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Protein

Ubiquitin-conjugating enzyme E2 L3

Gene

UBE2L3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 PARK2 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

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
  • poly(A) 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
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: Ensembl
  • regulation of transcription, DNA-templated Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • ubiquitin-dependent protein catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Transcription, Transcription regulation, Ubl conjugation pathway

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS05588-MONOMER.
BRENDAi2.3.2.B6. 2681.
ReactomeiR-HSA-8866652. Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
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

HGNCiHGNC:12488. UBE2L3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • nucleus Source: UniProtKB
  • ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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
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 residuei9N6-acetyllysineCombined sources1
Modified residuei131N6-acetyllysineCombined sources1
Modified residuei138N6-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.1 Publication

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-2DPAGEP68036.

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 PARK2; 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 NR3C1.12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARIH1Q9Y4X55EBI-711173,EBI-2514233
ARIH2O9537612EBI-711173,EBI-711158
MID1O153443EBI-711173,EBI-2340316
ospGQ99PZ63EBI-711173,EBI-9316527From a different organism.
RBCK1Q9BYM83EBI-711173,EBI-2340624
RNF19BQ6ZMZ02EBI-711173,EBI-2466594

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi113180. 136 interactors.
DIPiDIP-6124N.
IntActiP68036. 29 interactors.
MINTiMINT-5002693.
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[»]
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.
GeneTreeiENSGT00760000119012.
HOGENOMiHOG000233455.
HOVERGENiHBG063308.
InParanoidiP68036.
KOiK04552.
OMAiADGQIAC.
OrthoDBiEOG091G0QDO.
PhylomeDBiP68036.
TreeFamiTF313043.

Family and domain databases

Gene3Di3.10.110.10. 1 hit.
InterProiIPR000608. UBQ-conjugat_E2.
IPR023313. UBQ-conjugating_AS.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]
PfamiPF00179. UQ_con. 1 hit.
[Graphical view]
SUPFAMiSSF54495. SSF54495. 1 hit.
PROSITEiPS00183. UBIQUITIN_CONJUGAT_1. 1 hit.
PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
[Graphical view]

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

Cross-referencesi

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.

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[»]
ProteinModelPortaliP68036.
SMRiP68036.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113180. 136 interactors.
DIPiDIP-6124N.
IntActiP68036. 29 interactors.
MINTiMINT-5002693.
STRINGi9606.ENSP00000344259.

PTM databases

iPTMnetiP68036.
PhosphoSitePlusiP68036.
SwissPalmiP68036.

Polymorphism and mutation databases

BioMutaiUBE2L3.
DMDMi54039805.

2D gel databases

OGPiP51966.
UCD-2DPAGEP68036.

Proteomic databases

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

Protocols and materials databases

DNASUi7332.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi7332.
DisGeNETi7332.
GeneCardsiUBE2L3.
HGNCiHGNC:12488. UBE2L3.
HPAiHPA045609.
HPA062415.
MIMi603721. gene.
neXtProtiNX_P68036.
OpenTargetsiENSG00000185651.
Orphaneti536. Systemic lupus erythematosus.
PharmGKBiPA37137.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0422. Eukaryota.
COG5078. LUCA.
GeneTreeiENSGT00760000119012.
HOGENOMiHOG000233455.
HOVERGENiHBG063308.
InParanoidiP68036.
KOiK04552.
OMAiADGQIAC.
OrthoDBiEOG091G0QDO.
PhylomeDBiP68036.
TreeFamiTF313043.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:HS05588-MONOMER.
BRENDAi2.3.2.B6. 2681.
ReactomeiR-HSA-8866652. Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiP68036.

Miscellaneous databases

ChiTaRSiUBE2L3. human.
EvolutionaryTraceiP68036.
GeneWikiiUBE2L3.
GenomeRNAii7332.
PROiP68036.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185651.
CleanExiHS_UBE2L3.
ExpressionAtlasiP68036. baseline and differential.
GenevisibleiP68036. HS.

Family and domain databases

Gene3Di3.10.110.10. 1 hit.
InterProiIPR000608. UBQ-conjugat_E2.
IPR023313. UBQ-conjugating_AS.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]
PfamiPF00179. UQ_con. 1 hit.
[Graphical view]
SUPFAMiSSF54495. SSF54495. 1 hit.
PROSITEiPS00183. UBIQUITIN_CONJUGAT_1. 1 hit.
PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUB2L3_HUMAN
AccessioniPrimary (citable) accession number: P68036
Secondary accession number(s): B2R4A7
, B4DDG1, B4DSZ4, E7EWS7, P51966, P70653, Q9HAV1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: November 30, 2016
This is version 137 of the entry and version 1 of the sequence. [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

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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.