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UBE2M is a member of the ubiquitin-conjugating E2 family whose members perform the second step in the ubiquitination reaction. Initially identified as the main process for protein degradation, ubiquitination is believed nowadays to be crucial for a wider range of cellular processes. The outcome of the ubiquitin-conjugation reaction, and thereby the fate of the substrate, is heavily dependent on the number of ubiquitin molecules attached and how these ubiquitin molecules are inter-connected. To deal with this complexity and to allow adequate ubiquitination in time and space, a highly sophisticated conjugation machinery has been developed. In a sequential manner, ubiquitin becomes activated by an ubiquitin-activating enzyme (E1), which then transfers the ubiquitin to a group of ubiquitin-conjugating enzymes (E2s). Next, ubiquitin-loaded E2s are interacting with ubiquitin protein ligases (E3s) and ubiquitin is conjugated to substrates on recruitment by the E3. These three key enzymes are operating in a hierarchical system, wherein two E1s and 35 E2s have been found and hundreds of E3s have been identified in humans.
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UBE2M Related Areas
Enzyme>>Protease & Regulator>>Other Proteases>> UBE2M
Neuroscience>>Neurodegenerative Disease>>Ubiquitin-proteasome pathway>> UBE2M
UBE2M Related Pathways
UBE2M Alternative Names
UBC-RS2, UBC12, hUbc12 [Homo sapiens]
2510040H03Rik, UBC12, Ubc-rs2[Mus musculus]
Summaries for UBE2M
Entrez Gene summary for UBE2M:
The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. UBE2M gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein is linked with a ubiquitin-like protein, NEDD8, which can be conjugated to cellular proteins, such as Cdc53/culin. [provided by RefSeq, Jul 2008]
Wikipedia summary for UBE2M:
NEDD8-conjugating enzyme Ubc12 is a protein that in humans is encoded by the UBE2M gene.
The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein is linked with a ubiquitin-like protein, NEDD8, which can be conjugated to cellular proteins, such as Cdc53/culin.
Human UBE2M Protein General Information
| Protein names |
Ubiquitin-conjugating enzyme E2 M |
| Sequence length |
183 AA. |
| Domain |
Both the N-terminal docking peptide and the catalytic core domain must bind the UBA3-NAE1 complex simultaneously for optimal transfer of NEDD8. |
| Sequence similarities: |
Belongs to the ubiquitin-conjugating enzyme family. UBC12 subfamily. |
| Post-translational modification: |
The acetylation of Met-1 is cotranslational, and not regulatory. The N-acetylmethionine increases affinity for DCUN1D1 by about 2 orders of magnitude and is crucial for NEDD8 transfer to cullins. |
| Subunit structure |
Interacts with UBA3, DCUN1D1 and RBX1. |
| Pathway: | Protein modification; protein neddylation. |
| Catalytic activity |
ATP + NEDD8 + protein lysine = AMP + diphosphate + protein N-NEDD8yllysine. |
General information above from UniProt
Function for UBE2M Protein
UniProtKB:
UBE2M 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. UBE2M is involved in cell proliferation.
Genatlas:
- UBE2M is putative NEDD8 conjugation enzyme E2(Wada 2000)
- UBE2M ubiquitinates cellular proteins to mark them for degradation (second step in ubiquitin conjugation)
- UBE2M participates in the modification of CUL4A by NEDD8
Homology for human UBE2M
- homolog to Drosophila CG7375
- homolog to yeast S.cerevisiae Ubc12
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