atf2
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  • Official Full Name
  • activating transcription factor 2
  • Background
  • ATF2 (activating transcription factor 2) is a member of the ATF/CREB (cAMP response element binding protein) family of basic region leucine zipper proteins. Alternative names for ATF2 include: CREB2, cAMP responsive element binding protein 2, and CRE-BP1. The gene for human ATF2 maps to chromosome 2 (band 2q32). Human ATF2 is 94% homologous with mouse ATF2 and 38% homologous with the Y54E10A.6 protein in C. elegans. Three isoforms of human ATF2 are observed, designated CRE BP-1, -2, and -3, that result from differential splicing of a single transcript. The full length human ATF2 (CRE-BP1) is a protein with MW = 60 kDa, comprised of 487 amino acid residues. ATF2 localizes to the nucleus. Tissues that express the highest levels of ATF2 include brain, lung, liver, and kidney. ATF2 is a transcription factor that regulates expression of genes containing a cAMP response element (CRE; 5'gtgacgt(a/c)(a/g)3'), contained in the promoter region of regulated genes, including TNF-α, TGF-β, cyclin A, E-selectin, DNA polymerase β, and c-Jun. ATF2 also possesses histone acyltransferase activity, with histones H2B and H4 serving as its substrates. As with Fos, Jun, and CREB, ATF2 contains a C-terminal leucine zipper dimerization motif and a C-terminal basic stretch of amino acids that mediate binding to specific DNA sequences. The N-terminal region of ATF2 contains a transactivation domain. Within this transactivation domain is a putative MAPK docking site, similar to the docking site found in other MAPK substrates (designated the DEJL sequence [46KHKHEMTL53]) that mediates interaction of ATF2 with D313 and D316 of p38 α MAPK. Under resting conditions, ATF2 possesses low levels of transcriptional activity, because of an intramolecular inhibitory interaction in which the C-terminal DNA binding domain is bound to the N-terminal transactivation domain. This intramolecular inhibition can be relieved through protein:protein interactions, including ATF2's interaction with normal cell proteins (pRb, the high mobility group HMG, NF-κB, and c-Jun) and ATF2's interaction with viral proteins (adenovirus E1A, hepatitis B virus protein X, or human T-cell leukemia virus type I protein Tax). Intramolecular inhibition is also relieved through phosphorylation of ATF2 at threonine residues 69 and 71. Phosphorylation of these sites is also correlated with enhanced stability of ATF2. These phosphorylation events afford the protein resistance from ubiquitination and subsequent targeting to the 26S proteasome. Phosphorylation of ATF2 at Thr69/71 is catalyzed by several protein kinases. In response to treatment with proinflammatory cytokines, UV irradiation, and B-cell and T-cell receptor engagement, both Thr69 and Thr71 are phosphorylated by JNK and p38 MAPK by a two step mechanism in which the MAPK dissociates from the ATF2 after each phosphorylation event. ATF2 is also observed to be phosphorylated in response to stimuli which do not activate JNK or p38 MAPK, including treatment with insulin, epidermal growth factor, and serum. The sequential phosphorylation of ATF2 at 71 by ERK in the Raf/MEK/ERK cascade, followed by phosphorylation of Thr69 by p38 MAPK in a signaling pathway that includes Ral-RalGDS-Src-p38 MAPK in response to these other stimuli is currently under investigation. Activated ATF2 forms homodimers with other members of the ATF family or heterodimers with members of the c-Jun family of transcription factors. These ATF2 containing dimers bind to the the cAMP response element and with several other proteins including p300/CBP, p50/p65 NF-κB, SMAD3, SMAD4, NFAT family members, and the interferon regulatory factor 1 (IRF1). These ATF-containing protein complexes recruit RNA Pol II, and enhance the transcription of the responsive genes. Activation of ATF2 is observed in cellular responses to various types of stress and apoptotic signals, and is currently under investigation in studies of growth factor independent cell growth, cell cycle progression, differentiation, cytokine production in response to B-cell and T-cell receptor engagement, and inflammation. ATF2 appears to be especially important in cancer. ATF2 has recently been shown to render melanoma cells resistant to irradiation. A peptide that contains that ATF2 sequence corresponding to amino acid residues 50 through 100 (containing both the phosphorylated threonines and possibly a site for interaction with p300) has been shown to enhance sensitivity of melanoma to chemotherapeutic drugs. The interaction of ATF2 with v-Jun (the avian sarcoma virus 17 transforming protein, a viral homolog of the c-Jun protein) is also implicated in the development of fibrosarcoma.
  • Synonyms
  • CRE-BP1; CREB2; HB16; TREB7; CREB-2; activating transcription factor 2 splice variant ATF2-var2; cAMP response element-binding protein CRE-BP1; cAMP responsive element binding protein 2, formerly; cAMP-dependent transcription factor ATF-2; cAMP-responsive element-binding protein 2; cyclic AMP-dependent transcription factor ATF-2; cyclic AMP-responsive element-binding protein 2
Cat.#:ATF2-1432HTag:GST
Source (Host):E. coliSpecies:Human
Product nameRecombinant Human Activating Transcription Factor 2, GST-tagged
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Cat.#:ATF2-26187THTag:
Source (Host):E. coliSpecies:Human
Product nameRecombinant Human ATF2
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Cat.#:ATF2-27043THTag:His
Source (Host):E. coliSpecies:Human
Product nameRecombinant Human ATF2, His-tagged
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Cat.#:ATF2-27044THTag:
Source (Host):E. coliSpecies:Human
Product nameRecombinant Human ATF2
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Cat.#:ATF2-6867HTag:His/GST
Source (Host):Baculovirus-Insect CellsSpecies:Human
Product nameRecombinant Human ATF2, His & GST tagged
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Cat.#:ATF2-692HTag:GST
Source (Host):E. coliSpecies:Human
Product nameRecombinant Human ATF2, GST-tagged
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Cat.#:ATF2-849HTag:His
Source (Host):Sf9 cellsSpecies:Human
Product nameRecombinant Human ATF2 Protein, His-tagged
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Cat.#:ATF2-8502HTag:His
Source (Host):E. coliSpecies:Human
Product nameRecombinant Huamn ATF2, His-tagged
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Cat.#:ATF2-937HTag:GST
Source (Host):Wheat GermSpecies:Human
Product nameRecombinant Human ATF2 protein, GST-tagged
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Cat.#:ATF2-838RTag:His
Source (Host):Mammalian CellsSpecies:Rat
Product nameRecombinant Rat ATF2 Protein
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Cat.#:ATF2-6466CTag:His
Source (Host):Mammalian CellsSpecies:Chicken
Product nameRecombinant Chicken ATF2
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Cat.#:ATF2-518HCLTag:
Source (Host):Baculovirus-Insect CellsSpecies:Human
Product nameRecombinant Human ATF2 cell lysate
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Cat.#:Kit-0111Tag:
Source (Host):Species:
Product nameATF2 (pT69/pT71) Transcription Factor Assay Kit
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Involved Pathway

ATF2 involved in several pathways and played different roles in them. We selected most pathways ATF2 participated on our site, such as AGE/RAGE pathway, ATF-2 transcription factor network, Activated TLR4 signalling, which may be useful for your reference. Also, other proteins which involved in the same pathway with ATF2 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.
Pathway Name
Pathway Related Protein
AGE/RAGE pathway
MAPK14; LGALS3; TIRAP; JUN; EGFR; MMP13; DDOST; ATF2; DIAPH1; AGER
ATF-2 transcription factor network
JUND; HRK; ATF2; DUSP5; CREB1; JUN; DDIT3; RUVBL2; JDP2; DUSP10
Activated TLR4 signalling
APPA; MAP3K8; S100B; CHST13; JUN; AGER; PELI3; RIPK3; TAB1; SIGIRR
Activation of the AP-1 family of transcription factors
MAPK14; ATF2; JUN
Adrenergic signaling in cardiomyocytes
TNNT2A; SLC9A1; PPP2R2D; CACNG2; PIK3CD; ATP1A1A.1; CAMK2B; CAMK2A; SCN5A; CACNA2D2
Alcoholism
HIST2H3A; H2AFB1; HIST1H3H; HIST2H2AC; HIST3H2BB-PS; HIST1H4I; HIST2H2AA4; GM14483; HIST1H2BC; HIST1H3D
Aldosterone synthesis and secretion
PLCB2; SLC14A2; GNAS; CALML3; HSD3B6; CREB3L2; CYP21A2; HSD3B1; CREB3L3; CAMK1
Amphetamine addiction
CREB3L2; ATF2; SLC14A2; GRIN2C; CALM3; CALM2; GRIN3B; SIRT1; ATF4; SLC6A3

Protein Function

ATF2 has several biochemical functions, for example, RNA polymerase II activating transcription factor binding, RNA polymerase II distal enhancer sequence-specific DNA binding, RNA polymerase II regulatory region sequence-specific DNA binding. Some of the functions are cooperated with other proteins, some of the functions could acted by ATF2 itself. We selected most functions ATF2 had, and list some proteins which have the same functions with ATF2. You can find most of the proteins on our site.
Function
Related Protein
Function RNA polymerase II activating transcription factor binding
Related Protein DUSP26; JUN; IFI27; POU1F1; NCOR1; HNF4A; CTNNB1; EGR2; HEY2; TBX20
Function RNA polymerase II distal enhancer sequence-specific DNA binding
Related Protein SFPI1; NFE2L2; NFATC1; ZBTB16; HOXB5; BACH1A; GZF1; CREB1; NR1H4; BACH2
Function RNA polymerase II regulatory region sequence-specific DNA binding
Related Protein PKNOX2; GATA2; MYOD1; CGGBP1; AEBP1; ZNF691; BARHL1B; FOXF1; GFI1AA; ZNF773
Function cAMP response element binding
Related Protein ATF6; CREB3L3A; HMGA2; E4F1; CREB3L3; CREB1; CREB3L1; CREB3L3L; CREB3L2; CREB3
Function cAMP response element binding protein binding
Related Protein CRTC1A; CRTC3; DDIT3; CREM; CRTC2; CRTC1; KCNA3; DAPK3; CREB3; ATF2
Function chromatin binding
Related Protein HMGA1; MAZ; L3MBTL1; SUPT5H; JARID2; BAP1; NCAPD2; MNT; ATF2; CRTC2
Function enhancer sequence-specific DNA binding
Related Protein GATA3; YY1; FOXN4; KLF6A; ATF2; GATA1; XBP1; GATA5; SOX11; MYT1
Function histone acetyltransferase activity
Related Protein KAT2A; EP300; TAF1; NCOA1; KAT5; KAT7A; KAT6A; HAT1; KAT8; CREBBP
Function metal ion binding
Related Protein KSR2; ZNF544; VPS29; ADIPOR1; ESR2B; CHORDC1B; SCRT1B; CASZ1; CCDC76; FHL2B
Function protein binding
Related Protein CDC7; P4HA3; TUB; SERTAD1; PRTFDC1; TARS; HCK; SUGP1; DBNDD2; GLYCTK
Function protein heterodimerization activity
Related Protein TOP2A; PDSS1; MEF2A; GABPB1; MID1; HER11; CABYR; HEXA; TFDP3; DDIT3
Function protein kinase binding
Related Protein HNRNPA0; IL31RA; TTN; GRB7; RICTOR; CNPPD1; GPRC5B; NR4A3; PPME1; RAD9
Function transcription coactivator activity
Related Protein SOX10; TAF12; HAND1; RIPK3; APEX1; JUP; NR2F1; RXRA; BRDT; SOX17
Function transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
Related Protein PAX3; NR5A1; SPI1; SOX17; SNAI2; MYOG; FOXF2A; FOXF1; HNF4A; CEBPB
Function transcription factor activity, RNA polymerase II transcription factor binding
Related Protein GTF2E1; SRF; ATF4; MAMSTR; GATA4; ATF2; YAP1; ZNF296; THRAA; HIF1A
Function transcription factor activity, sequence-specific DNA binding
Related Protein ZNF773; MAP3K7; NKX6-1; FOXO1B; POU3F2; POU4F1; SS18L1; TRIM29; ZNF573; MYNN
Function transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
Related Protein LEF1; NR6A1; TBX20; GRHL1; ELF3; PAX5; RUNX2; NR5A2; OTX2; HEYL
Function transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
Related Protein MAFBB; FOXC1; EAF2; CSRNP3; GATA1; GATA2B; GABPA; BARHL1B; MAFG; NEUROD2

Interacting Protein

ATF2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with ATF2 here. Most of them are supplied by our site. Hope this information will be useful for your research of ATF2.
JUN; FOS; JUNB; HK1

ATF2 Related Articles

Endo, M; Su, L; et al. Activating transcription factor 2 in mesenchymal tumors. HUMAN PATHOLOGY 45:276-284(2014).
Eke, I; Storch, K; et al. Cetuximab Attenuates Its Cytotoxic and Radiosensitizing Potential by Inducing Fibronectin Biosynthesis. CANCER RESEARCH 73:5869-5879(2013).