Overview
| Uniprot ID | Q8TDB6 |
|---|
| Protein Name | E3 ubiquitin-protein ligase DTX3L |
|---|
| Gene Name | DTX3L |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 25 |
SGPRVRRKLESYFQS |
| 253 |
FKYICPDKINSIEKR |
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)
Protein Sequence
10
MASHLRPPSP
20
LLVRVYKSGP
30
RVRRKLESYF
40
QSSKSSGGGE
50
CTVSTQEHEA
60
PGTFRVEFSE
70
RAAKERVLKK
80
GEHQILVDEK
90
PVPIFLVPTE
100
NSIKKNTRPQ
110
ISSLTQSQAE
120
TPSGDMHQHE
130
GHIPNAVDSC
140
LQKIFLTVTA
150
DLNCNLFSKE
160
QRAYITTLCP
170
SIRKMEGHDG
180
IEKVCGDFQD
190
IERIHQFLSE
200
QFLESEQKQQ
210
FSPSMTERKP
220
LSQQERDSCI
230
SPSEPETKAE
240
QKSNYFEVPL
250
PYFEYFKYIC
260
PDKINSIEKR
270
FGVNIEIQES
280
SPNMVCLDFT
290
SSRSGDLEAA
300
RESFASEFQK
310
NTEPLKQECV
320
SLADSKQANK
330
FKQELNHQFT
340
KLLIKEKGGE
350
LTLLGTQDDI
360
SAAKQKISEA
370
FVKIPVKLFA
380
ANYMMNVIEV
390
DSAHYKLLET
400
ELLQEISEIE
410
KRYDICSKVS
420
EKGQKTCILF
430
ESKDRQVDLS
440
VHAYASFIDA
450
FQHASCQLMR
460
EVLLLKSLGK
470
ERKHLHQTKF
480
ADDFRKRHPN
490
VHFVLNQESM
500
TLTGLPNHLA
510
KAKQYVLKGG
520
GMSSLAGKKL
530
KEGHETPMDI
540
DSDDSKAASP
550
PLKGSVSSEA
560
SELDKKEKGI
570
CVICMDTISN
580
KKVLPKCKHE
590
FCAPCINKAM
600
SYKPICPTCQ
610
TSYGIQKGNQ
620
PEGSMVFTVS
630
RDSLPGYESF
640
GTIVITYSMK
650
AGIQTEEHPN
660
PGKRYPGIQR
670
TAYLPDNKEG
680
RKVLKLLYRA
690
FDQKLIFTVG
700
YSRVLGVSDV
710
ITWNDIHHKT
720
SRFGGPEMYG
730
YPDPSYLKRV
740
KEELKAKGIE
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0031901 |
early endosome membrane |
| Cellular Component |
GO:0005765 |
lysosomal membrane |
| Cellular Component |
GO:0005764 |
lysosome |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0032991 |
protein-containing complex |
| Molecular Function |
GO:0019899 |
enzyme binding |
| Molecular Function |
GO:0004857 |
enzyme inhibitor activity |
| Molecular Function |
GO:0042393 |
histone binding |
| Molecular Function |
GO:0141000 |
histone H4K91 ubiquitin ligase activity |
| Molecular Function |
GO:0140852 |
histone ubiquitin ligase activity |
| Molecular Function |
GO:0140768 |
protein ADP-ribosyltransferase-substrate adaptor activity |
| Molecular Function |
GO:0097677 |
STAT family protein binding |
| Molecular Function |
GO:0061630 |
ubiquitin protein ligase activity |
| Molecular Function |
GO:0044389 |
ubiquitin-like protein ligase binding |
| Molecular Function |
GO:0004842 |
ubiquitin-protein transferase activity |
| Molecular Function |
GO:0008270 |
zinc ion binding |
| Biological Process |
GO:0051607 |
defense response to virus |
| Biological Process |
GO:0000077 |
DNA damage checkpoint signaling |
| Biological Process |
GO:0140861 |
DNA repair-dependent chromatin remodeling |
| Biological Process |
GO:0006302 |
double-strand break repair |
| Biological Process |
GO:0008333 |
endosome to lysosome transport |
| Biological Process |
GO:0045087 |
innate immune response |
| Biological Process |
GO:0051444 |
negative regulation of ubiquitin-protein transferase activity |
| Biological Process |
GO:0007219 |
Notch signaling pathway |
| Biological Process |
GO:0035563 |
positive regulation of chromatin binding |
| Biological Process |
GO:0002230 |
positive regulation of defense response to virus by host |
| Biological Process |
GO:0045893 |
positive regulation of DNA-templated transcription |
| Biological Process |
GO:0032092 |
positive regulation of protein binding |
| Biological Process |
GO:1902966 |
positive regulation of protein localization to early endosome |
| Biological Process |
GO:1900182 |
positive regulation of protein localization to nucleus |
| Biological Process |
GO:2000646 |
positive regulation of receptor catabolic process |
| Biological Process |
GO:0051865 |
protein autoubiquitination |
| Biological Process |
GO:0070936 |
protein K48-linked ubiquitination |
| Biological Process |
GO:0015031 |
protein transport |
| Biological Process |
GO:0016567 |
protein ubiquitination |
| Biological Process |
GO:0006511 |
ubiquitin-dependent protein catabolic process |
Reference
[1] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.