Q15386 (UBE3C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin-protein ligase E3C
EC=6.3.2.-

Gene names

Name:	UBE3C
Synonyms:	KIAA0010, KIAA10

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1083 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E3 ubiquitin-protein ligase that accepts ubiquitin from the E2 ubiquitin-conjugating enzyme UBE2D1 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Can assemble unanchored poly-ubiquitin chains in either 'Lys-29'- or 'Lys-48'-linked polyubiquitin chains. Has preference for 'Lys-48' linkages. It can target itself for ubiquitination in vitro and may promote its own degradation in vivo. Ref.6 Ref.7 Ref.8 Ref.9
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with 26S proteasomes. Interacts (via the N-terminal) with CAND2; the interaction stimulates ubiquitination of CAND2 in vitro. Ref.6 Ref.7 Ref.10
Subcellular location	Nucleus Potential.
Tissue specificity	Highly expressed in skeletal muscle. Detected at much lower levels in kidney and pancreas. Ref.6 Ref.7
Domain	The C-terminal is necessary and sufficient for the poly-ubiquitin chain assembly.
Miscellaneous	A cysteine residue is required for ubiquitin-thioester formation.
Sequence similarities	Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain. Contains 1 IQ domain.
Sequence caution	The sequence BAA02799.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Nucleus Proteasome
Coding sequence diversity	Alternative splicing
Molecular function	Ligase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	protein polyubiquitination Inferred from direct assay Ref.6. Source: UniProtKB protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell proteasome complex Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein binding Inferred from physical interaction Ref.6Ref.7. Source: UniProtKB ubiquitin-protein ligase activity Inferred from direct assay Ref.6. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q15386-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q15386-2)

The sequence of this isoform differs from the canonical sequence as follows:
     640-649: TQLYVPASRH → LLKDLFNIYH
     650-1083: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q15386-3)

The sequence of this isoform differs from the canonical sequence as follows:
     23-65: Missing.
     445-447: LLY → VYK
     448-1083: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1083	1083	Ubiquitin-protein ligase E3C		PRO_0000194982
Regions
	Domain	45 – 74	30	IQ
	Domain	744 – 1083	340	HECT
	Region	1 – 60	60	Cis-determinant of acceptor ubiquitin-binding
Sites
	Active site	1051	1	Glycyl thioester intermediate
Natural variations
	Alternative sequence	23 – 65	43	Missing in isoform 3.		VSP_013953
	Alternative sequence	445 – 447	3	LLY → VYK in isoform 3.		VSP_013954
	Alternative sequence	448 – 1083	636	Missing in isoform 3.		VSP_013955
	Alternative sequence	640 – 649	10	TQLYVPASRH → LLKDLFNIYH in isoform 2.		VSP_013956
	Alternative sequence	650 – 1083	434	Missing in isoform 2.		VSP_013957
Experimental info
	Mutagenesis	1051	1	C → A: No stimulation of in vitro CAND2 ubiquitination. Ref.7
	Sequence conflict	822	1	G → A in BAA02799. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 7, 2005. Version 3. Checksum: BD437ABA457A0DDA	FASTA	1,083	123,923
	10 20 30 40 50 60 MFSFEGDFKT RPKVSLGGAS RKEEKASLLH RTQEERRKRE EERRRLKNAI IIQSFIRGYR 70 80 90 100 110 120 DRKQQYSIQR SAFDRCATLS QSGGAFPIAN GPNLTLLVRQ LLFFYKQNED SKRLIWLYQN 130 140 150 160 170 180 LIKHSSLFVK QLDGSERLTC LFQIKRLMSL CCRLLQNCND DSLNVALPMR MLEVFSSENT 190 200 210 220 230 240 YLPVLQDASY VVSVIEQILH YMIHNGYYRS LYLLINSKLP SSIEYSDLSR VPIAKILLEN 250 260 270 280 290 300 VLKPLHFTYN SCPEGARQQV FTAFTEEFLA APFTDQIFHF IIPALADAQT VFPYEPFLNA 310 320 330 340 350 360 LLLIESRCSR KSGGAPWLFY FVLTVGENYL GALSEEGLLV YLRVLQTFLS QLPVSPASAS 370 380 390 400 410 420 CHDSASDSEE ESEEADKPSS PEDGRLSVSY ITEECLKKLD TKQQTNTLLN LVWRDSASEE 430 440 450 460 470 480 VFTTMASVCH TLMVQHRMMV PKVRLLYSLA FNARFLRHLW FLISSMSTRM ITGSMVPLLQ 490 500 510 520 530 540 VISRGSPMSF EDSSRIIPLF YLFSSLFSHS LISIHDNEFF GDPIEVVGQR QSSMMPFTLE 550 560 570 580 590 600 ELIMLSRCLR DACLGIIKLA YPETKPEVRE EYITAFQSIG VTTSSEMQQC IQMEQKRWIQ 610 620 630 640 650 660 LFKVITNLVK MLKSRDTRRN FCPPNHWLSE QEDIKADKVT QLYVPASRHV WRFRRMGRIG 670 680 690 700 710 720 PLQSTLDVGL ESPPLSVSEE RQLAVLTELP FVVPFEERVK IFQRLIYADK QEVQGDGPFL 730 740 750 760 770 780 DGINVTIRRN YIYEDAYDKL SPENEPDLKK RIRVHLLNAH GLDEAGIDGG GIFREFLNEL 790 800 810 820 830 840 LKSGFNPNQG FFKTTNEGLL YPNPAAQMLV GDSFARHYYF LGRMLGKALY ENMLVELPFA 850 860 870 880 890 900 GFFLSKLLGT SADVDIHHLA SLDPEVYKNL LFLKSYEDDV EELGLNFTVV NNDLGEAQVV 910 920 930 940 950 960 ELKFGGKDIP VTSANRIAYI HLVADYRLNR QIRQHCLAFR QGLANVVSLE WLRMFDQQEI 970 980 990 1000 1010 1020 QVLISGAQVP ISLEDLKSFT NYSGGYSADH PVIKVFWRVV EGFTDEEKRK LLKFVTSCSR 1030 1040 1050 1060 1070 1080 PPLLGFKELY PAFCIHNGGS DLERLPTAST CMNLLKLPEF YDETLLRSKL LYAIECAAGF ELS
	Isoform 2 [UniParc]. Checksum: 10FD919A38C3D361	FASTA	649	74,796
	10 20 30 40 50 60 MFSFEGDFKT RPKVSLGGAS RKEEKASLLH RTQEERRKRE EERRRLKNAI IIQSFIRGYR 70 80 90 100 110 120 DRKQQYSIQR SAFDRCATLS QSGGAFPIAN GPNLTLLVRQ LLFFYKQNED SKRLIWLYQN 130 140 150 160 170 180 LIKHSSLFVK QLDGSERLTC LFQIKRLMSL CCRLLQNCND DSLNVALPMR MLEVFSSENT 190 200 210 220 230 240 YLPVLQDASY VVSVIEQILH YMIHNGYYRS LYLLINSKLP SSIEYSDLSR VPIAKILLEN 250 260 270 280 290 300 VLKPLHFTYN SCPEGARQQV FTAFTEEFLA APFTDQIFHF IIPALADAQT VFPYEPFLNA 310 320 330 340 350 360 LLLIESRCSR KSGGAPWLFY FVLTVGENYL GALSEEGLLV YLRVLQTFLS QLPVSPASAS 370 380 390 400 410 420 CHDSASDSEE ESEEADKPSS PEDGRLSVSY ITEECLKKLD TKQQTNTLLN LVWRDSASEE 430 440 450 460 470 480 VFTTMASVCH TLMVQHRMMV PKVRLLYSLA FNARFLRHLW FLISSMSTRM ITGSMVPLLQ 490 500 510 520 530 540 VISRGSPMSF EDSSRIIPLF YLFSSLFSHS LISIHDNEFF GDPIEVVGQR QSSMMPFTLE 550 560 570 580 590 600 ELIMLSRCLR DACLGIIKLA YPETKPEVRE EYITAFQSIG VTTSSEMQQC IQMEQKRWIQ 610 620 630 640 LFKVITNLVK MLKSRDTRRN FCPPNHWLSE QEDIKADKVL LKDLFNIYH
	Isoform 3 [UniParc]. Checksum: E1174F92839412C4	FASTA	404	45,845
	10 20 30 40 50 60 MFSFEGDFKT RPKVSLGGAS RKYSIQRSAF DRCATLSQSG GAFPIANGPN LTLLVRQLLF 70 80 90 100 110 120 FYKQNEDSKR LIWLYQNLIK HSSLFVKQLD GSERLTCLFQ IKRLMSLCCR LLQNCNDDSL 130 140 150 160 170 180 NVALPMRMLE VFSSENTYLP VLQDASYVVS VIEQILHYMI HNGYYRSLYL LINSKLPSSI 190 200 210 220 230 240 EYSDLSRVPI AKILLENVLK PLHFTYNSCP EGARQQVFTA FTEEFLAAPF TDQIFHFIIP 250 260 270 280 290 300 ALADAQTVFP YEPFLNALLL IESRCSRKSG GAPWLFYFVL TVGENYLGAL SEEGLLVYLR 310 320 330 340 350 360 VLQTFLSQLP VSPASASCHD SASDSEEESE EADKPSSPED GRLSVSYITE ECLKKLDTKQ 370 380 390 400 QTNTLLNLVW RDSASEEVFT TMASVCHTLM VQHRMMVPKV RVYK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1." Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S., Nagase T., Seki N., Ishikawa K., Tabata S. DNA Res. 1:27-35(1994) [PubMed: 7584026] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Bone marrow.
[2]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). Tissue: Lung and Placenta.
[6]	"A HECT domain E3 enzyme assembles novel polyubiquitin chains." You J., Pickart C.M. J. Biol. Chem. 276:19871-19878(2001) [PubMed: 11278995] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, FUNCTION, INTERACTION WITH UBE2D1, AUTOUBIQUITINATION, TISSUE SPECIFICITY.
[7]	"Proteolytic targeting of transcriptional regulator TIP120B by a HECT domain E3 ligase." You J., Wang M., Aoki T., Tamura T.-A., Pickart C.M. J. Biol. Chem. 278:23369-23375(2003) [PubMed: 12692129] [Abstract] Cited for: FUNCTION IN CAND2 UBIQUITINATION, INTERACTION WITH CAND2 AND 26S PROTEASOMES, MUTAGENESIS OF CYS-1051, TISSUE SPECIFICITY.
[8]	"Different HECT domain ubiquitin ligases employ distinct mechanisms of polyubiquitin chain synthesis." Wang M., Pickart C.M. EMBO J. 24:4324-4333(2005) [PubMed: 16341092] [Abstract] Cited for: FUNCTION.
[9]	"Molecular determinants of polyubiquitin linkage selection by an HECT ubiquitin ligase." Wang M., Cheng D., Peng J., Pickart C.M. EMBO J. 25:1710-1719(2006) [PubMed: 16601690] [Abstract] Cited for: FUNCTION, MASS SPECTROMETRY.
[10]	"Mass spectrometric characterization of the affinity-purified human 26S proteasome complex." Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L. Biochemistry 46:3553-3565(2007) [PubMed: 17323924] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], INTERACTION WITH PROTEASOME. Tissue: Embryonic kidney.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D13635 mRNA. Translation: BAA02799.2. Different initiation. AC004898 Genomic DNA. No translation available. AC004975 Genomic DNA. Translation: AAD51453.1. CH236954 Genomic DNA. Translation: EAL23922.1. CH471149 Genomic DNA. Translation: EAX04568.1. BC014029 mRNA. Translation: AAH14029.1. BC026241 mRNA. Translation: AAH26241.1.
IPI	IPI00411748. IPI00472810. IPI00604464.
PIR	A38919.
RefSeq	NP_055486.2. NM_014671.2.
UniGene	Hs.118351.
3D structure databases
ProteinModelPortal	Q15386.
SMR	Q15386. Positions 682-1077.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q15386. 3 interactions.
STRING	Q15386.
PTM databases
PhosphoSite	Q15386.
Polymorphism databases
DMDM	67462009.
Proteomic databases
PRIDE	Q15386.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000348165; ENSP00000309198; ENSG00000009335.
GeneID	9690.
KEGG	hsa:9690.
UCSC	uc003wnf.2. human. uc003wng.2. human. uc010lqs.1. human.
Organism-specific databases
CTD	9690.
GeneCards	GC07P156931.
H-InvDB	HIX0007256.
HGNC	HGNC:16803. UBE3C.
HPA	HPA039915.
neXtProt	NX_Q15386.
PharmGKB	PA134905339.
HUGE	Search... Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG08976.
GeneTree	ENSGT00550000074668.
HOGENOM	HBG314453.
HOVERGEN	HBG073375.
InParanoid	Q15386.
OMA	LYVPSAR.
OrthoDB	EOG48SGS8.
PhylomeDB	Q15386.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q15386.
Bgee	Q15386.
CleanEx	HS_UBE3C.
Genevestigator	Q15386.
GermOnline	ENSG00000009335. Homo sapiens.
Family and domain databases
InterPro	IPR000569. HECT. IPR000048. IQ_motif_EF-hand-BS. [Graphical view]
KO	K10589.
Pfam	PF00632. HECT. 1 hit. [Graphical view]
SMART	SM00119. HECTc. 1 hit. SM00015. IQ. 1 hit. [Graphical view]
SUPFAM	SSF56204. HECT. 1 hit.
PROSITE	PS50237. HECT. 1 hit. PS50096. IQ. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	36397.

Entry information

Entry name

UBE3C_HUMAN

Accession

Primary (citable) accession number: Q15386
Secondary accession number(s): A4D235 , A6NCP3, Q8TC15, Q96CR4, Q9UDU3

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2005
Last sequence update:	June 7, 2005
Last modified:	January 25, 2012
This is version 98 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.