ATF4

Aktivacijski transkripcijski faktor 4 (taks- pojačivač odgovora B67)', također poznat kao ATF4, je protein koji je kod ljudi kodiran genom ATF4 sa hromosoma 22.

ATF4
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 1CI6
Identifikatori
Aliasi	ATF4
Vanjski ID-jevi	OMIM: 604064 MGI: 88096 HomoloGene: 1266 GeneCards: ATF4
Lokacija gena (čovjek) Hrom. Hromosom 22 (čovjek) Bend 22q13.1 Početak 39,519,695 bp Kraj 39,522,683 bp
Lokacija gena (miš) Hrom. Hromosom 15 (miš) Bend 15 E1|15 37.85 cM Početak 80,139,385 bp Kraj 80,141,742 bp
Ontologija gena Molekularna funkcija • vezivanje sa DNK • sequence-specific DNA binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • transcription factor binding • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • core promoter sequence-specific DNA binding • protein C-terminus binding • GO:0001948, GO:0016582 vezivanje za proteine • leucine zipper domain binding • protein heterodimerization activity • protein kinase binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • RNA polymerase II transcription regulatory region sequence-specific DNA binding Ćelijska komponenta • citoplazma • ATF1-ATF4 transcription factor complex • ATF4-CREB1 transcription factor complex • transcription regulator complex • dendrite membrane • jedro • Lewy body core • nuclear periphery • membrana • ćelijska membrana • nukleoplazma • centar organizacije mikrotubula • neuron projection • citoskelet • CHOP-ATF4 complex • centrosom • GO:0009327 makromolekulani kompleks • RNA polymerase II transcription regulator complex Biološki proces • gamma-aminobutyric acid signaling pathway • Glukoneogeneza • GO:0009373 regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress • GO:0044324, GO:0003256, GO:1901213, GO:0046019, GO:0046020, GO:1900094, GO:0061216, GO:0060994, GO:1902064, GO:0003258, GO:0072212 regulation of transcription by RNA polymerase II • negative regulation of oxidative stress-induced neuron death • cellular response to amino acid starvation • mRNA transcription by RNA polymerase II • circadian regulation of gene expression • response to endoplasmic reticulum stress • PERK-mediated unfolded protein response • response to manganese-induced endoplasmic reticulum stress • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated • positive regulation of neuron apoptotic process • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress • GO:1901313 positive regulation of gene expression • positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress • Jednodnevni biološki ritam • negative regulation of potassium ion transport • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II • positive regulation of transcription from RNA polymerase II promoter in response to arsenic-containing substance • cellular response to glucose starvation • negative regulation of translational initiation in response to stress • rhythmic process • cellular response to UV • positive regulation of transcription from RNA polymerase II promoter in response to stress • cellular amino acid metabolic process • transcription by RNA polymerase II • transcription, DNA-templated • positive regulation of apoptotic process • positive regulation of vascular endothelial growth factor production • positive regulation of transcription by RNA polymerase I • cellular response to dopamine • response to toxic substance • neuron differentiation • cellular response to oxygen-glucose deprivation • positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway • cellular calcium ion homeostasis • positive regulation of biomineral tissue development • negative regulation of cold-induced thermogenesis • positive regulation of vascular associated smooth muscle cell apoptotic process • positive regulation of sodium-dependent phosphate transport Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	468	11911
Ensembl	ENSG00000128272	ENSMUSG00000042406
UniProt	P18848	Q06507
RefSeq (mRNK)	NM_182810 NM_001675	NM_001287180 NM_009716
RefSeq (bjelančevina)	NP_001666 NP_877962	NP_001274109 NP_033846
Lokacija (UCSC)	Chr 22: 39.52 – 39.52 Mb	Chr 15: 80.14 – 80.14 Mb
PubMed pretraga
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Aminokiselinska sekvenca

Dužina polipeptidnojg lanca je 351 aminokiselina, a molekulska težina 38.590 Da.

• C: Cistein
• D: Asparaginska kiselina
• E: Glutaminska kiselina
• F: Fenilalanin
• G: Glicin
• H: Histidin
• I: Izoleucin
• K: Lizin
• L: Leucin
• M: Metionin
• N: Asparagin
• P: Prolin
• Q: Glutamin
• R: Arginin
• S: Serin
• T: Treonin
• V: Valin
• W: Triptofan
• Y: Tirozin

10		20		30		40		50
MTEMSFLSSE		VLVGDLMSPF		DQSGLGAEES		LGLLDDYLEV		AKHFKPHGFS
SDKAKAGSSE		WLAVDGLVSP		SNNSKEDAFS		GTDWMLEKMD		LKEFDLDALL
GIDDLETMPD		DLLTTLDDTC		DLFAPLVQET		NKQPPQTVNP		IGHLPESLTK
PDQVAPFTFL		QPLPLSPGVL		SSTPDHSFSL		ELGSEVDITE		GDRKPDYTAY
VAMIPQCIKE		EDTPSDNDSG		ICMSPESYLG		SPQHSPSTRG		SPNRSLPSPG
VLCGSARPKP		YDPPGEKMVA		AKVKGEKLDK		KLKKMEQNKT		AATRYRQKKR
AEQEALTGEC		KELEKKNEAL		KERADSLAKE		IQYLKDLIEE		VRKARGKKRV
P

Funkcija

Ovaj gen kodira transkripcijski faktor, prvobitno identificiran kao široko eksprimirani DNK vezujući protein sisara koji bi mogao vezati pojačivač reakcije na taksov e u LTR HTLV-1. Kodirani protein je takođe izolovan i okarakterisan kao cAMP-odgovorn i element koji vezuje protein 2 (CREB-2). Protein kodiran ovim genom pripada porodici proteina koji se vezuju za DNK koja uključuje porodicu transkripcionih faktora AP-1, cAMP-odgovora elementa vezujućih proteina (CREB) i proteina sličnih CREB-u. Ovi transkripcijski faktori dijele regiju leucinskog zatvarača koja je uključena u interakcije protein-protein, na C-terminalu dijela osnovnih aminokiselina koji funkcionira kao DNK-vezujući domen. Opisana su dva alternativna transkripta koje kodiraju isti protein. Dva pseudogena nalaze se na X hromosomu, regija na q28 koja sadrži veliku obrnutu duplikaciju.

Također je poznato da transkripcijski faktor ATF4 ima ulogu u diferencijaciji osteoblasta, zajedno sa RUNX2 i osteriksom. Terminalna diferencijacija osteoblasta, predstavljena mineralizacijom matriksa, značajno je inhibirana inaktivacijom JNK. Inaktivacija JNK, posljedično smanjuje ekspresiju ATF-4 i mineralizaciju matriksa. Protein IMPACT reguliše ATF4 u C. elegans kako bi produžio životni vijek.

Translacija

Translacija ATF4 ovisi o izvodnom otvorenom okviru čitanje koji se nalazi u 5' UTR-u. Lokacija drugog ORF-a, prikladno nazvanog uORF2, preklapa se sa okvirom otvorenog čitanja ATF4. U normalnim uslovima, uORF1 se prevodi, a zatim se translacija uORF2 dešava tek nakon što se ponovo dobije eIF2-TC. Translacija uORF2 zahtijeva da ribosomi prođu pored "ATF4" ORF, čiji se početni kodon nalazi unutar uORF2. To dovodi do njegove represije. Međutim, tokom stresnih uslova, ribosomski 40S će zaobići uORF2, zbog smanjenja koncentracije eIF2-TC, što znači da nijkedan ribosom ne dobije na vrijeme uputu da prevede uORF2. Umjesto toga, translatira se "ATF4".

Također pogledajte

• Aktivirajući transkripcijski faktor

Dopunska literatura

• Rutkowski DT, Kaufman RJ (april 2003). "All roads lead to ATF4". Developmental Cell. 4 (4): 442–4. doi:10.1016/S1534-5807(03)00100-X. PMID 12689582.
• Nishizawa M, Nagata S (mart 1992). "cDNA clones encoding leucine-zipper proteins which interact with G-CSF gene promoter element 1-binding protein". FEBS Letters. 299 (1): 36–8. doi:10.1016/0014-5793(92)80094-W. PMID 1371974. S2CID 34097395.
• Karpinski BA, Morle GD, Huggenvik J, Uhler MD, Leiden JM (juni 1992). "Molecular cloning of human CREB-2: an ATF/CREB transcription factor that can negatively regulate transcription from the cAMP response element". Proceedings of the National Academy of Sciences of the United States of America. 89 (11): 4820–4. Bibcode:1992PNAS...89.4820K. doi:10.1073/pnas.89.11.4820. PMC 49179. PMID 1534408.
• Hai T, Curran T (maj 1991). "Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity". Proceedings of the National Academy of Sciences of the United States of America. 88 (9): 3720–4. Bibcode:1991PNAS...88.3720H. doi:10.1073/pnas.88.9.3720. PMC 51524. PMID 1827203.
• Tsujimoto A, Nyunoya H, Morita T, Sato T, Shimotohno K (mart 1991). "Isolation of cDNAs for DNA-binding proteins which specifically bind to a tax-responsive enhancer element in the long terminal repeat of human T-cell leukemia virus type I". Journal of Virology. 65 (3): 1420–6. doi:10.1128/JVI.65.3.1420-1426.1991. PMC 239921. PMID 1847461.
• Hai TW, Liu F, Coukos WJ, Green MR (decembar 1989). "Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers". Genes & Development. 3 (12B): 2083–90. doi:10.1101/gad.3.12b.2083. PMID 2516827.
• Kokame K, Kato H, Miyata T (novembar 1996). "Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis. GRP78/BiP and novel genes". The Journal of Biological Chemistry. 271 (47): 29659–65. doi:10.1074/jbc.271.47.29659. PMID 8939898.
• Reddy TR, Tang H, Li X, Wong-Staal F (juni 1997). "Functional interaction of the HTLV-1 transactivator Tax with activating transcription factor-4 (ATF4)". Oncogene. 14 (23): 2785–92. doi:10.1038/sj.onc.1201119. PMID 9190894.
• Liang G, Hai T (septembar 1997). "Characterization of human activating transcription factor 4, a transcriptional activator that interacts with multiple domains of cAMP-responsive element-binding protein (CREB)-binding protein". The Journal of Biological Chemistry. 272 (38): 24088–95. doi:10.1074/jbc.272.38.24088. PMID 9295363.
• Kawai T, Matsumoto M, Takeda K, Sanjo H, Akira S (mart 1998). "ZIP kinase, a novel serine/threonine kinase which mediates apoptosis". Molecular and Cellular Biology. 18 (3): 1642–51. doi:10.1128/mcb.18.3.1642. PMC 108879. PMID 9488481.
• Outinen PA, Sood SK, Pfeifer SI, Pamidi S, Podor TJ, Li J, Weitz JI, Austin RC (august 1999). "Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells". Blood. 94 (3): 959–67. doi:10.1182/blood.V94.3.959.415k20_959_967. PMID 10419887.
• Podust LM, Krezel AM, Kim Y (januar 2001). "Crystal structure of the CCAAT box/enhancer-binding protein beta activating transcription factor-4 basic leucine zipper heterodimer in the absence of DNA". The Journal of Biological Chemistry. 276 (1): 505–13. doi:10.1074/jbc.M005594200. PMID 11018027.
• Murphy P, Kolstø A (oktobar 2000). "Expression of the bZIP transcription factor TCF11 and its potential dimerization partners during development". Mechanisms of Development. 97 (1–2): 141–8. doi:10.1016/S0925-4773(00)00413-5. PMID 11025215. S2CID 17474070.
• White JH, McIllhinney RA, Wise A, Ciruela F, Chan WY, Emson PC, Billinton A, Marshall FH (decembar 2000). "The GABAB receptor interacts directly with the related transcription factors CREB2 and ATFx". Proceedings of the National Academy of Sciences of the United States of America. 97 (25): 13967–72. Bibcode:2000PNAS...9713967W. doi:10.1073/pnas.240452197. PMC 17684. PMID 11087824.
• He CH, Gong P, Hu B, Stewart D, Choi ME, Choi AM, Alam J (juni 2001). "Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation". The Journal of Biological Chemistry. 276 (24): 20858–65. doi:10.1074/jbc.M101198200. PMID 11274184.
• Siu F, Bain PJ, LeBlanc-Chaffin R, Chen H, Kilberg MS (juli 2002). "ATF4 is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene". The Journal of Biological Chemistry. 277 (27): 24120–7. doi:10.1074/jbc.M201959200. PMID 11960987.
• Bowers AJ, Scully S, Boylan JF (maj 2003). "SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human tumors and is regulated by hypoxia". Oncogene. 22 (18): 2823–35. doi:10.1038/sj.onc.1206367. PMID 12743605.
• Seo J, Fortuno ES, Suh JM, Stenesen D, Tang W, Parks EJ, Adams CM, Townes T, Graff JM (novembar 2009). "Atf4 regulates obesity, glucose homeostasis, and energy expenditure". Diabetes. 58 (11): 2565–73. doi:10.2337/db09-0335. PMC 2768187. PMID 19690063.
• Ebert, S. M., Bullard, S. A., Basisty, N., Marcotte, G. R., Skopec, Z. P., Dierdorff, J. M., ... & Bodine, S. C. (2020). "Activating transcription factor 4 (ATF4) promotes skeletal muscle atrophy by forming a heterodimer with the transcriptional regulator C/EBPβ". Journal of Biological Chemistry, 295(9), 2787–2803. doi:10.1074/jbc.RA119.012095 PMC 7049960 PubMed

Vanjski linkovi

• ATF4 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)
• Lokacija ljudskog genoma ATF4 i stranica sa detaljima o genu ATF4 u UCSC Genome Browseru.
• PDBe-KB provides an overview of all the structure information available in the PDB for Human Cyclic AMP-dependent transcription factor ATF-4

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.