CPLM-009298

Genbank Nucleotide ID

Ubiquitin-conjugating enzyme E2 D3

Protein Synonyms/Alias

Ubiquitin carrier protein D3; Ubiquitin-conjugating enzyme E2(17)KB 3; Ubiquitin-conjugating enzyme E2-17 kDa 3; Ubiquitin-protein ligase D3

Homo sapiens (Human)

Position	Peptide	Type	References
8	MALKRINKELSDLAR	acetylation	[1]
8	MALKRINKELSDLAR	ubiquitination	[2, 3, 4, 5]
144	ISREWTQKYAM****	acetylation	[1]
144	ISREWTQKYAM****	ubiquitination	[4, 6]

[1] Proteome-wide mapping of the Drosophila acetylome demonstrates a high degree of conservation of lysine acetylation.
Weinert BT, Wagner SA, Horn H, Henriksen P, Liu WR, Olsen JV, Jensen LJ, Choudhary C.
Sci Signal. 2011 Jul 26;4(183):ra48. [PMID: 21791702]
[2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[3] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
[4] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
[5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[6] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]

Functional Description

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).

ACT_SITE 85 85 Glycyl thioester intermediate (By
DISULFID 21 107

3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cell membrane; Complete proteome; Disulfide bond; DNA damage; DNA repair; Endosome; Ligase; Membrane; Nucleotide-binding; Reference proteome; Ubl conjugation pathway.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; TAS:Reactome.
GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
GO:0005654; C:nucleoplasm; TAS:Reactome.
GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
GO:0030509; P:BMP signaling pathway; TAS:Reactome.
GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
GO:0045087; P:innate immune response; TAS:Reactome.
GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; TAS:Reactome.
GO:0032480; P:negative regulation of type I interferon production; TAS:Reactome.
GO:0043161; P:proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
GO:0070979; P:protein K11-linked ubiquitination; IDA:UniProtKB.
GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
GO:0061418; P:regulation of transcription from RNA polymerase II promoter in response to hypoxia; TAS:Reactome.
GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome.
GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome.
GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.

IPR000608; UBQ-conjugat_E2.
IPR023313; UBQ-conjugating_AS.
IPR016135; UBQ-conjugating_enzyme/RWD.

PS00183; UBIQUITIN_CONJUGAT_1
PS50127; UBIQUITIN_CONJUGAT_2