DTX3L

DTX3L
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3PG6
Identifiers
Aliases	DTX3L, BBAP, deltex 3 like, E3 ubiquitin ligase, deltex E3 ubiquitin ligase 3L, RNF143
External IDs	OMIM: 613143; MGI: 2656973; HomoloGene: 51375; GeneCards: DTX3L; OMA:DTX3L - orthologs
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q21.1 Start 122,564,338 bp[1] End 122,575,203 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16|16 B3 Start 35,746,881 bp[2] End 35,759,521 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of ileum pancreatic ductal cell lower lobe of lung decidua epithelium of nasopharynx pericardium mucosa of paranasal sinus germinal epithelium pylorus human penis Top expressed in mesenteric lymph nodes jejunum seminal vesicula submandibular gland blood lumbar spinal ganglion ileum cervix subcutaneous adipose tissue thymus More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding metal ion binding ubiquitin-protein transferase activity transferase activity enzyme inhibitor activity enzyme activator activity enzyme binding histone binding ubiquitin-like protein ligase binding STAT family protein binding Cellular component cytoplasm nucleus nucleoplasm cytosol early endosome lysosome lysosomal membrane endosome membrane early endosome membrane protein-containing complex Biological process histone monoubiquitination double-strand break repair DNA repair protein ubiquitination cellular response to DNA damage stimulus protein polyubiquitination positive regulation of defense response to virus by host endosome to lysosome transport positive regulation of protein binding histone H2A ubiquitination histone H2B ubiquitination positive regulation of chromatin binding positive regulation of transcription, DNA-templated negative regulation of ubiquitin-protein transferase activity protein autoubiquitination protein K48-linked ubiquitination positive regulation of protein localization to nucleus positive regulation of NAD+ ADP-ribosyltransferase activity positive regulation of protein localization to early endosome positive regulation of receptor catabolic process positive regulation of double-strand break repair via nonhomologous end joining immune system process protein transport innate immune response defense response to virus chromatin organization ubiquitin-dependent protein catabolic process Notch signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 151636 209200 Ensembl ENSG00000163840 ENSMUSG00000049502 UniProt Q8TDB6 Q3UIR3 RefSeq (mRNA) NM_138287 NM_001013371 RefSeq (protein) NP_612144 NP_001013389 Location (UCSC) Chr 3: 122.56 – 122.58 Mb Chr 16: 35.75 – 35.76 Mb PubMed search [3] [4]
Wikidata
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Deltex E3 ubiquitin ligase 3L is a protein that in humans is encoded by the DTX3L gene.^[5] It functions as an ubiquitin ligase (E3),^[6] and is over-expressed in chemotherapy-resistant lymphomas.^[7] It is a member of the DTX family of proteins.^[8] Among other roles it has a function in DNA damage repair.

It was discovered through two-hybrid screening during a search for binding partners of PARP9 (formerly BAL^[9]), a gene related to the risk of B-cell lymphoma. and was originally named BBAP (B-lymphoma- and BAL-associated protein).^[6]

DTX3L and PARP9 are both located in the same 48kB region of the genome, and are both regulated by a IFN-γ-responsive bidirectional promoter.^[10] DTX3L has a long N-terminus domain distinct from other DTX-family proteins that allows it form dimers with itself and other proteins.^[8] It has been found to be up-regulated by METTL3.^[8]

DTX3L functions as an ubiquitin ligase or E3.^[6] These proteins bind to ubiquitin-conjugating enzymes (E2s), and then transfer and bind the ubiquitin (activated by E1s) from the E2s to the target protein.^[11] Along with all other known DTX-family proteins (as of 2023), DTX3L is involved in the regulation of Notch signaling.^[8]

DTX3L also plays a role in DNA damage repair,^[8] which has been associated with its ability to selectively mono-ubiquitylate (bind one ubiquitin to) histone H4.^[7][8] It helps to protect cells exposed to DNA damaging agents.^[7]

DTX3L can form a complex with PARP9.^[12] This complex functions as a ubiquitin ligase and ubiquitinates both host histone H2BJ, to promote expression of interferon-stimulated genes, and viral 3C protease to disrupt viral assembly.^[12] This can help to control viral infection.^[12] PARP9 can also affect DXT3L's function in DNA damage repair.^[8] The DXT3L-PARP9 complex mediates mono-ADP-ribosylation of ubiquitin; this prevents it from being conjugated^[13] and inhibits DXT3L's function as an ubiquitin ligase.^[8] The NAD+ dependent binding of PARP9 to poly-ADP-ribose, instead, enhances the activity of DXT3L as a ubiquitin ligase.^[8][why?] DTX3L can also form a complex with DTX1.^[8]

DTX3L also affects signaling by inhibiting the sorting of the G-protein coupled receptor CXCR4 through the endosomes to degradation in the lysosomes.^[14] When CXCR4 is activated, DXT3L localizes to early endosomes and inhibits the E3 ubiquitin ligase atrophin-1 interacting protein 4.^[14] This reduces the extent to which the protein ESCRT-0 is ubiquitinated, which reduces its ability to sort CXCR4 into the lysosomes.^[14] The implications of this effect (as of 2023) in cancer biology are unknown.^[8]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.