Alternative titles; symbols
HGNC Approved Gene Symbol: TSNAX
Cytogenetic location: 1q42.2 Genomic coordinates (GRCh38) : 1:231,528,669-231,566,524 (from NCBI)
Translin (TSN; 600575) is a DNA-binding protein that specifically binds to consensus sequences at breakpoint junctions of chromosomal translocations in many cases of lymphoid malignancies. Aoki et al. (1997) used a yeast 2-hybrid system to screen a human spleen cDNA library for potential interactions of TSN with other proteins. They isolated a TSNAX cDNA, termed TRAX (translin-associated factor X) by the authors, whose product specifically interacted with TSN in cotransformation and in vitro interaction assays. The cDNA encodes a putative 290-amino acid protein with a predicted molecular mass of 33 kD. The protein contains a heptad repeat of hydrophobic amino acids consistent with the hypothetical leucine zipper structure. The authors found 28% amino acid sequence identity between TSNAX and TSN, with 38% identity in the C-terminal regions. Northern blot analysis revealed a single TSNAX transcript of 2.7 kb, with a tissue distribution similar to that of the TSN transcript.
Liu et al. (2009) reconstituted long double-stranded RNA- and duplex siRNA-initiated RISC (RNA-induced silencing complex) activities with the use of recombinant Drosophila Dicer-2 (see 606241), R2D2, and Ago2 (606229) proteins. They used this core reconstitution system to purify an RNAi regulator that they termed C3PO (component 3 promoter of RISC), a complex of translin and TRAX. C3PO is a magnesium ion-dependent endoribonuclease that promotes RISC activation by removing siRNA passenger strand cleavage products. Liu et al. (2009) showed that TRAX is unstable without translin and that TRAX is the catalytic subunit of C3PO. Liu et al. (2009) concluded that their study established an in vitro RNAi reconstitution system and identified C3PO as a key activator of the core RNAi machinery.
Meng et al. (2000) determined that the genomic structure of TSNAX is similar to that of TSN, consisting of 6 exons encompassing approximately 27 kb of genomic DNA.
By fluorescence in situ hybridization, Meng et al. (2000) mapped the TSNAX gene to chromosome 1q41.
Cannon et al. (2005) conducted a population-based twin cohort study in Finland to examine the association of SNPs of DISC1 (605210) and TRAX with schizophrenia (SCZD9; 604906) and several endophenotypic traits thought to be involved in the disease pathogenesis. Two hundred and thirty-six subjects consisting of 7 pairs concordant for schizophrenia (6 monozygotic, 1 dizygotic), 52 pairs discordant for schizophrenia (20 monozygotic, 32 dizygotic), and 59 demographically balanced normal pairs (28 monozygotic, 31 dizygotic) were drawn from a twin cohort consisting of all same-sex twins born in Finland from 1940 through 1957. Diagnosis was confirmed, and performance measurements on neurocognitive tests of short- and long-term memory as well as gray matter volume measurements as assessed on MRI images were recorded. A common haplotype incorporating 3 SNPs near the translocation breakpoint of DISC1 (HEP1; odds ratio, 2.6, p = 0.02) and a rare haplotype incorporating 4 markers from the DISC1 and TRAX genes (combined HEP2/HEP3; odds ratio, 13.0, p = 0.001) were significantly overrepresented among individuals with schizophrenia. These haplotypes were also associated with several quantitative and endophenotypic traits including impairments in short- and long-term memory, functioning, and reduced gray matter density in the prefrontal cortex.
Aoki, K., Ishida, R., Kasai, M. Isolation and characterization of a cDNA encoding a translin-like protein, TRAX. FEBS Lett. 401: 109-112, 1997. [PubMed: 9013868] [Full Text: https://doi.org/10.1016/s0014-5793(96)01444-5]
Cannon, T. D., Hennah, W., van Erp, T. G. M., Thompson, P. M., Lonnqvist, J., Huttenen, M., Gasperoni, T., Tuulio-Henriksson, A., Pirkola, T., Toga, A. W., Kaprio, J., Mazziotta, J., Peltonen, L. Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory. Arch. Gen. Psychiat. 62: 1205-1213, 2005. [PubMed: 16275808] [Full Text: https://doi.org/10.1001/archpsyc.62.11.1205]
Liu, Y., Ye, X., Jiang, F., Liang, C., Chen, D., Peng, J., Kinch, L. N., Grishin, N. V., Liu, Q. C3PO, an endoribonuclease that promotes RNAi by facilitating RISC activation. Science 325: 750-753, 2009. [PubMed: 19661431] [Full Text: https://doi.org/10.1126/science.1176325]
Meng, G., Aoki, K., Tokura, K., Nakahara, K., Inazawa, J., Kasai, M. Genomic structure and chromosomal localization of the gene encoding TRAX, a translin-associated factor X. J. Hum. Genet. 45: 305-308, 2000. [PubMed: 11043515] [Full Text: https://doi.org/10.1007/s100380070022]