UB2D3_HUMAN
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 03-AUG-2022, entry version 184.
DE RecName: Full=Ubiquitin-conjugating enzyme E2 D3;
DE EC=2.3.2.23 {ECO:0000269|PubMed:20061386};
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, AND INTERACTION WITH DDX58 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 [28]
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 [29]
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 [30]
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.
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 (PubMed:28469175).
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:28469175}.
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 -!- 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 -!- 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 (PubMed:24211586). Interacts with DDX58 and RNF135; involved
CC in DDX58 ubiquitination and activation (PubMed:28469175).
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:24211586,
CC ECO:0000269|PubMed:28469175, ECO:0000269|Ref.30}.
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=5; 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}.
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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_181887.2. [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_181890.2. [P61077-1]
DR RefSeq; NP_871620.1; NM_181891.2. [P61077-1]
DR RefSeq; NP_871621.1; NM_181892.3. [P61077-2]
DR RefSeq; NP_871622.1; NM_181893.2. [P61077-3]
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 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 AlphaFoldDB; P61077; -.
DR BMRB; P61077; -.
DR SMR; P61077; -.
DR BioGRID; 113171; 270.
DR CORUM; P61077; -.
DR DIP; DIP-29062N; -.
DR IntAct; P61077; 111.
DR MINT; P61077; -.
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 EPD; P61077; -.
DR jPOST; P61077; -.
DR MassIVE; P61077; -.
DR MaxQB; P61077; -.
DR PeptideAtlas; P61077; -.
DR PRIDE; P61077; -.
DR ProteomicsDB; 57258; -. [P61077-1]
DR ProteomicsDB; 57259; -. [P61077-2]
DR ProteomicsDB; 57260; -. [P61077-3]
DR TopDownProteomics; P61077-1; -. [P61077-1]
DR TopDownProteomics; P61077-2; -. [P61077-2]
DR Antibodypedia; 26052; 228 antibodies from 30 providers.
DR DNASU; 7323; -.
DR Ensembl; ENST00000321805.11; ENSP00000318494.7; ENSG00000109332.20. [P61077-1]
DR Ensembl; ENST00000338145.7; ENSP00000337208.3; ENSG00000109332.20. [P61077-1]
DR Ensembl; ENST00000343106.9; ENSP00000345285.5; ENSG00000109332.20. [P61077-2]
DR Ensembl; ENST00000349311.12; ENSP00000344069.8; ENSG00000109332.20. [P61077-1]
DR Ensembl; ENST00000357194.10; ENSP00000349722.6; ENSG00000109332.20. [P61077-3]
DR Ensembl; ENST00000394801.8; ENSP00000378280.4; ENSG00000109332.20. [P61077-1]
DR Ensembl; ENST00000394803.9; ENSP00000378282.5; ENSG00000109332.20. [P61077-1]
DR Ensembl; ENST00000394804.6; ENSP00000378283.2; ENSG00000109332.20. [P61077-1]
DR Ensembl; ENST00000453744.7; ENSP00000396901.2; ENSG00000109332.20. [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 CTD; 7323; -.
DR DisGeNET; 7323; -.
DR GeneCards; UBE2D3; -.
DR HGNC; HGNC:12476; UBE2D3.
DR HPA; ENSG00000109332; Low tissue specificity.
DR MIM; 602963; gene.
DR neXtProt; NX_P61077; -.
DR OpenTargets; ENSG00000109332; -.
DR PharmGKB; PA37126; -.
DR VEuPathDB; HostDB:ENSG00000109332; -.
DR GeneTree; ENSGT00940000153169; -.
DR InParanoid; P61077; -.
DR OMA; QMDICLL; -.
DR OrthoDB; 1337945at2759; -.
DR PhylomeDB; P61077; -.
DR TreeFam; TF101108; -.
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-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 SignaLink; P61077; -.
DR SIGNOR; P61077; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 7323; 568 hits in 1058 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 205 other tissues.
DR ExpressionAtlas; P61077; baseline and differential.
DR Genevisible; P61077; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
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; IDA:ParkinsonsUK-UCL.
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:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
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:1903955; P:positive regulation of protein targeting 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: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 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 3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cell membrane;
KW Disulfide bond; DNA damage; DNA repair; Endosome; Membrane;
KW Nucleotide-binding; Phosphoprotein; 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.29"
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 RING-
FT containing E3 ubiquitin-protein ligases. Exhibits ubiquitin
FT 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:4R8P"
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
