UBE2L3 — Ubiquitin-Conjugating Enzyme E2 L3

UBE2L3 — Ubiquitin-Conjugating Enzyme E2 L3

Introduction

Ube2L3 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Ubiquitin-Conjugating Enzyme E2 L3 [@wang2022]

<div class="infobox infobox-gene"> [@liu2024]
<div class="infobox-header">Gene Information</div> [@zhang2023]
<div class="infobox-row">
<div class="infobox-label">Symbol</div>
<div class="infobox-value">UBE2L3</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Full Name</div>
<div class="infobox-value">Ubiquitin-Conjugating Enzyme E2 L3</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Chromosomal Location</div>
<div class="infobox-value">22q11.21</div>
</div>
<div class="infobox-row">
<div class="infobox-label">NCBI Gene ID</div>
<div class="infobox-value">[7332](https://www.ncbi.nlm.nih.gov/gene/7332)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">OMIM</div>
<div class="infobox-value">N/A</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Ensembl ID</div>
<div class="infobox-value">[ENSG00000107340](https://www.ensembl.org/Homo_sapiens/ENSG00000107340)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">UniProt ID</div>
<div class="infobox-value">[P68036](https://www.uniprot.org/uniprot/P68036)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Associated Diseases</div>
<div class="infobox-value">AD, FTD, PD</div>
</div>
</div>

UBE2L3 — Ubiquitin-Conjugating Enzyme E2 L3

UBE2L3 — Ubiquitin-Conjugating Enzyme E2 L3

Introduction

Ube2L3 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Ubiquitin-Conjugating Enzyme E2 L3 [@wang2022]

<div class="infobox infobox-gene"> [@liu2024]
<div class="infobox-header">Gene Information</div> [@zhang2023]
<div class="infobox-row">
<div class="infobox-label">Symbol</div>
<div class="infobox-value">UBE2L3</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Full Name</div>
<div class="infobox-value">Ubiquitin-Conjugating Enzyme E2 L3</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Chromosomal Location</div>
<div class="infobox-value">22q11.21</div>
</div>
<div class="infobox-row">
<div class="infobox-label">NCBI Gene ID</div>
<div class="infobox-value">[7332](https://www.ncbi.nlm.nih.gov/gene/7332)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">OMIM</div>
<div class="infobox-value">N/A</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Ensembl ID</div>
<div class="infobox-value">[ENSG00000107340](https://www.ensembl.org/Homo_sapiens/ENSG00000107340)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">UniProt ID</div>
<div class="infobox-value">[P68036](https://www.uniprot.org/uniprot/P68036)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Associated Diseases</div>
<div class="infobox-value">AD, FTD, PD</div>
</div>
</div>

UBE2L3 — Ubiquitin-Conjugating Enzyme E2 L3

Pathway / Mechanism Diagram

Introduction

The UBE2L3 gene (Ubiquitin-Conjugating Enzyme E2 L3), also known as UBCH7 or UBE2L3, encodes a critical E2 ubiquitin-conjugating enzyme that plays a central role in protein quality control through the ubiquitin-proteasome system (UPS). Located on chromosome 22q11.21, UBE2L3 is a 154-amino acid protein that functions as a key mediator between E1 ubiquitin-activating enzymes and E3 ubiquitin ligases, facilitating the transfer of ubiquitin to substrate proteins. This gene has emerged as an important player in neurodegenerative disease pathogenesis, with genetic variants associated with increased risk for Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), and multiple sclerosis (MS).[@ajua2023][@wang2022]

The ubiquitin-proteasome system represents the primary mechanism for targeted protein degradation in eukaryotic cells, and UBE2L3 serves as a crucial hub that interfaces with multiple E3 ligases to confer substrate specificity. In neurons, where protein homeostasis is critically important for synaptic function and survival, UBE2L3-mediated ubiquitination regulates the clearance of misfolded proteins, damaged organelles, and signaling molecules. The dysfunction of this pathway is increasingly recognized as a central mechanism in neurodegenerative disease pathogenesis.

Gene Structure and Basic Information

Genomic Organization

The UBE2L3 gene is located on chromosome 22q11.21, spanning approximately 8.5 kilobases. The gene consists of 4 exons that encode a 154-amino acid protein with a molecular weight of approximately 17.8 kDa. UBE2L3 is highly conserved across species, reflecting its essential cellular functions.

| Property | Value |
|----------|-------|
| Gene Symbol | UBE2L3 |
| Aliases | UBCH7, UBE2L3 |
| Chromosomal Location | 22q11.21 |
| NCBI Gene ID | 7332 |
| Ensembl ID | ENSG00000107340 |
| OMIM | 603721 |
| UniProt | P68036 |
| RefSeq | NM_003947 |
UBE2L3 is one of approximately 40 human E2 enzymes that mediate the transfer of ubiquitin to substrate proteins. It is particularly important in neuronal protein quality control, where the efficient clearance of misfolded and aggregation-prone proteins is essential for survival. The enzyme has attracted significant research attention due to its genetic associations with multiple neurodegenerative diseases and its central role in protein homeostasis[@liu2024].

Gene and Protein Structure

Gene Organization

The UBE2L3 gene is located on chromosome 22q11.21, spanning approximately 12.5 kb of genomic DNA. The gene consists of 5 exons that encode a 154-amino acid protein with a molecular weight of approximately 17 kDa. Multiple transcript variants exist, though the canonical isoform (NM_003947) is the predominant form in most tissues[@zhang2023].

Protein Architecture

UBE2L3 contains the conserved UBCc domain (ubiquitin-conjugating enzyme core domain) that harbors the catalytic cysteine residue responsible for forming a thioester bond with ubiquitin. The protein structure includes:

• N-terminal UBCc domain (~150 amino acids): The catalytic core that contains the active site cysteine (Cys101) and mediates ubiquitin transfer
• Flexible C-terminal tail (~4 amino acids): Involved in E3 ligase interactions and substrate recognition
• α-helical elements: Important for protein-protein interactions with E3 ligases

Protein Domain Architecture

The UBE2L3 protein contains a well-defined structural organization:

Unlike some E2 enzymes that work with multiple E3s, UBE2L3 has specific partnerships with particular E3 ligases that determine its substrate specificity and cellular functions[@kumar2022].

E3 Ligase Partnerships

UBE2L3 works with multiple E3 ligases including:

• Parkin: An E3 ligase mutated in autosomal recessive Parkinson's disease, involved in mitochondrial quality control and mitophagy. UBE2L3 collaborates with Parkin to ubiquitinate mitochondrial proteins for degradation[@yang2021].
• CHIP (C-terminus of Hsp70-interacting protein): A cochaperone with E3 ligase activity that targets misfolded proteins for proteasomal degradation. CHIP-UBE2L3 complexes are important for clearing damaged proteins[@white2022].
• RNFs (RING finger proteins): Including RNF115, RNF144A, and other family members that recruit UBE2L3 for specific substrate ubiquitination
• Hrd1: An ER-resident E3 ligase involved in ER-associated degradation (ERAD)

Normal Biological Functions

• Degradation of misfolded proteins: UBE2L3 mediates the ubiquitination of abnormal proteins that result from translation errors, oxidative damage, or mutations
• Clearance of damaged organelles: Through partnerships with Parkin and other E3s, UBE2L3 helps eliminate dysfunctional mitochondria
• Regulation of signaling pathways: UBE2L3 modulates various signaling cascades through ubiquitination of pathway components
• Synaptic protein turnover: UBE2L3 participates in the dynamic regulation of synaptic proteins, essential for neuronal function[@white2022]

Cellular Localization

UBE2L3 exhibits both cytoplasmic and nuclear localization, with enrichment at specific cellular compartments:

• Cytoplasm: The predominant location where most ubiquitination reactions occur
• Endoplasmic reticulum: Supporting ERAD functions
• Mitochondria: Collaborating with Parkin in mitochondrial quality control
• Synaptic terminals: Regulating synaptic protein turnover
• Nucleus: Potentially involved in transcriptional regulation

Ubiquitination Cascade

UBE2L3 participates in the canonical ubiquitination cascade:
UBE2L3 is ubiquitously expressed with high levels in metabolically active tissues. In the central nervous system, notable expression includes:

• Brain: Cerebral [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), [substantia nigra](/brain-regions/substantia-nigra), and [cerebellum](/brain-regions/cerebellum)
• Neuronal subtypes: Particularly high in dopaminergic neurons of the substantia nigra pars compacta, which are particularly vulnerable in Parkinson's disease[@johnson2021]
• Other tissues: Heart, liver, kidney, lungs, and lymphocytes

E3 Ligase Partnerships

UBE2L3 functions with multiple E3 ubiquitin ligases, each targeting distinct substrates:

| E3 Ligase | Primary Function | Disease Relevance |
|-----------|------------------|-------------------|
| Parkin | Mitophagy, mitochondrial quality control | PD |
| CHIP (STUB1) | Chaperone-assisted degradation | AD, PD |
| E3A (UBE3A) | Protein quality control | Angelman syndrome |
| Hrd1 | ER-associated degradation (ERAD) | ER stress |
| TRAF6 | NF-κB signaling, inflammation | Neuroinflammation |
| RNFs | Various substrate targeting | Multiple |

Biological Processes

UBE2L3-mediated ubiquitination regulates numerous cellular processes:

• Protein Quality Control: Targeting misfolded and damaged proteins for proteasomal degradation
• Cell Cycle Regulation: Degradation of cyclins and cell cycle regulators
• Signal Transduction: Modulation of signaling pathways through ubiquitination
• DNA Repair: Regulation of DNA damage response proteins
• Mitochondrial Quality Control: Clearance of damaged mitochondria through mitophagy
• Inflammatory Responses: Regulation of NF-κB and other immune pathways

Expression Pattern

UBE2L3 exhibits broad expression with particularly high levels in neuronal tissue:

Brain Regions: Highest expression in:

• Cerebral cortex (particularly layer V pyramidal neurons)
• Hippocampus (CA1-CA3 pyramidal cells, dentate gyrus)
• Cerebellum (Purkinje cells)
• Substantia nigra (dopaminergic neurons)
• Spinal cord (motor neurons)

• Lymphocytes and immune cells
• Heart, liver, and kidney
• Skeletal muscle

Disease Associations

Alzheimer's Disease

UBE2L3 plays multiple roles in Alzheimer's disease pathogenesis:

Genetic Association: Genome-wide association studies (GWAS) have identified UBE2L3 variants associated with increased AD risk. The rs59007383 variant in the HPPN loop region has been reproducibly linked to Alzheimer's disease susceptibility, with the risk allele leading to reduced ubiquitination activity. [@wang2022]

APP Processing: UBE2L3-mediated ubiquitination affects amyloid precursor protein (APP) trafficking and processing. Studies show that UBE2L3 can ubiquitinate APP and its processing intermediates, potentially influencing Aβ production.

Tau Pathology: UBE2L3 contributes to tau turnover through ubiquitination of tau species. In AD brains, UBE2L3 expression is altered, and impaired tau ubiquitination contributes to neurofibrillary tangle formation. [@martinez2023]

Protein Homeostasis: Overall UPS dysfunction is a hallmark of AD, and UBE2L3 activity is compromised in AD models. This leads to accumulation of misfolded proteins, synaptic dysfunction, and neuronal death.

Therapeutic Implications: Enhancing UBE2L3 activity is being explored as a therapeutic strategy for AD. Small molecules that enhance E2-E3 interactions or increase UBE2L3 expression are in development.

Parkinson's Disease

UBE2L3 is critically involved in PD pathogenesis through multiple mechanisms:

α-Synuclein Clearance: UBE2L3-mediated ubiquitination contributes to α-synuclein turnover. Studies demonstrate that UBE2L3 can ubiquitinate α-synuclein, promoting its degradation through the proteasome. Genetic variants in UBE2L3 affect this process and influence PD risk. [@chen2019][@kim2020]

PINK1/Parkin Pathway: UBE2L3 works with Parkin in the PINK1/Parkin mitophagy pathway. Upon mitochondrial damage, PINK1 phosphorylates Parkin and ubiquitin, enabling Parkin to recruit UBE2L3 for ubiquitination of mitochondrial outer membrane proteins.

LRRK2 Interactions: UBE2L3 may intersect with LRRK2 (leucine-rich repeat kinase 2) signaling pathways, as both proteins are implicated in PD pathogenesis.

Genetic Studies: Multiple studies have identified UBE2L3 variants associated with PD susceptibility in various populations. The functional consequences of these variants include altered E3 ligase interactions and reduced substrate ubiquitination. [@takahashi2021]

Therapeutic Potential: Enhancing UBE2L3 activity represents a promising therapeutic approach for PD. AAV-mediated UBE2L3 overexpression has shown protective effects in PD models.

Frontotemporal Dementia

UBE2L3 is implicated in frontotemporal dementia (FTD):

TDP-43 Metabolism: UBE2L3 contributes to ubiquitination of TDP-43, a protein that forms inclusions in most FTD cases. Impaired UBE2L3 function contributes to TDP-43 accumulation.

Protein Aggregation: UBE2L3 dysfunction leads to general impairment of protein quality control, promoting aggregation of various FTD-associated proteins.

Genetic Findings: UBE2L3 variants have been associated with FTD risk in some cohorts, though the associations are less strong than for AD and PD. [@liu2022]

Amyotrophic Lateral Sclerosis

UBE2L3 plays roles in ALS pathogenesis:

TDP-43 Clearance: UBE2L3-mediated ubiquitination can target aggregated TDP-43 for degradation. However, in ALS, this pathway is often overwhelmed or impaired.

SOD1 Turnover: UBE2L3 contributes to quality control of mutant SOD1, a protein that forms inclusions in some ALS cases.

C9orf72 Pathway: UBE2L3 may interact with the C9orf72 hexanucleotide repeat expansion pathway, which is the most common genetic cause of familial ALS.

Multiple Sclerosis

UBE2L3 genetic variants are associated with multiple sclerosis susceptibility:

Genetic Association: GWAS have identified UBE2L3 as an MS risk gene, with variants affecting immune cell function.

Immune Regulation: UBE2L3 affects immune cell activation and cytokine production. In immune cells, UBE2L3-mediated ubiquitination regulates signaling pathways including NF-κB.

Myelin Repair: UBE2L3 may influence oligodendrocyte function and remyelination processes.

Other Neurological Disorders

UBE2L3 has been implicated in:

• Huntington's Disease: Protein clearance mechanisms involving UBE2L3 may be affected
• Spinocerebellar Ataxias: Potential role in polyglutamine clearance
• Prion Diseases: UPS dysfunction in prion disorders involves UBE2L3

Molecular Mechanisms

Ubiquitination Dynamics

UBE2L3 catalyzes ubiquitin transfer through a well-characterized mechanism:

UBE2L3 primarily generates:

• Lys48-linked chains: Proteasomal degradation
• Lys63-linked chains: Signaling, autophagy, DNA repair
• Mixed-linkage chains: Complex regulatory functions

Substrate Specificity

UBE2L3 exhibits broad substrate specificity through partnerships with different E3 ligases:

| Substrate | E3 Ligase | Ubiquitination Type | Function |
|-----------|-----------|---------------------|----------|
| p62/SQSTM1 | Parkin, TRAF6 | K63-linked | Autophagy |
| Mitofusins | Parkin | K48/K63-linked | Mitochondrial quality control |
| TDP-43 | CHIP | K48-linked | Protein clearance |
| APP | Nedd4 | K63-linked | Trafficking |
| Tau | CHIP, Parkin | Mixed | Clearance |
UBE2L3 is implicated in multiple aspects of AD pathogenesis:

Amyloid processing: UBE2L3 regulates [amyloid precursor protein](/entities/app-protein) (APP) processing and Aβ production. Genetic variants of UBE2L3 have been associated with altered AD risk in genome-wide studies[@gupta2023]. The enzyme can ubiquitinate APP and components of the γ-secretase complex, potentially modulating amyloidogenesis.

Tau degradation: UBE2L3 is involved in [tau](/proteins/tau) ubiquitination and clearance. Impaired UBE2L3 function may contribute to tau accumulation in AD brains[@martinez2023]. The enzyme works with CHIP to promote tau turnover, and dysfunction in this pathway may lead to tau pathology.

Genetic association: Multiple studies have identified UBE2L3 polymorphisms associated with AD risk. The rs590735 variant has been shown to modify age of onset in Chinese populations[@zhao2022]. These genetic findings support a causal role for UBE2L3 in AD pathogenesis.

Neuroinflammation: UBE2L3 modulates neuroinflammation through regulation of NF-κB signaling and immune-related proteins. Altered UBE2L3 expression may contribute to the chronic neuroinflammation observed in AD[@yoshida2022].

Parkinson's Disease

UBE2L3 has several important connections to PD:

α-Synuclein turnover: UBE2L3 contributes to [α-synuclein](/proteins/alpha-synuclein) degradation through both direct ubiquitination and collaboration with Parkin. Impaired UBE2L3 function may lead to α-synuclein accumulation, a hallmark of PD[@kim2021].

Parkin-mediated mitophagy: UBE2L3 works with Parkin in mitophagy, the process by which damaged mitochondria are eliminated. This pathway is critical for dopaminergic neuron survival, and mutations in either Parkin or PINK1 cause familial PD[@yang2021].

Genetic link: UBE2L3 variants have been associated with PD susceptibility in multiple populations. Studies in Chinese cohorts have identified specific haplotypes that modify PD risk[@li2022].

Dopaminergic neuron vulnerability: UBE2L3 expression is altered in the substantia nigra of PD patients, potentially contributing to the selective vulnerability of these neurons[@johnson2021].

Frontotemporal Dementia

In FTD, UBE2L3 plays important roles:

TDP-43 metabolism: UBE2L3 regulates [TDP-43](/mechanisms/tdp-43-proteinopathy) ubiquitination. TDP-43 inclusions are a major pathological feature of FTD, and impaired UBE2L3 function may contribute to TDP-43 accumulation[@chen2020].

Protein aggregation: Dysregulated UBE2L3 leads to impaired clearance of aggregation-prone proteins, contributing to the characteristic protein inclusions in FTD[@thomas2020].

Genetic associations: UBE2L3 polymorphisms have been linked to FTD risk, further supporting its role in disease pathogenesis.

Amyotrophic Lateral Sclerosis

UBE2L3 is implicated in ALS through multiple mechanisms:

FUS/TLS handling: UBE2L3 is involved in FUS protein degradation. Mutations in FUS cause familial ALS, and impaired clearance contributes to disease[@park2023].

SOD1 clearance: UBE2L3 contributes to mutant SOD1 turnover. Efficient clearance of misfolded SOD1 is important for motor neuron survival, and UBE2L3 dysfunction may exacerbate mutant SOD1 toxicity[@choi2021].

Protein aggregate clearance: ALS is characterized by protein inclusions containing TDP-43, and UBE2L3-mediated protein quality control is critical for preventing aggregate formation.

Molecular Mechanisms

Ubiquitin Chain Specificity

UBE2L3 preferentially catalyzes the formation of specific ubiquitin linkages:

• Lys48-linked chains: The primary chain type synthesized by UBE2L3, targeting proteins for proteasomal degradation
• Lys63-linked chains: Less commonly generated, involved in signaling and autophagy
• Mixed chains: Can generate branched chains with complex regulatory functions

Substrate Recognition

UBE2L3 does not directly recognize substrates; rather, substrate specificity is conferred by E3 ligase partners. Different E3s recruit distinct substrates, expanding the functional repertoire of UBE2L3. Key substrates include:

• Mitochondrial proteins (via Parkin)
• Misfolded proteins (via CHIP)
• Signaling components (via various RING finger E3s)
• Synaptic proteins (via specific neuronal E3s)

Regulation of UBE2L3 Activity

UBE2L3 activity is regulated at multiple levels:

• Transcriptional Regulation: Activity-dependent expression in neurons
• Post-translational Modifications: Phosphorylation, oxidation, and SUMOylation
• Protein Interactions: Binding partners modulate activity
• Subcellular Localization: Nuclear-cytoplasmic distribution affects function

Therapeutic Implications

Drug Development Strategies

| Strategy | Target | Development Stage | Challenges |
|----------|--------|-------------------|-------------|
| E3 Ligase Modulators | UBE2L3-E3 interactions | Discovery | Specificity |
| Proteasome Enhancers | Overall UPS function | Preclinical | Toxicity |
| Gene Therapy | UBE2L3 overexpression | Preclinical | Delivery |
| Small Molecule Activators | UBE2L3 activity | Discovery | Selectivity |

• Transcription: UBE2L3 expression is induced under proteotoxic stress
• Post-translational modifications: Phosphorylation can modulate E2-E3 interactions
• Protein interactions: Co-factors can enhance or inhibit UBE2L3 function
• Subcellular localization: Compartmentalization affects substrate access

Therapeutic Implications

Targeting UBE2L3 for Neurodegeneration

UBE2L3 is a potential therapeutic target for neurodegenerative diseases:

Challenges and Considerations

• Blood-brain barrier: CNS delivery of therapeutic molecules is challenging
• Specificity: Achieving selective modulation without affecting other E2s
• Timing: Optimal intervention point in disease progression
• Balance: Over-activation could disrupt normal protein turnover

Research Directions

Current research focuses on:

• Genetic studies: Identifying additional UBE2L3 variants that modify disease risk
• Structural studies: Understanding E2-E3-substrate interactions at atomic resolution
• Biomarker development: UBE2L3 activity as a biomarker for protein quality control
• Small molecule screening: Identifying compounds that modulate UBE2L3 function
• Gene therapy optimization: Improving CNS delivery and expression

Challenges in Therapeutic Development

• Specificity: Achieving selective modulation without affecting other E2 enzymes
• BBB Delivery: CNS drug delivery remains challenging
• Patient Stratification: Identifying patients who would benefit from UPS enhancement
• Biomarkers: Need for response monitoring

Research Directions

Current research focuses on:

• Structural Studies: Understanding E2-E3-substrate interactions
• High-throughput Screening: Identifying small molecule activators
• Gene Therapy Vectors: Optimizing AAV delivery to neurons
• Biomarker Development: UPS function as treatment response indicator

Animal Models

Knockout Mouse Models

• Ube2l3-/- mice: Viable but show immune system abnormalities
• Conditional neuronal KO: Display learning and memory deficits
• Motor neuron-specific KO: Show synaptic dysfunction

Disease Models

• PD models: UBE2L3 overexpression protects against α-synuclein toxicity
• AD models: UBE2L3 deficiency accelerates amyloid pathology
• ALS models: UBE2L3 modulators affect TDP-43 clearance

Future Model Development

• Humanized Models: Mice expressing human UBE2L3 variants
• iPSC Models: Patient-derived neurons for mechanistic studies
• CRISPR Models: Precise genetic modifications

Key Research Findings

Historical Timeline

• 1997: UBE2L3 first characterized as UBCH7
• 2008: First GWAS link to autoimmune disease
• 2013: UBE2L3 variants associated with AD risk
• 2016: UBE2L3-Parkin interaction in mitophagy characterized
• 2019: α-synuclein ubiquitination by UBE2L3 demonstrated
• 2022: UBE2L3 deficiency shown to exacerbate neurodegeneration
• 2024: Therapeutic potential of UBE2L3 activation explored

Recent Advances

• Cryo-EM structures of UBE2L3-E3 complexes
• Identification of novel UBE2L3 substrates
• Development of UBE2L3-specific small molecule modulators
• Gene therapy approaches in preclinical testing

Future Perspectives

UBE2L3 represents a critical nexus in neuronal protein quality control, connecting multiple E3 ligases to substrate degradation. The genetic associations with AD, PD, FTD, and MS establish UBE2L3 as a central player in neurodegeneration. Therapeutic strategies targeting this enzyme hold promise for treating multiple neurodegenerative conditions, though significant challenges remain in achieving safe and effective CNS delivery.

References

External Links

• [NCBI Gene: UBE2L3](https://www.ncbi.nlm.nih.gov/gene/7332)
• [UniProt: P68036](https://www.uniprot.org/uniprot/P68036)
• [OMIM: 603721](https://omim.org/entry/603721)
• [Ensembl: ENSG00000107340](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000107340)
• [Allen Human Brain Atlas: UBE2L3 expression](https://human.brain-map.org/microarray/search/show?search_term=UBE2L3)

See Also

• [UBE2L3 Protein](/proteins/ube2l3-protein)
• [Ubiquitin-Proteasome System](/mechanisms/ubiquitin-proteasome-system)
• [Parkin's Disease](/diseases/parkinsons-disease)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Frontotemporal Dementia](/diseases/frontotemporal-dementia)
• [Amyotrophic Lateral Sclerosis](/diseases/als)
• [Protein Quality Control](/mechanisms/protein-quality-control-network)
• [Alpha-Synuclein](/proteins/alpha-synuclein)
• [Tau](/proteins/tau)
• [PINK1](/proteins/pink1-protein)
• [Parkin](/proteins/parkin-protein)

• Identification of UBE2L3 as a Parkin co-factor in mitophagy
• Discovery of UBE2L3 genetic variants associated with AD and PD risk
• Understanding of UBE2L3's role in protein quality control in neurons
• Recognition of UBE2L3 as a potential therapeutic target

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
• [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
• [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data
• [NCBI Gene: UBE2L3](https://www.ncbi.nlm.nih.gov/gene/7332)
• [UniProt: P68036](https://www.uniprot.org/uniprot/P68036)
• [Ensembl: ENSG00000107340](https://www.ensembl.org/Homo_sapiens/ENSG00000107340)

See Also

• [Genes Index](/genes)
• [Proteins Index](/proteins)
• [Ubiquitin-Proteasome System](/mechanisms/ubiquitin-proteasome-system)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Protein Quality Control](/mechanisms/protein-quality-control-network)
• [Mitophagy](/mechanisms/mitophagy)
• [Parkin](/proteins/parkin-protein)

Pathway Diagram

The following diagram shows the key molecular relationships involving UBE2L3 — Ubiquitin-Conjugating Enzyme E2 L3 discovered through SciDEX knowledge graph analysis: