ATF2
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Official Full Name
activating transcription factor 2 -
Overview
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
Recombinant Proteins
- Human
- Chicken
- Rat
- E.coli
- Mammalian Cells
- Insect Cells
- Sf9 Cells
- Wheat Germ
- In Vitro Cell Free System
- HEK293
- GST
- Non
- His
- GST&His
- His&SUMO
- Avi&Fc&His
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 | DDOST,CHUK,LGALS3,MMP13,JUN,AGER,TIRAP,JAK2,MAPK14,EGFR |
| Aldosterone synthesis and secretion | NPR1,PRKCG,ATF4,ADCY9,CACNA1H,ORAI1,HSD3B4,KCNK9,PRKACG,PRKACB |
| Adrenergic signaling in cardiomyocytes | PPP1R1A,PPP2CB,GNAI2B,PRKACAA,ADRA1BB,ATP2B2,SCN1BA,PPP2R5EB,ATP1B2A,CAMK2G1 |
| ATF-2 transcription factor network | DUSP10,GADD45A,POU2F1,CREB1,KCNA3,HRK,MAPK14,DDIT3,JUN,JUNB |
| Activation of the AP-1 family of transcription factors | JUN,MAPK14 |
| Alcoholism | GNB5,HIST1H2AC,DRD2,HIST1H4D,HIST1H3D,GNAO1,HIST4H4,HDAC2,H3F3A,CREB5 |
| Activated TLR4 signalling | MAPKAPK2B,TLR6,APPB,JUN,S100B,DUSP3B,CHST13,PELI3,SAA1,ALCAMB |
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 |
|---|---|
| transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding | MYOCD,FOXF2,ZGLP1,CSRNP1,MYF5,MYF6,CTCF,NKX2-5,CREB3L3,BARX1 |
| RNA polymerase II distal enhancer sequence-specific DNA binding | MSC,BACH2,GATA2,TAL1,NONO,H2AFZ,HNRNPC,MEOX2,T,PAX4 |
| histone acetyltransferase activity | KAT6A,NCOA3,TAF1,HAT1,KAT2B,KAT2A,KAT8,KAT5,CREBBP,KAT6B |
| chromatin binding | KDM6B,LMO2,HMGB2,SIN3A,WDHD1,CHD7,ATOH1A,HDGF2,CDC45,SMC1A |
| protein binding | LIG3,CDX4,LSM4,ELOVL6,HSPG2,ARHGAP4,PRKCE,RAPGEF4,OPRM1,C9orf86 |
| cAMP response element binding protein binding | CRTC2,KCNA3,CREB3,CRTC1A,CRTC1,CRTC3,DDIT3,CREM,DAPK3 |
| enhancer sequence-specific DNA binding | KLF6A,ISL1,TBX19,MYT1,YY1,LMO4,XBP1,GATA3,HMGB2,GATA1 |
| cAMP response element binding | CREB3L3,CREB3L3L,ATF6,HMGA2,CREB1,E4F1,ATF6B,CREB3L2,CREB3,CREB3L3A |
| RNA polymerase II activating transcription factor binding | NCOR1,EGR2,TBX3,CREBBP,MAD2L2,LMO2,IFI27,RB1,NHLH2,LDB1 |
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
Resources
Research Area
Transcription Factors in the Akt PathwayCancer Stem Cell Transcription Factors
Neural Stem Cell Transcription Factors
TGF-beta Family Receptor
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References
- 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).
