CHST14 - Carbohydrate Sulfotransferase 14

CHST14 - Carbohydrate Sulfotransferase 14

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Carbohydrate Sulfotransferase 14</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>CHST14</td></tr>
<tr><td><strong>Full Name</strong></td><td>Carbohydrate Sulfotransferase 14</td></tr>
<tr><td><strong>Chromosome</strong></td><td>19p13.12</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[5657](https://www.ncbi.nlm.nih.gov/gene/5657)</td></tr>
<tr><td><strong>OMIM</strong></td><td>[608429](https://www.omim.org/entry/608429)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000110876</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q8IWW4](https://www.uniprot.org/uniprot/Q8IWW4)</td></tr>
<tr><td><strong>Protein Class</strong></div>Sulfotransferase</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Ehlers-Danlos Syndrome (musculocontractural), Wound Healing Disorders</td></tr>
</table>
</div>

Overview

CHST14 (Carbohydrate Sulfotransferase 14), also known as D4ST1 (Dermatan 4-O-sulfotransferase 1), is a crucial enzyme in the biosynthesis of dermatan sulfate proteoglycans. Located on chromosome 19p13.12 with NCBI Gene ID 5657, CHST14 catalyzes the transfer of sulfate groups from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to the C4 position of the N-acetylgalactosamine (GalNAc) residue in dermatan sulfate chains[@migake2010][@kinoshita2012].

CHST14 - Carbohydrate Sulfotransferase 14

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Carbohydrate Sulfotransferase 14</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>CHST14</td></tr>
<tr><td><strong>Full Name</strong></td><td>Carbohydrate Sulfotransferase 14</td></tr>
<tr><td><strong>Chromosome</strong></td><td>19p13.12</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[5657](https://www.ncbi.nlm.nih.gov/gene/5657)</td></tr>
<tr><td><strong>OMIM</strong></td><td>[608429](https://www.omim.org/entry/608429)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000110876</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q8IWW4](https://www.uniprot.org/uniprot/Q8IWW4)</td></tr>
<tr><td><strong>Protein Class</strong></div>Sulfotransferase</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Ehlers-Danlos Syndrome (musculocontractural), Wound Healing Disorders</td></tr>
</table>
</div>

Overview

CHST14 (Carbohydrate Sulfotransferase 14), also known as D4ST1 (Dermatan 4-O-sulfotransferase 1), is a crucial enzyme in the biosynthesis of dermatan sulfate proteoglycans. Located on chromosome 19p13.12 with NCBI Gene ID 5657, CHST14 catalyzes the transfer of sulfate groups from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to the C4 position of the N-acetylgalactosamine (GalNAc) residue in dermatan sulfate chains[@migake2010][@kinoshita2012].

CHST14 has attracted attention in connective tissue biology due to its essential role in extracellular matrix assembly and its involvement in musculocontractural Ehlers-Danlos syndrome (MC-EDS). Recent research also suggests potential roles in neural development and neuroplasticity through modulation of chondroitin/dermatan sulfate proteoglycans[@mizumoto2014][@schwartz2017].

Gene and Protein Structure

Gene Organization

The CHST14 gene spans approximately 14 kb on chromosome 19p13.12 and consists of 3 exons. The gene produces a single transcript encoding a 424-amino acid protein with a molecular weight of approximately 48 kDa.

Protein Architecture

The CHST14 protein contains:

• N-terminal transmembrane domain: Type II membrane protein orientation
• Stem region: Projects into the Golgi lumen
• Sulfotransferase domain: Contains the catalytic site
• C-terminal region: Required for enzyme activity

Catalytic Mechanism

CHST14 transfers sulfate groups in a stereospecific manner:

Expression Pattern

Tissue Distribution

CHST14 exhibits broad but specific expression:

| Tissue | Expression Level | Function |
|--------|------------------|----------|
| Skin | Very high | Dermatan sulfate synthesis |
| Blood vessels | High | Vascular ECM |
| Cartilage | High | Proteoglycan assembly |
| Brain | Moderate | Neural development |
| Lung | Moderate | Connective tissue |
| Fetal tissues | High | Development |

Brain Expression

In the central nervous system, CHST14 is expressed in:

• Cerebral cortex: Neurons and glia
• Hippocampus: Pyramidal neurons
• Cerebellum: Purkinje cells
• Subventricular zone: Neural stem cells

Physiological Functions

Dermatan Sulfate Biosynthesis

CHST14 is essential for dermatan sulfate chain modification[@habichi2013][@nakashima2015]:

• 4-O-sulfation: Adds sulfate groups to GalNAc residues
• Iduronic acid formation: Works alongside epimerases
• Chain elongation: Modulates chain properties
• Proteoglycan assembly: Critical for decorin and biglycan

Extracellular Matrix Assembly

CHST14 contributes to ECM organization:

• Collagen organization: Dermatan sulfate binds collagen
• Proteoglycan function: Affects tissue hydration
• Growth factor binding: Modulates signaling
• Mechanical properties: Influences tissue strength

Neural Development

CHST14 plays roles in neural systems[@mizumoto2014][@shimizu2020]:

• Neuronal migration: Chondroitin/dermatan sulfate gradients
• Axon guidance: Repulsive cues in developing brain
• Synapse formation: Proteoglycans at synaptic cleft
• Neural plasticity: CSPG modification in adults

Disease Associations

Musculocontractural Ehlers-Danlos Syndrome

CHST14 mutations cause MC-EDS[@miyake2010][@hson2019]:

Clinical Features

• Joint hypermobility: Generalized joint laxity
• Contractures: Multiple congenital contractures
• Characteristic facies: Distinctive facial features
• Skin hyperextensibility: Fragile, soft skin
• Developmental delay: Motor and speech delays

Molecular Pathogenesis

• Loss of enzyme activity: Missense/null mutations
• Reduced sulfation: Impaired dermatan sulfate
• ECM disruption: Abnormal collagen organization
• Tissue fragility: Connective tissue weakness

Wound Healing and Fibrosis

CHST14 is implicated in tissue repair[@pacini2016]:

• Scar formation: Dermatan sulfate in wound healing
• Fibrosis: Excessive tissue scarring
• Angiogenesis: Vascular ECM remodeling

Neurodegenerative Implications

While not a primary cause, CHST14 may influence[@sarker2021]:

• CSPG metabolism: Chondroitin sulfate in AD/PD
• Neural regeneration: Proteoglycans in repair
• Neuroinflammation: ECM in glial responses

Therapeutic Implications

Biomarker Potential

CHST14 shows potential as a biomarker:

• Serum levels: Detectable in circulation
• Disease correlation: Altered in connective tissue disorders
• Treatment monitoring: Tracks therapy response

Therapeutic Targets

Targeting CHST14 could provide benefits:

| Approach | Rationale | Status |
|----------|-----------|--------|
| Enzyme replacement | Restore function | Experimental |
| Gene therapy | Increase expression | Preclinical |
| Small molecule modulators | Enhance activity | Early development |

Interaction Network

Glycosaminoglycan Pathway

CHST14 interacts with:

• D4ST1: Identical enzyme activity
• CHST7: Related sulfotransferase
• DSE: Dermatan sulfate epimerase
• CSPGs: Chondroitin sulfate proteoglycans

ECM Components

CHST14 associates with:

• Decorin: Major dermatan sulfate proteoglycan
• Biglycan: Small leucine-rich proteoglycan
• Collagen I/III: Fibrillar collagens
• Fibronectin: ECM glycoprotein

Research Methods

Detection Techniques

• qPCR: Gene expression analysis
• Western blot: Protein detection
• Enzyme assay: Sulfotransferase activity
• Mass spectrometry: GAG analysis

Model Systems

• Cell lines: Fibroblasts, chondrocytes
• Animal models: Knockout mice
• Patient cells: Primary fibroblasts
• Organoids: Tissue engineering

See Also

• [Proteoglycans](/mechanisms/proteoglycans)
• [Extracellular Matrix](/mechanisms/extracellular-matrix)
• [Ehlers-Danlos Syndrome](/diseases/ehlers-danlos-syndrome)
• [Glycosaminoglycans](/mechanisms/glycosaminoglycans)

References