Alternative titles; symbols
HGNC Approved Gene Symbol: SSH2
Cytogenetic location: 17q11.2 Genomic coordinates (GRCh38): 17:29,625,938-29,930,228 (from NCBI)
The ADF (actin-depolymerizing factor)/cofilin family (see 601442) is composed of stimulus-responsive mediators of actin dynamics. ADF/cofilin proteins are inactivated by kinases such as LIM domain kinase-1 (LIMK1; 601329). The SSH family appears to play a role in actin dynamics by reactivating ADF/cofilin proteins in vivo (Niwa et al., 2002).
Niwa et al. (2002) identified the Drosophila 'slingshot' (ssh) gene, which encodes a 1,045-amino acid phosphatase that binds F actin. The phosphatase domain of ssh is distantly related to those of the family of mitogen-activated protein kinase phosphatases (MKPs; see 602749). Niwa et al. (2002) identified 3 human homologs of ssh, SSH1 (606778), SSH2, and SSH3 (606780), by genomic sequence analysis. Transcript analysis suggested that at least 6 polypeptides would be produced from these genes. SSH1 encodes 3 isoforms, SSH1L (1,049 amino acids), SSH1S (692 amino acids), and SSH1B (148 amino acids), and SSH2 encodes 2 isoforms, SSH2 (449 amino acids) and SSH2B (195 amino acids). The SSH3 protein has 471 amino acids. Besides the catalytic domain, 2 other domains are conserved between Drosophila ssh and the human SSHs (domains A and B) and are unique to the SSH family.
Niwa et al. (2002) found that loss of ssh function in Drosophila dramatically increased levels of both F actin and phospho-cofilin (P-cofilin) and disorganized epidermal cell morphogenesis. Two of the human proteins, SSH1L and SSH2, were enzymatically active when reacted with an artificial substrate, p-nitrophenyl phosphate. SSH3 did not exhibit activity toward p-nitrophenyl phosphate, and its expression did not reduce the level of P-cofilin in COS-7 cells. In mammalian cells, SSH1L and SSH2 suppressed LIMK1-induced actin reorganization. Furthermore, ssh, SSH1L, and SSH2 dephosphorylated P-cofilin in cultured cells and in cell-free assays. These results suggested that the SSH gene family plays a pivotal role in actin dynamics by reactivating ADF/cofilin in vivo.
The International Radiation Hybrid Mapping Consortium mapped the SSH2 gene to chromosome 17 (stSG62656).
Niwa, R., Nagata-Ohashi, K., Takeichi, M., Mizuno, K., Uemura, T. Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin. Cell 108: 233-246, 2002. [PubMed: 11832213] [Full Text: https://doi.org/10.1016/s0092-8674(01)00638-9]