ZZ zinc finger

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Symbol ZZ
Pfam PF00569
Pfam clan CL0006
InterPro IPR000433
CDD cd02249

In molecular biology the ZZ-type zinc finger domain is a type of protein domain that was named because of its ability to bind two zinc ions.[1] These domains contain 4-6 Cys residues that participate in zinc binding (plus additional Ser/His residues), including a Cys-X2-Cys motif found in other zinc finger domains. These zinc fingers are thought to be involved in protein-protein interactions. The structure of the ZZ domain shows that it belongs to the family of cross-brace zinc finger motifs that include the PHD, RING, and FYVE domains.[2] ZZ-type zinc finger domains are found in:

Single copies of the ZZ zinc finger occur in the transcriptional adaptor/coactivator proteins P300, in cAMP response element-binding protein (CREB)-binding protein (CBP) and ADA2. CBP provides several binding sites for transcriptional coactivators. The site of interaction with the tumour suppressor protein p53 and the oncoprotein E1A with CBP/P300 is a Cys-rich region that incorporates two zinc-binding motifs: ZZ-type and TAZ2-type. The ZZ-type zinc finger of CBP contains two twisted anti-parallel beta-sheets and a short alpha-helix, and binds two zinc ions.[2] One zinc ion is coordinated by four cysteine residues via 2 Cys-X2-Cys motifs, and the third zinc ion via a third Cys-X-Cys motif and a His-X-His motif. The first zinc cluster is strictly conserved, whereas the second zinc cluster displays variability in the position of the two His residues.

In Arabidopsis thaliana (Mouse-ear cress), the hypersensitive to red and blue 1 (Hrb1) protein, which regulating both red and blue light responses, contains a ZZ-type zinc finger domain.[3]

ZZ-type zinc finger domains have also been identified in the testis-specific E3 ubiquitin ligase MEX that promotes death receptor-induced apoptosis.[4] MEX has four putative zinc finger domains: one ZZ-type, one SWIM-type and two RING-type. The region containing the ZZ-type and RING-type zinc fingers is required for interaction with UbcH5a and MEX self-association, whereas the SWIM domain was critical for MEX ubiquitination.

In addition, the Cys-rich domains of dystrophin, utrophin and an 87kDa post-synaptic protein contain a ZZ-type zinc finger with high sequence identity to P300/CBP ZZ-type zinc fingers. In dystrophin and utrophin, the ZZ-type zinc finger lies between a WW domain (flanked by and EF hand) and the C-terminal coiled-coil domain. Dystrophin is thought to act as a link between the actin cytoskeleton and the extracellular matrix, and perturbations of the dystrophin-associated complex, for example, between dystrophin and the transmembrane glycoprotein beta-dystroglycan, may lead to muscular dystrophy. Dystrophin and its autosomal homologue utrophin interact with beta-dystroglycan via their C-terminal regions, which are composed of a WW domain, an EF hand domain, and a ZZ-type zinc finger domain.[5] The WW domain is the primary site of interaction between dystrophin or utrophin and dystroglycan, while the EF hand and ZZ-type zinc finger domains stabilise and strengthen this interaction.


  1. ^ Ponting CP, Blake DJ, Davies KE, Kendrick-Jones J, Winder SJ (January 1996). "ZZ and TAZ: new putative zinc fingers in dystrophin and other proteins". Trends Biochem. Sci. 21 (1): 11–13. PMID 8848831. doi:10.1016/s0968-0004(06)80020-4. 
  2. ^ a b Legge GB, Martinez-Yamout MA, Hambly DM, Trinh T, Lee BM, Dyson HJ, Wright PE (October 2004). "ZZ domain of CBP: an unusual zinc finger fold in a protein interaction module". J. Mol. Biol. 343 (4): 1081–93. PMID 15476823. doi:10.1016/j.jmb.2004.08.087. 
  3. ^ Kang X, Chong J, Ni M (March 2005). "HYPERSENSITIVE TO RED AND BLUE 1, a ZZ-type zinc finger protein, regulates phytochrome B-mediated red and cryptochrome-mediated blue light responses". Plant Cell. 17 (3): 822–35. PMC 1069701Freely accessible. PMID 15705950. doi:10.1105/tpc.104.029165. 
  4. ^ Nishito Y, Hasegawa M, Inohara N, Núñez G (June 2006). "MEX is a testis-specific E3 ubiquitin ligase that promotes death receptor-induced apoptosis". Biochem. J. 396 (3): 411–7. PMC 1482824Freely accessible. PMID 16522193. doi:10.1042/BJ20051814. 
  5. ^ Hnia K, Zouiten D, Cantel S, Chazalette D, Hugon G, Fehrentz JA, Masmoudi A, Diment A, Bramham J, Mornet D, Winder SJ (February 2007). "ZZ domain of dystrophin and utrophin: topology and mapping of a beta-dystroglycan interaction site". Biochem. J. 401 (3): 667–77. PMC 1770854Freely accessible. PMID 17009962. doi:10.1042/BJ20061051. 

This article incorporates text from the public domain Pfam and InterPro IPR000433