Aktivacijski transkripcijski faktor 4 (taks- pojačivač odgovora B67)', također poznat kao ATF4, je protein koji je kod ljudi kodiran genom ATF4 sa hromosoma 22.[5][6]

ATF4
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1CI6

Identifikatori
AliasiATF4
Vanjski ID-jeviOMIM: 604064 MGI: 88096 HomoloGene: 1266 GeneCards: ATF4
Lokacija gena (čovjek)
Hromosom 22 (čovjek)
Hrom.Hromosom 22 (čovjek)[1]
Hromosom 22 (čovjek)
Genomska lokacija za ATF4
Genomska lokacija za ATF4
Bend22q13.1Početak39,519,695 bp[1]
Kraj39,522,683 bp[1]
Lokacija gena (miš)
Hromosom 15 (miš)
Hrom.Hromosom 15 (miš)[2]
Hromosom 15 (miš)
Genomska lokacija za ATF4
Genomska lokacija za ATF4
Bend15 E1|15 37.85 cMPočetak80,139,385 bp[2]
Kraj80,141,742 bp[2]
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
VrsteČovjekMiš
Entrez
Ensembl
UniProt
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 MbChr 15: 80.14 – 80.14 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Aminokiselinska sekvenca

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Dužina polipeptidnojg lanca je 351 aminokiselina, a molekulska težina 38.590 Da.[7]

1020304050
MTEMSFLSSEVLVGDLMSPFDQSGLGAEESLGLLDDYLEVAKHFKPHGFS
SDKAKAGSSEWLAVDGLVSPSNNSKEDAFSGTDWMLEKMDLKEFDLDALL
GIDDLETMPDDLLTTLDDTCDLFAPLVQETNKQPPQTVNPIGHLPESLTK
PDQVAPFTFLQPLPLSPGVLSSTPDHSFSLELGSEVDITEGDRKPDYTAY
VAMIPQCIKEEDTPSDNDSGICMSPESYLGSPQHSPSTRGSPNRSLPSPG
VLCGSARPKPYDPPGEKMVAAKVKGEKLDKKLKKMEQNKTAATRYRQKKR
AEQEALTGECKELEKKNEALKERADSLAKEIQYLKDLIEEVRKARGKKRV
P

Funkcija

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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.[8]

Također je poznato da transkripcijski faktor ATF4 ima ulogu u diferencijaciji osteoblasta, zajedno sa RUNX2 i osteriksom.[9] Terminalna diferencijacija osteoblasta, predstavljena mineralizacijom matriksa, značajno je inhibirana inaktivacijom JNK. Inaktivacija JNK, posljedično smanjuje ekspresiju ATF-4 i mineralizaciju matriksa.[10] Protein IMPACT reguliše ATF4 u C. elegans kako bi produžio životni vijek.[11]

Translacija

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Translacija ATF4 ovisi o izvodnom otvorenom okviru čitanje koji se nalazi u 5' UTR-u.[12] 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".[12]

Također pogledajte

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Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000128272 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000042406 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ 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.
  7. ^ "UniProt, P18848" (jezik: англ.). Pristupljeno 12-09-2017. Provjerite vrijednost datuma u parametru: |access-date= (pomoć)CS1 održavanje: nepoznati jezik (link)
  8. ^ "Entrez Gene: ATF4 activating transcription factor 4 (tax-responsive enhancer element B67)".
  9. ^ Franceschi RT, Ge C, Xiao G, Roca H, Jiang D (2009). "Transcriptional regulation of osteoblasts". Cells Tissues Organs. 189 (1–4): 144–52. doi:10.1159/000151747. PMC 3512205. PMID 18728356.
  10. ^ Matsuguchi T, Chiba N, Bandow K, Kakimoto K, Masuda A, Ohnishi T (mart 2009). "JNK activity is essential for Atf4 expression and late-stage osteoblast differentiation". Journal of Bone and Mineral Research. 24 (3): 398–410. doi:10.1359/jbmr.081107. PMID 19016586. S2CID 13111270.
  11. ^ Ferraz RC, Camara H, De-Souza EA, Pinto S, Pinca AP, Silva RC, Sato VN, Castilho BA, Mori MA (oktobar 2016). "IMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans". BMC Biology. 14 (1): 87. doi:10.1186/s12915-016-0301-2. PMC 5054600. PMID 27717342.
  12. ^ a b Somers J, Pöyry T, Willis AE (august 2013). "A perspective on mammalian upstream open reading frame function". The International Journal of Biochemistry & Cell Biology. 45 (8): 1690–700. doi:10.1016/j.biocel.2013.04.020. PMC 7172355. PMID 23624144.

Dopunska literatura

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Vanjski linkovi

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


Šablon:Regulom