UB2D3_MOUSE
ID UB2D3_MOUSE Reviewed; 147 AA.
AC P61079;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2004, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Ubiquitin-conjugating enzyme E2 D3;
DE EC=2.3.2.23;
DE AltName: Full=(E3-independent) E2 ubiquitin-conjugating enzyme D3;
DE EC=2.3.2.24;
DE AltName: Full=E2 ubiquitin-conjugating enzyme D3;
DE AltName: Full=Ubiquitin carrier protein D3;
DE AltName: Full=Ubiquitin-conjugating enzyme E2(17)KB 3;
DE AltName: Full=Ubiquitin-conjugating enzyme E2-17 kDa 3;
DE AltName: Full=Ubiquitin-protein ligase D3;
GN Name=Ube2d3;
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].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Hippocampus, and 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; 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 [3]
RP INTERACTION WITH DAPK3.
RX PubMed=18515077; DOI=10.1016/j.bbrc.2008.05.113;
RA Ohbayashi N., Okada K., Kawakami S., Togi S., Sato N., Ikeda O.,
RA Kamitani S., Muromoto R., Sekine Y., Kawai T., Akira S., Matsuda T.;
RT "Physical and functional interactions between ZIP kinase and UbcH5.";
RL Biochem. Biophys. Res. Commun. 372:708-712(2008).
RN [4]
RP PHOSPHORYLATION.
RX PubMed=24034696; DOI=10.1016/j.molcel.2013.08.022;
RA Frangini A., Sjoberg M., Roman-Trufero M., Dharmalingam G., Haberle V.,
RA Bartke T., Lenhard B., Malumbres M., Vidal M., Dillon N.;
RT "The Aurora B kinase and the Polycomb protein Ring1B combine to regulate
RT active promoters in quiescent lymphocytes.";
RL Mol. Cell 51:647-661(2013).
CC -!- FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its
CC covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-, as
CC well as 'Lys-48'-linked polyubiquitination. Cooperates with the E2
CC CDC34 and the SCF(FBXW11) E3 ligase complex for the polyubiquitination
CC of NFKBIA leading to its subsequent proteasomal degradation. Acts as an
CC initiator E2, priming the phosphorylated NFKBIA target at positions
CC 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Ubiquitin chain
CC elongation is then performed by CDC34, building ubiquitin chains from
CC the UBE2D3-primed NFKBIA-linked ubiquitin. Acts also as an initiator
CC E2, in conjunction with RNF8, for the priming of PCNA.
CC Monoubiquitination of PCNA, and its subsequent polyubiquitination, are
CC essential events in the operation of the DNA damage tolerance (DDT)
CC pathway that is activated after DNA damage caused by UV or chemical
CC agents during S-phase. Associates with the BRCA1/BARD1 E3 ligase
CC complex to perform ubiquitination at DNA damage sites following
CC ionizing radiation leading to DNA repair. Targets DAPK3 for
CC ubiquitination which influences promyelocytic leukemia protein nuclear
CC body (PML-NB) formation in the nucleus. In conjunction with the MDM2
CC and TOPORS E3 ligases, functions ubiquitination of p53/TP53. Supports
CC NRDP1-mediated ubiquitination and degradation of ERBB3 and of BRUCE
CC which triggers apoptosis. In conjunction with the CBL E3 ligase,
CC targets EGFR for polyubiquitination at the plasma membrane as well as
CC during its internalization and transport on endosomes. In conjunction
CC with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded
CC proteins to catalyze their immediate destruction. Together with RNF135,
CC catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of
CC RIG-I/DDX58 to activate the downstream signaling pathway that leads to
CC interferon beta production (By similarity).
CC {ECO:0000250|UniProtKB:P61077}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine +
CC [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-
CC activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-
CC conjugating enzyme]-L-cysteine.; EC=2.3.2.23;
CC Evidence={ECO:0000250|UniProtKB:P61077, ECO:0000255|PROSITE-
CC ProRule:PRU00388, ECO:0000255|PROSITE-ProRule:PRU10133};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E1 ubiquitin-activating enzyme]-L-
CC cysteine + N(6)-monoubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.24; Evidence={ECO:0000250|UniProtKB:P61077};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000255|PROSITE-ProRule:PRU00388}.
CC -!- SUBUNIT: Interacts with SCF (SKP1-CUL1-F-box protein) E3 ubiquitin
CC ligase complex; when Cullin is neddylated, the interaction between the
CC E2 and the SCF complex is strengthened. Interacts with DAPK3. Interacts
CC with BRCA1; the DNA damage checkpoint promotes the association with
CC BRCA1 after ionizing radiation. Interacts non-covalently with
CC ubiquitin. Interacts with E3 ubiquitin-protein ligase CBLC. Interacts
CC with UBTD1 (By similarity). Interacts with DDX58 and RNF135; involved
CC in DDX58 ubiquitination and activation (By similarity).
CC {ECO:0000250|UniProtKB:P61077, ECO:0000269|PubMed:18515077}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P61077};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P61077}. Endosome
CC membrane {ECO:0000250|UniProtKB:P61077}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P61077}.
CC -!- PTM: Phosphorylated by AURKB. {ECO:0000269|PubMed:24034696}.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC {ECO:0000255|PROSITE-ProRule:PRU00388}.
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; AK004001; BAB23116.1; -; mRNA.
DR EMBL; AK032885; BAC28070.1; -; mRNA.
DR EMBL; AK049906; BAC33981.1; -; mRNA.
DR EMBL; AK077666; BAC36940.1; -; mRNA.
DR EMBL; AK088448; BAC40357.1; -; mRNA.
DR EMBL; BC057941; AAH57941.1; -; mRNA.
DR CCDS; CCDS38644.1; -.
DR RefSeq; NP_079632.1; NM_025356.4.
DR RefSeq; XP_006501936.1; XM_006501873.2.
DR RefSeq; XP_006501937.1; XM_006501874.2.
DR RefSeq; XP_006501938.1; XM_006501875.2.
DR AlphaFoldDB; P61079; -.
DR BMRB; P61079; -.
DR SMR; P61079; -.
DR BioGRID; 211216; 15.
DR IntAct; P61079; 1.
DR STRING; 10090.ENSMUSP00000130096; -.
DR ChEMBL; CHEMBL4105725; -.
DR iPTMnet; P61079; -.
DR PhosphoSitePlus; P61079; -.
DR SwissPalm; P61079; -.
DR EPD; P61079; -.
DR jPOST; P61079; -.
DR PaxDb; P61079; -.
DR PeptideAtlas; P61079; -.
DR PRIDE; P61079; -.
DR ProteomicsDB; 298347; -.
DR TopDownProteomics; P61079; -.
DR DNASU; 66105; -.
DR Ensembl; ENSMUST00000106291; ENSMUSP00000101898; ENSMUSG00000078578.
DR Ensembl; ENSMUST00000166033; ENSMUSP00000130096; ENSMUSG00000078578.
DR Ensembl; ENSMUST00000196446; ENSMUSP00000142974; ENSMUSG00000078578.
DR Ensembl; ENSMUST00000197539; ENSMUSP00000143065; ENSMUSG00000078578.
DR Ensembl; ENSMUST00000197859; ENSMUSP00000143608; ENSMUSG00000078578.
DR Ensembl; ENSMUST00000199613; ENSMUSP00000143301; ENSMUSG00000078578.
DR GeneID; 66105; -.
DR KEGG; mmu:66105; -.
DR UCSC; uc008rln.1; mouse.
DR CTD; 7323; -.
DR MGI; MGI:1913355; Ube2d3.
DR VEuPathDB; HostDB:ENSMUSG00000078578; -.
DR eggNOG; KOG0417; Eukaryota.
DR GeneTree; ENSGT00940000153169; -.
DR InParanoid; P61079; -.
DR OrthoDB; 1337945at2759; -.
DR PhylomeDB; P61079; -.
DR TreeFam; TF101108; -.
DR Reactome; R-MMU-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-MMU-201451; Signaling by BMP.
DR Reactome; R-MMU-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR Reactome; R-MMU-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-9033241; Peroxisomal protein import.
DR Reactome; R-MMU-937041; IKK complex recruitment mediated by RIP1.
DR Reactome; R-MMU-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 66105; 16 hits in 79 CRISPR screens.
DR ChiTaRS; Ube2d3; mouse.
DR PRO; PR:P61079; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P61079; protein.
DR Bgee; ENSMUSG00000078578; Expressed in undifferentiated genital tubercle and 257 other tissues.
DR ExpressionAtlas; P61079; baseline and differential.
DR Genevisible; P61079; MM.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0061631; F:ubiquitin conjugating enzyme activity; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISO:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:MGI.
DR GO; GO:0070979; P:protein K11-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISO:MGI.
DR CDD; cd00195; UBCc; 1.
DR Gene3D; 3.10.110.10; -; 1.
DR InterPro; IPR000608; UBQ-conjugat_E2.
DR InterPro; IPR023313; UBQ-conjugating_AS.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR Pfam; PF00179; UQ_con; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR PROSITE; PS00183; UBC_1; 1.
DR PROSITE; PS50127; UBC_2; 1.
PE 1: Evidence at protein level;
KW Apoptosis; ATP-binding; Cell membrane; Disulfide bond; DNA damage;
KW DNA repair; Endosome; Membrane; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation pathway.
FT CHAIN 1..147
FT /note="Ubiquitin-conjugating enzyme E2 D3"
FT /id="PRO_0000082467"
FT DOMAIN 1..147
FT /note="UBC core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT ACT_SITE 85
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388,
FT ECO:0000255|PROSITE-ProRule:PRU10133"
FT DISULFID 21..107
FT /evidence="ECO:0000250|UniProtKB:P61077"
SQ SEQUENCE 147 AA; 16687 MW; ADD74A8A708EFEE3 CRC64;
MALKRINKEL SDLARDPPAQ CSAGPVGDDM FHWQATIMGP NDSPYQGGVF FLTIHFPTDY
PFKPPKVAFT TRIYHPNINS NGSICLDILR SQWSPALTIS KVLLSICSLL CDPNPDDPLV
PEIARIYKTD RDKYNRISRE WTQKYAM
