ZnF_C4

c4 zinc finger in nuclear hormone receptors		 ZnF_C4
SMART accession number:SM00399
Description:
Interpro abstract (IPR001628):

Steroid or nuclear hormone receptors constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. The receptors function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner. Nuclear hormone receptors consist of a highly conserved DNA-binding domain that recognises specific sequences, connected via a linker region to a C-terminal ligand-binding domain (IPR000536). In addition, certain nuclear hormone receptors have an N-terminal modulatory domain (IPR001292). The DNA-binding domain can elicit either an activating or repressing effect by binding to specific regions of the DNA known as hormone-response elements (PUBMED:15242341), (PUBMED:15242339). These response elements position the receptors, and the complexes recruited by them, close to the genes of which transcription is affected. The DNA-binding domains of nuclear receptors consist of two zinc-nucleated modules and a C-terminal extension, where residues in the first zinc module determine the specificity of the DNA recognition and residues in the second zinc module are involved in dimerisation. The DNA-binding domain is furthermore involved in several other functions including nuclear localization, and interaction with transcription factors and co-activators (PUBMED:15242339).

Zinc finger (Znf) domains are relatively small protein motifs that bind one or more zinc atoms, and which usually contain multiple finger-like protrusions that make tandem contacts with their target molecule. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis, however they are now recognised to bind DNA, RNA, protein and/or lipid substrates (PUBMED:10529348), (PUBMED:15963892), (PUBMED:15718139), (PUBMED:17210253), (PUBMED:12665246). Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few (PUBMED:11179890). Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

(Note that in certain cases, some Znf domains have diverged such that they still maintain their core structure, but have lost their ability to bind zinc, using other means such as salt bridges or binding to other metals to stabilise the finger-like folds. These domains can show strong sequence identity to zinc-binding motifs, and may therefore be included in Znf entries).

This entry represents the two C4-type zinc finger modules involved in DNA-binding.

More information about these proteins can be found at Protein of the Month: Zinc Fingers.

GO process:regulation of transcription, DNA-dependent (GO:0006355)
GO component:nucleus (GO:0005634)
GO function:transcription factor activity (GO:0003700), sequence-specific DNA binding (GO:0043565), zinc ion binding (GO:0008270)
Family alignment:
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There are 3070 ZnF_C4 domains in 3063 proteins in SMART's nrdb database.

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