Protein-coding gene in the species Homo sapiens
UBA3 Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1R4M , 1R4N , 1TT5 , 1Y8X , 1YOV , 2LQ7 , 2NVU , 3DBH , 3DBL , 3DBR , 3FN1 , 3GZN
Identifiers Aliases UBA3 External IDs OMIM : 603172 ; MGI : 1341217 ; HomoloGene : 2951 ; GeneCards : UBA3 ; OMA :UBA3 - orthologs Wikidata
NEDD8-activating enzyme E1 catalytic subunit is a protein that in humans is encoded by the UBA3 gene .[ 5] [ 6]
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.[ 6]
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 .[ 7]
UBE1C has been shown to interact with NEDD8 ,[ 8] APPBP1 [ 9] UBE2M .[ 7]
^ a b c GRCh38: Ensembl release 89: ENSG00000144744 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030061 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ Osaka F, Kawasaki H, Aida N, Saeki M, Chiba T, Kawashima S, Tanaka K, Kato S (August 1998). "A new NEDD8-ligating system for cullin-4A" . Genes Dev . 12 (15): 2263–8. doi :10.1101/gad.12.15.2263 . PMC 317039 PMID 9694792 . ^ a b "Entrez Gene: UBE1C ubiquitin-activating enzyme E1C (UBA3 homolog, yeast)" .^ a b Huang 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 PMID 15694336 . ^ Gong, L; Yeh E T (April 1999). "Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway" . J. Biol. Chem . 274 (17). UNITED STATES: 12036–42. doi :10.1074/jbc.274.17.12036 ISSN 0021-9258 . PMID 10207026 . ^ 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 . 275 (12). UNITED STATES: 8929–35. doi :10.1074/jbc.275.12.8929 ISSN 0021-9258 . PMID 10722740 . 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 PMID 10207026 . 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 . PMID 10409428 . 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 PMID 10722740 . Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination" . Genome Res . 10 (11): 1788–95. doi :10.1101/gr.143000 . PMC 310948 PMID 11076863 . Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs" . Genome Res . 11 (3): 422–35. doi :10.1101/gr.GR1547R . PMC 311072 PMID 11230166 . Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing" . EMBO Rep . 1 (3): 287–92. doi :10.1093/embo-reports/kvd058 . PMC 1083732 PMID 11256614 . Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences" . Proc. Natl. Acad. Sci. U.S.A . 99 (26): 16899–903. Bibcode :2002PNAS...9916899M . doi :10.1073/pnas.242603899 PMC 139241 PMID 12477932 . 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 . PMID 12646924 . S2CID 4370095 . 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 PMID 12740388 . 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 PMID 14690597 . 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 PMID 14702039 . Huang DT, Miller DW, Mathew R, et al. (2004). "A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8" . Nat. Struct. Mol. Biol . 11 (10): 927–35. doi :10.1038/nsmb826 . PMC 2862556 PMID 15361859 . Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)" . Genome Res . 14 (10B): 2121–7. doi :10.1101/gr.2596504 . PMC 528928 PMID 15489334 . Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to biology: a functional genomics pipeline" . Genome Res . 14 (10B): 2136–44. doi :10.1101/gr.2576704 . PMC 528930 PMID 15489336 . 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 PMID 15694336 . Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb database in 2006" . Nucleic Acids Res . 34 (Database issue): D415–8. doi :10.1093/nar/gkj139 . PMC 1347501 PMID 16381901 . Hiller M, Huse K, Szafranski K, et al. (2007). "Single-nucleotide polymorphisms in NAGNAG acceptors are highly predictive for variations of alternative splicing" . Am. J. Hum. Genet . 78 (2): 291–302. doi :10.1086/500151 . PMC 1380236 PMID 16400609 . 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 . PMID 16503656 . 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 . PMID 16620772 . PDBe-KB provides an overview of all the structure information available in the PDB for Human NEDD8-activating enzyme E1 catalytic subunit (UBE1C)
PDB gallery
1r4m : APPBP1-UBA3-NEDD8, an E1-ubiquitin-like protein complex
1r4n : APPBP1-UBA3-NEDD8, an E1-ubiquitin-like protein complex with ATP
1tt5 : Structure of APPBP1-UBA3-Ubc12N26: a unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8
1y8x : Structural basis for recruitment of Ubc12 by an E2-binding domain in NEDD8's E1
1yov : Insights into the Ubiquitin Transfer Cascade from the refined structure of the activating enzyme for NEDD8
2nvu : Structure of APPBP1-UBA3~NEDD8-NEDD8-MgATP-Ubc12(C111A), a trapped ubiquitin-like protein activation complex
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