Pathways & interactions
ADD domain (IPR025766)
Short name: ADD
Overlapping homologous superfamilies
One of the largest protein families in the human genome is the zinc finger family that contains members involved in the regulation of transcription processes. The zinc finger domains have been classified based on the order of cysteine (C) and histidine (H) residues. Zinc fingers are thought to mediate protein-DNA and protein-protein interactions. The ADD (ATRX, DNMT3, DNMT3L) domain is a cysteine-rich region that consists of a C2C2-type zinc finger and a closely located domain of an imperfect PHD-type zinc finger with C4C4. The region between the two subdomains has a constant length, and it contains identical and conserved amino acids [PMID: 10857753, PMID: 17609377]. The ADD domain binds to the histone H3 tail that is unmethylated at lysine 4 [PMID: 17687327, PMID: 19834512].
The ADD domain is present in chromatin-associated proteins that play a role in establishing and/or maintaining a normal pattern of DNA methylation:
- DNMT3A, DNMT3B, DNA methyltransferases.
- DNMT3L, a DNMT3-like enzymatically inactive regulatory factor.
- ATRX, a large nuclear protein predominantly localized to heterochromatin and nuclear PML bodies. At the C terminus is a helicase/ATPase domain, which characterises ATRX as a member of the SNF2 (SWI/SNF) family of chromatin-associated proteins.
The ADD domain is composed of three clearly distinguishable modules that pack together through extensive hydrophobic interactions to form a single globular domain. Packed against this GATA-like finger is a second subdomain, which binds two zinc ions and closely resembles the structure reported for several PHD fingers. Finally, there is a long C-terminal alpha-helix that runs out from the PHD finger and makes extensive hydrophobic contacts with the N- terminal GATA finger, bringing the N- and C-termini of the ADD domain close together. This combination of fused GATA-like and PHD fingers within a single domain is thus far unique [PMID: 17609377, PMID: 19834512].
- PS51533 (ADD)