SPOC (Spen paralog and ortholog C-terminal) domain found in PHD finger protein 3 (PHF3), death-inducer obliterator (Dido) variants, and similar proteins
PHF3 is a human homolog of yeast protein bypass of Ess1 (Bye1), a nuclear protein with a domain resembling the central domain in the transcription elongation factor TFIIS. It is ubiquitously expressed in normal tissues including brain, but its expression is significantly reduced or lost in glioblastomas. This group also includes the protein products of the Dido gene that encodes three alternative splicing variants (Dido1, 2, and 3), which have been implicated in several cellular processes such as apoptosis and chromosomal segregation, particularly in the hematopoietic system. The Dido gene is a bone morphogenetic protein (BMP) target gene and promotes BMP-induced melanoma progression. Dido1 is important for maintaining embryonic stem (ES) cells and directly regulates the expression of pluripotency factors. It is the shortest isoform that contains only a highly conserved PHD finger responsible for the binding of histone H3 with a higher affinity for trimethylated lysine4 (H3K4me3). It also triggers apoptosis after nuclear translocation and caspase upregulation. Dido3 is the largest isoform and is ubiquitously expressed in all human tissues. It is dispensable for ES cell self-renewal and pluripotency, but is involved in the maintenance of stem cell genomic stability and tumorigenesis. This model corresponds to the SPOC domain of the PHF3-like group; the SPOC domain is involved in developmental signaling and has also been proposed to be a phosphorylation binding module.
Jiyao W et al.(2023). "The conserved domain database in 2023.",