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Ube3a

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Title: Ube3a  
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Ube3a

Ubiquitin protein ligase E3A
Structure of an E6AP-UbcH7 complex PDB rendering based on 1c4z.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; ANCR; AS; E6-AP; EPVE6AP; HPVE6A
External IDs GeneCards:
EC number
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Ubiquitin-protein ligase E3A (UBE3A) also known as E6AP ubiquitin-protein ligase (E6AP) is an enzyme that in humans is encoded by the UBE3A gene. This enzyme is involved in targeting proteins for degradation within cells.

Protein degradation is a normal process that removes damaged or unnecessary proteins and helps maintain the normal functions of cells. Ubiquitin protein ligase E3A attaches a small marker protein called ubiquitin to proteins that should be degraded. Cellular structures called proteasomes recognize and digest proteins tagged with ubiquitin.

Both copies of the UBE3A gene are active in most of the body's tissues. In the brain, however, only the copy inherited from a person's mother (the maternal copy) is normally active; this is known as paternal imprinting. The UBE3A gene is located on the long (q) arm of chromosome 15 between positions 11 and 13, from base pair 23,133,488 to base pair 23,235,220.

Contents

  • Clinical significance 1
  • Interactions 2
  • References 3
  • Further reading 4
  • External links 5

Clinical significance

Mutations within the UBE3A gene are responsible for some cases of Angelman syndrome and Prader-Willi syndrome. Most of these mutations result in an abnormally short, nonfunctional version of ubiquitin protein ligase E3A. Because the copy of the gene inherited from a person's father (the paternal copy) is normally inactive in the brain, a mutation in the remaining maternal copy prevents any of the enzyme from being produced in the brain. This loss of enzyme function likely causes the characteristic features of these two conditions.

The UBE3A gene lies within the human chromosomal region 15q11-13. Other abnormalities in this region of chromosome 15 can also cause Angelman syndrome. These chromosomal changes include deletions, rearrangements (translocations) of genetic material, and other abnormalities. Like mutations within the gene, these chromosomal changes prevent any functional ubiquitin protein ligase E3A from being produced in the brain.

Interactions

UBE3A has been shown to interact with:

References

  1. ^ a b Oda H, Kumar S, Howley PM (1999). "Regulation of the Src family tyrosine kinase Blk through E6AP-mediated ubiquitination". Proc. Natl. Acad. Sci. U.S.A. 96 (17): 9557–62.  
  2. ^ Kühne C, Banks L (1998). "E3-ubiquitin ligase/E6-AP links multicopy maintenance protein 7 to the ubiquitination pathway by a novel motif, the L2G box". J. Biol. Chem. 273 (51): 34302–9.  
  3. ^ Kim S, Chahrour M, Ben-Shachar S, Lim J (31 May 2013). "Ube3a/E6AP is involved in a subset of MeCP2 functions". Biochem. Biophys. Res. Commun. 437 (1): 67–73.  
  4. ^ Nawaz Z, Lonard DM, Smith CL, Lev-Lehman E, Tsai SY, Tsai MJ, O'Malley BW (1999). "The Angelman syndrome-associated protein, E6-AP, is a coactivator for the nuclear hormone receptor superfamily". Mol. Cell. Biol. 19 (2): 1182–9.  
  5. ^ Lu Z, Hu X, Li Y, Zheng L, Zhou Y, Jiang H, Ning T, Basang Z, Zhang C, Ke Y (2004). "Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin". J. Biol. Chem. 279 (34): 35664–70.  
  6. ^ Zheng L, Ding H, Lu Z, Li Y, Pan Y, Ning T, Ke Y (2008). "E3 ubiquitin ligase E6AP-mediated TSC2 turnover in the presence and absence of HPV16 E6". Genes Cells 13 (3): 285–94.  
  7. ^ a b Nuber U, Schwarz S, Kaiser P, Schneider R, Scheffner M (1996). "Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1) and characterization of their interaction with E6-AP and RSP5". J. Biol. Chem. 271 (5): 2795–800.  
  8. ^ Nuber U, Scheffner M (1999). "Identification of determinants in E2 ubiquitin-conjugating enzymes required for hect E3 ubiquitin-protein ligase interaction". J. Biol. Chem. 274 (11): 7576–82.  
  9. ^ a b Anan T, Nagata Y, Koga H, Honda Y, Yabuki N, Miyamoto C, Kuwano A, Matsuda I, Endo F, Saya H, Nakao M (1998). "Human ubiquitin-protein ligase Nedd4: expression, subcellular localization and selective interaction with ubiquitin-conjugating enzymes". Genes Cells 3 (11): 751–63.  
  10. ^ Hatakeyama S, Jensen JP, Weissman AM (1997). "Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases". J. Biol. Chem. 272 (24): 15085–92.  
  11. ^ Huang L, Kinnucan E, Wang G, Beaudenon S, Howley PM, Huibregtse JM, Pavletich NP (1999). "Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade". Science 286 (5443): 1321–6.  
  12. ^ a b Kleijnen MF, Shih AH, Zhou P, Kumar S, Soccio RE, Kedersha NL, Gill G, Howley PM (2000). "The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome". Mol. Cell 6 (2): 409–19.  

Further reading

  • Bittel DC, Kibiryeva N, Talebizadeh Z, Driscoll DJ, Butler MG (2005). "Microarray analysis of gene/transcript expression in Angelman syndrome: deletion versus UPD". Genomics 85 (1): 85–91.  
  • Cassidy SB, Dykens E, Williams CA (2000). " 
  • Clayton-Smith J, Laan L (2003). "Angelman syndrome: a review of the clinical and genetic aspects". J Med Genet 40 (2): 87–95.  
  • Fang P, Lev-Lehman E, Tsai TF, Matsuura T, Benton CS, Sutcliffe JS, Christian SL, Kubota T, Halley DJ, Meijers-Heijboer H, Langlois S, Graham JM Jr, Beuten J, Willems PJ, Ledbetter DH, Beaud; et al. (1999). "The spectrum of mutations in UBE3A causing Angelman syndrome". Hum Mol Genet 8 (1): 129–35.   Category:CS1 maint: Explicit use of et al.)
  • Moncla A, Malzac P, Livet MO, Voelckel MA, Mancini J, Delaroziere JC, Philip N, Mattei JF (1999). "Angelman syndrome resulting from UBE3A mutations in 14 patients from eight families: clinical manifestations and genetic counselling". J Med Genet 36 (7): 554–60.  
  • Williams CA (2005). "Neurological aspects of the Angelman syndrome". Brain Dev 27 (2): 88–94.  

External links

  • GeneReviews/NCBI/NIH/UW entry on Angelman syndrome
  • OMIM entries on Angelman syndrome
  • GeneCard
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