ID UB2D3_HUMAN Reviewed; 147 AA. AC P61077; A6NJ93; A6NJB1; A6NM99; P47986; Q6IB88; Q6NXS4; Q8N924; DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 26-APR-2004, sequence version 1. DT 02-SEP-2026, entry version 203. DE RecName: Full=Ubiquitin-conjugating enzyme E2 D3; DE EC=2.3.2.23 {ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:28685749}; DE AltName: Full=(E3-independent) E2 ubiquitin-conjugating enzyme D3; DE EC=2.3.2.24 {ECO:0000269|PubMed:17588522}; 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; Synonyms=UBC5C, UBCH5C; 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). RX PubMed=8530467; DOI=10.1074/jbc.270.51.30408; RA Jensen J.P., Bates P.W., Yang M., Vierstra R.D., Weissman A.M.; RT "Identification of a family of closely related human ubiquitin conjugating RT enzymes."; RL J. Biol. Chem. 270:30408-30414(1995). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Chang H.-M., Tsai S.-F.; RT "Genome sequencing of the chromosome 4q region implicated in human RT hepatocellular carcinoma pathogenesis."; RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Chondrocyte, and Testis; 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 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain, and Placenta; 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 [8] RP FUNCTION, AND MUTAGENESIS OF CYS-85. RX PubMed=10329681; DOI=10.1074/jbc.274.21.14823; RA Gonen H., Bercovich B., Orian A., Carrano A., Takizawa C., Yamanaka K., RA Pagano M., Iwai K., Ciechanover A.; RT "Identification of the ubiquitin carrier proteins, E2s, involved in signal- RT induced conjugation and subsequent degradation of IkappaBalpha."; RL J. Biol. Chem. 274:14823-14830(1999). RN [9] RP FUNCTION. RX PubMed=11743028; DOI=10.1093/embo-reports/kve246; RA Murata S., Minami Y., Minami M., Chiba T., Tanaka K.; RT "CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded RT protein."; RL EMBO Rep. 2:1133-1138(2001). RN [10] RP FUNCTION. RX PubMed=12646252; DOI=10.1016/s0006-291x(03)00282-1; RA Yogosawa S., Miyauchi Y., Honda R., Tanaka H., Yasuda H.; RT "Mammalian Numb is a target protein of Mdm2, ubiquitin ligase."; RL Biochem. Biophys. Res. Commun. 302:869-872(2003). RN [11] RP FUNCTION. RX PubMed=15247280; DOI=10.1074/jbc.c400300200; RA Rajendra R., Malegaonkar D., Pungaliya P., Marshall H., Rasheed Z., RA Brownell J., Liu L.F., Lutzker S., Saleem A., Rubin E.H.; RT "Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and RT ubiquitinates p53."; RL J. Biol. Chem. 279:36440-36444(2004). RN [12] RP FUNCTION. RX PubMed=15280377; DOI=10.1074/jbc.m403362200; RA Saville M.K., Sparks A., Xirodimas D.P., Wardrop J., Stevenson L.F., RA Bourdon J.C., Woods Y.L., Lane D.P.; RT "Regulation of p53 by the ubiquitin-conjugating enzymes UbcH5B/C in vivo."; RL J. Biol. Chem. 279:42169-42181(2004). RN [13] RP FUNCTION. RX PubMed=15496420; DOI=10.1074/jbc.m410583200; RA Huang J., Huang Q., Zhou X., Shen M.M., Yen A., Yu S.X., Dong G., Qu K., RA Huang P., Anderson E.M., Daniel-Issakani S., Buller R.M., Payan D.G., RA Lu H.H.; RT "The poxvirus p28 virulence factor is an E3 ubiquitin ligase."; RL J. Biol. Chem. 279:54110-54116(2004). RN [14] RP INTERACTION WITH BRCA1, AND FUNCTION. RX PubMed=16628214; DOI=10.1038/sj.emboj.7601102; RA Polanowska J., Martin J.S., Garcia-Muse T., Petalcorin M.I.R., RA Boulton S.J.; RT "A conserved pathway to activate BRCA1-dependent ubiquitylation at DNA RT damage sites."; RL EMBO J. 25:2178-2188(2006). RN [15] RP CATALYTIC ACTIVITY AS E3-INDEPENDENT E2 UBIQUITIN-CONJUGATING ENZYME. RX PubMed=17588522; DOI=10.1016/j.molcel.2007.05.014; RA Hoeller D., Hecker C.M., Wagner S., Rogov V., Doetsch V., Dikic I.; RT "E3-independent monoubiquitination of ubiquitin-binding proteins."; RL Mol. Cell 26:891-898(2007). RN [16] RP INTERACTION WITH DAPK3, AND FUNCTION. 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 [17] RP FUNCTION. RX PubMed=18948756; DOI=10.4161/cc.7.21.6949; RA Zhang S., Chea J., Meng X., Zhou Y., Lee E.Y.C., Lee M.Y.W.T.; RT "PCNA is ubiquitinated by RNF8."; RL Cell Cycle 7:3399-3404(2008). RN [18] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=18508924; DOI=10.1091/mbc.e07-10-0988; RA Umebayashi K., Stenmark H., Yoshimori T.; RT "Ubc4/5 and c-Cbl continue to ubiquitinate EGF receptor after RT internalization to facilitate polyubiquitination and degradation."; RL Mol. Biol. Cell 19:3454-3462(2008). RN [19] RP INTERACTION WITH SCF COMPLEX. RX PubMed=18851830; DOI=10.1016/j.molcel.2008.08.021; RA Saha A., Deshaies R.J.; RT "Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation."; RL Mol. Cell 32:21-31(2008). RN [20] RP FUNCTION. RX PubMed=18284575; DOI=10.1111/j.1365-2958.2008.06124.x; RA Kubori T., Hyakutake A., Nagai H.; RT "Legionella translocates an E3 ubiquitin ligase that has multiple U-boxes RT with distinct functions."; RL Mol. Microbiol. 67:1307-1319(2008). RN [21] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=20061386; DOI=10.1074/jbc.m109.089003; RA David Y., Ziv T., Admon A., Navon A.; RT "The E2 ubiquitin-conjugating enzymes direct polyubiquitination to RT preferred lysines."; RL J. Biol. Chem. 285:8595-8604(2010). RN [22] RP INTERACTION WITH CBLC. RX PubMed=20525694; DOI=10.1074/jbc.m109.091157; RA Ryan P.E., Sivadasan-Nair N., Nau M.M., Nicholas S., Lipkowitz S.; RT "The N terminus of Cbl-c regulates ubiquitin ligase activity by modulating RT affinity for the ubiquitin-conjugating enzyme."; RL J. Biol. Chem. 285:23687-23698(2010). RN [23] RP FUNCTION. RX PubMed=20347421; DOI=10.1016/j.molcel.2010.02.025; RA Wu K., Kovacev J., Pan Z.Q.; RT "Priming and extending: a UbcH5/Cdc34 E2 handoff mechanism for RT polyubiquitination on a SCF substrate."; RL Mol. Cell 37:784-796(2010). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [25] RP FUNCTION, AND MUTAGENESIS OF ASN-77; ASP-87 AND ASP-117. RX PubMed=21532592; DOI=10.1038/nature09966; RA Wenzel D.M., Lissounov A., Brzovic P.S., Klevit R.E.; RT "UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT RT hybrids."; RL Nature 474:105-108(2011). RN [26] RP INTERACTION WITH UBTD1. RX PubMed=24211586; DOI=10.1016/j.bbrc.2013.10.137; RA Uhler J.P., Spaahr H., Farge G., Clavel S., Larsson N.G., Falkenberg M., RA Samuelsson T., Gustafsson C.M.; RT "The UbL protein UBTD1 stably interacts with the UBE2D family of E2 RT ubiquitin conjugating enzymes."; RL Biochem. Biophys. Res. Commun. 443:7-12(2014). RN [27] RP FUNCTION. RX PubMed=28322253; DOI=10.1038/cr.2017.40; RA Peng H., Yang J., Li G., You Q., Han W., Li T., Gao D., Xie X., Lee B.H., RA Du J., Hou J., Zhang T., Rao H., Huang Y., Li Q., Zeng R., Hui L., Wang H., RA Xia Q., Zhang X., He Y., Komatsu M., Dikic I., Finley D., Hu R.; RT "Ubiquitylation of p62/sequestosome1 activates its autophagy receptor RT function and controls selective autophagy upon ubiquitin stress."; RL Cell Res. 27:657-674(2017). RN [28] RP FUNCTION, AND INTERACTION WITH RIGI AND RNF135. RX PubMed=28469175; DOI=10.1038/ncomms15138; RA Shi Y., Yuan B., Zhu W., Zhang R., Li L., Hao X., Chen S., Hou F.; RT "Ube2D3 and Ube2N are essential for RIG-I-mediated MAVS aggregation in RT antiviral innate immunity."; RL Nat. Commun. 8:15138-15138(2017). RN [29] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND INTERACTION WITH ZNF598. RX PubMed=28685749; DOI=10.1038/ncomms16056; RA Garzia A., Jafarnejad S.M., Meyer C., Chapat C., Gogakos T., Morozov P., RA Amiri M., Shapiro M., Molina H., Tuschl T., Sonenberg N.; RT "The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates RT ribosome quality control of premature polyadenylated mRNAs."; RL Nat. Commun. 8:16056-16056(2017). RN [30] RP FUNCTION. RX PubMed=36528027; DOI=10.1016/j.molcel.2022.11.021; RA Jiang C., Dai X., He S., Zhou H., Fang L., Guo J., Liu S., Zhang T., RA Pan W., Yu H., Fu T., Li D., Inuzuka H., Wang P., Xiao J., Wei W.; RT "Ring domains are essential for GATOR2-dependent mTORC1 activation."; RL Mol. Cell 83:74-89(2023). RN [31] RP STRUCTURE BY NMR OF 2-147 IN COMPLEX WITH THE BRCA1/BARD1 RING-DOMAIN RP HETERODIMER, AND INTERACTION WITH BRCA1. RX PubMed=16543155; DOI=10.1016/j.molcel.2006.02.008; RA Brzovic P.S., Lissounov A., Christensen D.E., Hoyt D.W., Klevit R.E.; RT "A UbcH5/ubiquitin noncovalent complex is required for processive BRCA1- RT directed ubiquitination."; RL Mol. Cell 21:873-880(2006). RN [32] RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 1-147, AND DISULFIDE BOND. RA Nakanishi M., Teshima N., Mizushima T., Murata S., Tanaka K., Yamane T.; RT "Crystal structure of UBCH5C."; RL Submitted (FEB-2009) to the PDB data bank. RN [33] RP X-RAY CRYSTALLOGRAPHY (3.17 ANGSTROMS) OF 1-147 IN COMPLEX WITH U-BOX RP DOMAIN OF UBE4B. RA Benirschke R., Thompson J.R., Mer G.; RT "Crystal structure of the U-Box domain of human e4b ubiquitin ligase in RT complex with UBCH5C E2 ubiquitin conjugating enzyme."; RL Submitted (MAY-2010) to the PDB data bank. RN [34] {ECO:0007744|PDB:3L1Z} RP X-RAY CRYSTALLOGRAPHY (3.17 ANGSTROMS), AND INTERACTION WITH UBE4B. RX PubMed=20696396; DOI=10.1016/j.str.2010.04.017; RA Benirschke R.C., Thompson J.R., Nomine Y., Wasielewski E., Juranic N., RA Macura S., Hatakeyama S., Nakayama K.I., Botuyan M.V., Mer G.; RT "Molecular basis for the association of human E4B U box ubiquitin ligase RT with E2-conjugating enzymes UbcH5c and Ubc4."; RL Structure 18:955-965(2010). RN [35] {ECO:0007744|PDB:9LPK} RP STRUCTURE BY ELECTRON MICROSCOPY (3.03 ANGSTROMS) IN COMPLEX WITH PADI6 AND RP UHRF1, AND ACTIVITY REGULATION. RX PubMed=41772195; DOI=10.1038/s41594-026-01758-y; RA Li J., Lu Y., Xia Z., Chi P., Qi Q., Liu S., Ju S., Li J., Zhang Z., RA Han Z., Liu Q., Meng W., Chen J., Wang X., Guo L., Li L., Huang W., Dai L., RA Han J., Gao S., Deng D.; RT "The maternal PADI6-UHRF1-UBE2D complex regulates ubiquitination during RT oocyte maturation and embryogenesis."; RL Nat. Struct. Mol. Biol. 33:512-524(2026). CC -!- FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its CC covalent attachment to other proteins (PubMed:15247280, CC PubMed:15496420, PubMed:18284575, PubMed:20061386, PubMed:21532592, CC PubMed:28322253). In vitro catalyzes 'Lys-11'-, as well as 'Lys-48'- CC linked polyubiquitination (PubMed:15247280, PubMed:15496420, CC PubMed:18284575, PubMed:20061386, PubMed:21532592). Cooperates with the CC E2 CDC34 and the SCF(FBXW11) E3 ligase complex for the CC polyubiquitination of NFKBIA leading to its subsequent proteasomal CC degradation (PubMed:20347421). Acts as an initiator E2, priming the CC phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with CC a monoubiquitin (PubMed:10329681). Ubiquitin chain elongation is then CC performed by CDC34, building ubiquitin chains from the UBE2D3-primed CC NFKBIA-linked ubiquitin (PubMed:10329681). Also acts as an initiator CC E2, in conjunction with RNF8, for the priming of PCNA CC (PubMed:18948756). Monoubiquitination of PCNA, and its subsequent CC polyubiquitination, are essential events in the operation of the DNA CC damage tolerance (DDT) pathway that is activated after DNA damage CC caused by UV or chemical agents during S-phase (PubMed:18948756). CC Associates with the BRCA1/BARD1 E3 ligase complex to perform CC ubiquitination at DNA damage sites following ionizing radiation leading CC to DNA repair (PubMed:16628214). Targets DAPK3 for ubiquitination which CC influences promyelocytic leukemia protein nuclear body (PML-NB) CC formation in the nucleus (PubMed:18515077). In conjunction with the CC MDM2 and TOPORS E3 ligases, functions ubiquitination of p53/TP53 CC (PubMed:12646252, PubMed:15280377). In conjunction with the CBL E3 CC ligase, targets EGFR for polyubiquitination at the plasma membrane as CC well as during its internalization and transport on endosomes CC (PubMed:18508924). In conjunction with the STUB1 E3 quality control E3 CC ligase, ubiquitinates unfolded proteins to catalyze their immediate CC destruction (PubMed:11743028). Together with RNF135, catalyzes the CC viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIGI to CC activate the downstream signaling pathway that leads to interferon beta CC production (PubMed:28469175). Together with ZNF598, catalyzes CC ubiquitination of 40S ribosomal proteins in response to ribosome CC collisions (PubMed:28685749). In cooperation with the GATOR2 complex, CC catalyzes 'Lys-6'-linked ubiquitination of NPRL2 (PubMed:36528027). CC {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:11743028, CC ECO:0000269|PubMed:12646252, ECO:0000269|PubMed:15247280, CC ECO:0000269|PubMed:15280377, ECO:0000269|PubMed:15496420, CC ECO:0000269|PubMed:16628214, ECO:0000269|PubMed:18284575, CC ECO:0000269|PubMed:18508924, ECO:0000269|PubMed:18515077, CC ECO:0000269|PubMed:18948756, ECO:0000269|PubMed:20061386, CC ECO:0000269|PubMed:20347421, ECO:0000269|PubMed:21532592, CC ECO:0000269|PubMed:28322253, ECO:0000269|PubMed:28469175, CC ECO:0000269|PubMed:28685749, ECO:0000269|PubMed:36528027}. 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:0000255|PROSITE-ProRule:PRU00388, ECO:0000255|PROSITE- CC ProRule:PRU10133, ECO:0000269|PubMed:20061386, CC ECO:0000269|PubMed:28685749}; 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:0000269|PubMed:17588522}; CC -!- ACTIVITY REGULATION: In oocytes and preimplantation embryos, E2 CC ubiquitin-protein transferase activity is inhibited by cytoplasmic CC lattices, which trap UBE2D3 in a compact autoinhibited conformation. CC {ECO:0000269|PubMed:41772195}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000255|PROSITE-ProRule:PRU00388, ECO:0000269|PubMed:28685749}. 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 (PubMed:24211586). Interacts with RIGI and RNF135; involved CC in RIGI ubiquitination and activation (PubMed:28469175). Interacts with CC E3 ubiquitin-protein ligase UBE4B (PubMed:20696396). CC {ECO:0000269|PubMed:16543155, ECO:0000269|PubMed:16628214, CC ECO:0000269|PubMed:18515077, ECO:0000269|PubMed:18851830, CC ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:20696396, CC ECO:0000269|PubMed:24211586, ECO:0000269|PubMed:28469175, CC ECO:0000269|Ref.33}. CC -!- INTERACTION: CC P61077; Q86UW9: DTX2; NbExp=9; IntAct=EBI-348268, EBI-740376; CC P61077; Q8N9I9: DTX3; NbExp=4; IntAct=EBI-348268, EBI-2340258; CC P61077; P62879: GNB2; NbExp=3; IntAct=EBI-348268, EBI-356942; CC P61077; O15344: MID1; NbExp=8; IntAct=EBI-348268, EBI-2340316; CC P61077; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-348268, EBI-10172526; CC P61077; Q96FW1: OTUB1; NbExp=14; IntAct=EBI-348268, EBI-1058491; CC P61077; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-348268, EBI-396669; CC P61077; Q6ZNA4: RNF111; NbExp=5; IntAct=EBI-348268, EBI-2129175; CC P61077; Q9Y4L5: RNF115; NbExp=11; IntAct=EBI-348268, EBI-2129242; CC P61077; Q9BV68: RNF126; NbExp=4; IntAct=EBI-348268, EBI-357322; CC P61077; Q99496: RNF2; NbExp=6; IntAct=EBI-348268, EBI-722416; CC P61077; Q96BH1: RNF25; NbExp=9; IntAct=EBI-348268, EBI-2129220; CC P61077; Q68DV7: RNF43; NbExp=2; IntAct=EBI-348268, EBI-1647060; CC P61077; Q99942: RNF5; NbExp=11; IntAct=EBI-348268, EBI-348482; CC P61077; Q9Y4K3: TRAF6; NbExp=2; IntAct=EBI-348268, EBI-359276; CC P61077; Q9HCM9: TRIM39; NbExp=6; IntAct=EBI-348268, EBI-739510; CC P61077; Q9HCM9-2: TRIM39; NbExp=5; IntAct=EBI-348268, EBI-11523450; CC P61077; Q9BVG3: TRIM62; NbExp=3; IntAct=EBI-348268, EBI-6929619; CC P61077; Q9HAC8: UBTD1; NbExp=6; IntAct=EBI-348268, EBI-745871; CC P61077; P98170: XIAP; NbExp=2; IntAct=EBI-348268, EBI-517127; CC P61077; Q8ND25: ZNRF1; NbExp=3; IntAct=EBI-348268, EBI-2129250; CC P61077; O54784: Dapk3; Xeno; NbExp=2; IntAct=EBI-348268, EBI-77359; CC P61077; Q99PZ6: ospG; Xeno; NbExp=6; IntAct=EBI-348268, EBI-9316527; CC P61077; P0CE12: sspH2; Xeno; NbExp=7; IntAct=EBI-348268, EBI-10761075; CC P61077-1; O95155-1: UBE4B; NbExp=3; IntAct=EBI-15567256, EBI-15869194; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18508924}; CC Peripheral membrane protein {ECO:0000269|PubMed:18508924}. Endosome CC membrane {ECO:0000269|PubMed:18508924}; Peripheral membrane protein CC {ECO:0000269|PubMed:18508924}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P61077-1; Sequence=Displayed; CC Name=2; CC IsoId=P61077-2; Sequence=VSP_038097; CC Name=3; CC IsoId=P61077-3; Sequence=VSP_038096; CC -!- PTM: Phosphorylated by AURKB. {ECO:0000250|UniProtKB:P61079}. 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; U39318; AAA91461.1; -; mRNA. DR EMBL; AF213884; AAF35234.1; -; Genomic_DNA. DR EMBL; AK095822; BAC04632.1; -; mRNA. DR EMBL; DB045280; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; CR456916; CAG33197.1; -; mRNA. DR EMBL; AC018797; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471057; EAX06138.1; -; Genomic_DNA. DR EMBL; CH471057; EAX06143.1; -; Genomic_DNA. DR EMBL; BC003395; AAH03395.1; -; mRNA. DR EMBL; BC037894; AAH37894.1; -; mRNA. DR EMBL; BC066917; AAH66917.1; -; mRNA. DR CCDS; CCDS3659.1; -. [P61077-3] DR CCDS; CCDS3660.1; -. [P61077-1] DR CCDS; CCDS3661.1; -. [P61077-2] DR RefSeq; NP_003331.1; NM_003340.6. [P61077-1] DR RefSeq; NP_871615.1; NM_181886.3. [P61077-1] DR RefSeq; NP_871616.1; NM_181887.3. [P61077-1] DR RefSeq; NP_871617.1; NM_181888.3. [P61077-1] DR RefSeq; NP_871618.1; NM_181889.2. [P61077-1] DR RefSeq; NP_871619.1; NM_181890.3. [P61077-1] DR RefSeq; NP_871620.1; NM_181891.3. [P61077-1] DR RefSeq; NP_871621.1; NM_181892.4. [P61077-2] DR RefSeq; NP_871622.1; NM_181893.3. [P61077-3] DR RefSeq; XP_024309970.1; XM_024454202.2. [P61077-1] DR RefSeq; XP_054206763.1; XM_054350788.1. [P61077-1] DR PDB; 1X23; X-ray; 1.85 A; A/B/C/D=1-147. DR PDB; 2FUH; NMR; -; A=2-147. DR PDB; 3L1Z; X-ray; 3.17 A; A=1-147. DR PDB; 3RPG; X-ray; 2.65 A; A=2-147. DR PDB; 3UGB; X-ray; 2.35 A; A=1-147. DR PDB; 4BVU; X-ray; 2.70 A; B=1-147. DR PDB; 4R8P; X-ray; 3.28 A; L/N=2-147. DR PDB; 4S3O; X-ray; 2.00 A; A/D=2-147. DR PDB; 5EGG; X-ray; 1.76 A; A=1-147. DR PDB; 5IFR; X-ray; 2.20 A; A=2-147. DR PDB; 6CP0; X-ray; 3.01 A; B=1-147. DR PDB; 6T7F; X-ray; 2.58 A; B=2-147. DR PDB; 7JZV; EM; 3.90 A; A=2-147. DR PDB; 7LYB; EM; 3.28 A; P=2-147. DR PDB; 8AMS; X-ray; 2.40 A; A/B=1-147. DR PDB; 8GRQ; EM; 3.87 A; N=1-147. DR PDB; 8SMW; EM; 3.30 A; L=1-147. DR PDB; 8SMX; EM; 3.20 A; L=1-147. DR PDB; 8SMY; EM; 3.20 A; L=1-147. DR PDB; 8SMZ; EM; 3.20 A; L=1-147. DR PDB; 8SN0; EM; 3.20 A; L=1-147. DR PDB; 8SN1; EM; 3.30 A; L=1-147. DR PDB; 8SN2; EM; 3.60 A; L=1-147. DR PDB; 8SN3; EM; 3.80 A; L=1-147. DR PDB; 8SN4; EM; 3.70 A; L=1-147. DR PDB; 8SN5; EM; 3.90 A; L=1-147. DR PDB; 8SN6; EM; 3.70 A; L=1-147. DR PDB; 8SN7; EM; 3.70 A; L=1-147. DR PDB; 8SN8; EM; 3.70 A; L=1-147. DR PDB; 8SN9; EM; 3.90 A; L=1-147. DR PDB; 8SNA; EM; 4.00 A; L=1-147. DR PDB; 8U14; EM; 3.90 A; L=2-147. DR PDB; 8UPF; EM; 3.20 A; L=2-147. DR PDB; 8UQ8; X-ray; 2.34 A; A/a=2-147. DR PDB; 8UQ9; X-ray; 2.30 A; A/a=2-147. DR PDB; 8UQA; X-ray; 2.05 A; K=2-147. DR PDB; 8UQB; X-ray; 2.48 A; A=2-147. DR PDB; 8UQC; X-ray; 2.61 A; A=2-147. DR PDB; 8UQD; X-ray; 3.89 A; B=2-147. DR PDB; 8UQE; X-ray; 3.56 A; B=2-147. DR PDB; 8X7I; EM; 3.27 A; K=1-147. DR PDB; 8X7J; EM; 3.39 A; K=1-147. DR PDB; 8X7K; EM; 3.27 A; K=1-147. DR PDB; 9IPU; EM; 4.30 A; K=1-147. DR PDB; 9LPK; EM; 3.03 A; D/E=1-147. DR AlphaFoldDB; P61077; -. DR BMRB; P61077; -. DR EMDB; EMD-22581; -. DR EMDB; EMD-23591; -. DR EMDB; EMD-34212; -. DR EMDB; EMD-38099; -. DR EMDB; EMD-38100; -. DR EMDB; EMD-38101; -. DR EMDB; EMD-40604; -. DR EMDB; EMD-40605; -. DR EMDB; EMD-40606; -. DR EMDB; EMD-40607; -. DR EMDB; EMD-40608; -. DR EMDB; EMD-40609; -. DR EMDB; EMD-40610; -. DR EMDB; EMD-40611; -. DR EMDB; EMD-40612; -. DR EMDB; EMD-40613; -. DR EMDB; EMD-40614; -. DR EMDB; EMD-40615; -. DR EMDB; EMD-40616; -. DR EMDB; EMD-40617; -. DR EMDB; EMD-40618; -. DR EMDB; EMD-41801; -. DR EMDB; EMD-42446; -. DR EMDB; EMD-60781; -. DR EMDB; EMD-63270; -. DR SMR; P61077; -. DR BioGRID; 113171; 338. DR CORUM; P61077; -. DR DIP; DIP-29062N; -. DR FunCoup; P61077; 3976. DR IntAct; P61077; 115. DR MINT; P61077; -. DR NDEx; IQUERY-CP-UBE2D3; 5 NDEx IQuery Curated Pathways. DR BindingDB; P61077; -. DR ChEMBL; CHEMBL4105911; -. DR MoonDB; P61077; Predicted. DR GlyGen; P61077; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P61077; -. DR PhosphoSitePlus; P61077; -. DR SwissPalm; P61077; -. DR BioMuta; UBE2D3; -. DR DMDM; 46577654; -. DR jPOST; P61077; -. DR MassIVE; P61077; -. DR PeptideAtlas; P61077; -. DR ProteomicsDB; 57258; -. [P61077-1] DR ProteomicsDB; 57259; -. [P61077-2] DR ProteomicsDB; 57260; -. [P61077-3] DR Pumba; P61077; -. DR TopDownProteomics; P61077-1; -. [P61077-1] DR TopDownProteomics; P61077-2; -. [P61077-2] DR Antibodypedia; 26052; 234 antibodies from 33 providers. DR DNASU; 7323; -. DR Ensembl; ENST00000321805.11; ENSP00000318494.7; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000338145.7; ENSP00000337208.3; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000343106.9; ENSP00000345285.5; ENSG00000109332.21. [P61077-2] DR Ensembl; ENST00000349311.12; ENSP00000344069.8; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000357194.10; ENSP00000349722.6; ENSG00000109332.21. [P61077-3] DR Ensembl; ENST00000394801.8; ENSP00000378280.4; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000394803.9; ENSP00000378282.5; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000394804.6; ENSP00000378283.2; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000453744.7; ENSP00000396901.2; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895034.1; ENSP00000565093.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895035.1; ENSP00000565094.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895036.1; ENSP00000565095.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895037.1; ENSP00000565096.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895039.1; ENSP00000565098.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895040.1; ENSP00000565099.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895042.1; ENSP00000565101.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895043.1; ENSP00000565102.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895044.1; ENSP00000565103.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895046.1; ENSP00000565106.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895048.1; ENSP00000565107.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895049.1; ENSP00000565108.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895050.1; ENSP00000565109.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895051.1; ENSP00000565110.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895052.1; ENSP00000565111.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895055.1; ENSP00000565114.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895056.1; ENSP00000565115.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895057.1; ENSP00000565116.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895058.1; ENSP00000565117.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895059.1; ENSP00000565118.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895061.1; ENSP00000565120.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895062.1; ENSP00000565121.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000895063.1; ENSP00000565122.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000917675.1; ENSP00000587734.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000917676.1; ENSP00000587735.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000917678.1; ENSP00000587737.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000917679.1; ENSP00000587738.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000917680.1; ENSP00000587739.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000917681.1; ENSP00000587740.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000917682.1; ENSP00000587741.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000917683.1; ENSP00000587742.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000917686.1; ENSP00000587745.1; ENSG00000109332.21. [P61077-1] DR Ensembl; ENST00000917687.1; ENSP00000587746.1; ENSG00000109332.21. [P61077-1] DR GeneID; 7323; -. DR KEGG; hsa:7323; -. DR MANE-Select; ENST00000453744.7; ENSP00000396901.2; NM_181891.3; NP_871620.1. DR UCSC; uc003hwi.5; human. [P61077-1] DR AGR; HGNC:12476; -. DR ClinPGx; PA37126; -. DR CTD; 7323; -. DR DisGeNET; 7323; -. DR GeneCards; UBE2D3; -. DR HGNC; HGNC:12476; UBE2D3. DR HPA; ENSG00000109332; Low tissue specificity. DR MIM; 602963; gene. DR OpenTargets; ENSG00000109332; -. DR VEuPathDB; HostDB:ENSG00000109332; -. DR GeneTree; ENSGT00940000153169; -. DR InParanoid; P61077; -. DR OMA; NQMAREW; -. DR OrthoDB; 7851174at2759; -. DR PAN-GO; P61077; 5 GO annotations based on evolutionary models. DR PhylomeDB; P61077; -. DR BRENDA; 2.3.2.23; 2681. DR BRENDA; 2.3.2.24; 2681. DR PathwayCommons; P61077; -. DR Reactome; R-HSA-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha. DR Reactome; R-HSA-168927; TICAM1, RIP1-mediated IKK complex recruitment. DR Reactome; R-HSA-201451; Signaling by BMP. DR Reactome; R-HSA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity. DR Reactome; R-HSA-5205685; PINK1-PRKN Mediated Mitophagy. DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling. DR Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins. DR Reactome; R-HSA-8951664; Neddylation. DR Reactome; R-HSA-9033241; Peroxisomal protein import. DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling. DR Reactome; R-HSA-937041; IKK complex recruitment mediated by RIP1. DR Reactome; R-HSA-9705462; Inactivation of CSF3 (G-CSF) signaling. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR Reactome; R-HSA-9954716; ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA. DR SignaLink; P61077; -. DR SIGNOR; P61077; -. DR UniPathway; UPA00143; -. DR Agora; ENSG00000109332; -. DR BioGRID-ORCS; 7323; 583 hits in 1135 CRISPR screens. DR ChiTaRS; UBE2D3; human. DR EvolutionaryTrace; P61077; -. DR GeneWiki; UBE2D3; -. DR GenomeRNAi; 7323; -. DR Pharos; P61077; Tchem. DR PRO; PR:P61077; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P61077; protein. DR Bgee; ENSG00000109332; Expressed in secondary oocyte and 207 other cell types or tissues. DR ExpressionAtlas; P61077; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0010008; C:endosome membrane; EXP:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0061631; F:ubiquitin conjugating enzyme activity; IDA:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:GO_Central. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; TAS:Reactome. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; TAS:Reactome. DR GO; GO:1903749; P:positive regulation of protein localization to mitochondrion; HMP:ParkinsonsUK-UCL. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR GO; GO:0051865; P:protein autoubiquitination; IDA:ParkinsonsUK-UCL. DR GO; GO:0070979; P:protein K11-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0085020; P:protein K6-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0036211; P:protein modification process; TAS:ProtInc. DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB. DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central. DR CDD; cd23792; UBCc_UBE2D; 1. DR FunFam; 3.10.110.10:FF:000101; Ubiquitin-conjugating enzyme E2 D2; 1. DR Gene3D; 3.10.110.10; Ubiquitin Conjugating Enzyme; 1. DR InterPro; IPR000608; UBC. DR InterPro; IPR023313; UBQ-conjugating_AS. DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD. DR PANTHER; PTHR24068; UBIQUITIN-CONJUGATING ENZYME E2; 1. DR Pfam; PF00179; UQ_con; 1. DR SMART; SM00212; UBCc; 1. DR SUPFAM; SSF54495; UBC-like; 1. DR PROSITE; PS00183; UBC_1; 1. DR PROSITE; PS50127; UBC_2; 1. DR PDBsum; 1X23; -. DR PDBsum; 2FUH; -. DR PDBsum; 3L1Z; -. DR PDBsum; 3RPG; -. DR PDBsum; 3UGB; -. DR PDBsum; 4BVU; -. DR PDBsum; 4R8P; -. DR PDBsum; 4S3O; -. DR PDBsum; 5EGG; -. DR PDBsum; 5IFR; -. DR PDBsum; 6CP0; -. DR PDBsum; 6T7F; -. DR PDBsum; 7JZV; -. DR PDBsum; 7LYB; -. DR PDBsum; 8AMS; -. DR PDBsum; 8GRQ; -. DR PDBsum; 8SMW; -. DR PDBsum; 8SMX; -. DR PDBsum; 8SMY; -. DR PDBsum; 8SMZ; -. DR PDBsum; 8SN0; -. DR PDBsum; 8SN1; -. DR PDBsum; 8SN2; -. DR PDBsum; 8SN3; -. DR PDBsum; 8SN4; -. DR PDBsum; 8SN5; -. DR PDBsum; 8SN6; -. DR PDBsum; 8SN7; -. DR PDBsum; 8SN8; -. DR PDBsum; 8SN9; -. DR PDBsum; 8SNA; -. DR PDBsum; 8U14; -. DR PDBsum; 8UPF; -. DR PDBsum; 8UQ8; -. DR PDBsum; 8UQ9; -. DR PDBsum; 8UQA; -. DR PDBsum; 8UQB; -. DR PDBsum; 8UQC; -. DR PDBsum; 8UQD; -. DR PDBsum; 8UQE; -. DR PDBsum; 8X7I; -. DR PDBsum; 8X7J; -. DR PDBsum; 8X7K; -. DR PDBsum; 9IPU; -. DR PDBsum; 9LPK; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Cell membrane; KW Disulfide bond; DNA damage; DNA repair; Endosome; Membrane; Phosphoprotein; KW Proteomics identification; Reference proteome; Transferase; KW Ubl conjugation pathway. FT CHAIN 1..147 FT /note="Ubiquitin-conjugating enzyme E2 D3" FT /id="PRO_0000082466" 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:0000269|Ref.32" FT VAR_SEQ 1..8 FT /note="MALKRINK -> MLSNRKCLSK (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_038096" FT VAR_SEQ 134..147 FT /note="YNRISREWTQKYAM -> YNRLAREWTEKYAML (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_038097" FT MUTAGEN 77 FT /note="N->S: Activity is restricted HECT-type and not FT RING-containing E3 ubiquitin-protein ligases. Exhibits FT ubiquitin transfer with ARIH1 and PRKN." FT /evidence="ECO:0000269|PubMed:21532592" FT MUTAGEN 85 FT /note="C->A: Loss of function." FT /evidence="ECO:0000269|PubMed:10329681" FT MUTAGEN 87 FT /note="D->E,P: Has intermediate lysine reactivity." FT /evidence="ECO:0000269|PubMed:21532592" FT MUTAGEN 87 FT /note="D->K: Abolishes affect lysine reactivity." FT /evidence="ECO:0000269|PubMed:21532592" FT MUTAGEN 87 FT /note="D->N: Does not affect lysine reactivity." FT /evidence="ECO:0000269|PubMed:21532592" FT MUTAGEN 117 FT /note="D->H: Strongly impairs lysine reactivity but retains FT some ability to transfer ubiquitin to BRCA1." FT /evidence="ECO:0000269|PubMed:21532592" FT CONFLICT 50 FT /note="Missing (in Ref. 3; DB045280)" FT /evidence="ECO:0000305" FT CONFLICT 123 FT /note="I -> L (in Ref. 7; AAH66917)" FT /evidence="ECO:0000305" FT CONFLICT 137 FT /note="I -> V (in Ref. 3; CAG33197)" FT /evidence="ECO:0000305" FT CONFLICT 147 FT /note="M -> I (in Ref. 3; CAG33197)" FT /evidence="ECO:0000305" FT HELIX 1..15 FT /evidence="ECO:0007829|PDB:5EGG" FT STRAND 19..21 FT /evidence="ECO:0007829|PDB:2FUH" FT STRAND 22..28 FT /evidence="ECO:0007829|PDB:5EGG" FT STRAND 32..38 FT /evidence="ECO:0007829|PDB:5EGG" FT STRAND 41..43 FT /evidence="ECO:0007829|PDB:4S3O" FT TURN 44..47 FT /evidence="ECO:0007829|PDB:5EGG" FT STRAND 49..55 FT /evidence="ECO:0007829|PDB:5EGG" FT TURN 58..61 FT /evidence="ECO:0007829|PDB:5EGG" FT STRAND 66..71 FT /evidence="ECO:0007829|PDB:5EGG" FT STRAND 76..78 FT /evidence="ECO:0007829|PDB:8SMZ" FT STRAND 80..84 FT /evidence="ECO:0007829|PDB:4R8P" FT HELIX 87..89 FT /evidence="ECO:0007829|PDB:5EGG" FT TURN 90..92 FT /evidence="ECO:0007829|PDB:5EGG" FT HELIX 99..111 FT /evidence="ECO:0007829|PDB:5EGG" FT STRAND 115..117 FT /evidence="ECO:0007829|PDB:6CP0" FT HELIX 121..129 FT /evidence="ECO:0007829|PDB:5EGG" FT HELIX 131..145 FT /evidence="ECO:0007829|PDB:5EGG" SQ SEQUENCE 147 AA; 16687 MW; ADD74A8A708EFEE3 CRC64; MALKRINKEL SDLARDPPAQ CSAGPVGDDM FHWQATIMGP NDSPYQGGVF FLTIHFPTDY PFKPPKVAFT TRIYHPNINS NGSICLDILR SQWSPALTIS KVLLSICSLL CDPNPDDPLV PEIARIYKTD RDKYNRISRE WTQKYAM //