DTX1_MOUSE
ID DTX1_MOUSE Reviewed; 627 AA.
AC Q61010; Q3TER5; Q8C2H2; Q9ER09;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2003, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=E3 ubiquitin-protein ligase DTX1;
DE EC=2.3.2.27 {ECO:0000269|PubMed:15684388};
DE AltName: Full=FXI-T1;
DE AltName: Full=Protein deltex-1;
DE Short=Deltex1;
DE Short=mDTX1;
DE AltName: Full=RING-type E3 ubiquitin transferase DTX1 {ECO:0000305};
GN Name=Dtx1;
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 [MRNA] (ISOFORM 3).
RC STRAIN=C57BL/6J;
RX PubMed=8853908;
RA Pampeno C.L., Meruelo D.;
RT "A novel cDNA transcript expressed in fractionated X-irradiation-induced
RT murine thymomas.";
RL Cell Growth Differ. 7:1113-1123(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, MULTIMERIZATION, AND INTERACTION WITH NOTCH1.
RX PubMed=11226752; DOI=10.1016/s0736-5748(00)00071-x;
RA Kishi N., Tang Z., Maeda Y., Hirai A., Mo R., Ito M., Suzuki S., Nakao K.,
RA Kinoshita T., Kadesch T., Hui C.-C., Artavanis-Tsakonas S., Okano H.,
RA Matsuno K.;
RT "Murine homologs of deltex define a novel gene family involved in
RT vertebrate Notch signaling and neurogenesis.";
RL Int. J. Dev. Neurosci. 19:21-35(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Thymus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; 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 [5]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=11731257; DOI=10.1016/s0925-4773(01)00534-2;
RA Mitsiadis T.A., Gayet O., Zhang N., Carroll P.;
RT "Expression of Deltex1 during mouse embryogenesis: comparison with Notch1,
RT 2 and 3 expression.";
RL Mech. Dev. 109:399-403(2001).
RN [6]
RP FUNCTION AS AN E3 LIGASE, AND CATALYTIC ACTIVITY.
RX PubMed=15684388; DOI=10.1128/mcb.25.4.1367-1378.2005;
RA Liu W.H., Lai M.Z.;
RT "Deltex regulates T-cell activation by targeted degradation of active
RT MEKK1.";
RL Mol. Cell. Biol. 25:1367-1378(2005).
CC -!- FUNCTION: Regulator of Notch signaling, a signaling pathway involved in
CC cell-cell communications that regulates a broad spectrum of cell-fate
CC determinations. Mainly acts as a positive regulator of Notch, but it
CC also acts as a negative regulator, depending on the developmental and
CC cell context. Mediates the antineural activity of Notch, possibly by
CC inhibiting the transcriptional activation mediated by MATCH1. Involved
CC in neurogenesis, lymphogenesis and myogenesis, and may also be involved
CC in MZB (Marginal zone B) cell differentiation. Promotes B-cell
CC development at the expense of T-cell development, suggesting that it
CC can antagonize NOTCH1. Functions as an ubiquitin ligase protein in
CC vivo, mediating ubiquitination and promoting degradation of MEKK1,
CC suggesting that it may regulate the Notch pathway via some ubiquitin
CC ligase activity. {ECO:0000269|PubMed:15684388}.
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:15684388};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer. May form a heterodimer with other members of the
CC Deltex family. Interacts with NOTCH1 via its N-terminal region and
CC EIF3F, the interaction is required for NOTCH1 deubiquitination.
CC Interacts with EP300. Forms a heterodimer with BBAP; the
CC heterodimerization leading to an increase of in vitro ubiquitin ligase
CC activity. Interacts with ITCH. {ECO:0000250|UniProtKB:Q86Y01}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q86Y01}. Nucleus
CC {ECO:0000250|UniProtKB:Q86Y01}. Note=Predominantly cytoplasmic.
CC Associates with endocytic vesicles. Partially nuclear.
CC {ECO:0000250|UniProtKB:Q86Y01}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q61010-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q61010-2; Sequence=VSP_008348;
CC Name=3;
CC IsoId=Q61010-3; Sequence=VSP_008349;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the brain and testis.
CC Weakly expressed in the thymus, spleen and ovary. Predominantly
CC expressed in regions containing post-mitotic differentiating neurons.
CC {ECO:0000269|PubMed:11226752, ECO:0000269|PubMed:11731257}.
CC -!- DEVELOPMENTAL STAGE: In the CNS, it is expressed in the developing
CC neural tube starting from 10.5 dpc in the spinal cord and around 11.5
CC dpc in the telencephalon. Expressed ubiquitously throughout the spinal
CC cord and telencephalon during neurogenesis. Expressed throughout the
CC developing retina from 12.5 to 15.5 dpc. Expressed in the developing
CC thymus. Not expressed in the somite or presomite during somitogenesis.
CC Expressed slightly later that Dtx2. {ECO:0000269|PubMed:11226752,
CC ECO:0000269|PubMed:11731257}.
CC -!- DOMAIN: The WWE domains are thought to mediate some protein-protein
CC interaction, and are frequently found in ubiquitin ligases.
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated; undergoes 'Lys-29'-linked polyubiquitination
CC catalyzed by ITCH. {ECO:0000250|UniProtKB:Q86Y01}.
CC -!- MISCELLANEOUS: [Isoform 2]: Splicing acceptor site not canonical.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the Deltex family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U38252; AAB02905.1; -; mRNA.
DR EMBL; AB015422; BAB18939.1; -; mRNA.
DR EMBL; AK088630; BAC40465.1; -; mRNA.
DR EMBL; AK169455; BAE41183.1; -; mRNA.
DR EMBL; BC053055; AAH53055.1; -; mRNA.
DR CCDS; CCDS19624.1; -. [Q61010-1]
DR RefSeq; NP_032078.2; NM_008052.3. [Q61010-1]
DR AlphaFoldDB; Q61010; -.
DR SMR; Q61010; -.
DR BioGRID; 199771; 2.
DR STRING; 10090.ENSMUSP00000031607; -.
DR iPTMnet; Q61010; -.
DR PhosphoSitePlus; Q61010; -.
DR PaxDb; Q61010; -.
DR PRIDE; Q61010; -.
DR ProteomicsDB; 277634; -. [Q61010-1]
DR ProteomicsDB; 277635; -. [Q61010-2]
DR ProteomicsDB; 277636; -. [Q61010-3]
DR Antibodypedia; 45356; 236 antibodies from 31 providers.
DR DNASU; 14357; -.
DR Ensembl; ENSMUST00000031607; ENSMUSP00000031607; ENSMUSG00000029603. [Q61010-1]
DR GeneID; 14357; -.
DR KEGG; mmu:14357; -.
DR UCSC; uc008zht.1; mouse. [Q61010-1]
DR CTD; 1840; -.
DR MGI; MGI:1352744; Dtx1.
DR VEuPathDB; HostDB:ENSMUSG00000029603; -.
DR eggNOG; ENOG502QQ9M; Eukaryota.
DR GeneTree; ENSGT00940000160943; -.
DR HOGENOM; CLU_030422_4_0_1; -.
DR InParanoid; Q61010; -.
DR OMA; QFRQDTX; -.
DR OrthoDB; 600021at2759; -.
DR PhylomeDB; Q61010; -.
DR TreeFam; TF325526; -.
DR Reactome; R-MMU-2122948; Activated NOTCH1 Transmits Signal to the Nucleus.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 14357; 1 hit in 71 CRISPR screens.
DR PRO; PR:Q61010; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q61010; protein.
DR Bgee; ENSMUSG00000029603; Expressed in embryonic brain and 199 other tissues.
DR Genevisible; Q61010; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005112; F:Notch binding; ISO:MGI.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0010001; P:glial cell differentiation; IMP:MGI.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; ISO:MGI.
DR GO; GO:0045581; P:negative regulation of T cell differentiation; IDA:MGI.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; ISO:MGI.
DR GO; GO:0030217; P:T cell differentiation; IDA:MGI.
DR CDD; cd09633; Deltex_C; 1.
DR Gene3D; 3.30.390.130; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.30.720.50; -; 2.
DR InterPro; IPR039396; Deltex_C.
DR InterPro; IPR039399; Deltex_C_sf.
DR InterPro; IPR039398; Deltex_fam.
DR InterPro; IPR004170; WWE-dom.
DR InterPro; IPR018123; WWE-dom_subgr.
DR InterPro; IPR037197; WWE_dom_sf.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR12622; PTHR12622; 1.
DR Pfam; PF18102; DTC; 1.
DR Pfam; PF02825; WWE; 2.
DR Pfam; PF00097; zf-C3HC4; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00678; WWE; 2.
DR SUPFAM; SSF117839; SSF117839; 2.
DR PROSITE; PS50918; WWE; 2.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Metal-binding; Notch signaling pathway;
KW Nucleus; Reference proteome; Repeat; SH3-binding; Transferase;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..627
FT /note="E3 ubiquitin-protein ligase DTX1"
FT /id="PRO_0000219081"
FT DOMAIN 14..94
FT /note="WWE 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT DOMAIN 95..171
FT /note="WWE 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT ZN_FING 418..479
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 222..254
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 269..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 368..398
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 240..243
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 229..251
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 272..291
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 292..316
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..88
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8853908"
FT /id="VSP_008349"
FT VAR_SEQ 1..78
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008348"
FT CONFLICT 451
FT /note="C -> Y (in Ref. 3; BAC40465)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 627 AA; 68119 MW; 6ED8C152EF5A55FD CRC64;
MSRPGQGVMV PVNGLGFPPQ NVARVVVWEW LNEHSRWRPY TATVCHHIEN VLKEDARGSV
VLGQVDAQLV PYIIDLQSMH QFRQDTGTMR PVRRNFYDPS SAPGKGIVWE WENDGGAWTA
YDMDICITIQ NAYEKQHPWL DLSSLGFCYL IYFNSMSQMN RQTRRRRRLR RRLDLAYPLT
VGSIPKSQSW PVGASSGQPC SCQQCLLVNS TRAASNAILA SQRRKAPIAP AAPPAPPPPP
PPLPPGGPPG ALVVRPSATF AGAALWAAPA TGPTEPAPPP GVPPRSPSAP NGAPTPGQNN
LSRPGPQRST SVSARASIPP GVPALPVKNL NGTGPVHPAL AGMTGILLCA AGLPVCLTRA
PKPILHPPPV SKSDVKPVPG VPGVCRKTKK KHLKKSKNPE DVVRRYMQKV KNPPDEDCTI
CMERLVTASG YEGVLRNKSV RPELVGRLGR CGHMYHLLCL VAMYSNGNKD GSLQCPTCKA
IYGEKTGTQP PGKMEFHLIP HSLPGFADTQ TIRIVYDIPT GIQGPEHPNP GKKFTARGFP
RHCYLPNNEK GRKVLRLLIT AWERRLIFTI GTSNTTGESD TVVWNEIHHK TEFGSNLTGH
GYPDASYLDN VLAELTAQGV SEAMAKA
