UBE1C

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 , NAE2, UBE1C, hubiquitin like modifier activating enzyme 3
External IDs	OMIM: 603172 MGI: 1341217 HomoloGene: 2951 GeneCards: UBA3
Gene location (Human) Chr. Chromosome 3 (human) [1] Band 3p14.1 Start 69,054,730 bp [1] End 69,080,408 bp [1]
Gene location (Mouse) Chr. Chromosome 6 (mouse) [2] Band 6|6 D3 Start 97,160,631 bp [2] End 97,182,608 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in palpebral conjunctiva monocyte secondary oocyte germinal epithelium right ventricle visceral pleura Achilles tendon myocardium endothelial cell parietal pleura Top expressed in otic placode saccule medullary collecting duct barrel cortex renal corpuscle primitive streak medial ganglionic eminence superior cervical ganglion atrioventricular valve pineal gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding ligase activity protein binding protein heterodimerization activity acid-amino acid ligase activity NEDD8 activating enzyme activity ubiquitin-like modifier activating enzyme activity ATP binding identical protein binding NEDD8 transferase activity nuclear receptor binding Cellular component nucleus cytosol cytoplasm protein-containing complex Biological process proteolysis regulation of cell cycle mitotic cell cycle endomitotic cell cycle cell cycle negative regulation of transcription, DNA-templated post-translational protein modification protein neddylation protein modification by small protein conjugation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9039 22200 Ensembl ENSG00000144744 ENSMUSG00000030061 UniProt Q8TBC4 Q8C878 RefSeq (mRNA) NM_003968 NM_198195 NM_198197 NM_001363861 NM_001111106 NM_001301857 NM_001301858 NM_001301859 NM_011666 RefSeq (protein) NP_003959 NP_937838 NP_001350790 NP_001104576 NP_001288786 NP_001288787 NP_001288788 NP_035796 Location (UCSC) Chr 3: 69.05 – 69.08 Mb Chr 6: 97.16 – 97.18 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. ^{[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]

Interactions

UBE1C has been shown to interact with NEDD8, ^[8] APPBP1 ^[9] and UBE2M. ^[7]

References

1. GRCh38: Ensembl release 89: ENSG00000144744 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030061 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. "Entrez Gene: UBE1C ubiquitin-activating enzyme E1C (UBA3 homolog, yeast)".
7. 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.
8. 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 . ISSN   0021-9258. PMID   10207026.
9. 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 . ISSN   0021-9258. PMID   10722740.

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 . 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.

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