NEDD8-activating enzyme E1 catalytic subunit is a protein that in humans is encoded by the UBA3gene.[1][2]
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 E1 ubiquitin-activating enzyme family. The encoded enzyme associates with AppBp1, an amyloid beta precursor protein binding protein, to form a heterodimer, and then the enzyme complex activates NEDD8, a ubiquitin-like protein, which regulates cell division, signaling and embryogenesis. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[2]
This enzyme contains an E2 binding domain, which resembles ubiquitin, and recruits the catalytic core of the E2 enzyme UBE2M (Ubc12) in a similar manner to that in which ubiquitin interacts with ubiquitin binding domains.[3]
↑ 3.03.1Huang DT, Paydar A, Zhuang M, Waddell MB, Holton JM, Schulman BA (February 2005). "Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1". Mol. Cell. 17 (3): 341–50. doi:10.1016/j.molcel.2004.12.020. PMID15694336.
↑Gong, L; Yeh E T (April 1999). "Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway". J. Biol. Chem. UNITED STATES. 274 (17): 12036–42. doi:10.1074/jbc.274.17.12036. ISSN0021-9258. PMID10207026.
↑Chen, Y; McPhie D L; Hirschberg J; Neve R L (March 2000). "The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in neurons". J. Biol. Chem. UNITED STATES. 275 (12): 8929–35. doi:10.1074/jbc.275.12.8929. ISSN0021-9258. PMID10722740.
Further reading
Gong L, Yeh ET (1999). "Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway". J. Biol. Chem. 274 (17): 12036–42. doi:10.1074/jbc.274.17.12036. PMID10207026.
Gubin AN, Njoroge JM, Bouffard GG, Miller JL (1999). "Gene expression in proliferating human erythroid cells". Genomics. 59 (2): 168–77. doi:10.1006/geno.1999.5855. PMID10409428.
Chen Y, McPhie DL, Hirschberg J, Neve RL (2000). "The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in neurons". J. Biol. Chem. 275 (12): 8929–35. doi:10.1074/jbc.275.12.8929. PMID10722740.
Walden H, Podgorski MS, Schulman BA (2003). "Insights into the ubiquitin transfer cascade from the structure of the activating enzyme for NEDD8". Nature. 422 (6929): 330–4. Bibcode:2003Natur.422..330W. doi:10.1038/nature01456. PMID12646924.
Bohnsack RN, Haas AL (2003). "Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer". J. Biol. Chem. 278 (29): 26823–30. doi:10.1074/jbc.M303177200. PMID12740388.
Walden H, Podgorski MS, Huang DT, et al. (2004). "The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1". Mol. Cell. 12 (6): 1427–37. doi:10.1016/S1097-2765(03)00452-0. PMID14690597.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
Huang DT, Paydar A, Zhuang M, et al. (2005). "Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1". Mol. Cell. 17 (3): 341–50. doi:10.1016/j.molcel.2004.12.020. PMID15694336.
Norman JA, Shiekhattar R (2006). "Analysis of Nedd8-associated polypeptides: a model for deciphering the pathway for ubiquitin-like modifications". Biochemistry. 45 (9): 3014–9. doi:10.1021/bi052435a. PMID16503656.
Li T, Santockyte R, Shen RF, et al. (2006). "A general approach for investigating enzymatic pathways and substrates for ubiquitin-like modifiers". Arch. Biochem. Biophys. 453 (1): 70–4. doi:10.1016/j.abb.2006.03.002. PMID16620772.