EGR1

EGR1
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	4R2A, 4R2C, 4R2D, 4X9J
Identifikatori
Aliasi	EGR1
Vanjski ID-jevi	OMIM: 128990 MGI: 95295 HomoloGene: 56394 GeneCards: EGR1
Lokacija gena (čovjek)
Hrom.	Hromosom 5 (čovjek)
Kraj	138,469,303 bp
Lokacija gena (miš)
Hrom.	Hromosom 18 (miš)
Kraj	34,998,037 bp
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
	1958
	13653
	ENSG00000120738
	ENSMUSG00000038418
	P18146
	P08046
	NM_001964
	NM_007913
	NP_001955
	NP_031939
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/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

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

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
MAAAKAEMQL	MSPLQISDPF	GSFPHSPTMD	NYPKLEEMML	LSNGAPQFLG
AAGAPEGSGS	NSSSSSSGGG	GGGGGGSNSS	SSSSTFNPQA	DTGEQPYEHL
TAESFPDISL	NNEKVLVETS	YPSQTTRLPP	ITYTGRFSLE	PAPNSGNTLW
PEPLFSLVSG	LVSMTNPPAS	SSSAPSPAAS	SASASQSPPL	SCAVPSNDSS
PIYSAAPTFP	TPNTDIFPEP	QSQAFPGSAG	TALQYPPPAY	PAAKGGFQVP
MIPDYLFPQQ	QGDLGLGTPD	QKPFQGLESR	TQQPSLTPLS	TIKAFATQSG
SQDLKALNTS	YQSQLIKPSR	MRKYPNRPSK	TPPHERPYAC	PVESCDRRFS
RSDELTRHIR	IHTGQKPFQC	RICMRNFSRS	DHLTTHIRTH	TGEKPFACDI
CGRKFARSDE	RKRHTKIHLR	QKDKKADKSV	VASSATSSLS	SYPSPVATSY
PSPVTTSYPS	PATTSYPSPV	PTSFSSPGSS	TYPSPVHSGF	PSPSVATTYS
SVPPAFPAQV	SSFPSSAVTN	SFSASTGLSD	MTATFSPRTI	EIC

Funkcija

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

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

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

Pokazalo se da EGR-1 stupa u interakcije sa:

Također pogledajte

Cinkov prst

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000120738 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000038418 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "UniProt, P18146" (jezik: engleski). Pristupljeno 14. 10. 2021.
^ "Entrez Gene: EGR1 early growth response 1".
^ 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.
^ 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
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^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.
^ 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.
^ 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.
^ 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

Heath RG (mart 1975). "Brain function and behavior. I. Emotion and sensory phenomena in psychotic patients and in experimental animals". The Journal of Nervous and Mental Disease. 160 (3): 159–75. doi:10.1097/00005053-197503000-00002. PMID 1090709. S2CID 23024944.
Silverman ES, Collins T (mart 1999). "Pathways of Egr-1-mediated gene transcription in vascular biology". The American Journal of Pathology. 154 (3): 665–70. doi:10.1016/S0002-9440(10)65312-6. PMC 1866415. PMID 10079243.
Adamson ED, Mercola D (2002). "Egr1 transcription factor: multiple roles in prostate tumor cell growth and survival". Tumour Biology. 23 (2): 93–102. doi:10.1159/000059711. PMID 12065847. S2CID 46795197.
Blaschke F, Bruemmer D, Law RE (august 2004). "Egr-1 is a major vascular pathogenic transcription factor in atherosclerosis and restenosis". Reviews in Endocrine & Metabolic Disorders. 5 (3): 249–54. doi:10.1023/B:REMD.0000032413.88756.ee. PMID 15211096. S2CID 11968305.
Abdulkadir SA (novembar 2005). "Mechanisms of prostate tumorigenesis: roles for transcription factors Nkx3.1 and Egr1". Annals of the New York Academy of Sciences. 1059: 33–40. doi:10.1196/annals.1339.018. PMID 16382041. S2CID 6774788.
Khachigian LM (februar 2006). "Early growth response-1 in cardiovascular pathobiology". Circulation Research. 98 (2): 186–91. doi:10.1161/01.RES.0000200177.53882.c3. PMID 16456111.

Vanjski linkovi

Zif 268 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)
FactorBook Egr-1
P18146
P08046

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000120738 - Ensembl, maj 2017

[refGRCm38Ensembl-2] 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.

[UniProt-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.

[pmid12947119-15] 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.

[pmid9806899-16] 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.

[pmid7624335-17] 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.

[pmid11251186-18] 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.

[pmid12379479-19] 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.

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																				-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

																				-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

																				-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