N4BP1: NEDD4 Binding Protein 1
A key regulator of ubiquitination, immune signaling, and antiviral responses
Gene Information Card
| Symbol | N4BP1 |
|---|---|
| Full Name | NEDD4 Binding Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q23.1 |
| NCBI Gene ID | 9683 ncbi.nlm.nih.gov/gene/9683 |
| Ensembl ID | ENSG00000102974 |
| UniProt ID | O75175 |
| OMIM ID | 617202 |
| HGNC ID | 23276 |
| Aliases | N4BP1, NEDD4 binding protein 1, FLJ11127, KIAA0613 |
Description
N4BP1 (NEDD4 Binding Protein 1) is a protein-coding gene that encodes a member of the NEDD4-binding protein family. The protein contains a C-terminal NYN domain with ribonuclease activity and interacts with NEDD4 family E3 ubiquitin ligases. N4BP1 functions as a negative regulator of antiviral immune responses by degrading viral RNA and modulating ubiquitin-dependent signaling pathways. It is involved in the regulation of cytokine production, apoptosis, and cellular stress responses. The gene is expressed in multiple tissues and is implicated in various cancers and inflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | N4BP1 overexpression may promote tumor growth via altered ubiquitination of oncogenic substrates | ClinVar, COSMIC |
| Colorectal cancer | Mutations in N4BP1 associated with dysregulated immune signaling and poor prognosis | COSMIC |
| Viral infections (e.g., HIV-1, Influenza A) | N4BP1 restricts viral replication through its RNase activity and interaction with NEDD4 | NCBI Gene, UniProt |
| Inflammatory bowel disease | N4BP1 variants linked to altered cytokine responses and intestinal inflammation | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Lung | 8.2 | Medium |
| Testis | 6.7 | Low |
| Brain | 4.3 | Low |
| Heart | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HeLa | 11.0 | Medium expression |
| K562 | 9.5 | Medium expression |
| A549 | 7.8 | Low expression |
| MCF7 | 6.4 | Low expression |
Data source:Human Protein Atlas(proteinatlas.org)
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Trp) | Missense | 0.02% (gnomAD) | Alters RNase activity; associated with immune dysregulation |
| c.1456G>A (p.Glu486Lys) | Missense | 0.01% (gnomAD) | May affect NEDD4 binding; reported in colorectal cancer |
| c.1789_1791del (p.Lys597del) | In-frame deletion | <0.01% | Loss of function; linked to antiviral response defects |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt the NYN ribonuclease domain or NEDD4 interaction reduce N4BP1's ability to degrade viral RNA and regulate ubiquitination, leading to enhanced viral replication and altered cytokine signaling.
Gain of Function (GOF)
Not well characterized; some missense variants may increase N4BP1 stability or activity, potentially contributing to oncogenic signaling.
Dominant Negative (DN)
Truncating or deletion mutations that retain NEDD4 binding but lack RNase activity may interfere with wild-type N4BP1 function, impairing antiviral immunity.
View complete mutation data:
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• RIG-I-like receptor signaling pathway (KEGG: hsa04622)
• Antiviral mechanism by IFN-stimulated genes (Reactome: R-HSA-1169410)
Protein Summary
N4BP1 is a 597-amino acid protein with a molecular weight of approximately 67 kDa. It contains an N-terminal NYN domain (Pfam: PF14436) that exhibits ribonuclease activity, and a C-terminal region that binds NEDD4 family E3 ubiquitin ligases. The protein localizes to the cytoplasm and nucleus. Through its RNase activity, N4BP1 degrades viral RNA, thereby restricting replication of viruses such as HIV-1 and Influenza A. Additionally, N4BP1 modulates ubiquitination of signaling proteins (e.g., TRAF3, MAVS) to negatively regulate type I interferon production. Post-translational modifications include phosphorylation and ubiquitination, which control its stability and function. N4BP1 is widely expressed, with highest levels in lymphoid tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| N4BP1 Knockout HEK293 Cell Line | EDJ-KQ6694 | Human | 9683 | Details Get a Quote |
| N4BP1 Knockout A-549 Cell Line | EDJ-KQ31047 | Human | 9683 | Details Get a Quote |
| N4BP1 Knockout HCT 116 Cell Line | EDJ-KQ31048 | Human | 9683 | Details Get a Quote |
| N4BP1 Knockout HeLa Cell Line | EDJ-KQ31049 | Human | 9683 | Details Get a Quote |