Full text data of UBE2L3
UBE2L3
(UBCE7, UBCH7)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Ubiquitin-conjugating enzyme E2 L3; 6.3.2.19 (L-UBC; UbcH7; Ubiquitin carrier protein L3; Ubiquitin-conjugating enzyme E2-F1; Ubiquitin-protein ligase L3)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ubiquitin-conjugating enzyme E2 L3; 6.3.2.19 (L-UBC; UbcH7; Ubiquitin carrier protein L3; Ubiquitin-conjugating enzyme E2-F1; Ubiquitin-protein ligase L3)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P68036
ID UB2L3_HUMAN Reviewed; 154 AA.
AC P68036; B2R4A7; B4DDG1; B4DSZ4; E7EWS7; P51966; P70653; Q9HAV1;
read moreDT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 22-JAN-2014, entry version 104.
DE RecName: Full=Ubiquitin-conjugating enzyme E2 L3;
DE EC=6.3.2.19;
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Moynihan T.P., 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-
RT F1) and 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
RT human 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
RT enzyme 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA 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.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA 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.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Schwartz A.L., Ciechanover A.;
RT "Purification and characterization of a novel species of ubiquitin-
RT carrier protein, E2, that is involved in degradation of non-'N-end
RT rule' protein 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
RT family UBE2L1-4, including UBE2L3 which encodes UbcH7.";
RL Biochim. Biophys. Acta 1491:57-64(2000).
RN [12]
RP FUNCTION, INTERACTION WITH PARK2, 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-
RT protein 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
RT ligase 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
RT regulate its interaction with the ubiquitin-conjugating enzyme,
RT 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
RT mitotic 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
RT steroid 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
RT receptor autoregulation.";
RL J. Endocrinol. 190:621-629(2006).
RN [19]
RP INTERACTION WITH RNF19B.
RX PubMed=16709802;
RA Fortier J.M., Kornbluth J.;
RT "NK lytic-associated molecule, involved in NK cytotoxic function, is
RT an E3 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.,
RA Wissink W., Jansen P., Swarts H.G., Hibbert R.G., de Witte T.,
RA Sixma T.K., Jansen J.H., van der Reijden B.A.;
RT "The ubiquitin ligase Triad1 inhibits myelopoiesis through UbcH7 and
RT Ubc13 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
RT enzyme H7.";
RL Mol. Biol. Cell 20:1-9(2009).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-9; LYS-131 AND LYS-138, AND
RP MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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.
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.,
RA Buerckstuemmer T., 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 PARK2 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 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.,
RA Huibregtse J.M., Pavletich N.P.;
RT "Structure of an E6AP-UbcH7 complex: insights into ubiquitination by
RT the E2-E3 enzyme cascade.";
RL Science 286:1321-1326(1999).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH 47-434 OF CBL
RP AND 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
RT ubiquitin-protein ligases.";
RL Cell 102:533-539(2000).
CC -!- FUNCTION: Ubiquitin-conjugating enzyme E2 that specifically acts
CC with HECT-type and RBR family E3 ubiquitin-protein ligases. Does
CC not function with most RING-containing E3 ubiquitin-protein
CC ligases because it lacks intrinsic E3-independent reactivity with
CC lysine: in contrast, it has activity with the RBR family E3
CC enzymes, such as PARK2 and ARIH1, that function like function like
CC RING-HECT hybrids. Accepts ubiquitin from the E1 complex and
CC catalyzes its covalent attachment to other proteins. In vitro
CC 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
CC the cell cycle. Regulates nuclear hormone receptors
CC transcriptional activity. May play a role in myelopoiesis.
CC -!- CATALYTIC ACTIVITY: ATP + ubiquitin + protein lysine = AMP +
CC diphosphate + protein N-ubiquityllysine.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with PARK2; involved in ubiquitination and
CC degradation of misfolded proteins. Interacts with UBE3A; used by
CC the papilloma virus HPV-16 E6 protein to ubiquitinate p53/TP53.
CC Interacts with CCNB1IP1, CBL, ZAP70, RNF19A, RNF19B and RNF144B.
CC Interacts with ARIH1. Interacts with ARIH2 (via RING-type 1).
CC Interacts with NCOA1; they functionally interact to regulate
CC progesterone receptor transcriptional activity. May interact with
CC NR3C1.
CC -!- INTERACTION:
CC O95376:ARIH2; NbExp=3; IntAct=EBI-711173, EBI-711158;
CC Q6ZMZ0:RNF19B; NbExp=2; IntAct=EBI-711173, EBI-2466594;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm.
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 Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitous, with highest expression in testis.
CC -!- DOMAIN: In contrast to other ubiquitin-conjugating enzymes E2,
CC residues essential for lysine reactivity are absent: Pro and a His
CC residues are present instead of an Asp and an Asp residues in
CC positions 88 and 119,respectively.
CC -!- PTM: Ubiquitinated. The alteration of UBE2L3 protein levels during
CC the S-phase of the cell cycle is due to ubiquitin-dependent
CC proteasomal degradation.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC -!- CAUTION: PubMed:10760570 reported that UBE2L1, UBE2L2 and UBE2L4
CC are most likely pseudogenes and the only expressed member of this
CC subfamily seems to be UBE2L3.
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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 RefSeq; NP_001243284.1; NM_001256355.1.
DR RefSeq; NP_001243285.1; NM_001256356.1.
DR RefSeq; NP_003338.1; NM_003347.3.
DR UniGene; Hs.108104; -.
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 PDBsum; 1C4Z; -.
DR PDBsum; 1FBV; -.
DR PDBsum; 3SQV; -.
DR PDBsum; 3SY2; -.
DR ProteinModelPortal; P68036; -.
DR SMR; P68036; 4-147.
DR DIP; DIP-6124N; -.
DR IntAct; P68036; 22.
DR MINT; MINT-5002693; -.
DR STRING; 9606.ENSP00000344259; -.
DR PhosphoSite; P68036; -.
DR DMDM; 54039805; -.
DR OGP; P51966; -.
DR UCD-2DPAGE; P68036; -.
DR PaxDb; P68036; -.
DR PRIDE; P68036; -.
DR DNASU; 7332; -.
DR Ensembl; ENST00000342192; ENSP00000344259; ENSG00000185651.
DR Ensembl; ENST00000458578; ENSP00000400906; ENSG00000185651.
DR Ensembl; ENST00000545681; ENSP00000445931; ENSG00000185651.
DR GeneID; 7332; -.
DR KEGG; hsa:7332; -.
DR UCSC; uc011aig.3; human.
DR CTD; 7332; -.
DR GeneCards; GC22P021903; -.
DR HGNC; HGNC:12488; UBE2L3.
DR HPA; HPA045609; -.
DR MIM; 603721; gene.
DR neXtProt; NX_P68036; -.
DR PharmGKB; PA37137; -.
DR eggNOG; COG5078; -.
DR HOGENOM; HOG000233455; -.
DR HOVERGEN; HBG063308; -.
DR InParanoid; P68036; -.
DR KO; K04552; -.
DR OMA; IALVNDX; -.
DR OrthoDB; EOG7GXPD8; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P68036; -.
DR UniPathway; UPA00143; -.
DR ChiTaRS; UBE2L3; human.
DR EvolutionaryTrace; P68036; -.
DR GeneWiki; UBE2L3; -.
DR GenomeRNAi; 7332; -.
DR NextBio; 28696; -.
DR PRO; PR:P68036; -.
DR ArrayExpress; P68036; -.
DR Bgee; P68036; -.
DR CleanEx; HS_UBE2L3; -.
DR Genevestigator; P68036; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; TAS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; TAS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
DR GO; GO:0008283; P:cell proliferation; IMP:UniProtKB.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IDA:UniProtKB.
DR GO; GO:0070979; P:protein K11-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IDA:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:UniProtKB.
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; UBIQUITIN_CONJUGAT_1; 1.
DR PROSITE; PS50127; UBIQUITIN_CONJUGAT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Ligase;
KW Nucleotide-binding; Nucleus; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1 154 Ubiquitin-conjugating enzyme E2 L3.
FT /FTId=PRO_0000082476.
FT ACT_SITE 86 86 Glycyl thioester intermediate (By
FT similarity).
FT MOD_RES 9 9 N6-acetyllysine.
FT MOD_RES 131 131 N6-acetyllysine.
FT MOD_RES 138 138 N6-acetyllysine.
FT VAR_SEQ 1 9 MAASRRLMK -> MQVAAGTRGDTRLQEVALLPQLFDLLVL
FT GQRRARLLRQVPSALAGKDLAQLQAGATLAGYRRAHGPE
FT (in isoform 3).
FT /FTId=VSP_047342.
FT VAR_SEQ 10 41 Missing (in isoform 2).
FT /FTId=VSP_045152.
FT MUTAGEN 86 86 C->S: Loss of catalytic activity.
FT Prevents ubiquitin-dependent proteasomal
FT degradation of UBE2L3.
FT MUTAGEN 88 88 P->D: Does not convert into a lysine
FT reactive E2; when associated with D-119.
FT MUTAGEN 119 119 H->D: Does not convert into a lysine
FT reactive E2; when associated with D-88.
FT CONFLICT 15 15 R -> S (in Ref. 6; BAG61806).
FT CONFLICT 23 23 R -> C (in Ref. 4; AAG17922).
FT CONFLICT 118 118 E -> K (in Ref. 4; AAG17922).
FT HELIX 7 11
FT STRAND 15 17
FT STRAND 23 25
FT STRAND 30 39
FT STRAND 43 45
FT STRAND 51 56
FT TURN 59 63
FT STRAND 67 72
FT STRAND 77 79
FT STRAND 81 84
FT TURN 88 90
FT STRAND 91 94
FT HELIX 101 113
FT STRAND 117 119
FT HELIX 123 130
FT HELIX 137 144
SQ SEQUENCE 154 AA; 17862 MW; F5A30243BE3C9985 CRC64;
MAASRRLMKE LEEIRKCGMK NFRNIQVDEA NLLTWQGLIV PDNPPYDKGA FRIEINFPAE
YPFKPPKITF KTKIYHPNID EKGQVCLPVI SAENWKPATK TDQVIQSLIA LVNDPQPEHP
LRADLAEEYS KDRKKFCKNA EEFTKKYGEK RPVD
//
ID UB2L3_HUMAN Reviewed; 154 AA.
AC P68036; B2R4A7; B4DDG1; B4DSZ4; E7EWS7; P51966; P70653; Q9HAV1;
read moreDT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 22-JAN-2014, entry version 104.
DE RecName: Full=Ubiquitin-conjugating enzyme E2 L3;
DE EC=6.3.2.19;
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Moynihan T.P., 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-
RT F1) and 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
RT human 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
RT enzyme 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA 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.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA 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.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Schwartz A.L., Ciechanover A.;
RT "Purification and characterization of a novel species of ubiquitin-
RT carrier protein, E2, that is involved in degradation of non-'N-end
RT rule' protein 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
RT family UBE2L1-4, including UBE2L3 which encodes UbcH7.";
RL Biochim. Biophys. Acta 1491:57-64(2000).
RN [12]
RP FUNCTION, INTERACTION WITH PARK2, 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-
RT protein 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
RT ligase 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
RT regulate its interaction with the ubiquitin-conjugating enzyme,
RT 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
RT mitotic 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
RT steroid 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
RT receptor autoregulation.";
RL J. Endocrinol. 190:621-629(2006).
RN [19]
RP INTERACTION WITH RNF19B.
RX PubMed=16709802;
RA Fortier J.M., Kornbluth J.;
RT "NK lytic-associated molecule, involved in NK cytotoxic function, is
RT an E3 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.,
RA Wissink W., Jansen P., Swarts H.G., Hibbert R.G., de Witte T.,
RA Sixma T.K., Jansen J.H., van der Reijden B.A.;
RT "The ubiquitin ligase Triad1 inhibits myelopoiesis through UbcH7 and
RT Ubc13 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
RT enzyme H7.";
RL Mol. Biol. Cell 20:1-9(2009).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-9; LYS-131 AND LYS-138, AND
RP MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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.
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.,
RA Buerckstuemmer T., 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 PARK2 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 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.,
RA Huibregtse J.M., Pavletich N.P.;
RT "Structure of an E6AP-UbcH7 complex: insights into ubiquitination by
RT the E2-E3 enzyme cascade.";
RL Science 286:1321-1326(1999).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH 47-434 OF CBL
RP AND 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
RT ubiquitin-protein ligases.";
RL Cell 102:533-539(2000).
CC -!- FUNCTION: Ubiquitin-conjugating enzyme E2 that specifically acts
CC with HECT-type and RBR family E3 ubiquitin-protein ligases. Does
CC not function with most RING-containing E3 ubiquitin-protein
CC ligases because it lacks intrinsic E3-independent reactivity with
CC lysine: in contrast, it has activity with the RBR family E3
CC enzymes, such as PARK2 and ARIH1, that function like function like
CC RING-HECT hybrids. Accepts ubiquitin from the E1 complex and
CC catalyzes its covalent attachment to other proteins. In vitro
CC 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
CC the cell cycle. Regulates nuclear hormone receptors
CC transcriptional activity. May play a role in myelopoiesis.
CC -!- CATALYTIC ACTIVITY: ATP + ubiquitin + protein lysine = AMP +
CC diphosphate + protein N-ubiquityllysine.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with PARK2; involved in ubiquitination and
CC degradation of misfolded proteins. Interacts with UBE3A; used by
CC the papilloma virus HPV-16 E6 protein to ubiquitinate p53/TP53.
CC Interacts with CCNB1IP1, CBL, ZAP70, RNF19A, RNF19B and RNF144B.
CC Interacts with ARIH1. Interacts with ARIH2 (via RING-type 1).
CC Interacts with NCOA1; they functionally interact to regulate
CC progesterone receptor transcriptional activity. May interact with
CC NR3C1.
CC -!- INTERACTION:
CC O95376:ARIH2; NbExp=3; IntAct=EBI-711173, EBI-711158;
CC Q6ZMZ0:RNF19B; NbExp=2; IntAct=EBI-711173, EBI-2466594;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm.
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 Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitous, with highest expression in testis.
CC -!- DOMAIN: In contrast to other ubiquitin-conjugating enzymes E2,
CC residues essential for lysine reactivity are absent: Pro and a His
CC residues are present instead of an Asp and an Asp residues in
CC positions 88 and 119,respectively.
CC -!- PTM: Ubiquitinated. The alteration of UBE2L3 protein levels during
CC the S-phase of the cell cycle is due to ubiquitin-dependent
CC proteasomal degradation.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC -!- CAUTION: PubMed:10760570 reported that UBE2L1, UBE2L2 and UBE2L4
CC are most likely pseudogenes and the only expressed member of this
CC subfamily seems to be UBE2L3.
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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 RefSeq; NP_001243284.1; NM_001256355.1.
DR RefSeq; NP_001243285.1; NM_001256356.1.
DR RefSeq; NP_003338.1; NM_003347.3.
DR UniGene; Hs.108104; -.
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 PDBsum; 1C4Z; -.
DR PDBsum; 1FBV; -.
DR PDBsum; 3SQV; -.
DR PDBsum; 3SY2; -.
DR ProteinModelPortal; P68036; -.
DR SMR; P68036; 4-147.
DR DIP; DIP-6124N; -.
DR IntAct; P68036; 22.
DR MINT; MINT-5002693; -.
DR STRING; 9606.ENSP00000344259; -.
DR PhosphoSite; P68036; -.
DR DMDM; 54039805; -.
DR OGP; P51966; -.
DR UCD-2DPAGE; P68036; -.
DR PaxDb; P68036; -.
DR PRIDE; P68036; -.
DR DNASU; 7332; -.
DR Ensembl; ENST00000342192; ENSP00000344259; ENSG00000185651.
DR Ensembl; ENST00000458578; ENSP00000400906; ENSG00000185651.
DR Ensembl; ENST00000545681; ENSP00000445931; ENSG00000185651.
DR GeneID; 7332; -.
DR KEGG; hsa:7332; -.
DR UCSC; uc011aig.3; human.
DR CTD; 7332; -.
DR GeneCards; GC22P021903; -.
DR HGNC; HGNC:12488; UBE2L3.
DR HPA; HPA045609; -.
DR MIM; 603721; gene.
DR neXtProt; NX_P68036; -.
DR PharmGKB; PA37137; -.
DR eggNOG; COG5078; -.
DR HOGENOM; HOG000233455; -.
DR HOVERGEN; HBG063308; -.
DR InParanoid; P68036; -.
DR KO; K04552; -.
DR OMA; IALVNDX; -.
DR OrthoDB; EOG7GXPD8; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P68036; -.
DR UniPathway; UPA00143; -.
DR ChiTaRS; UBE2L3; human.
DR EvolutionaryTrace; P68036; -.
DR GeneWiki; UBE2L3; -.
DR GenomeRNAi; 7332; -.
DR NextBio; 28696; -.
DR PRO; PR:P68036; -.
DR ArrayExpress; P68036; -.
DR Bgee; P68036; -.
DR CleanEx; HS_UBE2L3; -.
DR Genevestigator; P68036; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; TAS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; TAS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
DR GO; GO:0008283; P:cell proliferation; IMP:UniProtKB.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IDA:UniProtKB.
DR GO; GO:0070979; P:protein K11-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IDA:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:UniProtKB.
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; UBIQUITIN_CONJUGAT_1; 1.
DR PROSITE; PS50127; UBIQUITIN_CONJUGAT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Ligase;
KW Nucleotide-binding; Nucleus; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1 154 Ubiquitin-conjugating enzyme E2 L3.
FT /FTId=PRO_0000082476.
FT ACT_SITE 86 86 Glycyl thioester intermediate (By
FT similarity).
FT MOD_RES 9 9 N6-acetyllysine.
FT MOD_RES 131 131 N6-acetyllysine.
FT MOD_RES 138 138 N6-acetyllysine.
FT VAR_SEQ 1 9 MAASRRLMK -> MQVAAGTRGDTRLQEVALLPQLFDLLVL
FT GQRRARLLRQVPSALAGKDLAQLQAGATLAGYRRAHGPE
FT (in isoform 3).
FT /FTId=VSP_047342.
FT VAR_SEQ 10 41 Missing (in isoform 2).
FT /FTId=VSP_045152.
FT MUTAGEN 86 86 C->S: Loss of catalytic activity.
FT Prevents ubiquitin-dependent proteasomal
FT degradation of UBE2L3.
FT MUTAGEN 88 88 P->D: Does not convert into a lysine
FT reactive E2; when associated with D-119.
FT MUTAGEN 119 119 H->D: Does not convert into a lysine
FT reactive E2; when associated with D-88.
FT CONFLICT 15 15 R -> S (in Ref. 6; BAG61806).
FT CONFLICT 23 23 R -> C (in Ref. 4; AAG17922).
FT CONFLICT 118 118 E -> K (in Ref. 4; AAG17922).
FT HELIX 7 11
FT STRAND 15 17
FT STRAND 23 25
FT STRAND 30 39
FT STRAND 43 45
FT STRAND 51 56
FT TURN 59 63
FT STRAND 67 72
FT STRAND 77 79
FT STRAND 81 84
FT TURN 88 90
FT STRAND 91 94
FT HELIX 101 113
FT STRAND 117 119
FT HELIX 123 130
FT HELIX 137 144
SQ SEQUENCE 154 AA; 17862 MW; F5A30243BE3C9985 CRC64;
MAASRRLMKE LEEIRKCGMK NFRNIQVDEA NLLTWQGLIV PDNPPYDKGA FRIEINFPAE
YPFKPPKITF KTKIYHPNID EKGQVCLPVI SAENWKPATK TDQVIQSLIA LVNDPQPEHP
LRADLAEEYS KDRKKFCKNA EEFTKKYGEK RPVD
//
MIM
603721
*RECORD*
*FIELD* NO
603721
*FIELD* TI
*603721 UBIQUITIN-CONJUGATING ENZYME E2L 3; UBE2L3
;;UBIQUITIN-CONJUGATING ENZYME UBCH7; UBCH7
read more*FIELD* TX
DESCRIPTION
Ubiquitin-conjugating enzymes (E2s or UBCs) are essential components of
the posttranslational protein ubiquitination pathway, mediating the
transfer of activated ubiquitin to substrate proteins.
CLONING
The S. cerevisiae UBC1, UBC4, and UBC5 enzymes appear to participate in
the degradation of short-lived and abnormal proteins. Human UBE2L1
(600012) is a homolog of yeast UBC4 and UBC5. By screening a genomic
library with a UBE2L1 probe, Moynihan et al. (1996) isolated clones
corresponding to a novel gene, UBE2L3.
Nuber et al. (1996) cloned human keratinocyte cDNAs encoding UBE2L3,
which they referred to as UBCH7. The predicted 154-amino acid protein
has 64% sequence similarity to UBCH5. UBCH7 efficiently mediated E6AP
(UBE3A; 601623)-dependent ubiquitination in an in vitro assay.
By RT-PCR, Moynihan et al. (1998) determined that UBE2L3 is expressed as
4 mRNAs that differ in the length of the 3-prime untranslated region
(UTR). Sequence comparisons revealed that the human and mouse UBE2L3
cDNAs share 97% DNA sequence identity in the coding region and 93%
identity for 287 nucleotides extending into the 3-prime UTR. The
predicted mouse and human UBE2L3 proteins are identical.
GENE STRUCTURE
Moynihan et al. (1996) demonstrated that the UBE2L3 and UBE2L1 genes are
identical except that the UBE2L1 gene is intronless, while the UBE2L3
coding sequence is interrupted by 3 introns. Moynihan et al. (1998)
determined that the UBE2L3 gene spans approximately 57 kb.
MAPPING
By analysis of somatic cell hybrids and by FISH, Moynihan et al. (1996)
mapped the UBE2L3 gene to chromosome 22q11.2-q13.1. They also mapped a
pseudogene, UBE2L2, to 12q12. Ardley et al. (1997) found that another
pseudogene, UBE2L4, was located at 19q13.1-q13.2.
GENE FUNCTION
Shimura et al. (2001) hypothesized that alpha-synuclein (163890) and
parkin (602544) interact functionally, namely, that parkin ubiquitinates
alpha-synuclein normally and that this process is altered in autosomal
recessive Parkinson disease (600116). Shimura et al. (2001) identified a
protein complex in normal human brain that includes parkin as the E3
ubiquitin ligase, UBCH7 as its associated E2 ubiquitin-conjugating
enzyme, and a novel 22-kD glycosylated form of alpha-synuclein
(alpha-Sp22) as its substrate. In contrast to normal parkin, mutant
parkin associated with autosomal recessive Parkinson disease failed to
bind alpha-Sp22. In an in vitro ubiquitination assay, alpha-Sp22 was
modified by normal, but not mutant, parkin into polyubiquitinated, high
molecular weight species. Accordingly, alpha-Sp22 accumulated in a
nonubiquitinated form in parkin-deficient Parkinson disease brains.
Shimura et al. (2001) concluded that alpha-Sp22 is a substrate for
parkin's ubiquitin ligase activity in normal human brain and that loss
of parkin function causes pathologic accumulation of alpha-Sp22. These
findings demonstrated a critical biochemical reaction between the 2
Parkinson disease-linked gene products and suggested that this reaction
underlies the accumulation of ubiquitinated alpha-synuclein in
conventional Parkinson disease.
Carrano et al. (2009) identified the E3 ubiquitin ligase Wwp1 (602307)
as a positive regulator of life span in C. elegans in response to
dietary restriction. Overexpression of Wwp1 in worms extended life span
by up to 20% under conditions of ad libitum feeding. Conversely,
reduction of Wwp1 completely suppressed the extended longevity of
diet-restricted animals. The E2 ubiquitin-conjugating enzyme Ubc18,
which is homologous to human UBE2L3, interacted with Wwp1 and was
required for Wwp1 ubiquitin ligase activity and the extended longevity
of worms overexpressing Wwp1. Carrano et al. (2009) concluded that Wwp1
and Ubc18 function to ubiquitinate substrates that regulate longevity
induced by diet restriction.
Wenzel et al. (2011) showed that, unlike many ubiquitin-conjugating
enzymes (E2s) that transfer ubiquitin with RINGs, UBCH7 lacks intrinsic
ubiquitin ligase (E3)-independent reactivity with lysine, explaining its
preference for HECTs. Despite lacking lysine reactivity, UBCH7 exhibits
activity with the RING-in-between-RING (RBR) family of E3s that includes
parkin (602544) and human homolog of ariadne (HHARI; 605624). Found in
all eukaryotes, RBRs regulate processes such as translation and immune
signaling. RBRs contain a canonical C3HC4-type RING, followed by 2
conserved cys/his-rich zinc-binding domains, in-between-RING (IBR) and
RING2 domains, which together define this E3 family. Wenzel et al.
(2011) showed that RBRs function like RING/HECT hybrids: they bind E2s
via a RING domain, but transfer ubiquitin through an obligate
thioester-linked ubiquitin, requiring a conserved cysteine residue in
RING2. Wenzel et al. (2011) concluded that their results defined the
functional cadre of E3s for UBCH7, an E2 involved in cell proliferation
and immune function, and indicated a novel mechanism for an entire class
of E3s.
*FIELD* RF
1. Ardley, H. C.; Moynihan, T. P.; Thompson, J.; Leek, J. P.; Markham,
A. F.; Robinson, P. A.: Rapid isolation of genomic clones for individual
members of human multigene families: identification and localisation
of UBE2L4, a novel member of a ubiquitin conjugating enzyme dispersed
gene family. Cytogenet. Cell Genet. 79: 188-192, 1997.
2. Carrano, A. C.; Liu, Z.; Dillin, A.; Hunter, T.: A conserved ubiquitination
pathway determines longevity in response to diet restriction. Nature 460:
396-399, 2009.
3. Moynihan, T. P.; Ardley, H. C.; Leek, J. P.; Thompson, J.; Brindle,
N. S.; Markham, A. F.; Robinson, P. A.: Characterization of a human
ubiquitin-conjugating enzyme gene UBE2L3. Mammalian Genome 7: 520-525,
1996.
4. Moynihan, T. P.; Cole, C. G.; Dunham, I.; O'Neil, L.; Markham,
A. F.; Robinson, P. A.: Fine-mapping, genomic organization, and transcript
analysis of the human ubiquitin-conjugating enzyme gene UBE2L3. Genomics 51:
124-127, 1998.
5. Nuber, U.; Schwarz, S.; Kaiser, P.; Schneider, R.; Scheffner, M.
: Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1)
and characterization of their interaction with E6-AP and RSP5. J.
Biol. Chem. 271: 2795-2800, 1996.
6. Shimura, H.; Schlossmacher, M. G.; Hattori, N.; Frosch, M. P.;
Trockenbacher, A.; Schneider, R.; Mizuno, Y.; Kosik, K. S.; Selkoe,
D. J.: Ubiquitination of a new form of alpha-synuclein by parkin
from human brain: implications for Parkinson's disease. Science 293:
263-269, 2001.
7. Wenzel, D. M.; Lissounov, A.; Brzovic, P. S.; Klevit, R. E.: UBCH7
reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature 474:
105-108, 2011.
*FIELD* CN
Ada Hamosh - updated: 6/22/2011
Patricia A. Hartz - updated: 8/17/2009
Ada Hamosh - updated: 8/13/2001
*FIELD* CD
Rebekah S. Rasooly: 4/12/1999
*FIELD* ED
alopez: 06/23/2011
terry: 6/22/2011
wwang: 9/1/2009
mgross: 8/17/2009
alopez: 8/13/2001
terry: 8/13/2001
mgross: 4/15/1999
*RECORD*
*FIELD* NO
603721
*FIELD* TI
*603721 UBIQUITIN-CONJUGATING ENZYME E2L 3; UBE2L3
;;UBIQUITIN-CONJUGATING ENZYME UBCH7; UBCH7
read more*FIELD* TX
DESCRIPTION
Ubiquitin-conjugating enzymes (E2s or UBCs) are essential components of
the posttranslational protein ubiquitination pathway, mediating the
transfer of activated ubiquitin to substrate proteins.
CLONING
The S. cerevisiae UBC1, UBC4, and UBC5 enzymes appear to participate in
the degradation of short-lived and abnormal proteins. Human UBE2L1
(600012) is a homolog of yeast UBC4 and UBC5. By screening a genomic
library with a UBE2L1 probe, Moynihan et al. (1996) isolated clones
corresponding to a novel gene, UBE2L3.
Nuber et al. (1996) cloned human keratinocyte cDNAs encoding UBE2L3,
which they referred to as UBCH7. The predicted 154-amino acid protein
has 64% sequence similarity to UBCH5. UBCH7 efficiently mediated E6AP
(UBE3A; 601623)-dependent ubiquitination in an in vitro assay.
By RT-PCR, Moynihan et al. (1998) determined that UBE2L3 is expressed as
4 mRNAs that differ in the length of the 3-prime untranslated region
(UTR). Sequence comparisons revealed that the human and mouse UBE2L3
cDNAs share 97% DNA sequence identity in the coding region and 93%
identity for 287 nucleotides extending into the 3-prime UTR. The
predicted mouse and human UBE2L3 proteins are identical.
GENE STRUCTURE
Moynihan et al. (1996) demonstrated that the UBE2L3 and UBE2L1 genes are
identical except that the UBE2L1 gene is intronless, while the UBE2L3
coding sequence is interrupted by 3 introns. Moynihan et al. (1998)
determined that the UBE2L3 gene spans approximately 57 kb.
MAPPING
By analysis of somatic cell hybrids and by FISH, Moynihan et al. (1996)
mapped the UBE2L3 gene to chromosome 22q11.2-q13.1. They also mapped a
pseudogene, UBE2L2, to 12q12. Ardley et al. (1997) found that another
pseudogene, UBE2L4, was located at 19q13.1-q13.2.
GENE FUNCTION
Shimura et al. (2001) hypothesized that alpha-synuclein (163890) and
parkin (602544) interact functionally, namely, that parkin ubiquitinates
alpha-synuclein normally and that this process is altered in autosomal
recessive Parkinson disease (600116). Shimura et al. (2001) identified a
protein complex in normal human brain that includes parkin as the E3
ubiquitin ligase, UBCH7 as its associated E2 ubiquitin-conjugating
enzyme, and a novel 22-kD glycosylated form of alpha-synuclein
(alpha-Sp22) as its substrate. In contrast to normal parkin, mutant
parkin associated with autosomal recessive Parkinson disease failed to
bind alpha-Sp22. In an in vitro ubiquitination assay, alpha-Sp22 was
modified by normal, but not mutant, parkin into polyubiquitinated, high
molecular weight species. Accordingly, alpha-Sp22 accumulated in a
nonubiquitinated form in parkin-deficient Parkinson disease brains.
Shimura et al. (2001) concluded that alpha-Sp22 is a substrate for
parkin's ubiquitin ligase activity in normal human brain and that loss
of parkin function causes pathologic accumulation of alpha-Sp22. These
findings demonstrated a critical biochemical reaction between the 2
Parkinson disease-linked gene products and suggested that this reaction
underlies the accumulation of ubiquitinated alpha-synuclein in
conventional Parkinson disease.
Carrano et al. (2009) identified the E3 ubiquitin ligase Wwp1 (602307)
as a positive regulator of life span in C. elegans in response to
dietary restriction. Overexpression of Wwp1 in worms extended life span
by up to 20% under conditions of ad libitum feeding. Conversely,
reduction of Wwp1 completely suppressed the extended longevity of
diet-restricted animals. The E2 ubiquitin-conjugating enzyme Ubc18,
which is homologous to human UBE2L3, interacted with Wwp1 and was
required for Wwp1 ubiquitin ligase activity and the extended longevity
of worms overexpressing Wwp1. Carrano et al. (2009) concluded that Wwp1
and Ubc18 function to ubiquitinate substrates that regulate longevity
induced by diet restriction.
Wenzel et al. (2011) showed that, unlike many ubiquitin-conjugating
enzymes (E2s) that transfer ubiquitin with RINGs, UBCH7 lacks intrinsic
ubiquitin ligase (E3)-independent reactivity with lysine, explaining its
preference for HECTs. Despite lacking lysine reactivity, UBCH7 exhibits
activity with the RING-in-between-RING (RBR) family of E3s that includes
parkin (602544) and human homolog of ariadne (HHARI; 605624). Found in
all eukaryotes, RBRs regulate processes such as translation and immune
signaling. RBRs contain a canonical C3HC4-type RING, followed by 2
conserved cys/his-rich zinc-binding domains, in-between-RING (IBR) and
RING2 domains, which together define this E3 family. Wenzel et al.
(2011) showed that RBRs function like RING/HECT hybrids: they bind E2s
via a RING domain, but transfer ubiquitin through an obligate
thioester-linked ubiquitin, requiring a conserved cysteine residue in
RING2. Wenzel et al. (2011) concluded that their results defined the
functional cadre of E3s for UBCH7, an E2 involved in cell proliferation
and immune function, and indicated a novel mechanism for an entire class
of E3s.
*FIELD* RF
1. Ardley, H. C.; Moynihan, T. P.; Thompson, J.; Leek, J. P.; Markham,
A. F.; Robinson, P. A.: Rapid isolation of genomic clones for individual
members of human multigene families: identification and localisation
of UBE2L4, a novel member of a ubiquitin conjugating enzyme dispersed
gene family. Cytogenet. Cell Genet. 79: 188-192, 1997.
2. Carrano, A. C.; Liu, Z.; Dillin, A.; Hunter, T.: A conserved ubiquitination
pathway determines longevity in response to diet restriction. Nature 460:
396-399, 2009.
3. Moynihan, T. P.; Ardley, H. C.; Leek, J. P.; Thompson, J.; Brindle,
N. S.; Markham, A. F.; Robinson, P. A.: Characterization of a human
ubiquitin-conjugating enzyme gene UBE2L3. Mammalian Genome 7: 520-525,
1996.
4. Moynihan, T. P.; Cole, C. G.; Dunham, I.; O'Neil, L.; Markham,
A. F.; Robinson, P. A.: Fine-mapping, genomic organization, and transcript
analysis of the human ubiquitin-conjugating enzyme gene UBE2L3. Genomics 51:
124-127, 1998.
5. Nuber, U.; Schwarz, S.; Kaiser, P.; Schneider, R.; Scheffner, M.
: Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1)
and characterization of their interaction with E6-AP and RSP5. J.
Biol. Chem. 271: 2795-2800, 1996.
6. Shimura, H.; Schlossmacher, M. G.; Hattori, N.; Frosch, M. P.;
Trockenbacher, A.; Schneider, R.; Mizuno, Y.; Kosik, K. S.; Selkoe,
D. J.: Ubiquitination of a new form of alpha-synuclein by parkin
from human brain: implications for Parkinson's disease. Science 293:
263-269, 2001.
7. Wenzel, D. M.; Lissounov, A.; Brzovic, P. S.; Klevit, R. E.: UBCH7
reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature 474:
105-108, 2011.
*FIELD* CN
Ada Hamosh - updated: 6/22/2011
Patricia A. Hartz - updated: 8/17/2009
Ada Hamosh - updated: 8/13/2001
*FIELD* CD
Rebekah S. Rasooly: 4/12/1999
*FIELD* ED
alopez: 06/23/2011
terry: 6/22/2011
wwang: 9/1/2009
mgross: 8/17/2009
alopez: 8/13/2001
terry: 8/13/2001
mgross: 4/15/1999