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Updated: Aug 25, 2026
Multiomics Analysis of TMEM200A as a Pan-Cancer Biomarker
Published on: September 15, 2023
Identification and characterization of TMEM16E and TMEM16F genes in silico
1M&M Medical BioInformatics, Narashino 275-0022, Japan.
Abstract:
TMEM16A (FLJ10261 or ORAOV2) gene within the CCND1-FGF4-EMS1 amplicon at human chromosome 11q13.3 encodes transmembrane protein homologous to TMEM16B (C12orf3), TMEM16C (C11orf25), and TMEM16D (FLJ34272). Here, we identified novel TMEM16 family genes by using bioinformatics. Novel genes corresponding to DKFZp451A148 cDNA (AL833271.1) and 9330162L24 cDNA (AK034197.1) were designated human TMEM16E gene and mouse Tmem16e gene, respectively. Novel genes corresponding to DKFZp451M105 cDNA (AL832340.1) and F730003B03 cDNA (BC060732.1) were designated human TMEM16F gene and mouse Tmem16f gene, respectively. NELL1-TMEM16E locus at human chromosome 11p15.1-p14.3 and NELL2-TMEM16F locus at human chromosome 12q12 were paralogous regions within the human genome. TMEM16E mRNA was expressed in testis and pancreatic islet, while TMEM16F mRNA was expressed in embryonic stem cell, fetal liver, retina, chronic myelogenous leukemia, and intestinal cancer. TMEM16E (913 aa) and TMEM16F (892 aa) showed 50.3% total-amino-acid identity. Eight-transmembrane domains were identified within TMEM16E and TMEM16F proteins by using the TMHMM2 program. Phylogenetic analysis revealed that TMEM16E and TMEM16F constitute a subfamily among TMEM16 family proteins. TM16H1 domain around transmembrane domain 1 (TM1)-TM2, TM16H2 domain around TM5, and TM16H3 domain around TM6-TM7 were identified as conserved regions among TMEM16 family proteins. TMEM16 family members were eight-transmenbrane proteins with TM16H1-TM16H3 domains and a conserved Asn glycosylation site. This is the first report on TMEM16E and TMEM16F genes.
Insights
Bioinformatics identified novel TMEM16E and TMEM16F genes in humans and mice. These transmembrane protein genes show conserved domains and distinct expression patterns, forming a new subfamily within the TMEM16 family.
Area of Science:
- Genomics and Molecular Biology
- Bioinformatics and Computational Biology
Background:
- The TMEM16A gene, located on chromosome 11q13.3, encodes a transmembrane protein homologous to other TMEM16 family members.
- Previous studies have identified several TMEM16 family members, but the full extent of the family and their evolutionary relationships were not fully elucidated.
Purpose of the Study:
- To identify novel TMEM16 family genes using bioinformatics approaches.
- To characterize the newly identified human TMEM16E and TMEM16F genes and their mouse orthologs.
- To analyze the expression patterns, protein structure, and phylogenetic relationships of these novel TMEM16 family members.
Main Methods:
- Bioinformatic analysis of genomic databases to identify novel TMEM16 family genes.
- Sequence analysis and comparison to determine gene homology and identify conserved domains.
- Phylogenetic analysis to establish evolutionary relationships within the TMEM16 family.
- Expression analysis of TMEM16E and TMEM16F mRNA in various human and mouse tissues.
Main Results:
- Identification and designation of human TMEM16E and TMEM16F genes, and their mouse orthologs (Tmem16e, Tmem16f).
- TMEM16E and TMEM16F genes are located on human chromosomes 11p15.1-p14.3 and 12q12, respectively, in paralogous regions.
- TMEM16E mRNA is expressed in testis and pancreatic islet; TMEM16F mRNA is expressed in embryonic stem cells, fetal liver, retina, CML, and intestinal cancer.
- TMEM16E and TMEM16F proteins share 50.3% amino acid identity and possess eight transmembrane domains, forming a distinct subfamily within the TMEM16 family.
- Conserved regions (TM16H1, TM16H2, TM16H3 domains) and a conserved Asn glycosylation site were identified across TMEM16 family proteins.
Conclusions:
- This study reports the first identification and characterization of the TMEM16E and TMEM16F genes.
- TMEM16E and TMEM16F represent novel members of the TMEM16 family, characterized by conserved structural features and distinct tissue-specific expression patterns.
- The findings provide a foundation for further research into the functions and potential roles of TMEM16E and TMEM16F in biological processes and disease.
