Alternative titles; symbols
HGNC Approved Gene Symbol: TNFRSF19
Cytogenetic location: 13q12.12 Genomic coordinates (GRCh38) : 13:23,570,412-23,676,093 (from NCBI)
Tumor necrosis factor receptor (TNFR) superfamily members are usually type I membrane proteins that share significant homology in their extracellular domains. The cytoplasmic domains of TNFRs are divergent in both length and sequence. Some apoptosis-inducing members of this superfamily have an 80-amino acid intracellular death domain (e.g., FAS; 134637), while others are capable of inducing apoptosis without a death domain (e.g., CD30; 153243). TAJ is a TNFR superfamily member that is highly expressed during embryonic development.
By searching EST databases for sequences with homology to the extracellular domain of DR3 (TNFRSF12; 603366), Eby et al. (2000) identified cDNAs encoding human TAJ and splice variants of murine Taj. The deduced 423-amino acid human protein, which is 68% identical to the full-length mouse protein, has a typical TNFR superfamily extracellular ligand-binding domain but lacks an intracellular death domain. Northern blot analysis revealed expression of 4.4-kb Taj transcripts in mouse embryos from days 11, 15, and 17. In human tissues, TAJ was expressed in adult prostate and at very low levels in most other tissues.
Using a signal sequence trap method on a mouse brain cDNA library and by screening a human cDNA library derived from a gliosarcoma cell line, Kojima et al. (2000) isolated mouse and human cDNAs encoding TROY. Northern blot analysis detected strong expression of Troy in mouse brain. In situ hybridization analysis of mouse day-13.5 embryos revealed exclusive expression in epithelia of various tissues, whereas in neonatal mice expression was predominantly in hair follicles, similar to the expression of the death domain-containing EDAR protein (604095), and in neuron-like cells in the cerebrum.
By luciferase reporter and GST pull-down analyses, Eby et al. (2000) determined that expression of TAJ activates the JNK (see 602896) pathway but only weakly induces nuclear factor kappa-B (NFKB; see 164011). Fluorescence microscopy demonstrated that TAJ expression induces caspase-independent cell death in 293T and 293 EBNA cells but not COS cells. Coimmunoprecipitation analysis indicated that TAJ interacts with TRAF proteins (e.g., TRAF5; 602356) but not with FADD (602457).
Kojima et al. (2000) noted that TROY contains a TRAF2 (601895)-binding sequence in its cytoplasmic domain. Using luciferase reporter analysis, they observed that TROY overexpression led to NFKB activation in a human embryonic kidney cell line.
Scott (2001) mapped the TAJ gene to 13q12.11-q12.3 based on similarity between the TAJ sequence (GenBank AB040434) and a chromosome 13 clone (GenBank AL139080). Kojima et al. (2000) mapped the mouse Troy gene to chromosome 14, near the 'waved coat' (Wc) locus.
Eby, M. T., Jasmin, A., Kumar, A., Sharma, K., Chaudhary, P. M. TAJ, a novel member of the tumor necrosis factor receptor family, activates the c-Jun N-terminal kinase pathway and mediates caspase-independent cell death. J. Biol. Chem. 275: 15336-15342, 2000. [PubMed: 10809768] [Full Text: https://doi.org/10.1074/jbc.275.20.15336]
Kojima, T., Morikawa, Y., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Senba, E., Kitamura, T. TROY, a newly identified member of the tumor necrosis factor receptor superfamily, exhibits a homology with Edar and is expressed in embryonic skin and hair follicles. J. Biol. Chem. 275: 20742-20747, 2000. [PubMed: 10764796] [Full Text: https://doi.org/10.1074/jbc.M002691200]
Scott, A. F. Personal Communication. Baltimore, Md. 7/18/2001.