SLC39A2 — Solute Carrier Family 39 Member 2 <table class="infobox infobox-gene">Symbol </td>Full Name </td>Chromosome </td>NCBI Gene ID </td>OMIM </td>Ensembl ID </td>UniProt ID </td>Associated Diseases </td>Gene Symbol </td>Protein Name </td>Gene Family </td>Chromosomal Location </td>Gene ID (NCBI) </td>Protein Length </td>UniProt ID </td>
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SLC39A2 — Solute Carrier Family 39 Member 2 <table class="infobox infobox-gene">Symbol </td>Full Name </td>Chromosome </td>NCBI Gene ID </td>OMIM </td>Ensembl ID </td>UniProt ID </td>Associated Diseases </td>Gene Symbol </td>Protein Name </td>Gene Family </td>Chromosomal Location </td>Gene ID (NCBI) </td>Protein Length </td>UniProt ID </td>Tissue Specificity </td>
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Overview SLC39A2 (Solute Carrier Family 39 Member 2), also known as ZIP2 , is a zinc transporter protein that belongs to the ZIP (Zrt-, Irt-like Protein) family of metal ion transporters.[@kim2004] This protein plays a critical role in cellular zinc homeostasis by facilitating zinc uptake into the cytoplasm from the extracellular space and intracellular compartments.
Zinc is an essential trace metal that serves as a catalytic cofactor for over 300 enzymes and a structural component of numerous proteins. In the brain, zinc is particularly important for neuronal function, synaptic signaling, and antioxidant defense. Dysregulation of zinc homeostasis has been implicated in various neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD).[@grabrucker2011]
Protein Structure and Function
Structure ZIP2 is a multi-pass transmembrane protein predicted to contain 8 transmembrane domains. Like other ZIP family members, it features a histidine-rich motif in the extracellular loop that may serve as a zinc-binding site. The protein is localized to the plasma membrane where it functions as a zinc importer.
Mechanism of Action ZIP2 facilitates zinc transport through a proton-coupled mechanism:
Zinc ions enter the cell through a channel formed by the transmembrane domains
Transport is driven by the electrochemical gradient, often coupled to proton influx
The protein can transport zinc in both directions depending on concentration gradients
Regulation ZIP2 expression is regulated at multiple levels:
Transcriptional regulation : Zinc availability, oxidative stress, and hormonal signalsPost-translational modification : Glycosylation and potential phosphorylationTranscriptional repressors : MTF1 (Metal-responsive transcription factor-1)Role in Neurodegeneration
Alzheimer's Disease Zinc homeostasis is critically disrupted in Alzheimer's disease:[@bush2003]
Amyloid-β metabolism : Zinc binds to amyloid-β peptides and influences their aggregationZinc dysregulation : Altered zinc levels in AD brain regionsSynaptic zinc : Disrupted synaptic zinc signaling in ADOxidative stress : ZIP2-mediated zinc transport affects antioxidant responsesParkinson's Disease
Nigral zinc levels : Altered zinc homeostasis in the substantia nigraProtein aggregation : Zinc influences [alpha-synuclein](/proteins/alpha-synuclein) aggregationMitochondrial function : Zinc is essential for mitochondrial enzymesNeuroinflammation : Zinc modulates microglial activationAmyotrophic Lateral Sclerosis (ALS)
Motor neuron vulnerability : Zinc dysregulation may contribute to motor neuron deathOxidative stress : Impaired zinc homeostasis increases oxidative damageProtein aggregation : Zinc affects [TDP-43](/mechanisms/tdp-43-proteinopathy) and SOD1 aggregationTherapeutic Implications
Zinc-Based Therapies
Drug Targets
ZIP2 modulators : Selective modulators of zinc transporter activityZinc ionophores : Compounds that facilitate cellular zinc uptakeChelators : Selective zinc chelators for specific brain regions
Clinical Significance
Acrodermatitis Enteropathica
Genetic basis : SLC39A2 mutations cause autosomal recessive acrodermatitis enteropathicaClinical features : Periorificial dermatitis, alopecia, diarrheaTreatment : Zinc supplementationCancer
Prostate cancer : ZIP2 expression is altered in prostate carcinomaBreast cancer : ZIP family members are overexpressed in certain breast cancersTherapeutic target : ZIP inhibitors as anticancer agentsResearch Directions Key areas of ongoing research include:
Developing selective ZIP family inhibitors
Understanding ZIP2 regulation in neurodegeneration
Identifying disease-specific expression patterns
Elucidating the role of zinc in protein aggregation
See Also
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Zinc](/genes/gatad2a)
[Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
External Links
[NCBI Gene: 54101](https://www.ncbi.nlm.nih.gov/gene/54101)
[Ensembl: ENSG00000141882](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000141882)
[UniProt: Q9H3Y0](https://www.uniprot.org/uniprot/Q9H3Y0)
References
[Kim et al., ZIP family zinc transporters (2004) (2004)](https://pubmed.ncbi.nlm.nih.gov/15525651/)
[Grabrucker et al., Zinc homeostasis in the brain (2011) (2011)](https://pubmed.ncbi.nlm.nih.gov/21395583/)
[Bush et al., Zinc and Alzheimer's disease (2003) (2003)](https://pubmed.ncbi.nlm.nih.gov/14687782/)
[Coleman et al., ZIP2 in prostate cancer (2000) (2000)](https://pubmed.ncbi.nlm.nih.gov/10821863/)
[Cousins et al., Zinc transporters (2006) (2006)](https://pubmed.ncbi.nlm.nih.gov/16423824/) Show full description