DTX2_MOUSE
ID DTX2_MOUSE Reviewed; 619 AA.
AC Q8R3P2; Q9CZV3; Q9ER07; Q9ER08;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2003, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Probable E3 ubiquitin-protein ligase DTX2;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q61010};
DE AltName: Full=Protein deltex-2;
DE Short=Deltex2;
DE Short=mDTX2;
DE AltName: Full=RING-type E3 ubiquitin transferase DTX2 {ECO:0000305};
GN Name=Dtx2;
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] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY,
RP DEVELOPMENTAL 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Brain cortex, Embryo, and Ovary;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Mammary tumor;
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 RETROVIRAL INSERTION.
RX PubMed=12185365; DOI=10.1038/ng949;
RA Suzuki T., Shen H., Akagi K., Morse H.C. III, Malley J.D., Naiman D.Q.,
RA Jenkins N.A., Copeland N.G.;
RT "New genes involved in cancer identified by retroviral tagging.";
RL Nat. Genet. 32:166-174(2002).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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).
RN [6]
RP STRUCTURE BY NMR OF 389-489.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the RING-H2 finger domain of mouse deltex protein
RT 2.";
RL Submitted (JUN-2004) to the PDB data bank.
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. Probably acts both as a positive and negative regulator
CC of Notch, depending on the developmental and cell context. Mediates the
CC antineural activity of Notch, possibly by inhibiting the
CC transcriptional activation mediated by MATCH1. Functions as a ubiquitin
CC ligase protein in vitro, suggesting that it may regulate the Notch
CC pathway via some ubiquitin ligase activity (By similarity).
CC {ECO:0000250}.
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:Q61010};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer. May form a heterodimer with other members of the
CC Deltex family. Interacts with NOTCH1. {ECO:0000269|PubMed:11226752}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q86UW9}. Nucleus
CC {ECO:0000250|UniProtKB:Q86UW9}. Note=Predominantly cytoplasmic.
CC Partially nuclear. {ECO:0000250|UniProtKB:Q86UW9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8R3P2-1; Sequence=Displayed;
CC Name=2; Synonyms=DeltaE;
CC IsoId=Q8R3P2-2; Sequence=VSP_008351;
CC Name=3;
CC IsoId=Q8R3P2-3; Sequence=VSP_008352, VSP_008353;
CC -!- TISSUE SPECIFICITY: Expressed in testis and the CNS.
CC {ECO:0000269|PubMed:11226752}.
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 at 15.5 dpc. Not expressed in the somite or presomite
CC during somitogenesis. Expressed slightly earlier that Dtx1 and Dtx3.
CC {ECO:0000269|PubMed:11226752}.
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 -!- DISEASE: Note=Recurrent site of retroviral integration in murine B-cell
CC lymphomas.
CC -!- MISCELLANEOUS: [Isoform 3]: Splicing donor site not canonical.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the Deltex family. {ECO:0000305}.
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DR EMBL; AB015423; BAB18940.1; -; mRNA.
DR EMBL; AB015424; BAB18941.1; -; mRNA.
DR EMBL; AK012137; BAB28055.1; -; mRNA.
DR EMBL; AK044105; BAC31780.1; -; mRNA.
DR EMBL; AK054443; BAC35781.1; -; mRNA.
DR EMBL; BC024925; AAH24925.1; -; mRNA.
DR CCDS; CCDS57389.1; -. [Q8R3P2-1]
DR CCDS; CCDS57390.1; -. [Q8R3P2-2]
DR RefSeq; NP_001243025.1; NM_001256096.1. [Q8R3P2-1]
DR RefSeq; NP_001243026.1; NM_001256097.1. [Q8R3P2-2]
DR RefSeq; NP_001243027.1; NM_001256098.1. [Q8R3P2-2]
DR RefSeq; NP_076231.1; NM_023742.2.
DR RefSeq; XP_006504569.1; XM_006504506.3. [Q8R3P2-1]
DR RefSeq; XP_006504570.1; XM_006504507.2. [Q8R3P2-1]
DR RefSeq; XP_006504571.1; XM_006504508.1. [Q8R3P2-1]
DR RefSeq; XP_017176609.1; XM_017321120.1. [Q8R3P2-2]
DR PDB; 1V87; NMR; -; A=389-489.
DR PDBsum; 1V87; -.
DR AlphaFoldDB; Q8R3P2; -.
DR BMRB; Q8R3P2; -.
DR SMR; Q8R3P2; -.
DR BioGRID; 216569; 1.
DR IntAct; Q8R3P2; 1.
DR STRING; 10090.ENSMUSP00000106772; -.
DR iPTMnet; Q8R3P2; -.
DR PhosphoSitePlus; Q8R3P2; -.
DR EPD; Q8R3P2; -.
DR MaxQB; Q8R3P2; -.
DR PaxDb; Q8R3P2; -.
DR PRIDE; Q8R3P2; -.
DR ProteomicsDB; 277524; -. [Q8R3P2-1]
DR ProteomicsDB; 277525; -. [Q8R3P2-2]
DR ProteomicsDB; 277526; -. [Q8R3P2-3]
DR Antibodypedia; 35109; 199 antibodies from 30 providers.
DR DNASU; 74198; -.
DR Ensembl; ENSMUST00000111142; ENSMUSP00000106772; ENSMUSG00000004947. [Q8R3P2-1]
DR Ensembl; ENSMUST00000111144; ENSMUSP00000106774; ENSMUSG00000004947. [Q8R3P2-2]
DR Ensembl; ENSMUST00000111145; ENSMUSP00000106775; ENSMUSG00000004947. [Q8R3P2-2]
DR Ensembl; ENSMUST00000125827; ENSMUSP00000115122; ENSMUSG00000004947. [Q8R3P2-3]
DR GeneID; 74198; -.
DR KEGG; mmu:74198; -.
DR UCSC; uc008zzm.2; mouse. [Q8R3P2-1]
DR UCSC; uc008zzo.2; mouse. [Q8R3P2-2]
DR CTD; 113878; -.
DR MGI; MGI:1921448; Dtx2.
DR VEuPathDB; HostDB:ENSMUSG00000004947; -.
DR eggNOG; ENOG502QQ9M; Eukaryota.
DR GeneTree; ENSGT00940000157641; -.
DR HOGENOM; CLU_030422_4_0_1; -.
DR InParanoid; Q8R3P2; -.
DR OMA; DAPEEDC; -.
DR OrthoDB; 600021at2759; -.
DR PhylomeDB; Q8R3P2; -.
DR TreeFam; TF325526; -.
DR Reactome; R-MMU-2122948; Activated NOTCH1 Transmits Signal to the Nucleus.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 74198; 4 hits in 77 CRISPR screens.
DR ChiTaRS; Dtx2; mouse.
DR EvolutionaryTrace; Q8R3P2; -.
DR PRO; PR:Q8R3P2; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8R3P2; protein.
DR Bgee; ENSMUSG00000004947; Expressed in secondary oocyte and 264 other tissues.
DR ExpressionAtlas; Q8R3P2; baseline and differential.
DR Genevisible; Q8R3P2; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
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 3D-structure; Acetylation; Alternative splicing; Cytoplasm; Metal-binding;
KW Methylation; Notch signaling pathway; Nucleus; Reference proteome; Repeat;
KW Transferase; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..619
FT /note="Probable E3 ubiquitin-protein ligase DTX2"
FT /id="PRO_0000219084"
FT DOMAIN 7..97
FT /note="WWE 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT DOMAIN 98..174
FT /note="WWE 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT ZN_FING 409..470
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 243..271
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 283..328
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 355..389
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 213
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q86UW9"
FT MOD_RES 215
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q86UW9"
FT MOD_RES 232
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q86UW9"
FT MOD_RES 248
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q86UW9"
FT MOD_RES 255
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q86UW9"
FT VAR_SEQ 337..382
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11226752,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_008351"
FT VAR_SEQ 338..357
FT /note="MTSVLSAIGLPVCLSRAPRP -> EDRRVYWLLVLYSGYRELDN (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008352"
FT VAR_SEQ 358..619
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008353"
FT CONFLICT 383
FT /note="Missing (in Ref. 1; BAB18940)"
FT /evidence="ECO:0000305"
FT HELIX 390..397
FT /evidence="ECO:0007829|PDB:1V87"
FT STRAND 398..400
FT /evidence="ECO:0007829|PDB:1V87"
FT TURN 410..413
FT /evidence="ECO:0007829|PDB:1V87"
FT TURN 422..425
FT /evidence="ECO:0007829|PDB:1V87"
FT STRAND 429..431
FT /evidence="ECO:0007829|PDB:1V87"
FT STRAND 437..442
FT /evidence="ECO:0007829|PDB:1V87"
FT HELIX 448..457
FT /evidence="ECO:0007829|PDB:1V87"
FT TURN 467..469
FT /evidence="ECO:0007829|PDB:1V87"
FT STRAND 472..475
FT /evidence="ECO:0007829|PDB:1V87"
FT STRAND 477..479
FT /evidence="ECO:0007829|PDB:1V87"
SQ SEQUENCE 619 AA; 67195 MW; A3A9F16F5B855697 CRC64;
MAMAPSSSLP QVYPSHVVVA VWEWQDGLGI WHPYSATVCS FIEQHFVRQR GQHFGLGSLA
HSIPLGQADP SLAPYIIDLP SWTQFRQNTG TMRSVRRHLF SQNSAPGQGI VWEWLGDDGS
WVAYEARICD YLEQQVARGI QVVDLAPLGY NYTVNYATLT QTNKTSSFCR SVRRQVGPVY
PVTSDIAVPR QMGLICFCQQ CLHGSGTGPV SGRYRHSMTN LPAYPAPQAP HRTTTVSGAH
QAFAPYNKPS LSGARSAPRL NTTNPWAAAP PVAGNQSLFH SSLSHLGPQL LPSGPSTSSG
ASASFPSGPS SSSPGSAPTT VPVQMPKASR VQQALAGMTS VLSAIGLPVC LSRAPRPTGP
PASRPASKSH SSVKRLRKMS VKEGAPKPEP EQVIRKYTEE LKVAPEEDCI ICMEKLAVAS
GYSDMTDSKA LGPMVVGRLT KCSHAFHLLC LLAMYCNGNK DGSLQCPSCK TIYGEKTGTQ
PWGKMEVFRF QMSLPGHEDC GTILIVYNIP HGIQGPEHPS PGKPFTARGF PRQCYLPDSP
QGRKVLELLK VAWKRRLIFT VGTSSTTGET DTVVWNEIHH KTEMDRNVTG HGYPDPNYLQ
NVLAELAAQG VTEDCLEQQ
