Full text data of UBE3C
UBE3C
(KIAA0010, KIAA10)
[Confidence: low (only semi-automatic identification from reviews)]
Ubiquitin-protein ligase E3C; 6.3.2.- (HectH2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ubiquitin-protein ligase E3C; 6.3.2.- (HectH2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q15386
ID UBE3C_HUMAN Reviewed; 1083 AA.
AC Q15386; A4D235; A6NCP3; Q8TC15; Q96CR4; Q9UDU3;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-JUN-2005, sequence version 3.
DT 22-JAN-2014, entry version 115.
DE RecName: Full=Ubiquitin-protein ligase E3C;
DE EC=6.3.2.-;
DE AltName: Full=HectH2;
GN Name=UBE3C; Synonyms=KIAA0010, KIAA10;
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 [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.,
RA Sato S., Nagase T., Seki N., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. I.
RT The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by
RT analysis of randomly sampled cDNA clones from human immature myeloid
RT 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.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA 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.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., 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.,
RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA 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.,
RA Mural R.J., 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.,
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 [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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, INTERACTION WITH UBE2D1,
RP 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 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
RT interaction with UbcH5 and UbcH7.";
RL J. Biol. Chem. 273:12148-12154(1998).
RN [8]
RP FUNCTION IN CAND2 UBIQUITINATION, INTERACTION WITH CAND2 AND 26S
RP PROTEASOMES, 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, AND 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
RT 26S proteasome complex.";
RL Biochemistry 46:3553-3565(2007).
RN [12]
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).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that accepts ubiquitin from
CC the E2 ubiquitin-conjugating enzyme UBE2D1 in the form of a
CC thioester and then directly transfers the ubiquitin to targeted
CC substrates. Can assemble unanchored poly-ubiquitin chains in
CC either 'Lys-29'- or 'Lys-48'-linked polyubiquitin chains. Has
CC preference for 'Lys-48' linkages. It can target itself for
CC ubiquitination in vitro and may promote its own degradation in
CC vivo.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with 26S proteasomes. Interacts (via the N-
CC terminal) with CAND2; the interaction stimulates ubiquitination of
CC CAND2 in vitro. May interact (via the HECT domain) with UBE2D1
CC and, less efficiently, with UBE2L3.
CC -!- SUBCELLULAR LOCATION: Nucleus (Potential).
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 Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q15386-3; Sequence=VSP_013953, VSP_013954, VSP_013955;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle. Detected
CC at much lower levels in kidney and pancreas.
CC -!- DOMAIN: The C-terminal is necessary and sufficient for the poly-
CC ubiquitin chain assembly.
CC -!- MISCELLANEOUS: A cysteine residue is required for ubiquitin-
CC thioester formation.
CC -!- SIMILARITY: Contains 1 HECT (E6AP-type E3 ubiquitin-protein
CC ligase) domain.
CC -!- SIMILARITY: Contains 1 IQ domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA02799.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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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 PIR; A38919; A38919.
DR RefSeq; NP_055486.2; NM_014671.2.
DR UniGene; Hs.118351; -.
DR ProteinModelPortal; Q15386; -.
DR SMR; Q15386; 723-1077.
DR IntAct; Q15386; 4.
DR STRING; 9606.ENSP00000309198; -.
DR PhosphoSite; Q15386; -.
DR DMDM; 67462009; -.
DR PaxDb; Q15386; -.
DR PRIDE; Q15386; -.
DR DNASU; 9690; -.
DR Ensembl; ENST00000348165; ENSP00000309198; ENSG00000009335.
DR Ensembl; ENST00000389103; ENSP00000373755; ENSG00000009335.
DR GeneID; 9690; -.
DR KEGG; hsa:9690; -.
DR UCSC; uc010lqs.3; human.
DR CTD; 9690; -.
DR GeneCards; GC07P156931; -.
DR HGNC; HGNC:16803; UBE3C.
DR HPA; HPA039915; -.
DR MIM; 614454; gene.
DR neXtProt; NX_Q15386; -.
DR PharmGKB; PA134905339; -.
DR eggNOG; COG5021; -.
DR HOGENOM; HOG000030618; -.
DR HOVERGEN; HBG073375; -.
DR InParanoid; Q15386; -.
DR KO; K10589; -.
DR OMA; KVRLLYS; -.
DR OrthoDB; EOG7R56RN; -.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00143; -.
DR ChiTaRS; UBE3C; human.
DR GeneWiki; UBE3C; -.
DR GenomeRNAi; 9690; -.
DR NextBio; 36397; -.
DR PRO; PR:Q15386; -.
DR ArrayExpress; Q15386; -.
DR Bgee; Q15386; -.
DR CleanEx; HS_UBE3C; -.
DR Genevestigator; Q15386; -.
DR GO; GO:0005737; C:cytoplasm; IBA:RefGenome.
DR GO; GO:0005634; C:nucleus; IBA:RefGenome.
DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IBA:RefGenome.
DR InterPro; IPR000569; HECT.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
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 Alternative splicing; Complete proteome; Direct protein sequencing;
KW Ligase; Nucleus; Proteasome; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1 1083 Ubiquitin-protein ligase E3C.
FT /FTId=PRO_0000194982.
FT DOMAIN 45 74 IQ.
FT DOMAIN 744 1083 HECT.
FT REGION 1 60 Cis-determinant of acceptor ubiquitin-
FT binding.
FT ACT_SITE 1051 1051 Glycyl thioester intermediate.
FT VAR_SEQ 23 65 Missing (in isoform 3).
FT /FTId=VSP_013953.
FT VAR_SEQ 445 447 LLY -> VYK (in isoform 3).
FT /FTId=VSP_013954.
FT VAR_SEQ 448 1083 Missing (in isoform 3).
FT /FTId=VSP_013955.
FT VAR_SEQ 640 649 TQLYVPASRH -> LLKDLFNIYH (in isoform 2).
FT /FTId=VSP_013956.
FT VAR_SEQ 650 1083 Missing (in isoform 2).
FT /FTId=VSP_013957.
FT MUTAGEN 1051 1051 C->A: No stimulation of in vitro CAND2
FT ubiquitination.
FT CONFLICT 822 822 G -> A (in Ref. 1; BAA02799).
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
//
ID UBE3C_HUMAN Reviewed; 1083 AA.
AC Q15386; A4D235; A6NCP3; Q8TC15; Q96CR4; Q9UDU3;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-JUN-2005, sequence version 3.
DT 22-JAN-2014, entry version 115.
DE RecName: Full=Ubiquitin-protein ligase E3C;
DE EC=6.3.2.-;
DE AltName: Full=HectH2;
GN Name=UBE3C; Synonyms=KIAA0010, KIAA10;
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 [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.,
RA Sato S., Nagase T., Seki N., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. I.
RT The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by
RT analysis of randomly sampled cDNA clones from human immature myeloid
RT 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.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA 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.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., 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.,
RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA 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.,
RA Mural R.J., 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.,
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 [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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, INTERACTION WITH UBE2D1,
RP 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 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
RT interaction with UbcH5 and UbcH7.";
RL J. Biol. Chem. 273:12148-12154(1998).
RN [8]
RP FUNCTION IN CAND2 UBIQUITINATION, INTERACTION WITH CAND2 AND 26S
RP PROTEASOMES, 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, AND 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
RT 26S proteasome complex.";
RL Biochemistry 46:3553-3565(2007).
RN [12]
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).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that accepts ubiquitin from
CC the E2 ubiquitin-conjugating enzyme UBE2D1 in the form of a
CC thioester and then directly transfers the ubiquitin to targeted
CC substrates. Can assemble unanchored poly-ubiquitin chains in
CC either 'Lys-29'- or 'Lys-48'-linked polyubiquitin chains. Has
CC preference for 'Lys-48' linkages. It can target itself for
CC ubiquitination in vitro and may promote its own degradation in
CC vivo.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with 26S proteasomes. Interacts (via the N-
CC terminal) with CAND2; the interaction stimulates ubiquitination of
CC CAND2 in vitro. May interact (via the HECT domain) with UBE2D1
CC and, less efficiently, with UBE2L3.
CC -!- SUBCELLULAR LOCATION: Nucleus (Potential).
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 Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q15386-3; Sequence=VSP_013953, VSP_013954, VSP_013955;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle. Detected
CC at much lower levels in kidney and pancreas.
CC -!- DOMAIN: The C-terminal is necessary and sufficient for the poly-
CC ubiquitin chain assembly.
CC -!- MISCELLANEOUS: A cysteine residue is required for ubiquitin-
CC thioester formation.
CC -!- SIMILARITY: Contains 1 HECT (E6AP-type E3 ubiquitin-protein
CC ligase) domain.
CC -!- SIMILARITY: Contains 1 IQ domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA02799.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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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 PIR; A38919; A38919.
DR RefSeq; NP_055486.2; NM_014671.2.
DR UniGene; Hs.118351; -.
DR ProteinModelPortal; Q15386; -.
DR SMR; Q15386; 723-1077.
DR IntAct; Q15386; 4.
DR STRING; 9606.ENSP00000309198; -.
DR PhosphoSite; Q15386; -.
DR DMDM; 67462009; -.
DR PaxDb; Q15386; -.
DR PRIDE; Q15386; -.
DR DNASU; 9690; -.
DR Ensembl; ENST00000348165; ENSP00000309198; ENSG00000009335.
DR Ensembl; ENST00000389103; ENSP00000373755; ENSG00000009335.
DR GeneID; 9690; -.
DR KEGG; hsa:9690; -.
DR UCSC; uc010lqs.3; human.
DR CTD; 9690; -.
DR GeneCards; GC07P156931; -.
DR HGNC; HGNC:16803; UBE3C.
DR HPA; HPA039915; -.
DR MIM; 614454; gene.
DR neXtProt; NX_Q15386; -.
DR PharmGKB; PA134905339; -.
DR eggNOG; COG5021; -.
DR HOGENOM; HOG000030618; -.
DR HOVERGEN; HBG073375; -.
DR InParanoid; Q15386; -.
DR KO; K10589; -.
DR OMA; KVRLLYS; -.
DR OrthoDB; EOG7R56RN; -.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00143; -.
DR ChiTaRS; UBE3C; human.
DR GeneWiki; UBE3C; -.
DR GenomeRNAi; 9690; -.
DR NextBio; 36397; -.
DR PRO; PR:Q15386; -.
DR ArrayExpress; Q15386; -.
DR Bgee; Q15386; -.
DR CleanEx; HS_UBE3C; -.
DR Genevestigator; Q15386; -.
DR GO; GO:0005737; C:cytoplasm; IBA:RefGenome.
DR GO; GO:0005634; C:nucleus; IBA:RefGenome.
DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IBA:RefGenome.
DR InterPro; IPR000569; HECT.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
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 Alternative splicing; Complete proteome; Direct protein sequencing;
KW Ligase; Nucleus; Proteasome; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1 1083 Ubiquitin-protein ligase E3C.
FT /FTId=PRO_0000194982.
FT DOMAIN 45 74 IQ.
FT DOMAIN 744 1083 HECT.
FT REGION 1 60 Cis-determinant of acceptor ubiquitin-
FT binding.
FT ACT_SITE 1051 1051 Glycyl thioester intermediate.
FT VAR_SEQ 23 65 Missing (in isoform 3).
FT /FTId=VSP_013953.
FT VAR_SEQ 445 447 LLY -> VYK (in isoform 3).
FT /FTId=VSP_013954.
FT VAR_SEQ 448 1083 Missing (in isoform 3).
FT /FTId=VSP_013955.
FT VAR_SEQ 640 649 TQLYVPASRH -> LLKDLFNIYH (in isoform 2).
FT /FTId=VSP_013956.
FT VAR_SEQ 650 1083 Missing (in isoform 2).
FT /FTId=VSP_013957.
FT MUTAGEN 1051 1051 C->A: No stimulation of in vitro CAND2
FT ubiquitination.
FT CONFLICT 822 822 G -> A (in Ref. 1; BAA02799).
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
//
MIM
614454
*RECORD*
*FIELD* NO
614454
*FIELD* TI
*614454 UBIQUITIN PROTEIN LIGASE E3C; UBE3C
;;HECTH2;;
KIAA0010;;
KIAA10
*FIELD* TX
read more
DESCRIPTION
Ubiquitin (UBB; 191339) modification of lysine residues targets proteins
for degradation via the proteasome (see 606223). Ubiquitination requires
a ubiquitin-activating enzyme (E1; see 314370), a ubiquitin-carrier
protein (E2; see 602961), and a ubiquitin-protein ligase (E3), such as
UBE3C. E3 enzymes transiently accept ubiquitin from the E2 in a thiol
ester linkage prior to transferring ubiquitin to the target lysine
(summary by You and Pickart, 2001).
CLONING
By sequencing clones obtained from a size-fractionated human immature
myeloid cell line KG-1, Nomura et al. (1994) obtained a partial UBE3C
clone, which they designated KIAA0010. The deduced protein shares
significant similarity with E6AP (UBE3A; 601623), and it contains a
lipid attachment site and a tyrosine kinase phosphorylation site.
Northern blot analysis detected KIAA0010 expression in all tissues and
cell lines examined, with highest expression in lung, liver, skeletal
muscle, kidney, spleen, testis, and ovary, and weakest expression in
thymus.
You and Pickart (2001) cloned full-length UBE3C, which they called
KIAA10. The deduced 1,083-amino acid protein has a calculated molecular
mass of about 120 kD. KIAA10 has a unique N-terminal domain predicted to
mediate substrate binding and a C-terminal HECT domain, suggesting that
it functions as a HECT domain family E3 ligase.
GENE FUNCTION
Schwarz et al. (1998) showed that in vitro-translated human UBE3C, which
they called HECTH2, formed a thioester complex with ubiquitin in the
presence of an E1 enzyme and the E2 enzyme UBCH5 (UBE2D1; 602961), with
reduced efficiency with the E2 UBCH7 (UBE2L3; 603721).
You and Pickart (2001) showed that full-length KIAA10 and its isolated
428-amino acid C terminus, including the HECT domain, assembled
polyubiquitin chains linked through lys29 or lys48. KIAA10 also
displayed autoubiquitination. The N-terminal KIAA10 domain was devoid of
activity. Mutation analysis revealed that the N terminus of KIAA10
interacted directly with the S2 subunit of the proteasome 26S complex
(PSMD2; 606223).
MAPPING
By PCR of a human-rodent hybrid cell line panel, Nomura et al. (1994)
mapped the UBE3C gene to chromosome 7.
Hartz (2012) mapped the UBE3C gene to chromosome 7q36.3 based on an
alignment of the UBE3C sequence (GenBank GENBANK D13635) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Hartz, P. A.: Personal Communication. Baltimore, Md. 1/10/2012.
2. Nomura, N.; Miyajima, N.; Sazuka, T.; Tanaka, A.; Kawarabayasi,
Y.; Sato, S.; Nagase, T.; Seki, N.; Ishikawa, K.; Tabata, S.: Prediction
of the coding sequences of unidentified human genes. I. The coding
sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis
of randomly samples cDNA clones from human immature myeloid cell line
KG-1. DNA Res. 1: 27-35, 1994. Note: Erratum: DNA Res. 2: 210 only,
1995.
3. Schwarz, S. E.; Rosa, J. L.; Scheffner, M.: Characterization of
human hect domain family members and their interaction with UbcH5
and UbcH7. J. Biol. Chem. 273: 12148-12154, 1998.
4. You, J.; Pickart, C. M.: A HECT domain E3 enzyme assembles novel
polyubiquitin chains. J. Biol. Chem. 276: 19871-19878, 2001.
*FIELD* CD
Patricia A. Hartz: 1/27/2012
*FIELD* ED
alopez: 04/30/2013
mgross: 1/27/2012
*RECORD*
*FIELD* NO
614454
*FIELD* TI
*614454 UBIQUITIN PROTEIN LIGASE E3C; UBE3C
;;HECTH2;;
KIAA0010;;
KIAA10
*FIELD* TX
read more
DESCRIPTION
Ubiquitin (UBB; 191339) modification of lysine residues targets proteins
for degradation via the proteasome (see 606223). Ubiquitination requires
a ubiquitin-activating enzyme (E1; see 314370), a ubiquitin-carrier
protein (E2; see 602961), and a ubiquitin-protein ligase (E3), such as
UBE3C. E3 enzymes transiently accept ubiquitin from the E2 in a thiol
ester linkage prior to transferring ubiquitin to the target lysine
(summary by You and Pickart, 2001).
CLONING
By sequencing clones obtained from a size-fractionated human immature
myeloid cell line KG-1, Nomura et al. (1994) obtained a partial UBE3C
clone, which they designated KIAA0010. The deduced protein shares
significant similarity with E6AP (UBE3A; 601623), and it contains a
lipid attachment site and a tyrosine kinase phosphorylation site.
Northern blot analysis detected KIAA0010 expression in all tissues and
cell lines examined, with highest expression in lung, liver, skeletal
muscle, kidney, spleen, testis, and ovary, and weakest expression in
thymus.
You and Pickart (2001) cloned full-length UBE3C, which they called
KIAA10. The deduced 1,083-amino acid protein has a calculated molecular
mass of about 120 kD. KIAA10 has a unique N-terminal domain predicted to
mediate substrate binding and a C-terminal HECT domain, suggesting that
it functions as a HECT domain family E3 ligase.
GENE FUNCTION
Schwarz et al. (1998) showed that in vitro-translated human UBE3C, which
they called HECTH2, formed a thioester complex with ubiquitin in the
presence of an E1 enzyme and the E2 enzyme UBCH5 (UBE2D1; 602961), with
reduced efficiency with the E2 UBCH7 (UBE2L3; 603721).
You and Pickart (2001) showed that full-length KIAA10 and its isolated
428-amino acid C terminus, including the HECT domain, assembled
polyubiquitin chains linked through lys29 or lys48. KIAA10 also
displayed autoubiquitination. The N-terminal KIAA10 domain was devoid of
activity. Mutation analysis revealed that the N terminus of KIAA10
interacted directly with the S2 subunit of the proteasome 26S complex
(PSMD2; 606223).
MAPPING
By PCR of a human-rodent hybrid cell line panel, Nomura et al. (1994)
mapped the UBE3C gene to chromosome 7.
Hartz (2012) mapped the UBE3C gene to chromosome 7q36.3 based on an
alignment of the UBE3C sequence (GenBank GENBANK D13635) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Hartz, P. A.: Personal Communication. Baltimore, Md. 1/10/2012.
2. Nomura, N.; Miyajima, N.; Sazuka, T.; Tanaka, A.; Kawarabayasi,
Y.; Sato, S.; Nagase, T.; Seki, N.; Ishikawa, K.; Tabata, S.: Prediction
of the coding sequences of unidentified human genes. I. The coding
sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis
of randomly samples cDNA clones from human immature myeloid cell line
KG-1. DNA Res. 1: 27-35, 1994. Note: Erratum: DNA Res. 2: 210 only,
1995.
3. Schwarz, S. E.; Rosa, J. L.; Scheffner, M.: Characterization of
human hect domain family members and their interaction with UbcH5
and UbcH7. J. Biol. Chem. 273: 12148-12154, 1998.
4. You, J.; Pickart, C. M.: A HECT domain E3 enzyme assembles novel
polyubiquitin chains. J. Biol. Chem. 276: 19871-19878, 2001.
*FIELD* CD
Patricia A. Hartz: 1/27/2012
*FIELD* ED
alopez: 04/30/2013
mgross: 1/27/2012