Family with sequence similarity 180A

Family with sequence similarity 180 member A (FAM180A) is a protein, which in humans is encoded by the FAM180A gene. This protein is primarily found in the heart, liver, and kidneys.

Molecular features

Gene In the human genome, FAM180A is located on the minus strand of Chromosome 7, at 7q33 and has 3 exons in the sequence. The gene spans 19,222 base pairs. FAM180A is also known as UNQ1940.

Expression The expression of the FAM180A mRNA is exceedingly high in the heart, followed by heightened expression in the kidneys and liver. However, in all other tissues, the expression of this gene's mRNA is low. Similar expression levels were found in the ortholog, mouse (Mus musculus).

mRNA The mRNA has 1774 nucleotides. Only one known isoform of FAM180A exists, known as FAM180A transcript variant 2 (TV2). The TV2 contains 5,138 nucleotides (Accession Number: NM_001369697.2).

Protein

The FAM180A protein contains 173 amino acids. a signal peptide, mature peptide, and a regulatory site. A molecular weight of about 19733 kD (kilodaltons). Human FAM180A is neutral at a pH of 8.59. The protein contains a Domain of Unknown Function (DUF3326), located from 15-77 AA.

FAM180A protein contains significantly lower levels of Glycine. Glycine was two standard deviations less than the average amount of Glycine present in the typical human protein. Additionally, Leucine was one standard deviation above the average amount of Leucine in a typical human protein. Compositional analysis was run with Mouse (Mus musculus) and Chicken (Gallus gallus) orthologs where Glycine remained consistently low, while Leucine counts remained high.

Subcellular localization The FAM180A protein was highly localized in the extracellular region and Golgi Apparatus. The proteins predicted to interact with FAM180A were also highly localized in the extracellular region.

Post translational modifications There is a high likelihood of a signal peptide located including a six-leucine chain and adjacent Amino acids at the beginning of the protein (1-18AA). PSORT predicted a possible cleavable signal peptide from 1-17AA. Only one potential cleavage site was predicted from amino acids 16-18. The single site had a probability of 0.961 out of 1.000. The mass of FAM180A post-cut and the cleavage site is 17628 kD (kilodaltons) and the new pH is 8.64. Interacting proteins Abbreviated NameNameProtein JobC17orf67Chromosome 17 open reading frame 67Enables protein binding.COL28A1Collagen alpha-1(XXVIII) chainCell binding protein.GLT6D1Glycosyltransferase 6 domain containing 1Enables transferase activity.PI15Peptidase inhibitor 15Facial patterning during embryonic development.GCC2GRIP and coiled-coil domain-containing protein 2Enables protein binding, GTPase binding.ANKS1AAnkyrin repeat and SAM domain-containing protein 1ARegulates EPHA8 receptor tyrosine kinase signaling to control cell migration and neurite retraction.KLHL35Kelch-like protein 35Enables ubiquitin-like ligase-substrate adaptor activity.TCP11T-complex protein 11 homologPlays a role in the process of sperm capacitation and acrosome reactions.FANCEFanconi anemia group E proteinRequired for the nuclear accumulation of FANCC and provides a critical bridge between the FA complex and FANCD2.SLC25A29Mitochondrial basic amino acids transporterTransports arginine, lysine, homoarginine, methylarginine and, to a much lesser extent, ornithine and histidine. Table 1: Proteins predicted to interact with FAM180A (Homo sapiens) protein. All interacting proteins were localized in the extracellular region or Golgi apparatus. All interacting proteins were found via textmining where research papers link genes based on similar cellular location or expression.

Homologs

Orthologs

Orthologs for the FAM180A gene are evolutionarily tied back to cartilaginous fishes.

In humans and chimpanzees, FAM180A is expressed the most in the heart, liver, and kidneys. Unlike the heart, the liver and kidneys are consistently expressed across a wider range of organisms. According to Uniprot, the FAM180A protein is secreted outside of the cell membrane.

Reptiles were split in Figure 3 due to differing evolutionary branches. The Python and Ko Dragon are part of the taxonomic group Lepidosauria, whereas birds, turtles and crocodilians follow a separate branch. Genus SpeciesCommon NameTaxonomic GroupDate of DivergenceAccession NumberSequence Length (aa)Sequence Identity to Human FAM180ASequence Similarity to Human FAM180AMammalsHomo sapiensHumansPrimates0 MYANP_995327.1173100.0%100.0%Mus musculusHouse mouseRodentia87 MYANP_775551.117378.6%87.3%Bos taurusCattleArtiodactyls94 MYAXP_002687015.217383.8%92.5%Orcinus orcaOrcaArtiodactyls94 MYAXP_004272298.117385.5%92.5%Ornithorhynchus anatinusPlatypusMonotreme180 MYAXP_001512643.117375.1%85.5%BirdsHaliaeetus leucocephalusBald eagleAccipitriformes319 MYAXP_010564551.117265.7%80.6%Taeniopygia guttataZebra finchPasseriformes319 MYAXP_072779629.117953.5%63.1%Meleagris gallopavoWild turkeyGalliformes319 MYAXP_010712878.114655.6%66.9%ReptilesGopherus flavomarginatusBolson tortoiseTestudines319 MYAXP_050775007.117464.2%79.0%Chelonia mydasGreen sea turtleTestudines319 MYAXP_007072368.117464.2%79.0%Gavialis gangeticusGharialCrododillia319 MYAXP_019370992.117155.2%65.1%Crocodylus porosusAustralian saltwater crododileCrododillia319 MYAXP_019400203.117365.2%78.7%Varanus komodoensisKomodo dragonSquamata319 MYAXP_044290164.117664.4%80.2%Python bivittatusBurmese pythonSquamata319 MYAXP_007431419.117661.8%75.8%AmphibiansAquarana catesbeianaAmerican bullfrogAnura352 MYAXP_073477904.120442.9%57.6%Ambystoma mexicanumAxolotlUrodela352 MYAXP_069484866.123644.3%54.9%FishesErpetoichthys calabaricusReedfishPolypteriformes429 MYAXP_028647364.116341.0%59.5%Esox luciusNorthern pikeSalmoniformes429 MYANP_001291030.118336.2%52.3%Lepisosteus oculatusSpotted garLepisosteiformes429 MYAXP_015208634.116345.1%64.0%Anguilla rostrataAmerican eelAnguilliformes429 MYAXP_064199015.117041.4%59.7%Carcharodon carchariasGreat white sharkMackerel Sharks462 MYAXP_041071418.116649.1%65.7% Table 2: Spreadsheet of 20 orthologs of the FAM180A protein. Sequence Identity and Similarity ran by ClustalW. Date of Divergence calculated by TimeTree.

Paralogs FAM180A has one known paralog, referred to as Family With Sequence Similarity 180B (FAM180B). FAM180B is associated with Leprosy which is a chronic bacterial infection which attacks the skin and peripheral nervous system. FAM180B is primarily expressed in the skin and has been identified as a genetic factor, influencing the susceptibility to Leprosy as is differentiated in skin lesions. FAM180B is also associated with Mosaic Variegated Aneuploidy Syndrome (MVA) which is caused by an improper division of chromosomes leading to a plethora or abnormalities in body functionality. Abnormal FAM180B expression was reported to increase the chances of acquiring MVA syndrome though less common than other genetic indicators (BUB1B and CEP57). FAM180B is similarly found in the extracellular matrix with trace presence in the cytosol

Clinical significance There is no direct connection between the FAM180A gene and any disease. Expression/association datasets often connect FAM180A to Fibro-sarcomatous osteosarcoma, chondroblastic osteosarcoma and bone osteosarcoma. The FAM180A gene has significantly greater expression rates in adult mesenchymal stem cells (MSCs) at both the mRNA and protein level compared to fetal mesenchymal stem cells (MSCs). RNA isolation was performed on collected proteins from cultured MSC. RNA libraries were generated and sequenced by computer where the presence of FAM180A was found. FAM180A was involved in an expression/association study as a potential bladder cancer indicator. Seven genes were found to be up-regulated in human bladder cancer, FAM180A was of the seven genes. But FAM180A may not be directly associated with bladder cancer.

CD34+ cells were extracted by fat tissue that was harvested through liposuction (aspirate) and from white blood cells that were harvested from blood samples (leukapheresis). The CD34+ cells are Hematopoietic stem cells (HSC) which are cells that give rise to blood cell lineages. The CD34+ cells from adipose tissue had significantly higher expression levels of FAM180A than white blood cell CD34+ cells (refer to GEO profile figure). Adipose tissue groups had average ranks of 85–88. White blood cell groups had ranks of 32–35.

References