DTX3L_HUMAN
ID DTX3L_HUMAN Reviewed; 740 AA.
AC Q8TDB6; B3KWH6; Q53ZZ3; Q5MJP7;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=E3 ubiquitin-protein ligase DTX3L;
DE EC=2.3.2.27 {ECO:0000269|PubMed:12670957, ECO:0000269|PubMed:19818714, ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28525742};
DE AltName: Full=B-lymphoma- and BAL-associated protein;
DE AltName: Full=Protein deltex-3-like;
DE AltName: Full=RING-type E3 ubiquitin transferase DTX3L {ECO:0000305};
DE AltName: Full=Rhysin-2;
DE Short=Rhysin2;
GN Name=DTX3L; Synonyms=BBAP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP PATHWAY, SUBUNIT, AND INTERACTION WITH PARP9 AND DTX1.
RX PubMed=12670957; DOI=10.1074/jbc.m301157200;
RA Takeyama K., Aguiar R.C.T., Gu L., He C., Freeman G.J., Kutok J.L.,
RA Aster J.C., Shipp M.A.;
RT "The BAL-binding protein BBAP and related Deltex family members exhibit
RT ubiquitin-protein isopeptide ligase activity.";
RL J. Biol. Chem. 278:21930-21937(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Roberts R.C., Kendrick-Jones J., Jensen O.N.;
RT "Rhysin2 is a novel protein identified by mass spectrometry found in a
RT myosin VI-containing complex isolated by immunoprecipitation.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LYS-425.
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Lin L., Nong W., Li H., Ke R., Zhong G., Zhou G., Shen C., Yang S.;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT LYS-425.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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 [7]
RP SUBCELLULAR LOCATION, AND INDUCTION BY IFNG.
RX PubMed=16809771; DOI=10.1128/mcb.02351-05;
RA Juszczynski P., Kutok J.L., Li C., Mitra J., Aguiar R.C.T., Shipp M.A.;
RT "BAL1 and BBAP are regulated by a gamma interferon-responsive bidirectional
RT promoter and are overexpressed in diffuse large B-cell lymphomas with a
RT prominent inflammatory infiltrate.";
RL Mol. Cell. Biol. 26:5348-5359(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-221, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RX PubMed=19818714; DOI=10.1016/j.molcel.2009.08.019;
RA Yan Q., Dutt S., Xu R., Graves K., Juszczynski P., Manis J.P., Shipp M.A.;
RT "BBAP monoubiquitylates histone H4 at lysine 91 and selectively modulates
RT the DNA damage response.";
RL Mol. Cell 36:110-120(2009).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-9, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE
RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-202 AND SER-532, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9; SER-202 AND SER-532, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PARP9.
RX PubMed=23230272; DOI=10.1128/mcb.00990-12;
RA Yan Q., Xu R., Zhu L., Cheng X., Wang Z., Manis J., Shipp M.A.;
RT "BAL1 and its partner E3 ligase, BBAP, link Poly(ADP-ribose) activation,
RT ubiquitylation, and double-strand DNA repair independent of ATM, MDC1, and
RT RNF8.";
RL Mol. Cell. Biol. 33:845-857(2013).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-532 AND SER-539, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH ITCH,
RP IDENTIFICATION IN A COMPLEX WITH ITCH; STAM AND HGS, SUBCELLULAR LOCATION,
RP UBIQUITINATION, AND MUTAGENESIS OF CYS-561; CYS-596 AND CYS-599.
RX PubMed=24790097; DOI=10.1091/mbc.e13-10-0612;
RA Holleman J., Marchese A.;
RT "The ubiquitin ligase deltex-3l regulates endosomal sorting of the G
RT protein-coupled receptor CXCR4.";
RL Mol. Biol. Cell 25:1892-1904(2014).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH PARP9 AND STAT1,
RP INTERACTION WITH HRV C3 PROTEASE AND EMCV C3 PROTEASE (MICROBIAL
RP INFECTION), IDENTIFICATION IN A COMPLEX WITH PARP9; STAT1 AND H2BC9,
RP SUBCELLULAR LOCATION, INDUCTION, AND MUTAGENESIS OF 561-CYS--CYS-564.
RX PubMed=26479788; DOI=10.1038/ni.3279;
RA Zhang Y., Mao D., Roswit W.T., Jin X., Patel A.C., Patel D.A., Agapov E.,
RA Wang Z., Tidwell R.M., Atkinson J.J., Huang G., McCarthy R., Yu J.,
RA Yun N.E., Paessler S., Lawson T.G., Omattage N.S., Brett T.J.,
RA Holtzman M.J.;
RT "PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C
RT protease to enhance interferon signaling and control viral infection.";
RL Nat. Immunol. 16:1215-1227(2015).
RN [19]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, ACTIVITY REGULATION, AND
RP IDENTIFICATION IN A COMPLEX WITH PARP9.
RX PubMed=28525742; DOI=10.1016/j.molcel.2017.04.028;
RA Yang C.S., Jividen K., Spencer A., Dworak N., Ni L., Oostdyk L.T.,
RA Chatterjee M., Kusmider B., Reon B., Parlak M., Gorbunova V., Abbas T.,
RA Jeffery E., Sherman N.E., Paschal B.M.;
RT "Ubiquitin Modification by the E3 Ligase/ADP-Ribosyltransferase
RT Dtx3L/Parp9.";
RL Mol. Cell 66:503-516(2017).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 601-740.
RX PubMed=22411408; DOI=10.1002/prot.24054;
RA Obiero J., Walker J.R., Dhe-Paganon S.;
RT "Fold of the conserved DTC domain in deltex proteins.";
RL Proteins 80:1495-1499(2012).
RN [21]
RP VARIANT [LARGE SCALE ANALYSIS] ASN-209.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
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 (PubMed:12670957,
CC PubMed:19818714, PubMed:26479788, PubMed:23230272). Monoubiquitinates
CC several histones, including histone H2A, H2B, H3 and H4
CC (PubMed:28525742). In response to DNA damage, mediates
CC monoubiquitination of 'Lys-91' of histone H4 (H4K91ub1)
CC (PubMed:19818714). The exact role of H4K91ub1 in DNA damage response is
CC still 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) (PubMed:19818714). PARP1-dependent PARP9-DTX3L-
CC mediated ubiquitination promotes the rapid and specific recruitment of
CC 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites
CC (PubMed:23230272). By monoubiquitinating histone H2B H2BC9/H2BJ and
CC thereby promoting chromatin remodeling, positively regulates STAT1-
CC dependent interferon-stimulated gene transcription and thus STAT1-
CC mediated control of viral replication (PubMed:26479788). Independently
CC of its catalytic activity, promotes the sorting of chemokine receptor
CC CXCR4 from early endosome to lysosome following CXCL12 stimulation by
CC reducing E3 ligase ITCH activity and thus ITCH-mediated ubiquitination
CC of endosomal sorting complex required for transport ESCRT-0 components
CC HGS and STAM (PubMed:24790097). In addition, required for the
CC recruitment of HGS and STAM to early endosomes (PubMed:24790097). In
CC association with PARP9, plays a role in antiviral responses by
CC mediating 'Lys-48'-linked ubiquitination of encephalomyocarditis virus
CC (EMCV) and human rhinovirus (HRV) C3 proteases and thus promoting their
CC proteosomal-mediated degradation (PubMed:26479788).
CC {ECO:0000269|PubMed:12670957, ECO:0000269|PubMed:19818714,
CC ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:24790097,
CC ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28525742}.
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:0000269|PubMed:12670957,
CC ECO:0000269|PubMed:19818714, ECO:0000269|PubMed:24790097,
CC ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28525742};
CC -!- ACTIVITY REGULATION: Binding to PARP9 enhances DTX3L catalytic
CC activity. {ECO:0000269|PubMed:28525742}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:12670957, ECO:0000269|PubMed:19818714,
CC ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:26479788,
CC ECO:0000269|PubMed:28525742}.
CC -!- SUBUNIT: Homodimer and heterodimer (PubMed:12670957, PubMed:28525742).
CC Can heterodimerize with DTX1, enhancing its ubiquitin ligase activity
CC in vitro (PubMed:12670957). Interacts (via N-terminus) with ADP
CC ribosyltransferase PARP9/BAL1 (via PARP catalytic domain) forming a
CC stable complex; the interaction is required to activate PARP9 but is
CC dispensable for DTX3L catalytic activity (PubMed:12670957,
CC PubMed:23230272, PubMed:26479788, PubMed:28525742). Forms a complex
CC with STAT1 and PARP9 independently of IFNB1 or IFNG-mediated STAT1
CC 'Tyr-701' phosphorylation (PubMed:26479788). Found in a complex with
CC PARP9, STAT1 and H2BC9 (PubMed:26479788). Found in a complex with E3
CC ligase ITCH and ESCRT-0 components HGS and STAM (PubMed:24790097).
CC Interacts (via C-terminus) with ITCH; the interaction is increased upon
CC CXCL12 stimulation and inhibits ITCH catalytic activity; the
CC interaction is direct (PubMed:24790097). Interacts with HGS and STAM;
CC the interaction brings together HGS and STAM and promotes their
CC recruitment to early endosomes (PubMed:24790097).
CC {ECO:0000269|PubMed:12670957, ECO:0000269|PubMed:23230272,
CC ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:26479788,
CC ECO:0000269|PubMed:28525742}.
CC -!- SUBUNIT: (Microbial infection) Interacts with encephalomyocarditis
CC virus (EMCV) C3 protease; the interaction results in C3 protease 'Lys-
CC 48'-linked ubiquitination. {ECO:0000269|PubMed:26479788}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human rhinovirus (HRV) C3
CC protease; the interaction results in C3 protease 'Lys-48'-linked
CC ubiquitination. {ECO:0000269|PubMed:26479788}.
CC -!- INTERACTION:
CC Q8TDB6; Q9NZD8: SPG21; NbExp=10; IntAct=EBI-2340392, EBI-742688;
CC Q8TDB6; P61086: UBE2K; NbExp=3; IntAct=EBI-2340392, EBI-473850;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23230272,
CC ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:26479788}. Nucleus
CC {ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26479788}. Early
CC endosome membrane {ECO:0000269|PubMed:24790097}; Peripheral membrane
CC protein {ECO:0000305|PubMed:24790097}; Cytoplasmic side
CC {ECO:0000305|PubMed:24790097}. Lysosome membrane
CC {ECO:0000269|PubMed:24790097}; Peripheral membrane protein
CC {ECO:0000305|PubMed:24790097}; Cytoplasmic side
CC {ECO:0000305|PubMed:24790097}. Note=Translocates to the nucleus in
CC response to IFNG or IFNB1 stimulation (PubMed:26479788). Localizes at
CC sites of DNA damage in a PARP1-dependent manner (PubMed:23230272).
CC Localization to early endosomes is increased upon CXCL12 stimulation
CC where it co-localizes with ITCH, CXCL4, HGS and STAM (PubMed:24790097).
CC A minor proportion localizes to lysosomes (PubMed:24790097).
CC {ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:24790097,
CC ECO:0000269|PubMed:26479788}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TDB6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TDB6-2; Sequence=VSP_038522;
CC -!- INDUCTION: Induced by IFNG (PubMed:16809771, PubMed:26479788). Induced
CC by IFNB1 (PubMed:26479788). {ECO:0000269|PubMed:16809771,
CC ECO:0000269|PubMed:26479788}.
CC -!- PTM: Autoubiquitinated. {ECO:0000269|PubMed:24790097}.
CC -!- SIMILARITY: Belongs to the Deltex family. {ECO:0000305}.
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DR EMBL; AY225123; AAP57517.1; -; mRNA.
DR EMBL; AF484416; AAL90859.1; -; mRNA.
DR EMBL; AK125086; BAG54138.1; -; mRNA.
DR EMBL; AY780792; AAV98362.1; -; mRNA.
DR EMBL; CH471052; EAW79476.1; -; Genomic_DNA.
DR EMBL; BC042191; AAH42191.1; -; mRNA.
DR EMBL; BC060509; AAH60509.1; -; mRNA.
DR CCDS; CCDS3015.1; -. [Q8TDB6-1]
DR RefSeq; NP_612144.1; NM_138287.3. [Q8TDB6-1]
DR PDB; 3PG6; X-ray; 1.70 A; A/B/C/D=601-740.
DR PDBsum; 3PG6; -.
DR AlphaFoldDB; Q8TDB6; -.
DR SASBDB; Q8TDB6; -.
DR SMR; Q8TDB6; -.
DR BioGRID; 127392; 57.
DR CORUM; Q8TDB6; -.
DR IntAct; Q8TDB6; 22.
DR MINT; Q8TDB6; -.
DR STRING; 9606.ENSP00000296161; -.
DR GlyGen; Q8TDB6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8TDB6; -.
DR PhosphoSitePlus; Q8TDB6; -.
DR BioMuta; DTX3L; -.
DR DMDM; 37077418; -.
DR EPD; Q8TDB6; -.
DR jPOST; Q8TDB6; -.
DR MassIVE; Q8TDB6; -.
DR MaxQB; Q8TDB6; -.
DR PaxDb; Q8TDB6; -.
DR PeptideAtlas; Q8TDB6; -.
DR PRIDE; Q8TDB6; -.
DR ProteomicsDB; 74256; -. [Q8TDB6-1]
DR ProteomicsDB; 74257; -. [Q8TDB6-2]
DR Antibodypedia; 2147; 150 antibodies from 28 providers.
DR DNASU; 151636; -.
DR Ensembl; ENST00000296161.9; ENSP00000296161.4; ENSG00000163840.10. [Q8TDB6-1]
DR Ensembl; ENST00000383661.3; ENSP00000373157.3; ENSG00000163840.10. [Q8TDB6-2]
DR GeneID; 151636; -.
DR KEGG; hsa:151636; -.
DR MANE-Select; ENST00000296161.9; ENSP00000296161.4; NM_138287.3; NP_612144.1.
DR UCSC; uc003efk.4; human. [Q8TDB6-1]
DR CTD; 151636; -.
DR DisGeNET; 151636; -.
DR GeneCards; DTX3L; -.
DR HGNC; HGNC:30323; DTX3L.
DR HPA; ENSG00000163840; Low tissue specificity.
DR MIM; 613143; gene.
DR neXtProt; NX_Q8TDB6; -.
DR OpenTargets; ENSG00000163840; -.
DR PharmGKB; PA134864792; -.
DR VEuPathDB; HostDB:ENSG00000163840; -.
DR eggNOG; ENOG502RGAW; Eukaryota.
DR GeneTree; ENSGT00940000154578; -.
DR HOGENOM; CLU_024295_0_0_1; -.
DR InParanoid; Q8TDB6; -.
DR OMA; KVCGDFQ; -.
DR OrthoDB; 143182at2759; -.
DR PhylomeDB; Q8TDB6; -.
DR TreeFam; TF325526; -.
DR PathwayCommons; Q8TDB6; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q8TDB6; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 151636; 15 hits in 1130 CRISPR screens.
DR ChiTaRS; DTX3L; human.
DR GenomeRNAi; 151636; -.
DR Pharos; Q8TDB6; Tbio.
DR PRO; PR:Q8TDB6; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q8TDB6; protein.
DR Bgee; ENSG00000163840; Expressed in ileal mucosa and 190 other tissues.
DR Genevisible; Q8TDB6; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
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; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0008047; F:enzyme activator activity; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0004857; F:enzyme inhibitor activity; IMP:UniProtKB.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0097677; F:STAT family protein binding; IPI:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IPI:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP: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; IMP:UniProtKB.
DR GO; GO:0008333; P:endosome to lysosome transport; IMP:UniProtKB.
DR GO; GO:0033522; P:histone H2A ubiquitination; IMP:UniProtKB.
DR GO; GO:0033523; P:histone H2B ubiquitination; IMP:UniProtKB.
DR GO; GO:0010390; P:histone monoubiquitination; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; IMP:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IBA:GO_Central.
DR GO; GO:0035563; P:positive regulation of chromatin binding; IGI:UniProtKB.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IGI:UniProtKB.
DR GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; IMP:UniProtKB.
DR GO; GO:1901666; P:positive regulation of NAD+ ADP-ribosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; IMP:UniProtKB.
DR GO; GO:1902966; P:positive regulation of protein localization to early endosome; IMP:UniProtKB.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IGI:UniProtKB.
DR GO; GO:2000646; P:positive regulation of receptor catabolic process; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IGI:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IMP:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
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; IMP:UniProtKB.
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 3D-structure; Acetylation; Alternative splicing; Antiviral defense;
KW Chromatin regulator; Cytoplasm; DNA damage; DNA repair; Endosome;
KW Host-virus interaction; Immunity; Innate immunity; Lysosome; Membrane;
KW Metal-binding; Nucleus; Phosphoprotein; Protein transport;
KW Reference proteome; Transferase; Transport; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19369195"
FT CHAIN 2..740
FT /note="E3 ubiquitin-protein ligase DTX3L"
FT /id="PRO_0000219087"
FT ZN_FING 561..600
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 96..119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 195..231
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 524..551
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 96..114
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 195..229
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 202
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 221
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 532
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 539
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 134..645
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_038522"
FT VARIANT 209
FT /note="K -> N (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036098"
FT VARIANT 425
FT /note="R -> K (in dbSNP:rs2332285)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.5"
FT /id="VAR_048895"
FT VARIANT 668
FT /note="K -> M (in dbSNP:rs9868175)"
FT /id="VAR_048896"
FT MUTAGEN 561..564
FT /note="CVIC->SVIS: Loss of catalytic activity. Loss of
FT histone H2B ubiquitination. No effect on STAT1
FT phosphorylation and on the interaction with PARP9 and
FT STAT1."
FT /evidence="ECO:0000269|PubMed:26479788"
FT MUTAGEN 561
FT /note="C->A: Loss of catalytic activity but does not affect
FT its capacity to inhibit ITCH catalytic activity; when
FT associated with A-596 and A-599."
FT /evidence="ECO:0000269|PubMed:24790097"
FT MUTAGEN 596
FT /note="C->A: Loss of catalytic activity but does not affect
FT its capacity to inhibit ITCH catalytic activity; when
FT associated with A-561 and A-599."
FT /evidence="ECO:0000269|PubMed:24790097"
FT MUTAGEN 599
FT /note="C->A: Loss of catalytic activity but does not affect
FT its capacity to inhibit ITCH catalytic activity; when
FT associated with A-561 and A-596."
FT /evidence="ECO:0000269|PubMed:24790097"
FT CONFLICT 701
FT /note="I -> T (in Ref. 4; AAV98362)"
FT /evidence="ECO:0000305"
FT STRAND 612..622
FT /evidence="ECO:0007829|PDB:3PG6"
FT STRAND 630..639
FT /evidence="ECO:0007829|PDB:3PG6"
FT STRAND 648..650
FT /evidence="ECO:0007829|PDB:3PG6"
FT STRAND 658..667
FT /evidence="ECO:0007829|PDB:3PG6"
FT HELIX 668..682
FT /evidence="ECO:0007829|PDB:3PG6"
FT STRAND 686..692
FT /evidence="ECO:0007829|PDB:3PG6"
FT TURN 693..696
FT /evidence="ECO:0007829|PDB:3PG6"
FT STRAND 697..703
FT /evidence="ECO:0007829|PDB:3PG6"
FT STRAND 712..714
FT /evidence="ECO:0007829|PDB:3PG6"
FT HELIX 716..718
FT /evidence="ECO:0007829|PDB:3PG6"
FT HELIX 726..736
FT /evidence="ECO:0007829|PDB:3PG6"
SQ SEQUENCE 740 AA; 83554 MW; C413BB744CEE6223 CRC64;
MASHLRPPSP LLVRVYKSGP RVRRKLESYF QSSKSSGGGE CTVSTQEHEA PGTFRVEFSE
RAAKERVLKK GEHQILVDEK PVPIFLVPTE NSIKKNTRPQ ISSLTQSQAE TPSGDMHQHE
GHIPNAVDSC LQKIFLTVTA DLNCNLFSKE QRAYITTLCP SIRKMEGHDG IEKVCGDFQD
IERIHQFLSE QFLESEQKQQ FSPSMTERKP LSQQERDSCI SPSEPETKAE QKSNYFEVPL
PYFEYFKYIC PDKINSIEKR FGVNIEIQES SPNMVCLDFT SSRSGDLEAA RESFASEFQK
NTEPLKQECV SLADSKQANK FKQELNHQFT KLLIKEKGGE LTLLGTQDDI SAAKQKISEA
FVKIPVKLFA ANYMMNVIEV DSAHYKLLET ELLQEISEIE KRYDICSKVS EKGQKTCILF
ESKDRQVDLS VHAYASFIDA FQHASCQLMR EVLLLKSLGK ERKHLHQTKF ADDFRKRHPN
VHFVLNQESM TLTGLPNHLA KAKQYVLKGG GMSSLAGKKL KEGHETPMDI DSDDSKAASP
PLKGSVSSEA SELDKKEKGI CVICMDTISN KKVLPKCKHE FCAPCINKAM SYKPICPTCQ
TSYGIQKGNQ PEGSMVFTVS RDSLPGYESF GTIVITYSMK AGIQTEEHPN PGKRYPGIQR
TAYLPDNKEG RKVLKLLYRA FDQKLIFTVG YSRVLGVSDV ITWNDIHHKT SRFGGPEMYG
YPDPSYLKRV KEELKAKGIE
