Discovering and Characterizing DNL3-Like Proteins: Implications for Protein Biology and Therapeutic Strategies

Target Name: DTX3L

NCBI ID: G151636

Discovering and Characterizing DNL3-Like Proteins: Implications for Protein Biology and Therapeutic Strategies

Deltex 3 like (DNL3) is a protein that belongs to the ubiquitin ligase family, which is a subset of the proteinases superfamily. DNL3 is characterized by its ability to catalyze the hydrolysis of a specific target protein, ubiquitin, which is a key protein involved in various cellular processes such as cell signaling, DNA replication, and response to stress. The discovery and characterization of DNL3-like proteins have important implications for our understanding of protein biology and the development of new therapeutic strategies. In this article, we will explore the structure and function of DNL3-like proteins, with a focus on their potential as drug targets or biomarkers.

Structure and mechanism

The protein encoded by the DNL3 gene is a 166 amino acid protein that contains a single transmembrane domain and a distinct N-terminus. The N-terminus of DNL3 is unique, as it contains a short polyglutamyl extension that is specific to this protein. This extension is involved in the formation of a complex with the protein ubiquitin, which is a large and complex protein that plays a central role in various cellular processes.

The catalytic center of DNL3 is the active site, which is a unique region that is present in all ubiquitin ligases. The active site consists of a specific amino acid sequence that is involved in the substrate recognition and catalytic activity of the enzyme. In the case of DNL3, the active site is composed of the amino acids Asp221, Asp222, Asp223, and Asp224, which are all Asp residues.

The mechanism of DNL3-mediated ubiquitin cleavage is based on a specific active site loop, which is a region of the protein that is involved in the substrate recognition and the formation of the active site. The active site loop is a parallel beta-sheet structure that is composed of multiple conserved helices. This structure allows the enzyme to recognize and interact with specific ubiquitin molecules, which are then cleaved by the active site loop.

DNL3-like proteins as drug targets

The discovery of DNL3-like proteins has important implications for the development of new therapeutic strategies. DNL3-like proteins can be targeted by small molecules or antibodies, which can modulate their activity and function. One of the potential benefits of targeting DNL3-like proteins is the ability to inhibit their activity and reduce the production of harmful products that can be harmful to the cell.

In addition to their potential as therapeutic targets, DNL3-like proteins have also been identified as potential biomarkers. The ability to detect and measure the expression of DNL3-like proteins can be used to monitor the effectiveness of different therapeutic strategies, such as cancer treatments. In addition, the DNL3-like proteins can be used as a proxy for the overall health of the cell, as changes in their expression levels can indicate the presence of stress or other cellular changes.

DNL3-like proteins as biomarkers

DNL3-like proteins have been identified as potential biomarkers for a variety of diseases, including cancer, neurodegenerative diseases, and autoimmune diseases. One of the key advantages of using DNL3-like proteins as biomarkers is their ability to be easily detected and measured. This is because they are typically expressed at relatively high levels in the cell, and the changes in their expression can be detected using techniques such as qRT-PCR, western blotting, or immunofluorescence.

In addition to their ease of use, DNL3-like proteins have also been shown to be sensitive to various therapeutic treatments. For example, studies have shown that inhibiting the activity of DNL3-like proteins can be an effective way to

Protein Name: Deltex E3 Ubiquitin Ligase 3L

Functions: E3 ubiquitin-protein ligase which, in association with ADP-ribosyltransferase PARP9, plays a role in DNA damage repair and in interferon-mediated antiviral responses (PubMed:12670957, PubMed:19818714, PubMed:26479788, PubMed:23230272). Monoubiquitinates several histones, including histone H2A, H2B, H3 and H4 (PubMed:28525742). In response to DNA damage, mediates monoubiquitination of 'Lys-91' of histone H4 (H4K91ub1) (PubMed:19818714). The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 'Lys-20' methylation (H4K20me) (PubMed:19818714). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272). By monoubiquitinating histone H2B H2BC9/H2BJ and thereby promoting chromatin remodeling, positively regulates STAT1-dependent interferon-stimulated gene transcription and thus STAT1-mediated control of viral replication (PubMed:26479788). Independently of its catalytic activity, promotes the sorting of chemokine receptor CXCR4 from early endosome to lysosome following CXCL12 stimulation by reducing E3 ligase ITCH activity and thus ITCH-mediated ubiquitination of endosomal sorting complex required for transport ESCRT-0 components HGS and STAM (PubMed:24790097). In addition, required for the recruitment of HGS and STAM to early endosomes (PubMed:24790097). In association with PARP9, plays a role in antiviral responses by mediating 'Lys-48'-linked ubiquitination of encephalomyocarditis virus (EMCV) and human rhinovirus (HRV) C3 proteases and thus promoting their proteosomal-mediated degradation (PubMed:26479788)

More Common Targets