SLC39A6 (solute carrier family 39 (zinc transporter), member 6)
2010-11-01 Shin Hamada , Kennichi Satoh , Tooru Shimosegawa AffiliationDivision of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai city, Miyagi, Japan
Identity
HGNC
LOCATION
18q12.2
LOCUSID
ALIAS
LIV-1,ZIP6
FUSION GENES
DNA/RNA
Description
SLC39A6 gene contains ten exons. The length of this gene is 20864 bases. This gene encodes two transcript variants. Isoform 1 utilizes all of ten exons, while isoform 2 lacks exon 2 and 10. Consequently, isoform 2 gives rise to shorter protein than isoform 1.
Transcription
Isoform 1; 3637 bases mRNA; 2265 bases of coding region. Isoform 2; 1681 bases mRNA; 1299 bases of coding region.
Pseudogene
None reported.
Proteins
Description
SLC39A6 encodes the zinc transporter ZIP6. Isoform 1 consists of 755 amino acids; Isoform 2 consists of 433 amino acids. The molecular weight of ZIP6 is 85 kDa. SLC39A6 is a multi-pass membrane protein and showing the characteristics of zinc transporter (Taylor and Nicholson, 2003).
Expression
ZIP6 is highly expressed in normal breast tissue, prostate, placenta, kidney, pituitary and corpus callosum (Taylor et al., 2003). Elevated expressions in malignancy of epithelial origin, such as pancreatic cancer are reported (Unno et al., 2009). Its expression is also reported in the second heart field progenitors, which contribute to the cardiac outflow tract formation (Barth et al., 2010).
Localisation
Located at cell membrane.
Function
According to the structural similarity, may act as a zinc influx transporter. Accelerates nuclear translocation of the transcriptional factor Snail, the inducer of epithelial-mesenchymal transition (EMT), as a downstream target of STAT3 pathway in the zebrafish gastrula organizer (Yamashita et al., 2004). SLC39A6 is induced by histone deacetylase inhibitors treatment in cancer cells, and involved in the apoptosis induction by histone deacetylase inhibitors (Ma et al., 2009).
Homology
Mus musculus Slc39a6; Rattus norvegicus Slc39a6; Bos Taurus SLC39A6; Pan troglodytes SLC39A6.
Mutations
Note
No disease related mutations are reported.
Implicated in
Entity name
Pancreatic cancer
Note
SLC39A6 is highly expressed in pancreatic cancer cell line and pancreatic cancer tissue. Knockdown of SLC39A6 expression in the human pancreatic cancer cell line Panc-1 resulted in the reduced tumorigenicity in nude mice and acquisition of epithelial phenotype, such as increased E-cadherin expression (Unno et al., 2009).
Entity name
Breast cancer
Note
SLC39A6 regulates the expression level of E-cadherin, a epithelial marker in human breast cancer cell line MCF-7 (Shen et al., 2009). Higher expression of SLC39A6 in breast cancer tissue correlates with the better outcome of breast cancer patients (Kasper et al., 2005).
SLC39A6 is induced upon the treatment of breast cancer and cervical cancer cell lines by the histone deacetylase inhibitor, TSA. Knockdown of SLC39A6 resulted in the decreased cell death of TSA-treated cancer cells, which indicates the requirement of SLC39A6 during the apoptosis induction (Ma et al., 2009).
SLC39A6 is induced upon the treatment of breast cancer and cervical cancer cell lines by the histone deacetylase inhibitor, TSA. Knockdown of SLC39A6 resulted in the decreased cell death of TSA-treated cancer cells, which indicates the requirement of SLC39A6 during the apoptosis induction (Ma et al., 2009).
Entity name
Cervical cancer
Note
SLC39A6 is involved in the cellular invasion of HeLa cells by controlling the ERK-mediated Snail and Slug expression (Zhao et al., 2007).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 20549724 | 2010 | Jarid2 is among a set of genes differentially regulated by Nkx2.5 during outflow tract morphogenesis. | Barth JL et al |
| 15986450 | 2005 | Expression levels of the putative zinc transporter LIV-1 are associated with a better outcome of breast cancer patients. | Kasper G et al |
| 19887557 | 2009 | Identification of LIV1, a putative zinc transporter gene responsible for HDACi-induced apoptosis, using a functional gene screen approach. | Ma X et al |
| 18330719 | 2009 | Concordant correlation of LIV-1 and E-cadherin expression in human breast cancer cell MCF-7. | Shen H et al |
| 12839489 | 2003 | Structure-function analysis of LIV-1, the breast cancer-associated protein that belongs to a new subfamily of zinc transporters. | Taylor KM et al |
| 12659941 | 2003 | The LZT proteins; the LIV-1 subfamily of zinc transporters. | Taylor KM et al |
| 19724917 | 2009 | LIV-1 enhances the aggressive phenotype through the induction of epithelial to mesenchymal transition in human pancreatic carcinoma cells. | Unno J et al |
| 15129296 | 2004 | Zinc transporter LIVI controls epithelial-mesenchymal transition in zebrafish gastrula organizer. | Yamashita S et al |
| 17825787 | 2007 | LIV-1 suppression inhibits HeLa cell invasion by targeting ERK1/2-Snail/Slug pathway. | Zhao L et al |
Other Information
Locus ID:
NCBI: 25800
MIM: 608731
HGNC: 18607
Ensembl: ENSG00000141424
Variants:
dbSNP: 25800
ClinVar: 25800
TCGA: ENSG00000141424
COSMIC: SLC39A6
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000141424 | ENST00000269187 | Q13433 |
| ENSG00000141424 | ENST00000440549 | Q13433 |
| ENSG00000141424 | ENST00000586829 | K7EQ91 |
| ENSG00000141424 | ENST00000590986 | Q13433 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38345361 | 2024 | Expression of cell surface zinc transporter LIV1 in triple negative breast cancer is an indicator of poor prognosis and therapy failure. | 0 |
| 38345361 | 2024 | Expression of cell surface zinc transporter LIV1 in triple negative breast cancer is an indicator of poor prognosis and therapy failure. | 0 |
| 37435980 | 2023 | Suppression of SLC39A6-CREB1 axis in liver cancer causes PCK1-mediated mitochondrial dysfunction. | 0 |
| 37435980 | 2023 | Suppression of SLC39A6-CREB1 axis in liver cancer causes PCK1-mediated mitochondrial dysfunction. | 0 |
| 32797246 | 2021 | The ZIP6/ZIP10 heteromer is essential for the zinc-mediated trigger of mitosis. | 17 |
| 34394081 | 2021 | Zap70 Regulates TCR-Mediated Zip6 Activation at the Immunological Synapse. | 3 |
| 34453638 | 2021 | Oestrogen-regulated protein SLC39A6: a biomarker of good prognosis in luminal breast cancer. | 4 |
| 32797246 | 2021 | The ZIP6/ZIP10 heteromer is essential for the zinc-mediated trigger of mitosis. | 17 |
| 34394081 | 2021 | Zap70 Regulates TCR-Mediated Zip6 Activation at the Immunological Synapse. | 3 |
| 34453638 | 2021 | Oestrogen-regulated protein SLC39A6: a biomarker of good prognosis in luminal breast cancer. | 4 |
| 30339739 | 2019 | The epithelial zinc transporter ZIP10 epigenetically regulates human epidermal homeostasis by modulating histone acetyltransferase activity. | 10 |
| 30552163 | 2019 | Zip6 Transporter Is an Essential Component of the Lymphocyte Activation Machinery. | 14 |
| 31636012 | 2019 | The LIV-1-GRPEL1 axis adjusts cell fate during anti-mitotic agent-damaged mitosis. | 1 |
| 31703635 | 2019 | Involvement of SLC39A6 in gastric adenocarcinoma and correlation of the SLC39A6 polymorphism rs1050631 with clinical outcomes after resection. | 2 |
| 30339739 | 2019 | The epithelial zinc transporter ZIP10 epigenetically regulates human epidermal homeostasis by modulating histone acetyltransferase activity. | 10 |
Citation
Shin Hamada ; Kennichi Satoh ; Tooru Shimosegawa
SLC39A6 (solute carrier family 39 (zinc transporter), member 6)
Atlas Genet Cytogenet Oncol Haematol. 2010-11-01
Online version: http://atlasgeneticsoncology.org/gene/44189/slc39a6-(solute-carrier-family-39-(zinc-transporter)-member-6)
