GEPHE SUMMARY
Gephebase Gene
Entry Status
Published
GepheID
GP00001720
Main curator
Courtier
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
Other Carnivora
Trait State in Taxon B
Resistance to Erabu Sea Snake (Laticauda semifasciata) - Egyptian cobra
Ancestral State
Taxon A
Taxonomic Status
Taxon A
Latin Name
Common Name
carnivores
Synonyms
carnivores
Rank
order
Lineage
Show more ... uterostomia; Chordata; Craniata; Vertebrata; Gnathostomata; Teleostomi; Euteleostomi; Sarcopterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Laurasiatheria
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B
Latin Name
Common Name
-
Synonyms
ZMB 2820; ZMB:2820
Rank
species
Lineage
Show more ... i; Sarcopterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Sauropsida; Sauria; Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera; Serpentes; Colubroidea; Elapidae; Elapinae; Naja
NCBI Taxonomy ID
is Taxon B an Infraspecies?
No
GENOTYPIC CHANGE
Generic Gene Name
CHRNA1
Synonyms
ACHRA; ACHRD; CHRNA; CMS1A; CMS1B; CMS2A; FCCMS; SCCMS; CHNRA
Sequence Similarities
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-1/CHRNA1 sub-subfamily.
UniProtKB
Homo sapiens
GenebankID or UniProtKB
Presumptive Null
No
Molecular Type
Aberration Type
SNP
SNP Coding Change
-
Molecular Details of the Mutation
Phe189Asn - The inhibitory effect on the pharmacological action of the toxin is primarily attributed to the presence of glycosylation at position N189.
Experimental Evidence
Taxon A Taxon B Position
Codon - - -
Amino-acid Phe Asn 189
Authors
Takacs Z; Wilhelmsen KC; Sorota S
Abstract
Snake alpha-neutotoxins of Elapidae venoms are grouped into two structural classes, short-chain and long-chain alpha-neutotoxins. While these two classes share many chemical and biological characteristics, there are also distinct dissimilarities between them, including their binding site on the nicotinic acetylcholine receptor (nAChR), specificity among species of Chordata, and the associated pharmacological effects. In the present study we test the hypothesis that structural motifs that evolved to confer natural resistance against conspecific long-chain alpha-neurotoxins in Elapidae snakes also interfere with the biological action of short-chain alpha-neurotoxins. We expressed functional nAChRs that contains segments or single residues of the Elapidae nAChR ligand binding domain and tested the effect of short-chain alpha-neurotoxin erabutoxin-a (ETX-a) from the Erabu sea snake Laticauda semifasciata on the acetylcholine-induced currents as measured by two-microelectrode voltage clamp. Our results show that the Elapidae nAChR alpha subunit segment T(154)-L(208) ligand binding domain has an inhibitory effect on the pharmacological action of ETX-a. This effect is primarily attributed to the presence of glycosylation at position N(189). If the glycosylation is removed from the T(154)-L(208) segment, the nAChR will be inhibited, however, to a lesser extent than seen in the mouse. This effect correlates with the variations in alpha-neurotoxin sensitivity of different species and, importantly, reflects the evolutionary conservation of the binding site on the nAChR polypeptide backbone per se. Phylogenetic analysis of alpha-neurotoxin resistance suggests that alpha-neurotoxin-resistant nAChR evolved first, which permitted the evolution of snake venom alpha-neurotoxins. A model describing alpha-neurotoxin resistance in Elapidae snakes is presented.
Additional References
RELATED GEPHE
Related Genes
No matches found.
Related Haplotypes
4
COMMENTS
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