InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: UBE2D3

Summary

InnateDB Protein

IDBP-51479.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

UBE2D3

Protein Name

ubiquitin-conjugating enzyme E2D 3

Synonyms

E2(17)KB3; UBC4/5; UBCH5C;

Species

Homo sapiens

Ensembl Protein

ENSP00000344069

InnateDB Gene

IDBG-32113 (UBE2D3)

Protein Structure

UniProt Annotation

Function

Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys- 11'-, as well as 'Lys-48'-linked polyubiquitination. Cooperates with the E2 CDC34 and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Ubiquitin chain elongation is then performed by CDC34, building ubiquitin chains from the UBE2D3-primed NFKBIA- linked ubiquitin. Acts also as an initiator E2, in conjunction with RNF8, for the priming of PCNA. 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. Associates with the BRCA1/BARD1 E3 ligase complex to perform ubiquitination at DNA damage sites following ionizing radiation leading to DNA repair. Targets DAPK3 for ubiquitination which influences promyelocytic leukemia protein nuclear body (PML- NB) formation in the nucleus. In conjunction with the MDM2 and TOPORS E3 ligases, functions ubiquitination of p53/TP53. Supports NRDP1-mediated ubiquitination and degradation of ERBB3 and of BRUCE which triggers apoptosis. 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. In conjunction with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded proteins to catalyze their immediate destruction (By similarity). {ECO:0000250}.

Subcellular Localization

Cell membrane {ECO:0000269PubMed:18508924}; Peripheral membrane protein {ECO:0000269PubMed:18508924}. Endosome membrane {ECO:0000269PubMed:18508924}; Peripheral membrane protein {ECO:0000269PubMed:18508924}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 248 experimentally validated interaction(s) in this database.

Experimentally validated
Total	248 [view]
Protein-Protein	244 [view]
Protein-DNA	4 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016881	acid-amino acid ligase activity

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0000209	protein polyubiquitination
GO:0002224	toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006281	DNA repair
GO:0006351	transcription, DNA-templated
GO:0006367	transcription initiation from RNA polymerase II promoter
GO:0006464	cellular protein modification process
GO:0006511	ubiquitin-dependent protein catabolic process
GO:0006513	protein monoubiquitination
GO:0006915	apoptotic process
GO:0007179	transforming growth factor beta receptor signaling pathway
GO:0008152	metabolic process
GO:0010467	gene expression
GO:0016567	protein ubiquitination
GO:0030509	BMP signaling pathway
GO:0032480	negative regulation of type I interferon production
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0045087	innate immune response
GO:0061418	regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0070936	protein K48-linked ubiquitination
GO:0070979	protein K11-linked ubiquitination
GO:0071456	cellular response to hypoxia