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Zif268




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
Symbol(s) EGR1; AT225; G0S30; KROX-24; NGFI-A; TIS8; ZIF-268; ZNF225
External IDs OMIM: 128990 MGI: 95295 Homologene: 56394
RNA expression pattern

More reference expression data

Orthologs
Human Mouse
Entrez 1958 13653
Ensembl ENSG00000120738 ENSMUSG00000038418
Uniprot P18146 Q3UM09
Refseq NM_001964 (mRNA)
NP_001955 (protein) 		NM_007913 (mRNA)
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 differentitation and mitogenesis. Studies suggest this is a cancer suppresor gene.[1]


Contents

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'-GC[G/T]GGGCG-3.[3][4]

It has a distinct pattern of expression in the brain, and its induction has been shown to be assiociated 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]

See also

References

  1. ^ Entrez Gene: EGR1 early growth response 1.
  2. ^ 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.
  3. ^ Christy, B. and D. Nathans (1989). "DNA binding site of the growth factor-inducible protein Zif268." Proc Natl Acad Sci U S An 86(22): 8737-41.
  4. ^ Swirnoff, A. H. and J. Milbrandt (1995). "DNA-binding specificity of NGFI-A and related zinc finger transcription factors." Mol Cell Biol 15(4): 2275-87.
  5. ^ 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
  6. ^ 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

Further reading

  • Heath RG (1975). "Brain function and behavior. I. Emotion and sensory phenomena in psychotic patients and in experimental animals.". J. Nerv. Ment. Dis. 160 (3): 159-75. PMID 1090709.
  • Silverman ES, Collins T (1999). "Pathways of Egr-1-mediated gene transcription in vascular biology.". Am. J. Pathol. 154 (3): 665-70. PMID 10079243.
  • Adamson ED, Mercola D (2002). "Egr1 transcription factor: multiple roles in prostate tumor cell growth and survival.". Tumour Biol. 23 (2): 93-102. PMID 12065847.
  • Blaschke F, Bruemmer D, Law RE (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.
  • Abdulkadir SA (2006). "Mechanisms of prostate tumorigenesis: roles for transcription factors Nkx3.1 and Egr1.". Ann. N. Y. Acad. Sci. 1059: 33-40. doi:10.1196/annals.1339.018. PMID 16382041.
v • d • e
Transcription factors and intracellular receptors
(1) Basic domains
(1.1) Basic leucine zipper (bZIP) Activating transcription factor (1, 2, 3, 4, 5, 6) • AP-1 (c-Fos, FOSB, FOSL1, FOSL2, c-Jun, JUNB, JUND) • BACH (1, 2) • C/EBP (α, β, γ, δ, ε, ζ) • CREB (1, 3) • GABPA • MAF (B, F, G, K) • NRL • NRF1 • XBP1
(1.2) Basic helix-loop-helix (bHLH) ATOH1 • AhR • AHRR • ARNT • ASCL1 • BMAL (ARNTL, ARNTL2) • CLOCK • HIF (1A, 3A) • Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) • NEUROD1 • Twist • USF1
(1.3) bHLH-ZIP Myc • MITF • SREBP (1, 2)
(1.6) Basic helix-span-helix (bHSH) AP-2
(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 (Estrogen (α, β), Estrogen related (α, β, γ), Androgen, Glucocorticoid, Mineralocorticoid, Progesterone)) • 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)
(2.3) Cys2His2 General transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH: 1, 2) • GLI-Krüppel family (1, 2, 3, YY1) • KLF (2, 4, 5, 6, 10, 11, 12, 13) • Sp1 • zinc finger (3, 35, 43, 146, 148, 165, 217, 268, 281, 350) • Zbtb7 (7A) • ZBT (16, 17, 33)
(2.4) Cys6 HIVEP1
(3) Helix-turn-helix
domains
(3.1) Homeo domain ARX • Homeobox (A1, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C6, C8, C9, C13, D1, D3, D4, D9, D10, D11, D12, D13) • NANOG • NKX (2-1, 2-5, 3-1) • POU domain (PIT-1, BRN-3: 1, 2, Octamer transcription factor: 1, 2, 3/4, 6, 7)
(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, E1, G1, H1, L2, M1, N3, O3, O4, P1, P2, P3)
(3.4) Heat Shock Factors HSF1
(3.5) Tryptophan clusters ELF (4, 5) • Interferon regulatory factors (1, 2, 3, 4, 5, 6, 7, 8) • MYB
(3.6) TEA domain transcriptional enhancer factor 1, 2
(4) β-Scaffold factors with
minor groove contacts
(4.1) Rel homology region NF-κB (NFKB1, NFKB2, REL, RELA, RELB) • NFAT (5, C1, C2, C3, C4)
(4.2) STAT STAT (1, 2, 3, 4, 5, 6)
(4.3) p53 p53
(4.4) MADS box Mef2 (A, B, C, D) • SRF
(4.7) High mobility group HNF (1A, 1B) • LEF1 • SOX (3, 4, 6, 9, 10, 13, 18) • SRY • SSRP1
(4.10) Cold-shock domain CSDA
(4.11) Runt CBF (RUNX1, RUNX2, RUNX3)
(0) Other
transcription factors
(0.2) HMGI(Y) HMGA (1, 2)
(0.3) Pocket domain Rb • RBL1 • RBL2
(0.6) Miscellaneous ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • Rho/Sigma • R-SMAD
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Zif268". A list of authors is available in Wikipedia.
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