FAM221A
{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
Family with sequence similarity 221 member A is a protein in humans that is encoded by the FAM221A gene. FAM221A is a gene that is not yet well understood by the scientific community. However, it appears that this gene may have a role in Parkinson's disease and prostate cancer.
Gene
=Location and Aliases=
FAM221A is located on Chromosome 7. Its exact location is 7p15.3.
{{cite web
| title = Entrez Gene: Family with sequence similarity 221 member A
| url = https://www.ncbi.nlm.nih.gov/gene/340277
| access-date = 2016-07-20
}} It has one alias, which is C7orf46.{{cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=FAM221A|title=FAM221A Gene - GeneCards - F221A Protein - F221A Antibody|first=GeneCards Human Gene|last=Database|website=www.genecards.org}}
=Expression=
FAM221A has higher levels of expression in the liver, brain, fetal brain, thyroid and colon, but FAM221A has the highest level of expression in the spinal cord, pancreas and retina.{{cite web|url=https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS3113:125374|title=GDS3113 / 125374|website=www.ncbi.nlm.nih.gov}}
The promoter region of FAM221A is 1222 base pairs long. This was found using ElDorado at Genomatix.{{Cite web|url=https://www.genomatix.de/cgi-bin/eldorado/eldorado.pl?s=e23a735dbdf26edc22cf0a7b2fd63173|title=Genomatix|website=www.genomatix.de|language=en-US}}{{Dead link|date=December 2024 |bot=InternetArchiveBot |fix-attempted=yes }}
Protein
=Protein Analysis=
The molecular weight of FAM221A is 33.1 kDa,{{cite web|url=https://www.ebi.ac.uk/Tools/seqstats/saps/|title=SAPS < Sequence Statistics < EMBL-EBI}} and the isoelectric point is 6.01.{{cite web|url=http://isoelectric.org/calculate.php|title=Calculation of Protein Isoelectric Point}} Relative to other proteins in humans, FAM221A has a lower level of asparagine.
=Post-Translational Modifications=
Post-translational modifications of FAM221A include phosphorylation sites, glycosylation sites and sulfation sites. These have been conserved in mammals other than Homo sapiens, including the macaque, whale, finch and sometimes alligator. These sites were predicted using NetPhos 3.1,{{cite web|url=http://www.cbs.dtu.dk/services/NetPhos|title=NetPhos 3.1 Server|website=www.cbs.dtu.dk}} YinOYang 1.2{{cite web|url=http://www.cbs.dtu.dk/services/YinOYang/|title=YinOYang 1.2 Server|website=www.cbs.dtu.dk}} and The Sulfinator.{{cite web|url=https://web.expasy.org/sulfinator/|title=ExPASy - Sulfinator tool|website=web.expasy.org}}
=Secondary Structure=
Key structures predicted in FAM221A are random coils and alpha helices, with 71% of the protein being random coils and 21% being helices. Extended strands were also found with 7% of the protein being these. Secondary structure was predicted using RaptorX,{{cite web|url=http://raptorx.uchicago.edu/|archive-url=https://web.archive.org/web/20110825161343/http://raptorx.uchicago.edu/|url-status=dead|archive-date=August 25, 2011}} and a diagram of the predicted secondary structure is included below.
Homology/evolution
=Paralogs=
=Orthologs=
Orthologs have been found in mammals, birds, reptiles and fish. FAM221A has also been conserved in invertebrates, but the similarity levels decrease at a faster rate. Orthologs were discovered using BLAST {{cite web|url=https://blast.ncbi.nlm.nih.gov/Blast.cgi| title=NCBI BLAST}} and BLAT.{{cite web|url=https://genome.ucsc.edu/cgi-bin/hgBlat| title=UCSC BLAT}} While these are not the only orthologs that exist for FAM221A, a table of 20 orthologs is provided below. The ortholog with no accession number was created using BLAT.
| class="wikitable"
|+ 20 Orthologs of FAM221A ! Species ! Common Name ! Divergence (mya) ! Accession Number ! Length (aa) ! % Identity ! % Similarity |
| style="text-align: center;"|Homo sapiens
| style="text-align: center;"|Human | style="text-align: center;"|0 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/NP_954587.2?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 NP_954587.2] | style="text-align: center;"|298 | style="text-align: center;"|100 | style="text-align: center;"|100 |
| style="text-align: center;"|Macaca nemestrina
| style="text-align: center;"|Southern pig-tailed macaque | style="text-align: center;"|28.1 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/XP_011729478.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 XP_011729478.1] | style="text-align: center;"|298 | style="text-align: center;"|96 | style="text-align: center;"|96 |
| style="text-align: center;"|Condylura cristata
| style="text-align: center;"|Star-nosed mole | style="text-align: center;"|94 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/XP_004677186.2?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 XP_004677186.2] | style="text-align: center;"|284 | style="text-align: center;"|90 | style="text-align: center;"|94 |
| style="text-align: center;"|Cervus elaphus hippelaphus
| style="text-align: center;"|Central European red deer | style="text-align: center;"|94 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/OWK06795.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 OWK06795.1] | style="text-align: center;"|289 | style="text-align: center;"|90 | style="text-align: center;"|93 |
| style="text-align: center;"|Delphinapterus leucas
| style="text-align: center;"|Beluga whale | style="text-align: center;"|94 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/XP_022440764.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 XP_022440764.1] | style="text-align: center;"|298 | style="text-align: center;"|90 | style="text-align: center;"|92 |
| style="text-align: center;"|Alligator mississippiensis
| style="text-align: center;"|American alligator | style="text-align: center;"|320 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/KYO26809.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 KYO26809.1] | style="text-align: center;"|366 | style="text-align: center;"|78 | style="text-align: center;"|86 |
| style="text-align: center;"|Phalacrocorax carbo
| style="text-align: center;"|Great cormorant | style="text-align: center;"|320 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/KFW96932.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 KFW96932.1] | style="text-align: center;"|258 | style="text-align: center;"|77 | style="text-align: center;"|87 |
| style="text-align: center;"|Lonchura striata domestica
| style="text-align: center;"|Society finch | style="text-align: center;"|320 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/XP_021393915.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 XP_021393915.1] | style="text-align: center;"|298 | style="text-align: center;"|76 | style="text-align: center;"|85 |
| style="text-align: center;"|Pelodiscus sinensis
| style="text-align: center;"|Chinese softshell turtle | style="text-align: center;"|320 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/XP_014436679.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 XP_014436679.1] | style="text-align: center;"|236 | style="text-align: center;"|76 | style="text-align: center;"|85 |
| style="text-align: center;"|Gallus Gallus
| style="text-align: center;"|Red junglefowl | style="text-align: center;"|320 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/XP_418719.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 XP_418719.1] | style="text-align: center;"|296 | style="text-align: center;"|75 | style="text-align: center;"|84 |
| style="text-align: center;"|Crocodylus porosus
| style="text-align: center;"|Saltwater crocodile | style="text-align: center;"|320 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/XP_019390202.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 XP_019390202.1] | style="text-align: center;"|236 | style="text-align: center;"|75 | style="text-align: center;"|84 |
| style="text-align: center;"|Amphiprion ocellaris
| style="text-align: center;"|Ocellaris clownfish | style="text-align: center;"|432 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/XP_023141881.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 XP_023141881.1] | style="text-align: center;"|248 | style="text-align: center;"|63 | style="text-align: center;"|75 |
| style="text-align: center;"|Salvelinus alpinus
| style="text-align: center;"|Arctic char | style="text-align: center;"|432 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/XP_023832019.1?report=genbank&log$=prottop&blast_rank=6&RID=EGWZ33MG014 XP_023832019.1] | style="text-align: center;"|372 | style="text-align: center;"|59 | style="text-align: center;"|71 |
| style="text-align: center;"|Esox lucius
| style="text-align: center;"|Northern pike | style="text-align: center;"|432 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/XP_010891304.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 XP_010891304.1] | style="text-align: center;"|332 | style="text-align: center;"|55 | style="text-align: center;"|69 |
| style="text-align: center;"|Ciona intestinalis
| style="text-align: center;"|Vase tunicate | style="text-align: center;"|678 | style="text-align: center;"|N/A | style="text-align: center;"|212 | style="text-align: center;"|77 | style="text-align: center;"|87 |
| style="text-align: center;"|Stylophora pistillata
| style="text-align: center;"|Stylophora pistillata | style="text-align: center;"|685 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/XP_022787363.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 XP_022787363.1] | style="text-align: center;"|344 | style="text-align: center;"|58 | style="text-align: center;"|73 |
| style="text-align: center;"|Schistosoma haematobium
| style="text-align: center;"|Uniary blood fluke | style="text-align: center;"|692 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/XP_012794504.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 XP_012794504.1] | style="text-align: center;"|241 | style="text-align: center;"|45 | style="text-align: center;"|61 |
| style="text-align: center;"|Crassostrea virginica
| style="text-align: center;"|Eastern oyster | style="text-align: center;"|794 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/XP_022337450.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 XP_022337450.1] | style="text-align: center;"|324 | style="text-align: center;"|59 | style="text-align: center;"|72 |
| style="text-align: center;"|Mizuhopecten yessoensis
| style="text-align: center;"|Patinopecten yessoensis | style="text-align: center;"|794 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/XP_021377417.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 XP_021377417.1] | style="text-align: center;"|326 | style="text-align: center;"|55 | style="text-align: center;"|70 |
| style="text-align: center;"|Phytophthora nicotianae
| style="text-align: center;"|Black shank | style="text-align: center;"|1781 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/KUF80258.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 KUF80258.1] | style="text-align: center;"|297 | style="text-align: center;"|34 | style="text-align: center;"|48 |
| style="text-align: center;"|Chrysochromulina sp. CCMP291
| style="text-align: center;"|Chrysochromulina tobin | style="text-align: center;"|1781 | style="text-align: center;"|[https://www.ncbi.nlm.nih.gov/protein/KOO33212.1?report=genbank&log$=prottop&blast_rank=1&RID=EGWZ33MG014 KOO33212.1] | style="text-align: center;"|280 | style="text-align: center;"|28 | style="text-align: center;"|42 |
=Divergence of FAM221A=
To understand the times when FAM221A diverged from different species, a graph was created. This compares the evolutionary history of FAM221A to Fibrinogen, which evolves quickly, and Cytochrome C, which evolves slowly. As seen in the graph, FAM221A diverges from other species at a moderate pace.
Clinical significance
FAM221A has a relatively high amount of expression in the brain{{cite journal | vauthors = Mariani E, Frabetti F, Tarozzi A, Pelleri MC, Pizzetti F, Casadei R | title = Meta-Analysis of Parkinson's Disease Transcriptome Data Using TRAM Software: Whole Substantia Nigra Tissue and Single Dopamine Neuron Differential Gene Expression | journal = PLOS ONE | volume = 11 | issue = 9 | pages = e0161567 | year = 2016 | pmid = 27611585 | pmc = 5017670 | doi = 10.1371/journal.pone.0161567 | bibcode = 2016PLoSO..1161567M | doi-access = free }} and has been seen to have an association with neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease.{{cite journal | vauthors = Thonberg H, Chiang HH, Lilius L, Forsell C, Lindström AK, Johansson C, Björkström J, Thordardottir S, Sleegers K, Van Broeckhoven C, Rönnbäck A, Graff C | title = Identification and description of three families with familial Alzheimer disease that segregate variants in the SORL1 gene | journal = Acta Neuropathologica Communications | volume = 5 | issue = 1 | pages = 43 | date = June 2017 | pmid = 28595629 | pmc = 5465543 | doi = 10.1186/s40478-017-0441-9 | doi-access = free }} FAM221A has also been seen to have a higher level of expression in those who have prostate cancer versus healthy individuals.{{cite journal | vauthors = Arredouani MS, Lu B, Bhasin M, Eljanne M, Yue W, Mosquera JM, Bubley GJ, Li V, Rubin MA, Libermann TA, Sanda MG | title = Identification of the transcription factor single-minded homologue 2 as a potential biomarker and immunotherapy target in prostate cancer | journal = Clinical Cancer Research | volume = 15 | issue = 18 | pages = 5794–802 | date = September 2009 | pmid = 19737960 | pmc = 5573151 | doi = 10.1158/1078-0432.CCR-09-0911 }} Furthermore, FAM221A has also been expressed in those with colorectal tumors.{{cite journal | vauthors = Khamas A, Ishikawa T, Shimokawa K, Mogushi K, Iida S, Ishiguro M, Mizushima H, Tanaka H, Uetake H, Sugihara K | title = Screening for epigenetically masked genes in colorectal cancer Using 5-Aza-2'-deoxycytidine, microarray and gene expression profile | journal = Cancer Genomics & Proteomics | volume = 9 | issue = 2 | pages = 67–75 | year = 2012 | pmid = 22399497 }}
Interacting Proteins
Three interacting proteins were found, which are [https://www.genecards.org/cgi-bin/carddisp.pl?gene=SNX2 SNX2], [https://www.genecards.org/cgi-bin/carddisp.pl?gene=SNX5 SNX5] and [https://www.genecards.org/cgi-bin/carddisp.pl?gene=SNX6&keywords=snx6 SNX6].
SNX2 and SNX6 share the same function, which is being involved in the stages of intracellular trafficking. SNX5 facilitates cargo retrieval from endosomes to the trans-golgi network.
References
{{reflist}}