Home  |  Contact
PROSITE documentation PDOC51533 [for PROSITE entry PS51533]

ADD domain profile





Description

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 (see <PDOC50016>). The region between the two subdomains has a constant length, and it contains identical and conserved amino acids [1,2]. The ADD domain binds to the histone H3 tail that is unmethylated at lysine 4 [3,4].

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 characterizes 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 (see <PDB:2JM1). Starting at the N terminus, there is first a subdomain that binds a single zinc ion through four cysteines and is structurally very similar to the zinc fingers of the erythroid transcription factor GATA-1 (see <PDOC00300>). 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 α-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 [2,4].

The profile we developed covers the entire ADD domain.

Last update:

April 2011 / First entry.

Technical section

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

ADD, PS51533; ADD domain profile  (MATRIX)


References

1AuthorsAapola U. Kawasaki K. Scott H.S. Ollila J. Vihinen M. Heino M. Shintani A. Kawasaki K. Minoshima S. Krohn K. Antonarakis S.E. Shimizu N. Kudoh J. Peterson P.
TitleIsolation and initial characterization of a novel zinc finger gene, DNMT3L, on 21q22.3, related to the cytosine-5-methyltransferase 3 gene family.
SourceGenomics 65:293-298(2000).
PubMed ID10857753
DOI10.1006/geno.2000.6168

2AuthorsArgentaro A. Yang J.-C. Chapman L. Kowalczyk M.S. Gibbons R.J. Higgs D.R. Neuhaus D. Rhodes D.
TitleStructural consequences of disease-causing mutations in the ATRX-DNMT3-DNMT3L (ADD) domain of the chromatin-associated protein ATRX.
SourceProc. Natl. Acad. Sci. U.S.A. 104:11939-11944(2007).
PubMed ID17609377
DOI10.1073/pnas.0704057104

3AuthorsOoi S.K.T. Qiu C. Bernstein E. Li K. Jia D. Yang Z. Erdjument-Bromage H. Tempst P. Lin S.-P. Allis C.D. Cheng X. Bestor T.H.
TitleDNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA.
SourceNature 448:714-717(2007).
PubMed ID17687327
DOI10.1038/nature05987

4AuthorsOtani J. Nankumo T. Arita K. Inamoto S. Ariyoshi M. Shirakawa M.
TitleStructural basis for recognition of H3K4 methylation status by the DNA methyltransferase 3A ATRX-DNMT3-DNMT3L domain.
SourceEMBO Rep. 10:1235-1241(2009).
PubMed ID19834512
DOI10.1038/embor.2009.218



PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)