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Database: UniProt
Entry: P68036
LinkDB: P68036
Original site: P68036 
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   29-SEP-2021, entry version 175.
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;
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   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   [30]
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).
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 and ARIH1,
CC       that function like RING-HECT hybrids. Accepts ubiquitin from the E1
CC       complex and catalyzes its covalent attachment to other proteins. 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}.
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   -!- 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=6; IntAct=EBI-711173, EBI-2514233;
CC       P68036; O95376: ARIH2; NbExp=11; 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}.
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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_001256356.1. [P68036-2]
DR   RefSeq; NP_003338.1; NM_003347.3. [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   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   BMRB; P68036; -.
DR   SMR; P68036; -.
DR   BioGRID; 113180; 191.
DR   CORUM; P68036; -.
DR   DIP; DIP-6124N; -.
DR   IntAct; P68036; 36.
DR   STRING; 9606.ENSP00000485133; -.
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   UCD-2DPAGE; P68036; -.
DR   EPD; P68036; -.
DR   jPOST; P68036; -.
DR   MassIVE; P68036; -.
DR   MaxQB; P68036; -.
DR   PaxDb; P68036; -.
DR   PeptideAtlas; P68036; -.
DR   PRIDE; P68036; -.
DR   ProteomicsDB; 18904; -.
DR   ProteomicsDB; 3856; -.
DR   ProteomicsDB; 57528; -. [P68036-1]
DR   TopDownProteomics; P68036-1; -. [P68036-1]
DR   TopDownProteomics; P68036-2; -. [P68036-2]
DR   Antibodypedia; 8540; 464 antibodies.
DR   DNASU; 7332; -.
DR   Ensembl; ENST00000342192; ENSP00000344259; ENSG00000185651. [P68036-1]
DR   Ensembl; ENST00000458578; ENSP00000400906; ENSG00000185651. [P68036-3]
DR   Ensembl; ENST00000545681; ENSP00000445931; ENSG00000185651. [P68036-2]
DR   GeneID; 7332; -.
DR   KEGG; hsa:7332; -.
DR   UCSC; uc002zva.2; human. [P68036-1]
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   neXtProt; NX_P68036; -.
DR   OpenTargets; ENSG00000185651; -.
DR   Orphanet; 536; Systemic lupus erythematosus.
DR   PharmGKB; PA37137; -.
DR   VEuPathDB; HostDB:ENSG00000185651; -.
DR   eggNOG; KOG0422; Eukaryota.
DR   GeneTree; ENSGT00940000153654; -.
DR   HOGENOM; CLU_030988_13_3_1; -.
DR   InParanoid; P68036; -.
DR   OMA; HPNITND; -.
DR   OrthoDB; 1420213at2759; -.
DR   PhylomeDB; P68036; -.
DR   TreeFam; TF313043; -.
DR   BRENDA; 2.3.2.24; 2681.
DR   PathwayCommons; P68036; -.
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   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 7332; 651 hits in 984 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 C1 segment of cervical spinal cord and 240 other tissues.
DR   ExpressionAtlas; P68036; baseline and differential.
DR   Genevisible; P68036; HS.
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; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0006464; P:cellular protein modification process; TAS: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:1903955; P:positive regulation of protein targeting to mitochondrion; HMP:ParkinsonsUK-UCL.
DR   GO; GO:0031398; P:positive regulation of protein ubiquitination; IGI:ParkinsonsUK-UCL.
DR   GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; IGI:ParkinsonsUK-UCL.
DR   GO; GO:0070979; P:protein K11-linked ubiquitination; IDA: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 transcription, DNA-templated; IDA:UniProtKB.
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   IDEAL; IID00592; -.
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; Acetylation; Alternative splicing; ATP-binding; Cytoplasm;
KW   Direct protein sequencing; Nucleotide-binding; Nucleus; Reference proteome;
KW   Transcription; Transcription regulation; Transferase; Ubl conjugation;
KW   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."
FT                   /evidence="ECO:0000269|PubMed:22496338"
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           1..17
FT                   /evidence="ECO:0007829|PDB:4Q5E"
FT   STRAND          20..27
FT                   /evidence="ECO:0007829|PDB:4Q5E"
FT   TURN            29..31
FT                   /evidence="ECO:0007829|PDB:1FBV"
FT   STRAND          34..39
FT                   /evidence="ECO:0007829|PDB:4Q5E"
FT   TURN            44..48
FT                   /evidence="ECO:0007829|PDB:4Q5E"
FT   STRAND          49..56
FT                   /evidence="ECO:0007829|PDB:4Q5E"
FT   TURN            59..62
FT                   /evidence="ECO:0007829|PDB:4Q5E"
FT   STRAND          67..72
FT                   /evidence="ECO:0007829|PDB:4Q5E"
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:4Q5E"
FT   TURN            92..94
FT                   /evidence="ECO:0007829|PDB:4Q5E"
FT   HELIX           101..113
FT                   /evidence="ECO:0007829|PDB:4Q5E"
FT   STRAND          117..119
FT                   /evidence="ECO:0007829|PDB:3SQV"
FT   HELIX           123..131
FT                   /evidence="ECO:0007829|PDB:4Q5E"
FT   HELIX           133..147
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
//
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