Biology:FAM163A

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Short description: Protein-coding gene in the species Homo sapiens
A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

FAM163A, also known as cebelin and neuroblastoma-derived secretory protein (NDSP) is a protein that in humans is encoded by the FAM163A gene.[1] This protein has been implicated in promoting proliferation and anchorage-independent growth of neuroblastoma cancer cells.[2][3] In addition, this protein has been found to be up-regulated in the lung tissue of chronic smokers.[4] FAM163A is found on human chromosome 1q25.2; its protein product is 167 amino acids long. FAM163A contains a very highly conserved signal peptide sequence, coded for by the first ~37 amino acids in its sequence; albeit only conserved in eukaryotes, the most distant of which being the Japanese Rice Fish.

Gene

FAM163A relative location on Human Chromosome 1

FAM163A is approximately 2,927 base pairs long, containing five exons. While no domains of unknown function have been documented, the coding region of the gene is very short (~500 base pairs), with an exceptionally long and as-of-yet uncharacterized 3' untranslated region (UTR). FAM163A is located on the positive strand of chromosome 1, in loci126860, near three other genes: TOR1AIP1, TOR1AIP2, and TDRD5.[5]

More in-depth look at gene neighborhood of FAM163A, produced by AceView[6]

mRNA

mRNA levels were tested in 45 neuroblastoma tumor samples; in 43 of these samples, elevated levels of NDSP were found, as well as in five bone marrow samples. NDSP is associated with increased risk for development of cancer metastasis in bone marrow as well as neural tissue.[2] RNA inhibition techniques applied against NDSP decreased cellular proliferation and cancer cell colony formation. Further, this protein has been determined to act as a growth factor through an ERK-mediated pathway.[3]

Splice variants

Several programs can be used to generate possible splice variants of the Fam163A mRNA. The Ensembl database yields one possible splice variant, which coded for the FAM163A protein.[7] NCBI's Aceview yields 23 possible splice variants, but no experimental evidence is associated with these.[8]

Protein

The human protein has a molecular weight of 17.6 kilodaltons (kDa), and an isoelectric point of 5.56.[9] When compared across orthologs, these values are well conserved. Lastly the ExPASy program PSORTII predicts a 39.1% chance of the protein's localization in the nucleus; this being the highest probability for any location.[10]

Localization Area Chances of Localization (%)
Nucleus 39.1%
Cytoplasm 21.7%
Extracellular Matrix 17.4%
Mitochondria 17.4%
Cytoskeleton 4.3%

Homology

The following data was generated using the NCBI BLAST program.[11] An interesting motif in all of these sequences is the exceptional conservation of the signal peptide sequence; Vasudevan, et al.'s studies included bioinformatic analysis that compared a paralogous protein (FAM163B) in humans and the FAM163A ortholog in mice.[2] Their results aligned with the analysis of the orthologs presented below; while many, many more orthologs exist for FAM163A in species not listed, the Japanese Rice Fish is the last orthologous species that shares the signal peptide sequence, with the next closest result having a percent identity of less than 30% and no putative domains of conservation.

Genus and species Common name Evolutionary time to human divergence (MYA) Accession # Protein sequence length Sequence identity to human protein (%) Sequence similarity to human protein (%)
Homo sapiens Human - NP_775780.1 167aa - -
Homo sapiens Human (FAM163B - Paralog) - NP_001073984 166aa 42% 52%
Gorilla gorilla gorilla Gorilla 8.8 XP_004028035 167aa 99% 98%
Felis catus Cat 94.2 XP_003999284 166aa 92% 92%
Pteropus alecto Black Flying Fox 94.2 XP_006907838 167aa 89% 90%
Odobenus rosmarus divergens Pacific Walrus 94.2 XP_004398165 166aa 88% 89%
Dasypus novemcinctus 9-Banded Armadillo 104.2 XP_004461936 165aa 87% 88%
Ochotona princeps American Pika 92.3 XP_004598689 165aa 86% 89%
Mus musculus Mouse 92.3 Q8CAA5 168aa 85% 87%
Alligator mississippiensis American Alligator 296 XP_006276882 161aa 66% 74%
Pelodiscus sinensis Chinese Soft-Shelled Turtle 296 XP_004461936 164aa 64% 73%
Gallus gallus Chicken 296 XP_001234382 159aa 61% 67%
Ophiophagus hannah King Cobra 296 ETE64717 166aa 53% 65%
Danio rerio Zebrafish 400.1 XP_002660900 150aa 50% 63%
Xiphophorus maculatus Southern Platyfish 400.1 XP_005800930 163aa 48% 60%
Oryzias latipes Japanese Rice Fish 400.1 XP_004067975 163aa 46% 60%

Paralogs

FAM163A has only one paralog: FAM163B, located on chromosome 9q34.2. Comparison between the two proteins reveals that the signal peptide sequence is identical; using the CLUSTALW program through SDSC's Biology Workbench, it was possible to visualize the sequences' identity.[12]

Tissue distribution

FAM163A is ubiquitously expressed at very low levels in most tissues of the body; expression is higher in juveniles, and as previously seen, in chronic smokers' lungs and neuroblastoma cells.[13]

References

  1. ↑ "FAM163a Gene". GeneCards. Weizmann Institute of Science. https://www.genecards.org/cgi-bin/carddisp.pl?gene=FAM163A&search=FAM163A. 
  2. ↑ 2.0 2.1 2.2 "Neuroblastoma-derived secretory protein is a novel secreted factor overexpressed in neuroblastoma". Mol. Cancer Ther. 8 (8): 2478–89. 2009. doi:10.1158/1535-7163.MCT-08-1132. PMID 19671756. 
  3. ↑ 3.0 3.1 "Neuroblastoma-derived secretory protein messenger RNA levels correlate with high-risk neuroblastoma". J. Pediatr. Surg. 42 (1): 148–52. 2007. doi:10.1016/j.jpedsurg.2006.09.064. PMID 17208556. 
  4. ↑ Tobacco and Genetics Consortium (2010). "Genome-wide meta-analyses identify multiple loci associated with smoking behavior". Nat. Genet. 42 (5): 441–7. doi:10.1038/ng.571. PMID 20418890. 
  5. ↑ "NCBI Gene". https://www.ncbi.nlm.nih.gov/gene?LinkName=nuccore_gene&from_uid=34222229. 
  6. ↑ "NCBI AceView". NCBI. https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=FAM163A&submit=Go. 
  7. ↑ "Gene: FAM163A". Ensembl Genome Browser. Wellcome Trust Genome Campus. http://useast.ensembl.org/Homo_sapiens/Gene/Splice?db=core;g=ENSG00000143340;r=1:179712298-179785333;t=ENST00000341785. 
  8. ↑ "AceView: FAM163A". NCBI's AceView. https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=FAM163A&submit=Go. 
  9. ↑ "ExPASy: pI/Mw". ExPASy. CBS. http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=53770B9E0000648E8EE5E200&wait=20. 
  10. ↑ "ExPASy: PSORTII". ExPASy. CBS. http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=53770B9E0000648E8EE5E200&wait=20. 
  11. ↑ "NCBI BLAST". NCBI. http://blast.ncbi.nlm.nih.gov/Blast.cgi. 
  12. ↑ "CLUSTALW". SDSC Biology Workbench. University of California, San Diego. http://workbench.sdsc.edu/. 
  13. ↑ "NCBI GEO: mining tens of millions of expression profiles--database and tools update". Nucleic Acids Res. 35 (Database issue): D760–5. January 2007. doi:10.1093/nar/gkl887. PMID 17099226. 

Further reading



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