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

Written2010-11Shin Hamada, Kennichi Satoh, Tooru Shimosegawa
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai city, Miyagi, Japan

(Note : for Links provided by Atlas : click)

Identity

Alias_namessolute carrier family 39 (metal ion transporter), member 6
solute carrier family 39 (zinc transporter), member 6
Alias_symbol (synonym)LIV-1
Other aliasZIP6
HGNC (Hugo) SLC39A6
LocusID (NCBI) 25800
Atlas_Id 44189
Location 18q12.2  [Link to chromosome band 18q12]
Location_base_pair Starts at 36111000 and ends at 36129394 bp from pter ( according to hg19-Feb_2009)  [Mapping SLC39A6.png]
Fusion genes
(updated 2016)
ELF3 (1q32.1) / SLC39A6 (18q12.2)RPRD1A (18q12.2) / SLC39A6 (18q12.2)SLC39A6 (18q12.2) / GLT1D1 (12q24.33)
SLC39A6 (18q12.2) / LRIG1 (3p14.1)SLC39A6 (18q12.2) / PTMA (2q37.1)SLC39A6 (18q12.2) / RHOA (3p21.31)
SLC39A6 (18q12.2) / SLC39A6 (18q12.2)

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.

Protein

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

Note
  
Entity 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 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 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

Jarid2 is among a set of genes differentially regulated by Nkx2.5 during outflow tract morphogenesis.
Barth JL, Clark CD, Fresco VM, Knoll EP, Lee B, Argraves WS, Lee KH.
Dev Dyn. 2010 Jul;239(7):2024-33.
PMID 20549724
 
Expression levels of the putative zinc transporter LIV-1 are associated with a better outcome of breast cancer patients.
Kasper G, Weiser AA, Rump A, Sparbier K, Dahl E, Hartmann A, Wild P, Schwidetzky U, Castanos-Velez E, Lehmann K.
Int J Cancer. 2005 Dec 20;117(6):961-73.
PMID 15986450
 
Identification of LIV1, a putative zinc transporter gene responsible for HDACi-induced apoptosis, using a functional gene screen approach.
Ma X, Ma Q, Liu J, Tian Y, Wang B, Taylor KM, Wu P, Wang D, Xu G, Meng L, Wang S, Ma D, Zhou J.
Mol Cancer Ther. 2009 Nov;8(11):3108-16. Epub 2009 Nov 3.
PMID 19887557
 
Concordant correlation of LIV-1 and E-cadherin expression in human breast cancer cell MCF-7.
Shen H, Qin H, Guo J.
Mol Biol Rep. 2009 Apr;36(4):653-9. Epub 2008 Mar 11.
PMID 18330719
 
Structure-function analysis of LIV-1, the breast cancer-associated protein that belongs to a new subfamily of zinc transporters.
Taylor KM, Morgan HE, Johnson A, Hadley LJ, Nicholson RI.
Biochem J. 2003 Oct 1;375(Pt 1):51-9.
PMID 12839489
 
The LZT proteins; the LIV-1 subfamily of zinc transporters.
Taylor KM, Nicholson RI.
Biochim Biophys Acta. 2003 Apr 1;1611(1-2):16-30. (REVIEW)
PMID 12659941
 
LIV-1 enhances the aggressive phenotype through the induction of epithelial to mesenchymal transition in human pancreatic carcinoma cells.
Unno J, Satoh K, Hirota M, Kanno A, Hamada S, Ito H, Masamune A, Tsukamoto N, Motoi F, Egawa S, Unno M, Horii A, Shimosegawa T.
Int J Oncol. 2009 Oct;35(4):813-21.
PMID 19724917
 
Zinc transporter LIVI controls epithelial-mesenchymal transition in zebrafish gastrula organizer.
Yamashita S, Miyagi C, Fukada T, Kagara N, Che YS, Hirano T.
Nature. 2004 May 20;429(6989):298-302. Epub 2004 May 5.
PMID 15129296
 
LIV-1 suppression inhibits HeLa cell invasion by targeting ERK1/2-Snail/Slug pathway.
Zhao L, Chen W, Taylor KM, Cai B, Li X.
Biochem Biophys Res Commun. 2007 Nov 9;363(1):82-8. Epub 2007 Aug 30.
PMID 17825787
 

Citation

This paper should be referenced as such :
Hamada, S ; Satoh, K ; Shimosegawa, T
SLC39A6 (solute carrier family 39 (zinc transporter), member 6)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(7):586-587.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/SLC39A6ID44189ch18q12.html


External links

Nomenclature
HGNC (Hugo)SLC39A6   18607
Cards
AtlasSLC39A6ID44189ch18q12
Entrez_Gene (NCBI)SLC39A6  25800  solute carrier family 39 member 6
AliasesLIV-1; ZIP6
GeneCards (Weizmann)SLC39A6
Ensembl hg19 (Hinxton)ENSG00000141424 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000141424 [Gene_View]  chr18:36111000-36129394 [Contig_View]  SLC39A6 [Vega]
ICGC DataPortalENSG00000141424
TCGA cBioPortalSLC39A6
AceView (NCBI)SLC39A6
Genatlas (Paris)SLC39A6
WikiGenes25800
SOURCE (Princeton)SLC39A6
Genetics Home Reference (NIH)SLC39A6
Genomic and cartography
GoldenPath hg38 (UCSC)SLC39A6  -     chr18:36111000-36129394 -  18q12.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SLC39A6  -     18q12.2   [Description]    (hg19-Feb_2009)
EnsemblSLC39A6 - 18q12.2 [CytoView hg19]  SLC39A6 - 18q12.2 [CytoView hg38]
Mapping of homologs : NCBISLC39A6 [Mapview hg19]  SLC39A6 [Mapview hg38]
OMIM608731   
Gene and transcription
Genbank (Entrez)AK097938 AK299102 AK301539 AK304079 BC008317
RefSeq transcript (Entrez)NM_001099406 NM_012319
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SLC39A6
Cluster EST : UnigeneHs.79136 [ NCBI ]
CGAP (NCI)Hs.79136
Alternative Splicing GalleryENSG00000141424
Gene ExpressionSLC39A6 [ NCBI-GEO ]   SLC39A6 [ EBI - ARRAY_EXPRESS ]   SLC39A6 [ SEEK ]   SLC39A6 [ MEM ]
Gene Expression Viewer (FireBrowse)SLC39A6 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)25800
GTEX Portal (Tissue expression)SLC39A6
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13433   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ13433  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ13433
Splice isoforms : SwissVarQ13433
PhosPhoSitePlusQ13433
Domains : Interpro (EBI)ZIP   
Domain families : Pfam (Sanger)Zip (PF02535)   
Domain families : Pfam (NCBI)pfam02535   
Conserved Domain (NCBI)SLC39A6
DMDM Disease mutations25800
Blocks (Seattle)SLC39A6
SuperfamilyQ13433
Human Protein AtlasENSG00000141424
Peptide AtlasQ13433
HPRD12285
IPIIPI00298702   IPI00607564   IPI00910302   
Protein Interaction databases
DIP (DOE-UCLA)Q13433
IntAct (EBI)Q13433
FunCoupENSG00000141424
BioGRIDSLC39A6
STRING (EMBL)SLC39A6
ZODIACSLC39A6
Ontologies - Pathways
QuickGOQ13433
Ontology : AmiGOzinc ion transmembrane transporter activity  zinc ion transmembrane transporter activity  endoplasmic reticulum  plasma membrane  plasma membrane  integral component of plasma membrane  cellular zinc ion homeostasis  cell surface  lamellipodium membrane  zinc II ion transmembrane transport  zinc II ion transmembrane import  
Ontology : EGO-EBIzinc ion transmembrane transporter activity  zinc ion transmembrane transporter activity  endoplasmic reticulum  plasma membrane  plasma membrane  integral component of plasma membrane  cellular zinc ion homeostasis  cell surface  lamellipodium membrane  zinc II ion transmembrane transport  zinc II ion transmembrane import  
REACTOMEQ13433 [protein]
REACTOME PathwaysR-HSA-442380 [pathway]   
NDEx NetworkSLC39A6
Atlas of Cancer Signalling NetworkSLC39A6
Wikipedia pathwaysSLC39A6
Orthology - Evolution
OrthoDB25800
GeneTree (enSembl)ENSG00000141424
Phylogenetic Trees/Animal Genes : TreeFamSLC39A6
HOVERGENQ13433
HOGENOMQ13433
Homologs : HomoloGeneSLC39A6
Homology/Alignments : Family Browser (UCSC)SLC39A6
Gene fusions - Rearrangements
Fusion : MitelmanELF3/SLC39A6 [1q32.1/18q12.2]  [t(1;18)(q32;q12)]  
Fusion : MitelmanRPRD1A/SLC39A6 [18q12.2/18q12.2]  [t(18;18)(q12;q12)]  
Fusion : MitelmanSLC39A6/LRIG1 [18q12.2/3p14.1]  [t(3;18)(p14;q12)]  
Fusion: TCGARPRD1A 18q12.2 SLC39A6 18q12.2 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSLC39A6 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SLC39A6
dbVarSLC39A6
ClinVarSLC39A6
1000_GenomesSLC39A6 
Exome Variant ServerSLC39A6
ExAC (Exome Aggregation Consortium)SLC39A6 (select the gene name)
Genetic variants : HAPMAP25800
Genomic Variants (DGV)SLC39A6 [DGVbeta]
DECIPHERSLC39A6 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSLC39A6 
Mutations
ICGC Data PortalSLC39A6 
TCGA Data PortalSLC39A6 
Broad Tumor PortalSLC39A6
OASIS PortalSLC39A6 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSLC39A6  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSLC39A6
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch SLC39A6
DgiDB (Drug Gene Interaction Database)SLC39A6
DoCM (Curated mutations)SLC39A6 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SLC39A6 (select a term)
intoGenSLC39A6
NCG5 (London)SLC39A6
Cancer3DSLC39A6(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM608731   
Orphanet
MedgenSLC39A6
Genetic Testing Registry SLC39A6
NextProtQ13433 [Medical]
TSGene25800
GENETestsSLC39A6
Target ValidationSLC39A6
Huge Navigator SLC39A6 [HugePedia]
snp3D : Map Gene to Disease25800
BioCentury BCIQSLC39A6
ClinGenSLC39A6
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD25800
Chemical/Pharm GKB GenePA134905551
Clinical trialSLC39A6
Miscellaneous
canSAR (ICR)SLC39A6 (select the gene name)
Probes
Litterature
PubMed35 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSLC39A6
EVEXSLC39A6
GoPubMedSLC39A6
iHOPSLC39A6
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Jun 30 11:18:24 CEST 2017

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