ATF4
Encyclopedia
Activating transcription factor 4 (tax-responsive enhancer element B67), also known as ATF4, is a protein
that in humans is encoded by the ATF4 gene
.
that was originally identified as a widely expressed mammalian DNA binding protein that could bind a tax-responsive enhancer element in the LTR of HTLV-1. The encoded protein was also isolated and characterized as the cAMP-response element binding protein 2 (CREB-2
). The protein encoded by this gene belongs to a family of DNA-binding proteins that includes the AP-1
family of transcription factors, cAMP-response element binding proteins (CREB
s) and CREB-like proteins. These transcription factors share a leucine zipper
region that is involved in protein–protein interactions, located C-terminal to a stretch of basic amino acids that functions as a DNA-binding domain
. Two alternative transcripts encoding the same protein have been described. Two pseudogene
s are located on the X chromosome at q28 in a region containing a large inverted duplication.
ATF4 transcription factor is also known to play role in osteoblast
differentiation along with RUNX2
and osterix. Terminal osteoblast differentiation, represented by matrix mineralization, is significantly inhibited by the inactivation of JNK
. JNK inactivation downregulates expression of ATF-4 and, subsequently, matrix mineralization.
with POLR2C
, TRIB3
and GABBR1
.
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 ATF4 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
This gene encodes a transcription factorTranscription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
that was originally identified as a widely expressed mammalian DNA binding protein that could bind a tax-responsive enhancer element in the LTR of HTLV-1. The encoded protein was also isolated and characterized as the cAMP-response element binding protein 2 (CREB-2
Activating transcription factor 2
Activating transcription factor 2, also known as ATF2, is a protein that, in humans, is encoded by the ATF2 gene.-Function:This gene encodes a transcription factor that is a member of the leucine zipper family of DNA-binding proteins. This protein binds to the cAMP-responsive element , an octameric...
). The protein encoded by this gene belongs to a family of DNA-binding proteins that includes the AP-1
AP-1 (transcription factor)
In the field of molecular biology, the activator protein 1 is a transcription factor which is a heterodimeric protein composed of proteins belonging to the c-Fos, c-Jun, ATF and JDP families. It regulates gene expression in response to a variety of stimuli, including cytokines, growth factors,...
family of transcription factors, cAMP-response element binding proteins (CREB
CREB
CREB is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements , thereby increasing or decreasing the transcription of the downstream genes....
s) and CREB-like proteins. These transcription factors share a leucine zipper
Leucine zipper
A leucine zipper, aka leucine scissors, is a common three-dimensional structural motif in proteins. These motifs are usually found as part of a DNA-binding domain in various transcription factors, and are therefore involved in regulating gene expression...
region that is involved in protein–protein interactions, located C-terminal to a stretch of basic amino acids that functions as a DNA-binding domain
DNA-binding domain
A DNA-binding domain is an independently folded protein domain that contains at least one motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence or have a general affinity to DNA...
. Two alternative transcripts encoding the same protein have been described. Two pseudogene
Pseudogene
Pseudogenes are dysfunctional relatives of known genes that have lost their protein-coding ability or are otherwise no longer expressed in the cell...
s are located on the X chromosome at q28 in a region containing a large inverted duplication.
ATF4 transcription factor is also known to play role in osteoblast
Osteoblast
Osteoblasts are mononucleate cells that are responsible for bone formation; in essence, osteoblasts are specialized fibroblasts that in addition to fibroblastic products, express bone sialoprotein and osteocalcin.Osteoblasts produce a matrix of osteoid, which is composed mainly of Type I collagen...
differentiation along with RUNX2
Runx2
Runt-related transcription factor 2 also known as core-binding factor subunit alpha-1 is a protein that in humans is encoded by the RUNX2 gene RUNX2 is a key transcription factor associated with osteoblast differentiation....
and osterix. Terminal osteoblast differentiation, represented by matrix mineralization, is significantly inhibited by the inactivation of JNK
C-Jun N-terminal kinases
c-Jun N-terminal kinases , were originally identified as kinases that bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. They belong to the mitogen-activated protein kinase family, and are responsive to stress stimuli, such as cytokines, ultraviolet...
. JNK inactivation downregulates expression of ATF-4 and, subsequently, matrix mineralization.
Interactions
ATF4 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 POLR2C
POLR2C
DNA-directed RNA polymerase II subunit RPB3 is an enzyme that in humans is encoded by the POLR2C gene.-Interactions:POLR2C has been shown to interact with TAF15, POLR2F, POLR2G, POLR2H, POLR2J, POLR2K, POLR2L, ATF4, CCHCR1, POLR2A, POLR2B, POLR2E and Myogenin.-Further reading:...
, TRIB3
TRIB3
Tribbles homolog 3 is a protein that in humans is encoded by the TRIB3 gene.-Interactions:TRIB3 has been shown to interact with CSNK2B, TIAF1, RELA, MCM3AP, ATF5, Granulin, ATF4, AKT1, Fibronectin and SIAH1.-Further reading:...
and GABBR1
GABBR1
Gamma-aminobutyric acid B receptor, 1 , is a G-protein coupled receptor subunit encoded by the GABBR1 gene.-Interactions:GABBR1 has been shown to interact with ATF4 and GABBR2.-Further reading:...
.