UBE3C_HUMAN
ID UBE3C_HUMAN Reviewed; 1083 AA.
AC Q15386; A4D235; A6NCP3; Q8TC15; Q96CR4; Q9UDU3;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 3.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Ubiquitin-protein ligase E3C {ECO:0000305};
DE EC=2.3.2.26 {ECO:0000269|PubMed:11278995, ECO:0000269|PubMed:24811749, ECO:0000269|PubMed:25752573, ECO:0000269|PubMed:25752577, ECO:0000269|PubMed:32039437, ECO:0000269|PubMed:33637724, ECO:0000269|PubMed:34239127};
DE AltName: Full=HECT-type ubiquitin transferase E3C {ECO:0000305};
DE AltName: Full=Homologous to E6AP carboxyl terminus homologous protein 2 {ECO:0000303|PubMed:9575161};
DE Short=HectH2 {ECO:0000303|PubMed:9575161};
DE AltName: Full=RTA-associated ubiquitin ligase {ECO:0000303|PubMed:21167755};
DE Short=RAUL {ECO:0000303|PubMed:21167755};
GN Name=UBE3C {ECO:0000303|PubMed:17323924, ECO:0000312|HGNC:HGNC:16803};
GN Synonyms=KIAA0010 {ECO:0000303|PubMed:7584026},
GN KIAA10 {ECO:0000303|PubMed:11278995};
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=7584026; DOI=10.1093/dnares/1.1.27;
RA Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S.,
RA Nagase T., Seki N., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. I. The
RT coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of
RT randomly sampled cDNA clones from human immature myeloid cell line KG-1.";
RL DNA Res. 1:27-35(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Lung, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP INTERACTION WITH UBE2D1, AUTOUBIQUITINATION, AND TISSUE SPECIFICITY.
RX PubMed=11278995; DOI=10.1074/jbc.m100034200;
RA You J., Pickart C.M.;
RT "A HECT domain E3 enzyme assembles novel polyubiquitin chains.";
RL J. Biol. Chem. 276:19871-19878(2001).
RN [7]
RP FUNCTION, INTERACTION WITH UBE2D1 AND UBE2L3, AND TISSUE SPECIFICITY.
RX PubMed=9575161; DOI=10.1074/jbc.273.20.12148;
RA Schwarz S.E., Rosa J.L., Scheffner M.;
RT "Characterization of human hect domain family members and their interaction
RT with UbcH5 and UbcH7.";
RL J. Biol. Chem. 273:12148-12154(1998).
RN [8]
RP FUNCTION IN CAND2 UBIQUITINATION, PATHWAY, INTERACTION WITH CAND2 AND 26S
RP PROTEASOMES, ACTIVE SITE, MUTAGENESIS OF CYS-1051, AND TISSUE SPECIFICITY.
RX PubMed=12692129; DOI=10.1074/jbc.m212887200;
RA You J., Wang M., Aoki T., Tamura T.-A., Pickart C.M.;
RT "Proteolytic targeting of transcriptional regulator TIP120B by a HECT
RT domain E3 ligase.";
RL J. Biol. Chem. 278:23369-23375(2003).
RN [9]
RP FUNCTION.
RX PubMed=16341092; DOI=10.1038/sj.emboj.7600895;
RA Wang M., Pickart C.M.;
RT "Different HECT domain ubiquitin ligases employ distinct mechanisms of
RT polyubiquitin chain synthesis.";
RL EMBO J. 24:4324-4333(2005).
RN [10]
RP FUNCTION, PATHWAY, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16601690; DOI=10.1038/sj.emboj.7601061;
RA Wang M., Cheng D., Peng J., Pickart C.M.;
RT "Molecular determinants of polyubiquitin linkage selection by an HECT
RT ubiquitin ligase.";
RL EMBO J. 25:1710-1719(2006).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17323924; DOI=10.1021/bi061994u;
RA Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L.;
RT "Mass spectrometric characterization of the affinity-purified human 26S
RT proteasome complex.";
RL Biochemistry 46:3553-3565(2007).
RN [12]
RP FUNCTION, PATHWAY, ACTIVE SITE, AND MUTAGENESIS OF CYS-1051.
RX PubMed=21167755; DOI=10.1016/j.immuni.2010.11.027;
RA Yu Y., Hayward G.S.;
RT "The ubiquitin E3 ligase RAUL negatively regulates type i interferon
RT through ubiquitination of the transcription factors IRF7 and IRF3.";
RL Immunity 33:863-877(2010).
RN [13]
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 [14]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, ACTIVE SITE, AND MUTAGENESIS OF
RP CYS-1051.
RX PubMed=24811749; DOI=10.1002/embj.201386906;
RA Besche H.C., Sha Z., Kukushkin N.V., Peth A., Hock E.M., Kim W., Gygi S.,
RA Gutierrez J.A., Liao H., Dick L., Goldberg A.L.;
RT "Autoubiquitination of the 26S proteasome on Rpn13 regulates breakdown of
RT ubiquitin conjugates.";
RL EMBO J. 33:1159-1176(2014).
RN [15]
RP FUNCTION, INTERACTION WITH THE 26S PROTEASOME, CATALYTIC ACTIVITY, PATHWAY,
RP ACTIVE SITE, AND MUTAGENESIS OF CYS-1051.
RX PubMed=24158444; DOI=10.1074/jbc.m113.499350;
RA Chu B.W., Kovary K.M., Guillaume J., Chen L.C., Teruel M.N., Wandless T.J.;
RT "The E3 ubiquitin ligase UBE3C enhances proteasome processivity by
RT ubiquitinating partially proteolyzed substrates.";
RL J. Biol. Chem. 288:34575-34587(2013).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AUTOUBIQUITINATION, PATHWAY, AND
RP MUTAGENESIS OF CYS-1051.
RX PubMed=25752573; DOI=10.1016/j.molcel.2015.01.041;
RA Kristariyanto Y.A., Abdul Rehman S.A., Campbell D.G., Morrice N.A.,
RA Johnson C., Toth R., Kulathu Y.;
RT "K29-selective ubiquitin binding domain reveals structural basis of
RT specificity and heterotypic nature of K29 polyubiquitin.";
RL Mol. Cell 58:83-94(2015).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=25752577; DOI=10.1016/j.molcel.2015.01.042;
RA Michel M.A., Elliott P.R., Swatek K.N., Simicek M., Pruneda J.N.,
RA Wagstaff J.L., Freund S.M., Komander D.;
RT "Assembly and specific recognition of K29- and K33-linked polyubiquitin.";
RL Mol. Cell 58:95-109(2015).
RN [18]
RP FUNCTION.
RX PubMed=28396413; DOI=10.1073/pnas.1701734114;
RA Kuo C.L., Goldberg A.L.;
RT "Ubiquitinated proteins promote the association of proteasomes with the
RT deubiquitinating enzyme Usp14 and the ubiquitin ligase Ube3c.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E3404-E3413(2017).
RN [19]
RP FUNCTION.
RX PubMed=31375563; DOI=10.1074/jbc.ra119.009654;
RA Gottlieb C.D., Thompson A.C.S., Ordureau A., Harper J.W., Kopito R.R.;
RT "Acute unfolding of a single protein immediately stimulates recruitment of
RT ubiquitin protein ligase E3C (UBE3C) to 26S proteasomes.";
RL J. Biol. Chem. 294:16511-16524(2019).
RN [20]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=34239127; DOI=10.1038/s41589-021-00823-5;
RA Yu Y., Zheng Q., Erramilli S.K., Pan M., Park S., Xie Y., Li J., Fei J.,
RA Kossiakoff A.A., Liu L., Zhao M.;
RT "K29-linked ubiquitin signaling regulates proteotoxic stress response and
RT cell cycle.";
RL Nat. Chem. Biol. 17:896-905(2021).
RN [21]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=33637724; DOI=10.1038/s41467-021-21715-1;
RA Chen Y.H., Huang T.Y., Lin Y.T., Lin S.Y., Li W.H., Hsiao H.J., Yan R.L.,
RA Tang H.W., Shen Z.Q., Chen G.C., Wu K.P., Tsai T.F., Chen R.H.;
RT "VPS34 K29/K48 branched ubiquitination governed by UBE3C and TRABID
RT regulates autophagy, proteostasis and liver metabolism.";
RL Nat. Commun. 12:1322-1322(2021).
RN [22] {ECO:0007744|PDB:6K2C}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 693-1083, FUNCTION, CATALYTIC
RP ACTIVITY, AUTOUBIQUITINATION, UBIQUITINATION AT LYS-903, AND MUTAGENESIS OF
RP 758-ASN--LEU-762; GLN-961; LYS-1013 AND SER-1049.
RX PubMed=32039437; DOI=10.1042/bcj20200027;
RA Singh S., Sivaraman J.;
RT "Crystal structure of HECT domain of UBE3C E3 ligase and its ubiquitination
RT activity.";
RL Biochem. J. 477:905-923(2020).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that specifically catalyzes 'Lys-
CC 29'- and 'Lys-48'-linked polyubiquitin chains (PubMed:11278995,
CC PubMed:12692129, PubMed:16341092, PubMed:16601690, PubMed:24811749,
CC PubMed:24158444, PubMed:25752573, PubMed:25752577, PubMed:34239127,
CC PubMed:33637724, PubMed:32039437). Accepts ubiquitin from the E2
CC ubiquitin-conjugating enzyme UBE2D1 in the form of a thioester and then
CC directly transfers the ubiquitin to targeted substrates
CC (PubMed:9575161, PubMed:32039437). Associates with the proteasome and
CC promotes elongation of ubiquitin chains on substrates bound to the 26S
CC proteasome (PubMed:24158444, PubMed:28396413, PubMed:31375563). Also
CC catalyzes 'Lys-29'- and 'Lys-48'-linked ubiquitination of 26S
CC proteasome subunit ADRM1/RPN13 in response to proteotoxic stress,
CC impairing the ability of the proteasome to bind and degrade ubiquitin-
CC conjugated proteins (PubMed:24811749, PubMed:31375563). Acts as a
CC negative regulator of autophagy by mediating 'Lys-29'- and 'Lys-48'-
CC linked ubiquitination of PIK3C3/VPS34, promoting its degradation
CC (PubMed:33637724). Can assemble unanchored poly-ubiquitin chains in
CC either 'Lys-29'- or 'Lys-48'-linked polyubiquitin chains; with some
CC preference for 'Lys-48' linkages (PubMed:11278995, PubMed:16601690,
CC PubMed:25752577). Acts as a negative regulator of type I interferon by
CC mediating 'Lys-48'-linked ubiquitination of IRF3 and IRF7, leading to
CC their degradation by the proteasome (PubMed:21167755). Catalyzes
CC ubiquitination and degradation of CAND2 (PubMed:12692129).
CC {ECO:0000269|PubMed:11278995, ECO:0000269|PubMed:12692129,
CC ECO:0000269|PubMed:16341092, ECO:0000269|PubMed:16601690,
CC ECO:0000269|PubMed:21167755, ECO:0000269|PubMed:24158444,
CC ECO:0000269|PubMed:24811749, ECO:0000269|PubMed:25752573,
CC ECO:0000269|PubMed:25752577, ECO:0000269|PubMed:28396413,
CC ECO:0000269|PubMed:31375563, ECO:0000269|PubMed:32039437,
CC ECO:0000269|PubMed:33637724, ECO:0000269|PubMed:34239127,
CC ECO:0000269|PubMed:9575161}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.26; Evidence={ECO:0000269|PubMed:11278995,
CC ECO:0000269|PubMed:24158444, ECO:0000269|PubMed:24811749,
CC ECO:0000269|PubMed:25752573, ECO:0000269|PubMed:25752577,
CC ECO:0000269|PubMed:32039437, ECO:0000269|PubMed:33637724,
CC ECO:0000269|PubMed:34239127};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:11278995, ECO:0000269|PubMed:12692129,
CC ECO:0000269|PubMed:16601690, ECO:0000269|PubMed:21167755,
CC ECO:0000269|PubMed:24158444, ECO:0000269|PubMed:24811749,
CC ECO:0000269|PubMed:25752573, ECO:0000269|PubMed:25752577,
CC ECO:0000269|PubMed:33637724, ECO:0000269|PubMed:34239127}.
CC -!- SUBUNIT: Interacts with 26S proteasomes (PubMed:12692129,
CC PubMed:24158444). Interacts (via the HECT domain) with UBE2D1 and, less
CC efficiently, with UBE2L3 (PubMed:11278995, PubMed:9575161).
CC {ECO:0000269|PubMed:11278995, ECO:0000269|PubMed:12692129,
CC ECO:0000269|PubMed:24158444, ECO:0000269|PubMed:9575161}.
CC -!- INTERACTION:
CC Q15386; Q08379: GOLGA2; NbExp=3; IntAct=EBI-1058871, EBI-618309;
CC Q15386-3; P23560-2: BDNF; NbExp=3; IntAct=EBI-25833079, EBI-12275524;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q15386-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15386-2; Sequence=VSP_013956, VSP_013957;
CC Name=3;
CC IsoId=Q15386-3; Sequence=VSP_013953, VSP_013954, VSP_013955;
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle. Detected at
CC much lower levels in kidney and pancreas. {ECO:0000269|PubMed:11278995,
CC ECO:0000269|PubMed:12692129, ECO:0000269|PubMed:9575161}.
CC -!- PTM: Autoubiquitinated; promoting its own degradation.
CC {ECO:0000269|PubMed:11278995, ECO:0000269|PubMed:25752573,
CC ECO:0000269|PubMed:32039437}.
CC -!- SIMILARITY: Belongs to the UBE3C family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA02799.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D13635; BAA02799.2; ALT_INIT; mRNA.
DR EMBL; AC004898; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC004975; AAD51453.1; -; Genomic_DNA.
DR EMBL; CH236954; EAL23922.1; -; Genomic_DNA.
DR EMBL; CH471149; EAX04568.1; -; Genomic_DNA.
DR EMBL; BC014029; AAH14029.1; -; mRNA.
DR EMBL; BC026241; AAH26241.1; -; mRNA.
DR CCDS; CCDS34789.1; -. [Q15386-1]
DR PIR; A38919; A38919.
DR RefSeq; NP_055486.2; NM_014671.2. [Q15386-1]
DR PDB; 6K2C; X-ray; 2.70 A; A=693-1083.
DR PDBsum; 6K2C; -.
DR AlphaFoldDB; Q15386; -.
DR SMR; Q15386; -.
DR BioGRID; 115043; 191.
DR IntAct; Q15386; 28.
DR MINT; Q15386; -.
DR STRING; 9606.ENSP00000309198; -.
DR GlyGen; Q15386; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q15386; -.
DR PhosphoSitePlus; Q15386; -.
DR BioMuta; UBE3C; -.
DR DMDM; 67462009; -.
DR EPD; Q15386; -.
DR jPOST; Q15386; -.
DR MassIVE; Q15386; -.
DR MaxQB; Q15386; -.
DR PaxDb; Q15386; -.
DR PeptideAtlas; Q15386; -.
DR PRIDE; Q15386; -.
DR ProteomicsDB; 60555; -. [Q15386-1]
DR ProteomicsDB; 60556; -. [Q15386-2]
DR ProteomicsDB; 60557; -. [Q15386-3]
DR Antibodypedia; 33178; 163 antibodies from 26 providers.
DR DNASU; 9690; -.
DR Ensembl; ENST00000348165.10; ENSP00000309198.8; ENSG00000009335.18. [Q15386-1]
DR Ensembl; ENST00000389103.4; ENSP00000373755.4; ENSG00000009335.18. [Q15386-3]
DR Ensembl; ENST00000611269.4; ENSP00000481584.1; ENSG00000009335.18. [Q15386-3]
DR GeneID; 9690; -.
DR KEGG; hsa:9690; -.
DR MANE-Select; ENST00000348165.10; ENSP00000309198.8; NM_014671.3; NP_055486.2.
DR UCSC; uc003wnf.3; human. [Q15386-1]
DR CTD; 9690; -.
DR DisGeNET; 9690; -.
DR GeneCards; UBE3C; -.
DR HGNC; HGNC:16803; UBE3C.
DR HPA; ENSG00000009335; Low tissue specificity.
DR MIM; 614454; gene.
DR neXtProt; NX_Q15386; -.
DR OpenTargets; ENSG00000009335; -.
DR PharmGKB; PA134905339; -.
DR VEuPathDB; HostDB:ENSG00000009335; -.
DR eggNOG; KOG0942; Eukaryota.
DR GeneTree; ENSGT00940000156321; -.
DR HOGENOM; CLU_002173_2_1_1; -.
DR InParanoid; Q15386; -.
DR OMA; TDNKLYP; -.
DR OrthoDB; 1163565at2759; -.
DR PhylomeDB; Q15386; -.
DR TreeFam; TF106144; -.
DR BRENDA; 2.3.2.26; 2681.
DR PathwayCommons; Q15386; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q15386; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 9690; 25 hits in 1131 CRISPR screens.
DR ChiTaRS; UBE3C; human.
DR GeneWiki; UBE3C; -.
DR GenomeRNAi; 9690; -.
DR Pharos; Q15386; Tbio.
DR PRO; PR:Q15386; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q15386; protein.
DR Bgee; ENSG00000009335; Expressed in sural nerve and 206 other tissues.
DR ExpressionAtlas; Q15386; baseline and differential.
DR Genevisible; Q15386; HS.
DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0035519; P:protein K29-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR CDD; cd00078; HECTc; 1.
DR InterPro; IPR044611; E3B/C.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR PANTHER; PTHR45700; PTHR45700; 1.
DR Pfam; PF00632; HECT; 1.
DR SMART; SM00119; HECTc; 1.
DR SMART; SM00015; IQ; 1.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS50096; IQ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Isopeptide bond; Proteasome; Reference proteome; Transferase;
KW Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..1083
FT /note="Ubiquitin-protein ligase E3C"
FT /id="PRO_0000194982"
FT DOMAIN 45..74
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT DOMAIN 744..1083
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 1..60
FT /note="Cis-determinant of acceptor ubiquitin-binding"
FT /evidence="ECO:0000269|PubMed:16341092"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 355..385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 16..40
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1051
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000305|PubMed:12692129,
FT ECO:0000305|PubMed:21167755, ECO:0000305|PubMed:24158444,
FT ECO:0000305|PubMed:24811749, ECO:0000305|PubMed:25752573"
FT CROSSLNK 903
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); by autocatalysis"
FT /evidence="ECO:0000269|PubMed:32039437"
FT VAR_SEQ 23..65
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013953"
FT VAR_SEQ 445..447
FT /note="LLY -> VYK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013954"
FT VAR_SEQ 448..1083
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013955"
FT VAR_SEQ 640..649
FT /note="TQLYVPASRH -> LLKDLFNIYH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013956"
FT VAR_SEQ 650..1083
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013957"
FT MUTAGEN 758..762
FT /note="NAHGL->AAAAA: Abolished E3 ubiquitin-protein ligase
FT activity."
FT /evidence="ECO:0000269|PubMed:32039437"
FT MUTAGEN 961
FT /note="Q->A,E: Reduced E3 ubiquitin-protein ligase
FT activity."
FT /evidence="ECO:0000269|PubMed:32039437"
FT MUTAGEN 1013
FT /note="K->Q: Increased E3 ubiquitin-protein ligase
FT activity."
FT /evidence="ECO:0000269|PubMed:32039437"
FT MUTAGEN 1049
FT /note="S->H: Reduced E3 ubiquitin-protein ligase activity."
FT /evidence="ECO:0000269|PubMed:32039437"
FT MUTAGEN 1051
FT /note="C->A: Abolishes E3 ubiquitin-protein ligase
FT activity. No stimulation of in vitro CAND2 ubiquitination."
FT /evidence="ECO:0000269|PubMed:12692129,
FT ECO:0000269|PubMed:21167755, ECO:0000269|PubMed:24158444,
FT ECO:0000269|PubMed:24811749, ECO:0000269|PubMed:25752573"
FT CONFLICT 822
FT /note="G -> A (in Ref. 1; BAA02799)"
FT /evidence="ECO:0000305"
FT HELIX 695..712
FT /evidence="ECO:0007829|PDB:6K2C"
FT STRAND 723..727
FT /evidence="ECO:0007829|PDB:6K2C"
FT HELIX 729..731
FT /evidence="ECO:0007829|PDB:6K2C"
FT HELIX 732..739
FT /evidence="ECO:0007829|PDB:6K2C"
FT TURN 742..744
FT /evidence="ECO:0007829|PDB:6K2C"
FT STRAND 752..756
FT /evidence="ECO:0007829|PDB:6K2C"
FT HELIX 770..784
FT /evidence="ECO:0007829|PDB:6K2C"
FT HELIX 787..789
FT /evidence="ECO:0007829|PDB:6K2C"
FT STRAND 790..794
FT /evidence="ECO:0007829|PDB:6K2C"
FT STRAND 796..798
FT /evidence="ECO:0007829|PDB:6K2C"
FT STRAND 800..802
FT /evidence="ECO:0007829|PDB:6K2C"
FT HELIX 806..810
FT /evidence="ECO:0007829|PDB:6K2C"
FT HELIX 814..830
FT /evidence="ECO:0007829|PDB:6K2C"
FT HELIX 841..848
FT /evidence="ECO:0007829|PDB:6K2C"
FT TURN 929..932
FT /evidence="ECO:0007829|PDB:6K2C"
FT HELIX 933..944
FT /evidence="ECO:0007829|PDB:6K2C"
FT HELIX 949..952
FT /evidence="ECO:0007829|PDB:6K2C"
FT HELIX 957..965
FT /evidence="ECO:0007829|PDB:6K2C"
FT HELIX 973..978
FT /evidence="ECO:0007829|PDB:6K2C"
FT STRAND 981..983
FT /evidence="ECO:0007829|PDB:6K2C"
FT HELIX 991..1001
FT /evidence="ECO:0007829|PDB:6K2C"
FT HELIX 1005..1016
FT /evidence="ECO:0007829|PDB:6K2C"
FT HELIX 1026..1028
FT /evidence="ECO:0007829|PDB:6K2C"
FT STRAND 1034..1037
FT /evidence="ECO:0007829|PDB:6K2C"
FT STRAND 1047..1049
FT /evidence="ECO:0007829|PDB:6K2C"
FT HELIX 1050..1052
FT /evidence="ECO:0007829|PDB:6K2C"
FT STRAND 1054..1057
FT /evidence="ECO:0007829|PDB:6K2C"
FT HELIX 1063..1077
FT /evidence="ECO:0007829|PDB:6K2C"
SQ SEQUENCE 1083 AA; 123923 MW; BD437ABA457A0DDA CRC64;
MFSFEGDFKT RPKVSLGGAS RKEEKASLLH RTQEERRKRE EERRRLKNAI IIQSFIRGYR
DRKQQYSIQR SAFDRCATLS QSGGAFPIAN GPNLTLLVRQ LLFFYKQNED SKRLIWLYQN
LIKHSSLFVK QLDGSERLTC LFQIKRLMSL CCRLLQNCND DSLNVALPMR MLEVFSSENT
YLPVLQDASY VVSVIEQILH YMIHNGYYRS LYLLINSKLP SSIEYSDLSR VPIAKILLEN
VLKPLHFTYN SCPEGARQQV FTAFTEEFLA APFTDQIFHF IIPALADAQT VFPYEPFLNA
LLLIESRCSR KSGGAPWLFY FVLTVGENYL GALSEEGLLV YLRVLQTFLS QLPVSPASAS
CHDSASDSEE ESEEADKPSS PEDGRLSVSY ITEECLKKLD TKQQTNTLLN LVWRDSASEE
VFTTMASVCH TLMVQHRMMV PKVRLLYSLA FNARFLRHLW FLISSMSTRM ITGSMVPLLQ
VISRGSPMSF EDSSRIIPLF YLFSSLFSHS LISIHDNEFF GDPIEVVGQR QSSMMPFTLE
ELIMLSRCLR DACLGIIKLA YPETKPEVRE EYITAFQSIG VTTSSEMQQC IQMEQKRWIQ
LFKVITNLVK MLKSRDTRRN FCPPNHWLSE QEDIKADKVT QLYVPASRHV WRFRRMGRIG
PLQSTLDVGL ESPPLSVSEE RQLAVLTELP FVVPFEERVK IFQRLIYADK QEVQGDGPFL
DGINVTIRRN YIYEDAYDKL SPENEPDLKK RIRVHLLNAH GLDEAGIDGG GIFREFLNEL
LKSGFNPNQG FFKTTNEGLL YPNPAAQMLV GDSFARHYYF LGRMLGKALY ENMLVELPFA
GFFLSKLLGT SADVDIHHLA SLDPEVYKNL LFLKSYEDDV EELGLNFTVV NNDLGEAQVV
ELKFGGKDIP VTSANRIAYI HLVADYRLNR QIRQHCLAFR QGLANVVSLE WLRMFDQQEI
QVLISGAQVP ISLEDLKSFT NYSGGYSADH PVIKVFWRVV EGFTDEEKRK LLKFVTSCSR
PPLLGFKELY PAFCIHNGGS DLERLPTAST CMNLLKLPEF YDETLLRSKL LYAIECAAGF
ELS
