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Protein

Ubiquitin-protein ligase E3C

Gene

UBE3C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.4 Publications

Miscellaneous

A cysteine residue is required for ubiquitin-thioester formation.

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei1051Glycyl thioester intermediate1

GO - Molecular functioni

  • ubiquitin protein ligase activity Source: GO_Central
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  • protein polyubiquitination Source: UniProtKB

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin-protein ligase E3C (EC:2.3.2.26)
Alternative name(s):
HECT-type ubiquitin transferase E3C
HectH2
Gene namesi
Name:UBE3C
Synonyms:KIAA0010, KIAA10
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000009335.17
HGNCiHGNC:16803 UBE3C
MIMi614454 gene
neXtProtiNX_Q15386

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus, Proteasome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1051C → A: No stimulation of in vitro CAND2 ubiquitination. 1 Publication1

Organism-specific databases

DisGeNETi9690
OpenTargetsiENSG00000009335
PharmGKBiPA134905339

Polymorphism and mutation databases

BioMutaiUBE3C
DMDMi67462009

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001949821 – 1083Ubiquitin-protein ligase E3CAdd BLAST1083

Proteomic databases

EPDiQ15386
MaxQBiQ15386
PaxDbiQ15386
PeptideAtlasiQ15386
PRIDEiQ15386
ProteomicsDBi60555
60556 [Q15386-2]
60557 [Q15386-3]

PTM databases

iPTMnetiQ15386
PhosphoSitePlusiQ15386

Expressioni

Tissue specificityi

Highly expressed in skeletal muscle. Detected at much lower levels in kidney and pancreas.3 Publications

Gene expression databases

BgeeiENSG00000009335
CleanExiHS_UBE3C
ExpressionAtlasiQ15386 baseline and differential
GenevisibleiQ15386 HS

Organism-specific databases

HPAiHPA039915

Interactioni

Subunit structurei

Interacts with 26S proteasomes. Interacts (via the N-terminal) with CAND2; the interaction stimulates ubiquitination of CAND2 in vitro. May interact (via the HECT domain) with UBE2D1 and, less efficiently, with UBE2L3.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GOLGA2Q083793EBI-1058871,EBI-618309

Protein-protein interaction databases

BioGridi115043, 56 interactors
IntActiQ15386, 12 interactors
MINTiQ15386
STRINGi9606.ENSP00000309198

Structurei

3D structure databases

ProteinModelPortaliQ15386
SMRiQ15386
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini45 – 74IQPROSITE-ProRule annotationAdd BLAST30
Domaini744 – 1083HECTPROSITE-ProRule annotationAdd BLAST340

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 60Cis-determinant of acceptor ubiquitin-bindingAdd BLAST60

Domaini

The C-terminal is necessary and sufficient for the poly-ubiquitin chain assembly.

Phylogenomic databases

eggNOGiKOG0942 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00550000074668
HOGENOMiHOG000030618
HOVERGENiHBG073375
InParanoidiQ15386
KOiK10589
OMAiGGYSADH
OrthoDBiEOG091G029A
PhylomeDBiQ15386
TreeFamiTF106144

Family and domain databases

CDDicd00078 HECTc, 1 hit
InterProiView protein in InterPro
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR000048 IQ_motif_EF-hand-BS
PfamiView protein in Pfam
PF00632 HECT, 1 hit
SMARTiView protein in SMART
SM00119 HECTc, 1 hit
SM00015 IQ, 1 hit
SUPFAMiSSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50237 HECT, 1 hit
PS50096 IQ, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q15386-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MFSFEGDFKT RPKVSLGGAS RKEEKASLLH RTQEERRKRE EERRRLKNAI
60 70 80 90 100
IIQSFIRGYR DRKQQYSIQR SAFDRCATLS QSGGAFPIAN GPNLTLLVRQ
110 120 130 140 150
LLFFYKQNED SKRLIWLYQN LIKHSSLFVK QLDGSERLTC LFQIKRLMSL
160 170 180 190 200
CCRLLQNCND DSLNVALPMR MLEVFSSENT YLPVLQDASY VVSVIEQILH
210 220 230 240 250
YMIHNGYYRS LYLLINSKLP SSIEYSDLSR VPIAKILLEN VLKPLHFTYN
260 270 280 290 300
SCPEGARQQV FTAFTEEFLA APFTDQIFHF IIPALADAQT VFPYEPFLNA
310 320 330 340 350
LLLIESRCSR KSGGAPWLFY FVLTVGENYL GALSEEGLLV YLRVLQTFLS
360 370 380 390 400
QLPVSPASAS CHDSASDSEE ESEEADKPSS PEDGRLSVSY ITEECLKKLD
410 420 430 440 450
TKQQTNTLLN LVWRDSASEE VFTTMASVCH TLMVQHRMMV PKVRLLYSLA
460 470 480 490 500
FNARFLRHLW FLISSMSTRM ITGSMVPLLQ VISRGSPMSF EDSSRIIPLF
510 520 530 540 550
YLFSSLFSHS LISIHDNEFF GDPIEVVGQR QSSMMPFTLE ELIMLSRCLR
560 570 580 590 600
DACLGIIKLA YPETKPEVRE EYITAFQSIG VTTSSEMQQC IQMEQKRWIQ
610 620 630 640 650
LFKVITNLVK MLKSRDTRRN FCPPNHWLSE QEDIKADKVT QLYVPASRHV
660 670 680 690 700
WRFRRMGRIG PLQSTLDVGL ESPPLSVSEE RQLAVLTELP FVVPFEERVK
710 720 730 740 750
IFQRLIYADK QEVQGDGPFL DGINVTIRRN YIYEDAYDKL SPENEPDLKK
760 770 780 790 800
RIRVHLLNAH GLDEAGIDGG GIFREFLNEL LKSGFNPNQG FFKTTNEGLL
810 820 830 840 850
YPNPAAQMLV GDSFARHYYF LGRMLGKALY ENMLVELPFA GFFLSKLLGT
860 870 880 890 900
SADVDIHHLA SLDPEVYKNL LFLKSYEDDV EELGLNFTVV NNDLGEAQVV
910 920 930 940 950
ELKFGGKDIP VTSANRIAYI HLVADYRLNR QIRQHCLAFR QGLANVVSLE
960 970 980 990 1000
WLRMFDQQEI QVLISGAQVP ISLEDLKSFT NYSGGYSADH PVIKVFWRVV
1010 1020 1030 1040 1050
EGFTDEEKRK LLKFVTSCSR PPLLGFKELY PAFCIHNGGS DLERLPTAST
1060 1070 1080
CMNLLKLPEF YDETLLRSKL LYAIECAAGF ELS
Length:1,083
Mass (Da):123,923
Last modified:June 7, 2005 - v3
Checksum:iBD437ABA457A0DDA
GO
Isoform 2 (identifier: Q15386-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:649
Mass (Da):74,796
Checksum:i10FD919A38C3D361
GO
Isoform 3 (identifier: Q15386-3) [UniParc]FASTAAdd to basket

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.
Show »
Length:404
Mass (Da):45,845
Checksum:iE1174F92839412C4
GO

Sequence cautioni

The sequence BAA02799 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti822G → A in BAA02799 (PubMed:7584026).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01395323 – 65Missing in isoform 3. 1 PublicationAdd BLAST43
Alternative sequenceiVSP_013954445 – 447LLY → VYK in isoform 3. 1 Publication3
Alternative sequenceiVSP_013955448 – 1083Missing in isoform 3. 1 PublicationAdd BLAST636
Alternative sequenceiVSP_013956640 – 649TQLYVPASRH → LLKDLFNIYH in isoform 2. 1 Publication10
Alternative sequenceiVSP_013957650 – 1083Missing in isoform 2. 1 PublicationAdd BLAST434

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS34789.1 [Q15386-1]
PIRiA38919
RefSeqiNP_055486.2, NM_014671.2 [Q15386-1]
UniGeneiHs.118351

Genome annotation databases

EnsembliENST00000348165; ENSP00000309198; ENSG00000009335 [Q15386-1]
ENST00000389103; ENSP00000373755; ENSG00000009335 [Q15386-3]
ENST00000611269; ENSP00000481584; ENSG00000009335 [Q15386-3]
GeneIDi9690
KEGGihsa:9690
UCSCiuc003wnf.3 human [Q15386-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiUBE3C_HUMAN
AccessioniPrimary (citable) accession number: Q15386
Secondary accession number(s): A4D235
, A6NCP3, Q8TC15, Q96CR4, Q9UDU3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: June 7, 2005
Last modified: June 20, 2018
This is version 156 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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