IKBKAP
Encyclopedia
IKBKAP is a human
gene
that provides instructions to make the IKAP protein, which is found in a variety of cells throughout the body, including brain cell
s. Although the exact function of the IKAP protein is not clearly understood, it probably plays a role in transcription
, which is the process of making a blueprint of a gene for protein
production. Researchers have identified the IKAP protein as part of a six-protein complex (called the holo-elongator complex) that interacts with enzyme
s necessary for transcription. The IKAP protein probably performs other functions in the cell as well, such as responding to stress. Its homolog in fly (D-elp1) has RNA-dependent RNA polymerase
activity and is involved in RNA interference
.
The IKBKAP gene is located on the long (q) arm of chromosome 9
at position 31, from base pair
108,709,355 to base pair 108,775,950.
is caused by mutation
s in the IKBKAP gene. Nearly all individuals with familial dysautonomia have two copies of the same mutation in each cell, which causes part of the IKBKAP gene to be skipped during transcription
. (This alteration is often called exon skipping.) This skipping mutation results in a decreased amount of IKAP protein in their cells. This mutation, however, behaves inconsistently. As a result, some cells produce near normal amounts of IKAP protein, and other cells (particularly cells in the nervous system
) have very little IKAP protein.
In a small number of reported familial dysautonomia cases, researchers have identified other mutations that cause a change in amino acid
s (the building blocks of protein
s). In these cases, arginine
is replaced by proline
at position 696 in the IKAP protein's chain of amino acids (also written as Arg696Pro), or proline
is replaced by leucine
at position 914 (also written as Pro914Leu). People with one of these improper amino acid substitutions also have the skipping mutation. Together, these mutations cause the resulting IKAP protein to malfunction.
It is unclear how mutations in the IKBKAP gene lead to the signs and symptoms of familial dysautonomia. Critical activities in brain and nerve cells are probably disrupted by reduced amounts or the absence of functional IKAP protein.
Human
Humans are the only living species in the Homo genus...
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...
that provides instructions to make the IKAP protein, which is found in a variety of cells throughout the body, including brain cell
Brain Cell
Brain Cell is a mail art project begun by Ryosuke Cohen in June 1985. The project is basically a networked art project where individual artists create their own 30x42cm work of art with stamps, drawings, stickers and so forth. This is sent to Cohen, who prints each cell - 150 copies each - with a...
s. Although the exact function of the IKAP protein is not clearly understood, it probably plays a role in transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
, which is the process of making a blueprint of a gene for 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...
production. Researchers have identified the IKAP protein as part of a six-protein complex (called the holo-elongator complex) that interacts with enzyme
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...
s necessary for transcription. The IKAP protein probably performs other functions in the cell as well, such as responding to stress. Its homolog in fly (D-elp1) has RNA-dependent RNA polymerase
RNA-dependent RNA polymerase
RNA-dependent RNA polymerase , , or RNA replicase, is an enzyme that catalyzes the replication of RNA from an RNA template...
activity and is involved in RNA interference
RNA interference
RNA interference is a process within living cells that moderates the activity of their genes. Historically, it was known by other names, including co-suppression, post transcriptional gene silencing , and quelling. Only after these apparently unrelated processes were fully understood did it become...
.
The IKBKAP gene is located on the long (q) arm of chromosome 9
Chromosome 9 (human)
125px|rightChromosome 9 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome, as they normally do with all chromosomes...
at position 31, 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...
108,709,355 to base pair 108,775,950.
Related conditions
Familial dysautonomiaFamilial dysautonomia
Familial dysautonomia is a disorder of the autonomic nervous system which affects the development and survival of sensory, sympathetic and some parasympathetic neurons in the autonomic and sensory nervous system resulting in variable symptoms including: insensitivity to pain, inability to produce...
is caused by mutation
Mutation
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 in the IKBKAP gene. Nearly all individuals with familial dysautonomia have two copies of the same mutation in each cell, which causes part of the IKBKAP gene to be skipped during transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
. (This alteration is often called exon skipping.) This skipping mutation results in a decreased amount of IKAP protein in their cells. This mutation, however, behaves inconsistently. As a result, some cells produce near normal amounts of IKAP protein, and other cells (particularly cells in the nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
) have very little IKAP protein.
In a small number of reported familial dysautonomia cases, researchers have identified other mutations that cause a change in amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s (the building blocks of 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). In these cases, arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
is replaced by proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
at position 696 in the IKAP protein's chain of amino acids (also written as Arg696Pro), or proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
is replaced by leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
at position 914 (also written as Pro914Leu). People with one of these improper amino acid substitutions also have the skipping mutation. Together, these mutations cause the resulting IKAP protein to malfunction.
It is unclear how mutations in the IKBKAP gene lead to the signs and symptoms of familial dysautonomia. Critical activities in brain and nerve cells are probably disrupted by reduced amounts or the absence of functional IKAP protein.