GDD1 Is Identical to TMEM16E, a Member of the TMEM16 Family
2004; Elsevier BV; Volume: 75; Issue: 5 Linguagem: Inglês
10.1086/425341
ISSN1537-6605
Autores Tópico(s)interferon and immune responses
ResumoTo the Editor:In the June 2004 issue of The American Journal of Human Genetics, Tsutsumi et al. (2004xThe novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia (GDD). Tsutsumi, S, Kamata, N, Vokes, TJ, Maruoka, Y, Nakakuki, K, Enomoto, S, Omura, K, Amagasa, T, Nagayama, M, Saito-Ohara, F, Inazawa, J, Moritani, M, Yamaoka, T, Inoue, H, and Itakura, M. Am J Hum Genet. 2004; 74: 1255–1261Abstract | Full Text | Full Text PDF | PubMed | Scopus (73)See all References2004) reported the identification and characterization of the GDD1 gene, which is mutated in patients with gnathodiaphyseal dysplasia (MIM 166260). They claimed that human GDD1 is a novel gene without any human homologs (Tsutsumi et al. 2004xThe novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia (GDD). Tsutsumi, S, Kamata, N, Vokes, TJ, Maruoka, Y, Nakakuki, K, Enomoto, S, Omura, K, Amagasa, T, Nagayama, M, Saito-Ohara, F, Inazawa, J, Moritani, M, Yamaoka, T, Inoue, H, and Itakura, M. Am J Hum Genet. 2004; 74: 1255–1261Abstract | Full Text | Full Text PDF | PubMed | Scopus (73)See all References2004); however, we found that GDD1 was identical to TMEM16E (MIM 608662), a member of the TMEM16 gene family (Katoh and Katoh 2003xFLJ10261 gene, located within the CCND1-EMS1 locus on human chromosome 11q13, encodes the eight-transmembrane protein homologous to C12orf3, C11orf25 and FLJ34272 gene products. Katoh, M and Katoh, M. Int J Oncol. 2003; 22: 1375–1381PubMedSee all References2003, 2004axIdentification and characterization of human TP53I5 and mouse Tp53i5 genes in silico. Katoh, M and Katoh, M. Int J Oncol. 2004a; 25: 225–230PubMedSee all References2004a, 2004bxIdentification and characterization of TMEM16E and TMEM16F genes in silico. Katoh, M and Katoh, M. Int J Oncol. 2004b; 24: 1345–1349PubMedSee all References2004b).In 2003, we identified and characterized the TMEM16A (FLJ10261) gene, which is located within the 11q13.3 amplicon (Katoh and Katoh 2003xFLJ10261 gene, located within the CCND1-EMS1 locus on human chromosome 11q13, encodes the eight-transmembrane protein homologous to C12orf3, C11orf25 and FLJ34272 gene products. Katoh, M and Katoh, M. Int J Oncol. 2003; 22: 1375–1381PubMedSee all References2003). The CCND1-ORAOV1-FGF19-FGF4-FGF3-TMEM16A-FADD-PPFIA1-EMS1 amplicon at human chromosome 11q13.3 is one of the most frequently amplified regions in the human genome (Schwab 1998xAmplification of oncogenes in human cancer cells. Schwab, M. Bioessays. 1998; 20: 473–479Crossref | PubMed | Scopus (137)See all References1998; Katoh and Katoh 2003xFLJ10261 gene, located within the CCND1-EMS1 locus on human chromosome 11q13, encodes the eight-transmembrane protein homologous to C12orf3, C11orf25 and FLJ34272 gene products. Katoh, M and Katoh, M. Int J Oncol. 2003; 22: 1375–1381PubMedSee all References2003). The FLJ10261, C12orf3, C11orf25, and FLJ34272 genes, which encode mutually homologous eight-transmembrane proteins with N- and C-terminal tails facing the cytoplasm, were designated as “TMEM16A,” “TMEM16B,” “TMEM16C,” and “TMEM16D,” respectively, on the basis of our communication with the Human Gene Nomenclature Committee (see the HUGO Gene Nomenclature CommitteeHUGO Gene Nomenclature Committee Web site).We then searched for novel members of the TMEM16 gene family and identified the TMEM16E, TMEM16F (MIM 608663), and TP53I5 genes (Katoh and Katoh 2004axIdentification and characterization of human TP53I5 and mouse Tp53i5 genes in silico. Katoh, M and Katoh, M. Int J Oncol. 2004a; 25: 225–230PubMedSee all References2004a, 2004bxIdentification and characterization of TMEM16E and TMEM16F genes in silico. Katoh, M and Katoh, M. Int J Oncol. 2004b; 24: 1345–1349PubMedSee all References2004b). TMEM16A, TMEM16B, TMEM16C, TMEM16D, TMEM16E, TMEM16F, and TP53I5 are eight-transmembrane proteins with TMEM16 homologous (TM16H1, TM16H2, and TM16H3) domains. Several Cys residues and Asn-linked glycosylation sites are included in the conserved residues (or the consensus sequence) of the TM16H1, TM16H2, and TM16H3 domains.The TMEM16E-NELL1 locus at human chromosome 11p15.1-p14.3 and the TMEM16F-NELL2 locus at human chromosome 12q12 are paralogous regions (paralogons) within the human genome. Phylogenetic analysis revealed that TMEM16E and TMEM16F constitute a subfamily among TMEM16 family proteins. On the basis of these facts, we concluded that the TMEM16E and TMEM16F genes are paralogs within the human genome (Katoh and Katoh 2004bxIdentification and characterization of TMEM16E and TMEM16F genes in silico. Katoh, M and Katoh, M. Int J Oncol. 2004b; 24: 1345–1349PubMedSee all References2004b).Tsutsumi et al. (2004xThe novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia (GDD). Tsutsumi, S, Kamata, N, Vokes, TJ, Maruoka, Y, Nakakuki, K, Enomoto, S, Omura, K, Amagasa, T, Nagayama, M, Saito-Ohara, F, Inazawa, J, Moritani, M, Yamaoka, T, Inoue, H, and Itakura, M. Am J Hum Genet. 2004; 74: 1255–1261Abstract | Full Text | Full Text PDF | PubMed | Scopus (73)See all References2004) suggested that the human GDD1 protein showed no significant similarity to any other known proteins or protein classes except GDD1 orthologs in other species. They also reported that the human GDD1 protein showed 79%, 56%, 40%, and 41% identity with mouse, zebrafish, fruit fly, and mosquito orthologs (or homologs), respectively.However, TMEM16E is identical to GDD1, as mentioned above, and BLAST programs reveal that TMEM16E (GDD1) is homologous to other members of the TMEM16 family, such as TMEM16F, TMEM16A, TMEM16B, TMEM16C, and TMEM16D. Human TMEM16E (GDD1) shows 50.3% total amino acid identity with human TMEM16F (Katoh and Katoh 2004bxIdentification and characterization of TMEM16E and TMEM16F genes in silico. Katoh, M and Katoh, M. Int J Oncol. 2004b; 24: 1345–1349PubMedSee all References2004b). Human TMEM16E (GDD1) is more homologous to human TMEM16F than to fruit fly or mosquito Tmem16e homologs.Cys 356 of TMEM16E (GDD1) is substituted with Arg or Gly in patients with gnathodiaphyseal dysplasia (Tsutsumi et al. 2004xThe novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia (GDD). Tsutsumi, S, Kamata, N, Vokes, TJ, Maruoka, Y, Nakakuki, K, Enomoto, S, Omura, K, Amagasa, T, Nagayama, M, Saito-Ohara, F, Inazawa, J, Moritani, M, Yamaoka, T, Inoue, H, and Itakura, M. Am J Hum Genet. 2004; 74: 1255–1261Abstract | Full Text | Full Text PDF | PubMed | Scopus (73)See all References2004). Because Cys 356 is conserved among members of the TMEM16 family (Katoh and Katoh 2004bxIdentification and characterization of TMEM16E and TMEM16F genes in silico. Katoh, M and Katoh, M. Int J Oncol. 2004b; 24: 1345–1349PubMedSee all References2004b), we can now predict that Cys residues might also be essential for the biological function of members of the TMEM16 family. In the postgenome era, comprehensive identification of related genes within the human genome is important for the progression of genome science and medical science.
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