CPLM-009307

Genbank Nucleotide ID

Ubiquitin-conjugating enzyme E2 N

Protein Synonyms/Alias

Bendless-like ubiquitin-conjugating enzyme; Ubc13; UbcH13; Ubiquitin carrier protein N; Ubiquitin-protein ligase N

Homo sapiens (Human)

Position	Peptide	Type	References
10	GLPRRIIKETQRLLA	acetylation	[1, 2]
10	GLPRRIIKETQRLLA	ubiquitination	[3]
24	AEPVPGIKAEPDESN	ubiquitination	[3, 4, 5, 6, 7, 8, 9]
68	EYPMAAPKVRFMTKI	ubiquitination	[3, 5, 6, 7, 8]
74	PKVRFMTKIYHPNVD	ubiquitination	[3, 5, 7, 9]
82	IYHPNVDKLGRICLD	acetylation	[1, 2]
82	IYHPNVDKLGRICLD	ubiquitination	[3, 5, 6, 7, 8, 9, 10, 11]
92	RICLDILKDKWSPAL	acetylation	[1, 2]
92	RICLDILKDKWSPAL	ubiquitination	[3, 4, 5, 6, 7, 8, 9, 10, 11, 12]
94	CLDILKDKWSPALQI	acetylation	[1, 2]
94	CLDILKDKWSPALQI	ubiquitination	[3, 5, 6, 7, 8, 9, 11]

[1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
[2] 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]
[3] 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]
[4] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
[5] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[6] 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]
[7] 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]
[8] 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]
[9] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
[10] 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]
[11] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[12] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
Xu G, Paige JS, Jaffrey SR.
Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]

Functional Description

The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes (By similarity).

ACT_SITE 87 87 Glycyl thioester intermediate.
MOD_RES 82 82 N6-acetyllysine.
CROSSLNK 92 92 Glycyl lysine isopeptide (Lys-Gly)

3D-structure; Acetylation; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; DNA damage; DNA repair; Isopeptide bond; Ligase; Nucleotide-binding; Nucleus; Reference proteome; Ubl conjugation; Ubl conjugation pathway.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; TAS:Reactome.
GO:0005634; C:nucleus; IDA:UniProtKB.
GO:0031372; C:UBC13-MMS2 complex; IDA:HGNC.
GO:0035370; C:UBC13-UEV1A complex; IDA:UniProtKB.
GO:0000151; C:ubiquitin ligase complex; IDA:UniProtKB.
GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO:0043130; F:ubiquitin binding; IDA:HGNC.
GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
GO:0000729; P:DNA double-strand break processing; IMP:HGNC.
GO:0000724; P:double-strand break repair via homologous recombination; IMP:HGNC.
GO:0016574; P:histone ubiquitination; IMP:HGNC.
GO:0045087; P:innate immune response; TAS:Reactome.
GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
GO:0070423; P:nucleotide-binding oligomerization domain containing signaling pathway; TAS:Reactome.
GO:0045739; P:positive regulation of DNA repair; IMP:HGNC.
GO:0031058; P:positive regulation of histone modification; IMP:HGNC.
GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IMP:HGNC.
GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
GO:0051443; P:positive regulation of ubiquitin-protein ligase activity; IMP:HGNC.
GO:0006301; P:postreplication repair; IMP:HGNC.
GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
GO:0006508; P:proteolysis; TAS:ProtInc.
GO:0033182; P:regulation of histone ubiquitination; IMP:HGNC.
GO:0050852; P:T cell receptor signaling pathway; IMP:UniProtKB.
GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:Compara.

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

PS00183; UBIQUITIN_CONJUGAT_1
PS50127; UBIQUITIN_CONJUGAT_2