{PDOC51293} {PS51293; SANT} {BEGIN} *********************** * SANT domain profile * *********************** The myb family can be classified into three groups: the myb-type HTH domain, which binds DNA (see ), 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 ), 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 ), the ZZ-type zinc finger (see ), the C2H2-type zinc finger (see ), the GATA-type zinc finger (see ), the MPN-domain (see ) and DEAH ATP-helicase domain (see ). 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 alpha helices (see ) [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 ). 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. -Sequences known to belong to this class detected by the profile: ALL, except 2. -Other sequence(s) detected in Swiss-Prot: NONE. -Note: The SANT domain profile is in competition with profiles of related domains, which include the myb-type HTH DNA-binding domain and myb-like domain (see ). -Last update: February 2007 / First entry. [ 1] Aasland R., Stewart A.F., Gibson T. "The SANT domain: a putative DNA-binding domain in the SWI-SNF and ADA complexes, the transcriptional co-repressor N-CoR and TFIIIB." Trends Biochem. Sci. 21:87-88(1996). PubMed=8882580 [ 2] Gruene T., Brzeski J., Eberharter A., Clapier C.R., Corona D.F.V., Becker P.B., Mueller C.W. "Crystal structure and functional analysis of a nucleosome recognition module of the remodeling factor ISWI." Mol. Cell 12:449-460(2003). PubMed=14536084 [ 3] Boyer L.A., Latek R.R., Peterson C.L. "The SANT domain: a unique histone-tail-binding module?" Nat. Rev. Mol. Cell Biol. 5:158-163(2004). PubMed=15040448 [ 4] Yao Y.-L., Yang W.-M. "The metastasis-associated proteins 1 and 2 form distinct protein complexes with histone deacetylase activity." J. Biol. Chem. 278:42560-42568(2003). PubMed=12920132; DOI=10.1074/jbc.M302955200 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}