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 ...

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 b ...

. 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, res ...

s for degradation within

cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

. 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 whi ...

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 ...

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 Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myel ...

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 UBE3A-ATS/Ube3a-ATS (human/mouse), otherwise known as ubiquitin ligase E3A-ATS, is the name for the antisense DNA strand that is transcribed as part of a larger transcript called ''LNCAT'' (large non-coding antisense transcript) at the ''Ube3a'' ...

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 ...

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 D ...

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, m ...

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 ...

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

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, doing business as, 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 trai ...

with: * BLK, * Lck, *

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 ...

, *

Progesterone receptor The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone. In humans, PR is encoded by a single ''PGR'' gene resid ...

, *

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, * UBE2L3, *

UBQLN1 Ubiquilin-1 is a protein that in humans is encoded by the ''UBQLN1'' gene. Ubiquilins contain two domains, an N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and u ...

, and *

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

External links

GeneReviews/NCBI/NIH/UW entry on Angelman syndrome

OMIM entries on Angelman syndrome

GeneCard
{{DEFAULTSORT:Ube3a

Clinical significance

Interactions

References

Further reading

External links