P61077 · UB2D3_HUMAN
- ProteinUbiquitin-conjugating enzyme E2 D3
- GeneUBE2D3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids147 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins (PubMed:15247280, PubMed:15496420, PubMed:18284575, PubMed:20061386, PubMed:21532592, PubMed:28322253).
In vitro catalyzes 'Lys-11'-, as well as 'Lys-48'-linked polyubiquitination (PubMed:15247280, PubMed:15496420, PubMed:18284575, PubMed:20061386, PubMed:21532592).
Cooperates with the E2 CDC34 and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation (PubMed:20347421).
Acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin (PubMed:10329681).
Ubiquitin chain elongation is then performed by CDC34, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin (PubMed:10329681).
Acts also as an initiator E2, in conjunction with RNF8, for the priming of PCNA (PubMed:18948756).
Monoubiquitination of PCNA, and its subsequent polyubiquitination, are essential events in the operation of the DNA damage tolerance (DDT) pathway that is activated after DNA damage caused by UV or chemical agents during S-phase (PubMed:18948756).
Associates with the BRCA1/BARD1 E3 ligase complex to perform ubiquitination at DNA damage sites following ionizing radiation leading to DNA repair (PubMed:16628214).
Targets DAPK3 for ubiquitination which influences promyelocytic leukemia protein nuclear body (PML-NB) formation in the nucleus (PubMed:18515077).
In conjunction with the MDM2 and TOPORS E3 ligases, functions ubiquitination of p53/TP53 (PubMed:12646252, PubMed:15280377).
In conjunction with the CBL E3 ligase, targets EGFR for polyubiquitination at the plasma membrane as well as during its internalization and transport on endosomes (PubMed:18508924).
In conjunction with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded proteins to catalyze their immediate destruction (PubMed:11743028).
Together with RNF135, catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIGI to activate the downstream signaling pathway that leads to interferon beta production (PubMed:28469175).
Together with ZNF598, catalyzes ubiquitination of 40S ribosomal proteins in response to ribosome collisions (PubMed:28685749).
In cooperation with the GATOR2 complex, catalyzes 'Lys-6'-linked ubiquitination of NPRL2 (PubMed:36528027).
In vitro catalyzes 'Lys-11'-, as well as 'Lys-48'-linked polyubiquitination (PubMed:15247280, PubMed:15496420, PubMed:18284575, PubMed:20061386, PubMed:21532592).
Cooperates with the E2 CDC34 and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation (PubMed:20347421).
Acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin (PubMed:10329681).
Ubiquitin chain elongation is then performed by CDC34, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin (PubMed:10329681).
Acts also as an initiator E2, in conjunction with RNF8, for the priming of PCNA (PubMed:18948756).
Monoubiquitination of PCNA, and its subsequent polyubiquitination, are essential events in the operation of the DNA damage tolerance (DDT) pathway that is activated after DNA damage caused by UV or chemical agents during S-phase (PubMed:18948756).
Associates with the BRCA1/BARD1 E3 ligase complex to perform ubiquitination at DNA damage sites following ionizing radiation leading to DNA repair (PubMed:16628214).
Targets DAPK3 for ubiquitination which influences promyelocytic leukemia protein nuclear body (PML-NB) formation in the nucleus (PubMed:18515077).
In conjunction with the MDM2 and TOPORS E3 ligases, functions ubiquitination of p53/TP53 (PubMed:12646252, PubMed:15280377).
In conjunction with the CBL E3 ligase, targets EGFR for polyubiquitination at the plasma membrane as well as during its internalization and transport on endosomes (PubMed:18508924).
In conjunction with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded proteins to catalyze their immediate destruction (PubMed:11743028).
Together with RNF135, catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIGI to activate the downstream signaling pathway that leads to interferon beta production (PubMed:28469175).
Together with ZNF598, catalyzes ubiquitination of 40S ribosomal proteins in response to ribosome collisions (PubMed:28685749).
In cooperation with the GATOR2 complex, catalyzes 'Lys-6'-linked ubiquitination of NPRL2 (PubMed:36528027).
Catalytic activity
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 85 | Glycyl thioester intermediate | ||||
Sequence: C |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameUbiquitin-conjugating enzyme E2 D3
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP61077
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Peripheral membrane protein
Endosome membrane ; Peripheral membrane protein
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 77 | Activity is restricted HECT-type and not RING-containing E3 ubiquitin-protein ligases. Exhibits ubiquitin transfer with ARIH1 and PRKN. | ||||
Sequence: N → S | ||||||
Mutagenesis | 85 | Loss of function. | ||||
Sequence: C → A | ||||||
Mutagenesis | 87 | Has intermediate lysine reactivity. | ||||
Sequence: D → E or P | ||||||
Mutagenesis | 87 | Abolishes affect lysine reactivity. | ||||
Sequence: D → K | ||||||
Mutagenesis | 87 | Does not affect lysine reactivity. | ||||
Sequence: D → N | ||||||
Mutagenesis | 117 | Strongly impairs lysine reactivity but retains some ability to transfer ubiquitin to BRCA1. | ||||
Sequence: D → H |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 81 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, disulfide bond, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000082466 | 1-147 | UniProt | Ubiquitin-conjugating enzyme E2 D3 | |||
Sequence: MALKRINKELSDLARDPPAQCSAGPVGDDMFHWQATIMGPNDSPYQGGVFFLTIHFPTDYPFKPPKVAFTTRIYHPNINSNGSICLDILRSQWSPALTISKVLLSICSLLCDPNPDDPLVPEIARIYKTDRDKYNRISREWTQKYAM | |||||||
Disulfide bond | 21↔107 | UniProt | |||||
Sequence: CSAGPVGDDMFHWQATIMGPNDSPYQGGVFFLTIHFPTDYPFKPPKVAFTTRIYHPNINSNGSICLDILRSQWSPALTISKVLLSIC | |||||||
Modified residue (large scale data) | 83 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated by AURKB.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Interacts with SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex; when Cullin is neddylated, the interaction between the E2 and the SCF complex is strengthened. Interacts with DAPK3. Interacts with BRCA1; the DNA damage checkpoint promotes the association with BRCA1 after ionizing radiation. Interacts non-covalently with ubiquitin. Interacts with E3 ubiquitin-protein ligase CBLC. Interacts with UBTD1 (PubMed:24211586).
Interacts with RIGI and RNF135; involved in RIGI ubiquitination and activation (PubMed:28469175).
Interacts with RIGI and RNF135; involved in RIGI ubiquitination and activation (PubMed:28469175).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 1-147 | UBC core | ||||
Sequence: MALKRINKELSDLARDPPAQCSAGPVGDDMFHWQATIMGPNDSPYQGGVFFLTIHFPTDYPFKPPKVAFTTRIYHPNINSNGSICLDILRSQWSPALTISKVLLSICSLLCDPNPDDPLVPEIARIYKTDRDKYNRISREWTQKYAM |
Sequence similarities
Belongs to the ubiquitin-conjugating enzyme family.
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
P61077-1
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.
- Name1
- Length147
- Mass (Da)16,687
- Last updated2004-04-26 v1
- ChecksumADD74A8A708EFEE3
P61077-2
- Name2
- Differences from canonical
- 134-147: YNRISREWTQKYAM → YNRLAREWTEKYAML
P61077-3
- Name3
- Differences from canonical
- 1-8: MALKRINK → MLSNRKCLSK
Computationally mapped potential isoform sequences
There are 11 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
D6RIZ3 | D6RIZ3_HUMAN | UBE2D3 | 78 | ||
D6RJB3 | D6RJB3_HUMAN | UBE2D3 | 19 | ||
D6RGD0 | D6RGD0_HUMAN | UBE2D3 | 49 | ||
D6RAW0 | D6RAW0_HUMAN | UBE2D3 | 72 | ||
D6RAH7 | D6RAH7_HUMAN | UBE2D3 | 118 | ||
D6RA11 | D6RA11_HUMAN | UBE2D3 | 96 | ||
D6R9F6 | D6R9F6_HUMAN | UBE2D3 | 35 | ||
D6R933 | D6R933_HUMAN | UBE2D3 | 48 | ||
D6R980 | D6R980_HUMAN | UBE2D3 | 55 | ||
A0A087WY85 | A0A087WY85_HUMAN | UBE2D3 | 148 | ||
H9KV45 | H9KV45_HUMAN | UBE2D3 | 141 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_038096 | 1-8 | in isoform 3 | |||
Sequence: MALKRINK → MLSNRKCLSK | ||||||
Sequence conflict | 50 | in Ref. 3; DB045280 | ||||
Sequence: Missing | ||||||
Sequence conflict | 123 | in Ref. 7; AAH66917 | ||||
Sequence: I → L | ||||||
Alternative sequence | VSP_038097 | 134-147 | in isoform 2 | |||
Sequence: YNRISREWTQKYAM → YNRLAREWTEKYAML | ||||||
Sequence conflict | 137 | in Ref. 3; CAG33197 | ||||
Sequence: I → V | ||||||
Sequence conflict | 147 | in Ref. 3; CAG33197 | ||||
Sequence: M → I |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U39318 EMBL· GenBank· DDBJ | AAA91461.1 EMBL· GenBank· DDBJ | mRNA | ||
AF213884 EMBL· GenBank· DDBJ | AAF35234.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AK095822 EMBL· GenBank· DDBJ | BAC04632.1 EMBL· GenBank· DDBJ | mRNA | ||
DB045280 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
CR456916 EMBL· GenBank· DDBJ | CAG33197.1 EMBL· GenBank· DDBJ | mRNA | ||
AC018797 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471057 EMBL· GenBank· DDBJ | EAX06138.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471057 EMBL· GenBank· DDBJ | EAX06143.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC003395 EMBL· GenBank· DDBJ | AAH03395.1 EMBL· GenBank· DDBJ | mRNA | ||
BC037894 EMBL· GenBank· DDBJ | AAH37894.1 EMBL· GenBank· DDBJ | mRNA | ||
BC066917 EMBL· GenBank· DDBJ | AAH66917.1 EMBL· GenBank· DDBJ | mRNA |