SHPRH subfamily

The SHPRH proteins are a particularly interesting example of ‘modular’ insertions in the helicase-like region of the Snf2 family. The subfamily derives its name from the ordered sequence of domains Snf2_N, Linker_Histone (ie H1), PHD finger, Zf_C3HC4 (ie RING finger), Helicase_C in the human member 1, which reflects the insertion of three additional domains within the canonical helicase-like region (Snf2_N and Helicase C are the common bipartite homology blocks of the Snf2 family helicase-like region).

The additional domains are accommodated at two sites: the Linker_Histone and PHD finger motifs are adjacent to each other, inserted between helicase motif I and Ia at the minor insertion site between motifs I and Ia.

The linker histone-related domain in human SHPRH corresponds to the sequences forming the globular winged helix structure of histone H1 2 and transcription factor HNF3 3, 4. The PHD finger motifs are specialised zinc finger structures which occur in a range of proteins involved in chromatin-mediated transcriptional regulation but whose exact function is unclear 5, 6.

Like the other subfamilies containing the RING finger domain, this motif is located at the major insertion site between motifs III and IV (see below). In addition, immediately upstream of the RING finger domain and within the major insertion region, animal SHPRH members contain an addition 50kD polypeptide sequence without an identifiable motif. This region has a number of cysteines suggestive of a zinc finger type coordination and has some 30% charged residues.

Fungal SHPRH members typically do not contain the linker histone-related motif, although they retain the PHD and RING finger domains and also contain a large domain with high number of charged residues ahead of the RING finger.

names associated with subfamily members
1: Sood, R., I. Makalowska, et al. (2003). Cloning and characterization of a novel gene, SHPRH, encoding a conserved putative protein with SNF2/helicase and PHD-finger domains from the 6q24 region. Genomics 82(2): 153-61. PubMed
2: Ramakrishnan, V., J. T. Finch, et al. (1993). Crystal structure of globular domain of histone H5 and its implications for nucleosome binding. Nature 362(6417): 219-23. PubMed
3: Clark, K. L., E. D. Halay, et al. (1993). Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5. Nature 364(6436): 412-20. PubMed
4: Burley, S. K., X. Xie, et al. (1997). Histone-like transcription factors in eukaryotes. Curr Opin Struct Biol 7(1): 94-102. PubMed
5: Aasland, R., T. J. Gibson, et al. (1995). The PHD finger: implications for chromatin-mediated transcriptional regulation. Trends Biochem Sci 20(2): 56-9. PubMed
6: Ragvin, A., H. Valvatne, et al. (2004). Nucleosome binding by the bromodomain and PHD finger of the transcriptional cofactor p300. J Mol Biol 337(4): 773-88. PubMed