SMARCAL1 subfamily

The SMARCAL1 subfamily name is derived from the HGNC official designation for the human SMARCA-like 1 protein 1.

This subfamily is unusual because it encompasses two subtypes with highly similar helicase-like regions but flanked by completely different auxiliary domains which imply distinct functions.

The first subtype consists of SMARCAL1 subfamily members related in organisation to human SMARCAL1, also known as HARP or ADAAD, and are found only in higher eukaryotes. The helicase-like region is located centrally, and members have one or more characteristic Harp motifs immediately N-terminal to this. Mutants in the helicase-like region of human SMARCAL1 have been linked to a genetic disorder Schimke immuno-osseous dysplasia 2 although the molecular function of the SMARCAL1 protein is unknown. Interestingly, the bovine homologue ADAAD is stimulated by DNA single-double strand boundaries 3.

The second subtype is found in animal, plant and some protist genomes and contains SMARCAL1 subfamily members related in overall domain organisation to the human ZRANB3 protein, whose official HGNC name derives from the systematic description “Zinc finger, RAN-Binding domain containing 3”. These polypeptides have the helicase region located at the N-terminus, followed by an unusual type of zinc finger structure and putative HNH type endonuclease domain at the C-terminus 4. The zinc finger is related to those found in Ran protein binding proteins, although such fingers can also interact with RNA 5. No functional information about the proteins in the subtype appears to be available.

names associated with subfamily members
1: Coleman, M. A., J. A. Eisen, et al. (2000). Cloning and characterization of HARP/SMARCAL1: a prokaryotic HepA-related SNF2 helicase protein from human and mouse. Genomics 65(3): 274-82. PubMed
2: Boerkoel, C. F., H. Takashima, et al. (2002). Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia. Nat Genet 30(2): 215-20. PubMed
3: Muthuswami, R., P. A. Truman, et al. (2000). A eukaryotic SWI2/SNF2 domain, an exquisite detector of double-stranded to single-stranded DNA transition elements. J Biol Chem 275(11): 7648-55. PubMed
4: Hsia, K. C., K. F. Chak, et al. (2004). DNA binding and degradation by the HNH protein ColE7. Structure (Camb) 12(2): 205-14. PubMed
5: Plambeck, C. A., A. H. Kwan, et al. (2003). The structure of the zinc finger domain from human splicing factor ZNF265 fold. J Biol Chem 278(25): 22805-11. PubMed