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   16-SEP-2015, entry version 122.
DE   RecName: Full=Probable E3 ubiquitin-protein ligase DTX2;
DE            EC=6.3.2.-;
DE   AltName: Full=Protein deltex-2;
DE            Short=Deltex2;
DE            Short=mDTX2;
GN   Name=Dtx2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; 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.,
RA   Nakao K., Kinoshita T., Kadesch T., Hui C.-C., Artavanis-Tsakonas S.,
RA   Okano H., 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.,
RA   Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
RA   Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
RA   Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
RA   Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
RA   Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
RA   di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
RA   Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
RA   Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
RA   Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
RA   Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
RA   Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
RA   Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
RA   Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
RA   Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
RA   Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
RA   Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
RA   Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
RA   Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
RA   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.,
RA   Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
RA   Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
RA   Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
RA   Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
RA   Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
RA   Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
RA   Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
RA   Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
RA   Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
RA   Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
RA   Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
RA   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
RT   project: 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.,
RA   Naiman D.Q., 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
RT   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
RT   protein 2.";
RL   Submitted (JUN-2004) to the PDB data bank.
CC   -!- FUNCTION: Regulator of Notch signaling, a signaling pathway
CC       involved in cell-cell communications that regulates a broad
CC       spectrum of cell-fate determinations. Probably acts both as a
CC       positive and negative regulator of Notch, depending on the
CC       developmental and cell context. Mediates the antineural activity
CC       of Notch, possibly by inhibiting the transcriptional activation
CC       mediated by MATCH1. Functions as a ubiquitin ligase protein in
CC       vitro, suggesting that it may regulate the Notch pathway via some
CC       ubiquitin ligase activity (By similarity). {ECO:0000250}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Homodimer. May form a heterodimer with other members of
CC       the Deltex family. Interacts with NOTCH1.
CC       {ECO:0000269|PubMed:11226752}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus
CC       {ECO:0000250}. Note=Predominantly cytoplasmic. Partially nuclear.
CC       {ECO:0000250}.
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         Note=Splicing donor site not canonical. No experimental
CC         confirmation available.;
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 E10.5 in the spinal cord and around
CC       E11.5 in the telencephalon. Expressed ubiquitously throughout the
CC       spinal cord and telencephalon during neurogenesis. Expressed
CC       throughout the developing retina at E15.5. Not expressed in the
CC       somite or presomite during somitogenesis. Expressed slightly
CC       earlier that Dtx1 and Dtx3. {ECO:0000269|PubMed:11226752}.
CC   -!- DOMAIN: The WWE domains are thought to mediate some protein-
CC       protein interaction, and are frequently found in ubiquitin
CC       ligases. {ECO:0000250}.
CC   -!- DISEASE: Note=Recurrent site of retroviral integration in murine
CC       B-cell lymphomas.
CC   -!- SIMILARITY: Belongs to the Deltex family. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 RING-type zinc finger.
CC       {ECO:0000255|PROSITE-ProRule:PRU00175}.
CC   -!- SIMILARITY: Contains 2 WWE domains. {ECO:0000255|PROSITE-
CC       ProRule:PRU00248}.
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; 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_006504506.2. [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_011239211.1; XM_011240909.1. [Q8R3P2-1]
DR   UniGene; Mm.275574; -.
DR   PDB; 1V87; NMR; -; A=389-489.
DR   PDBsum; 1V87; -.
DR   ProteinModelPortal; Q8R3P2; -.
DR   SMR; Q8R3P2; 19-182, 389-611.
DR   STRING; 10090.ENSMUSP00000106772; -.
DR   PhosphoSite; Q8R3P2; -.
DR   MaxQB; Q8R3P2; -.
DR   PRIDE; Q8R3P2; -.
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   eggNOG; NOG84763; -.
DR   GeneTree; ENSGT00440000035370; -.
DR   HOGENOM; HOG000007352; -.
DR   HOVERGEN; HBG007213; -.
DR   InParanoid; Q8R3P2; -.
DR   KO; K06058; -.
DR   OMA; QPQGKME; -.
DR   OrthoDB; EOG7J17ZB; -.
DR   PhylomeDB; Q8R3P2; -.
DR   TreeFam; TF325526; -.
DR   Reactome; R-MMU-2122948; Activated NOTCH1 Transmits Signal to the Nucleus.
DR   UniPathway; UPA00143; -.
DR   ChiTaRS; Dtx2; mouse.
DR   EvolutionaryTrace; Q8R3P2; -.
DR   NextBio; 340078; -.
DR   PRO; PR:Q8R3P2; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   Bgee; Q8R3P2; -.
DR   CleanEx; MM_DTX2; -.
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:0016874; F:ligase activity; IEA:UniProtKB-KW.
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; IEA:UniProtKB-UniPathway.
DR   Gene3D; 3.30.40.10; -; 1.
DR   InterPro; IPR004170; WWE-dom.
DR   InterPro; IPR018123; WWE-dom_subgr.
DR   InterPro; IPR018957; Znf_C3HC4_RING-type.
DR   InterPro; IPR001841; Znf_RING.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   Pfam; PF02825; WWE; 2.
DR   Pfam; PF00097; zf-C3HC4; 1.
DR   SMART; SM00184; RING; 1.
DR   SMART; SM00678; WWE; 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; Complete proteome;
KW   Cytoplasm; Ligase; Metal-binding; Notch signaling pathway; Nucleus;
KW   Reference proteome; Repeat; Ubl conjugation pathway; Zinc;
KW   Zinc-finger.
FT   CHAIN         1    619       Probable E3 ubiquitin-protein ligase
FT                                DTX2.
FT                                /FTId=PRO_0000219084.
FT   DOMAIN        7     97       WWE 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00248}.
FT   DOMAIN       98    174       WWE 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00248}.
FT   ZN_FING     409    470       RING-type. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00175}.
FT   MOD_RES     248    248       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q86UW9}.
FT   VAR_SEQ     337    382       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:11226752,
FT                                ECO:0000303|PubMed:16141072}.
FT                                /FTId=VSP_008351.
FT   VAR_SEQ     338    357       MTSVLSAIGLPVCLSRAPRP -> EDRRVYWLLVLYSGYRE
FT                                LDN (in isoform 3).
FT                                {ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_008352.
FT   VAR_SEQ     358    619       Missing (in isoform 3).
FT                                {ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_008353.
FT   CONFLICT    383    383       Missing (in Ref. 1; BAB18940).
FT                                {ECO:0000305}.
FT   HELIX       390    397       {ECO:0000244|PDB:1V87}.
FT   STRAND      398    400       {ECO:0000244|PDB:1V87}.
FT   TURN        410    413       {ECO:0000244|PDB:1V87}.
FT   TURN        422    425       {ECO:0000244|PDB:1V87}.
FT   STRAND      429    431       {ECO:0000244|PDB:1V87}.
FT   STRAND      437    442       {ECO:0000244|PDB:1V87}.
FT   HELIX       448    457       {ECO:0000244|PDB:1V87}.
FT   TURN        467    469       {ECO:0000244|PDB:1V87}.
FT   STRAND      472    475       {ECO:0000244|PDB:1V87}.
FT   STRAND      477    479       {ECO:0000244|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
//