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the 5th letter of the Roman alphabet (同)e

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/05/07 02:50:58」(JST)

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EGR-1 (Early growth response protein 1) also known as Zif268 (zinc finger protein 225) or NGFI-A (nerve growth factor-induced protein A) is a protein that in humans is encoded by the EGR1 gene.

EGR-1 is a mammalian transcription factor. It was also named Krox-24, TIS8, and ZENK. It was originally discovered in mice.

Function

The protein encoded by this gene belongs to the EGR family of Cys₂His₂-type zinc finger proteins. It is a nuclear protein and functions as a transcriptional regulator. The products of target genes it activates are required for differentiation and mitogenesis. Studies suggest this is a tumor suppressor gene.^[1]

It has a distinct pattern of expression in the brain, and its induction has been shown to be associated with neuronal activity. Several studies suggest it has a role in neuronal plasticity.^[2]

EGR-1 has also been found to regulate the expression of VAMP2 (a protein important for synaptic exocytosis).^[3]

Structure

The DNA-binding domain of EGR-1 consists of three zinc finger domains of the Cys₂His₂ type. The amino acid structure of the EGR-1 zinc finger domain is given in this table, using the single letter amino acid code. The fingers 1 to 3 are indicated by f1 - f3. The numbers are in reference to the residues (amino acids) of alpha helix (there is no zero). The residues marked 'x' are not part of the zinc fingers, but rather serve to connect them all together.

																				-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

Amino acid key: Alanine (Ala, A), Arginine (Arg, R), Asparagine (Asn, N), Aspartic acid (Asp, D), Cysteine (Cys, C), Glutamic acid (Glu, E), Glutamine (Gln, Q), Glycine (Gly, G), Histidine (His, H), Isoleucine (Ile, I), Leucine (Leu, L), Lysine (Lys, K), Methionine (Met, M), Phenylalanine (Phe, F), Proline (Pro, P), Serine (Ser, S), Threonine (Thr, T), Tryptophan (Trp, W), Tyrosine (Tyr, Y), Valine (Val, V)

The crystal structure of DNA bound by the zinc finger domain of EGR-1 was solved in 1991, which greatly aided early research in zinc finger DNA-binding domains.^[4]

The human EGR-1 protein contains (in its unprocessed form) 543 amino acids with a molecular weight of 57.5 kDa, and the gene is located on the chromosome 5.

DNA binding specificity

EGR-1 binds the DNA sequence 5'-GCG TGG GCG-3' (and similar ones like 5'-GCG GGG GCG-3').^[5]^[6] The f1 position 6 binds the 5' G (the first base count from the left); the f1 position 3 to the second base (C); f1 position -1 binds to the third position (G); f2 position 6 to the fourth base (T); and so on.

Interactions

EGR-1 has been shown to interact with:

CEBPB,^[7]
CREB-binding protein,^[8]
EP300,^[8]
NAB1,^[9]
P53,^[10] and
PSMA3^[11]

References

^ "Entrez Gene: EGR1 early growth response 1".
^ Knapska E, Kaczmarek L (2004). "A gene for Neuronal Plasticity in the Mammalian Brain: Zif286/Egr1/NGFI-A/Krox-24/TIS-8/ZENK?". Progress in Neurobiology 74: 2004.
^ Petersohn,D and Thiel. G (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, 1996
^ Pavletich NP, Pabo CO (May 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.
^ Christy B, Nathans D (Nov 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 (Apr 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 (Nov 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 (Nov 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 (1): 183–9. doi:10.1042/bj3360183. PMC 1219856. PMID 9806899.
^ Russo MW, Sevetson BR, Milbrandt J (Jul 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 (Apr 2001). "Physical interaction between p53 and primary response gene Egr-1". International Journal of Oncology 18 (4): 863–70. PMID 11251186.
^ Bae MH, Jeong CH, Kim SH, Bae MK, Jeong JW, Ahn MY, Bae SK, Kim ND, Kim CW, Kim KR, Kim KW (Oct 2002). "Regulation of Egr-1 by association with the proteasome component C8". Biochimica et Biophysica Acta 1592 (2): 163–7. doi:10.1016/s0167-4889(02)00310-5. PMID 12379479.

External links

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

English Journal

DIF-1 inhibits tumor growth in vivo reducing phosphorylation of GSK-3β and expressions of cyclin D1 and TCF7L2 in cancer model mice.

Takahashi-Yanaga F1, Yoshihara T2, Jingushi K2, Igawa K3, Tomooka K3, Watanabe Y4, Morimoto S2, Nakatsu Y5, Tsuzuki T5, Nakabeppu Y6, Sasaguri T7.
Biochemical pharmacology.Biochem Pharmacol.2014 Jun 1;89(3):340-8. doi: 10.1016/j.bcp.2014.03.006. Epub 2014 Mar 23.
We reported that differentiation-inducing factor-1 (DIF-1), synthesized by Dictyostelium discoideum, inhibited proliferation of various tumor cell lines in vitro by suppressing the Wnt/β-catenin signaling pathway. However, it remained unexplored whether DIF-1 also inhibits tumor growth in vivo. In
PMID 24670930

Mechanism of erythropoietin regulation by angiotensin II.

Kim YC1, Mungunsukh O, McCart EA, Roehrich PJ, Yee DK, Day RM.
Molecular pharmacology.Mol Pharmacol.2014 Jun;85(6):898-908. doi: 10.1124/mol.113.091157. Epub 2014 Apr 2.
Erythropoietin (EPO) is the primary regulator of red blood cell development. Although hypoxic regulation of EPO has been extensively studied, the mechanism(s) for basal regulation of EPO are not well understood. In vivo studies in healthy human volunteers and animal models indicated that angiotensin
PMID 24695083

Expression and effects of epidermal growth factor on human periodontal ligament cells.

Teramatsu Y1, Maeda H, Sugii H, Tomokiyo A, Hamano S, Wada N, Yuda A, Yamamoto N, Koori K, Akamine A.
Cell and tissue research.Cell Tissue Res.2014 May 22. [Epub ahead of print]
Repair of damaged periodontal ligament (PDL) tissue is an essential challenge in tooth preservation. Various researchers have attempted to develop efficient therapies for healing and regenerating PDL tissue based on tissue engineering methods focused on targeting signaling molecules in PDL stem cell
PMID 24850273

Japanese Journal

Y-7 卵巣癌間質の遺伝子発現解析を用いた新規バイオマーカーの探索 : 癌間質のEGR-1発現は上皮性卵巣癌の予後予測因子である(腫瘍,優秀演題賞候補プログラム,第63回日本産科婦人科学会学術講演会)

片岡史夫,津田浩史,野村弘行,千代田達幸,赤羽智子,平沢晃,進伸幸,青木大輔,吉村泰典
日本産科婦人科學會雜誌 63(2), 704, 2011-02-01
NAID 110008509534

The dusp1 immediate early gene is regulated by natural stimuli predominantly in sensory input neurons

Horita Haruhito,Wada Kazuhiro,Rivas Miriam V.,Hara Erina,Jarvis Erich D.
The Journal of Comparative Neurology 518(14), 2873-2901, 2010-07-15
… Here, we report the first such gene, dual specificity phosphatase 1 (dusp1). … Dusp1 is an inactivator of mitogen-activated protein kinase (MAPK), and MAPK in turn activates expression of egr1, one of the most commonly studied IEGs, as determined in cultured cells. …
NAID 120002317143

Related Pictures

★リンクテーブル★

リンク元	「early growth response protein 1」「初期増殖応答タンパク質1」
関連記事	「EGR」「E」

「early growth response protein 1」

Early growth response 1
	Cartoon representation of Zif268 (blue) containing three zinc fingers in complex with DNA (orange). The coordinating amino acid residues of the middle zinc ion (green) are highlighted.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	4R2A, 4R2C, 4R2D, 4X9J
Identifiers
Symbols	EGR1 ; AT225; G0S30; KROX-24; NGFI-A; TIS8; ZIF-268; ZNF225
External IDs	OMIM: 128990 MGI: 95295 HomoloGene: 56394 GeneCards: EGR1 Gene
Gene ontology
Molecular function	• transcription regulatory region sequence-specific DNA binding; • RNA polymerase II regulatory region sequence-specific DNA binding; • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; • DNA binding; • transcription factor activity, sequence-specific DNA binding; • protein binding; • histone acetyltransferase binding; • sequence-specific DNA binding; • metal ion binding;
Cellular component	• nucleus; • nucleoplasm; • cytoplasm;
Biological process	• negative regulation of transcription from RNA polymerase II promoter; • transcription from RNA polymerase II promoter; • response to glucose; • T cell differentiation; • BMP signaling pathway; • response to insulin; • regulation of protein sumoylation; • skeletal muscle cell differentiation; • regulation of apoptotic process; • positive regulation of transcription, DNA-templated; • positive regulation of transcription from RNA polymerase II promoter; • type I interferon signaling pathway; • regulation of transcription from RNA polymerase II promoter in response to hypoxia; • interleukin-1-mediated signaling pathway; • cellular response to gamma radiation; • cellular response to heparin; • cellular response to mycophenolic acid; • glomerular mesangial cell proliferation; • positive regulation of glomerular metanephric mesangial cell proliferation; • negative regulation of canonical Wnt signaling pathway;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;