EGR1

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

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 5:
138.47 – 138.47 Mb

Chr 18:
34.86 – 34.86 Mb

PubMed search

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:

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.
1 2 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

PDB gallery

1a1f: DSNR (ZIF268 VARIANT) ZINC FINGER-DNA COMPLEX (GACC SITE)

1a1g: DSNR (ZIF268 VARIANT) ZINC FINGER-DNA COMPLEX (GCGT SITE)

1a1h: QGSR (ZIF268 VARIANT) ZINC FINGER-DNA COMPLEX (GCAC SITE)

1a1i: RADR (ZIF268 VARIANT) ZINC FINGER-DNA COMPLEX (GCAC SITE)

1a1j: RADR (ZIF268 VARIANT) ZINC FINGER-DNA COMPLEX (GCGT SITE)

1a1k: RADR (ZIF268 VARIANT) ZINC FINGER-DNA COMPLEX (GACC SITE)

1a1l: ZIF268 ZINC FINGER-DNA COMPLEX (GCAC SITE)

1aay: ZIF268 ZINC FINGER-DNA COMPLEX

1f2i: COCRYSTAL STRUCTURE OF SELECTED ZINC FINGER DIMER BOUND TO DNA

1jk1: Zif268 D20A Mutant Bound to WT DNA Site

1jk2: Zif268 D20A mutant bound to the GCT DNA site

1p47: Crystal Structure of tandem Zif268 molecules complexed to DNA

1zaa: ZINC FINGER-DNA RECOGNITION: CRYSTAL STRUCTURE OF A ZIF268-DNA COMPLEX AT 2.1 ANGSTROMS

Transcription factors and intracellular receptors

(1) Basic domains

(1.1) Basic leucine zipper (bZIP)	Activating transcription factor AATF 1 2 3 4 5 6 7 AP-1 c-Fos FOSB FOSL1 FOSL2 JDP2 c-Jun JUNB JunD BACH 1 2 BATF BLZF1 C/EBP α β γ δ ε ζ CREB 1 3 L1 CREM DBP DDIT3 GABPA HLF MAF B F G K NFE 2 L1 L2 L3 NFIL3 NRL NRF 1 2 3 XBP1

(1.2) Basic helix-loop-helix (bHLH)	ATOH1 AhR AHRR ARNT ASCL1 BHLH 2 3 9 ARNTL ARNTL ARNTL2 CLOCK EPAS1 FIGLA HAND 1 2 HES 5 6 HEY 1 2 L HES1 HIF 1A 3A ID 1 2 3 4 LYL1 MESP2 MXD4 MYCL1 MYCN Myogenic regulatory factors MyoD Myogenin MYF5 MYF6 Neurogenins 1 2 3 NeuroD 1 2 NPAS 1 2 3 OLIG 1 2 Pho4 Scleraxis SIM 1 2 TAL 1 2 Twist USF1

(1.3) bHLH-ZIP	AP-4 MAX MXD3 MITF MNT MLX MXI1 Myc SREBP 1 2

(1.4) NF-1	NFI A B C X SMAD R-SMAD 1 2 3 5 9 I-SMAD 6 7 4)

(1.5) RF-X	RFX 1 2 3 4 5 6 ANK

(1.6) Basic helix-span-helix (bHSH)	AP-2 α β γ δ ε

(2) Zinc finger DNA-binding domains

(2.1) Nuclear receptor (Cys₄)

subfamily 1	Thyroid hormone α β CAR FXR LXR α β PPAR α β/δ γ PXR RAR α β γ ROR α β γ Rev-ErbA α β VDR

subfamily 2	COUP-TF (I II Ear-2 HNF4 α γ PNR RXR α β γ Testicular receptor 2 4 TLX

subfamily 3	Steroid hormone Androgen Estrogen α β Glucocorticoid Mineralocorticoid Progesterone Estrogen related α β γ

subfamily 4	NUR NGFIB NOR1 NURR1

subfamily 5	LRH-1 SF1

subfamily 6	GCNF

subfamily 0	DAX1 SHP

(2.2) Other Cys₄

GATA
- 1
- 2
- 3
- 4
- 5
- 6
MTA
- 1
- 2
- 3
TRPS1

(2.3) Cys₂His₂

General transcription factors
- TFIIA
- TFIIB
- TFIID
- TFIIE
  - 1
  - 2
- TFIIF
- 1
- 2
  - TFIIH
  - 1
  - 2
  - 4
  - 2I
  - 3A
  - 3C1
  - 3C2

ATBF1
BCL
- 6
- 11A
- 11B
CTCF
E4F1
EGR
- 1
- 2
- 3
- 4
ERV3
GFI1
GLI-Krüppel family
- 1
- 2
- 3
- REST
- S1
- S2
- YY1
HIC
- 1
- 2
HIVEP
- 1
- 2
- 3
IKZF
- 1
- 2
- 3
ILF
- 2
- 3
KLF
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 17
MTF1
MYT1
OSR1
PRDM9
SALL
- 1
- 2
- 3
- 4
SP
- 1
- 2
- 4
- 7
- 8
TSHZ3
WT1
Zbtb7
- 7A
- 7B
ZBTB
- 11
- 16
- 17
- 20
- 32
- 33
- 40
zinc finger
- 3
- 7
- 9
- 10
- 19
- 22
- 24
- 33B
- 34
- 35
- 41
- 43
- 44
- 51
- 74
- 143
- 146
- 148
- 165
- 202
- 217
- 219
- 238
- 239
- 259
- 267
- 268
- 281
- 295
- 300
- 318
- 330
- 346
- 350
- 365
- 366
- 384
- 423
- 451
- 452
- 471
- 593
- 638
- 644
- 649
- 655

(2.4) Cys₆

HIVEP1

(2.5) Alternating composition

AIRE
DIDO1
GRLF1
ING
- 1
- 2
- 4
JARID
- 1A
- 1B
- 1C
- 1D
- 2
JMJD1B

(2.6) WRKY

WRKY

(3) Helix-turn-helix domains

(3.1) Homeodomain	ARX CDX 1 2 CRX CUTL1 DBX 1 2 DLX 3 4 5 EMX 1 2 EN 1 2 FHL 1 2 3 HESX1 HHEX HLX Homeobox A1 A2 A3 A4 A5 A7 A9 A10 A11 A13 B1 B2 B3 B4 B5 B6 B7 B8 B9 B13 C4 C5 C6 C8 C9 C10 C11 C12 C13 D1 D3 D4 D8 D9 D10 D11 D12 D13 HOPX IRX 1 2 3 4 5 6 MKX LMX 1A 1B MEIS 1 2 MEOX2 MNX1 MSX 1 2 NANOG NKX 2-1 2-2 2-3 2-5 3-1 3-2 6-1 6-2 NOBOX PBX 1 2 3 PHF 1 3 6 8 10 16 17 20 21A PHOX 2A 2B PITX 1 2 3 POU domain PIT-1 BRN-3: A B C Octamer transcription factor: 1 2 3/4 6 7 11 OTX 1 2 PDX1 SATB2 SHOX2 SIX 1 2 3 4 5 VAX1 ZEB 1 2

(3.2) Paired box	PAX 1 2 3 4 5 6 7 8 9 PRRX 1 2 RAX

(3.3) Fork head / winged helix	E2F 1 2 3 4 5 FOX proteins A1 A2 A3 C1 C2 D3 D4 E1 E3 F1 G1 H1 I1 J1 J2 K1 K2 L2 M1 N1 N3 O1 O3 O4 P1 P2 P3 P4

(3.4) Heat shock factors	HSF 1 2 4

(3.5) Tryptophan clusters	ELF 2 4 5 EGF ELK 1 3 4 ERF ETS 1 2 ERG SPIB ETV 1 4 5 6 FLI1 Interferon regulatory factors 1 2 3 4 5 6 7 8 MYB MYBL2

(3.6) TEA domain	transcriptional enhancer factor 1 2 3 4

(4) β-Scaffold factors with minor groove contacts

(4.1) Rel homology region	NF-κB NFKB1 NFKB2 REL RELA RELB NFAT C1 C2 C3 C4 5

(4.2) STAT	STAT 1 2 3 4 5 6

(4.3) p53	p53 TBX 1 2 3 5 19 21 22 TBR1 TBR2 TFT MYRF TP63

(4.4) MADS box	Mef2 A B C D SRF

(4.6) TATA-binding proteins	TBP TBPL1

(4.7) High-mobility group	BBX HMGB 1 2 3 4 HMGN 1 2 3 4 HNF 1A 1B LEF1 SOX 1 2 3 4 5 6 8 9 10 11 12 13 14 15 18 21 SRY SSRP1 TCF 3 4 TOX 1 2 3 4

(4.9) Grainyhead	TFCP2

(4.10) Cold-shock domain	CSDA YBX1

(4.11) Runt	CBF CBFA2T2 CBFA2T3 RUNX1 RUNX2 RUNX3 RUNX1T1

(0) Other transcription factors

(0.2) HMGI(Y)	HMGA 1 2 HBP1

(0.3) Pocket domain	Rb RBL1 RBL2

(0.5) AP-2/EREBP-related factors	Apetala 2 EREBP B3

(0.6) Miscellaneous	ARID 1A 1B 2 3A 3B 4A CAP IFI 16 35 MLL 2 3 T1 MNDA NFY A B C Rho/Sigma

see also transcription factor/coregulator deficiencies

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