The human gene SLC39A1 encodes the human zinc transporter hZIP1. It is ubiquitously expressed (Lioumi M et al, 1999) and mediates the influx of zinc into cells (Gaither LA and Eide DJ, 2001).
The human gene SLC39A2 encodes the zinc transporter hZIP2. It is expressed exclusively in prostate and uterine epithelial cells and mediates zinc transport into cells (Gaither LA and Eide DJ, 2000).
Normal prostate cells have the ability to accumulate high levels of zinc. In prostate cancer, hZIP1-3 transporters are down-regulated and the cells lose the ability to accumulate zinc. Zinc plays a role as a tumour-suppressing agent thus prostate cells can become cancerous. Silencing of the genes that express hZIP1-3 transporters is a required event for malignancy (Costello LC et al, 1999; Desouki MM et al, 2007).
The human gene SLC39A4 encodes the zinc transporter hZIP4 (Kury S et al, 2002). The role of zinc in tumour progression is complicated and, subsequently, so are the role of ZIP transporters. For example, ZIP4 can actually enhance cancer progression (Li M et al, 2007; Li M et al, 2009). Defects in SLC39A4 result in the inherited condition acrodermatitis enteropathica (AE) results from defective absorption of dietary zinc from the duodenum and jejunum. Clinical features include growth retardation, immune system dysfunction, severe dermatitis and mental disorders (Wang K et al, 2002).
|SLC39A1-4||zinc ion transmembrane transporter activity (0005385)|
|11301334||The human ZIP1 transporter mediates zinc uptake in human K562 erythroleukemia cells||J Biol Chem||2001|
|10610721||Isolation and characterization of human and mouse ZIRTL, a member of the IRT1 family of transporters, mapping within the epidermal differentiation complex||Genomics||1999|
|10681536||Functional expression of the human hZIP2 zinc transporter||J Biol Chem||2000|
|17550612||hZip2 and hZip3 zinc transporters are down regulated in human prostate adenocarcinomatous glands||Mol Cancer||2007|
|10364181||Evidence for a zinc uptake transporter in human prostate cancer cells which is regulated by prolactin and testosterone||J Biol Chem||1999|
|12068297||Identification of SLC39A4, a gene involved in acrodermatitis enteropathica||Nat Genet||2002|
|12032886||A novel member of a zinc transporter family is defective in acrodermatitis enteropathica||Am J Hum Genet||2002|
|18003899||Aberrant expression of zinc transporter ZIP4 (SLC39A4) significantly contributes to human pancreatic cancer pathogenesis and progression||Proc Natl Acad Sci U S A||2007|
|19755388||Down-regulation of ZIP4 by RNA interference inhibits pancreatic cancer growth and increases the survival of nude mice with pancreatic cancer xenografts||Clin Cancer Res||2009|