SLC39A1-4 transports Zn2+ from extracellular region to cytosol

Stable Identifier
R-HSA-442422
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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).

Literature References
PubMed ID Title Journal Year
19755388 Down-regulation of ZIP4 by RNA interference inhibits pancreatic cancer growth and increases the survival of nude mice with pancreatic cancer xenografts

Li, M, Zhang, Y, Bharadwaj, U, Zhai, QJ, Ahern, CH, Fisher, WE, Brunicardi, FC, Logsdon, CD, Chen, C, Yao, Q

Clin Cancer Res 2009
12068297 Identification of SLC39A4, a gene involved in acrodermatitis enteropathica

Kury, S, Dreno, B, Bezieau, S, Giraudet, S, Kharfi, M, Kamoun, R, Moisan, JP

Nat Genet 2002
18003899 Aberrant expression of zinc transporter ZIP4 (SLC39A4) significantly contributes to human pancreatic cancer pathogenesis and progression

Li, M, Zhang, Y, Liu, Z, Bharadwaj, U, Wang, H, Wang, X, Zhang, S, Liuzzi, JP, Chang, SM, Cousins, RJ, Fisher, WE, Brunicardi, FC, Logsdon, CD, Chen, C, Yao, Q

Proc Natl Acad Sci U S A 2007
11301334 The human ZIP1 transporter mediates zinc uptake in human K562 erythroleukemia cells

Gaither, LA, Eide, DJ

J Biol Chem 2001
17550612 hZip2 and hZip3 zinc transporters are down regulated in human prostate adenocarcinomatous glands

Desouki, MM, Geradts, J, Milon, B, Franklin, RB, Costello, LC

Mol Cancer 2007
10681536 Functional expression of the human hZIP2 zinc transporter

Gaither, LA, Eide, DJ

J Biol Chem 2000
12032886 A novel member of a zinc transporter family is defective in acrodermatitis enteropathica

Wang, K, Zhou, B, Kuo, YM, Zemansky, J, Gitschier, J

Am J Hum Genet 2002
10364181 Evidence for a zinc uptake transporter in human prostate cancer cells which is regulated by prolactin and testosterone

Costello, LC, Liu, Y, Zou, J, Franklin, RB

J Biol Chem 1999
10610721 Isolation and characterization of human and mouse ZIRTL, a member of the IRT1 family of transporters, mapping within the epidermal differentiation complex

Lioumi, M, Ferguson, CA, Sharpe, PT, Freeman, T, Marenholz, I, Mischke, D, Heizmann, C, Ragoussis, J

Genomics 1999
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
zinc ion transmembrane transporter activity of SLC39A1-4 [plasma membrane]
Physical Entity
Activity
Orthologous Events
Cross References
Rhea
Authored
Reviewed
Created