EIF2S1
Encyclopedia
Eukaryotic translation initiation factor 2 subunit 1 is a protein
that in humans is encoded by the EIF2S1 gene
.
encoded by this gene is the alpha subunit of the translation initiation factor
eIF2
complex which catalyzes the first regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA to 40S
ribosomal
subunits. Binding occurs as a ternary complex of methionyl
-tRNA
, eIF2, and GTP
. eIF2 is composed of 3 nonidentical subunits, alpha (36 kD, this article), beta
(38 kD), and gamma
(52 kD). The rate of formation of the ternary complex is modulated by the phosphorylation
state of eIF2-alpha.
, there is inhibition of neuron protein synthesis due to phosphorylation of Eif2-alpha. There is colocalization between phosphorylated Eif2-alpha and cytosolic
cytochrome c
, which is released from mitochondria in apoptosis
. Phosphorylated Eif2-alpha appeared before cytochrome c release, suggesting that phosphorylation of Eif2-alpha triggers cytochrome c release during apoptotic cell death.
Mice heterozygous for the S51A mutation
become obese and diabetic on a high-fat diet. Glucose intolerance resulted from reduced insulin
secretion, defective transport of proinsulin, and a reduced number of insulin granules in beta cell
s. Hence proper functioning of EIF2S1 appears essential for preventing diet-induced type II diabetes
.
is a selective inhibitor of enzymes that dephosphorylate EIF2-alpha. Salubrinal also blocks EIF2-alpha dephosphorylation by a herpes simplex virus
protein and inhibits viral replication. EIF2-alpha phosphorylation is cytoprotective during endoplasmic reticulum
stress.
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...
that in humans is encoded by the EIF2S1 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...
.
Function
The proteinProtein
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...
encoded by this gene is the alpha subunit of the translation initiation factor
Eukaryotic initiation factor
Eukaryotic initiation factors are proteins involved in the initiation phase of eukaryotic translation. They function in forming a complex with the 40S ribosomal subunit and Met-tRNAi called the 43S preinitation complex , recognizing the 5' cap structure of mRNA and recruiting the 43S PIC to mRNA,...
eIF2
EIF2
Eukaryotic Initiation Factor 2 is a eukaryotic initiation factor. It is required in the initiation of translation. In this fundamental process of life, the ribosome builds proteins according to the information encoded on the mRNA. eIF2 mediates the binding of tRNAmet to the ribosome in a...
complex which catalyzes the first regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA to 40S
40S
40S is the small subunit of eukaryotic ribosomes.It interacts with the internal ribosome entry site of the hepatitis C virus.The following is a list of proteins contained in the 40S ribosome:...
ribosomal
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
subunits. Binding occurs as a ternary complex of methionyl
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
-tRNA
Transfer RNA
Transfer RNA is an adaptor molecule composed of RNA, typically 73 to 93 nucleotides in length, that is used in biology to bridge the three-letter genetic code in messenger RNA with the twenty-letter code of amino acids in proteins. The role of tRNA as an adaptor is best understood by...
, eIF2, and GTP
Guanosine triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...
. eIF2 is composed of 3 nonidentical subunits, alpha (36 kD, this article), beta
EIF2S2
Eukaryotic translation initiation factor 2 subunit 2 is a protein that in humans is encoded by the EIF2S2 gene.-Function:Eukaryotic translation initiation factor 2 functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA and binding to a 40S...
(38 kD), and gamma
EIF2S3
Eukaryotic translation initiation factor 2 subunit 3 is a protein that in humans is encoded by the EIF2S3 gene.-Function:Eukaryotic translation initiation factor 2 functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA and binding to a 40S...
(52 kD). The rate of formation of the ternary complex is modulated by the phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
state of eIF2-alpha.
Clinical significance
After reperfusion following brain ischemiaIschemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
, there is inhibition of neuron protein synthesis due to phosphorylation of Eif2-alpha. There is colocalization between phosphorylated Eif2-alpha and cytosolic
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
cytochrome c
Cytochrome c
The Cytochrome complex, or cyt c is a small heme protein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins. Cytochrome c is a highly soluble protein, unlike other cytochromes, with a solubility of about 100 g/L and is an...
, which is released from mitochondria in apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. Phosphorylated Eif2-alpha appeared before cytochrome c release, suggesting that phosphorylation of Eif2-alpha triggers cytochrome c release during apoptotic cell death.
Mice heterozygous for the S51A 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...
become obese and diabetic on a high-fat diet. Glucose intolerance resulted from reduced insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
secretion, defective transport of proinsulin, and a reduced number of insulin granules in beta cell
Beta cell
Beta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. They make up 65-80% of the cells in the islets.-Function:...
s. Hence proper functioning of EIF2S1 appears essential for preventing diet-induced type II diabetes
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
.
Dephosphorylation inhibitors
SalubrinalSalubrinal
Salubrinal is a drug which acts as a specific inhibitor of eIF2α phosphatase enzymes and is primarily used experimentally, to study stress responses in eukaryotic cells associated with the action of eIF2...
is a selective inhibitor of enzymes that dephosphorylate EIF2-alpha. Salubrinal also blocks EIF2-alpha dephosphorylation by a herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
protein and inhibits viral replication. EIF2-alpha phosphorylation is cytoprotective during endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
stress.