SLC39A13 — Solute Carrier Family 39 Member 13

SLC39A13 — Solute Carrier Family 39 Member 13

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SLC39A13 — Solute Carrier Family 39 Member 13</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>SLC39A13</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>SLC39A13 — Solute Carrier Family 39 Member 13</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=SLC39A13" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

SLC39A13, also known as ZIP13, is a member of the solute carrier family 39 (SLC39) zinc transporter family[@liuzzi2004]. ZIP13 facilitates zinc transport across cellular membranes, playing a crucial role in maintaining intracellular zinc homeostasis. This transporter is particularly important for collagen biosynthesis in fibroblasts and has been implicated in connective tissue development[@jeong2012].

Mutations in the SLC39A13 gene cause a specific form of Ehlers-Danlos syndrome (EDS), characterized by spondylocheirodysplasia - a condition affecting the skeleton and connective tissues[@bin2007]. While primarily studied in the context of connective tissue disorders, zinc homeostasis is increasingly recognized as important for neuronal function and neurodegeneration[@himi2009].

Molecular Biology

Gene Structure

SLC39A13 — Solute Carrier Family 39 Member 13

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SLC39A13 — Solute Carrier Family 39 Member 13</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>SLC39A13</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>SLC39A13 — Solute Carrier Family 39 Member 13</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=SLC39A13" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

SLC39A13, also known as ZIP13, is a member of the solute carrier family 39 (SLC39) zinc transporter family[@liuzzi2004]. ZIP13 facilitates zinc transport across cellular membranes, playing a crucial role in maintaining intracellular zinc homeostasis. This transporter is particularly important for collagen biosynthesis in fibroblasts and has been implicated in connective tissue development[@jeong2012].

Mutations in the SLC39A13 gene cause a specific form of Ehlers-Danlos syndrome (EDS), characterized by spondylocheirodysplasia - a condition affecting the skeleton and connective tissues[@bin2007]. While primarily studied in the context of connective tissue disorders, zinc homeostasis is increasingly recognized as important for neuronal function and neurodegeneration[@himi2009].

Molecular Biology

Gene Structure

The SLC39A13 gene is located on chromosome 11p11.2 and encodes a 403-amino acid protein[@liuzzi2004]. The gene consists of multiple exons and is expressed in various tissues, with highest levels in skin fibroblasts, cartilage, and brain.

Protein Structure

ZIP13 is a multipass transmembrane protein with the following features:

• Six transmembrane domains: Forming the channel for zinc transport
• Histidine-rich domains: Putative zinc-binding sites on the extracellular side
• HAMP domain: Histidine-rich amiloride-binding protein domain involved in metal ion sensing
• ER retrieval signals: Ensuring proper subcellular localization

Transport Mechanism

ZIP13 operates as a symporter or antiporter, transporting zinc ions across membranes in association with other ions or substrates[@fukada2008]. Unlike ZIP8 (SLC39A8), which transports zinc in exchange for bicarbonate, ZIP13 appears to function primarily as a zinc importer, bringing zinc into the cytoplasm from the extracellular space or intracellular compartments.

Biological Function

Connective Tissue Development

ZIP13's most well-characterized function is in collagen biosynthesis[@jeong2012]:

• Fibroblast function: ZIP13 is essential for proper fibroblast function and collagen type I and type II production
• Proline hydroxylation: Zinc is a cofactor for prolyl hydroxylase, an enzyme critical for collagen triple helix formation
• Bone development: ZIP13 deficiency leads to impaired bone mineralization
• Cartilage: Essential for chondrocyte function and cartilage matrix production

Zinc Homeostasis

ZIP13 contributes to cellular zinc homeostasis through[@fukada2008]:

• Zinc uptake: Imports zinc from the extracellular space
• Intracellular distribution: Regulates zinc distribution between cellular compartments
• ER zinc pool: Maintains zinc availability in the endoplasmic reticulum for protein folding

Interaction with Other Proteins

ZIP13 interacts with several proteins involved in zinc metabolism and protein folding:

• ZIP10 (SLC39A10): May form heteromers for coordinated zinc transport
• ZIP14 (SLC39A14): Another zinc transporter with overlapping functions
• Prolyl hydroxylases: Require zinc as a cofactor for collagen processing
• Metallothioneins: Buffer intracellular zinc levels

Expression Patterns

Tissue Distribution

ZIP13 is expressed in various tissues[@liuzzi2004]:

• Connective tissues: Skin fibroblasts, chondrocytes, osteoblasts
• Cartilage: Epiphyseal cartilage, intervertebral discs
• Brain: Multiple brain regions including hippocampus and cortex
• Liver: Hepatocytes
• Kidney: Tubular cells

Cellular Localization

At the cellular level, ZIP13 localizes to:

• Plasma membrane: For zinc uptake from extracellular sources
• Endoplasmic reticulum: Where it supplies zinc for protein folding
• Golgi apparatus: Possibly involved in zinc trafficking

Role in Neurodegeneration

While primarily studied in connective tissue disorders, zinc homeostasis is increasingly recognized in neurodegeneration[@himi2009]:

Alzheimer's Disease

Zinc dyshomeostasis is implicated in Alzheimer's disease pathogenesis[@takiguchi2013]:

• Amyloid-beta interaction: Zinc binds to amyloid-beta peptides, affecting aggregation
• Synaptic zinc: Zinc modulates synaptic transmission and plasticity
• Neuroprotective role: Adequate zinc levels protect against neuronal death

Parkinson's Disease

Zinc may play complex roles in Parkinson's disease[@sato2010]:

• Lewy body formation: Zinc promotes alpha-synuclein aggregation
• Mitochondrial function: Zinc is essential for mitochondrial enzyme function
• Oxidative stress: Zinc has antioxidant properties but excess zinc can be pro-oxidant

Neuroplasticity

Zinc signaling is important for neural plasticity[@connor2014]:

• Synaptic plasticity: Zinc modulates NMDA receptor function
• Learning and memory: Zinc-dependent processes are involved in hippocampal learning
• Neurogenesis: Zinc affects neural progenitor cell proliferation and differentiation

Disease Associations

Spondylocheirodysplastic EDS

Biallelic mutations in SLC39A13 cause a specific form of Ehlers-Danlos syndrome characterized by[@bin2007]:

• Skeletal abnormalities: Short stature, skeletal dysplasia
• Cheiroarthropathy: Hand contractures with characteristic finger positioning
• Hyperextensible skin: Mild skin hyperelasticity
• Bone fragility: Increased fracture risk

Neurological Associations

While not directly causative, ZIP13 dysfunction may contribute to neurological conditions:

• Neurodevelopmental disorders: Possible role in developmental brain disorders
• Neurodegeneration: Zinc dyshomeostasis is a feature of multiple neurodegenerative diseases
• Psychiatric conditions: Altered zinc levels reported in depression and schizophrenia

Therapeutic Implications

Zinc Supplementation

Therapeutic approaches targeting ZIP13 and zinc homeostasis include[@takiguchi2013]:

• Zinc supplementation: May help in conditions of zinc deficiency
• Chelation therapy: For conditions of zinc excess or mislocalization
• Prolyl hydroxylase modulators: To enhance collagen biosynthesis

Challenges

• Biphasic effects: Both zinc deficiency and excess can be harmful
• Cell-type specificity: Different cell types have different zinc requirements
• Transport coordination: ZIP13 function must be coordinated with other zinc transporters

Genetic Variation

SLC39A13 polymorphisms have been studied in:

• Connective tissue disorders: EDS susceptibility
• Bone mineral density: Osteoporosis risk
• Neurological conditions: Possible associations with neurodegenerative diseases

See Also

• [Zinc Transporters](/entities/zinc-transporters)
• [Ehlers-Danlos Syndrome](/diseases/ehlers-danlos-syndrome)
• [Collagen](/entities/collagen)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Zinc Signaling](/mechanisms/zinc-signaling)

References