SLC39A6 (solute carrier family 39 (zinc transporter), member 6)

2010-11-01   Shin Hamada , Kennichi Satoh , Tooru Shimosegawa 

Division 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).
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).

Bibliography

Pubmed IDLast YearTitleAuthors
205497242010Jarid2 is among a set of genes differentially regulated by Nkx2.5 during outflow tract morphogenesis.Barth JL et al
159864502005Expression levels of the putative zinc transporter LIV-1 are associated with a better outcome of breast cancer patients.Kasper G et al
198875572009Identification of LIV1, a putative zinc transporter gene responsible for HDACi-induced apoptosis, using a functional gene screen approach.Ma X et al
183307192009Concordant correlation of LIV-1 and E-cadherin expression in human breast cancer cell MCF-7.Shen H et al
128394892003Structure-function analysis of LIV-1, the breast cancer-associated protein that belongs to a new subfamily of zinc transporters.Taylor KM et al
126599412003The LZT proteins; the LIV-1 subfamily of zinc transporters.Taylor KM et al
197249172009LIV-1 enhances the aggressive phenotype through the induction of epithelial to mesenchymal transition in human pancreatic carcinoma cells.Unno J et al
151292962004Zinc transporter LIVI controls epithelial-mesenchymal transition in zebrafish gastrula organizer.Yamashita S et al
178257872007LIV-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 IDTranscript IDUniprot
ENSG00000141424ENST00000269187Q13433
ENSG00000141424ENST00000440549Q13433
ENSG00000141424ENST00000586829K7EQ91
ENSG00000141424ENST00000590986Q13433

Expression (GTEx)

0
10
20
30
40
50
60
70
80

Pathways

PathwaySourceExternal ID
Transmembrane transport of small moleculesREACTOMER-HSA-382551
SLC-mediated transmembrane transportREACTOMER-HSA-425407
Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compoundsREACTOMER-HSA-425366
Metal ion SLC transportersREACTOMER-HSA-425410
Zinc transportersREACTOMER-HSA-435354
Zinc influx into cells by the SLC39 gene familyREACTOMER-HSA-442380

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
129604272003Gene expression patterns in ovarian carcinomas.94
126599412003The LZT proteins; the LIV-1 subfamily of zinc transporters.73
128394892003Structure-function analysis of LIV-1, the breast cancer-associated protein that belongs to a new subfamily of zinc transporters.41
128394892003Structure-function analysis of LIV-1, the breast cancer-associated protein that belongs to a new subfamily of zinc transporters.41
221107402011LIV-1 promotes prostate cancer epithelial-to-mesenchymal transition and metastasis through HB-EGF shedding and EGFR-mediated ERK signaling.40
236444922013Genome-wide association study identifies common variants in SLC39A6 associated with length of survival in esophageal squamous-cell carcinoma.40
239194972013A mechanism for epithelial-mesenchymal transition and anoikis resistance in breast cancer triggered by zinc channel ZIP6 and STAT3 (signal transducer and activator of transcription 3).24
159864502005Expression levels of the putative zinc transporter LIV-1 are associated with a better outcome of breast cancer patients.23
266842412016miR-192, a prognostic indicator, targets the SLC39A6/SNAIL pathway to reduce tumor metastasis in human hepatocellular carcinoma.23
190663932009Acquired variation outweighs inherited variation in whole genome analysis of methotrexate polyglutamate accumulation in leukemia.22

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