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

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

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai city, Miyagi, Japan

Identity

HGNC

SLC39A6

LOCATION

18q12.2

LOCUSID

25800

ALIAS

LIV-1,ZIP6

FUSION GENES

Show Gene Fusions

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).

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)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Transmembrane transport of small molecules	REACTOME	R-HSA-382551
SLC-mediated transmembrane transport	REACTOME	R-HSA-425407
Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds	REACTOME	R-HSA-425366
Metal ion SLC transporters	REACTOME	R-HSA-425410
Zinc transporters	REACTOME	R-HSA-435354
Zinc influx into cells by the SLC39 gene family	REACTOME	R-HSA-442380

Protein levels (Protein atlas)

Not detected

Low

Medium

High

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)