Alternative titles; symbols
HGNC Approved Gene Symbol: SUPT20H
Cytogenetic location: 13q13.3 Genomic coordinates (GRCh38): 13:37,009,312-37,059,688 (from NCBI)
Using differential display PCR to identify genes downregulated in malignant prostate tissue, followed by screening a prostate cDNA library and 5-prime RACE, Schmidt et al. (2001) cloned FAM48A, which they designated C13. The transcript contains a short upstream ORF and a major ORF that encodes a deduced 733-amino acid protein with a calculated molecular mass of 80 kD. The protein has an N-terminal nuclear targeting signal, followed by an alpha helix-rich domain, a PEST motif, and a C-terminal glutamine cluster. It also has several potential serine phosphorylation sites. Northern blot analysis detected transcripts of 3.0 and 4.4 kb in all tissues examined. Northern blot and expression array analyses showed highest expression in testis, followed by various adult brain regions and several fetal tissues, including lung, brain, spleen, thymus, and kidney. In situ hybridization of normal human prostate detected FAM48A mainly in the epithelium.
Zohn et al. (2006) noted that human FAM48A, which they called p38IP, contains 2 C-terminal serine-rich domains. In contrast, the 530-amino acid mouse protein has only 1 serine-rich domain.
Zohn et al. (2006) demonstrated that endogenous p38 (MAPK14; 600289) and p38IP interacted in human embryonic kidney cells. Yeast 2-hybrid analysis confirmed the interaction in HeLa cells. p38IP did not interact with other MAP kinases examined. Mutation analysis revealed that the C-terminal half of p38IP, including the 2 serine-rich domains, was required for interaction with p38.
Using FISH and radiation hybrid analyses, Schmidt et al. (2001) mapped the FAM48A gene to chromosome 13q13.3.
The mouse mutant 'droopy eye' (drey) was identified by Zohn et al. (2006) in an N-ethyl-N-nitrosourea mutagenesis screen. Drey mutant mice displayed incompletely penetrant defects in neural tube closure, eye development, and gastrulation. Zohn et al. (2006) showed that drey was a splice-site mutation in p38ip that introduced a premature stop codon. Drey mutant mice produced a small proportion of wildtype transcripts, likely accounting for the incomplete penetrance. Drey mutant p38ip did not bind p38, resulting in impaired activation of p38 and its downstream substrates in embryonic tissues. Zohn et al. (2006) also identified mice homozygous for a more severe p38ip mutation, p38ip(RRK), that resulted in completely penetrant gastrulation defects in which mesoderm migration away from the primitive streak was impaired. Mice homozygous for p38ip(RRK) failed to activate p38 in the primitive streak, resulting in failure to downregulate E-cadherin (CDH1; 192090), which blocked the epithelial-to-mesenchymal transition required for normal mesoderm migration and gastrulation.
Schmidt, U., Fiedler, U., Pilarsky, C. P., Ehlers, W., Fussel, S., Haase, M., Faller, G., Sauter, G., Wirth, M. P. Identification of a novel gene on chromosome 13 between BRCA-2 and RB-1. Prostate 47: 91-101, 2001. [PubMed: 11340631] [Full Text: https://doi.org/10.1002/pros.1051]
Zohn, I. E., Li, Y., Skolnik, E. Y., Anderson, K. V., Han, J., Niswander, L. p38 and a p38-interacting protein are critical for downregulation of E-cadherin during mouse gastrulation. Cell 125: 957-969, 2006. [PubMed: 16751104] [Full Text: https://doi.org/10.1016/j.cell.2006.03.048]