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Protein

E3 ubiquitin-protein ligase DTX3L

Gene

Dtx3l

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 HIST1H2BH/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.By similarity

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.By similarity

Enzyme regulationi

Binding to PARP9 enhances DTX3L catalytic activity.By similarity

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.By similarity
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri569 – 608RING-typePROSITE-ProRule annotationAdd BLAST40

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, Transferase
Biological processAntiviral defense, DNA damage, DNA repair, Immunity, Innate immunity, Protein transport, Transport, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-983168. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase DTX3L (EC:2.3.2.27By similarity)
Alternative name(s):
Protein deltex-3-like
RING-type E3 ubiquitin transferase DTX3LCurated
Gene namesi
Name:Dtx3l
Synonyms:Bbap
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:2656973. Dtx3l.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endosome, Lysosome, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00003904702 – 748E3 ubiquitin-protein ligase DTX3LAdd BLAST747

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei9PhosphoserineBy similarity1
Modified residuei215PhosphoserineBy similarity1
Modified residuei536PhosphoserineBy similarity1

Post-translational modificationi

Autoubiquitinated.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ3UIR3.
MaxQBiQ3UIR3.
PaxDbiQ3UIR3.
PeptideAtlasiQ3UIR3.
PRIDEiQ3UIR3.

PTM databases

iPTMnetiQ3UIR3.
PhosphoSitePlusiQ3UIR3.

Expressioni

Developmental stagei

Developmentally regulated. Expressed prominently in the thymus and specific regions of the brain, and more weakly expressed in the gut. In adults, highly expressed in the thymus and intestine.1 Publication

Gene expression databases

BgeeiENSMUSG00000049502.
GenevisibleiQ3UIR3. MM.

Interactioni

Subunit structurei

Homodimer and heterodimer. Can heterodimerize with DTX1, enhancing its ubiquitin ligase activity in vitro. Interacts (via N-terminus) with ADP ribosyltransferase PARP9/BAL1 (via PARP catalytic domain) forming a stable complex; the interaction is required to activate PARP9 but is dispensable for DTX3L catalytic activity. Forms a complex with STAT1 and PARP9 independently of IFNB1 or IFNG-mediated STAT1 'Tyr-701' phosphorylation. Found in a complex with PARP9, STAT1 and HIST1H2BH. Found in a complex with E3 ligase ITCH and ESCRT-0 components HGS and STAM. Interacts (via C-terminus) with ITCH; the interaction is increased upon CXCL12 stimulation and inhibits ITCH catalytic activity; the interaction is direct. Interacts with HGS and STAM; the interaction brings together HGS and STAM and promotes their recruitment to early endosomes.By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ3UIR3. 4 interactors.
MINTiMINT-1858179.
STRINGi10090.ENSMUSP00000080601.

Structurei

3D structure databases

ProteinModelPortaliQ3UIR3.
SMRiQ3UIR3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the Deltex family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri569 – 608RING-typePROSITE-ProRule annotationAdd BLAST40

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IEH5. Eukaryota.
ENOG4111QEI. LUCA.
GeneTreeiENSGT00440000035370.
HOGENOMiHOG000112292.
HOVERGENiHBG051417.
InParanoidiQ3UIR3.
KOiK06058.
OMAiCNLFSKE.
OrthoDBiEOG091G06M5.
PhylomeDBiQ3UIR3.
TreeFamiTF325526.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiView protein in InterPro
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
SMARTiView protein in SMART
SM00184. RING. 1 hit.
PROSITEiView protein in PROSITE
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q3UIR3-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MASSPDPPSP LLVRLRESIP KAHRKLEIYF QSRASGGGEC SVQPVGPSAP
60 70 80 90 100
DTYEVKFLKK ADKEKVLKKS EHEMLVHNKP VTIVLETTKK PVEDLRPRLP
110 120 130 140 150
SLTQPVETPS SRPPSLTGSL DEALCDDIHP QDGLVSNSVD SVVQKIFLAV
160 170 180 190 200
TAELNCDLLS KEQRASITTV CPHIIKSMEG SDGIKKVCGN FKDIEKIHHF
210 220 230 240 250
LSEQLLEREQ KRKGSEQKRK CAPQKHTPPD VEREPPDQSS IQVPVLLLEY
260 270 280 290 300
FKHVNPGRLE FIEYKFGVNI EIQASSPNMV TVGFTSSPFG NVEEASQSFV
310 320 330 340 350
RDFQKCSQSL KQDCISLEEH QRAKEVRQEL SRCFPKLLIK GQGRTLTLLG
360 370 380 390 400
SPADISAATE KVSQGLGLRP VKITASGYTT GIEVDSTRFK LLEPELLQEI
410 420 430 440 450
SEIEQKFNTR GKVQEKGQKT CILFVPKDKD LDLSVQSYTG FTDAFQRATW
460 470 480 490 500
QLRTEVLSLK GLGKERARLH NTKFADNFKK EHPNVHFVTS QESVTLTGLP
510 520 530 540 550
HHLAQAMQYV SKRMGLAPSS GEKLAMDQET PMEISSSDPH GDQQENAALP
560 570 580 590 600
APRGTSSSPA ASKGTEDYCV ICMDTISNKH VLPKCKHEFC TSCISKAMLI
610 620 630 640 650
KPVCPVCLTS YGIQKGNQPE GTMSYSTQKG SLPGYEGCGT IVINYEIKDG
660 670 680 690 700
IQTKEHPNPG KAYHGTRRTA YLPDNTEGRK VLDLLHEAFK HRLTFTIGYS
710 720 730 740
RATGVSDVIT WNDIHHKTSK FGGPANFGYP DPDYLKRVKE ELKAKGIE
Length:748
Mass (Da):83,044
Last modified:October 11, 2005 - v1
Checksum:iC9CD9704F66DCF1B
GO
Isoform 2 (identifier: Q3UIR3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     654-748: KEHPNPGKAY...KEELKAKGIE → VSVPEEHGFL...NDFPRKSFIL

Note: No experimental confirmation available.
Show »
Length:691
Mass (Da):76,579
Checksum:i782067CD356EA5F6
GO

Sequence cautioni

The sequence BAC41115 differs from that shown. Reason: Frameshift at position 746.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_038533654 – 748KEHPN…AKGIE → VSVPEEHGFLFAMLELPKSN EASYSLLDNDFPRKSFIL in isoform 2. 1 PublicationAdd BLAST95

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK146802 mRNA. Translation: BAE27443.1.
AK090152 mRNA. Translation: BAC41115.1. Frameshift.
CH466521 Genomic DNA. Translation: EDK97899.1.
BC137694 mRNA. Translation: AAI37695.1.
CCDSiCCDS37325.1. [Q3UIR3-1]
RefSeqiNP_001013389.2. NM_001013371.2. [Q3UIR3-1]
UniGeneiMm.390852.

Genome annotation databases

EnsembliENSMUST00000081933; ENSMUSP00000080601; ENSMUSG00000049502. [Q3UIR3-1]
ENSMUST00000114885; ENSMUSP00000110535; ENSMUSG00000049502. [Q3UIR3-2]
GeneIDi209200.
KEGGimmu:209200.
UCSCiuc007zbv.1. mouse. [Q3UIR3-1]
uc007zbw.1. mouse. [Q3UIR3-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiDTX3L_MOUSE
AccessioniPrimary (citable) accession number: Q3UIR3
Secondary accession number(s): Q8BN11
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 2009
Last sequence update: October 11, 2005
Last modified: November 22, 2017
This is version 109 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families