
An amidation of Cys-63 increases potency against alpha-7 (2.6-fold) and alpha-3-beta-2 (2-fold) nAChR. On the other, the peptide has no more activity on alpha-4-beta-2 nAChR with an amidated C-63.1 Publication

Keywords - PTMi

Disulfide bond, Gamma-carboxyglutamic acid, Hydroxylation

Expressioni

Tissue specificityi

Expressed by the venom duct.Curated

Structurei

Secondary structure

166
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni49 – 51Combined sources3
Helixi53 – 58Combined sources6

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP60274.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni45 – 47N-terminal tail important for activity on alpha-4-beta-2 nAChR2 Publications3

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 1 - 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

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: August 30, 2017
This is version 59 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families