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
Aliases	FAM221A, C7orf46, family with sequence similarity 221 member A
External IDs	MGI: 2442161 HomoloGene: 18214 GeneCards: FAM221A
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7p15.3 Start 23,680,130 bp[1] End 23,703,249 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6|6 B2.3 Start 49,367,739 bp[2] End 49,390,539 bp[2]
Orthologs
Species	Human	Mouse
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 Mb	Chr 6: 49.37 – 49.39 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/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. https://www.ebi.ac.uk/Tools/seqstats/saps/. Missing or empty |title= (help)
10. http://isoelectric.org/calculate.php. Missing or empty |title= (help)
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/. 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.