DTX3L
entrez
151636
canonical
uniprot
Q8TDB6
canonical
ensembl
ENSG00000163840
resolver
ensp
ENSP00000296161
resolver
genesymbol
DTX3L
resolver
genesymbol_syn
BBAP
resolver
hgnc
HGNC:30323
resolver
uniprot
B3KWH6
resolver
uniprot
Q53ZZ3
resolver
uniprot
Q5MJP7
resolver
uniprot_entry
DTX3L_HUMAN
resolver
uniprot_sec
B3KWH6
resolver
uniprot_sec
Q53ZZ3
resolver
uniprot_sec
Q5MJP7
resolver
activity_regulation
ACTIVITY REGULATION: Binding to PARP9 enhances DTX3L catalytic activity. {ECO:0000269|PubMed:28525742}.
uniprot
proteins
amino_acid_sequence
MASHLRPPSPLLVRVYKSGPRVRRKLESYFQSSKSSGGGECTVSTQEHEAPGTFRVEFSERAAKERVLKKGEHQILVDEKPVPIFLVPTENSIKKNTRPQISSLTQSQAETPSGDMHQHEGHIPNAVDSCLQKIFLTVTADLNCNLFSKEQRAYITTLCPSIRKMEGHDGIEKVCGDFQDIERIHQFLSEQFLESEQKQQFSPSMTERKPLSQQERDSCISPSEPETKAEQKSNYFEVPLPYFEYFKYICPDKINSIEKRFGVNIEIQESSPNMVCLDFTSSRSGDLEAARESFASEFQKNTEPLKQECVSLADSKQANKFKQELNHQFTKLLIKEKGGELTLLGTQDDISAAKQKISEAFVKIPVKLFAANYMMNVIEVDSAHYKLLETELLQEISEIEKRYDICSKVSEKGQKTCILFESKDRQVDLSVHAYASFIDAFQHASCQLMREVLLLKSLGKERKHLHQTKFADDFRKRHPNVHFVLNQESMTLTGLPNHLAKAKQYVLKGGGMSSLAGKKLKEGHETPMDIDSDDSKAASPPLKGSVSSEASELDKKEKGICVICMDTISNKKVLPKCKHEFCAPCINKAMSYKPICPTCQTSYGIQKGNQPEGSMVFTVSRDSLPGYESFGTIVITYSMKAGIQTEEHPNPGKRYPGIQRTAYLPDNKEGRKVLKLLYRAFDQKLIFTVGYSRVLGVSDVITWNDIHHKTSRFGGPEMYGYPDPSYLKRVKEELKAKGIE
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
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:23230272, PubMed:26479788). 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 proteasomal-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}.
uniprot
proteins
mass_dalton
83554
uniprot
proteins
mutagenesis
MUTAGEN 561..564; /note="CVIC->SVIS: Loss of catalytic activity. Loss of histone H2B ubiquitination. No effect on STAT1 phosphorylation and on the interaction with PARP9 and STAT1."; /evidence="ECO:0000269|PubMed:26479788"; MUTAGEN 561; /note="C->A: Loss of catalytic activity but does not affect its capacity to inhibit ITCH catalytic activity; when associated with A-596 and A-599."; /evidence="ECO:0000269|PubMed:24790097"; MUTAGEN 596; /note="C->A: Loss of catalytic activity but does not affect its capacity to inhibit ITCH catalytic activity; when associated with A-561 and A-599."; /evidence="ECO:0000269|PubMed:24790097"; MUTAGEN 599; /note="C->A: Loss of catalytic activity but does not affect its capacity to inhibit ITCH catalytic activity; when associated with A-561 and A-596."; /evidence="ECO:0000269|PubMed:24790097
uniprot
proteins
pathway_participation
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}.
uniprot
proteins
post_translational_modification
PTM: Autoubiquitinated. {ECO:0000269|PubMed:24790097}.
uniprot
proteins
protein_family
Deltex family
uniprot
proteins
pubmed
12670957
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16809771
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19818714
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
22411408
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23230272
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24790097
uniprot
proteins
pubmed
26479788
uniprot
proteins
pubmed
28525742
uniprot
proteins
sequence_length
740
uniprot
proteins
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}.
uniprot
proteins