PROSITE documentation PDOC51802 [for PROSITE entry PS51802]Zinc finger CCHHC-type profile
Zinc finger (ZF) proteins are a large family of metalloproteins that utilize zinc for structural purposes. Zinc coordinates to a combination of cysteine thiol and histidine imidazole residues within the ZF polypetide sequence resulting in a folded and functional protein. The CCHHC family of ZFs is a small family of "nonclassical" ZFs that are essential for the development of the central nervous system. These proteins have up to seven putative zinc-binding sequences, usually arranged in sets of two or more sequences. The CCHHC-type zinc finger is able to bind specific double-stranded DNA sequences [1,2,3,4,5].
The CCHHC-type zinc finger contains five absolutely conserved cysteine and histidine residues (rather than the more usual four) with the sequence C-P-x-P-G-C-x-G-x-G-H-x(7)-H-R-x(4)-C. The second histidine has been shown to coordinate Zn(II) along with the three cysteines residues. The first His plays a different role in stabilizing the structure, stacking between the metal-binding core and an aromatic residue that is relatively conserved within this domain family. CCHHC-type zinc fingers form small compact structures that can sit entirely within the major groove of DNA (see <PDB:2JX1>) [1,2,3,4,5].
Some proteins known to contain a CCHHC-type zinc finger are listed below:
- Animal myelin transcription factor 1 (MyT1), or neural zinc finger 2 (NZF2), a transcription factor that contains seven copies of the CCHHC-type zinc finger. It binds to sites in the proteolipid protein promoter.
- Vertebrate MyT1-like (MyT1L/NZF1), appears to be involved in neural development.
- Vertebrate Suppressor of Tumorigenicity 18 (ST18/NZF3), a breast cancer tumor suppressor.
- Vertebrate L3MBTL, a member of the Polycomb group of proteins, which function as transcriptional repressors in large protein complexes.
- Vertebrate L3MBTL3, a possible tumor suppressor.
- Vertebrate L3MBTL4.
The profile we developed covers the entire CCHHC-type zinc finger.
Last update:June 2016 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Gamsjaeger R. Swanton M.K. Kobus F.J. Lehtomaki E. Lowry J.A. Kwan A.H. Matthews J.M. Mackay J.P. |
| Title | Structural and biophysical analysis of the DNA binding properties of myelin transcription factor 1. | |
| Source | J. Biol. Chem. 283:5158-5167(2008). | |
| PubMed ID | 18073212 | |
| DOI | 10.1074/jbc.M703772200 |
| 2 | Authors | Gamsjaeger R. O'Connell M.R. Cubeddu L. Shepherd N.E. Lowry J.A. Kwan A.H. Vandevenne M. Swanton M.K. Matthews J.M. Mackay J.P. |
| Title | A structural analysis of DNA binding by myelin transcription factor 1 double zinc fingers. | |
| Source | J. Biol. Chem. 288:35180-35191(2013). | |
| PubMed ID | 24097990 | |
| DOI | 10.1074/jbc.M113.482075 |
| 3 | Authors | Lee S.J. Michel S.L.J. |
| Title | Structural metal sites in nonclassical zinc finger proteins involved in transcriptional and translational regulation. | |
| Source | Acc. Chem. Res. 47:2643-2650(2014). | |
| PubMed ID | 25098749 | |
| DOI | 10.1021/ar500182d |
| 4 | Authors | Besold A.N. Michel S.L. |
| Title | Neural Zinc Finger Factor/Myelin Transcription Factor Proteins: Metal Binding, Fold, and Function. | |
| Source | Biochemistry 54:4443-4452(2015). | |
| PubMed ID | 26158299 | |
| DOI | 10.1021/bi501371a |
| 5 | Authors | Berkovits-Cymet H.J. Amann B.T. Berg J.M. |
| Title | Solution structure of a CCHHC domain of neural zinc finger factor-1 and its implications for DNA binding. | |
| Source | Biochemistry 43:898-903(2004). | |
| PubMed ID | 14744132 | |
| DOI | 10.1021/bi035159d |
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