UBE1C explained

Symbol:	E2_bind
E2 binding domain
Pfam:	PF08825
Interpro:	IPR014929

NEDD8-activating enzyme E1 catalytic subunit is a protein that in humans is encoded by the UBA3 gene.^{[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]

Interactions

UBE1C has been shown to interact with NEDD8,^[4] APPBP1^[5] and UBE2M.

Further reading

• Gong L, Yeh ET . Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. . J. Biol. Chem. . 274 . 17 . 12036–42 . 1999 . 10207026 . 10.1074/jbc.274.17.12036 . free .
• Gubin AN, Njoroge JM, Bouffard GG, Miller JL . Gene expression in proliferating human erythroid cells. . Genomics . 59 . 2 . 168–77 . 1999 . 10409428 . 10.1006/geno.1999.5855 .
• Chen Y, McPhie DL, Hirschberg J, Neve RL . 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 . 10722740 . 10.1074/jbc.275.12.8929 . free .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination. . Genome Res. . 10 . 11 . 1788–95 . 2001 . 11076863 . 10.1101/gr.143000 . 310948 .
• Wiemann S, Weil B, Wellenreuther R, etal . 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 . 11230166 . 10.1101/gr.GR1547R . 311072 .
• Simpson JC, Wellenreuther R, Poustka A, etal . Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing. . EMBO Rep. . 1 . 3 . 287–92 . 2001 . 11256614 . 10.1093/embo-reports/kvd058 . 1083732 .
• Strausberg RL, Feingold EA, Grouse LH, etal . 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 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Walden H, Podgorski MS, Schulman BA . Insights into the ubiquitin transfer cascade from the structure of the activating enzyme for NEDD8. . Nature . 422 . 6929 . 330–4 . 2003 . 12646924 . 10.1038/nature01456 . 2003Natur.422..330W . 4370095 .
• Bohnsack RN, Haas AL . Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer. . J. Biol. Chem. . 278 . 29 . 26823–30 . 2003 . 12740388 . 10.1074/jbc.M303177200 . free .
• Walden H, Podgorski MS, Huang DT, etal . 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 . 14690597 . 10.1016/S1097-2765(03)00452-0 . free .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Huang DT, Miller DW, Mathew R, etal . A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8. . Nat. Struct. Mol. Biol. . 11 . 10 . 927–35 . 2004 . 15361859 . 10.1038/nsmb826 . 2862556 .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Wiemann S, Arlt D, Huber W, etal . From ORFeome to biology: a functional genomics pipeline. . Genome Res. . 14 . 10B . 2136–44 . 2004 . 15489336 . 10.1101/gr.2576704 . 528930 .
• Huang DT, Paydar A, Zhuang M, etal . Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1. . Mol. Cell . 17 . 3 . 341–50 . 2005 . 15694336 . 10.1016/j.molcel.2004.12.020 . free .
• Mehrle A, Rosenfelder H, Schupp I, etal . The LIFEdb database in 2006. . Nucleic Acids Res. . 34 . Database issue . D415–8 . 2006 . 16381901 . 10.1093/nar/gkj139 . 1347501 .
• Hiller M, Huse K, Szafranski K, etal . Single-nucleotide polymorphisms in NAGNAG acceptors are highly predictive for variations of alternative splicing. . Am. J. Hum. Genet. . 78 . 2 . 291–302 . 2007 . 16400609 . 10.1086/500151 . 1380236 .
• Norman JA, Shiekhattar R . Analysis of Nedd8-associated polypeptides: a model for deciphering the pathway for ubiquitin-like modifications. . Biochemistry . 45 . 9 . 3014–9 . 2006 . 16503656 . 10.1021/bi052435a .
• Li T, Santockyte R, Shen RF, etal . A general approach for investigating enzymatic pathways and substrates for ubiquitin-like modifiers. . Arch. Biochem. Biophys. . 453 . 1 . 70–4 . 2006 . 16620772 . 10.1016/j.abb.2006.03.002 .

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)

Notes and References

1. Osaka F, Kawasaki H, Aida N, Saeki M, Chiba T, Kawashima S, Tanaka K, Kato S . A new NEDD8-ligating system for cullin-4A . Genes Dev . 12 . 15 . 2263–8 . August 1998 . 9694792 . 317039 . 10.1101/gad.12.15.2263 .
2. Web site: Entrez Gene: UBE1C ubiquitin-activating enzyme E1C (UBA3 homolog, yeast).
3. Huang DT, Paydar A, Zhuang M, Waddell MB, Holton JM, Schulman BA . Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1 . Mol. Cell . 17 . 3 . 341–50 . February 2005 . 15694336 . 10.1016/j.molcel.2004.12.020 . free .
4. 10.1074/jbc.274.17.12036 . Gong . L . Yeh E T . April 1999 . Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway . J. Biol. Chem. . 274 . 17 . 12036–42 . UNITED STATES. 0021-9258. 10207026 . free .
5. 10.1074/jbc.275.12.8929 . 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 . 8929–35 . UNITED STATES. 0021-9258. 10722740 . free .