Alternative titles; symbolsZINC TRANSPORTER 6; ZNT6HGNC Approved Gene Symbol: SLC30A6Cytogenetic location: 2p22.3 Genomic coordinates (GRCh38): 2:32,165,849-...
Alternative titles; symbols
HGNC Approved Gene Symbol: SLC30A6
Cytogenetic location: 2p22.3 Genomic coordinates (GRCh38): 2:32,165,849-32,224,378 (from NCBI)
Zinc functions as a cofactor for numerous enzymes, nuclear factors, and hormones and as an intra- and intercellular signal ion. Members of the zinc transporter (ZNT)/SLC30 subfamily of the cation diffusion facilitator family, such as SLC30A6, permit cellular efflux of zinc (Seve et al., 2004).
▼ Cloning and Expression
Huang et al. (2002) identified mouse and human SLC30A6, which they called ZNT6. The deduced mouse and human proteins contain 460 amino acids and share 92% identity. Mouse Znt6 has 6 transmembrane domains, a loop between transmembrane domains 4 and 5, and cytoplasmic N and C termini. In contrast to other Znt proteins, the loop region of Znt6 lacks multiple histidines. Northern blot analysis detected 2 Znt6 transcripts expressed at variable levels in all mouse tissues examined, with highest levels in liver and brain. Normal rat kidney cells expressed Znt6 in a perinuclear location and in a punctate/tubular pattern throughout the cytoplasm and under the plasma membrane. Disruption of the Golgi compartment also disrupted Znt6 localization.
By EST database analysis, Seve et al. (2004) found evidence of high SLC30A6 expression in B cells, colon, eye, and lung. Lower expression was present in bone, brain, cervix, ear, heart, kidney, muscle, nerve, pancreas, prostate, skin, stomach, and testis.
▼ Gene Function
Using yeast mutants defective in zinc transport, Huang et al. (2002) provided evidence that mouse Znt6 could export cytoplasmic zinc out of the cell or transport it into an intracellular pool. The intracellular localization of Znt6 in normal rat kidney cells was regulated by extracellular zinc in a concentration-dependent manner, with zinc causing Znt6 to diffuse from the perinuclear region toward cytoplasmic structures and the cell periphery.
Using chicken B cells lacking Znt5 (607819), Znt6, and Znt7 (611149), followed by reexpression of the human transgenes, Suzuki et al. (2005) showed that ZNT5 and ZNT6 had to be coexpressed to transport zinc for activation of tissue-nonspecific alkaline phosphatase (TNAP, or ALPL; 171760) in the Golgi lumen, whereas ZNT7 acted alone to perform the same function. Coimmunoprecipitation and immunofluorescence analyses showed that ZNT5 and ZNT6 formed heterooligomers and that ZNT7 formed homooligomers.
▼ Gene Structure
Huang et al. (2002) determined that the SLC30A6 gene contains 14 exons and spans 56 kb.
By genomic sequence analysis, Huang et al. (2002) mapped the SLC30A6 gene to chromosome 2p22-p21. The mouse Slc30a6 gene maps to a region of chromosome 17 that shares homology of synteny with human chromosome 2p22-p21.