SANTA domain: a novel conserved protein module in Eukaryota with potential involvement in chromatin regulation

Abstract

Since packaging of DNA in the chromatin structure restricts the accessibility for regulatory factors, chromatin remodeling is required to facilitate nuclear processes such as gene transcription, replication, and genome recombination. Many conserved non-enzymatic protein domains have been identified that contribute to the activities of multiprotein remodeling complexes. Here we identified a novel conserved protein domain in Eukaryota whose putative function may be in regulating chromatin remodeling. Since this domain is associated with a known SANT domain in several vertebrate proteins, we named it the SANTA (SANT Associated) domain. Sequence analysis showed that the SANTA domain is approximately a 90 amino acid module and likely composed of four central beta-sheets and three flanking alpha-helices. Many hydrophobic residues exhibited high conservation along the domain, implying a possible function in protein-protein interactions. The SANTA domain was identified in mammals, chicken, frog, fish, sea squirt, sea urchin, worms and plants. Furthermore, a phylogenetic tree of SANTA domains showed that one plant-specific duplication event happened in the Viridiplantae lineage.

Xenopus laevis M18BP1 Directly Binds Existing CENP-A Nucleosomes to Promote Centromeric Chromatin Assembly

“…The region between 747-944 is predicted to be largely unstructured, and was prone to aggregation during purification, thus the decreased binding of 747-944 versus full-length M18BP1 may reflect protein aggregation rather than truncation of additional binding residues. CENP-A nucleosome recognition was not dependent on M18BP1’s SANT DNA-binding domain or SANTA protein interaction domain (Figure 1D-F) (Zhang et al, 2006). Taken together, Xenopus laevis M18BP1 binds CENP-A nucleosomes directly via a binding site within amino acids 747-944.…”

Targeting of Arabidopsis KNL2 to Centromeres Depends on the Conserved CENPC-k Motif in Its C Terminus

“…KNL2 was first described in nematodes and in vertebrates (Maddox et al, 2007), where it is characterized by both a C-terminal SANT/ Myb domain (Boyer et al, 2002) and a unique N-terminal SANTA domain (Zhang et al, 2006). In Arabidopsis, KNL2 has a SANTA domain but lacks a SANT domain , suggesting that the SANTA domain is a conserved feature of KNL2 homologs.…”

Putting CENP-A in its place

“…Mis18BP1 KNL2 contains a SANT (Swi3-Ada2-NCoR-TFIIIB) domain as well as a SANT-Associated (SANTA) domain [64, 92]. The SANTA domain was found in silico as a domain that characteristically is present in proteins which also contain a SANT domain [92]. In the human proteome, the SANTA domain has been identified exclusively in Mis18BP1 KNL2 .…”

“…In the human proteome, the SANTA domain has been identified exclusively in Mis18BP1 KNL2 . The function of the SANTA domain is currently unknown, although, the conserved hydrophobic residues are proposed to be involved in protein–protein interactions, possibly mediating Mis18BP1 KNL2 interactions with its various binding partners at the centromere [92]. …”