Ubiquitin-protein ligase E3A (UBE3A) also known as E6AP ubiquitin-protein ligase (E6AP) is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
that in humans is encoded by the ''UBE3A''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. This enzyme is involved in targeting
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s 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
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...
to proteins that should be degraded. Cellular structures called
proteasome
Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases.
Proteasomes are part of a major mechanism by w ...
s recognize and digest proteins tagged with ubiquitin.
Both copies of the UBE3A gene are active in most of the body's tissues. In most
neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s, however, only the copy inherited from a person's mother (the maternal copy) is normally active; this is known as paternal
imprinting. Recent evidence shows that at least some
glial cells and neurons may exhibit biallelic expression of UBE3A. Further work is thus needed to delineate a complete map of UBE3A imprinting in humans and model organisms such as mice.
Silencing of Ube3a on the paternal allele is thought to occur through the
Ube3a-ATS part of a
lincRNA called "LNCAT",
(Large Non-Coding Antisense Transcript).
The UBE3A gene is located on the long (q) arm of
chromosome 15
Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 102 million base pairs (the building material of DNA) and represents between 3% and 3.5% of the total DN ...
between positions 11 and 13, from
base pair
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
23,133,488 to base pair 23,235,220.
Clinical significance
Mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s within the UBE3A gene are responsible for some cases of
Angelman syndrome
Angelman syndrome or Angelman's syndrome (AS) is a genetic disorder that mainly affects the nervous system. Symptoms include a small head and a specific facial appearance, severe intellectual disability, developmental disability, limited to no f ...
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
Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 102 million base pairs (the building material of DNA) and represents between 3% and 3.5% of the total DN ...
can also cause Angelman syndrome. These chromosomal changes include deletions, rearrangements (
translocations
In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertsonian translocation. Reciprocal translo ...
) 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
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
*
BLK,
*
Lck
Lck (or lymphocyte-specific protein tyrosine kinase) is a 56 kDa protein that is found inside specialized cells of the immune system called lymphocytes. The Lck is a member of Src kinase family (SFK), it is important for the activation of the T ...
,
[
* ]MCM7
DNA replication licensing factor MCM7 is a protein that in humans is encoded by the ''MCM7'' gene.
Function
The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the in ...
,MECP2
''MECP2'' (methyl CpG binding protein 2) is a gene that encodes the protein MECP2. MECP2 appears to be essential for the normal function of nerve cells. The protein seems to be particularly important for mature nerve cells, where it is present in ...
,TSC2
Tuberous Sclerosis Complex 2 (TSC2), also known as Tuberin, is a protein that in humans is encoded by the ''TSC2'' gene.
Function
Mutations in this gene lead to tuberous sclerosis. Its gene product is believed to be a tumor suppressor and is a ...
,UBE2D1
Ubiquitin-conjugating enzyme E2 D1 is a protein that in humans is encoded by the ''UBE2D1'' gene.
Function
The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degrad ...
,UBE2D2
Ubiquitin-conjugating enzyme E2 D2 is a protein that in humans is encoded by the ''UBE2D2'' gene.
Function
The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degrad ...
,UBE2L3
Ubiquitin-conjugating enzyme E2 L3 (UBE2L3), also called UBCH7, is a protein that in humans is encoded by the ''UBE2L3'' gene. As an E2 enzyme, UBE2L3 participates in ubiquitination to target proteins for degradation. The role of UBE2L3 in the ubi ...
,UBQLN2
Ubiquilin-2 is a protein that in humans is encoded by the ''UBQLN2'' gene.
Function
This gene encodes a ubiquitin-like protein ( ubiquilin) that shares high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain ...
.[
]
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Angelman syndrome
OMIM entries on Angelman syndrome
GeneCard
{{DEFAULTSORT:Ube3a