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HMDB Protein ID HMDBP00563
Secondary Accession Numbers
  • 5835
Name NEDD8-conjugating enzyme Ubc12
  1. NEDD8 carrier protein
  2. NEDD8 protein ligase
  3. Ubiquitin-conjugating enzyme E2 M
Gene Name UBE2M
Protein Type Enzyme
Biological Properties
General Function Involved in ATP binding
Specific Function 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.
  • protein neddylation
  • Ubiquitin mediated proteolysis
Adenosine triphosphate + NEDD8 + protein lysine → Adenosine monophosphate + Pyrophosphate + protein N-NEDD8yllysine details
GO Classification
Biological Process
protein neddylation
positive regulation of neuron apoptotic process
catalytic activity
small conjugating protein ligase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
ligase activity
ligase activity, forming carbon-nitrogen bonds
acid-amino acid ligase activity
Molecular Function
ubiquitin-protein ligase activity
ATP binding
NEDD8 ligase activity
ribosomal S6-glutamic acid ligase activity
metabolic process
regulation of protein metabolic process
macromolecule metabolic process
biological regulation
regulation of biological process
regulation of metabolic process
regulation of macromolecule metabolic process
post-translational protein modification
macromolecule modification
protein modification process
Cellular Location Not Available
Gene Properties
Chromosome Location 19
Locus 19q13.43
Gene Sequence
>552 bp
Protein Properties
Number of Residues 183
Molecular Weight 20899.8
Theoretical pI 7.695
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>NEDD8-conjugating enzyme Ubc12
GenBank ID Protein 3599674
UniProtKB/Swiss-Prot ID P61081
UniProtKB/Swiss-Prot Entry Name UBC12_HUMAN
GenBank Gene ID AB012191
GeneCard ID UBE2M
GenAtlas ID UBE2M
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  3. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  4. Osaka F, Kawasaki H, Aida N, Saeki M, Chiba T, Kawashima S, Tanaka K, Kato S: A new NEDD8-ligating system for cullin-4A. Genes Dev. 1998 Aug 1;12(15):2263-8. [PubMed:9694792 ]
  5. Gong L, Yeh ET: Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J Biol Chem. 1999 Apr 23;274(17):12036-42. [PubMed:10207026 ]
  6. Wada H, Yeh ET, Kamitani T: A dominant-negative UBC12 mutant sequesters NEDD8 and inhibits NEDD8 conjugation in vivo. J Biol Chem. 2000 Jun 2;275(22):17008-15. [PubMed:10828074 ]
  7. Huang DT, Ayrault O, Hunt HW, Taherbhoy AM, Duda DM, Scott DC, Borg LA, Neale G, Murray PJ, Roussel MF, Schulman BA: E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification. Mol Cell. 2009 Feb 27;33(4):483-95. doi: 10.1016/j.molcel.2009.01.011. [PubMed:19250909 ]
  8. Huang DT, Miller DW, Mathew R, Cassell R, Holton JM, Roussel MF, Schulman BA: A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8. Nat Struct Mol Biol. 2004 Oct;11(10):927-35. Epub 2004 Sep 7. [PubMed:15361859 ]
  9. Huang DT, Paydar A, Zhuang M, Waddell MB, Holton JM, Schulman BA: Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1. Mol Cell. 2005 Feb 4;17(3):341-50. [PubMed:15694336 ]