Idi na sadržaj

EGR1

S Wikipedije, slobodne enciklopedije
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
Ensembl
UniProt
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 (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.

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

Aminokiselinska sekvenca[uredi | uredi izvor]

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[uredi | uredi izvor]

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[uredi | uredi izvor]

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[uredi | uredi izvor]

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[uredi | uredi izvor]

Pokazalo se da EGR-1 stupa u interakcije sa:

Također pogledajte[uredi | uredi izvor]

Reference[uredi | uredi izvor]

  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[uredi | uredi izvor]

Vanjski linkovi[uredi | uredi izvor]