Alternative titles; symbols
HGNC Approved Gene Symbol: SPAG9
Cytogenetic location: 17q21.33 Genomic coordinates (GRCh38): 17:50,962,174-51,120,868 (from NCBI)
Shankar et al. (1998) cloned SPAG9 from a human testis cDNA library using antibodies against sperm proteins showing surface localization as probe. The deduced 766-amino acid protein has a calculated molecular mass of 84 kD and contains a large N-terminal extracellular domain, a short transmembrane helical domain, and a cytoplasmic domain. There are 6 putative N-glycosylation sites, several putative phosphorylation sites for cAMP/cGMP-dependent protein kinase, protein kinase C, and casein kinase II, and 10 putative myristoylation sites. There is also a leucine zipper motif, with 6 leucine repeats, that may aid in dimerization since there is no upstream basic domain characteristic of DNA binding proteins. Northern blot analysis detected testis-restricted expression of a 3-kb SPAG9 transcript. In situ hybridization of human testis sections revealed SPAG9 on round spermatids of stages I, II, and III of the human seminiferous cycle. Immunohistochemical staining showed that SPAG9 is exclusively associated with elongated spermatids and not with round spermatids, indicating posttranscriptional delay in expression. Analysis of the cDNA revealed 3 putative hairpin loop structures at key positions within the open reading frame that could stabilize the mRNA in vivo.
Bowman et al. (2000) identified a broadly conserved membrane-associated protein, which they termed 'sunday driver' (syd), required for the functional interaction of kinesin I (see 148760) with axonal cargo in Drosophila. Mutations in syd and the axonal transport motor kinesin I were found to cause similar phenotypes in Drosophila, including aberrant accumulations of axonal cargoes. By searching genomic and EST sequence databases for proteins similar to syd, Bowman et al. (2000) obtained full-length cDNAs encoding human SYD1 and mouse Syd2, as well as partial cDNAs encoding human SYD2 (605431) and mouse Syd1. Human SYD1 is 69% similar to mouse Syd2 and 55% similar to Drosophila syd. The predicted SYD proteins have a transmembrane region flanked by an N-terminal domain containing 2 coiled-coil regions and a C-terminal domain containing a conserved hydrophobic core. GFP-tagged mouse Syd2 localized to tubulovesicular structures that costained for kinesin I and a marker of the secretory pathway.
By immunoscreening a liver cell line cDNA library with systemic sclerosis (see 181750) serum, Yasuoka et al. (2003) identified a partial cDNA encoding PHET. RT-PCR detected PHET expression in testis only. Serum autoantibodies to a recombinant PHET fragment were detected in 8% of systemic sclerosis patients, but were not present in systemic lupus erythematosus (SLE; 152700) patients or healthy controls. In systemic sclerosis patients, anti-PHET autoantibodies were associated with diffuse cutaneous or lung disease. RT-PCR analysis detected increased PHET expression in systemic sclerosis patient fibroblasts compared with controls. Immunofluorescence microscopy demonstrated more intense cytoplasmic staining for PHET in patient fibroblasts. Yasuoka et al. (2003) concluded that PHET is a testicular antigenic variant of SPAG9 that is overexpressed in systemic sclerosis patient dermal fibroblasts.
By coimmunoprecipitation analysis, Bowman et al. (2000) found that Syd2 forms a complex with kinesin I in vivo. Yeast 2-hybrid analysis and in vitro interaction studies revealed that Syd2 directly binds kinesin I via the tetratricopeptide repeat (TPR) domain of kinesin light chain (KLC; 600025). The authors proposed that the SYD proteins mediate the axonal transport of at least 1 class of vesicles by interacting directly with KLC.
The International Radiation Hybrid Mapping Consortium mapped the SPAG9 gene to chromosome 17 (WI-9550). Scott (2002) refined the localization to 17q21.33 based on sequence similarity between the SPAG9 sequence (GenBank NM003971) and a chromosome 17 clone (GenBank AC005920).
Bowman, A. B., Kamal, A., Ritchings, B. W., Philp, A. V., McGrail, M., Gindhart, J. G., Goldstein, L. S. B. Kinesin-dependent axonal transport is mediated by the sunday driver (SYD) protein. Cell 103: 583-594, 2000. [PubMed: 11106729] [Full Text: https://doi.org/10.1016/s0092-8674(00)00162-8]
Scott, A. F. Personal Communication. Baltimore, Md. 2002.
Shankar, S., Mohapatra, B., Suri, A. Cloning of a novel human testis mRNA specifically expressed in testicular haploid germ cells, having unique palindromic sequences and encoding a leucine zipper dimerization motif. Biochem. Biophys. Res. Commun. 243: 561-565, 1998. [PubMed: 9480848] [Full Text: https://doi.org/10.1006/bbrc.1997.7943]
Yasuoka, H., Ihn, H., Medsger, T. A., Jr., Hirakata, M., Kawakami, Y., Ikeda, Y., Kuwana, M. A novel protein highly expressed in testis is overexpressed in systemic sclerosis fibroblasts and targeted by autoantibodies. J. Immun. 171: 6883-6890, 2003. [PubMed: 14662895] [Full Text: https://doi.org/10.4049/jimmunol.171.12.6883]