SLC39A1 (solute carrier family 39 (zinc transporter), member 1)

2011-10-01 Renty B Franklin , Leslie C Costello Affiliation

Department of Oncology, Diagnostic Sciences, Dental School, The Greenebaum Cancer Center, University of Maryland, Baltimore, MD, 21201, USA

Identity

HGNC

SLC39A1

LOCATION

1q21.3

LOCUSID

27173

ALIAS

ZIP1,ZIRTL

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

The SLC39A1 gene contains 5 exons, three of which are coding. The length of the gene is 8600 base pairs according to the Entrez Gene database. Several transcripts have been reported containing either 3, 4, or 5 exons. However, the coding sequence for SLC39A1 is the same for all reported transcripts.

Transcription

Only a single isoform has been reported; mRNA 2445 bases in length; coding region of 975 bases.

Pseudogene

None reported.

Proteins

Description

SLC39A1 encodes Zrt/Irt-like protein family member 1 (ZIP1).
ZIP1 is a 35 kDa molecular weight protein consisting of 324 amino acids. The protein contains 8 transmembrane spanning domains and shows the characteristics of a zinc transporter (Gaither and Eide, 2001).

Expression

ZIP1 is ubiquitously expressed in mammalian cells (Gaither and Eide, 2001). Expression is down regulated in prostate malignancy (Franklin et al., 2005). Its constitutive expression is reported to be regulated by SP and CREB1 (Makhov et al., 2009). Down regulation of expression in prostate malignancy is reported due to transcription repression by ras response element binding protein-1 (RREB-1) (Milon et al., 2010).

Localisation

ZIP1 is located at the cell membrane.

Function

ZIP1 is a facilitated zinc uptake transporter (Franklin et al., 2003). Activity of the transporter results in the intracellular accumulation of zinc. ZIP1 is involved in apoptosis induction in prostate cancer cells.

Homology

Mus musculus Slc39a1; Rattus norvegicus Slc39a1; Bos taurus Slc39a1; Danio rerio slc39a1.

Mutations

Note

No diseases related to mutation are reported.

Implicated in

Entity name

Prostate cancer

Note

SLC39A1 is down regulated in prostate cancer (Franklin et al., 2005). Knockdown of the SLC39A1 expression decreases cellular zinc and increases growth of PC-3 cells (Franklin et al., 2003). Over expression of SLC39A1 inhibits prostate tumor growth in a xenograft model (Golovine et al., 2008).

Bibliography

Pubmed ID	Last Year	Title	Authors
16153295	2005	hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer.	Franklin RB et al
11301334	2001	The human ZIP1 transporter mediates zinc uptake in human K562 erythroleukemia cells.	Gaither LA et al
18765529	2008	Overexpression of the zinc uptake transporter hZIP1 inhibits nuclear factor-kappaB and reduces the malignant potential of prostate cancer cells in vitro and in vivo.	Golovine K et al
19026724	2009	Transcriptional regulation of the major zinc uptake protein hZip1 in prostate cancer cells.	Makhov P et al
19802870	2010	Ras responsive element binding protein-1 (RREB-1) down-regulates hZIP1 expression in prostate cancer cells.	Milon BC et al

Other Information

Locus ID:

NCBI: 27173
MIM: 604740
HGNC: 12876
Ensembl: ENSG00000143570

Variants:

dbSNP: 27173
ClinVar: 27173
TCGA: ENSG00000143570
COSMIC: SLC39A1

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000143570	ENST00000310483	Q9NY26
ENSG00000143570	ENST00000356205	Q9NY26
ENSG00000143570	ENST00000368621	Q9NY26
ENSG00000143570	ENST00000368623	Q9NY26
ENSG00000143570	ENST00000413622	Q5T4K4
ENSG00000143570	ENST00000417348	Q5T4K2
ENSG00000143570	ENST00000429040	Q5T4K3
ENSG00000143570	ENST00000537590	A0A0A0MTL8
ENSG00000143570	ENST00000617697	Q9NY26
ENSG00000143570	ENST00000621013	Q9NY26

Expression (GTEx)

100

150

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

References

Pubmed ID	Year	Title	Citations
16153295	2005	hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer.	89
12888280	2003	Human ZIP1 is a major zinc uptake transporter for the accumulation of zinc in prostate cells.	54
14525987	2003	Structure, function, and regulation of a subfamily of mouse zinc transporter genes.	48
18765529	2008	Overexpression of the zinc uptake transporter hZIP1 inhibits nuclear factor-kappaB and reduces the malignant potential of prostate cancer cells in vitro and in vivo.	26
20705137	2010	Differential zinc accumulation and expression of human zinc transporter 1 (hZIP1) in prostate glands.	26
19644445	2009	ZIP: a novel transcription repressor, represses EGFR oncogene and suppresses breast carcinogenesis.	25
18279033	2008	Zinc supplementation in the elderly reduces spontaneous inflammatory cytokine release and restores T cell functions.	23
16203195	2006	Overexpression of the ZIP1 zinc transporter induces an osteogenic phenotype in mesenchymal stem cells.	22
21360563	2011	hZIP1 zinc transporter down-regulation in prostate cancer involves the overexpression of ras responsive element binding protein-1 (RREB-1).	15
19802870	2010	Ras responsive element binding protein-1 (RREB-1) down-regulates hZIP1 expression in prostate cancer cells.	14

Citation

Renty B Franklin ; Leslie C Costello

SLC39A1 (solute carrier family 39 (zinc transporter), member 1)

Atlas Genet Cytogenet Oncol Haematol. 2011-10-01

Online version: http://atlasgeneticsoncology.org/gene/46571/slc39a1