Alternative titles; symbols
HGNC Approved Gene Symbol: SRI
Cytogenetic location: 7q21.12 Genomic coordinates (GRCh38): 7:88,205,115-88,226,976 (from NCBI)
Van der Bliek et al. (1988) showed that the human homolog of the hamster sorcin gene resides on chromosome 7 like the P-glycoprotein-encoding genes (MDR1, 171050; MDR3, 171060). (The sorcin gene was assigned by Southern analysis of DNA from somatic cell hybrids.) Furthermore, gene classes designated 4, 5, and 6 were found to be coamplified with MDR1 and MDR3 in a human ovarian carcinoma cell line, which strongly suggested that the overall structure of the human MDR domain is the same as that in the hamster and mouse in which the domain which is amplified to result in multidrug resistance (MDR) comprises not only genes that encode P-glycoproteins, but also at least 5 unrelated genes, 1 of which encodes the calcium-binding protein sorcin. Sorcin, coded by the class 4 gene, is a small cytosolic protein that is overproduced in many MDR cells. It has a sequence similar to the regulatory light-chain of calpain (114170), including calcium-binding loops of the type found in calmodulin (114180). Van der Bliek et al. (1988) also found that a sorcin-related sequence segregated with human chromosome 4. The total area encompassed by the MDR1, MDR3, and classes 4-6 genes may be as much as 1500 kb.
Wang et al. (1995) found that the 22-kD sorcin protein was overexpressed in HOB1/VCR-1.0 cells, a multidrug-resistant human B immunoblastic lymphoma cell line. By PCR with primers based on the sequence of hamster sorcin, the authors recovered a partial human sorcin cDNA. Using the partial cDNA to screen a HOB1/VCR-1.0 library, they isolated cDNAs corresponding to the entire sorcin coding region. The predicted 198-amino acid human protein shares 95% sequence identity with hamster sorcin. Human sorcin contains 4 EF-hand calcium-binding motifs. Purified protein bound calcium in vitro. Southern and Northern blot analysis revealed that the sorcin gene is amplified and overexpressed in HOB1/VCR-1.0 cells. No expression was detected in parental HOB1 cells. Independently, Lee (1996) cloned the human sorcin gene.
In both heart and skeletal muscle, the geometry and close spatial relationship between sarcolemmal L-type calcium channels and sarcoplasmic reticulum ryanodine receptors (RyRs, see 180903) is critical in determining the time course of calcium release and excitation-contraction coupling. Meyers et al. (1998) stated that sorcin is 1 of a group of modulators of RyR gating. The authors demonstrated that sorcin also associates with cardiac and skeletal muscle L-type calcium channels specifically within the cytoplasmically oriented C-terminal region of the alpha-1 subunits. See 114204. Meyers et al. (1998) suggested that sorcin is a candidate regulator of interchannel communication during excitation-contraction coupling in heart and skeletal muscle.
Lee, W. P. Purification, cDNA cloning, and expression of human sorcin in vincristine-resistant HOB1 lymphoma cell lines. Arch. Biochem. Biophys. 325: 217-226, 1996. [PubMed: 8561500] [Full Text: https://doi.org/10.1006/abbi.1996.0027]
Meyers, M. B., Puri, T. S., Chien, A. J., Gao, T., Hsu, P.-H., Hosey, M. M., Fishman, G. I. Sorcin associates with the pore-forming subunit of voltage-dependent L-type Ca(2+) channels. J. Biol. Chem. 273: 18930-18935, 1998. [PubMed: 9668070] [Full Text: https://doi.org/10.1074/jbc.273.30.18930]
Van der Bliek, A. M., Baas, F., Van der Velde-Koerts, T., Biedler, J. L., Meyers, M. B., Ozols, R. F., Hamilton, T. C., Joenje, H., Borst, P. Genes amplified and overexpressed in human multidrug-resistant cell lines. Cancer Res. 48: 5927-5932, 1988. [PubMed: 2901906]
Wang, S.-L., Tam, M.-F., Ho, Y.-S., Pai, S.-H., Kao, M.-C. Isolation and molecular cloning of human sorcin a calcium-binding protein in vincristine-resistant HOB1 lymphoma cells. Biochim. Biophys. Acta 1260: 285-293, 1995. [PubMed: 7873602] [Full Text: https://doi.org/10.1016/0167-4781(94)00206-i]