| *601599 | ||||||||||||
| SARCOSPAN; SSPN | ||||||||||||
| Alternative titles; symbols | ||||||||||||
| SPN1 K-RAS ONCOGENE-ASSOCIATED GENE; KRAG KIRSTEN-RAS-ASSOCIATED GENE DYSTROPHIN-ASSOCIATED GLYCOPROTEIN, 25-KD DAGA5 | ||||||||||||
| HGNC Approved Gene Symbol: SSPN | ||||||||||||
| Cytogenetic location: 12p12.1 Genomic coordinates (GRCh37): 12:26,348,268 - 26,387,709 (from NCBI) | ||||||||||||
| TEXT | ||||||||||||
| Description | ||||||||||||
| The dystrophin-glycoprotein complex (DGC) is a multisubunit protein complex that spans the sarcolemma and provides structural linkage between the subsarcolemmal cytoskeleton and the extracellular matrix of muscle cells. There are 3 main subcomplexes of the DGC: the cytoplasmic proteins dystrophin (DMD; 300377) and syntrophin (SNTA1; 601017), the alpha- and beta-dystroglycans (see 128239), and the sarcoglycans (see, e.g., SGCA; 600119) (Crosbie et al., 2000). The SSPN gene encodes sarcospan, another member of the DGC. | ||||||||||||
| Cloning | ||||||||||||
| Scott et al. (1994) reported the sequence of a murine gene that is coamplified with Ki-ras (190070) in the Y1 murine adrenal carcinoma cell line. The gene, which they designated Krag (Kirsten ras-associated gene), encodes a predicted 216-amino acid protein with 4 potential hydrophobic domains. Its hydropathy plot resembles certain of the transmembrane-4 superfamily members such as CO-029 (600769) and ME491 (155740). Heighway et al. (1996) isolated the human KRAG gene and showed that the predicted amino acid sequence is 91% identical to the mouse sequence. Northern blot analysis showed that KRAG is expressed in a variety of tissues with highest levels in muscle, where alternative splice variants were also observed. One end of the YAC contained a sequence that was identical to that reported for inositol 1,4,5-triphosphate receptor type 2 (ITPR2; 600144), which had previously been mapped to 12p11. Crosbie et al. (1997) isolated a cDNA for the 25-kD dystrophin-associated protein from a human skeletal muscle cDNA library. The cDNA encodes a protein with 4 transmembrane spanning domains, which the authors termed 'sarcospan.' Northern blot analysis detected a 6.5-kb mRNA transcript exclusively in skeletal and cardiac muscle; a 4.5-kb mRNA transcript was also identified in skeletal and cardiac muscle as well as in thymus, prostate, testes, ovary, small intestine, colon, and spleen. Immunohistochemical analysis showed that sarcospan complexes with and is an integral component of the dystrophin-glycoprotein complex. | ||||||||||||
| Gene Structure | ||||||||||||
| Heighway et al. (1996) determined that the human KRAG gene contains 3 exons. Scott et al. (1994) determined that the murine Krag gene contains 3 exons and spans about 20 kb of genomic DNA. | ||||||||||||
| Mapping | ||||||||||||
| By fluorescence in situ hybridization, Heighway et al. (1996) mapped the human KRAG gene to chromosome 12p11.2. Scott et al. (1994) found that a homologous EST to murine Krag mapped to chromosome 12. | ||||||||||||
| Gene Function | ||||||||||||
| Heighway et al. (1996) showed that KRAS2, KRAG, and ITPR2 were all coamplified in lung and ovarian carcinoma cells. Several autosomal recessive limb-girdle muscular dystrophies (see 253600) are caused by primary mutations in sarcoglycan genes. Crosbie et al. (2000) showed that the sarcospan protein is lost in patients with either a complete or partial loss of alpha-, beta-, or gamma-sarcoglycan (SGCG; 608896). In particular, sarcospan was absent in a gamma-sarcoglycanopathy (LGDM2C; 253700) patient with normal levels of alpha-, beta- (600900), and delta-sarcoglycan (601411). The authors hypothesized that assembly of the complete, tetrameric sarcoglycan complex is a prerequisite for membrane targeting and localization of sarcospan. The authors screened over 50 autosomal recessive muscular dystrophy cases for mutations in sarcospan, but none was identified. | ||||||||||||
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