Tbio DTX3L E3 ubiquitin-protein ligase DTX3L

Protein Summary

Description

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 HIST1H2BH/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). DTX3L functions as an E3 ubiquitin ligase (Takeyama et al., 2003 [PubMed 12670957]).[supplied by OMIM, Nov 2009]

Uniprot Accession IDs

• Q8TDB6
• B3KWH6
• Q53ZZ3
• Q5MJP7

Gene Name

• DTX3L

Ensembl ID

• ENST00000296161
• ENSP00000296161
• ENSG00000163840
• ENST00000383661
• ENSP00000373157

Symbol

• BBAP
• BBAP
• RNF143

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
virus perturbation	1
histone modification site profile	0.89
gene perturbation	0.74
cell line	0.63
tissue sample	0.63

Protein Classes

PANTHER Classes

Protein / ... / Ubiquitin-protein Ligase / E3 Ubiquitin-protein Ligase Dtx3l

DTO Classes

Protein / Enzyme / Ligase / Ubiquitin-protein Ligase / E3 Ubiquitin-protein Ligase Dtx3l

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 25.64   (req: < 5)

Gene RIFs: 14   (req: <= 3)

Antibodies: 136   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 25.64   (req: >= 5)

Gene RIFs: 14   (req: > 3)

Antibodies: 136   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 32

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0