PROSITE documentation PDOC52014

SAMD1-like winged helix (WH) domain profile

The SAMD1-like winged helix (WH) domain forms a group of WH domains with shared sequence homology found in the following transcriptional regulators:

• Animal SAM domain-containing protein 1 (SAMD1) (also named Atherin), an unmethylated CGI-binding protein that cooperates with chromatin regulators to modulate the chromatin landscape and down-regulate its target genes [1].
• Animal Lysine Acetyltransferase 6A (KAT6A), also named MYST3 and MOZ Monocytic leukemic zinc-finger), a histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 [1].
• Animal Lysine Acetyltransferase 6B (KAT6B), also named MYST4 and MORF (Monocytic leukemia zinc finger protein-related factor), a histone acetyltransferase which may be involved in both positive and negative regulation of transcription.
• Animal zinc finger MYND-type containing 11 (ZMYND11), a transcriptional co- repressor that interacts selectively with histone H3.3.

Within this group, the SAMD1-like WH domains of KAT6A, -B and SAMD1 are similar to each other, while the one of ZMYND11 is more distant. The KAT6A, -B and SAMD1 SAMD1-like WH domain directly recognizes unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove [1,2].

The SAMD1-like WH domain has the fold of a winged helix domain that contains three α helices at the N-terminal half and two β strands at the C-terminal half (see <PDB:6LUI>). Wing-like loops between strands β1 and β2 (W1) and after β2 (W2) are observed. Both the major groove and the minor groove of the CpG-containing DNA are recognized. The C terminal end of the α1 helix inserts into the CpG-containing major groove. The DNA minor groove is contacted either trough the W1 loop (SAMD1) or through the W2 loop (KAT6A) [1,2].

The profile we developed covers the entire SAMD1-like WH domain.