Zif268: Information from Answers.com

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

1a1f, 1a1g, 1a1h, 1a1i, 1a1j, 1a1k, 1a1l, 1aay, 1f2i, 1jk1, 1jk2, 1p47, 1zaa

Identifiers

Symbols

EGR1; AT225; G0S30; KROX-24; NGFI-A; TIS8; ZIF-268; ZNF225

External IDs

OMIM: 128990 MGI: 95295 HomoloGene: 56394

Gene ontology
Molecular function	• transcription factor activity • zinc ion binding • metal ion binding
Cellular component	• intracellular • nucleus
Biological process	• transcription • regulation of transcription, DNA-dependent • T cell differentiation • positive regulation of transcription

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq

NM_001964 (mRNA)

NM_007913 (mRNA)

NP_001955 (protein)

NP_031939 (protein)

Location

Chr 5:
137.83 - 137.83 Mb

Chr 18:
34.99 - 34.99 Mb

PubMed search

[1]

[2]

Zif268 is a mammalian transcription factor that is now officially known as Egr1 (Early Growth Response Protein 1). It was also named Krox-24, NGFI-A, TIS8, and ZENK. It was originally discovered in mouse.

The protein encoded by this gene belongs to the EGR family of C2H2-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]

1 Structure
2 Function
3 Interactions
4 See also
5 References
6 Further reading
7 External links

Structure

The DNA binding domain of Zif268 consists of three zinc finger domains of the Cys₂His₂ type. The amino acid structure of the Zif268 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 '0'). 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	O	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

The crystal structure of DNA bound by the zinc finger domain of Zif268 was solved in 1991, which greatly aided early research in zinc finger DNA-binding domains.^[2]

The human Zif268/EGR1 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.

Function

Zif268 binds the DNA sequence 5'-GCG[G/T]GGGCG-3'.^[3]^[4]

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.^[5]

Zif268 has also been found to regulate the expression of synaptobrevin II (a protein important for synaptic exocytosis).^[6]

Interactions

Zif268 has been shown to interact with NAB1,^[7] CEBPB,^[8] EP300,^[9] CREB binding protein,^[9] PSMA3^[10] and P53.^[11]

References

^ "Entrez Gene: EGR1 early growth response 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1958.
^ Pavletich, N. P. and C. O. Pabo (1991). "Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A." Science 252(5007): 809-17.
^ Christy B, Nathans D (1989). "DNA binding site of the growth factor-inducible protein Zif268". Proc. Natl. Acad. Sci. U.S.A. 86 (22): 8737–41. doi:10.1073/pnas.86.22.8737. PMID 2510170. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=2510170.
^ Swirnoff AH, Milbrandt J (1995). "DNA-binding specificity of NGFI-A and related zinc finger transcription factors". Mol. Cell. Biol. 15 (4): 2275–87. PMID 7891721. http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=7891721.
^ Knapska, E and 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
^ Russo, M W; Sevetson B R, Milbrandt J (Jul. 1995). "Identification of NAB1, a repressor of NGFI-A- and Krox20-mediated transcription". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 92 (15): 6873-7. ISSN 0027-8424. PMID 7624335.
^ Zhang, Fang; Lin Meihong, Abidi Parveen, Thiel Gerald, Liu Jingwen (Nov. 2003). "Specific interaction of Egr1 and c/EBPbeta leads to the transcriptional activation of the human low density lipoprotein receptor gene". J. Biol. Chem. (United States) 278 (45): 44246-54. doi:10.1074/jbc.M305564200. ISSN 0021-9258. PMID 12947119.
^ ^a ^b Silverman, E S; Du J, Williams A J, Wadgaonkar R, Drazen J M, 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)". Biochem. J. (ENGLAND) 336 ( Pt 1): 183-9. ISSN 0264-6021. PMID 9806899.
^ Bae, Myung-Ho; Jeong Chul-Ho, Kim Se-Hee, Bae Moon-Kyoung, Jeong Joo-Won, Ahn Mee-Young, Bae Soo-Kyung, Kim Nam Deuk, Kim Chul Woo, Kim Kwang-Rok, Kim Kyu-Won (Oct. 2002). "Regulation of Egr-1 by association with the proteasome component C8". Biochim. Biophys. Acta (Netherlands) 1592 (2): 163-7. ISSN 0006-3002. PMID 12379479.
^ Liu, J; Grogan L, Nau M M, Allegra C J, Chu E, Wright J J (Apr. 2001). "Physical interaction between p53 and primary response gene Egr-1". Int. J. Oncol. (Greece) 18 (4): 863-70. ISSN 1019-6439. PMID 11251186.

External links

MeSH Zif+268+protein,+human

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, 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) · NFIL3 · NRL · NRF1 · XBP1

(1.2) Basic helix-loop-helix (bHLH)	ATOH1 · AhR · AHRR · ARNT · ASCL1 · BHLHB2 · BMAL (ARNTL, ARNTL2) · CLOCK · EPAS1 · HAND (1, 2) · HES (5, 6) · HEY (1, 2, L) · HES1 · HIF (1A, 3A) · ID (1, 2, 3, 4) · LYL1 · MXD4 · MYCL1 · MYCN · Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) · Neurogenins · NeuroD (1, 2) · NPAS (1, 2, 3) · OLIG (1, 2) · Pho4 · Scleraxis · TAL (1, 2) · Twist · USF1

(1.3) bHLH-ZIP	AP-4 · MAX · 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, 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, TFIIF (1, 2), TFIIH (1, 2, 4, 2I, 3A, 3C1, 3C2)) ATBF1 · BCL (6, 11A, 11B) · CTCF · E4F1 · EGR (2, 3) · ERV3 · GFI1 · GLI-Krüppel family (1, 2, 3, REST, S2, YY1) · HIC (1, 2) · HIVEP (1, 2, 3) · IKZF (1, 2, 3) · ILF (2, 3) · KLF (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 17) · MTF1 · MYT1 · OSR1 · SP (1, 2, 4, 7) · Zbtb7 (7A, 7B) · ZBTB (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, 318, 330, 346, 350, 365, 366, 384, 423, 451, 452, 471, 593, 638, 649, 655)

(2.4) Cys₆	HIVEP1

(2.5) Alternating composition	AIRE · DIDO1 · GRLF1 · ING (1, 2, 4) · JARID (1A, 1B, 1C, 1D, 2) · JMJD1B

(3) Helix-turn-helix domains

(3.1) Homeodomain	ARX · CDX (1, 2) · CRX · CUTL1 · DLX (3, 4, 5) · EMX2 · EN (1, 2) · FHL (1, 2, 3) · HESX1 · HHEX · HLX · Homeobox (A1, 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, C13, D1, D3, D4, D8, D9, D10, D11, D12, D13) · HOPX · 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) · PBX (1, 2, 3) · PHF (1, 3, 6, 8, 10, 16, 17, 20, 21A) · 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 · ZEB (1, 2)

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

(3.3) Fork head / winged helix	E2F (1, 2, 3, 4, 5) · FOX proteins (C1, C2, D3, E1, G1, H1, K2, L2, M1, N3, O1, O3, O4, P1, P2, P3)

(3.4) Heat Shock Factors	HSF (1, 2, 4)

(3.5) Tryptophan clusters	ELF (2, 4, 5) · EGF · ELK (1, 3, 4) · ERF · ERG · ETS (1, 2, 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)

(4.4) MADS box	Mef2 (A, B, C, D) · SRF

(4.6) TATA binding proteins	TBP · TBPL1

(4.7) High mobility group	HMGB (1, 2, 3) · 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)

(4.10) 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

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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	O	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

	MUT (zinc finger protein)
	C7 protein
	C7.GAT protein

																				-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	O	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

Zif268

Contents

Structure

Function

Interactions

See also

References

Further reading

External links

																				-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	O	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