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Protein

Ubiquitin-conjugating enzyme E2 L3

Gene

UBE2L3

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

Functioni

Ubiquitin-conjugating enzyme E2 that specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases. Does not function with most RING-containing E3 ubiquitin-protein ligases because it lacks intrinsic E3-independent reactivity with lysine: in contrast, it has activity with the RBR family E3 enzymes, such as PRKN and ARIH1, that function like function like RING-HECT hybrids. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-linked polyubiquitination. Involved in the selective degradation of short-lived and abnormal proteins. Down-regulated during the S-phase it is involved in progression through the cell cycle. Regulates nuclear hormone receptors transcriptional activity. May play a role in myelopoiesis.7 Publications

Caution

PubMed:10760570 reported that UBE2L1, UBE2L2 and UBE2L4 are most likely pseudogenes and the only expressed member of this subfamily seems to be UBE2L3.Curated

Catalytic activityi

S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine.PROSITE-ProRule annotation1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.PROSITE-ProRule annotation
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 sitei86Glycyl thioester intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • enzyme binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • transcription coactivator activity Source: UniProtKB
  • ubiquitin conjugating enzyme activity Source: MGI
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-protein transferase activator activity Source: ParkinsonsUK-UCL
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  • cell cycle phase transition Source: UniProtKB
  • cell proliferation Source: UniProtKB
  • cellular protein modification process Source: UniProtKB
  • cellular response to glucocorticoid stimulus Source: UniProtKB
  • cellular response to steroid hormone stimulus Source: UniProtKB
  • positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
  • positive regulation of protein ubiquitination Source: ParkinsonsUK-UCL
  • positive regulation of ubiquitin-protein transferase activity Source: ParkinsonsUK-UCL
  • protein K11-linked ubiquitination Source: UniProtKB
  • protein polyubiquitination Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • ubiquitin-dependent protein catabolic process Source: UniProtKB

Keywordsi

Molecular functionTransferase
Biological processTranscription, Transcription regulation, Ubl conjugation pathway
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.3.2.B6 2681
ReactomeiR-HSA-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiP68036
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin-conjugating enzyme E2 L3 (EC:2.3.2.231 Publication)
Alternative name(s):
E2 ubiquitin-conjugating enzyme L3
L-UBC
UbcH7
Ubiquitin carrier protein L3
Ubiquitin-conjugating enzyme E2-F1
Ubiquitin-protein ligase L3
Gene namesi
Name:UBE2L3
Synonyms:UBCE7, UBCH7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000185651.14
HGNCiHGNC:12488 UBE2L3
MIMi603721 gene
neXtProtiNX_P68036

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

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi9K → E: Marked decrease in autoubiquitination. 1 Publication1
Mutagenesisi63F → A: Decrease in autoubiquitination. 1 Publication1
Mutagenesisi86C → S: Loss of catalytic activity. Prevents ubiquitin-dependent proteasomal degradation of UBE2L3. 2 Publications1
Mutagenesisi88P → D: Does not convert into a lysine reactive E2; when associated with D-119. 1 Publication1
Mutagenesisi93E → R: Decrease in autoubiquitination. 1 Publication1
Mutagenesisi96K → E: Decrease in autoubiquitination. 1 Publication1
Mutagenesisi100K → E: Decrease in autoubiquitination. 1 Publication1
Mutagenesisi119H → D: Does not convert into a lysine reactive E2; when associated with D-88. 1 Publication1

Organism-specific databases

DisGeNETi7332
OpenTargetsiENSG00000185651
Orphaneti536 Systemic lupus erythematosus
PharmGKBiPA37137

Polymorphism and mutation databases

BioMutaiUBE2L3
DMDMi54039805

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000824761 – 154Ubiquitin-conjugating enzyme E2 L3Add BLAST154

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei131N6-acetyllysineCombined sources1

Post-translational modificationi

Ubiquitinated. The alteration of UBE2L3 protein levels during the S-phase of the cell cycle is due to ubiquitin-dependent proteasomal degradation. Autoubiquitinated in vitro (PubMed:22496338).2 Publications

Keywords - PTMi

Acetylation, Ubl conjugation

Proteomic databases

EPDiP68036
MaxQBiP68036
PaxDbiP68036
PeptideAtlasiP68036
PRIDEiP68036
TopDownProteomicsiP68036-1 [P68036-1]
P68036-2 [P68036-2]

2D gel databases

OGPiP51966
UCD-2DPAGEiP68036

PTM databases

iPTMnetiP68036
PhosphoSitePlusiP68036
SwissPalmiP68036

Expressioni

Tissue specificityi

Ubiquitous, with highest expression in testis.

Gene expression databases

BgeeiENSG00000185651
CleanExiHS_UBE2L3
ExpressionAtlasiP68036 baseline and differential
GenevisibleiP68036 HS

Organism-specific databases

HPAiHPA045609
HPA062415

Interactioni

Subunit structurei

Interacts with PRKN; involved in ubiquitination and degradation of misfolded proteins. Interacts with UBE3A; used by the papilloma virus HPV-16 E6 protein to ubiquitinate p53/TP53. Interacts with CCNB1IP1, CBL, ZAP70, RNF19A, RNF19B and RNF144B. Interacts with ARIH1. Interacts with ARIH2 (via RING-type 1). Interacts with NCOA1; they functionally interact to regulate progesterone receptor transcriptional activity. May interact with NR3C1. Interacts with NDFIP1 (via N-terminus); the interaction mediates recruitment of UBE2L3 to ITCH and causes MAP3K7 ubiquitination (PubMed:25632008).13 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113180, 142 interactors
CORUMiP68036
DIPiDIP-6124N
IntActiP68036, 39 interactors
MINTiP68036
STRINGi9606.ENSP00000344259

Structurei

Secondary structure

1154
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi1 – 17Combined sources17
Beta strandi20 – 27Combined sources8
Turni29 – 31Combined sources3
Beta strandi34 – 39Combined sources6
Turni44 – 48Combined sources5
Beta strandi49 – 56Combined sources8
Turni59 – 62Combined sources4
Beta strandi67 – 72Combined sources6
Beta strandi77 – 79Combined sources3
Beta strandi83 – 85Combined sources3
Helixi88 – 90Combined sources3
Turni92 – 94Combined sources3
Helixi101 – 113Combined sources13
Beta strandi117 – 119Combined sources3
Helixi123 – 131Combined sources9
Helixi133 – 147Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1C4ZX-ray2.60D1-154[»]
1FBVX-ray2.90C1-154[»]
3SQVX-ray3.30C/D1-154[»]
3SY2X-ray3.27C/D1-154[»]
4Q5EX-ray1.87C1-154[»]
4Q5HX-ray2.00C1-154[»]
5HPTX-ray2.84C/F2-154[»]
5TTEX-ray3.50E1-154[»]
5UDHX-ray3.24C/D1-154[»]
ProteinModelPortaliP68036
SMRiP68036
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP68036

Family & Domainsi

Domaini

In contrast to other ubiquitin-conjugating enzymes E2, residues essential for lysine reactivity are absent: Pro and a His residues are present instead of an Asp and an Asp residues in positions 88 and 119, respectively.1 Publication

Sequence similaritiesi

Belongs to the ubiquitin-conjugating enzyme family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0422 Eukaryota
COG5078 LUCA
GeneTreeiENSGT00910000143990
HOGENOMiHOG000233455
HOVERGENiHBG063308
InParanoidiP68036
KOiK04552
OrthoDBiEOG091G0QDO
PhylomeDBiP68036
TreeFamiTF313043

Family and domain databases

CDDicd00195 UBCc, 1 hit
Gene3Di3.10.110.10, 1 hit
InterProiView protein in InterPro
IPR000608 UBQ-conjugat_E2
IPR023313 UBQ-conjugating_AS
IPR016135 UBQ-conjugating_enzyme/RWD
PfamiView protein in Pfam
PF00179 UQ_con, 1 hit
SUPFAMiSSF54495 SSF54495, 1 hit
PROSITEiView protein in PROSITE
PS00183 UBIQUITIN_CONJUGAT_1, 1 hit
PS50127 UBIQUITIN_CONJUGAT_2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: P68036-1) [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
MAASRRLMKE LEEIRKCGMK NFRNIQVDEA NLLTWQGLIV PDNPPYDKGA
60 70 80 90 100
FRIEINFPAE YPFKPPKITF KTKIYHPNID EKGQVCLPVI SAENWKPATK
110 120 130 140 150
TDQVIQSLIA LVNDPQPEHP LRADLAEEYS KDRKKFCKNA EEFTKKYGEK

RPVD
Length:154
Mass (Da):17,862
Last modified:October 11, 2004 - v1
Checksum:iF5A30243BE3C9985
GO
Isoform 2 (identifier: P68036-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     10-41: Missing.

Show »
Length:122
Mass (Da):14,121
Checksum:iB6D14D8ABF26E365
GO
Isoform 3 (identifier: P68036-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: MAASRRLMK → MQVAAGTRGD...AGYRRAHGPE

Note: No experimental confirmation available.
Show »
Length:212
Mass (Da):24,004
Checksum:iFBA57DE90E19DA78
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti15R → S in BAG61806 (PubMed:14702039).Curated1
Sequence conflicti23R → C in AAG17922 (Ref. 4) Curated1
Sequence conflicti118E → K in AAG17922 (Ref. 4) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0473421 – 9MAASRRLMK → MQVAAGTRGDTRLQEVALLP QLFDLLVLGQRRARLLRQVP SALAGKDLAQLQAGATLAGY RRAHGPE in isoform 3. 1 Publication9
Alternative sequenceiVSP_04515210 – 41Missing in isoform 2. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S81003 mRNA Translation: AAB36017.1
X92962 mRNA Translation: CAA63538.1
AJ000519 mRNA Translation: CAA04156.1
AF300336 Genomic DNA Translation: AAG17922.1
CR456606 mRNA Translation: CAG30492.1
AK293179 mRNA Translation: BAG56722.1
AK299985 mRNA Translation: BAG61806.1
AK311761 mRNA Translation: BAG34704.1
AP000553 Genomic DNA No translation available.
AP000557 Genomic DNA No translation available.
AP000558 Genomic DNA No translation available.
CH471095 Genomic DNA Translation: EAW59459.1
BC053368 mRNA Translation: AAH53368.1
CCDSiCCDS13790.1 [P68036-1]
CCDS58795.1 [P68036-3]
CCDS58796.1 [P68036-2]
RefSeqiNP_001243284.1, NM_001256355.1 [P68036-3]
NP_001243285.1, NM_001256356.1 [P68036-2]
NP_003338.1, NM_003347.3 [P68036-1]
UniGeneiHs.108104

Genome annotation databases

EnsembliENST00000342192; ENSP00000344259; ENSG00000185651 [P68036-1]
ENST00000458578; ENSP00000400906; ENSG00000185651 [P68036-3]
ENST00000545681; ENSP00000445931; ENSG00000185651 [P68036-2]
GeneIDi7332
KEGGihsa:7332
UCSCiuc002zva.2 human [P68036-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiUB2L3_HUMAN
AccessioniPrimary (citable) accession number: P68036
Secondary accession number(s): B2R4A7
, B4DDG1, B4DSZ4, E7EWS7, P51966, P70653, Q9HAV1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: April 25, 2018
This is version 149 of the entry and version 1 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health