UBE3A

UBE3A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4GIZ, 1C4Z, 1D5F, 1EQX, 2KR1
Identifiers
Aliases	UBE3A, ANCR, AS, E6-AP, EPVE6AP, HPVE6A, ubiquitin protein ligase E3A
External IDs	MGI: 105098 HomoloGene: 7988 GeneCards: UBE3A
Genetically Related Diseases
obesity[1]
Gene ontology Molecular function • metal ion binding • ligase activity • transcription coactivator activity • ubiquitin-protein transferase activity • protein binding • ubiquitin protein ligase activity Cellular component • cytosol • proteasome complex • cytoplasm • nucleus Biological process • ubiquitin-dependent protein catabolic process • prostate gland growth • rhythmic process • proteolysis • positive regulation of phosphatidylinositol 3-kinase signaling • protein K48-linked ubiquitination • viral process • brain development • regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process • androgen receptor signaling pathway • ovarian follicle development • sperm entry • protein ubiquitination • positive regulation of protein ubiquitination • positive regulation of transcription from RNA polymerase II promoter • protein autoubiquitination • regulation of circadian rhythm Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7337	22215
Ensembl	ENSG00000114062	ENSMUSG00000025326
UniProt	Q05086	O08759
RefSeq (mRNA)	NM_000462 NM_130838 NM_130839	NM_001033962 NM_011668 NM_173010
RefSeq (protein)	NP_000453.2 NP_570853.1 NP_570854.1	NP_035798.2 NP_766598.1
Location (UCSC)	Chr 15: 25.33 – 25.44 Mb	Chr 7: 59.23 – 59.31 Mb
PubMed search	[2]	[3]
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. 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

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:

• BLK,^[4]
• Lck,^[4]
• MCM7,^[5]
• MECP2,^[6]
• Progesterone receptor,^[7]
• TSC2,^[8][9]
• UBE2D1,^[10][11]
• UBE2D2,^[12][13]
• UBE2L3,^[10][12][14]
• UBQLN1,^[15] and
• UBQLN2.^[15]

References

1. "Diseases that are genetically associated with UBE3A view/edit references on wikidata".
2. "Human PubMed Reference:".
3. "Mouse PubMed Reference:".
4. 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.
5. 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.
6. 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.
7. 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. doi:10.1128/mcb.19.2.1182. PMC 116047. PMID 9891052.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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

• 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. doi:10.1016/j.ygeno.2004.10.010. PMID 15607424.
• Cassidy SB, Dykens E, Williams CA (2000). "Prader-Willi and Angelman syndromes: sister imprinted disorders". Am J Med Genet. 97 (2): 136–46. doi:10.1002/1096-8628(200022)97:2<136::AID-AJMG5>3.0.CO;2-V. PMID 11180221.
• Clayton-Smith J, Laan L (2003). "Angelman syndrome: a review of the clinical and genetic aspects". J Med Genet. 40 (2): 87–95. doi:10.1136/jmg.40.2.87. PMC 1735357. PMID 12566516.
• 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, Beaudet AL (1999). "The spectrum of mutations in UBE3A causing Angelman syndrome". Hum Mol Genet. 8 (1): 129–35. doi:10.1093/hmg/8.1.129. PMID 9887341.
• 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. doi:10.1136/jmg.36.7.554. PMC 1734398. PMID 10424818.
• Williams CA (2005). "Neurological aspects of the Angelman syndrome". Brain Dev. 27 (2): 88–94. doi:10.1016/j.braindev.2003.09.014. PMID 15668046.

External links

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