PROSITE documentation PDOC51915
ZAD domain profile


C2H2 zinc-finger (ZF) motifs (see <PDOC00028>), which represent the most abundant nucleic acid binding motif in higher eukaryotes, are found in RNA-binding proteins, transcription factors and chromatin components. C2H2 zinc finger proteins frequently contain additional protein modules in their N-termini. The zinc finger-associated domain (ZAD) is found at the N-terminus of the C2H2 proteins of many arthropods [1]. In vertebrates, only one protein containing an N-terminal structure similar to the ZAD has been found, ZFO276. The ZAD-coding genes are subject to an ongoing lineage-specific expansion (LSE), which is most pronounced in the higher holometabolous insects. The ZAD is a protein-protein interaction module with the capability to form homodimers [2,3].

The ZAD size varies between 71 and 97 amino acids and consists of four conserved blocks linked by regions of varying lengths. The structure of the ZAD domain resembles that of a treble-cleft fold and is stabilized by zinc coordination via four cysteine residues found to be invariably present in all identified ZAD peptides (see <PDB:1PZW>). The N-terminal ZAD portion forms a globule around the zinc ion, and the C-terminal stem is formed by a long α-helix that comprises almost one-third of all amino acids in the ZAD. Two ZAD molecules are associated as an antiparallel dimer and most of the amino acid residues that are conserved in the ZAD family form contacts between the two subunits [4].

The profile we developed covers the entire ZAD domain.

Last update:

February 2020 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

ZAD, PS51915; ZAD domain profile  (MATRIX)


1AuthorsChung H.-R. Schaefer U. Jaeckle H. Boehm S.
TitleGenomic expansion and clustering of ZAD-containing C2H2 zinc-finger genes in Drosophila.
SourceEMBO. Rep. 3:1158-1162(2002).
PubMed ID12446571

2AuthorsChung H.-R. Loehr U. Jaeckle H.
TitleLineage-specific expansion of the zinc finger associated domain ZAD.
SourceMol. Biol. Evol. 24:1934-1943(2007).
PubMed ID17569752

3AuthorsFedotova A.A. Bonchuk A.N. Mogila V.A. Georgiev P.G.
TitleC2H2 Zinc Finger Proteins: The Largest but Poorly Explored Family of Higher Eukaryotic Transcription Factors.
SourceActa Naturae. 9:47-58(2017).
PubMed ID28740726

4AuthorsJauch R. Bourenkov G.P. Chung H.-R. Urlaub H. Reidt U. Jaeckle H. Wahl M.C.
TitleThe zinc finger-associated domain of the Drosophila transcription factor grauzone is a novel zinc-coordinating protein-protein interaction module.
SourceStructure 11:1393-1402(2003).
PubMed ID14604529

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