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Database: UniProt
Entry: P61077
LinkDB: P61077
Original site: P61077 
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   12-AUG-2020, entry version 175.
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; 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}.
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   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   SMR; P61077; -.
DR   BioGRID; 113171; 255.
DR   CORUM; P61077; -.
DR   DIP; DIP-29062N; -.
DR   IntAct; P61077; 110.
DR   MINT; P61077; -.
DR   BindingDB; P61077; -.
DR   ChEMBL; CHEMBL4105911; -.
DR   MoonDB; P61077; Predicted.
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; 213 antibodies.
DR   Ensembl; ENST00000321805; ENSP00000318494; ENSG00000109332. [P61077-1]
DR   Ensembl; ENST00000338145; ENSP00000337208; ENSG00000109332. [P61077-1]
DR   Ensembl; ENST00000343106; ENSP00000345285; ENSG00000109332. [P61077-2]
DR   Ensembl; ENST00000349311; ENSP00000344069; ENSG00000109332. [P61077-1]
DR   Ensembl; ENST00000357194; ENSP00000349722; ENSG00000109332. [P61077-3]
DR   Ensembl; ENST00000394801; ENSP00000378280; ENSG00000109332. [P61077-1]
DR   Ensembl; ENST00000394803; ENSP00000378282; ENSG00000109332. [P61077-1]
DR   Ensembl; ENST00000394804; ENSP00000378283; ENSG00000109332. [P61077-1]
DR   Ensembl; ENST00000453744; ENSP00000396901; ENSG00000109332. [P61077-1]
DR   GeneID; 7323; -.
DR   KEGG; hsa:7323; -.
DR   UCSC; uc003hwi.5; human. [P61077-1]
DR   CTD; 7323; -.
DR   DisGeNET; 7323; -.
DR   EuPathDB; HostDB:ENSG00000109332.19; -.
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   GeneTree; ENSGT00940000153169; -.
DR   InParanoid; P61077; -.
DR   KO; K06689; -.
DR   OMA; FKPPKVH; -.
DR   OrthoDB; 1337945at2759; -.
DR   PhylomeDB; P61077; -.
DR   TreeFam; TF101108; -.
DR   BRENDA; 2.3.2.B6; 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-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   SignaLink; P61077; -.
DR   SIGNOR; P61077; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 7323; 528 hits in 857 CRISPR screens.
DR   ChiTaRS; UBE2D3; human.
DR   EvolutionaryTrace; P61077; -.
DR   GeneWiki; UBE2D3; -.
DR   GenomeRNAi; 7323; -.
DR   Pharos; P61077; Tbio.
DR   PRO; PR:P61077; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; P61077; protein.
DR   Bgee; ENSG00000109332; Expressed in secondary oocyte and 245 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:0000151; C:ubiquitin ligase complex; IBA:GO_Central.
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:0031625; F:ubiquitin protein ligase binding; IBA: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:0030509; P:BMP signaling pathway; TAS:Reactome.
DR   GO; GO:0006464; P:cellular protein modification process; TAS:ProtInc.
DR   GO; GO:0071276; P:cellular response to cadmium ion; IEA:Ensembl.
DR   GO; GO:0071288; P:cellular response to mercury ion; IEA:Ensembl.
DR   GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR   GO; GO:0002756; P:MyD88-independent toll-like receptor 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:0006513; P:protein monoubiquitination; IDA:UniProtKB.
DR   GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR   GO; GO:0006625; P:protein targeting to peroxisome; TAS:Reactome.
DR   GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR   GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
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:0000244|PDB:5EGG"
FT   STRAND          19..21
FT                   /evidence="ECO:0000244|PDB:2FUH"
FT   STRAND          22..28
FT                   /evidence="ECO:0000244|PDB:5EGG"
FT   STRAND          32..38
FT                   /evidence="ECO:0000244|PDB:5EGG"
FT   STRAND          41..43
FT                   /evidence="ECO:0000244|PDB:4S3O"
FT   TURN            44..47
FT                   /evidence="ECO:0000244|PDB:5EGG"
FT   STRAND          49..55
FT                   /evidence="ECO:0000244|PDB:5EGG"
FT   TURN            58..61
FT                   /evidence="ECO:0000244|PDB:5EGG"
FT   STRAND          66..71
FT                   /evidence="ECO:0000244|PDB:5EGG"
FT   STRAND          76..78
FT                   /evidence="ECO:0000244|PDB:4R8P"
FT   STRAND          80..84
FT                   /evidence="ECO:0000244|PDB:4R8P"
FT   HELIX           87..89
FT                   /evidence="ECO:0000244|PDB:5EGG"
FT   TURN            90..92
FT                   /evidence="ECO:0000244|PDB:5EGG"
FT   HELIX           99..111
FT                   /evidence="ECO:0000244|PDB:5EGG"
FT   STRAND          115..117
FT                   /evidence="ECO:0000244|PDB:6CP0"
FT   HELIX           121..129
FT                   /evidence="ECO:0000244|PDB:5EGG"
FT   HELIX           131..145
FT                   /evidence="ECO:0000244|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
//
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