| IED ID | IndEnz0002016447 |
| Enzyme Type ID | protease016447 |
| Protein Name |
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 |
| Gene Name | DTX3L BBAP |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MASHLRPPSPLLVRVYKSGPRVRRKLESYFQSSKSSGGGECTVSTQEHEAPGTFRVEFSERAAKERVLKKGEHQILVDEKPVPIFLVPTENSIKKNTRPQISSLTQSQAETPSGDMHQHEGHIPNAVDSCLQKIFLTVTADLNCNLFSKEQRAYITTLCPSIRKMEGHDGIEKVCGDFQDIERIHQFLSEQFLESEQKQQFSPSMTERKPLSQQERDSCISPSEPETKAEQKSNYFEVPLPYFEYFKYICPDKINSIEKRFGVNIEIQESSPNMVCLDFTSSRSGDLEAARESFASEFQKNTEPLKQECVSLADSKQANKFKQELNHQFTKLLIKEKGGELTLLGTQDDISAAKQKISEAFVKIPVKLFAANYMMNVIEVDSAHYKLLETELLQEISEIEKRYDICSKVSEKGQKTCILFESKDRQVDLSVHAYASFIDAFQHASCQLMREVLLLKSLGKERKHLHQTKFADDFRKRHPNVHFVLNQESMTLTGLPNHLAKAKQYVLKGGGMSSLAGKKLKEGHETPMDIDSDDSKAASPPLKGSVSSEASELDKKEKGICVICMDTISNKKVLPKCKHEFCAPCINKAMSYKPICPTCQTSYGIQKGNQPEGSMVFTVSRDSLPGYESFGTIVITYSMKAGIQTEEHPNPGKRYPGIQRTAYLPDNKEGRKVLKLLYRAFDQKLIFTVGYSRVLGVSDVITWNDIHHKTSRFGGPEMYGYPDPSYLKRVKEELKAKGIE |
| Enzyme Length | 740 |
| Uniprot Accession Number | Q8TDB6 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: Binding to PARP9 enhances DTX3L catalytic activity. {ECO:0000269|PubMed:28525742}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; Evidence={ECO:0000269|PubMed:12670957, ECO:0000269|PubMed:19818714, ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28525742}; |
| DNA Binding | |
| EC Number | 2.3.2.27 |
| Enzyme Function | 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 (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). {ECO:0000269|PubMed:12670957, ECO:0000269|PubMed:19818714, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28525742}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:12670957, ECO:0000269|PubMed:19818714, ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28525742}. |
| nucleotide Binding | |
| Features | Alternative sequence (1); Beta strand (7); Chain (1); Compositional bias (2); Helix (3); Initiator methionine (1); Modified residue (6); Mutagenesis (4); Natural variant (3); Region (3); Sequence conflict (1); Turn (1); Zinc finger (1) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Antiviral defense;Chromatin regulator;Cytoplasm;DNA damage;DNA repair;Endosome;Host-virus interaction;Immunity;Innate immunity;Lysosome;Membrane;Metal-binding;Nucleus;Phosphoprotein;Protein transport;Reference proteome;Transferase;Transport;Ubl conjugation;Ubl conjugation pathway;Zinc;Zinc-finger |
| Interact With | Q9NZD8; P61086 |
| Induction | INDUCTION: Induced by IFNG (PubMed:16809771, PubMed:26479788). Induced by IFNB1 (PubMed:26479788). {ECO:0000269|PubMed:16809771, ECO:0000269|PubMed:26479788}. |
| Subcellular Location | 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}. |
| Modified Residue | MOD_RES 2; /note="N-acetylalanine"; /evidence="ECO:0007744|PubMed:19369195"; MOD_RES 9; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"; MOD_RES 202; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 221; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 532; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"; MOD_RES 539; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:24275569" |
| Post Translational Modification | PTM: Autoubiquitinated. {ECO:0000269|PubMed:24790097}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 3PG6; |
| Mapped Pubmed ID | 12646216; 16954532; 18618715; 19028597; 19489725; 19549727; 19874575; 22493164; 23764002; 24886089; 25416956; 28627634; 28653881; 34358560; |
| Motif | |
| Gene Encoded By | |
| Mass | 83,554 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |