UBE3A

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UBE3A
Protein UBE3A PDB 1c4z.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases UBE3A, ANCR, AS, E6-AP, EPVE6AP, HPVE6A, ubiquitin protein ligase E3A
External IDs MGI: 105098 HomoloGene: 7988 GeneCards: UBE3A
Gene location (Human)
Chromosome 15 (human)
Chr. Chromosome 15 (human)[1]
Chromosome 15 (human)
Genomic location for UBE3A
Genomic location for UBE3A
Band 15q11.2 Start 25,333,728 bp[1]
End 25,439,056 bp[1]
RNA expression pattern
PBB GE UBE3A 213128 s at fs.png

PBB GE UBE3A 211285 s at fs.png

PBB GE UBE3A 211575 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001033962
NM_011668
NM_173010

RefSeq (protein)

NP_001029134
NP_035798
NP_766598

Location (UCSC) Chr 15: 25.33 – 25.44 Mb Chr 15: 59.23 – 59.31 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. Silencing of Ube3a on the paternal allele is thought to occur through the Ube3a-ATS part of a lincRNA called "LNCAT",[5] (Large Non-Coding Antisense Transcript).

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.

Interactions[edit]

UBE3A has been shown to interact with:

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000114062 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025326 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Runte M, Hüttenhofer A, Gross S, Kiefmann M, Horsthemke B, Buiting K (November 2001). "The IC-SNURF-SNRPN transcript serves as a host for multiple small nucleolar RNA species and as an antisense RNA for UBE3A". Human Molecular Genetics. 10 (23): 2687–700. PMID 11726556. doi:10.1093/hmg/10.23.2687. 
  6. ^ a b Oda H, Kumar S, Howley PM (August 1999). "Regulation of the Src family tyrosine kinase Blk through E6AP-mediated ubiquitination". Proceedings of the National Academy of Sciences of the United States of America. 96 (17): 9557–62. PMC 22247Freely accessible. PMID 10449731. doi:10.1073/pnas.96.17.9557. 
  7. ^ Kühne C, Banks L (December 1998). "E3-ubiquitin ligase/E6-AP links multicopy maintenance protein 7 to the ubiquitination pathway by a novel motif, the L2G box". The Journal of Biological Chemistry. 273 (51): 34302–9. PMID 9852095. doi:10.1074/jbc.273.51.34302. 
  8. ^ Kim S, Chahrour M, Ben-Shachar S, Lim J (July 2013). "Ube3a/E6AP is involved in a subset of MeCP2 functions". Biochemical and Biophysical Research Communications. 437 (1): 67–73. PMID 23791832. doi:10.1016/j.bbrc.2013.06.036. 
  9. ^ Nawaz Z, Lonard DM, Smith CL, Lev-Lehman E, Tsai SY, Tsai MJ, O'Malley BW (February 1999). "The Angelman syndrome-associated protein, E6-AP, is a coactivator for the nuclear hormone receptor superfamily". Molecular and Cellular Biology. 19 (2): 1182–9. PMC 116047Freely accessible. PMID 9891052. doi:10.1128/mcb.19.2.1182. 
  10. ^ Lu Z, Hu X, Li Y, Zheng L, Zhou Y, Jiang H, Ning T, Basang Z, Zhang C, Ke Y (August 2004). "Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin". The Journal of Biological Chemistry. 279 (34): 35664–70. PMID 15175323. doi:10.1074/jbc.M403385200. 
  11. ^ Zheng L, Ding H, Lu Z, Li Y, Pan Y, Ning T, Ke Y (March 2008). "E3 ubiquitin ligase E6AP-mediated TSC2 turnover in the presence and absence of HPV16 E6". Genes to Cells. 13 (3): 285–94. PMID 18298802. doi:10.1111/j.1365-2443.2008.01162.x. 
  12. ^ a b Nuber U, Schwarz S, Kaiser P, Schneider R, Scheffner M (February 1996). "Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1) and characterization of their interaction with E6-AP and RSP5". The Journal of Biological Chemistry. 271 (5): 2795–800. PMID 8576257. doi:10.1074/jbc.271.5.2795. 
  13. ^ Nuber U, Scheffner M (March 1999). "Identification of determinants in E2 ubiquitin-conjugating enzymes required for hect E3 ubiquitin-protein ligase interaction". The Journal of Biological Chemistry. 274 (11): 7576–82. PMID 10066826. doi:10.1074/jbc.274.11.7576. 
  14. ^ a b Anan T, Nagata Y, Koga H, Honda Y, Yabuki N, Miyamoto C, Kuwano A, Matsuda I, Endo F, Saya H, Nakao M (November 1998). "Human ubiquitin-protein ligase Nedd4: expression, subcellular localization and selective interaction with ubiquitin-conjugating enzymes". Genes to Cells. 3 (11): 751–63. PMID 9990509. doi:10.1046/j.1365-2443.1998.00227.x. 
  15. ^ Hatakeyama S, Jensen JP, Weissman AM (June 1997). "Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases". The Journal of Biological Chemistry. 272 (24): 15085–92. PMID 9182527. doi:10.1074/jbc.272.24.15085. 
  16. ^ Huang L, Kinnucan E, Wang G, Beaudenon S, Howley PM, Huibregtse JM, Pavletich NP (November 1999). "Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade". Science. 286 (5443): 1321–6. PMID 10558980. doi:10.1126/science.286.5443.1321. 
  17. ^ a b Kleijnen MF, Shih AH, Zhou P, Kumar S, Soccio RE, Kedersha NL, Gill G, Howley PM (August 2000). "The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome". Molecular Cell. 6 (2): 409–19. PMID 10983987. doi:10.1016/S1097-2765(00)00040-X. 

Further reading[edit]

External links[edit]