UBE1C

Protein-coding gene in the species Homo sapiens
UBA3
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1R4M, 1R4N, 1TT5, 1Y8X, 1YOV, 2LQ7, 2NVU, 3DBH, 3DBL, 3DBR, 3FN1, 3GZN

Identifiers
AliasesUBA3, NAE2, UBE1C, hubiquitin like modifier activating enzyme 3
External IDsOMIM: 603172; MGI: 1341217; HomoloGene: 2951; GeneCards: UBA3; OMA:UBA3 - orthologs
Gene location (Human)
Chromosome 3 (human)
Chr.Chromosome 3 (human)[1]
Chromosome 3 (human)
Genomic location for UBA3
Genomic location for UBA3
Band3p14.1Start69,054,730 bp[1]
End69,080,408 bp[1]
Gene location (Mouse)
Chromosome 6 (mouse)
Chr.Chromosome 6 (mouse)[2]
Chromosome 6 (mouse)
Genomic location for UBA3
Genomic location for UBA3
Band6|6 D3Start97,160,631 bp[2]
End97,182,608 bp[2]
RNA expression pattern
Bgee
HumanMouse (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
SpeciesHumanMouse
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 MbChr 6: 97.16 – 97.18 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
E2 binding domain
appbp1-uba3-nedd8, an e1-ubiquitin-like protein complex with atp
Identifiers
SymbolE2_bind
PfamPF08825
InterProIPR014929
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure 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. ^ a b c GRCh38: Ensembl release 89: ENSG00000144744 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b "Entrez Gene: UBE1C ubiquitin-activating enzyme E1C (UBA3 homolog, yeast)".
  7. ^ 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.
  8. ^ 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.
  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. 275 (12). UNITED STATES: 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)


  • v
  • t
  • e
  • 1r4m: APPBP1-UBA3-NEDD8, an E1-ubiquitin-like protein complex
    1r4m: APPBP1-UBA3-NEDD8, an E1-ubiquitin-like protein complex
  • 1r4n: APPBP1-UBA3-NEDD8, an E1-ubiquitin-like protein complex with ATP
    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
    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
    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
    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
    2nvu: Structure of APPBP1-UBA3~NEDD8-NEDD8-MgATP-Ubc12(C111A), a trapped ubiquitin-like protein activation complex
This article incorporates text from the public domain Pfam and InterPro: IPR014929
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