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PROSITE documentation PDOC50103Zinc finger C3H1-type profile
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PURL: https://purl.expasy.org/prosite/documentation/PDOC50103
The well conserved cysteine-histidine arrangement, C-x(8)-C-x(5)-C-x(3)-H, of the C3H1-type zinc finger is present in many eukaryotic proteins from yeast to mammals. In various proteins the C3H1-type zinc finger has been shown to interact with the 3'-untranslated region of mRNAs (see below). It is very often present in two copies [1,2].
The structure of the two C3H1-type zinc fingers of the protein TIS11d bound to its target mRNA has been solved (see <PDB:1RGO>) [3]. The two zinc fingers fold independently to form small, compact domains connected by the linker sequence. The polypeptide backbone adopts little regular secondary structure. In each zinc finger, there is a short α-helix immediately after the first cysteine ligand and a turn of 3/10 helix between the second and third cysteine ligands. All amino acid residues that exhibit intermolecular contacts with the RNA are positioned on a single surface of each zinc finger.
Some proteins known to contain a C3H1-type zinc finger are listed below:
- Mammalian tristetraprolin (TTP) proteins, prototype of the C3H1 zinc finger proteins, inhibit TNF α production from macrophages by destabilizing its messenger RNA [2]. TTP is a specific RNA-binding protein; the region encompassing the two C3H1-type zinc fingers recognizes nonameric UUAUUUAUU sequences present in the 3'-untranslated region (UTR) of TNF α [4,5].
- Eukaryotic TIS/CTH family. Regulatory protein involved in regulating the response to growth factors similar to TTP. The tandem zinc finger domain of the protein TIS11d binds to the class II AU-rich element (ARE) in the 3' untranslated region (3' UTR) of target mRNAs and promotes their deadenylation and degradation [6].
- Eukaryotic U2AG, U2R1, U2R2 proteins, small nuclear ribonucleoproteins (1 or 2 copies).
- Caenorhabditis Elegans PIE1 protein. It is required for specification of embryonic germ cells lineage and for the lack of mRNA transcription in these cells (2 copies).
- Caenorhabditis Elegans POS-1 protein. A cytoplasmic protein similar to TIS11, essential for germ line specification in C. elegans (2 copies).
- Eukaryotic cleavage and polyadenylation specificity factor subunit 4 (Cpsf4) protein. It plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. Cpsf4 binds RNA polymers with a preference for poly(U) (5 copies).
- Schizosaccharomyces pombe ZFS1 protein. It was isolated as a suppressor of the sterility caused by overexpression of a double-stranded RNase (2 copies).
- Human Z183 protein, contains one ring finger and one C3H1-type zinc finger.
- Mammalian Nucleoporin-like 2, required for the export of mRNAs containing poly(A) tails from the nucleus into the cytoplasm (1 copy).
The profile we developed covers the entire C3H1-type zinc finger.
Last update:June 2008 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Hall T.M. |
| Title | Multiple modes of RNA recognition by zinc finger proteins. | |
| Source | Curr. Opin. Struct. Biol. 15:367-373(2005). | |
| PubMed ID | 15963892 | |
| DOI | 10.1016/j.sbi.2005.04.004 |
| 2 | Authors | Brown R.S. |
| Title | Zinc finger proteins: getting a grip on RNA. | |
| Source | Curr. Opin. Struct. Biol. 15:94-98(2005). | |
| PubMed ID | 15718139 | |
| DOI | 10.1016/j.sbi.2005.01.006 |
| 3 | Authors | Hudson B.P. Martinez-Yamout M.A. Dyson H.J. Wright P.E. |
| Title | Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d. | |
| Source | Nat. Struct. Mol. Biol. 11:257-264(2004). | |
| PubMed ID | 14981510 | |
| DOI | 10.1038/nsmb738 |
| 4 | Authors | Lai W.S. Carballo E. Strum J.R. Kennington E.A. Phillips R.S. Blackshear P.J. |
| Title | Evidence that tristetraprolin binds to AU-rich elements and promotes the deadenylation and destabilization of tumor necrosis factor alpha mRNA. | |
| Source | Mol. Cell. Biol. 19:4311-4323(1999). | |
| PubMed ID | 10330172 |
| 5 | Authors | Lai W.S. Parker J.S. Grissom S.F. Stumpo D.J. Blackshear P.J. |
| Title | Novel mRNA targets for tristetraprolin (TTP) identified by global analysis of stabilized transcripts in TTP-deficient fibroblasts. | |
| Source | Mol. Cell. Biol. 26:9196-9208(2006). | |
| PubMed ID | 17030620 | |
| DOI | 10.1128/MCB.00945-06 |
| 6 | Authors | Hudson B.P. Martinez-Yamout M.A. Dyson H.J. Wright P.E. |
| Title | Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d. | |
| Source | Nat. Struct. Mol. Biol. 11:257-264(2004). | |
| PubMed ID | 14981510 | |
| DOI | 10.1038/nsmb738 |
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