Biology:UBE1C

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

E2 binding domain
appbp1-uba3-nedd8, an e1-ubiquitin-like protein complex with atp
Identifiers
Symbol	E2_bind
Pfam	PF08825
InterPro	IPR014929
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

NEDD8-activating enzyme E1 catalytic subunit is a protein that in humans is encoded by the UBA3 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 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.

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.

Interactions

UBE1C has been shown to interact with NEDD8, APPBP1 and UBE2M.

Further reading

• "Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway.". J. Biol. Chem. 274 (17): 12036–42. 1999. doi:10.1074/jbc.274.17.12036. PMID 10207026. 
• "Gene expression in proliferating human erythroid cells.". Genomics 59 (2): 168–77. 1999. doi:10.1006/geno.1999.5855. PMID 10409428. https://zenodo.org/record/1229786. 
• "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. 2000. doi:10.1074/jbc.275.12.8929. PMID 10722740. 
• "DNA cloning using in vitro site-specific recombination.". Genome Res. 10 (11): 1788–95. 2001. doi:10.1101/gr.143000. PMID 11076863. 
• "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. 2001. doi:10.1101/gr.GR1547R. PMID 11230166. 
• "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing.". EMBO Rep. 1 (3): 287–92. 2001. doi:10.1093/embo-reports/kvd058. PMID 11256614. 
• "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. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M. 
• "Insights into the ubiquitin transfer cascade from the structure of the activating enzyme for NEDD8.". Nature 422 (6929): 330–4. 2003. doi:10.1038/nature01456. PMID 12646924. Bibcode: 2003Natur.422..330W. 
• "Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer.". J. Biol. Chem. 278 (29): 26823–30. 2003. doi:10.1074/jbc.M303177200. PMID 12740388. 
• "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. 2004. doi:10.1016/S1097-2765(03)00452-0. PMID 14690597. 
• "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. 2004. doi:10.1038/ng1285. PMID 14702039. 
• "A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8.". Nat. Struct. Mol. Biol. 11 (10): 927–35. 2004. doi:10.1038/nsmb826. PMID 15361859. 
• "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334. 
• "From ORFeome to biology: a functional genomics pipeline.". Genome Res. 14 (10B): 2136–44. 2004. doi:10.1101/gr.2576704. PMID 15489336. 
• "Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1.". Mol. Cell 17 (3): 341–50. 2005. doi:10.1016/j.molcel.2004.12.020. PMID 15694336. 
• "The LIFEdb database in 2006.". Nucleic Acids Res. 34 (Database issue): D415–8. 2006. doi:10.1093/nar/gkj139. PMID 16381901. 
• "Single-nucleotide polymorphisms in NAGNAG acceptors are highly predictive for variations of alternative splicing.". Am. J. Hum. Genet. 78 (2): 291–302. 2007. doi:10.1086/500151. PMID 16400609. 
• "Analysis of Nedd8-associated polypeptides: a model for deciphering the pathway for ubiquitin-like modifications.". Biochemistry 45 (9): 3014–9. 2006. doi:10.1021/bi052435a. PMID 16503656. 
• "A general approach for investigating enzymatic pathways and substrates for ubiquitin-like modifiers.". Arch. Biochem. Biophys. 453 (1): 70–4. 2006. doi:10.1016/j.abb.2006.03.002. PMID 16620772. https://zenodo.org/record/1258674. 

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human NEDD8-activating enzyme E1 catalytic subunit (UBE1C)

This article incorporates text from the public domain Pfam and InterPro: IPR014929