CPLM-009305

Genbank Nucleotide ID

Ubiquitin-conjugating enzyme E2 K

Protein Synonyms/Alias

Huntingtin-interacting protein 2; HIP-2; Ubiquitin carrier protein; Ubiquitin-conjugating enzyme E2-25 kDa; Ubiquitin-conjugating enzyme E2(25K); Ubiquitin-conjugating enzyme E2-25K; Ubiquitin-protein ligase

Homo sapiens (Human)

Position	Peptide	Type	References
14	QRIKREFKEVLKSEE	acetylation	[1, 2, 3]
14	QRIKREFKEVLKSEE	sumoylation	[4, 5]
18	REFKEVLKSEETSKN	ubiquitination	[6]
24	LKSEETSKNQIKVDL	ubiquitination	[6, 7]
61	GRYQLEIKIPETYPF	ubiquitination	[6, 7, 8]
72	TYPFNPPKVRFITKI	ubiquitination	[6, 8, 9, 10, 11]
142	KQNPEMFKQTARLWA	ubiquitination	[6, 7, 8, 12]
164	VSSPEYTKKIENLCA	ubiquitination	[6, 7, 8, 10, 11, 13]
165	SSPEYTKKIENLCAM	ubiquitination	[10, 11, 12]

[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] Regulation of cellular metabolism by protein lysine acetylation.
Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
[3] 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]
[4] SUMO modification of the ubiquitin-conjugating enzyme E2-25K.
Pichler A, Knipscheer P, Oberhofer E, van Dijk WJ, Körner R, Olsen JV, Jentsch S, Melchior F, Sixma TK.
Nat Struct Mol Biol. 2005 Mar;12(3):264-9. [PMID: 15723079]
[5] Ubiquitin proteolytic system: focus on SUMO.
Wilson VG, Heaton PR.
Expert Rev Proteomics. 2008 Feb;5(1):121-35. [PMID: 18282128]
[6] 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]
[7] 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]
[8] 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]
[9] 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]
[10] 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]
[11] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
[12] 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]
[13] 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]

Functional Description

Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates huntingtin. May mediate foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequence degradation of p53/TP53. Proposed to be involved in ubiquitination and proteolytic processing of NF-kappa-B; in vitro supports ubiquitination of NFKB1. In case of infection by cytomegaloviruses may be involved in the US11-dependent degradation of MHC class I heavy chains following their export from the ER to the cytosol. In case of viral infections may be involved in the HPV E7 protein- dependent degradation of RB1.

DOMAIN 160 200 UBA.
ACT_SITE 92 92 Glycyl thioester intermediate (By
MOD_RES 2 2 N-acetylalanine.
MOD_RES 14 14 N6-acetyllysine; alternate.
CROSSLNK 14 14 Glycyl lysine isopeptide (Lys-Gly)

3D-structure; Acetylation; Alternative splicing; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; Isopeptide bond; Ligase; Nucleotide-binding; Reference proteome; Ubl conjugation; Ubl conjugation pathway.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO:0034450; F:ubiquitin-ubiquitin ligase activity; IDA:UniProtKB.
GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:ProtInc.

IPR009060; UBA-like.
IPR000449; UBA/transl_elong_EF1B_N.
IPR015940; UBA/transl_elong_EF1B_N_euk.
IPR000608; UBQ-conjugat_E2.
IPR023313; UBQ-conjugating_AS.
IPR016135; UBQ-conjugating_enzyme/RWD.

PF00627; UBA
PF00179; UQ_con

PS50030; UBA
PS00183; UBIQUITIN_CONJUGAT_1
PS50127; UBIQUITIN_CONJUGAT_2