| FAM193A | |||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | FAM193A , C4orf8, RES4-22, family with sequence similarity 193 member A | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | MGI: 2447768; HomoloGene: 2746; GeneCards: FAM193A; OMA:FAM193A - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
Family with sequence similarity 193 member A is a protein that in humans is encoded by the FAM193A gene [5] located on locus p16.3 of chromosome 4. [6] FAM193A is also known as C4orf8, chromosome 4 open reading frame 8, RES4-22, protein IT143, and hypothetical protein LOC86032. [7]
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. [8] 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.
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. [9] 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. [10]
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. [11]
FAM193A has several specific chemical–gene interactions curated from published literature. Interactions with Aflatoxin, a naturally occurring 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 [12] implicates this gene in processes related to macromolecules, cellular organization, and regulation. [13]
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. [14]
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. [15]
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. [16]
Quantitative trait locus: [17]
| Trait | Chromosome | position | p value |
|---|---|---|---|
| Prostate tumor susceptibility QTL 185 | 4 | 751,056 - 26,751,056 | .0053 |
| Myocardial infarction susceptibility QTL 19 | 4 | 1 - 13,115,992 | |
| Prostate tumor susceptibility QTL 351 | 4 | 751,056 - 26,751,056 | .00012 |
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.
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.
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, and ultimately affect a phenotype. These products are often proteins, but in non-protein-coding genes such as transfer RNA (tRNA) and small nuclear RNA (snRNA), the product is a functional non-coding RNA. The process of gene expression is used by all known life—eukaryotes, prokaryotes, and utilized by viruses—to generate the macromolecular machinery for life.
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene may be included within or excluded from the final RNA product of the gene. This means the exons are joined in different combinations, leading to different splice variants. In the case of protein-coding genes, the proteins translated from these splice variants may contain differences in their amino acid sequence and in their biological functions.
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have unique functions. A set of protein isoforms may be formed from alternative splicings, variable promoter usage, or other post-transcriptional modifications of a single gene; post-translational modifications are generally not considered. Through RNA splicing mechanisms, mRNA has the ability to select different protein-coding segments (exons) of a gene, or even different parts of exons from RNA to form different mRNA sequences. Each unique sequence produces a specific form of a protein.
Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products. Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Virtually any step of gene expression can be modulated, from transcriptional initiation, to RNA processing, and to the post-translational modification of a protein. Often, one gene regulator controls another, and so on, in a gene regulatory network.
The transcriptome is the set of all RNA transcripts, including coding and non-coding, in an individual or a population of cells. The term can also sometimes be used to refer to all RNAs, or just mRNA, depending on the particular experiment. The term transcriptome is a portmanteau of the words transcript and genome; it is associated with the process of transcript production during the biological process of transcription.
LNCaP cells are a cell line of human cells commonly used in the field of oncology. LNCaP cells are androgen-sensitive human prostate adenocarcinoma cells derived from the left supraclavicular lymph node metastasis from a 50-year-old caucasian male in 1977. They are adherent epithelial cells growing in aggregates and as single cells.
The PAX3 gene encodes a member of the paired box or PAX family of transcription factors. The PAX family consists of nine human (PAX1-PAX9) and nine mouse (Pax1-Pax9) members arranged into four subfamilies. Human PAX3 and mouse Pax3 are present in a subfamily along with the highly homologous human PAX7 and mouse Pax7 genes. The human PAX3 gene is located in the 2q36.1 chromosomal region, and contains 10 exons within a 100 kb region.
Survivin, also called baculoviral inhibitor of apoptosis repeat-containing 5 or BIRC5, is a protein that, in humans, is encoded by the BIRC5 gene.
Acetyl-CoA acetyltransferase, mitochondrial, also known as acetoacetyl-CoA thiolase, is an enzyme that in humans is encoded by the ACAT1 gene.
Homeobox protein Nkx-3.1, also known as NKX3-1, NKX3, BAPX2, NKX3A and NKX3.1 is a protein that in humans is encoded by the NKX3-1 gene located on chromosome 8p. NKX3-1 is a prostatic tumor suppressor gene.
Acyl-CoA-binding protein in humans belongs to the family of Acyl-CoA-binding proteins.
ERG is an oncogene. ERG is a member of the ETS family of transcription factors. The ERG gene encodes for a protein, also called ERG, that functions as a transcriptional regulator. Genes in the ETS family regulate embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis.
Protein UXT also known as androgen receptor trapped clone 27 (ART-27) protein is a protein that in humans is encoded by the UXT gene.
Chloride transport protein 6 is a protein that in humans is encoded by the CLCN6 gene.
25-hydroxycholesterol 7-alpha-hydroxylase also known as oxysterol and steroid 7-alpha-hydroxylase is an enzyme that in humans is encoded by the CYP7B1 gene. This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids.
SOGA2, also known as Suppressor of glucose autophagy associated 2 or CCDC165, is a protein that in humans is encoded by the SOGA2 gene. SOGA2 has two human paralogs, SOGA1 and SOGA3. In humans, the gene coding sequence is 151,349 base pairs long, with an mRNA of 6092 base pairs, and a protein sequence of 1586 amino acids. The SOGA2 gene is conserved in gorilla, baboon, galago, rat, mouse, cat, and more. There is distant conservation seen in organisms such as zebra finches and anoles. SOGA2 is ubiquitously expressed in humans, with especially high expression in brain, colon, pituitary gland, small intestine, spinal cord, testis and fetal brain.
Forkhead box protein O1 (FOXO1), also known as forkhead in rhabdomyosarcoma (FKHR), is a protein that in humans is encoded by the FOXO1 gene. FOXO1 is a transcription factor that plays important roles in regulation of gluconeogenesis and glycogenolysis by insulin signaling, and is also central to the decision for a preadipocyte to commit to adipogenesis. It is primarily regulated through phosphorylation on multiple residues; its transcriptional activity is dependent on its phosphorylation state.
Solute carrier family 46 member 3 (SLC46A3) is a protein that in humans is encoded by the SLC46A3 gene. Also referred to as FKSG16, the protein belongs to the major facilitator superfamily (MFS) and SLC46A family. Most commonly found in the plasma membrane and endoplasmic reticulum (ER), SLC46A3 is a multi-pass membrane protein with 11 α-helical transmembrane domains. It is mainly involved in the transport of small molecules across the membrane through the substrate translocation pores featured in the MFS domain. The protein is associated with breast and prostate cancer, hepatocellular carcinoma (HCC), papilloma, glioma, obesity, and SARS-CoV. Based on the differential expression of SLC46A3 in antibody-drug conjugate (ADC)-resistant cells and certain cancer cells, current research is focused on the potential of SLC46A3 as a prognostic biomarker and therapeutic target for cancer. While protein abundance is relatively low in humans, high expression has been detected particularly in the liver, small intestine, and kidney.
PROSER2, also known as proline and serine rich 2, is a protein that in humans is encoded by the PROSER2 gene. PROSER2, or c10orf47(Chromosome 10 open reading frame 47), is found in band 14 of the short arm of chromosome 10 (10p14) and contains a highly conserved SARG domain. It is a fast evolving gene with two paralogs, c1orf116 and specifically androgen-regulated gene protein isoform 1. The PROSER2 protein has a currently uncharacterized function however, in humans, it may play a role in cell cycle regulation, reproductive functioning, and is a potential biomarker of cancer.
Uncharacterized protein Chromosome 16 Open Reading Frame 71 is a protein in humans, encoded by the C16orf71 gene. The gene is expressed in epithelial tissue of the respiratory system, adipose tissue, and the testes. Predicted associated biological processes of the gene include regulation of the cell cycle, cell proliferation, apoptosis, and cell differentiation in those tissue types. 1357 bp of the gene are antisense to spliced genes ZNF500 and ANKS3, indicating the possibility of regulated alternate expression.
