Alternative titles; symbols
HGNC Approved Gene Symbol: PSMA6
Cytogenetic location: 14q13.2 Genomic coordinates (GRCh38): 14:35,278,558-35,317,493 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 14q13.2 | {Myocardial infarction, susceptibility to} | 608446 | 3 |
DeMartino et al. (1991) cloned a partial sequence of a novel proteasomal subunit, PSMA6, which they termed 'iota.' Bey et al. (1993) cloned the PSMA6 cDNA encoding a protein that they termed p27K. The deduced 246-amino acid polypeptide contains an RNA-binding motif, a putative nuclear localization signal, and phosphorylation sites. PSMA6 binds to a specific HeLa cell RNA of approximately 120 nucleotides. Northern blot analysis showed PSMA6 expression as a 1.1-kb mRNA in HeLa cells. Southern blot analysis showed a pattern suggesting that PSMA6 is a single-copy gene.
Coux et al. (1996) reviewed the structures and functions of the 20S proteasome subunits. The alpha subunits comprise the outer rings of the proteasome. Some alpha subunits contain a functional nuclear localization signal; proteasomes are found in both the nuclear and cytoplasmic compartments of the cell. Alpha subunits may constitute a physical barrier that limits access of cytosolic proteins into the inner proteolytic chamber.
Bey et al. (1993) mapped the PSMA6 gene to chromosome 14q13 by fluorescence in situ hybridization.
Because inflammation is critical in the pathogenesis of myocardial infarction (608446) and because one of the mechanisms regulating the inflammatory process is the ubiquitin-proteasome system, Ozaki et al. (2006) investigated whether variants of the 20S proteasome are associated with susceptibility to myocardial infarction. They identified a common SNP (rs1048990; minor allele frequency of 0.35) in the PSMA6 gene (602855.0001) that was significantly associated with myocardial infarction in the Japanese population. The SNP enhanced the transcription of PSMA6. Moreover, suppression of PSMA6 expression using short interfering RNA in cultured cells reduced activation of the transcription factor NF-kappa-B (see 164011) by stabilizing phosphorylated I-kappa-B (see 164008).
Ozaki et al. (2006) found a significant association of susceptibility to myocardial infarction (608446) in the Japanese population with a -8C-G SNP (rs1048990) in the 5-prime UTR of exon 1 of the PSMA6 gene. The SNP enhanced the transcription of PSMA6.
Hinohara et al. (2009) analyzed the -8C-G polymorphism in a total of 1,330 patients with coronary artery disease (CAD) and 2,554 controls from Japanese and Korean populations but found no evidence for association. However, metaanalysis of data from this study and earlier studies yielded an odds ratio of 1.08 for the G allele (p = 0.0057), suggesting that the contribution of PSMA6 to CAD is not large enough to be readily replicated. Hinohara et al. (2009) concluded that further studies are required to establish the contribution of this variant in susceptibility to CAD.
Bey, F., Silva Pereira, I., Coux, O., Viegas-Pequignot, E., Recillas Targa, F., Nothwang, H. G., Dutrillaux, B., Scherrer, K. The prosomal RNA-binding protein p27K is a member of the alpha-type human prosomal gene family. Molec. Gen. Genet. 237: 193-205, 1993. [PubMed: 7681138] [Full Text: https://doi.org/10.1007/BF00282801]
Coux, O., Tanaka, K., Goldberg, A. L. Structure and functions of the 20S and 26S proteasomes. Ann. Rev. Biochem. 65: 801-847, 1996. [PubMed: 8811196] [Full Text: https://doi.org/10.1146/annurev.bi.65.070196.004101]
DeMartino, G. N., Orth, K., McCullough, M. L., Lee, L. W., Munn, T. Z., Moomaw, C. R., Dawson, P. A., Slaughter, C. A. The primary structures of four subunits of the human, high molecular weight proteinase, macropain (proteasome), are distinct but homologous. Biochim. Biophys. Acta 1079: 29-38, 1991. [PubMed: 1888762] [Full Text: https://doi.org/10.1016/0167-4838(91)90020-z]
Hinohara, K., Nakajima, T., Sasaoka, T., Sawabe, M., Lee, B.-S., Ban, J., Park, J.-E., Izumi, T., Kimura, A. Replication studies for the association of PSMA6 polymorphism with coronary artery disease in East Asian populations. J. Hum. Genet. 54: 248-251, 2009. [PubMed: 19282875] [Full Text: https://doi.org/10.1038/jhg.2009.22]
Ozaki, K., Sato, H., Iida, A., Mizuno, H., Nakamura, T., Miyamoto, Y., Takahashi, A., Tsunoda, T., Ikegawa, S., Kamatani, N., Hori, M., Nakamura, Y., Tanaka, T. A functional SNP in PSMA6 confers risk of myocardial infarction in the Japanese population. Nature Genet. 38: 921-925, 2006. [PubMed: 16845397] [Full Text: https://doi.org/10.1038/ng1846]