Alternative titles; symbols
HGNC Approved Gene Symbol: MALL
Cytogenetic location: 2q13 Genomic coordinates (GRCh38): 2:110,083,870-110,118,139 (from NCBI)
Searching for nonvariable-kappa transcripts in the human immunoglobulin kappa 'locus' at 2q12, Lautner-Rieske et al. (1995) identified a gene predicted to encode a 148-amino acid, 4-transmembrane domain protein that was 40% similar to the T-cell differentiation protein MAL (188860).
Following up on the observation that many patients with familial juvenile nephronophthisis (NPHP1; 256100) have a large homozygous deletion of the 2q13 region (Konrad et al., 1996), Hildebrandt et al. (1997) identified 2 genes homozygously deleted in patients from 16 of 22 families that showed linkage to the 2q13 region. One was the MAL-like gene, which they designated MALL, and the other was the NPHP1 gene (607100). In NPHP1 patients who carried a deletion on 1 chromosome only, point mutations were detected in the NPHP1 gene but not in the MALL gene.
Saunier et al. (1997) identified the same gene, which they termed BENE, near the NPHP1 locus at 2q13. By database searching, de Marco et al. (2001) identified additional 5-prime sequence of BENE, including an in-frame ATG. The predicted 153-amino acid protein is the same length as MAL and contains 3 consensus caveolin-1 (CAV1; 601047)-interaction motifs. Northern blot analysis revealed expression of a 2.7-kb transcript in renal epithelial, cervical carcinoma, and endothelial-like cell lines, but not in T-cell, liver, and kidney cell lines.
By generating a monoclonal antibody recognizing a 17-kD protein on Western blots, the predicted size of BENE, de Marco et al. (2001) showed expression on tonsillar endothelial cells by immunohistochemical analysis. Immunoblot analysis demonstrated selective expression of a proteolipid protein on the glycolipid- and cholesterol-enriched membrane (GEM) rafts of the endothelial cell line. Confocal immunofluorescence and immunoelectron microscopy displayed an intracellular colocalization of BENE with CAV1 and CD59 (107271) in the Golgi region. Immunoprecipitation analysis confirmed the interaction with CAV1 in solubilized GEM rafts. In response to cell surface cholesterol oxidation, BENE redistributed to dilated vesicular structures where most of the CAV1 originally on the cell surface was concentrated. De Marco et al. (2001) concluded that the BENE proteolipid is an element of the machinery for raft-mediated trafficking in endothelial cells.
Hildebrandt et al. (1997) determined that both the MALL and MAL genes contain 4 exons.
By sequence analysis, Lautner-Rieske et al. (1995) identified the MALL gene on chromosome 2q12. By the same method, Hildebrandt et al. (1997) and Saunier et al. (1997) mapped the gene to 2q13.
de Marco, M. C., Kremer, L., Albar, J. P., Martinez-Menarguez, J. A., Ballesta, J., Garcia-Lopez, M. A., Marazuela, M., Puertollano, R., Alonso, M. A. BENE, a novel raft-associated protein of the MAL proteolipid family, interacts with caveolin-1 in human endothelial-like ECV304 cells. J. Biol. Chem. 276: 23009-23017, 2001. [PubMed: 11294831] [Full Text: https://doi.org/10.1074/jbc.M009739200]
Hildebrandt, F., Otto, E., Rensing, C., Nothwang, H. G., Vollmer, M., Adolphs, J., Hanusch, H., Brandis, M. A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1. Nature Genet. 17: 149-153, 1997. [PubMed: 9326933] [Full Text: https://doi.org/10.1038/ng1097-149]
Konrad, M., Saunier, S., Heidet, L., Silbermann, F., Benessy, F., Calado, J., Le Paslier, D., Broyer, M., Gubler, M.-C., Antignac, C. Large homozygous deletions of the 2q13 region are a major cause of juvenile nephronophthisis. Hum. Molec. Genet. 5: 367-371, 1996. [PubMed: 8852662] [Full Text: https://doi.org/10.1093/hmg/5.3.367]
Lautner-Rieske, A., Thiebe, R., Zachau, H. G. Searching for non-V-kappa transcripts from the human immunoglobulin kappa locus. Gene 159: 199-202, 1995. [PubMed: 7622049] [Full Text: https://doi.org/10.1016/0378-1119(95)00161-x]
Saunier, S., Calado, J., Heilig, R., Silbermann, F., Benessy, F., Morin, G., Konrad, M., Broyer, M., Gubler, M.-C., Weissenbach, J., Antignac, C. A novel gene that encodes a protein with a putative src homology 3 domain is a candidate gene for familial juvenile nephronophthisis. Hum. Molec. Genet. 6: 2317-2323, 1997. [PubMed: 9361039] [Full Text: https://doi.org/10.1093/hmg/6.13.2317]