PRKN (Parkin RBR E3 Ubiquitin Protein Ligase)
A key regulator of mitochondrial quality control and a major cause of autosomal recessive early-onset Parkinson's disease.
Gene Information Card
| Symbol | PRKN |
|---|---|
| Full Name | Parkin RBR E3 Ubiquitin Protein Ligase |
| Gene Type | Protein coding |
| Chromosomal Location | 6q26 |
| NCBI Gene ID | 5071 ncbi.nlm.nih.gov/gene/5071 |
| Ensembl ID | ENSG00000185345 |
| UniProt ID | O60260 |
| OMIM ID | 602544 |
| HGNC ID | 8607 |
| Aliases | PARK2, AR-JP, LPRS2, PDJ |
Description
The PRKN gene encodes parkin, a cytosolic E3 ubiquitin ligase that plays a critical role in the ubiquitin-proteasome system and mitophagy. It is essential for the selective removal of damaged mitochondria, a process vital for cellular homeostasis, particularly in neurons. Mutations in PRKN are the most common cause of autosomal recessive early-onset Parkinson's disease (AR-JP), leading to mitochondrial dysfunction and dopaminergic neuron degeneration.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Parkinson's disease (autosomal recessive early-onset) | Loss-of-function mutations impair parkin's E3 ligase activity, leading to defective mitophagy and accumulation of damaged mitochondria, causing oxidative stress and neuronal death. | OMIM, ClinVar |
| Leprosy (susceptibility to) | Certain PRKN variants may influence immune response and susceptibility to Mycobacterium leprae infection. | OMIM, PubMed (via NCBI) |
| Cancer (various types) | Parkin is considered a tumor suppressor; loss of expression or function can promote tumorigenesis through dysregulation of cell cycle and apoptosis. | COSMIC, PubMed (via NCBI) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High |
| Testis | Medium | Medium |
| Heart | Medium | Medium |
| Skeletal Muscle | Medium | Medium |
| Liver | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High | Neuronal-like model, commonly used for Parkinson's research |
| HEK293 (embryonic kidney) | Medium | Widely used for overexpression studies |
| HeLa (cervical carcinoma) | Low | Endogenous expression is low; often used for transfection |
| U2OS (osteosarcoma) | Medium | Used in mitophagy studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.924C>T (p.Arg275Trp) | Missense | Rare | Impairs E3 ligase activity, reduces solubility, and disrupts mitophagy. |
| c.601A>G (p.Arg201Gly) | Missense | Rare | Affects ubiquitination function, leading to mitochondrial dysfunction. |
| Exon deletions (e.g., exon 3 deletion) | Copy number variant | Common in AR-JP | Frameshift or loss of functional domains, resulting in complete loss of parkin function. |
| c.823C>T (p.Arg275Trp) | Missense | Rare | Similar to other missense mutations, impairs ligase activity. |
Mutation functional classification
Loss of Function (LOF)
Most PRKN mutations are loss-of-function, either through missense changes that disrupt the catalytic RING domain or through deletions that remove entire exons. This leads to impaired ubiquitination of substrates and defective mitophagy.
Gain of Function (GOF)
Not well established; some rare variants may exhibit dominant-negative effects, but the primary mechanism is loss of function.
Dominant Negative (DN)
Certain missense mutations may exert a dominant-negative effect by dimerizing with wild-type parkin and interfering with its function, though this is less common.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity | • zinc ion binding |
| • protein binding | • mitochondrion |
| • cytoplasm | • ubiquitin-dependent protein catabolic process |
| • mitophagy | • autophagy |
| • protein ubiquitination | • negative regulation of apoptosis |
Pathways
• Parkin-ubiquitin proteasomal system
• Mitophagy (PINK1-Parkin pathway)
• Ubiquitin-mediated proteolysis
Protein Summary
Parkin is a 465-amino acid protein with an N-terminal ubiquitin-like domain and a C-terminal RBR (RING-between-RING) domain that confers E3 ubiquitin ligase activity. It is recruited to damaged mitochondria by PINK1, where it ubiquitinates outer mitochondrial membrane proteins to trigger mitophagy. Parkin also participates in the ubiquitin-proteasome system to degrade misfolded proteins. Loss of parkin function leads to mitochondrial accumulation, oxidative stress, and neurodegeneration, particularly in dopaminergic neurons of the substantia nigra.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PRKN Knockout HEK293 Cell Line | EDJ-KQ3360 | Human | 5071 | Details Get a Quote |
| PRKN Knockout HeLa Cell Line | EDJ-KQ54079 | Human | 5071 | Details Get a Quote |
| PRKN Knockout A-549 Cell Line | EDJ-KQ62567 | Human | 5071 | Details Get a Quote |
| PRKN Knockout HCT 116 Cell Line | EDJ-KQ71038 | Human | 5071 | Details Get a Quote |
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