slc39a11

slc39a11

<div class="infobox infobox-gene">
<h3>SLC39A11 (ZIP11)</h3>
<table>
<tr><th>Gene Symbol</th><td>SLC39A11</td></tr>
<tr><th>Alternative Names</th><td>ZIP11, Zrt- and Irt-like protein 11</td></tr>
<tr><th>Full Name</th><td>Solute Carrier Family 39 Member 11</td></tr>
<tr><th>Chromosomal Location</th><td>17p13</td></tr>
<tr><th>NCBI Gene ID</th><td>[201506](https://www.ncbi.nlm.nih.gov/gene/201506)</td></tr>
<tr><th>OMIM</th><td>607345</td></tr>
<tr><th>Ensembl</th><td>[ENSG00000133185](https://www.ensembl.org/Homo_sapiens/Gene?g=ENSG00000133185)</td></tr>
<tr><th>UniProt</th><td>[Q8N4W7](https://www.uniprot.org/uniprot/Q8N4W7)</td></tr>
<tr><th>Protein Class</th><td>Zinc transporter (ZIP family)</td></tr>
<tr><th>Expression</th><td>Testis, prostate, brain (lower), pancreas</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

SLC39A11 (also known as ZIP11) is a member of the ZIP (Zrt-, Irt-like Protein) family of zinc transporters[@liuzzi2004]. These transporters are essential for cellular zinc homeostasis, facilitating zinc uptake into cells from the extracellular environment or from intracellular compartments. Zinc is an essential trace element critical for numerous biological processes, including enzyme catalysis, protein structure stabilization, transcriptional regulation, and synaptic signaling in the brain.

slc39a11

<div class="infobox infobox-gene">
<h3>SLC39A11 (ZIP11)</h3>
<table>
<tr><th>Gene Symbol</th><td>SLC39A11</td></tr>
<tr><th>Alternative Names</th><td>ZIP11, Zrt- and Irt-like protein 11</td></tr>
<tr><th>Full Name</th><td>Solute Carrier Family 39 Member 11</td></tr>
<tr><th>Chromosomal Location</th><td>17p13</td></tr>
<tr><th>NCBI Gene ID</th><td>[201506](https://www.ncbi.nlm.nih.gov/gene/201506)</td></tr>
<tr><th>OMIM</th><td>607345</td></tr>
<tr><th>Ensembl</th><td>[ENSG00000133185](https://www.ensembl.org/Homo_sapiens/Gene?g=ENSG00000133185)</td></tr>
<tr><th>UniProt</th><td>[Q8N4W7](https://www.uniprot.org/uniprot/Q8N4W7)</td></tr>
<tr><th>Protein Class</th><td>Zinc transporter (ZIP family)</td></tr>
<tr><th>Expression</th><td>Testis, prostate, brain (lower), pancreas</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

SLC39A11 (also known as ZIP11) is a member of the ZIP (Zrt-, Irt-like Protein) family of zinc transporters[@liuzzi2004]. These transporters are essential for cellular zinc homeostasis, facilitating zinc uptake into cells from the extracellular environment or from intracellular compartments. Zinc is an essential trace element critical for numerous biological processes, including enzyme catalysis, protein structure stabilization, transcriptional regulation, and synaptic signaling in the brain.

The ZIP family consists of 14 members (ZIP1-14) in humans, divided into four subfamilies based on phylogenetic analysis. ZIP11 belongs to the LIV-1 subfamily and is characterized by specific tissue distribution patterns and regulatory mechanisms. While ZIP11 expression is highest in reproductive tissues (testis and prostate), it is also expressed in various other tissues including the brain, where it may contribute to neuronal zinc homeostasis.

Zinc dysregulation has been implicated in multiple neurodegenerative diseases, including [Alzheimer's disease](/diseases/alzheimers-disease) and [Parkinson's disease](/diseases/parkinsons-disease)[@dChart2011][@freitas2010]. Understanding the function of zinc transporters like ZIP11 provides insight into zinc homeostasis mechanisms and their potential role in neurodegeneration.

Gene Structure and Protein Biology

Gene Organization

The SLC39A11 gene is located on chromosome 17p13 and consists of 13 exons spanning approximately 25 kb. The gene encodes a 434-amino acid protein with a predicted molecular weight of approximately 47 kDa.

Protein Structure

ZIP transporters share a common topology with 8 transmembrane domains (TMDs), with both N-terminus and C-terminus located in the cytoplasm[@pin2014]. Key structural features include:

Transmembrane Domains:

• 8 membrane-spanning α-helices
• Long extracellular loop between TM3 and TM4
• Histidine-rich region in the extracellular domain (potential zinc-binding)

• N-terminal variable region
• HExxH motif in TM4 (zinc transporter signature)
• C-terminal regulatory domain

Transport Mechanism

ZIP transporters function as electroneutral symporters or antiporters, transporting zinc either with bicarbonate or in exchange for another ion. Unlike the ZnT (SLC30) family that exports zinc, ZIP transporters mediate zinc uptake into the cytoplasm.

Normal Biological Functions

Cellular Zinc Homeostasis

Zinc homeostasis is tightly regulated through the coordinated action of ZIP and ZnT transporters[@kim2008]:

Zinc Uptake (ZIP family):

• ZIP1, ZIP2, ZIP3: High-affinity zinc uptake
• ZIP4: Intestinal zinc absorption
• ZIP8, ZIP10: Manganese and zinc transport
• ZIP11: Tissue-specific zinc uptake

• ZnT1: General zinc efflux
• ZnT2, ZnT3: Zinc sequestration
• ZnT4, ZnT5: Vesicular zinc transport
• ZnT6, ZnT7: Golgi zinc homeostasis

Brain Zinc Homeostasis

Zinc plays crucial roles in neuronal function[@Sekler2010][@nakanishi2011]:

Synaptic Zinc:

• Synaptic vesicles contain high zinc concentrations
• Released during neuronal activity
• Modulates NMDA receptor activity
• Influences synaptic plasticity

• Cofactor for numerous enzymes
• Required for DNA binding by transcription factors
• Essential for protein structure and function

• Acts as a synaptic transmitter
• Modulates ion channel activity
• Participates in intracellular signaling cascades

Zinc in Neurodegeneration

Alzheimer's Disease

Zinc dysregulation is a well-documented feature of AD pathogenesis[@adlard2010][@dChart2011]:

Amyloid Metabolism:

• Zinc binds to amyloid-β peptides
• Influences Aβ aggregation and plaque formation
• Modulates Aβ toxicity

• Zinc affects tau phosphorylation
• Impacts microtubule stability

• Zinc homeostasis critical for synaptic plasticity
• Dysregulation contributes to cognitive decline

• Zinc supplementation trials in AD have yielded mixed results
• Targeted modulation of zinc transporters may be more effective

Parkinson's Disease

Zinc also plays roles in PD pathogenesis[@choi2020]:

Protein Aggregation:

• Zinc influences α-synuclein aggregation
• Modulates degradation pathways

• Zinc is essential for mitochondrial enzymes
• Dysregulation contributes to energy failure

• Zinc modulates microglial activation
• Alters inflammatory responses

• Zinc transporter modulators as PD therapeutics
• Zinc supplementation strategies under investigation

Other Neurodegenerative Conditions

Zinc dysregulation is implicated in:

• Amyotrophic lateral sclerosis (ALS)
• Huntington's disease
• Multiple sclerosis
• Frontotemporal dementia

Expression Pattern

Tissue Distribution

ZIP11 shows distinctive expression patterns[@kim2014][@kumar2019]:

High Expression:

• Testis (germ cells, Sertoli cells)
• Prostate (epithelial cells)
• Pancreas (islet cells)

• Kidney
• Small intestine
• Liver
• Brain (lower levels)

• Heart
• Lung
• Skeletal muscle

Brain Expression

In the brain, ZIP11 expression is lower compared to other ZIP transporters (ZIP1, ZIP3, ZIP10). It may contribute to:

• Neuronal zinc uptake
• Glial cell zinc homeostasis
• Regional variation in zinc levels

Cellular Localization

ZIP11 localizes to:

• Plasma membrane
• Intracellular vesicles
• Endoplasmic reticulum (some reports)

Interaction Network

Protein Interactions

ZIP11 likely interacts with:

Transport Partners:

• Carbonic anhydrases (for bicarbonate-dependent transport)
• Other zinc transporters (coordinate homeostasis)

• Zinc sensors (MTF1)
• Transcription factors
• Post-translational modification enzymes

Signaling Pathways

ZIP11 function relates to:

• Zinc-dependent signaling
• MTOR pathway (zinc-sensitive)
• p53 signaling (zinc-dependent)
• ROS response pathways

Animal Models

Knockout Studies

Zipl1 knockout mice (note: not ZIP11) show:

• Growth retardation
• Neurological deficits
• Impaired immunity

Limitations for ZIP11

• Limited mouse knockout data
• Species-specific expression patterns
• Need for tissue-specific models

Research Methods

Genetic Studies

• Expression analysis (qPCR, RNA-seq)
• Promoter studies
• eQTL analysis

Molecular Biology

• Western blotting
• Immunofluorescence
• Surface biotinylation

Functional Studies

• Zinc uptake assays
• Intracellular zinc measurements (FluoZin, fura-2)
• Transport kinetics

Clinical Translation

• Genetic association studies
• Biomarker development
• Therapeutic targeting

Therapeutic Implications

Zinc Transporter Modulation

Targeting ZIP transporters for neurodegeneration:

Rationale:

• Zinc dysregulation is a common feature
• ZIP transporters are druggable targets
• Tissue-specific delivery possible

• Small molecule ZIP activators/inhibitors
• Gene therapy approaches
• Combination with zinc supplementation

Challenges

• ZIP transporter redundancy
• Tissue-specific delivery
• Balancing zinc homeostasis
• Off-target effects

Cross-Linking to Related Concepts

Related Neurodegenerative Diseases

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

Related Mechanisms

• [Zinc Transporters](/mechanisms/zinc-transporters)
• [Zinc Homeostasis](/mechanisms/zinc-homeostasis)
• [Synaptic Zinc Signaling](/mechanisms/synaptic-zinc)
• [Neuroinflammation](/mechanisms/neuroinflammation)

Related Genes

• [SLC39A10 (ZIP10)](/genes/slc39a10) — Neuronal zinc transporter
• [SLC39A8 (ZIP8)](/genes/slc39a8) — Manganese/zinc transporter
• [SLC30A1 (ZnT1)](/genes/slc30a1) — Zinc efflux transporter
• [SLC30A3 (ZnT3)](/genes/slc30a3) — Synaptic zinc transporter

Future Directions

Key Research Questions

Emerging Areas

• Single-cell expression analysis
• Structure-function studies
• In vivo imaging of zinc dynamics
• Therapeutic development

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Zinc Transporters](/mechanisms/zinc-transporters)
• [Zinc Homeostasis](/mechanisms/zinc-homeostasis)
• [Neuroinflammation](/mechanisms/neuroinflammation)
• [Synaptic Signaling](/mechanisms/synaptic-signaling)

External Links

• [NCBI Gene: SLC39A11 (201506)](https://www.ncbi.nlm.nih.gov/gene/201506)
• [UniProt: Q8N4W7](https://www.uniprot.org/uniprot/Q8N4W7)
• [OMIM: 607345](https://www.omim.org/entry/607345)
• [Ensembl: ENSG00000133185](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000133185)
• [HGNC: 19864](https://www.genenames.org/data/hgnc_data.php?hgnc_id=19864)

Brain Atlas Resources

• [Allen Human Brain Atlas - SLC39A11](https://human.brain-map.org/microarray/search/show?search_term=SLC39A11)
• [BrainSpan Atlas of the Developing Human Brain](https://www.brainspan.org/search?gene=SLC39A11)
• [Allen Mouse Brain Atlas](https://mouse.brain-map.org/search?query=SLC39A11)
• [Allen Cell Type Atlas](https://celltypes.brain-map.org/?#)

References