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Activating transcription factor 2, also known as ATF2, is a
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 ...
that, in humans, is encoded by the ''ATF2''
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 ba ...
.


Function

This gene encodes a
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
that is a member of the
leucine zipper A leucine zipper (or leucine scissors) is a common three-dimensional structural motif in proteins. They were first described by Landschulz and collaborators in 1988 when they found that an enhancer binding protein had a very characteristic 30-amin ...
family of DNA-binding proteins. This protein binds to the cAMP-responsive element (CRE), an octameric palindrome. The protein forms a homodimer or heterodimer with
c-Jun Transcription factor Jun is a protein that in humans is encoded by the ''JUN'' gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only lat ...
. The protein is also a
histone acetyltransferase Histone acetyltransferases (HATs) are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl-CoA to form ε-''N''-acetyllysine. DNA is wrapped around histones, and, by transferring an ...
(HAT) that specifically acetylates histones H2B and H4 in vitro; thus, it may represent a class of sequence-specific factors that activate transcription by direct effects on
chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
components. Additional transcript variants have been identified but their biological validity has not been determined. The gene atf2 is located at human chromosome 2q32. The protein ATF-2 has 505 amino acids. Studies in mice indicate a role for ATF-2 in the development of nervous system and the skeleton. ATF-2 is normally activated in response to signals that converge on stress-activated protein kinases p38 and
JNK c-Jun N-terminal kinases (JNKs), 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 ar ...
. ATF-2 phosphorylation in response to treatment of cells with tumor promoter
phorbol Phorbol is a natural, plant-derived organic compound. It is a member of the tigliane family of diterpenes. Phorbol was first isolated in 1934 as the hydrolysis product of croton oil, which is derived from the seeds of the purging croton, '' Croto ...
ester has been demonstrated. Several studies implicate abnormal activation of ATF-2 in growth and progression of mammalian skin tumors. ATF-2 may mediate oncogenesis caused by mutant
Ras protein Ras, from "Rat sarcoma virus", is a family of related proteins that are expressed in all animal cell lineages and organs. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals ...
and regulate maintenance of the aggressive cancer phenotype of some types of epithelial cells. ATF2 has also been shown to be
phosphorylated In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, whi ...
at its
C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
(serine 472 and 480 in mouse; serine 490 and 498 in human) by ATM upon double-stranded breaks. Mice with mutations of these two serines are sensitive to irradiation and easier to tumorigenesis under p53 knockout background.


Interactions

Activating transcription factor 2 has been shown to
interact Advocates for Informed Choice, 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 traits. The organizati ...
with *
C-jun Transcription factor Jun is a protein that in humans is encoded by the ''JUN'' gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only lat ...
, *
Casein kinase 2, alpha 1 Casein kinase II subunit alpha is an enzyme that in humans is encoded by the ''CSNK2A1'' gene. Casein kinase II is a Serine/threonine-specific protein kinase, serine/threonine protein kinase that Phosphorylation, phosphorylates acidic proteins s ...
, *
CREB binding protein Cyclic adenosine monophosphate Response Element Binding protein Binding Protein (CREB-binding protein), also known as CREBBP or CBP or KAT3A, is a coactivator encoded by the ''CREBBP'' gene in humans, located on chromosome 16p13.3. CBP has intrin ...
, *
CSNK2A2 Casein kinase II subunit alpha' is an enzyme that in humans is encoded by the ''CSNK2A2'' gene. Interactions CSNK2A2 has been shown to interact with over 160 different substrates. CSNK2A2 has been shown to interact with: * Activating transcri ...
, * JDP2, *
MAPK14 Mitogen-activated protein kinase 14, also called p38-α, is an enzyme that in humans is encoded by the ''MAPK14'' gene. MAPK14 encodes p38α mitogen-activated protein kinase (MAPK) which is the prototypic member of the p38 MAPK family. p38 MAPKs ...
, * MAPK8, *
Mothers against decapentaplegic homolog 3 Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene. SMAD3 is a member of the SMAD family of proteins. It acts as a mediator of the signals initiated by t ...
*
NCOA6 Nuclear receptor coactivator 6 is a protein that in humans is encoded by the ''NCOA6'' gene. Function The protein encoded by this gene is a transcriptional coactivator that can interact with nuclear hormone receptors to enhance their transcrip ...
, *
RUVBL2 RuvB-like 2 (E. coli), also known as RUVBL2, is a human gene coding for a protein belonging to the AAA+ family of proteins. Function This gene encodes the second human homologue of the bacterial RuvB gene. Bacterial RuvB protein is a DNA helic ...
, *
UBE2I SUMO-conjugating enzyme UBC9 is an enzyme that in humans is encoded by the ''UBE2I'' gene. It is also sometimes referred to as "ubiquitin conjugating enzyme E2I" or "ubiquitin carrier protein 9", even though these names do not accurately describe ...
.


See also

*
Activating transcription factor Activating transcription factor, ATF, is a group of bZIP transcription factors, which act as homodimers or heterodimers with a range of other bZIP factors. First, they have been described as members of the CREB/ATF family, whereas it turned out la ...


References


External links

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Further reading

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External links


PDBe-KB
provides an overview of all the structure information available in the PDB for Human Cyclic AMP-dependent transcription factor ATF-2 {{DEFAULTSORT:Activating Transcription Factor 2 Transcription factors Moonlighting proteins