UBE3A

Ubiquitin protein ligase E3A
250px Structure of an E6AP-UbcH7 complex PDB rendering based on 1c4z.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1C4Z, 1D5F, 1EQX, 2KR1, 4GIZ
Identifiers
Symbols	UBE3A ; ANCR; AS; E6-AP; EPVE6AP; HPVE6A
External IDs	OMIM: 601623 MGI: 105098 HomoloGene: 7988 GeneCards: UBE3A Gene
EC number	6.3.2.19
Gene ontology Molecular function • transcription coactivator activity • ubiquitin-protein transferase activity • protein binding • ligase activity • metal ion binding • ubiquitin protein ligase activity Cellular component • proteasome complex • nucleus • cytoplasm • cytosol Biological process • ovarian follicle development • proteolysis • ubiquitin-dependent protein catabolic process • brain development • positive regulation of phosphatidylinositol 3-kinase signaling • viral process • androgen receptor signaling pathway • positive regulation of protein ubiquitination • sperm entry • regulation of circadian rhythm • protein ubiquitination involved in ubiquitin-dependent protein catabolic process • positive regulation of transcription from RNA polymerase II promoter • protein autoubiquitination • prostate gland growth • protein K48-linked ubiquitination • regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Sources: Amigo / QuickGO
RNA expression pattern
File:PBB GE UBE3A 211285 s at tn.png
File:PBB GE UBE3A 211575 s at tn.png
File:PBB GE UBE3A 213128 s at tn.png
More reference expression data
Orthologs
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

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,
• Lck,
• MCM7,
• MECP2,
• Progesterone receptor,
• TSC2,
• UBE2D1,
• UBE2D2,
• UBE2L3,
• UBQLN1, and
• UBQLN2.

External links

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