FAM136A

Family with sequence similarity 163, Member A (FAM163A) is a is_associated_with::protein encoded by a is_associated_with::gene of the same name. Common is_associated_with::aliases for this protein are: RP11-12M5.2, C1orf146, Neuroblastoma-Derived Secretory Protein (NDSP), and Cebelin. While its function is not yet completely understood, this protein has been implicated in promoting proliferation and anchorage-independent growth of is_associated_with::neuroblastoma is_associated_with::cancer cells. In addition, this protein has been found to be up-regulated in the is_associated_with::lung tissue of chronic smokers. FAM163A is found on human is_associated_with::chromosome 1q25.2; its protein product is 167 is_associated_with::amino acids long. FAM163A contains a very highly conserved is_associated_with::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 is_associated_with::Japanese Rice Fish.

Clinical significance
Mutations in FAM136A are associated to Meniere's disease.

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



mRNA
mRNA levels were tested in 45 neuroblastoma tumor samples in the Vasudevan, et al. paper; in 43 of these samples, elevated levels of NDSP were found, as well as in five is_associated_with::bone marrow samples. The conclusion of this study associates NDSP with increased risk for development of cancer metastasis in bone marrow as well as neural tissue. A second study done by the same primary author, RNA inhibition techniques applied against NDSP were successful in decreasing cellular proliferation and cancer cell colony formation. Further, this protein has been determined to act as a is_associated_with::growth factor through an ERK-mediated pathway.

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

General Properties
The sequence of FAM163A protein is as follows: "MTAGTVVITG GILATVILLC IIAVLCYCRL QYYCCKKSGT EVADEEEERE HDLPTHPRGP TCNACSSQAL DGRGSLAPLT SEPCSQPCGV AASHCTTCSP YSSPFYIRTA DMVPNGGGGE RLSFAPTYYK EGGPPSLKLA APQSYPVTWP GSGREAFTNP RAISTDV"

This protein has a is_associated_with::molecular weight of 17.6 kiloDaltons (kD), and an is_associated_with::isoelectric point of 5.56. 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.

Secondary Structure
Using the PELE program of the SDSC Biology Workbench, it was discovered that FAM163A has one alpha-helix and two beta-strands in its secondary structure. In addition, using the ExPASy program TMHMM, FAM163A is depicted to have one transmembrane region, spanning the signal peptide sequence. All amino acids before this transmembrane domain are extracellular, and all residues after this domain are intercellular.

Post-Translational Modifications
FAM163A has nine possible sites of phopshorylation, as yielded by the program PSORTII. When compared with close and distant orthologs, only seven of these sites are highly conserved, thus these are likely to be most important to the function of FAM163A.

Homology
The following data was generated using the NCBI BLAST program. 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. Their results aligned with the analysis of the orthologs presented below; while many, many more orthologs exist for FAM163A in is_associated_with::species not listed, the Japanese Rice Fish is the last orthologous specie 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.

Paralogs
FAM163A has only one is_associated_with::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.

Orthologs
In close is_associated_with::orthologs, it is clear that several patches of the overall sequence of the protein are conserved or similar; in more distant orthologs, perhaps more important amino acids are highlighted due to their conservation. Once again a CLUSTALW alignment assists in visualizing the relationship between the many orthologs to FAM163A.

Expression Patterns
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.