DTX3L

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

Full Name

Deltex E3 Ubiquitin Ligase 3L

Research Area

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).

Biological Process

Cellular response to DNA damage stimulus Source: UniProtKB
Defense response to virus Source: UniProtKB-KW
Double-strand break repair Source: UniProtKB
Endosome to lysosome transport Source: UniProtKB
Histone H2A ubiquitination Source: UniProtKB
Histone H2B ubiquitination Source: UniProtKB
Histone monoubiquitination Source: UniProtKB
Innate immune response Source: UniProtKB-KW
Negative regulation of ubiquitin-protein transferase activity Source: UniProtKB
Notch signaling pathway Source: GO_Central
Positive regulation of chromatin binding Source: UniProtKB
Positive regulation of defense response to virus by host Source: UniProtKB
Positive regulation of double-strand break repair via nonhomologous end joining Source: UniProtKB
Positive regulation of NAD+ ADP-ribosyltransferase activity Source: UniProtKB
Positive regulation of protein binding Source: UniProtKB
Positive regulation of protein localization to early endosome Source: UniProtKB
Positive regulation of protein localization to nucleus Source: UniProtKB
Positive regulation of receptor catabolic process Source: UniProtKB
Positive regulation of transcription, DNA-templated Source: UniProtKB
Protein autoubiquitination Source: UniProtKB
Protein K48-linked ubiquitination Source: UniProtKB
Protein transport Source: UniProtKB-KW
Protein ubiquitination Source: GO_Central
Ubiquitin-dependent protein catabolic process Source: UniProtKB

Cellular Location

Nucleus; Lysosome membrane; Cytoplasm; Early endosome membrane. Translocates to the nucleus in response to IFNG or IFNB1 stimulation (PubMed:26479788). Localizes at sites of DNA damage in a PARP1-dependent manner (PubMed:23230272). Localization to early endosomes is increased upon CXCL12 stimulation where it co-localizes with ITCH, CXCL4, HGS and STAM (PubMed:24790097). A minor proportion localizes to lysosomes (PubMed:24790097).

PTM

Autoubiquitinated.