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EGR1

EGR-1 (skraćenica od engleskog naziva Early Growth Response protein 1 = protein odgovora na rani faktor rasta ) znan i kao ZNF268 (engleska skraćenica za protein cinkovog prsta 268) ili NGFI-A (engleska skraćenica za protein A induciran fakrorom rasta) jest protein koji je kod ljudi kodiran genom EGR1.

EGR1
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

4R2A, 4R2C, 4R2D, 4X9J

Identifikatori
AliasiEGR1
Vanjski ID-jeviOMIM: 128990 MGI: 95295 HomoloGene: 56394 GeneCards: EGR1
Lokacija gena (čovjek)
Hromosom 5 (čovjek)
Hrom.Hromosom 5 (čovjek)[1]
Hromosom 5 (čovjek)
Genomska lokacija za EGR1
Genomska lokacija za EGR1
Bend5q31.2Početak138,465,479 bp[1]
Kraj138,469,303 bp[1]
Lokacija gena (miš)
Hromosom 18 (miš)
Hrom.Hromosom 18 (miš)[2]
Hromosom 18 (miš)
Genomska lokacija za EGR1
Genomska lokacija za EGR1
Bend18 B1|18 18.76 cMPočetak34,992,876 bp[2]
Kraj34,998,037 bp[2]
Obrazac RNK ekspresije


Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• vezivanje sa DNK
• sequence-specific DNA binding
• RNA polymerase II transcription regulatory region 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
• GO:0000975 transcription cis-regulatory region binding
• vezivanje iona metala
• transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding
• GO:0001948, GO:0016582 vezivanje za proteine
• histone acetyltransferase binding
• nucleic acid binding
• hemi-methylated DNA-binding
• double-stranded methylated DNA binding
• vezivanje iona cinka
• promoter-specific chromatin binding
• GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific
Ćelijska komponenta• nukleoplazma
• jedro
• citoplazma
Biološki proces• regulation of apoptotic process
• cellular response to organic substance
• GO:0009373 regulation of transcription, DNA-templated
• glomerular mesangial cell proliferation
• GO:1901227 negative regulation of transcription by RNA polymerase II
• response to glucose
• transcription by RNA polymerase II
• BMP signaling pathway
• transcription, DNA-templated
• GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated
• response to insulin
• interleukin-1-mediated signaling pathway
• cellular response to mycophenolic acid
• T cell differentiation
• type I interferon signaling pathway
• positive regulation of glomerular metanephric mesangial cell proliferation
• cellular response to gamma radiation
• regulation of transcription from RNA polymerase II promoter in response to hypoxia
• skeletal muscle cell differentiation
• cellular response to heparin
• regulation of protein sumoylation
• negative regulation of canonical Wnt signaling pathway
• GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II
• cellular response to interleukin-8
• response to hypoxia
• response to ischemia
• estrous cycle
• positive regulation of hormone biosynthetic process
• regulation of progesterone biosynthetic process
• 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
• GO:1901313 positive regulation of gene expression
• circadian regulation of gene expression
• locomotor rhythm
• rhythmic process
• circadian temperature homeostasis
• positive regulation of neuron death
• positive regulation of tau-protein kinase activity
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

1958

13653

Ensembl

ENSG00000120738

ENSMUSG00000038418

UniProt

P18146

P08046

RefSeq (mRNK)

NM_001964

NM_007913

RefSeq (bjelančevina)

NP_001955

NP_031939

Lokacija (UCSC)Chr 5: 138.47 – 138.47 MbChr 18: 34.99 – 35 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

EGR-1 je transkripcijski faktor. Nazvan je i Krox-24, TIS8 i ZENK. Prvobitno je otkriven kod miševa.

Aminokiselinska sekvenca

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Dužina polipeptidnog lanca je 543 aminokiselina, а molekulska težina 57.507 Da.[5]

1020304050
MAAAKAEMQLMSPLQISDPFGSFPHSPTMDNYPKLEEMMLLSNGAPQFLG
AAGAPEGSGSNSSSSSSGGGGGGGGGSNSSSSSSTFNPQADTGEQPYEHL
TAESFPDISLNNEKVLVETSYPSQTTRLPPITYTGRFSLEPAPNSGNTLW
PEPLFSLVSGLVSMTNPPASSSSAPSPAASSASASQSPPLSCAVPSNDSS
PIYSAAPTFPTPNTDIFPEPQSQAFPGSAGTALQYPPPAYPAAKGGFQVP
MIPDYLFPQQQGDLGLGTPDQKPFQGLESRTQQPSLTPLSTIKAFATQSG
SQDLKALNTSYQSQLIKPSRMRKYPNRPSKTPPHERPYACPVESCDRRFS
RSDELTRHIRIHTGQKPFQCRICMRNFSRSDHLTTHIRTHTGEKPFACDI
CGRKFARSDERKRHTKIHLRQKDKKADKSVVASSATSSLSSYPSPVATSY
PSPVTTSYPSPATTSYPSPVPTSFSSPGSSTYPSPVHSGFPSPSVATTYS
SVPPAFPAQVSSFPSSAVTNSFSASTGLSDMTATFSPRTIEIC

Funkcija

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Protein kodiran ovim genom pripada porodici EGR proteina Cys2 njegovog tipacinkovog prsta2 To je jedarni protein i funkcionira kao regulator transkripcije. Proizvodi ciljnih gena koje aktivira potrebni su za diferencijaciju i mitogenezu. Studije sugeriraju da se radi o tumor-supresorskom genu.[6]

Ima jasan obrazac ekspresije u mozgu, a pokazalo se da je njegova indukcija povezana s neuronskom aktivnošću. Nekoliko studija sugerira da ima ulogu u plastičnosti neurona.[7]

EGR-1 je važan faktor transkripcije u formaciji memorija. Ima bitnu ulogu u reprogramiranju epigenetičkih moždanih neurona. EGR-1 regrutuje protein TET1 koji pokreće put demetilacije DNK.[8] Uklanjanje oznaka metilacije DNK omogućuje aktivaciju nizvodnih gena. EGR-1, zajedno s TET1, koristi se za programiranje distribucije mjesta metilacije DNK mozga tokom njegovog razvoja, u učenju i dugoročnoj neuronskom plastičnosti. Takođe je utvrđeno da EGR-1 regulira ekspresiju VAMP2 (proteina važnog za sinapsne egzocitoze).[9]

Osim svoje funkcije u živčanom sistemu, postoje značajni dokazi da EGR-1 zajedno sa svojim paralogom EGR-2 inducira u fibroznim bolestima, ima ključne funkcije u fibrinogenezi i neophodan je za eksperimentalno induciranu fibrozu kod miševa.[10]

Može biti uključen i u funkciju jajnika.[11]

Struktura

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Domen koji veže DNK EGR-1 sastoji se od tri domena cinkovog prsta tipa Cys2His2. Struktura aminokiselina EGR-1 domena cinkovog prsta data je u ovoj tabeli, koristeći jednoznačni kod aminokiselina. Prsti od 1 do 3 označeni su sa f1 - f3. Brojevi se odnose na ostatke (aminokiseline) alfa-helikse (nema nule). Ostaci označeni sa "x" nisu dio cinkovih prstiju, već služe za njihovo povezivanje.

-1 1 2 3 4 5 6 7 8 9 x x x x x
f1 M A E E R P Y A C P V E S C D R R F S R S D E L T R H I R I H T G Q K P
f2 F Q C A I - - C M R N F S R S D H L T T H I A T H T G E K P
f3 F A C D I - - C G R K F A R S D E R K R H T K I H L R Q K D
Simboli
Alanin (Ala, A), Arginin (Arg, R), Asparagin (Asn, N), Aspartat (Asp, D), Cistein (Cys, C), Glutamat (Glu, E), Glutamin (Gln, Q), Glicin (Gly, G), Histidin (His, H), Izoleucin (Ile, I), Leucin (Leu, L), Lizin (Lys, K), Metionin (Met, M), Fenilalanin (Phe, F), Prolin (Pro, P), Serin (Ser, S), Treonin (Thr, T), Triptofan (Trp, W), Tirozin (Tyr, Y), Valin (Val, V)

Kristalna struktura DNK vezana domenom cinkovog prsta EGR-1 riješena je 1991. godine, što je uveliko pomoglo rano istraživanje u domenama vezanja DNK za cinkove prste.[12]

Ljudski protein EGR-1 sadrži (u neobrađenom obliku) 543 aminokiselina molekulske mase 57,5 kDa, a gen se nalazi na hromosomu 5.

Specifičnost vezivanja DNK

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EGR-1 veže DNK sekvencu 5'-GCG TGG GCG-3'(i slične 5'-GCG GGG GCG-3').[13][14] Položaj f1 veže 5 'G (prvi broj baze slijeva); položaj f1 3 prema drugoj bazi (C); pozicija f1 -1 veže se za treću poziciju (G); f2 položaj 6 do četvrte baze (T); i tako dalje.

Interakcije

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Pokazalo se da EGR-1 stupa u interakcije sa:

Također pogledajte

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Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000120738 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038418 - 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. ^ "UniProt, P18146" (jezik: engleski). Pristupljeno 14. 10. 2021.
  6. ^ "Entrez Gene: EGR1 early growth response 1".
  7. ^ Knapska E, Kaczmarek L (novembar 2004). "A gene for neuronal plasticity in the mammalian brain: Zif268/Egr-1/NGFI-A/Krox-24/TIS8/ZENK?". Progress in Neurobiology. 74 (4): 183–211. doi:10.1016/j.pneurobio.2004.05.007. PMID 15556287. S2CID 39251786.
  8. ^ Sun Z, Xu X, He J, Murray A, Sun MA, Wei X, Wang X, McCoig E, Xie E, Jiang X, Li L, Zhu J, Chen J, Morozov A, Pickrell AM, Theus MH, Xie H. EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity. Nat Commun. 2019 Aug 29;10(1):3892. doi: 10.1038/s41467-019-11905-3. PMID 31467272
  9. ^ Petersohn D, Thiel G (august 1996). "Role of zinc-finger proteins Sp1 and zif268/egr-1 in transcriptional regulation of the human synaptobrevin II gene". European Journal of Biochemistry. 239 (3): 827–34. doi:10.1111/j.1432-1033.1996.0827u.x. PMID 8774732.
  10. ^ Bhattacharyya S, Wu M, Fang F, Tourtellotte W, Feghali-Bostwick C, Varga J (maj 2011). "Early growth response transcription factors: key mediators of fibrosis and novel targets for anti-fibrotic therapy". Matrix Biology. 30 (4): 235–42. doi:10.1016/j.matbio.2011.03.005. PMC 3135176. PMID 21511034.
  11. ^ Han P, Guerrero-Netro H, Estienne A, Cao B, Price CA (oktobar 2017). "Regulation and action of early growth response 1 in bovine granulosa cells". Reproduction. 154 (4): 547–557. doi:10.1530/REP-17-0243. PMID 28733346.
  12. ^ Pavletich NP, Pabo CO (maj 1991). "Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A". Science. 252 (5007): 809–17. doi:10.1126/science.2028256. PMID 2028256. S2CID 38000717.
  13. ^ Christy B, Nathans D (novembar 1989). "DNA binding site of the growth factor-inducible protein Zif268". Proceedings of the National Academy of Sciences of the United States of America. 86 (22): 8737–41. doi:10.1073/pnas.86.22.8737. PMC 298363. PMID 2510170.
  14. ^ Swirnoff AH, Milbrandt J (april 1995). "DNA-binding specificity of NGFI-A and related zinc finger transcription factors". Molecular and Cellular Biology. 15 (4): 2275–87. doi:10.1128/mcb.15.4.2275. PMC 230455. PMID 7891721.
  15. ^ Zhang F, Lin M, Abidi P, Thiel G, Liu J (novembar 2003). "Specific interaction of Egr1 and c/EBPbeta leads to the transcriptional activation of the human low density lipoprotein receptor gene". The Journal of Biological Chemistry. 278 (45): 44246–54. doi:10.1074/jbc.M305564200. PMID 12947119.
  16. ^ a b Silverman ES, Du J, Williams AJ, Wadgaonkar R, Drazen JM, Collins T (novembar 1998). "cAMP-response-element-binding-protein-binding protein (CBP) and p300 are transcriptional co-activators of early growth response factor-1 (Egr-1)". The Biochemical Journal. 336 ( Pt 1) (1): 183–9. doi:10.1042/bj3360183. PMC 1219856. PMID 9806899.
  17. ^ Russo MW, Sevetson BR, Milbrandt J (juli 1995). "Identification of NAB1, a repressor of NGFI-A- and Krox20-mediated transcription". Proceedings of the National Academy of Sciences of the United States of America. 92 (15): 6873–7. doi:10.1073/pnas.92.15.6873. PMC 41432. PMID 7624335.
  18. ^ Liu J, Grogan L, Nau MM, Allegra CJ, Chu E, Wright JJ (april 2001). "Physical interaction between p53 and primary response gene Egr-1". International Journal of Oncology. 18 (4): 863–70. doi:10.3892/ijo.18.4.863. PMID 11251186.
  19. ^ Bae MH, Jeong CH, Kim SH, Bae MK, Jeong JW, Ahn MY, et al. (oktobar 2002). "Regulation of Egr-1 by association with the proteasome component C8". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1592 (2): 163–7. doi:10.1016/s0167-4889(02)00310-5. PMID 12379479.

Dopunska literatura

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Vanjski linkovi

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Preuzeto iz "https://bs.wikipedia.org/w/index.php?title=EGR1&oldid=3371046"