DTX3L_MOUSE
ID DTX3L_MOUSE Reviewed; 748 AA.
AC Q3UIR3; Q8BN11;
DT 15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=E3 ubiquitin-protein ligase DTX3L;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q8TDB6};
DE AltName: Full=Protein deltex-3-like;
DE AltName: Full=RING-type E3 ubiquitin transferase DTX3L {ECO:0000305};
GN Name=Dtx3l; Synonyms=Bbap;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Amnion, and Lymph node;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP DEVELOPMENTAL STAGE.
RX PubMed=18069692; DOI=10.1002/dvdy.21399;
RA Hakme A., Huber A., Dolle P., Schreiber V.;
RT "The macroPARP genes Parp-9 and Parp-14 are developmentally and
RT differentially regulated in mouse tissues.";
RL Dev. Dyn. 237:209-215(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Liver, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which, in association with ADP-
CC ribosyltransferase PARP9, plays a role in DNA damage repair and in
CC interferon-mediated antiviral responses. Monoubiquitinates several
CC histones, including histone H2A, H2B, H3 and H4. In response to DNA
CC damage, mediates monoubiquitination of 'Lys-91' of histone H4
CC (H4K91ub1). The exact role of H4K91ub1 in DNA damage response is still
CC unclear but it may function as a licensing signal for additional
CC histone H4 post-translational modifications such as H4 'Lys-20'
CC methylation (H4K20me). PARP1-dependent PARP9-DTX3L-mediated
CC ubiquitination promotes the rapid and specific recruitment of
CC 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites. By
CC monoubiquitinating histone H2B H2BC9/H2BJ and thereby promoting
CC chromatin remodeling, positively regulates STAT1-dependent interferon-
CC stimulated gene transcription and thus STAT1-mediated control of viral
CC replication. Independently of its catalytic activity, promotes the
CC sorting of chemokine receptor CXCR4 from early endosome to lysosome
CC following CXCL12 stimulation by reducing E3 ligase ITCH activity and
CC thus ITCH-mediated ubiquitination of endosomal sorting complex required
CC for transport ESCRT-0 components HGS and STAM. In addition, required
CC for the recruitment of HGS and STAM to early endosomes.
CC {ECO:0000250|UniProtKB:Q8TDB6}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q8TDB6};
CC -!- ACTIVITY REGULATION: Binding to PARP9 enhances DTX3L catalytic
CC activity. {ECO:0000250|UniProtKB:Q8TDB6}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q8TDB6}.
CC -!- SUBUNIT: Homodimer and heterodimer. Can heterodimerize with DTX1,
CC enhancing its ubiquitin ligase activity in vitro. Interacts (via N-
CC terminus) with ADP ribosyltransferase PARP9/BAL1 (via PARP catalytic
CC domain) forming a stable complex; the interaction is required to
CC activate PARP9 but is dispensable for DTX3L catalytic activity. Forms a
CC complex with STAT1 and PARP9 independently of IFNB1 or IFNG-mediated
CC STAT1 'Tyr-701' phosphorylation. Found in a complex with PARP9, STAT1
CC and H2BC9. Found in a complex with E3 ligase ITCH and ESCRT-0
CC components HGS and STAM. Interacts (via C-terminus) with ITCH; the
CC interaction is increased upon CXCL12 stimulation and inhibits ITCH
CC catalytic activity; the interaction is direct. Interacts with HGS and
CC STAM; the interaction brings together HGS and STAM and promotes their
CC recruitment to early endosomes. {ECO:0000250|UniProtKB:Q8TDB6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8TDB6}. Nucleus
CC {ECO:0000250|UniProtKB:Q8TDB6}. Early endosome membrane
CC {ECO:0000250|UniProtKB:Q8TDB6}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q8TDB6}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q8TDB6}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q8TDB6}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q8TDB6}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q8TDB6}. Note=Translocates to the nucleus in
CC response to IFNG or IFNB1 stimulation. Localizes at sites of DNA damage
CC in a PARP1-dependent manner. Localization to early endosomes is
CC increased upon CXCL12 stimulation where it co-localizes with ITCH,
CC CXCL4, HGS and STAM. A minor proportion localizes to lysosomes.
CC {ECO:0000250|UniProtKB:Q8TDB6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3UIR3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UIR3-2; Sequence=VSP_038533;
CC -!- DEVELOPMENTAL STAGE: Developmentally regulated. Expressed prominently
CC in the thymus and specific regions of the brain, and more weakly
CC expressed in the gut. In adults, highly expressed in the thymus and
CC intestine. {ECO:0000269|PubMed:18069692}.
CC -!- PTM: Autoubiquitinated. {ECO:0000250|UniProtKB:Q8TDB6}.
CC -!- SIMILARITY: Belongs to the Deltex family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC41115.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK146802; BAE27443.1; -; mRNA.
DR EMBL; AK090152; BAC41115.1; ALT_FRAME; mRNA.
DR EMBL; CH466521; EDK97899.1; -; Genomic_DNA.
DR EMBL; BC137694; AAI37695.1; -; mRNA.
DR CCDS; CCDS37325.1; -. [Q3UIR3-1]
DR RefSeq; NP_001013389.2; NM_001013371.2. [Q3UIR3-1]
DR AlphaFoldDB; Q3UIR3; -.
DR SMR; Q3UIR3; -.
DR IntAct; Q3UIR3; 2.
DR MINT; Q3UIR3; -.
DR STRING; 10090.ENSMUSP00000080601; -.
DR iPTMnet; Q3UIR3; -.
DR PhosphoSitePlus; Q3UIR3; -.
DR SwissPalm; Q3UIR3; -.
DR EPD; Q3UIR3; -.
DR jPOST; Q3UIR3; -.
DR MaxQB; Q3UIR3; -.
DR PaxDb; Q3UIR3; -.
DR PeptideAtlas; Q3UIR3; -.
DR PRIDE; Q3UIR3; -.
DR ProteomicsDB; 275408; -. [Q3UIR3-1]
DR ProteomicsDB; 275409; -. [Q3UIR3-2]
DR Antibodypedia; 2147; 150 antibodies from 28 providers.
DR DNASU; 209200; -.
DR Ensembl; ENSMUST00000081933; ENSMUSP00000080601; ENSMUSG00000049502. [Q3UIR3-1]
DR Ensembl; ENSMUST00000114885; ENSMUSP00000110535; ENSMUSG00000049502. [Q3UIR3-2]
DR GeneID; 209200; -.
DR KEGG; mmu:209200; -.
DR UCSC; uc007zbv.1; mouse. [Q3UIR3-1]
DR UCSC; uc007zbw.1; mouse. [Q3UIR3-2]
DR CTD; 151636; -.
DR MGI; MGI:2656973; Dtx3l.
DR VEuPathDB; HostDB:ENSMUSG00000049502; -.
DR eggNOG; ENOG502RGAW; Eukaryota.
DR GeneTree; ENSGT00940000154578; -.
DR HOGENOM; CLU_024295_0_0_1; -.
DR InParanoid; Q3UIR3; -.
DR OMA; KVCGDFQ; -.
DR OrthoDB; 143182at2759; -.
DR PhylomeDB; Q3UIR3; -.
DR TreeFam; TF325526; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 209200; 3 hits in 79 CRISPR screens.
DR ChiTaRS; Dtx3l; mouse.
DR PRO; PR:Q3UIR3; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q3UIR3; protein.
DR Bgee; ENSMUSG00000049502; Expressed in small intestine Peyer's patch and 186 other tissues.
DR Genevisible; Q3UIR3; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0008047; F:enzyme activator activity; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0004857; F:enzyme inhibitor activity; ISO:MGI.
DR GO; GO:0042393; F:histone binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0097677; F:STAT family protein binding; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; ISO:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0008333; P:endosome to lysosome transport; ISO:MGI.
DR GO; GO:0033522; P:histone H2A ubiquitination; ISO:MGI.
DR GO; GO:0033523; P:histone H2B ubiquitination; ISO:MGI.
DR GO; GO:0010390; P:histone monoubiquitination; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; ISO:MGI.
DR GO; GO:0007219; P:Notch signaling pathway; IBA:GO_Central.
DR GO; GO:0035563; P:positive regulation of chromatin binding; ISO:MGI.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; ISO:MGI.
DR GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; ISO:MGI.
DR GO; GO:1901666; P:positive regulation of NAD+ ADP-ribosyltransferase activity; ISO:MGI.
DR GO; GO:0032092; P:positive regulation of protein binding; ISO:MGI.
DR GO; GO:1902966; P:positive regulation of protein localization to early endosome; ISO:MGI.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:MGI.
DR GO; GO:2000646; P:positive regulation of receptor catabolic process; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0051865; P:protein autoubiquitination; ISO:MGI.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISO:MGI.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISO:MGI.
DR CDD; cd09633; Deltex_C; 1.
DR CDD; cd16712; RING-HC_DTX3L; 1.
DR Gene3D; 3.30.390.130; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR039396; Deltex_C.
DR InterPro; IPR039399; Deltex_C_sf.
DR InterPro; IPR039398; Deltex_fam.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR042843; TX3L_RING-HC.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR12622; PTHR12622; 1.
DR Pfam; PF18102; DTC; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Antiviral defense; Chromatin regulator;
KW Cytoplasm; DNA damage; DNA repair; Endosome; Immunity; Innate immunity;
KW Lysosome; Membrane; Metal-binding; Nucleus; Phosphoprotein;
KW Protein transport; Reference proteome; Transferase; Transport;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q8TDB6"
FT CHAIN 2..748
FT /note="E3 ubiquitin-protein ligase DTX3L"
FT /id="PRO_0000390470"
FT ZN_FING 569..608
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 94..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 209..238
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 528..562
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 103..117
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 209..233
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 530..562
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q8TDB6"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TDB6"
FT MOD_RES 215
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TDB6"
FT MOD_RES 536
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TDB6"
FT VAR_SEQ 654..748
FT /note="KEHPNPGKAYHGTRRTAYLPDNTEGRKVLDLLHEAFKHRLTFTIGYSRATGV
FT SDVITWNDIHHKTSKFGGPANFGYPDPDYLKRVKEELKAKGIE -> VSVPEEHGFLFA
FT MLELPKSNEASYSLLDNDFPRKSFIL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038533"
SQ SEQUENCE 748 AA; 83044 MW; C9CD9704F66DCF1B CRC64;
MASSPDPPSP LLVRLRESIP KAHRKLEIYF QSRASGGGEC SVQPVGPSAP DTYEVKFLKK
ADKEKVLKKS EHEMLVHNKP VTIVLETTKK PVEDLRPRLP SLTQPVETPS SRPPSLTGSL
DEALCDDIHP QDGLVSNSVD SVVQKIFLAV TAELNCDLLS KEQRASITTV CPHIIKSMEG
SDGIKKVCGN FKDIEKIHHF LSEQLLEREQ KRKGSEQKRK CAPQKHTPPD VEREPPDQSS
IQVPVLLLEY FKHVNPGRLE FIEYKFGVNI EIQASSPNMV TVGFTSSPFG NVEEASQSFV
RDFQKCSQSL KQDCISLEEH QRAKEVRQEL SRCFPKLLIK GQGRTLTLLG SPADISAATE
KVSQGLGLRP VKITASGYTT GIEVDSTRFK LLEPELLQEI SEIEQKFNTR GKVQEKGQKT
CILFVPKDKD LDLSVQSYTG FTDAFQRATW QLRTEVLSLK GLGKERARLH NTKFADNFKK
EHPNVHFVTS QESVTLTGLP HHLAQAMQYV SKRMGLAPSS GEKLAMDQET PMEISSSDPH
GDQQENAALP APRGTSSSPA ASKGTEDYCV ICMDTISNKH VLPKCKHEFC TSCISKAMLI
KPVCPVCLTS YGIQKGNQPE GTMSYSTQKG SLPGYEGCGT IVINYEIKDG IQTKEHPNPG
KAYHGTRRTA YLPDNTEGRK VLDLLHEAFK HRLTFTIGYS RATGVSDVIT WNDIHHKTSK
FGGPANFGYP DPDYLKRVKE ELKAKGIE
