“FAM193A”的意思、由来-开放百科全书

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.

Tissue distribution

The gene FAM193A is most abundantly expressed, by examination of spot intensity from its EST profile [https://www.ncbi.nlm.nih.gov/UniGene/clust.cgi?ORG=Hs&CID=652364 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.^[6]

A microarray from BRAINSPAN.org within the Prenatal LCM microarray data 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.^[7]

Regulation

Structure

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.^[11]

Protein interactions

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.^[12]

Quantitative trait locus

Related genes

Orthologs

Primates, chimp and gibbon, represented the closest group of orthologous proteins in relation to humans (E range = 0.0-0.0), these along with others were used make a multiple sequence alignment (MSA). The MSA of the closest clade to humans all fell under the same duplication event. The avian (Zebra finch, chicken, turkey) and fish (Zebra fish, Pufferfish). were the animals that had attained this protein before the duplication event. These were found by BLASTing against the human genome. RNA Transcripts searched for BLASTp against the human genome produced no results of significance. Similarly, distantly related animals were found using BLASTp, but of the protein sequences matched, only small portions correlated with FAM193A.

Paralogs

Support for one paralog, FAM193B, shows homology to FAM193A's C-terminus end. FAM193B is 2961 nts long while FAM193A is 4710 and when aligned using Biology Workbench received a low score of -4490.

References

1. ^{{cite web | title = Entrez Gene: Family with sequence similarity 193, member A | url = https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=retrieve&list_uids=8603 }}
2. ^{{Gene|FAM193A}}
3. ^{{GeneCard|FAM193A}}
4. ^ Ensemble
5. ^[https://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi?uglist=Hs.652364] Unigene
6. ^[https://www.ncbi.nlm.nih.gov/UniGeneESTProfileViewer.cgi?uglist=Hs.652364] Unigene
7. ^Prenatal LMD Microarray :: BrainSpan: Atlas of the Developing Human Brain
8. ^{{cite journal | vauthors = Reich M, Liefeld T, Gould J, Lerner J, Tamayo P, Mesirov JP | title = GenePattern 2.0 | journal = Nature Genetics | volume = 38 | issue = 5 | pages = 500–1 | date = May 2006 | pmid = 16642009 | pmc = | doi = 10.1038/ng0506-500 }}
9. ^{{cite journal | vauthors = Mathijs K, Brauers KJ, Jennen DG, Boorsma A, van Herwijnen MH, Gottschalk RW, Kleinjans JC, van Delft JH | title = Discrimination for genotoxic and nongenotoxic carcinogens by gene expression profiling in primary mouse hepatocytes improves with exposure time | journal = Toxicological Sciences | volume = 112 | issue = 2 | pages = 374–84 | date = December 2009 | pmid = 19770486 | pmc = | doi = 10.1093/toxsci/kfp229 }}
10. ^{{cite journal | vauthors = Coutinho-Camillo CM, Salaorni S, Sarkis AS, Nagai MA | title = Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen | journal = Cancer Genetics and Cytogenetics | volume = 166 | issue = 2 | pages = 130–8 | date = April 2006 | pmid = 16631469 | pmc = | doi = 10.1016/j.cancergencyto.2005.09.012 }}
11. ^[https://www.predictprotein.org//get_results.php?req_id=332213 PredictProtein - Sequence Analysis, Structure and Function Prediction]
12. ^{{cite journal | vauthors = Picchione F, Pritchard C, Lagutina I, Janke L, Grosveld GC | title = IRIZIO: a novel gene cooperating with PAX3-FOXO1 in alveolar rhabdomyosarcoma (ARMS) | journal = Carcinogenesis | volume = 32 | issue = 4 | pages = 452–61 | date = April 2011 | pmid = 21177767 | pmc = 3105580 | doi = 10.1093/carcin/bgq273 }}
13. ^FAM193A QTL (quantitative trait loci) Search Result - Rat Genome Database