UniProt Accession

 UBC12_HUMAN; P61081; O76069; Q8VC50 

Genbank Protein ID

 AB012191; AF075599; BT006754; BC058924 

Genbank Nucleotide ID

 BAA33145.1; AAC26141.1; AAP35400.1; AAH58924.1 

Protein Name

 NEDD8-conjugating enzyme Ubc12 

Protein Synonyms/Alias

 NEDD8 carrier protein; NEDD8 protein ligase; Ubiquitin-conjugating enzyme E2 M 

Gene Name

 UBE2M 

Gene Synonyms/Alias

 UBC12 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
3	*****MIKLFSLKQQ	acetylation	[1]
3	*****MIKLFSLKQQ	ubiquitination	[2, 3, 4, 5, 6]
8	MIKLFSLKQQKKEEE	ubiquitination	[2, 4, 5, 6, 7, 8]
11	LFSLKQQKKEEESAG	ubiquitination	[5]
36	AAQLRIQKDINELNL	ubiquitination	[2, 4, 6, 9]
45	INELNLPKTCDISFS	ubiquitination	[9]
72	CPDEGFYKSGKFVFS	ubiquitination	[2, 6]
75	EGFYKSGKFVFSFKV	ubiquitination	[2, 6, 8]
81	GKFVFSFKVGQGYPH	ubiquitination	[2, 6, 8]
92	GYPHDPPKVKCETMV	ubiquitination	[7]

Reference

 [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] 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] 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]
 [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] 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]
 [7] 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]
 [8] 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]
 [9] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094] 

Functional Description

 Accepts the ubiquitin-like protein NEDD8 from the UBA3- NAE1 E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction with the E3 ubiquitin ligase RBX1, but not RBX2, suggests that the RBX1-UBE2M complex neddylates specific target proteins, such as CUL1, CUL2, CUL3 and CUL4. Involved in cell proliferation. 

Sequence Annotation

 REGION 1 26 Interaction with UBA3.
 REGION 27 57 Interaction with UBA3.
 ACT_SITE 111 111 Glycyl thioester intermediate.
 MOD_RES 1 1 N-acetylmethionine.
 MOD_RES 3 3 N6-acetyllysine.
 MOD_RES 50 50 Phosphoserine.  

Keyword

 3D-structure; Acetylation; ATP-binding; Complete proteome; Ligase; Nucleotide-binding; Phosphoprotein; Reference proteome; Ubl conjugation pathway. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 183 AA 

Protein Sequence

Gene Ontology

 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0019788; F:NEDD8 ligase activity; IDA:UniProtKB.
 GO:0018169; F:ribosomal S6-glutamic acid ligase activity; IDA:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; IMP:UniProtKB.
 GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Compara.
 GO:0045116; P:protein neddylation; IDA:UniProtKB. 

Interpro

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

Pfam

 PF00179; UQ_con 

SMART

  

PROSITE

 PS00183; UBIQUITIN_CONJUGAT_1
 PS50127; UBIQUITIN_CONJUGAT_2 

PRINTS