D
IPR000571

Zinc finger, CCCH-type

InterPro entry
Short nameZnf_CCCH
Overlapping
homologous
superfamilies
 
domain relationships

Description

This entry represents C-x8-C-x5-C-x3-H (CCCH) type Zinc finger (Znf) domains. Proteins containing CCCH Znf domains include Znf proteins from eukaryotes involved in cell cycle or growth phase-related regulation, e.g. human TIS11B (butyrate response factor 1, also known as mRNA decay activator protein ZFP36L1), a probable regulatory protein involved in regulating the response to growth factors, and the mouse TTP growth factor-inducible nuclear protein, which has the same function. The mouse TTP protein is induced by growth factors. Another protein containing this domain is the human splicing factor U2AF 35kDa subunit, which plays a critical role in both constitutive and enhancer-dependent splicing by mediating essential protein-protein interactions and protein-RNA interactions required for 3' splice site selection. It has been shown that different CCCH-type Znf proteins interact with the 3'-untranslated region of various mRNA
[7, 8]
. This type of Znf is very often present in two copies.

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates
[1, 2, 3, 4, 6]
. 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
[5]
. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

References

1.Zinc finger peptides for the regulation of gene expression. Klug A. J. Mol. Biol. 293, 215-8, (1999). View articlePMID: 10529348

2.Multiple modes of RNA recognition by zinc finger proteins. Hall TM. Curr. Opin. Struct. Biol. 15, 367-73, (2005). View articlePMID: 15963892

3.Zinc finger proteins: getting a grip on RNA. Brown RS. Curr. Opin. Struct. Biol. 15, 94-8, (2005). View articlePMID: 15718139

4.Sticky fingers: zinc-fingers as protein-recognition motifs. Gamsjaeger R, Liew CK, Loughlin FE, Crossley M, Mackay JP. Trends Biochem. Sci. 32, 63-70, (2007). View articlePMID: 17210253

5.Zinc finger proteins: new insights into structural and functional diversity. Laity JH, Lee BM, Wright PE. Curr. Opin. Struct. Biol. 11, 39-46, (2001). View articlePMID: 11179890

6.Zinc fingers--folds for many occasions. Matthews JM, Sunde M. IUBMB Life 54, 351-5, (2002). View articlePMID: 12665246

7.Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin. Carballo E, Lai WS, Blackshear PJ. Science 281, 1001-5, (1998). View articlePMID: 9703499

8.Evidence that tristetraprolin binds to AU-rich elements and promotes the deadenylation and destabilization of tumor necrosis factor alpha mRNA. Lai WS, Carballo E, Strum JR, Kennington EA, Phillips RS, Blackshear PJ. Mol. Cell. Biol. 19, 4311-23, (1999). View articlePMID: 10330172

GO terms

biological process

  • None

cellular component

  • None

Cross References

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