Alternative titles; symbols
HGNC Approved Gene Symbol: STRADB
Cytogenetic location: 2q33.1 Genomic coordinates (GRCh38) : 2:201,451,740-201,480,846 (from NCBI)
By sequencing candidate genes in the ALS2 (205100) critical region, Hadano et al. (2001) identified ALS2CR2. The deduced 418-amino acid protein has a calculated molecular mass of about 47 kD. ALS2CR2 contains a typical protein kinase domain and shares significant homology with more than 30 serine/threonine protein kinases. Northern blot analysis revealed highest expression of a 2.4-kb transcript in heart, skeletal muscle, and colon. A 2.6-kb transcript, which may represent use of an alternate polyadenylation signal, was detected in testis.
Sanna et al. (2002) cloned ALS2CR2, which they called ILPIP, in a yeast 2-hybrid screen of a fetal brain cDNA library using XIAP (300079) as bait. They isolated the full-length cDNA by screening a liver cDNA library. The 418-amino acid ILPIP protein, which the authors termed ILPIP-alpha, contains a putative N-terminal ATP-binding site, a protein kinase domain, and several C-terminal phosphorylation sites. Sanna et al. (2002) also identified a 280-amino acid isoform, which they termed ILPIP-beta, that lacks the first 138 amino acids of the N terminus of ILPIP-alpha. Northern blot analysis detected expression of a 2.4-kb transcript in muscle, liver, and heart, as well as in embryonic kidney cells.
Sanna et al. (2002) determined that ILPIP potentiates the antiapoptotic activity of XIAP by enhancing XIAP-mediated activation of JNK1 (MAPK8; 601158) and other JNK family members, but not by modulating XIAP-mediated caspase inhibition. They also found that expression of a catalytically inactive TAK1 (MAP3K7; 602614) mutant blocked the XIAP/ILPIP activation of JNK1. In vivo coprecipitation experiments showed that both ILPIP and XIAP interact with TAK1 and TRAF6 (602355). Sanna et al. (2002) concluded that XIAP-mediated protection from apoptosis utilizes both a JNK1 activation pathway that involves ILPIP and a caspase inhibition pathway that is independent of ILPIP.
Hadano et al. (2001) determined that the ALS2CR2 gene contains 12 exons and spans 30 kb. It is transcribed in the centromere-to-telomere direction. The promoter for ALS2CR2 is close to, or overlaps, the promoter for ALS2CR3 (607334), which is transcribed in the opposite orientation.
Hadano et al. (2001) mapped the STRADB gene within the ALS2 critical region on chromosome 2q33-q34. They identified 2 intronless pseudogenes that map to chromosomes 1 and 9.
Hadano, S., Yanagisawa, Y., Skaug, J., Fichter, K., Nasir, J., Martindale, D., Koop, B. F., Scherer, S. W., Nicholson, D. W., Rouleau, G. A., Ikeda, J.-E., Hayden, M. R. Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, and ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) critical region at chromosome 2q33-q34: candidate genes for ALS2. Genomics 71: 200-213, 2001. [PubMed: 11161814] [Full Text: https://doi.org/10.1006/geno.2000.6392]
Sanna, M. G., da Silva Correia, J., Luo, Y., Chuang, B., Paulson, L. M., Nguyen, B., Deveraux, Q. L., Ulevitch, R. J. ILPIP, a novel anti-apoptotic protein that enhances XIAP-mediated activation of JNK1 and protection against apoptosis. J. Biol. Chem. 277: 30454-30462, 2002. [PubMed: 12048196] [Full Text: https://doi.org/10.1074/jbc.M203312200]