UBE3A
Encyclopedia
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 protein
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 3A attaches a small protein called ubiquitin
to proteins that should be degraded. Cellular structures called proteasome
s 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. 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.
s within the UBE3A gene are responsible for some cases of Angelman 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 due to paternal imprinting, 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 Angelman syndrome.
Abnormalities involving the region of chromosome 15
that contains the UBE3A gene 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.
with UBQLN1
, UBQLN2
, UBE2D1
, TSC2
, BLK
, Lck
, MCM7
, Progesterone receptor
, UBE2L3
and UBE2D2
.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that in humans is encoded by the UBE3A gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. This enzyme is involved in targeting protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s for degradation within cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
. Protein degradation is a normal process that removes damaged or unnecessary proteins and helps maintain the normal functions of cells.
Ubiquitin protein ligase 3A attaches a small protein called ubiquitin
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...
to proteins that should be degraded. Cellular structures called proteasome
Proteasome
Proteasomes are very large protein complexes inside all eukaryotes and archaea, and in some bacteria. In eukaryotes, they are located in the nucleus and the cytoplasm. The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks...
s 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
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, however, only the copy inherited from a person's mother (the maternal copy) is normally active. The UBE3A gene is located on the long (q) arm of chromosome 15 between positions 11 and 13, from base pair
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
23,133,488 to base pair 23,235,220.
Clinical significance
MutationMutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s within the UBE3A gene are responsible for some cases of Angelman syndrome
Angelman syndrome
Angelman syndrome is a neuro-genetic disorder characterized by intellectual and developmental delay, sleep disturbance, seizures, jerky movements , frequent laughter or smiling, and usually a happy demeanor....
. 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 due to paternal imprinting, 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 Angelman syndrome.
Abnormalities involving the region of chromosome 15
Chromosome 15 (human)
right|frame|Human chromosome 15Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 106 million base pairs and represents between 3% and 3.5% of the total DNA in cells.Identifying genes on each chromosome is an...
that contains the UBE3A gene also cause Angelman syndrome. These chromosomal changes include deletions, rearrangements (translocations
Chromosomal translocation
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
) 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 interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with UBQLN1
UBQLN1
Ubiquilin-1 is a protein that in humans is encoded by the UBQLN1 gene.Ubiquilins contain a N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain...
, UBQLN2
UBQLN2
Ubiquilin-2 is a protein that in humans is encoded by the UBQLN2 gene.- Function :This gene encodes a ubiquitin-like protein that shares high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain a N-terminal ubiquitin-like domain and a C-terminal...
, UBE2D1
UBE2D1
Ubiquitin-conjugating enzyme E2 D1 is a protein that in humans is encoded by the UBE2D1 gene.-Interactions:UBE2D1 has been shown to interact with BARD1, UBE3A and BRCA1.-Further reading:...
, TSC2
TSC2
Tuberous sclerosis protein 2, also known as TSC2 and Tuberin, is a human protein and gene.-Interactions:TSC2 has been shown to interact with FOXO1, GSK3B, Peptidylglycine alpha-amidating monooxygenase, RAP1A, MAPK1, AKT1, AXIN1, TSC1, PTK2, Protein kinase, AMP-activated, alpha 1, YWHAZ, RPS6KA1,...
, BLK
BLK (gene)
Tyrosine-protein kinase BLK also known as B lymphocyte kinase is an enzyme that in humans is encoded by the BLK gene.-Interactions:The tyrosine-protein kinase BLK has been shown to interact with UBE3A.-Further reading:...
, Lck
Lck
Lck is a protein that is found inside specialized cells of the immune system called lymphocytes. Lck is a tyrosine kinase, which phosphorylates tyrosine residues of certain proteins involved in the intracellular signaling pathways of these lymphocytes...
, MCM7
MCM7
DNA replication licensing factor MCM7 is a protein that in humans is encoded by the MCM7 gene.-Interactions:MCM7 has been shown to interact with Replication protein A1, ORC3L, Retinoblastoma protein, MCM5, MCM6, ORC1L, ORC2L, ORC5L, MCM4, MCM3, CDC6, MNAT1, DBF4, MCM2, UBE3A, CDC45-related protein...
, Progesterone receptor
Progesterone receptor
The progesterone receptor also known as NR3C3 , is an intracellular steroid receptor that specifically binds progesterone...
, UBE2L3
UBE2L3
Ubiquitin-conjugating enzyme E2 L3 is a protein that in humans is encoded by the UBE2L3 gene.-Interactions:UBE2L3 has been shown to interact with UBOX5, ARIH1, Cbl gene, UBE3A and NEDD4.-Further reading:...
and UBE2D2
UBE2D2
Ubiquitin-conjugating enzyme E2 D2 is a protein that in humans is encoded by the UBE2D2 gene.-Interactions:UBE2D2 has been shown to interact with PJA1, Baculoviral IAP repeat-containing protein 3, PJA2, UBE3A and NEDD4.-Further reading:...
.