NEURL2: Neuralized E3 Ubiquitin Protein Ligase 2
A key regulator of ubiquitination and Notch signaling in muscle and neural development.
Gene Information Card
| Symbol | NEURL2 |
|---|---|
| Full Name | Neuralized E3 Ubiquitin Protein Ligase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 20q13.33 |
| NCBI Gene ID | 140825 ncbi.nlm.nih.gov/gene/140825 |
| Ensembl ID | ENSG00000101204 |
| UniProt ID | Q9BZR6 |
| OMIM ID | 609174 |
| HGNC ID | 17601 |
| Aliases | OZZY, Ozz, Ozz-E3 |
Description
NEURL2 (Neuralized E3 Ubiquitin Protein Ligase 2) encodes a RING-type E3 ubiquitin ligase that regulates the ubiquitination and degradation of target proteins. It is involved in the negative regulation of Notch signaling and plays a critical role in myogenesis, sarcomere assembly, and neural development. The protein localizes to the Z-disc in muscle cells and interacts with components of the ubiquitin-proteasome system.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Myopathy, distal, 5 (MPD5) | Loss-of-function mutations in NEURL2 impair sarcomere maintenance, leading to muscle weakness and distal muscle wasting. | ClinVar, OMIM |
| Nemaline myopathy 10 (NEM10) | NEURL2 mutations disrupt actin filament organization and Z-disc integrity, causing nemaline rod formation. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 15.2 | High |
| Heart | 8.7 | Medium |
| Brain | 4.1 | Low |
| Testis | 3.5 | Low |
| Lung | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| RH-30 (rhabdomyosarcoma) | 12.5 | High expression |
| H9c2 (rat cardiomyoblasts) | 9.8 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 3.2 | Low expression |
| HEK293 (embryonic kidney) | 1.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.278G>A (p.Arg93His) | Missense | Rare | Loss of E3 ligase activity; associated with distal myopathy |
| c.421C>T (p.Arg141Trp) | Missense | Rare | Impaired protein stability; linked to nemaline myopathy |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss mutations reduce or abolish ubiquitin ligase activity, leading to defective sarcomere assembly and muscle disease.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Not described; all known pathogenic mutations are recessive or compound heterozygous.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• Notch signaling pathway (KEGG: hsa04330)
• Sarcomere assembly and maintenance (Reactome: R-HSA-5250913)
Protein Summary
NEURL2 is a 445-amino acid RING-type E3 ubiquitin ligase containing a neuralized homology repeat (NHR) domain and a C-terminal RING finger domain. It ubiquitinates target proteins such as β-catenin and components of the Notch receptor complex, targeting them for proteasomal degradation. In muscle, NEURL2 localizes to the Z-disc and is essential for sarcomere integrity. Loss of function leads to myopathic phenotypes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NEURL2 Knockout HEK293 Cell Line | EDJ-KQ9817 | Human | 140825 | Details Get a Quote |
| NEURL2 Knockout HeLa Cell Line | EDJ-KQ36666 | Human | 140825 | Details Get a Quote |
| NEURL2 Knockout A-549 Cell Line | EDJ-KQ66946 | Human | 140825 | Details Get a Quote |
| NEURL2 Knockout HCT 116 Cell Line | EDJ-KQ75348 | Human | 140825 | Details Get a Quote |
