DTX3L

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Description

The DTX3L (deltex E3 ubiquitin ligase 3L) is a protein-coding gene located on chromosome 3.

DTX3L (Deltex E3 ubiquitin ligase 3L) is a human protein encoded by the DTX3L gene. It functions as a ubiquitin ligase (E3), a type of enzyme that attaches ubiquitin molecules to other proteins, and is often overexpressed in chemotherapy-resistant lymphomas. It belongs to the DTX family of proteins and plays a crucial role in DNA damage repair. DTX3L was identified through a search for proteins interacting with PARP9, a gene associated with B-cell lymphoma. Both DTX3L and PARP9 are located within the same region of the genome and are regulated by a common promoter. DTX3L has a distinct long N-terminus domain that allows it to form dimers with itself and other proteins, including DTX1, which enhances its ubiquitin ligase activity. DTX3L's activity is regulated by the enzyme METTL3.

DTX3L, also known as B-lymphoma- and BAL-associated protein, plays a crucial role in both DNA damage repair and antiviral responses, often in conjunction with PARP9. It functions as a ubiquitin ligase, adding a single ubiquitin molecule (monoubiquitination) to various histones like H2A, H2B, H3, and H4, including histone H4 at lysine 91 (H4K91ub1) in response to DNA damage. This modification may act as a signal for further histone modifications, impacting DNA repair processes. Furthermore, DTX3L aids in the recruitment of important DNA repair proteins like 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites. DTX3L also contributes to antiviral responses by regulating interferon-stimulated gene transcription through histone H2B ubiquitination, leading to the control of viral replication. Additionally, DTX3L independently regulates the sorting of a chemokine receptor, CXCR4, from early endosomes to lysosomes, impacting cellular signaling pathways. In association with PARP9, DTX3L targets viral proteases from EMCV and HRV for degradation by attaching multiple ubiquitin molecules (polyubiquitination) through lysine 48 linkages, leading to their breakdown in the proteasome.

DTX3L is also known as BBAP, RNF143.

Associated Diseases

• plasma fibronectin deficiency
• isolated asymptomatic elevation of creatine phosphokinase
• hemoglobin E-beta-thalassemia syndrome
• hemoglobin D disease
• breast cancer
• dehydrated hereditary stomatocytosis
• microcytic anemia with liver iron overload