From Wikipedia, the free encyclopedia
Jump to: navigation, search
Ubiquitin protein ligase E3A
Protein UBE3A PDB 1c4z.png
Structure of an E6AP-UbcH7 complex PDB rendering based on 1c4z.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM601623 MGI105098 HomoloGene7988 GeneCards: UBE3A Gene
EC number
RNA expression pattern
PBB GE UBE3A 211285 s at tn.png
PBB GE UBE3A 211575 s at tn.png
PBB GE UBE3A 213128 s at tn.png
More reference expression data
Species Human Mouse
Entrez 7337 22215
Ensembl ENSG00000114062 ENSMUSG00000025326
UniProt Q05086 O08759
RefSeq (mRNA) NM_000462 NM_001033962
RefSeq (protein) NP_000453 NP_001029134
Location (UCSC) Chr 15:
25.33 – 25.44 Mb
Chr 7:
59.23 – 59.31 Mb
PubMed search [1] [2]

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.

Clinical significance[edit]

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.


UBE3A has been shown to interact with:


  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. doi:10.1073/pnas.96.17.9557. PMC 22247. PMID 10449731. 
  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. doi:10.1074/jbc.273.51.34302. PMID 9852095. 
  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. doi:10.1016/j.bbrc.2013.06.036. PMID 23791832. 
  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. PMC 116047. PMID 9891052. 
  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. doi:10.1074/jbc.M403385200. PMID 15175323. 
  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. doi:10.1111/j.1365-2443.2008.01162.x. PMID 18298802. 
  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. doi:10.1074/jbc.271.5.2795. PMID 8576257. 
  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. doi:10.1074/jbc.274.11.7576. PMID 10066826. 
  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. doi:10.1046/j.1365-2443.1998.00227.x. PMID 9990509. 
  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. doi:10.1074/jbc.272.24.15085. PMID 9182527. 
  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. doi:10.1126/science.286.5443.1321. PMID 10558980. 
  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. doi:10.1016/S1097-2765(00)00040-X. PMID 10983987. 

Further reading[edit]

External links[edit]