FAM221A

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.

FAM221A
Identifiers
AliasesFAM221A, C7orf46, family with sequence similarity 221 member A
External IDsMGI: 2442161 HomoloGene: 18214 GeneCards: FAM221A
Orthologs
SpeciesHumanMouse
Entrez

340277

231946

Ensembl

ENSG00000188732

ENSMUSG00000047115

UniProt

A4D161

Q8C790

RefSeq (mRNA)

NM_001127364
NM_001127365
NM_001300932
NM_199136

NM_001172216
NM_172727

RefSeq (protein)

NP_001120836
NP_001120837
NP_001287861
NP_954587

NP_001165687
NP_766315

Location (UCSC)Chr 7: 23.68 – 23.7 MbChr 6: 49.34 – 49.37 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Gene

Location and Aliases

FAM221A is located on Chromosome 7. Its exact location is 7p15.3.[5] It has one alias, which is C7orf46.[6]

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.[7]

The promoter region of FAM221A is 1222 base pairs long. This was found using ElDorado at Genomatix.[8]

Protein

Protein Analysis

The molecular weight of FAM221A is 33.1 kDa,[9] and the isoelectric point is 6.01.[10] Relative to other proteins in humans, FAM221A has a lower level of asparagine.[9]

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,[11] YinOYang 1.2[12] and The Sulfinator.[13]

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,[14] and a diagram of the predicted secondary structure is included below.

Secondary structure prediction of FAM221A using RaptorX.

Homology/evolution

Paralogs

There exists one paralog for FAM221A: FAM221B. This diverged from FAM221A approximately 1781 million years ago.

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 [15] and BLAT.[16] 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.

20 Orthologs of FAM221A
Species Common Name Divergence (mya) Accession Number Length (aa)  % Identity  % Similarity
Homo sapiens Human 0 NP_954587.2 298 100 100
Macaca nemestrina Southern pig-tailed macaque 28.1 XP_011729478.1 298 96 96
Condylura cristata Star-nosed mole 94 XP_004677186.2 284 90 94
Cervus elaphus hippelaphus Central European red deer 94 OWK06795.1 289 90 93
Delphinapterus leucas Beluga whale 94 XP_022440764.1 298 90 92
Alligator mississippiensis American alligator 320 KYO26809.1 366 78 86
Phalacrocorax carbo Great cormorant 320 KFW96932.1 258 77 87
Lonchura striata domestica Society finch 320 XP_021393915.1 298 76 85
Pelodiscus sinensis Chinese softshell turtle 320 XP_014436679.1 236 76 85
Gallus Gallus Red junglefowl 320 XP_418719.1 296 75 84
Crocodylus porosus Saltwater crocodile 320 XP_019390202.1 236 75 84
Amphiprion ocellaris Ocellaris clownfish 432 XP_023141881.1 248 63 75
Salvelinus alpinus Arctic char 432 XP_023832019.1 372 59 71
Esox lucius Northern pike 432 XP_010891304.1 332 55 69
Ciona intestinalis Vase tunicate 678 N/A 212 77 87
Stylophora pistillata Stylophora pistillata 685 XP_022787363.1 344 58 73
Schistosoma haematobium Uniary blood fluke 692 XP_012794504.1 241 45 61
Crassostrea virginica Eastern oyster 794 XP_022337450.1 324 59 72
Mizuhopecten yessoensis Patinopecten yessoensis 794 XP_021377417.1 326 55 70
Phytophthora nicotianae Black shank 1781 KUF80258.1 297 34 48
Chrysochromulina sp. CCMP291 Chrysochromulina tobin 1781 KOO33212.1 280 28 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.

Evolutionary timeline for FAM221A in orthologs found.

Clinical significance

FAM221A has a relatively high amount of expression in the brain[17] and has been seen to have an association with neurodegenerative disorders such as Parkinson's disease[17] and Alzheimer's disease.[18] FAM221A has also been seen to have a higher level of expression in those who have prostate cancer versus healthy individuals.[19] Furthermore, FAM221A has also been expressed in those with colorectal tumors.[20]

Interacting Proteins

Three interacting proteins were found, which are SNX2, SNX5 and 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
  1. GRCh38: Ensembl release 89: ENSG00000188732 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000047115 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: Family with sequence similarity 221 member A". Retrieved 2016-07-20.
  6. Database, GeneCards Human Gene. "FAM221A Gene - GeneCards - F221A Protein - F221A Antibody". www.genecards.org.
  7. "GDS3113 / 125374". www.ncbi.nlm.nih.gov.
  8. "Genomatix". www.genomatix.de.
  9. "SAPS < Sequence Statistics < EMBL-EBI".
  10. "Calculation of Protein Isoelectric Point".
  11. "NetPhos 3.1 Server". www.cbs.dtu.dk.
  12. "YinOYang 1.2 Server". www.cbs.dtu.dk.
  13. "ExPASy - Sulfinator tool". web.expasy.org.
  14. http://raptorx.uchicago.edu/. {{cite web}}: Missing or empty |title= (help)
  15. "NCBI BLAST".
  16. "UCSC BLAT".
  17. Mariani E, Frabetti F, Tarozzi A, Pelleri MC, Pizzetti F, Casadei R (2016). "Meta-Analysis of Parkinson's Disease Transcriptome Data Using TRAM Software: Whole Substantia Nigra Tissue and Single Dopamine Neuron Differential Gene Expression". PLOS ONE. 11 (9): e0161567. Bibcode:2016PLoSO..1161567M. doi:10.1371/journal.pone.0161567. PMC 5017670. PMID 27611585.
  18. 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 (June 2017). "Identification and description of three families with familial Alzheimer disease that segregate variants in the SORL1 gene". Acta Neuropathologica Communications. 5 (1): 43. doi:10.1186/s40478-017-0441-9. PMC 5465543. PMID 28595629.
  19. Arredouani MS, Lu B, Bhasin M, Eljanne M, Yue W, Mosquera JM, Bubley GJ, Li V, Rubin MA, Libermann TA, Sanda MG (September 2009). "Identification of the transcription factor single-minded homologue 2 as a potential biomarker and immunotherapy target in prostate cancer". Clinical Cancer Research. 15 (18): 5794–802. doi:10.1158/1078-0432.CCR-09-0911. PMC 5573151. PMID 19737960.
  20. Khamas A, Ishikawa T, Shimokawa K, Mogushi K, Iida S, Ishiguro M, Mizushima H, Tanaka H, Uetake H, Sugihara K (2012). "Screening for epigenetically masked genes in colorectal cancer Using 5-Aza-2'-deoxycytidine, microarray and gene expression profile". Cancer Genomics & Proteomics. 9 (2): 67–75. PMID 22399497.
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