FAM221A

Last updated
FAM221A
Identifiers
Aliases FAM221A , C7orf46, family with sequence similarity 221 member A
External IDs MGI: 2442161; HomoloGene: 18214; GeneCards: FAM221A; OMA:FAM221A - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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 Mb Chr 6: 49.34 – 49.37 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.

Contents

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. Secondary Structure of FAM221A.png
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
SpeciesCommon NameDivergence (mya)Accession NumberLength (aa)% Identity% Similarity
Homo sapiensHuman0 NP_954587.2 298100100
Macaca nemestrinaSouthern pig-tailed macaque28.1 XP_011729478.1 2989696
Condylura cristataStar-nosed mole94 XP_004677186.2 2849094
Cervus elaphus hippelaphusCentral European red deer94 OWK06795.1 2899093
Delphinapterus leucasBeluga whale94 XP_022440764.1 2989092
Alligator mississippiensisAmerican alligator320 KYO26809.1 3667886
Phalacrocorax carboGreat cormorant320 KFW96932.1 2587787
Lonchura striata domesticaSociety finch320 XP_021393915.1 2987685
Pelodiscus sinensisChinese softshell turtle320 XP_014436679.1 2367685
Gallus GallusRed junglefowl320 XP_418719.1 2967584
Crocodylus porosusSaltwater crocodile320 XP_019390202.1 2367584
Amphiprion ocellarisOcellaris clownfish432 XP_023141881.1 2486375
Salvelinus alpinusArctic char432 XP_023832019.1 3725971
Esox luciusNorthern pike432 XP_010891304.1 3325569
Ciona intestinalisVase tunicate678N/A2127787
Stylophora pistillataStylophora pistillata685 XP_022787363.1 3445873
Schistosoma haematobiumUniary blood fluke692 XP_012794504.1 2414561
Crassostrea virginicaEastern oyster794 XP_022337450.1 3245972
Mizuhopecten yessoensisPatinopecten yessoensis794 XP_021377417.1 3265570
Phytophthora nicotianaeBlack shank1781 KUF80258.1 2973448
Chrysochromulina sp. CCMP291Chrysochromulina tobin1781 KOO33212.1 2802842

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. Evolution of FAM221A.png
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. 1 2 3 GRCh38: Ensembl release 89: ENSG00000188732 Ensembl, May 2017
  2. 1 2 3 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.[ permanent dead link ]
  9. 1 2 "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. https://web.archive.org/web/20110825161343/http://raptorx.uchicago.edu/. Archived from the original on August 25, 2011.{{cite web}}: Missing or empty |title= (help)
  15. "NCBI BLAST".
  16. "UCSC BLAT".
  17. 1 2 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.