Structure Specific Recognition protein 1 (SSRP1) Pleckstrin homology (PH) domain, repeat 1
SSRP1 is a component of FACT (facilitator of chromatin transcription), an essential chromatin reorganizing factor. In yeast FACT (yFACT) is composed of three proteins: Spt16/Cdc68, Pob3, and Nhp6. In metazoans the Pob3 and Nhp6 orthologs are fused to form SSRP1/T160 in human and mouse, respectively. The middle domain of the Pob3 subunit (Pob3-M) has an unusual double pleckstrin homology (PH) architecture. yFACT interacts in a physiologically important way with the central single-strand DNA binding factor RPA to promote a step in DNA Replication. Coordinated function by yFACT and RPA is important during nucleosome deposition. These results support the model that the FACT family has an essential role in constructing nucleosomes during DNA replication, and suggest that RPA contributes to this process. Members of this cd are composed of the first PH-like repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.
Jiyao W et al.(2023). "The conserved domain database in 2023.",