PROSITE documentation PDOC51293

SANT domain profile

The myb family can be classified into three groups: the myb-type HTH domain, which binds DNA (see <PDOC00037>), the SANT domain, which is a protein-protein interaction module and the myb-like domain that can be involved in either of these functions.

The SANT domain is a motif of ~50 amino acids present in proteins involved in chromatin-remodelling and transcription regulation. This eukaryotic domain was identified in nuclear receptor co-repressors and named after switching-defective protein 3 (Swi3), adaptor 2 (Ada2), nuclear receptor co-repressor (N-CoR) and transcription factor (TF)IIIB [1]. Although SANT domains show remarkable sequence and structural similarity to the DNA-binding helix-turn-helix (HTH) domain of the myb-like tandem repeat (see <PDOC00037>), their function is not DNA binding. Instead, SANT domains are protein-protein interaction modules and some can bind to histone tails (e.g. in Ada2 and SMRT). SANT domains are found in combination with other domains, such as the SWIRM domain (see <PDOC50934>), the ZZ-type zinc finger (see <PDOC50135>), the C2H2-type zinc finger (see <PDOC00028>), the GATA-type zinc finger (see <PDOC00300>), the MPN-domain (see <QDOC50249>) and DEAH ATP-helicase domain (see <PDOC00039>). The SANT domain was proposed to function as a histone-interaction module that couples histone-tail binding to enzyme catalysis for the remodelling of nucleosomes [2,3].

The 3-dimensional structure of the SANT domain forms three α helices (see <PDB:1OFC>) [2] similar to the DNA-binding myb-type HTH domain. Because of the strong resemblance, the SANT domain can also be detected as a myb-like "DNA-binding" domain (see <PDOC00037>). Most SANT domains have acidic amino acids at the start of helix 2 and in helix 3, while myb-like DNA-binding domains have more positively charged residues, in particular in their third 'recognition' helix. The bulky aromatic and hydrophobic residues in the center of helix 3 that are incompatible with DNA contacts of myb-like DNA-binding domains form another distinguishing property of SANT domains.

Some proteins known to contain a SANT domain:

• Baker's yeast ada2, the transcriptional adaptor 2 protein, a subunit of many Gcn5 (general control of amino-acid synthesis protein 5)-containing histone-acetyltransferase complexes of histone modifying enzymes. Eukaryotic ada2-like proteins are associated with chromatin and mediate protein-protein interactions.
• Baker's yeast rsc8 protein of the RSC (remodel the structure of chromatin) complex of ATP-dependent chromatin-remodelling enzymes.
• Human N-CoR and SMRT (silencing mediator of retinoid and thyroid receptors), both are subunits of histone deacetylase complexes of histone-modifying enzymes. Both proteins contain a pair of SANT domains spaced by ~130 aa.
• Baker's yeast Swi3, a transcription regulatory protein of the SWI/SNF (switching-defective/sucrose non-fermenting) complex of ATP-dependent chromatin-remodelling enzymes.
• Fruit fly ISWI, imitation switch protein, an ATP-dependent chromatin remodelling enzyme conserved from yeast to human. In addition to the SANT domain, it contains a SLIDE (SANT-like ISWI) domain that can bind DNA [2].
• Human SMARCC1, SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily c protein.
• Mammalian MTA1 and MTA2, metastasis-associated proteins 1 and 2, components of distinct complexes with histone deacetylase activity and both repress transcription specifically [4].

The profile we developed covers the entire SANT domain. SANT-specific positions within the profile have been manually adapted.