ID UB2L3_HUMAN Reviewed; 154 AA. AC P68036; B2R4A7; B4DDG1; B4DSZ4; E7EWS7; P51966; P70653; Q9HAV1; DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2004, sequence version 1. DT 02-SEP-2026, entry version 197. DE RecName: Full=Ubiquitin-conjugating enzyme E2 L3; DE EC=2.3.2.23 {ECO:0000269|PubMed:20061386}; DE AltName: Full=E2 ubiquitin-conjugating enzyme L3; DE AltName: Full=L-UBC; DE AltName: Full=UbcH7; DE AltName: Full=Ubiquitin carrier protein L3; DE AltName: Full=Ubiquitin-conjugating enzyme E2-F1; DE AltName: Full=Ubiquitin-protein ligase L3; GN Name=UBE2L3; Synonyms=UBCE7, UBCH7; 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=8563171; DOI=10.1007/bf00354295; RA Robinson P.A., Leek J.P., Thompson J., Carr I.M., Bailey A., Moynihan T.P., RA Coletta P.L., Lench N.J., Markham A.F.; RT "A human ubiquitin conjugating enzyme, L-UBC, maps in the Alzheimer's RT disease locus on chromosome 14q24.3."; RL Mamm. Genome 6:725-731(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8576257; DOI=10.1074/jbc.271.5.2795; RA Nuber U., Schwarz S., Kaiser P., Schneider R., Scheffner M.; RT "Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1) and RT characterization of their interaction with E6-AP and RSP5."; RL J. Biol. Chem. 271:2795-2800(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Testis; RX PubMed=9693040; DOI=10.1006/geno.1998.5257; RA Moynihan T.P., Cole C.G., Dunham I., O'Neil L., Markham A.F., RA Robinson P.A.; RT "Fine-mapping, genomic organization, and transcript analysis of the human RT ubiquitin-conjugating enzyme gene UBE2L3."; RL Genomics 51:124-127(1998). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Blood; RA Poloumienko A.; RT "Is retroposition a common way of spreading ubiquitin-conjugating enzyme RT genes throughout mammalian genomes?"; RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Adrenal gland, and Thalamus; 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [8] 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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 [10] RP PROTEIN SEQUENCE OF 53-67; 67-74 AND 101-122. RX PubMed=8144544; DOI=10.1016/s0021-9258(17)36920-x; RA Blumenfeld N., Gonen H., Mayer A., Smith C.E., Siegel N.R., Schwartz A.L., RA Ciechanover A.; RT "Purification and characterization of a novel species of ubiquitin-carrier RT protein, E2, that is involved in degradation of non-'N-end rule' protein RT substrates."; RL J. Biol. Chem. 269:9574-9581(1994). RN [11] RP PROMOTER ANALYSIS. RX PubMed=10760570; DOI=10.1016/s0167-4781(00)00024-5; RA Ardley H.C., Moynihan T.P., Markham A.F., Robinson P.A.; RT "Promoter analysis of the human ubiquitin-conjugating enzyme gene family RT UBE2L1-4, including UBE2L3 which encodes UbcH7."; RL Biochim. Biophys. Acta 1491:57-64(2000). RN [12] RP FUNCTION, INTERACTION WITH PRKN, AND MUTAGENESIS OF CYS-86. RX PubMed=10888878; DOI=10.1038/77060; RA Shimura H., Hattori N., Kubo S., Mizuno Y., Asakawa S., Minoshima S., RA Shimizu N., Iwai K., Chiba T., Tanaka K., Suzuki T.; RT "Familial Parkinson disease gene product, parkin, is a ubiquitin-protein RT ligase."; RL Nat. Genet. 25:302-305(2000). RN [13] RP INTERACTION WITH RNF19A. RX PubMed=11237715; DOI=10.1006/bbrc.2001.4414; RA Niwa J., Ishigaki S., Doyu M., Suzuki T., Tanaka K., Sobue G.; RT "A novel centrosomal ring-finger protein, dorfin, mediates ubiquitin ligase RT activity."; RL Biochem. Biophys. Res. Commun. 281:706-713(2001). RN [14] RP INTERACTION WITH ARIH1, AND SUBCELLULAR LOCATION. RX PubMed=11278816; DOI=10.1074/jbc.m011028200; RA Ardley H.C., Tan N.G.S., Rose S.A., Markham A.F., Robinson P.A.; RT "Features of the parkin/ariadne-like ubiquitin ligase, HHARI, that regulate RT its interaction with the ubiquitin-conjugating enzyme, Ubch7."; RL J. Biol. Chem. 276:19640-19647(2001). RN [15] RP INTERACTION WITH CCNB1IP1. RX PubMed=12612082; DOI=10.1128/mcb.23.6.2109-2122.2003; RA Toby G.G., Gherraby W., Coleman T.R., Golemis E.A.; RT "A novel RING finger protein, human enhancer of invasion 10, alters mitotic RT progression through regulation of cyclin B levels."; RL Mol. Cell. Biol. 23:2109-2122(2003). RN [16] RP FUNCTION, AND INTERACTION WITH NCOA1. RX PubMed=15367689; DOI=10.1128/mcb.24.19.8716-8726.2004; RA Verma S., Ismail A., Gao X., Fu G., Li X., O'Malley B.W., Nawaz Z.; RT "The ubiquitin-conjugating enzyme UBCH7 acts as a coactivator for steroid RT hormone receptors."; RL Mol. Cell. Biol. 24:8716-8726(2004). RN [17] RP INTERACTION WITH RNF144B. RX PubMed=16427630; DOI=10.1016/j.febslet.2005.09.105; RA Huang J., Xu L.-G., Liu T., Zhai Z., Shu H.-B.; RT "The p53-inducible E3 ubiquitin ligase p53RFP induces p53-dependent RT apoptosis."; RL FEBS Lett. 580:940-947(2006). RN [18] RP FUNCTION, INTERACTION WITH NR3C1, AND SUBCELLULAR LOCATION. RX PubMed=17003263; DOI=10.1677/joe.1.06799; RA Garside H., Waters C., Berry A., Rice L., Ardley H.C., White A., RA Robinson P.A., Ray D.; RT "UbcH7 interacts with the glucocorticoid receptor and mediates receptor RT autoregulation."; RL J. Endocrinol. 190:621-629(2006). RN [19] RP INTERACTION WITH RNF19B. RX PubMed=16709802; DOI=10.4049/jimmunol.176.11.6454; RA Fortier J.M., Kornbluth J.; RT "NK lytic-associated molecule, involved in NK cytotoxic function, is an E3 RT ligase."; RL J. Immunol. 176:6454-6463(2006). RN [20] RP FUNCTION, AND INTERACTION WITH ARIH2. RX PubMed=19340006; DOI=10.1038/leu.2009.57; RA Marteijn J.A., van der Meer L.T., Smit J.J., Noordermeer S.M., Wissink W., RA Jansen P., Swarts H.G., Hibbert R.G., de Witte T., Sixma T.K., Jansen J.H., RA van der Reijden B.A.; RT "The ubiquitin ligase Triad1 inhibits myelopoiesis through UbcH7 and Ubc13 RT interacting domains."; RL Leukemia 23:1480-1489(2009). RN [21] RP FUNCTION, UBIQUITINATION, AND MUTAGENESIS OF CYS-86. RX PubMed=18946090; DOI=10.1091/mbc.e08-01-0036; RA Whitcomb E.A., Dudek E.J., Liu Q., Taylor A.; RT "Novel control of S phase of the cell cycle by ubiquitin-conjugating enzyme RT H7."; RL Mol. Biol. Cell 20:1-9(2009). RN [22] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-131, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [23] 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 [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, DOMAIN, INTERACTION WITH PRKN AND ARIH1, AND MUTAGENESIS OF RP PRO-88 AND HIS-119. 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 AUTOUBIQUITINATION, AND MUTAGENESIS OF LYS-9; PHE-63; GLU-93; LYS-96 AND RP LYS-100. RX PubMed=22496338; DOI=10.1074/mcp.o111.013706; RA Sheng Y., Hong J.H., Doherty R., Srikumar T., Shloush J., Avvakumov G.V., RA Walker J.R., Xue S., Neculai D., Wan J.W., Kim S.K., Arrowsmith C.H., RA Raught B., Dhe-Paganon S.; RT "A human ubiquitin conjugating enzyme (E2)-HECT E3 ligase structure- RT function screen."; RL Mol. Cell. Proteomics 11:329-341(2012). RN [27] RP INTERACTION WITH NDFIP1. RX PubMed=25632008; DOI=10.4049/jimmunol.1402742; RA Kathania M., Zeng M., Yadav V.N., Moghaddam S.J., Yang B., Venuprasad K.; RT "Ndfip1 regulates itch ligase activity and airway inflammation via UbcH7."; RL J. Immunol. 194:2160-2167(2015). RN [28] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [29] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF PHE-63. RX PubMed=38605244; DOI=10.1038/s41594-024-01257-y; RA Horn-Ghetko D., Hopf L.V.M., Tripathi-Giesgen I., Du J., Kostrhon S., RA Vu D.T., Beier V., Steigenberger B., Prabu J.R., Stier L., Bruss E.M., RA Mann M., Xiong Y., Schulman B.A.; RT "Noncanonical assembly, neddylation and chimeric cullin-RING/RBR RT ubiquitylation by the 1.8 MDa CUL9 E3 ligase complex."; RL Nat. Struct. Mol. Biol. 0:0-0(2024). RN [30] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH UBE3A. RX PubMed=10558980; DOI=10.1126/science.286.5443.1321; RA Huang L., Kinnucan E., Wang G., Beaudenon S., Howley P.M., Huibregtse J.M., RA Pavletich N.P.; RT "Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the RT E2-E3 enzyme cascade."; RL Science 286:1321-1326(1999). RN [31] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH 47-434 OF CBL AND RP ZAP70. RX PubMed=10966114; DOI=10.1016/s0092-8674(00)00057-x; RA Zheng N., Wang P., Jeffrey P.D., Pavletich N.P.; RT "Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin- RT protein ligases."; RL Cell 102:533-539(2000). RN [32] RP X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) IN COMPLEX WITH RNF31, AND FUNCTION. RX PubMed=35294289; DOI=10.1073/pnas.2116776119; RA Liu J., Wang Y., Wang D., Wang Y., Xu X., Zhang Y., Li Y., Zhang M., RA Gong X., Tang Y., Shen L., Li M., Pan L.; RT "Mechanistic insights into the subversion of the linear ubiquitin chain RT assembly complex by the E3 ligase IpaH1.4 of Shigella flexneri."; RL Proc. Natl. Acad. Sci. U.S.A. 119:e2116776119-e2116776119(2022). CC -!- FUNCTION: Ubiquitin-conjugating enzyme E2 that specifically acts with CC HECT-type and RBR family E3 ubiquitin-protein ligases. Does not CC function with most RING-containing E3 ubiquitin-protein ligases because CC it lacks intrinsic E3-independent reactivity with lysine; in contrast, CC it has activity with the RBR family E3 enzymes, such as PRKN, RNF31 and CC ARIH1, that function like RING-HECT hybrids. Accepts ubiquitin from the CC E1 complex and catalyzes its covalent attachment to other proteins. CC Mediates ubiquitination by the CUL9-RBX1 complex (PubMed:38605244). In CC vitro catalyzes 'Lys-11'-linked polyubiquitination. Involved in the CC selective degradation of short-lived and abnormal proteins. Down- CC regulated during the S-phase it is involved in progression through the CC cell cycle. Regulates nuclear hormone receptors transcriptional CC activity. May play a role in myelopoiesis. CC {ECO:0000269|PubMed:10888878, ECO:0000269|PubMed:15367689, CC ECO:0000269|PubMed:17003263, ECO:0000269|PubMed:18946090, CC ECO:0000269|PubMed:19340006, ECO:0000269|PubMed:20061386, CC ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:35294289, CC ECO:0000269|PubMed:38605244}. 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:38605244}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000255|PROSITE-ProRule:PRU00388}. CC -!- SUBUNIT: Interacts with PRKN; involved in ubiquitination and CC degradation of misfolded proteins. Interacts with UBE3A; used by the CC papilloma virus HPV-16 E6 protein to ubiquitinate p53/TP53. Interacts CC with CCNB1IP1, CBL, ZAP70, RNF19A, RNF19B and RNF144B. Interacts with CC ARIH1. Interacts with ARIH2 (via RING-type 1). Interacts with NCOA1; CC they functionally interact to regulate progesterone receptor CC transcriptional activity. May interact with NR3C1. Interacts with CC NDFIP1 (via N-terminus); the interaction mediates recruitment of UBE2L3 CC to ITCH and causes MAP3K7 ubiquitination (PubMed:25632008). CC {ECO:0000269|PubMed:10558980, ECO:0000269|PubMed:10888878, CC ECO:0000269|PubMed:10966114, ECO:0000269|PubMed:11237715, CC ECO:0000269|PubMed:11278816, ECO:0000269|PubMed:12612082, CC ECO:0000269|PubMed:15367689, ECO:0000269|PubMed:16427630, CC ECO:0000269|PubMed:16709802, ECO:0000269|PubMed:17003263, CC ECO:0000269|PubMed:19340006, ECO:0000269|PubMed:21532592, CC ECO:0000269|PubMed:25632008}. CC -!- INTERACTION: CC P68036; Q9Y4X5: ARIH1; NbExp=7; IntAct=EBI-711173, EBI-2514233; CC P68036; O95376: ARIH2; NbExp=12; IntAct=EBI-711173, EBI-711158; CC P68036; O15344: MID1; NbExp=4; IntAct=EBI-711173, EBI-2340316; CC P68036; O60260-5: PRKN; NbExp=3; IntAct=EBI-711173, EBI-21251460; CC P68036; Q9BYM8: RBCK1; NbExp=4; IntAct=EBI-711173, EBI-2340624; CC P68036; P50876: RNF144A; NbExp=4; IntAct=EBI-711173, EBI-2340657; CC P68036; Q8N6D2: RNF182; NbExp=3; IntAct=EBI-711173, EBI-2130099; CC P68036; Q6ZMZ0: RNF19B; NbExp=2; IntAct=EBI-711173, EBI-2466594; CC P68036; Q9NWF9: RNF216; NbExp=3; IntAct=EBI-711173, EBI-723313; CC P68036; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-711173, EBI-357085; CC P68036; Q99PZ6: ospG; Xeno; NbExp=3; IntAct=EBI-711173, EBI-9316527; CC P68036-1; Q9Y4X5: ARIH1; NbExp=3; IntAct=EBI-15556257, EBI-2514233; CC P68036-1; Q99PZ6: ospG; Xeno; NbExp=4; IntAct=EBI-15556257, EBI-9316527; CC P68036-1; Q8ZNR3: sopA; Xeno; NbExp=2; IntAct=EBI-15556257, EBI-15674008; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11278816, CC ECO:0000269|PubMed:17003263}. Cytoplasm {ECO:0000269|PubMed:11278816, CC ECO:0000269|PubMed:17003263}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P68036-1; Sequence=Displayed; CC Name=2; CC IsoId=P68036-2; Sequence=VSP_045152; CC Name=3; CC IsoId=P68036-3; Sequence=VSP_047342; CC -!- TISSUE SPECIFICITY: Ubiquitous, with highest expression in testis. CC -!- DOMAIN: In contrast to other ubiquitin-conjugating enzymes E2, residues CC essential for lysine reactivity are absent: Pro and a His residues are CC present instead of an Asp and an Asp residues in positions 88 and 119, CC respectively. {ECO:0000269|PubMed:21532592}. CC -!- PTM: Ubiquitinated. The alteration of UBE2L3 protein levels during the CC S-phase of the cell cycle is due to ubiquitin-dependent proteasomal CC degradation. Autoubiquitinated in vitro (PubMed:22496338). CC {ECO:0000269|PubMed:18946090, ECO:0000269|PubMed:22496338}. CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family. CC {ECO:0000255|PROSITE-ProRule:PRU00388}. CC -!- CAUTION: PubMed:10760570 reported that UBE2L1, UBE2L2 and UBE2L4 are CC most likely pseudogenes and the only expressed member of this subfamily CC seems to be UBE2L3. {ECO:0000305}. 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; S81003; AAB36017.1; -; mRNA. DR EMBL; X92962; CAA63538.1; -; mRNA. DR EMBL; AJ000519; CAA04156.1; -; mRNA. DR EMBL; AF300336; AAG17922.1; -; Genomic_DNA. DR EMBL; CR456606; CAG30492.1; -; mRNA. DR EMBL; AK293179; BAG56722.1; -; mRNA. DR EMBL; AK299985; BAG61806.1; -; mRNA. DR EMBL; AK311761; BAG34704.1; -; mRNA. DR EMBL; AP000553; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP000557; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP000558; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471095; EAW59459.1; -; Genomic_DNA. DR EMBL; BC053368; AAH53368.1; -; mRNA. DR CCDS; CCDS13790.1; -. [P68036-1] DR CCDS; CCDS58795.1; -. [P68036-3] DR CCDS; CCDS58796.1; -. [P68036-2] DR RefSeq; NP_001243284.1; NM_001256355.1. [P68036-3] DR RefSeq; NP_001243285.1; NM_001256356.2. [P68036-2] DR RefSeq; NP_003338.1; NM_003347.4. [P68036-1] DR PDB; 1C4Z; X-ray; 2.60 A; D=1-154. DR PDB; 1FBV; X-ray; 2.90 A; C=1-154. DR PDB; 3SQV; X-ray; 3.30 A; C/D=1-154. DR PDB; 3SY2; X-ray; 3.27 A; C/D=1-154. DR PDB; 4Q5E; X-ray; 1.87 A; C=1-154. DR PDB; 4Q5H; X-ray; 2.00 A; C=1-154. DR PDB; 5HPT; X-ray; 2.84 A; C/F=2-154. DR PDB; 5TTE; X-ray; 3.50 A; E=1-154. DR PDB; 5UDH; X-ray; 3.24 A; C/D=1-154. DR PDB; 6CP2; X-ray; 2.90 A; B=1-154. DR PDB; 6DJW; X-ray; 3.80 A; C=1-154. DR PDB; 6DJX; X-ray; 4.80 A; C=1-154. DR PDB; 6N13; NMR; -; C=1-154. DR PDB; 6XXU; NMR; -; A=1-154. DR PDB; 7B5L; EM; 3.80 A; D=1-154. DR PDB; 7B5N; EM; 3.60 A; D=1-154. DR PDB; 7OIK; EM; 3.50 A; B=1-154. DR PDB; 7V8F; X-ray; 1.66 A; A=1-154. DR PDB; 8EAZ; X-ray; 3.08 A; C/D=1-154. DR PDB; 8EB0; X-ray; 3.03 A; B=1-154. DR PDB; 9I1J; EM; 3.80 A; B=1-154. DR AlphaFoldDB; P68036; -. DR BMRB; P68036; -. DR EMDB; EMD-12037; -. DR EMDB; EMD-12041; -. DR EMDB; EMD-12931; -. DR EMDB; EMD-52571; -. DR MDposit; P68036; -. DR SMR; P68036; -. DR BioGRID; 113180; 242. DR CORUM; P68036; -. DR DIP; DIP-6124N; -. DR FunCoup; P68036; 3461. DR IntAct; P68036; 53. DR MINT; P68036; -. DR NDEx; IQUERY-CP-UBE2L3; 4 NDEx IQuery Curated Pathways. DR BindingDB; P68036; -. DR ChEMBL; CHEMBL4105871; -. DR MoonDB; P68036; Predicted. DR GlyGen; P68036; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P68036; -. DR PhosphoSitePlus; P68036; -. DR SwissPalm; P68036; -. DR BioMuta; UBE2L3; -. DR DMDM; 54039805; -. DR OGP; P51966; -. DR jPOST; P68036; -. DR MassIVE; P68036; -. DR PeptideAtlas; P68036; -. DR ProteomicsDB; 18904; -. DR ProteomicsDB; 3856; -. DR ProteomicsDB; 57528; -. [P68036-1] DR Pumba; P68036; -. DR TopDownProteomics; P68036-1; -. [P68036-1] DR TopDownProteomics; P68036-2; -. [P68036-2] DR Antibodypedia; 8540; 472 antibodies from 40 providers. DR DNASU; 7332; -. DR Ensembl; ENST00000342192.9; ENSP00000344259.5; ENSG00000185651.17. [P68036-1] DR Ensembl; ENST00000458578.6; ENSP00000400906.2; ENSG00000185651.17. [P68036-3] DR Ensembl; ENST00000545681.2; ENSP00000445931.1; ENSG00000185651.17. [P68036-2] DR GeneID; 7332; -. DR KEGG; hsa:7332; -. DR MANE-Select; ENST00000342192.9; ENSP00000344259.5; NM_003347.4; NP_003338.1. DR UCSC; uc002zva.2; human. [P68036-1] DR AGR; HGNC:12488; -. DR ClinPGx; PA37137; -. DR CTD; 7332; -. DR DisGeNET; 7332; -. DR GeneCards; UBE2L3; -. DR HGNC; HGNC:12488; UBE2L3. DR HPA; ENSG00000185651; Low tissue specificity. DR MalaCards; UBE2L3; -. DR MIM; 603721; gene. DR OpenTargets; ENSG00000185651; -. DR Orphanet; 536; Systemic lupus erythematosus. DR VEuPathDB; HostDB:ENSG00000185651; -. DR eggNOG; KOG0422; Eukaryota. DR GeneTree; ENSGT00940000153654; -. DR HOGENOM; CLU_030988_13_3_1; -. DR InParanoid; P68036; -. DR OMA; ADLHTWH; -. DR OrthoDB; 9973183at2759; -. DR PAN-GO; P68036; 4 GO annotations based on evolutionary models. DR PhylomeDB; P68036; -. DR BRENDA; 2.3.2.23; 2681. DR BRENDA; 2.3.2.24; 2681. DR PathwayCommons; P68036; -. DR Reactome; R-HSA-5205685; PINK1-PRKN Mediated Mitophagy. DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling. DR Reactome; R-HSA-5675482; Regulation of necroptotic cell death. DR Reactome; R-HSA-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes. DR Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; P68036; -. DR SIGNOR; P68036; -. DR UniPathway; UPA00143; -. DR Agora; ENSG00000185651; -. DR BioGRID-ORCS; 7332; 680 hits in 1137 CRISPR screens. DR ChiTaRS; UBE2L3; human. DR EvolutionaryTrace; P68036; -. DR GeneWiki; UBE2L3; -. DR GenomeRNAi; 7332; -. DR Pharos; P68036; Tbio. DR PRO; PR:P68036; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P68036; protein. DR Bgee; ENSG00000185651; Expressed in oocyte and 205 other cell types or tissues. DR ExpressionAtlas; P68036; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0000151; C:ubiquitin ligase complex; TAS:UniProtKB. DR GO; GO:0019899; F:enzyme binding; TAS:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0061631; F:ubiquitin conjugating enzyme activity; IDA:MGI. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0097027; F:ubiquitin-protein transferase activator activity; IGI:ParkinsonsUK-UCL. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0044770; P:cell cycle phase transition; IMP:UniProtKB. DR GO; GO:0008283; P:cell population proliferation; IMP:UniProtKB. DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IDA:UniProtKB. DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; IMP:UniProtKB. DR GO; GO:1903749; P:positive regulation of protein localization to mitochondrion; HMP:ParkinsonsUK-UCL. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IGI:ParkinsonsUK-UCL. DR GO; GO:0070979; P:protein K11-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0036211; P:protein modification process; TAS:UniProtKB. DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central. DR CDD; cd23801; UBCc_UBE2L3; 1. DR FunFam; 3.10.110.10:FF:000011; Ubiquitin-conjugating enzyme E2 L3; 1. DR Gene3D; 3.10.110.10; Ubiquitin Conjugating Enzyme; 1. DR IDEAL; IID00592; -. DR InterPro; IPR050113; Ub_conjugating_enzyme-E2-like. DR InterPro; IPR000608; UBC. DR InterPro; IPR023313; UBQ-conjugating_AS. DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD. DR PANTHER; PTHR24067; 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; 1C4Z; -. DR PDBsum; 1FBV; -. DR PDBsum; 3SQV; -. DR PDBsum; 3SY2; -. DR PDBsum; 4Q5E; -. DR PDBsum; 4Q5H; -. DR PDBsum; 5HPT; -. DR PDBsum; 5TTE; -. DR PDBsum; 5UDH; -. DR PDBsum; 6CP2; -. DR PDBsum; 6DJW; -. DR PDBsum; 6DJX; -. DR PDBsum; 6N13; -. DR PDBsum; 6XXU; -. DR PDBsum; 7B5L; -. DR PDBsum; 7B5N; -. DR PDBsum; 7OIK; -. DR PDBsum; 7V8F; -. DR PDBsum; 8EAZ; -. DR PDBsum; 8EB0; -. DR PDBsum; 9I1J; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; KW Direct protein sequencing; Nucleus; Proteomics identification; KW Reference proteome; Transcription; Transcription regulation; Transferase; KW Ubl conjugation; Ubl conjugation pathway. FT CHAIN 1..154 FT /note="Ubiquitin-conjugating enzyme E2 L3" FT /id="PRO_0000082476" FT DOMAIN 2..149 FT /note="UBC core" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388" FT ACT_SITE 86 FT /note="Glycyl thioester intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388, FT ECO:0000255|PROSITE-ProRule:PRU10133" FT MOD_RES 131 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VAR_SEQ 1..9 FT /note="MAASRRLMK -> MQVAAGTRGDTRLQEVALLPQLFDLLVLGQRRARLLRQV FT PSALAGKDLAQLQAGATLAGYRRAHGPE (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_047342" FT VAR_SEQ 10..41 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045152" FT MUTAGEN 9 FT /note="K->E: Marked decrease in autoubiquitination." FT /evidence="ECO:0000269|PubMed:22496338" FT MUTAGEN 63 FT /note="F->A: Decrease in autoubiquitination. Abolishes FT ubiquitination of TP53 by the CUL9-RBX1 complex." FT /evidence="ECO:0000269|PubMed:22496338, FT ECO:0000269|PubMed:38605244" FT MUTAGEN 86 FT /note="C->S: Loss of catalytic activity. Prevents FT ubiquitin-dependent proteasomal degradation of UBE2L3." FT /evidence="ECO:0000269|PubMed:10888878, FT ECO:0000269|PubMed:18946090" FT MUTAGEN 88 FT /note="P->D: Does not convert into a lysine reactive E2; FT when associated with D-119." FT /evidence="ECO:0000269|PubMed:21532592" FT MUTAGEN 93 FT /note="E->R: Decrease in autoubiquitination." FT /evidence="ECO:0000269|PubMed:22496338" FT MUTAGEN 96 FT /note="K->E: Decrease in autoubiquitination." FT /evidence="ECO:0000269|PubMed:22496338" FT MUTAGEN 100 FT /note="K->E: Decrease in autoubiquitination." FT /evidence="ECO:0000269|PubMed:22496338" FT MUTAGEN 119 FT /note="H->D: Does not convert into a lysine reactive E2; FT when associated with D-88." FT /evidence="ECO:0000269|PubMed:21532592" FT CONFLICT 15 FT /note="R -> S (in Ref. 6; BAG61806)" FT /evidence="ECO:0000305" FT CONFLICT 23 FT /note="R -> C (in Ref. 4; AAG17922)" FT /evidence="ECO:0000305" FT CONFLICT 118 FT /note="E -> K (in Ref. 4; AAG17922)" FT /evidence="ECO:0000305" FT HELIX 2..16 FT /evidence="ECO:0007829|PDB:7V8F" FT STRAND 20..27 FT /evidence="ECO:0007829|PDB:7V8F" FT TURN 29..31 FT /evidence="ECO:0007829|PDB:1FBV" FT STRAND 34..39 FT /evidence="ECO:0007829|PDB:7V8F" FT TURN 44..48 FT /evidence="ECO:0007829|PDB:4Q5E" FT STRAND 50..56 FT /evidence="ECO:0007829|PDB:7V8F" FT TURN 59..62 FT /evidence="ECO:0007829|PDB:7V8F" FT STRAND 67..72 FT /evidence="ECO:0007829|PDB:7V8F" FT STRAND 77..79 FT /evidence="ECO:0007829|PDB:1FBV" FT STRAND 83..85 FT /evidence="ECO:0007829|PDB:4Q5E" FT HELIX 88..90 FT /evidence="ECO:0007829|PDB:7V8F" FT TURN 92..94 FT /evidence="ECO:0007829|PDB:7V8F" FT HELIX 101..113 FT /evidence="ECO:0007829|PDB:7V8F" FT STRAND 117..119 FT /evidence="ECO:0007829|PDB:3SQV" FT HELIX 123..131 FT /evidence="ECO:0007829|PDB:7V8F" FT HELIX 133..147 FT /evidence="ECO:0007829|PDB:7V8F" FT HELIX 150..152 FT /evidence="ECO:0007829|PDB:4Q5E" SQ SEQUENCE 154 AA; 17862 MW; F5A30243BE3C9985 CRC64; MAASRRLMKE LEEIRKCGMK NFRNIQVDEA NLLTWQGLIV PDNPPYDKGA FRIEINFPAE YPFKPPKITF KTKIYHPNID EKGQVCLPVI SAENWKPATK TDQVIQSLIA LVNDPQPEHP LRADLAEEYS KDRKKFCKNA EEFTKKYGEK RPVD //