Characterization of human TMEM16G gene in silico

Area of Science:

• Genomics and Molecular Biology
• Protein Structure and Function
• Bioinformatics

Background:

• The TMEM16 family comprises eight-transmembrane proteins involved in various cellular processes.
• Specific TMEM16 family members (TMEM16A, TMEM16E) have known roles in cancer and genetic disorders.
• The TMEM16G gene's function and characteristics were previously less understood.

Purpose of the Study:

• To characterize the human TMEM16G gene using bioinformatics approaches.
• To determine the full coding sequence and protein structure of human TMEM16G.
• To investigate evolutionary changes in TMEM16G and their potential impact on protein topology and function.

Main Methods:

• Bioinformatic analysis of the human TMEM16G gene.
• Comparative genomics to identify unique genomic loci.
• mRNA expression analysis in normal and cancerous prostate tissues.
• Comparative proteomics to identify evolutionary amino acid substitutions.
• Protein structure prediction using TMHMM2 program.

Main Results:

• The human TMEM16G gene, located at chromosome 2q37.3 and composed of 25 exons, was identified.
• TMEM16G mRNA showed preferential expression in prostate tissues.
• An evolutionary T844N amino acid substitution was identified in human TMEM16G.
• This substitution alters the predicted membrane topology from eight-transmembrane to seven-transmembrane, affecting the eighth transmembrane helix.
• Mouse Tmem16g and artificial human TMEM16G (844T) were predicted as eight-transmembrane proteins, unlike wild-type human TMEM16G (844N).

Conclusions:

• The human TMEM16G gene encodes a 932-amino-acid protein with distinct structural features.
• An evolutionary amino acid substitution at codon 844 results in altered membrane topology of human TMEM16G.
• This altered topology suggests potential functional divergence of human TMEM16G compared to other TMEM16 family members.