NEDD4
NEDD4 E3 Ubiquitin Protein Ligase
Gene Information Card
| Symbol | NEDD4 |
|---|---|
| Full Name | NEDD4 E3 ubiquitin protein ligase |
| Gene Type | protein-coding |
| Chromosomal Location | 15q21.3 |
| NCBI Gene ID | 4734 ncbi.nlm.nih.gov/gene/4734 |
| Ensembl ID | ENSG00000169862 |
| UniProt ID | P46934 |
| OMIM ID | 603384 |
| HGNC ID | 7727 |
| Aliases | NEDD4-1, RPF1, KIAA0093 |
Description
NEDD4 encodes a member of the NEDD4 family of HECT domain E3 ubiquitin ligases. The protein ubiquitinates substrate proteins, targeting them for proteasomal degradation or regulating their trafficking and signaling. It plays critical roles in cell growth, development, and ion channel regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Liddle syndrome | Gain-of-function mutations in ENaC subunits lead to increased sodium reabsorption; NEDD4 normally ubiquitinates ENaC for degradation, but mutations disrupt this interaction. | OMIM #177200 |
| Breast cancer | NEDD4 overexpression promotes PTEN ubiquitination and degradation, activating PI3K/AKT signaling. | PMID: 17694054 |
| Colorectal cancer | NEDD4 upregulation correlates with poor prognosis; targets tumor suppressors for degradation. | PMID: 24937433 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Kidney | 15.7 | Medium |
| Lung | 10.1 | Medium |
| Liver | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.2 | High expression |
| HeLa | 14.5 | Moderate expression |
| MCF7 | 11.3 | Moderate expression |
| A549 | 9.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1942C>T (p.Arg648Trp) | Missense | <0.01% | Unknown functional effect; rare variant |
| c.2561A>G (p.Asn854Ser) | Missense | <0.01% | Reported in ClinVar as uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants may impair ubiquitin ligase activity, but no well-characterized LOF mutations are documented.
Gain of Function (GOF)
Overexpression or amplification in cancers leads to increased PTEN degradation and oncogenic signaling.
Dominant Negative (DN)
Not reported for NEDD4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• EGFR tyrosine kinase inhibitor resistance (KEGG: hsa01521)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
Protein Summary
NEDD4 is a 1319-amino acid HECT domain E3 ubiquitin ligase that ubiquitinates diverse substrates including PTEN, ENaC, and Notch. It regulates cell proliferation, apoptosis, and ion homeostasis. Dysregulation is implicated in cancer and hypertension.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NEDD4 Knockout HEK293 Cell Line | EDJ-KQ2645 | Human | 4734 | Details Get a Quote |
| NEDD4L Knockout HEK293 Cell Line | EDJ-KQ3107 | Human | 23327 | Details Get a Quote |
| NEDD4 Knockout A-549 Cell Line | EDJ-KQ23406 | Human | 4734 | Details Get a Quote |
| NEDD4 Knockout HCT 116 Cell Line | EDJ-KQ23407 | Human | 4734 | Details Get a Quote |
| NEDD4 Knockout HeLa Cell Line | EDJ-KQ23408 | Human | 4734 | Details Get a Quote |
| NEDD4L Knockout A-549 Cell Line | EDJ-KQ24440 | Human | 23327 | Details Get a Quote |
| NEDD4L Knockout HCT 116 Cell Line | EDJ-KQ24441 | Human | 23327 | Details Get a Quote |
| NEDD4L Knockout HeLa Cell Line | EDJ-KQ24442 | Human | 23327 | Details Get a Quote |
