UBE3A

Ubiquitin protein ligase E3A

Structure of an E6AP-UbcH7 complex PDB rendering based on 1c4z.
Identifiers
Symbols UBE3A; ANCR; AS; E6-AP; EPVE6AP; FLJ26981; HPVE6A
External IDs OMIM601623 MGI105098 HomoloGene7988 GeneCards: UBE3A Gene
EC number 6.3.2.19
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 7337 22215
Ensembl ENSG00000114062 ENSMUSG00000025326
UniProt Q05086 Q3TPQ9
RefSeq (mRNA) NM_000462.3 NM_001033962
RefSeq (protein) NP_000453.2 NP_001029134
Location (UCSC) Chr 15:
25.58 – 25.68 Mb
Chr 7:
66.48 – 66.56 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 3A attaches a small 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. 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

Mutations within the UBE3A gene are responsible for some cases of Angelman 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 due to paternal imprinting, 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 Angelman syndrome.

Abnormalities involving the region of chromosome 15 that contains the UBE3A gene 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 UBQLN1,[1] UBQLN2,[1] UBE2D1,[2][3] TSC2,[4][5] BLK,[6] Lck,[6] MCM7,[7] Progesterone receptor,[8] UBE2L3[2][9][10] and UBE2D2.[9][11]

References

  1. ^ a b Kleijnen, M F; Shih A H, Zhou P, Kumar S, Soccio R E, Kedersha N L, Gill G, Howley P M (Aug. 2000). "The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome". Mol. Cell (UNITED STATES) 6 (2): 409–19. doi:10.1016/S1097-2765(00)00040-X. ISSN 1097-2765. PMID 10983987. 
  2. ^ a b Nuber, U; Schwarz S, Kaiser P, Schneider R, Scheffner M (Feb. 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. (UNITED STATES) 271 (5): 2795–800. doi:10.1074/jbc.271.5.2795. ISSN 0021-9258. PMID 8576257. 
  3. ^ Nuber, U; Scheffner M (Mar. 1999). "Identification of determinants in E2 ubiquitin-conjugating enzymes required for hect E3 ubiquitin-protein ligase interaction". J. Biol. Chem. (UNITED STATES) 274 (11): 7576–82. doi:10.1074/jbc.274.11.7576. ISSN 0021-9258. PMID 10066826. 
  4. ^ Lu, Zheming; Hu Xiuhua, Li Yong, Zheng Li, Zhou Yue, Jiang Haidi, Ning Tao, Basang Zhuoma, Zhang Chunfeng, Ke Yang (Aug. 2004). "Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin". J. Biol. Chem. (United States) 279 (34): 35664–70. doi:10.1074/jbc.M403385200. ISSN 0021-9258. PMID 15175323. 
  5. ^ Zheng, Li; Ding Huirong, Lu Zheming, Li Yong, Pan Yaqi, Ning Tao, Ke Yang (Mar. 2008). "E3 ubiquitin ligase E6AP-mediated TSC2 turnover in the presence and absence of HPV16 E6". Genes Cells (England) 13 (3): 285–94. doi:10.1111/j.1365-2443.2008.01162.x. PMID 18298802. 
  6. ^ a b Oda, H; Kumar S, Howley P M (Aug. 1999). "Regulation of the Src family tyrosine kinase Blk through E6AP-mediated ubiquitination". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 96 (17): 9557–62. doi:10.1073/pnas.96.17.9557. ISSN 0027-8424. PMC 22247. PMID 10449731. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=22247. 
  7. ^ Kühne, C; Banks L (Dec. 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. (UNITED STATES) 273 (51): 34302–9. doi:10.1074/jbc.273.51.34302. ISSN 0021-9258. PMID 9852095. 
  8. ^ Nawaz, Z; Lonard D M, Smith C L, Lev-Lehman E, Tsai S Y, Tsai M J, O'Malley B W (Feb. 1999). "The Angelman syndrome-associated protein, E6-AP, is a coactivator for the nuclear hormone receptor superfamily". Mol. Cell. Biol. (UNITED STATES) 19 (2): 1182–9. ISSN 0270-7306. PMC 116047. PMID 9891052. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=116047. 
  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 (Nov. 1998). "Human ubiquitin-protein ligase Nedd4: expression, subcellular localization and selective interaction with ubiquitin-conjugating enzymes". Genes Cells (ENGLAND) 3 (11): 751–63. doi:10.1046/j.1365-2443.1998.00227.x. ISSN 1356-9597. PMID 9990509. 
  10. ^ Huang, L; Kinnucan E, Wang G, Beaudenon S, Howley P M, Huibregtse J M, Pavletich N P (Nov. 1999). "Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade". Science (UNITED STATES) 286 (5443): 1321–6. doi:10.1126/science.286.5443.1321. ISSN 0036-8075. PMID 10558980. 
  11. ^ Hatakeyama, S; Jensen J P, Weissman A M (Jun. 1997). "Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases". J. Biol. Chem. (UNITED STATES) 272 (24): 15085–92. doi:10.1074/jbc.272.24.15085. ISSN 0021-9258. PMID 9182527. 

Further reading

External links