Protein: E3 ubiquitin-protein ligase DTX3L (EC 2.3.2.27) (B-lymphoma- and BAL-associated protein) (Protein deltex-3-like) (RING-type E3 ubiquitin transferase DTX3L) (Rhysin-2) (Rhysin2) (Q8TDB6)
Organism: Homo sapiens (Human)
Function: E3 ubiquitin-protein ligase which, in association with ADP-ribosyltransferase PARP9, plays a role in DNA damage repair and in interferon-mediated antiviral responses. Monoubiquitinates several histones, including histone H2A, H2B, H3 and H4. In response to DNA damage, mediates monoubiquitination of 'Lys-91' of histone H4 (H4K91ub1). 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). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites. 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. 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. In addition, required for the recruitment of HGS and STAM to early endosomes. 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.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:26479788}. Nucleus {ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26479788}. Early endosome membrane {ECO:0000269|PubMed:24790097}; Peripheral membrane protein {ECO:0000305|PubMed:24790097}; Cytoplasmic side {ECO:0000305|PubMed:24790097}. Lysosome membrane {ECO:0000269|PubMed:24790097}; Peripheral membrane protein {ECO:0000305|PubMed:24790097}; Cytoplasmic side {ECO:0000305|PubMed:24790097}. Note=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). {ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:26479788}.
Interaction partners:
- Protein mono-ADP-ribosyltransferase PARP9
- Protein mono-ADP-ribosyltransferase PARP14
- Protein mono-ADP-ribosyltransferase PARP15
- Signal transducer and activator of transcription 1-alpha/beta
- Neurogenic locus notch homolog protein 2
- Ubiquitin-conjugating enzyme E2 D1
- E3 ubiquitin-protein ligase DTX1
- Interferon-induced GTP-binding protein Mx1
- Neurogenic locus notch homolog protein 1
- Interferon-induced protein 44-like
Sequence:
MASHLRPPSPLLVRVYKSGPRVRRKLESYFQSSKSSGGGECTVSTQEHEAPGTFRVEFSERAAKERVLKKGEHQILVDEKPVPIFLVPTENSIKKNTRPQISSLTQSQAETPSGDMHQHEGHIPNAVDSCLQKIFLTVTADLNCNLFSKEQRAYITTLCPSIRKMEGHDGIEKVCGDFQDIERIHQFLSEQFLESEQKQQFSPSMTERKPLSQQERDSCISPSEPETKAEQKSNYFEVPLPYFEYFKYICPDKINSIEKRFGVNIEIQESSPNMVCLDFTSSRSGDLEAARESFASEFQKNTEPLKQECVSLADSKQANKFKQELNHQFTKLLIKEKGGELTLLGTQDDISAAKQKISEAFVKIPVKLFAANYMMNVIEVDSAHYKLLETELLQEISEIEKRYDICSKVSEKGQKTCILFESKDRQVDLSVHAYASFIDAFQHASCQLMREVLLLKSLGKERKHLHQTKFADDFRKRHPNVHFVLNQESMTLTGLPNHLAKAKQYVLKGGGMSSLAGKKLKEGHETPMDIDSDDSKAASPPLKGSVSSEASELDKKEKGICVICMDTISNKKVLPKCKHEFCAPCINKAMSYKPICPTCQTSYGIQKGNQPEGSMVFTVSRDSLPGYESFGTIVITYSMKAGIQTEEHPNPGKRYPGIQRTAYLPDNKEGRKVLKLLYRAFDQKLIFTVGYSRVLGVSDVITWNDIHHKTSRFGGPEMYGYPDPSYLKRVKEELKAKGIE