NEDD8-conjugating enzyme Ubc12 (UBE2M)
The protein contains 183 amino acids for an estimated molecular weight of 20900 Da.
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. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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The reference OMIM entry for this protein is 603173
Ubiquitin-conjugating enzyme e2m; ube2m
Ubiquitin-conjugating enzyme 12, s. cerevisiae, homolog of; ubc12
CLONING
Ubiquitin (191339) is covalently attached to target proteins by a multienzymatic system consisting of E1 (ubiquitin-activating), E2 (ubiquitin-conjugating), and E3 (ubiquitin-ligating) enzymes. Osaka et al. (1998) found that NEDD8 (603171), a ubiquitin-like protein, is conjugated to target proteins in a manner analogous to ubiquitylation. They identified and partially sequenced a 22-kD protein in rabbit reticulocyte lysates that can bind to NEDD8. By searching sequence databases, the authors identified a cDNA encoding the human homolog of this 22-kD protein. The predicted 183-amino acid human protein shares 42% sequence identity with S. cerevisiae Ubc12, a member of the E2 enzyme family. Since human UBC12 formed a thioester linkage with NEDD8 in rabbit reticulocyte lysates, Osaka et al. (1998) suggested that UBC12 acts as an E2-like enzyme specific for the conjugation of NEDD8.GENE FUNCTION
Scott et al. (2011) found that N-terminal acetylation of the E2 enzyme UBC12 dictates distinctive E3-dependent ligation of the ubiquitin-like protein NEDD8 (603171) to CUL1 (603134). Structural, biochemical, biophysical, and genetic analyses revealed how complete burial of UBC12's N-acetyl-methionine in a hydrophobic pocket in the E3 DCN1 (DCUN1D1; 605905) promotes cullin neddylation. The results suggested that the N-terminal acetyl both directs UBC12's interactions with DCN1 and prevents repulsion of a charged N terminus. Scott et al. (2011) concluded that their data provided a link between acetylation and ubiquitin-like protein conjugation and defined a mechanism for N-terminal acetylation-dependent recognition.BIOCHEMICAL FEATURES
- Crystal Structure Huang et al. (2007) reported the structural analysis of a trapped ubiquitin-like protein (UBL) activation complex for the human NEDD8 pathway containing NEDD8's heterodimeric E1 (APPBP1, 603385-UBA3, 603172), 2 NEDD8s (1 thioester-linked to E1, 1 noncovalently associated for adenylation), a catalytically inactive E2 (UBC12), and MgATP. The results suggested that a thioester switch toggles E1-E2 affinities. Two E2 binding sites depend on NEDD8 being thioester-linked to E1. One is unmasked by a striking E1 conformational change. The other comes directly from the thioester-bound NEDD8. After NEDD8 transfer to E2, reversion to an alternate E1 conformation would facilitate release of the covalent E2-NEDD8 thioester product. Thus, Huang et al. (2007) concluded that transferring the UBL's thioester linkage between successive conjugation enzymes can induce conformational changes and alter interaction networks to drive consecutive steps in UBL cascades. ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603173 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed