N4BP1 is an 896 amino acid protein that belongs to the N4BP1 family. N4BP1 primarily localizes to nucleolus, however it also localizes to PML nuclear bodies when desumoylated. Detected in heart, lung, brain, liver, skeletal muscle, pancreas, kidney, spleen, testis and ovary, N4BP1 is phosphorylated upon DNA damage probably by ATM or ATR. N4BP1 interacts with Nedd4, a protein with a wide range of activities including modification of ubiquitin-protein ligase, regulation of membrane channels and potentiating hormone-dependent activation of transcription. N4BP1 inhibits the E3 ubiquitin-protein ligase ITCH, by interacting with the second WW domain of ITCH thereby competing with ITCH's substrates and impairing ubiquitination of substrates. N4BP1 has no obvious transmembrane regions, which raises the possibility that N4BP1 represents a soluble adaptor that could sequester ITCH within the cytosol. The N4BP1 gene maps to chromosome 16q12.1.
Function:
Inhibitor of the E3 ubiquitin-protein ligase ITCH. Acts by interacting with the second WW domain of ITCH, leading to compete with ITCH's substrates and impairing ubiquitination of substrates.
Subcellular Location:
Nucleus; nucleolus. Nucleus; PML body. Primarily localizes to the nucleolus. Also localizes to the PML nuclear bodies, when desumoylated.
Tissue Specificity:
Detected in heart, lung, brain, liver, skeletal muscle, pancreas, kidney, spleen, testis and ovary.
Post-translational modifications:
Monoubiquitinated by NEDD4. Polyubiquitinated, leading to its degradation by the proteasome. Sumoylated by SUMO1, abrogating polyubiquitination and subsequent degradation. Desumoylated by SENP1, leading to accumulation in PML nuclear bodies.
Phosphorylated upon DNA damage, probably by ATM or ATR.
Similarity:
Belongs to the N4BP1 family.
SWISS:
O75113
Gene ID:
9683
Database links:
Entrez Gene: 9683 Human
Entrez Gene: 80750 Mouse
Entrez Gene: 291921 Rat
SwissProt: O75113 Human
SwissProt: Q6A037 Mouse
Unigene: 511839 Human
Unigene: 25117 Mouse
Unigene: 428374 Mouse
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