Family with sequence similarity 180A
Family with sequence similarity 180 member A 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.mRNA
The mRNA has 1774 nucleotides. Only one known isoform of FAM180A exists, known as FAM180A transcript variant 2. The TV2 contains 5,138 nucleotides.Protein
The FAM180A protein contains 173 amino acids. a signal peptide, mature peptide, and a regulatory site. A molecular weight of about 19733 kD. Human FAM180A is neutral at a pH of 8.59. The protein contains a Domain of Unknown Function, 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 and Chicken 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. 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 and the new pH is 8.64.Interacting proteins
Table 1: Proteins predicted to interact with FAM180A 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 Species | Common Name | Taxonomic Group | Date of Divergence | Accession Number | Sequence Length | Sequence Identity to Human FAM180A | Sequence Similarity to Human FAM180A | |
| Mammals | Homo sapiens | Humans | Primates | 0 MYA | NP_995327.1 | 173 | 100.0% | 100.0% |
| Mammals | Mus musculus | House mouse | Rodentia | 87 MYA | NP_775551.1 | 173 | 78.6% | 87.3% |
| Mammals | Bos taurus | Cattle | Artiodactyls | 94 MYA | XP_002687015.2 | 173 | 83.8% | 92.5% |
| Mammals | Orcinus orca | Orca | Artiodactyls | 94 MYA | XP_004272298.1 | 173 | 85.5% | 92.5% |
| Mammals | Ornithorhynchus anatinus | Platypus | Monotreme | 180 MYA | XP_001512643.1 | 173 | 75.1% | 85.5% |
| Birds | Haliaeetus leucocephalus | Bald eagle | Accipitriformes | 319 MYA | XP_010564551.1 | 172 | 65.7% | 80.6% |
| Birds | Taeniopygia guttata | Zebra finch | Passeriformes | 319 MYA | XP_072779629.1 | 179 | 53.5% | 63.1% |
| Birds | Meleagris gallopavo | Wild turkey | Galliformes | 319 MYA | XP_010712878.1 | 146 | 55.6% | 66.9% |
| Reptiles | Gopherus flavomarginatus | Bolson tortoise | Testudines | 319 MYA | XP_050775007.1 | 174 | 64.2% | 79.0% |
| Reptiles | Chelonia mydas | Green sea turtle | Testudines | 319 MYA | XP_007072368.1 | 174 | 64.2% | 79.0% |
| Reptiles | Gavialis gangeticus | Gharial | Crododillia | 319 MYA | XP_019370992.1 | 171 | 55.2% | 65.1% |
| Reptiles | Crocodylus porosus | Australian saltwater crododile | Crododillia | 319 MYA | XP_019400203.1 | 173 | 65.2% | 78.7% |
| Reptiles | Varanus komodoensis | Komodo dragon | Squamata | 319 MYA | XP_044290164.1 | 176 | 64.4% | 80.2% |
| Reptiles | Python bivittatus | Burmese python | Squamata | 319 MYA | XP_007431419.1 | 176 | 61.8% | 75.8% |
| Amphibians | Aquarana catesbeiana | American bullfrog | Anura | 352 MYA | XP_073477904.1 | 204 | 42.9% | 57.6% |
| Amphibians | Ambystoma mexicanum | Axolotl | Urodela | 352 MYA | XP_069484866.1 | 236 | 44.3% | 54.9% |
| Fishes | Erpetoichthys calabaricus | Reedfish | Polypteriformes | 429 MYA | XP_028647364.1 | 163 | 41.0% | 59.5% |
| Fishes | Esox lucius | Northern pike | Salmoniformes | 429 MYA | NP_001291030.1 | 183 | 36.2% | 52.3% |
| Fishes | Lepisosteus oculatus | Spotted gar | Lepisosteiformes | 429 MYA | XP_015208634.1 | 163 | 45.1% | 64.0% |
| Fishes | Anguilla rostrata | American eel | Anguilliformes | 429 MYA | XP_064199015.1 | 170 | 41.4% | 59.7% |
| Fishes | Carcharodon carcharias | Great white shark | Mackerel Sharks | 462 MYA | XP_041071418.1 | 166 | 49.1% | 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 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 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. FAM180B is similarly found in the extracellular matrix with trace presence in the cytosolClinical 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 at both the mRNA and protein level compared to fetal mesenchymal stem cells. 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 and from white blood cells that were harvested from blood samples. The CD34+ cells are Hematopoietic stem cells 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. Adipose tissue groups had average ranks of 85–88. White blood cell groups had ranks of 32–35.