Alternative titles; symbols
HGNC Approved Gene Symbol: MYO18A
Cytogenetic location: 17q11.2 Genomic coordinates (GRCh38) : 17:29,071,122-29,180,398 (from NCBI)
By sequencing clones obtained from a size-fractionated immature myeloid cell line cDNA library, Nagase et al. (1996) cloned TIAF1, which they designated KIAA0216. The deduced 1,581-amino acid protein shares significant similarity with rat myosin heavy chain, and it contains an ATP/GTP-binding site motif A. Northern blot analysis detected TIAF1 in all tissues and cell lines examined, with highest expression in skeletal muscle.
Using differential display to identify genes whose expression correlated with the ability of mouse stromal cells to support hematopoiesis, Furusawa et al. (2000) cloned Tiaf1, which they designated Myspdz. The deduced 2,035-amino acid protein shares 94% homology with KIAA0216, but it contains an additional 458 N-terminal amino acids. By database analysis, Furusawa et al. (2000) identified a human genomic clone containing an exon with significant similarity to nucleotides 1 to 946 of the mouse Tiaf1 gene, suggesting that human TIAF1 may also encode a longer protein. Mouse Tiaf1 contains an N-terminal KE-rich region, followed by a PDZ domain, a head region with an ATP-binding site, a neck region with an IQ motif, and a coiled-coil C-terminal domain. Northern blot analysis detected Tiaf1 in all tissues examined. A 10.5-kb transcript was detected in heart and skeletal muscle, and a 7.0-kb transcript was detected in hematopoietic tissues and cells. Western blot analysis detected Tiaf1 at an apparent molecular mass of 230 kD. Immunostaining localized Tiaf1 in a filamentous network slightly concentrated in the perinuclear region of mouse stromal cells.
Ji et al. (2000) found that the C-terminal myosin tail motif of TIAF1 interacts with the N terminus of JAK3 (600173).
Schultz et al. (2004) showed that TIAF1 and p53 (TP53; 191170) induced apoptosis in human U937 myocytoma cells in both synergistic and antagonistic manners. At optimal levels, both TIAF1 and p53 mediated apoptosis cooperatively. Both proteins also suppressed adherence-independent growth in a mouse fibroblast cell line. In contrast, initiation of apoptosis by overexpressed TIAF1 was blocked by low doses of p53, and vice versa. Ectopic p53 blocked apoptosis in U937 cells stably expressing TIAF1. TIAF1 and p53 did not appear to physically interact; however, nuclear translocation of phosphorylated p53 was significantly reduced in TIAF1-silenced cells. Schultz et al. (2004) concluded that TIAF1 likely participates in the nuclear translocation of activated p53.
The TIAF1 gene resides within the 3-prime untranslated region of the MYO18A gene (610067) (Scott, 2006).
By radiation and somatic cell hybrid analyses, Nagase et al. (1996) mapped the TIAF1 gene to chromosome 17.
Furusawa, T., Ikawa, S., Yanai, N., Obinata, M. Isolation of a novel PDZ-containing myosin from hematopoietic supportive bone marrow stromal cell lines. Biochem. Biophys. Res. Commun. 270: 67-75, 2000. [PubMed: 10733906] [Full Text: https://doi.org/10.1006/bbrc.2000.2377]
Ji, H., Zhai, Q., Zhu, J., Yan, M., Sun, L., Liu, X., Zheng, Z. A novel protein MAJN binds to Jak3 and inhibits apoptosis induced by IL-2 deprival. Biochem. Biophys. Res. Commun. 270: 267-271, 2000. [PubMed: 10733938] [Full Text: https://doi.org/10.1006/bbrc.2000.2413]
Nagase, T., Seki, N., Ishikawa, K., Ohira, M., Kawarabayasi, Y., Ohara, O., Tanaka, A., Kotani, H., Miyajima, N., Nomura, N. Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain. DNA Res. 3: 321-329, 1996. [PubMed: 9039502] [Full Text: https://doi.org/10.1093/dnares/3.5.321]
Schultz, L., Khera, S., Sleve, D., Heath, J., Chang, N.-S. TIAF1 and p53 functionally interact in mediating apoptosis and silencing of TIAF1 abolishes nuclear translocation of serine 15-phosphorylated p53. DNA Cell Biol. 23: 67-74, 2004. [PubMed: 14965474] [Full Text: https://doi.org/10.1089/104454904322745943]
Scott, A. F. Personal Communication. Baltimore, Md. 4/20/2006.