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.

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 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
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