title: TRPV6 channels.
abstract: TRPV6 (former synonyms ECAC2, CaT1, CaT-like) displays several specific features which makes it unique among the members of the mammalian Trp gene family (1) TRPV6 (and its closest relative, TRPV5) are the only highly Ca(2+)-selective channels of the entire TRP superfamily (Peng et al. 1999; Wissenbach et al. 2001; Voets et al. 2004). (2) Translation of Trpv6 initiates at a non-AUG codon, at ACG, located upstream of the annotated AUG, which is not used for initiation (Fecher-Trost et al. 2013). The ACG codon is nevertheless decoded by methionine. Not only a very rare event in eukaryotic biology, the full-length TRPV6 protein existing in vivo comprises an amino terminus extended by 40 amino acid residues compared to the annotated truncated TRPV6 protein which has been used in most studies on TRPV6 channel activity so far. (In the following numbering occurs according to this full-length protein, with the numbers of the so far annotated truncated protein in brackets). (3) Only in humans a coupled polymorphism of Trpv6 exists causing three amino acid exchanges and resulting in an ancestral Trpv6 haplotype and a so-called derived Trpv6 haplotype (Wissenbach et al. 2001). The ancestral allele encodes the amino acid residues C197(157), M418(378) and M721(681) and the derived alleles R197(157), V418(378) and T721(681). The ancestral haplotype is found in all species, the derived Trpv6 haplotype has only been identified in humans, and its frequency increases with the distance to the African continent. Apparently the Trpv6 gene has been a strong target for selection in humans, and its derived variant is one of the few examples showing consistently differences to the orthologues genes of other primates (Akey et al. 2004, 2006; Stajich and Hahn 2005; Hughes et al. 2008). (4) The Trpv6 gene expression is significantly upregulated in several human malignancies including the most common cancers, prostate and breast cancer (Wissenbach et al. 2001; Zhuang et al. 2002; Fixemer et al. 2003; Bolanz et al. 2008). (5) Male mice lacking functional TRPV6 channels are hypo-/infertile making TRPV6 one of the very few channels essential for male fertility (Weissgerber et al. 2011, 2012).
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, 66421, Homburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fecher-Trost
authors.forename: Petra
authors.initials: P
authors.lastname: Weissgerber
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wissenbach
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000737:chemistry / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008564:Membrane Potentials; D049990:Membrane Transport Modulators / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010641:Phenotype; D011487:Protein Conformation; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000737:chemistry / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D049990:Membrane Transport Modulators; D050916:TRPV Cation Channels; C120776:TRPV6 channel; C422827:TRPV6 protein, human; C446923:Trpv6 protein, mouse