FAM163A

Last updated
FAM163A
Identifiers
Aliases FAM163A , C1orf76, NDSP, family with sequence similarity 163 member A
External IDs OMIM: 611727 MGI: 3618859 HomoloGene: 18306 GeneCards: FAM163A
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_177838

RefSeq (protein)

NP_808506

Location (UCSC)n/a Chr 1: 155.95 – 156.03 Mb
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

FAM163A, also known as cebelin and neuroblastoma-derived secretory protein (NDSP) is a protein that in humans is encoded by the FAM163A gene. [4] This protein has been implicated in promoting proliferation and anchorage-independent growth of neuroblastoma cancer cells. [5] [6] In addition, this protein has been found to be up-regulated in the lung tissue of chronic smokers. [7] 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 Ideogram of Human Chromosome 1, detailing the location of the FAM163A gene.PNG
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. [8]

More in-depth look at gene neighborhood of FAM163A, produced by AceView Gene neighborhood of FAM163A from AceView.png
More in-depth look at gene neighborhood of FAM163A, produced by AceView

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. [5] 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. [6]

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. [10] NCBI's Aceview yields 23 possible splice variants, but no experimental evidence is associated with these. [11]

Protein

The human protein has a molecular weight of 17.6 kilodaltons (kDa), and an isoelectric point of 5.56. [12] 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. [13]

Localization AreaChances of Localization (%)
Nucleus39.1%
Cytoplasm21.7%
Extracellular Matrix17.4%
Mitochondria17.4%
Cytoskeleton4.3%

Homology

The following data was generated using the NCBI BLAST program. [14] 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. [5] 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 speciesCommon nameEvolutionary time to human divergence (MYA)Accession #Protein sequence lengthSequence identity to human protein (%)Sequence similarity to human protein (%)
Homo sapiensHuman- NP_775780.1 167aa--
Homo sapiensHuman (FAM163B - Paralog)- NP_001073984 166aa42%52%
Gorilla gorilla gorillaGorilla8.8 XP_004028035 167aa99%98%
Felis catusCat94.2 XP_003999284 166aa92%92%
Pteropus alectoBlack Flying Fox94.2 XP_006907838 167aa89%90%
Odobenus rosmarus divergensPacific Walrus94.2 XP_004398165 166aa88%89%
Dasypus novemcinctus9-Banded Armadillo104.2 XP_004461936 165aa87%88%
Ochotona princepsAmerican Pika92.3 XP_004598689 165aa86%89%
Mus musculusMouse92.3 Q8CAA5 168aa85%87%
Alligator mississippiensisAmerican Alligator296 XP_006276882 161aa66%74%
Pelodiscus sinensisChinese Soft-Shelled Turtle296 XP_004461936 164aa64%73%
Gallus gallusChicken296 XP_001234382 159aa61%67%
Ophiophagus hannahKing Cobra296 ETE64717 166aa53%65%
Danio rerioZebrafish400.1 XP_002660900 150aa50%63%
Xiphophorus maculatusSouthern Platyfish400.1 XP_005800930 163aa48%60%
Oryzias latipesJapanese Rice Fish400.1 XP_004067975 163aa46%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. [15]

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. [16]

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References

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  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "FAM163a Gene". GeneCards. Weizmann Institute of Science. Retrieved 16 May 2014.
  5. 1 2 3 Vasudevan SA, Shang X, Shang X, Chang S, Ge N, Diaz-Miron JL, Russell HV, Hicks MJ, Ludwig AD, Wesson CL, Burlingame SM, Kim ES, Khan J, Yang J, Nuchtern JG (2009). "Neuroblastoma-derived secretory protein is a novel secreted factor overexpressed in neuroblastoma". Mol. Cancer Ther. 8 (8): 2478–89. doi:10.1158/1535-7163.MCT-08-1132. PMC   3618953 . PMID   19671756.
  6. 1 2 Vasudevan SA, Russell HV, Okcu MF, Burlingame SM, Liu ZJ, Yang J, Nuchtern JG (2007). "Neuroblastoma-derived secretory protein messenger RNA levels correlate with high-risk neuroblastoma". J. Pediatr. Surg. 42 (1): 148–52. doi:10.1016/j.jpedsurg.2006.09.064. PMID   17208556.
  7. 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. PMC   2914600 . PMID   20418890.
  8. "NCBI Gene" . Retrieved 16 May 2014.
  9. "NCBI AceView". NCBI.
  10. "Gene: FAM163A". Ensembl Genome Browser. Wellcome Trust Genome Campus. Retrieved 17 May 2014.
  11. "AceView: FAM163A". NCBI's AceView.
  12. "ExPASy: pI/Mw". ExPASy. CBS.
  13. "ExPASy: PSORTII". ExPASy. CBS.
  14. "NCBI BLAST". NCBI. Retrieved 17 May 2014.
  15. "CLUSTALW". SDSC Biology Workbench. University of California, San Diego. Retrieved 17 May 2014.
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Further reading