{PDOC51533}
{PS51533; ADD}
{BEGIN}
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* ADD domain profile *
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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 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 [2,4].

The profile we developed covers the entire ADD domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: April 2011 / First entry.

[ 1] Aapola 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.
     "Isolation and initial characterization of a novel zinc finger gene,
     DNMT3L, on 21q22.3, related to the cytosine-5-methyltransferase 3 gene
     family."
     Genomics 65:293-298(2000).
     PubMed=10857753; DOI=10.1006/geno.2000.6168
[ 2] Argentaro A., Yang J.-C., Chapman L., Kowalczyk M.S., Gibbons R.J.,
     Higgs D.R., Neuhaus D., Rhodes D.
     "Structural consequences of disease-causing mutations in the
     ATRX-DNMT3-DNMT3L (ADD) domain of the chromatin-associated protein
     ATRX."
     Proc. Natl. Acad. Sci. U.S.A. 104:11939-11944(2007).
     PubMed=17609377; DOI=10.1073/pnas.0704057104
[ 3] Ooi 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.
     "DNMT3L connects unmethylated lysine 4 of histone H3 to de novo
     methylation of DNA."
     Nature 448:714-717(2007).
     PubMed=17687327; DOI=10.1038/nature05987
[ 4] Otani J., Nankumo T., Arita K., Inamoto S., Ariyoshi M., Shirakawa M.
     "Structural basis for recognition of H3K4 methylation status by the
     DNA methyltransferase 3A ATRX-DNMT3-DNMT3L domain."
     EMBO Rep. 10:1235-1241(2009).
     PubMed=19834512; DOI=10.1038/embor.2009.218

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