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FAM193A
[edit]Family with sequence similarity 193 member A, also known as C4orf8, chromosome 4 open reading frame 8, RES4-22, Protein IT143, and hypothetical protein LOC86032, [1] [2] is located on Chromosome 4 (human)p16.3. The specific location of the gene exists on 107,315 bases from 2,626,988 bp from 2,734,302 bp on chromosome 4. [3]
Gene
[edit]FAM193A mRNA
[edit]Comparing variation of splicing throughout the FAM193A gene using Ensembl, 11 transcripts were found of which three are erroneous or truncated proteins and two being retained introns from non-CDS transcripts.[4] All transcripts represented reveal exactly same starting point with respect to exon 1. This continuity is seen throughout the 5’UTR in all alternatively spliced mRNAs, with the exception in splice variant 4. There are three areas within the expressed protein that possibly have motifs; leucine zipper within a coiled-coil. These three motifs lie within exon 5, 16 and 17. The areas are either expressed or entirely missed and other parts are expressed.
thumb|Transcript variants of FAM193A mRNA
Expression
[edit]The gene FAM193A is most abundantly expressed, by examination of spot intensity from its EST profile Hs.652364, in the embryonic, lymph node , nerve, uterus, testis, larynx tissues and somewhat in the blood.[5] The gene is expressed through a number of health states, for example, adrenal, chondrosarcoma and uterine tumors, it is also implicated in soft tissue/ muscle tissue tumors.[5]
Gene-Chemical Interactions
[edit]FAM193A has several specific chemical–gene interactions curated from published literature. Interactions with Aflatoxin,a naturally occuring mycotoxin, was looked into for carcinogenic potential evaluated through application of chronic rodent bioassays. This compound increases the expression of FAM193A mRNA and by hierarchical clustering [6] implicates this gene in processes related to macromolecules, cellular organization, and regulation [7].
Dihydrotestosterone is androgen of the male sex hormone. Androgen play an important role in maintenance and growth of prostate cells. In a study using prostate cancer cell line LNCaP treated with Dihydrotestosterone and bicalutamide for 6, 24, and 48 hours, researchers registered 56 different transcripts that showed homology to transcription factors, cell cycle regulators, metabolic enzymes, and hypothetical proteins. Of these FAM193A gene expression is upregulated in the presence of Dihydrotestosterone for 48 hours [8].
Protein
[edit]Protein Interactions
[edit]Interestingly, there is a novel gene, IRIZIO that cooperates with PAX3-FOXO1 fusion gene and may contribute to rhabdomyosarcomagenesis in children. This novel gene is homologous to the FAM193 A using the National Center for Biotechnology Information Basic Local Alignment Search Tool revealed an overall homology of 53%. Furthermore, the highest similarity is in the last 76 amino acids (89% homology) of both proteins. [9].
Protein Structure
[edit]Using NCBI’s cBLAST five structures were found that aligned somewhat to FAM193A. Of the structures only two were too were examined Chain A, RNA Polymerase Ii from Schizosaccharomyces Pombe and Chain A Tropomyosin. Comparison with the previous structure of the enzyme from the budding yeast Saccharomyces cerevisiae reveals differences in regions implicated in start site selection and transcription factor interaction. These aspects of the transcription mechanism differ between S. pombe and S. cerevisiae, but are conserved between S. pombe and humans. Amino acid changes apparently responsible for the structural differences are also conserved between S. pombe and humans, suggesting that the S. pombe structure may be a good surrogate for that of the human enzyme.
The predicted secondary structure of FAM193A examined through predictprotein.org showed that more than ¾ of the residues exposing more than 16% of their surface. This program also shows that FAM193A is approximately ½ alpha helical. [10]
Protein Abundance
[edit]A microarray from BRAINSPAN.org within the Prenatal LCM microarray data shows shows high abundance of FAM193A expression in humans ubiquitously throughout the brain. One of three probes showed very little gene expression of FAM193A (A_24_P126465). The most significant structures in terms of signal intensity from the microarray are; occipital lobe, hippocampal formation, globus pallidus, parahippocampal gyrus, amygdala, but relatively little expression in the insula.[11]
Orthologs=
[edit]References
[edit]- ^ [1]NCBI
- ^ [2]GeneNames
- ^ [3]GeneCard
- ^ [4]Ensemble
- ^ a b [5]Unigene Cite error: The named reference "Unigene" was defined multiple times with different content (see the help page).
- ^ Reich, M.; Liefeld, T.; Gould, J.; Lerner, J.; Tamayo, P.; Mesirov, J. P. (2006). "GenePattern 2.0". Nature Genetics. 38 (5): 500–501. doi:10.1038/ng0506-500. PMID 16642009.
- ^ Mathijs, K.; Brauers, K. J. J.; Jennen, D. G. J.; Boorsma, A.; Van Herwijnen, M. H. M.; Gottschalk, R. W. H.; Kleinjans, J. C. S.; Van Delft, J. H. M. (2009). "Discrimination for Genotoxic and Nongenotoxic Carcinogens by Gene Expression Profiling in Primary Mouse Hepatocytes Improves with Exposure Time". Toxicological Sciences. 112 (2): 374–384. doi:10.1093/toxsci/kfp229. PMID 19770486.
- ^ Coutinho-Camillo, C. U. M.; Salaorni, S.; Sarkis, Á. S.; Nagai, M. A. (2006). "Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen". Cancer Genetics and Cytogenetics. 166 (2): 130–138. doi:10.1016/j.cancergencyto.2005.09.012. PMID 16631469.
- ^ Picchione, F.; Pritchard, C.; Lagutina, I.; Janke, L.; Grosveld, G. C. (2010). "IRIZIO: A novel gene cooperating with PAX3-FOXO1 in alveolar rhabdomyosarcoma (ARMS)". Carcinogenesis. 32 (4): 452–461. doi:10.1093/carcin/bgq273. PMC 3105580. PMID 21177767.
- ^ [6]
- ^ [7]