FAM40A explained

Protein FAM40A is a protein that is located on chromosome 1 in humans and is encoded by the FAM40A gene.^{[1] [2] [3]}

Characteristics and secondary structure

FAM40A has an isoelectric point of 5.92 and a molecular weight of 95,575 daltons.^[4] It is predicted to have three transmembrane domains, making it a transmembrane protein.^[5] FAM40A does not contain a signal peptide and is also predicted to bind to DNA, possibly making it a membrane protein in the nuclear membrane.^{[6] [7]}

The secondary structure of FAM40A is predicted to contain twenty-six alpha helices and two beta sheets.^[8] The 5' untranslated region of FAM40A is predicted to contain one stem-loop and the 3' untranslated region is predicted to contain eight stem-loop structures.^[9] Two miRNAs are predicted to bind to two of the stem-loop structures present in the 3' UTR region.^[10]

Homology

FAM40A has no paralogs. However, it does have orthologs stretching all the way back to yeast. It has been suggested that FAM40A is a homolog to the yeast gene FAR11, which is involved in the recovery from cell cycle arrest.^{[11] [12]}

The following table represents a small selection of orthologs found using searches in BLAST^[13] and BLAT.^[14] This is by no means a comprehensive list, however it does show the vast diversity of species where FAM40A orthologs are found.

Scientific Name	Common Name	Accession number (from NCBI)	Sequence Length	Percent Identity	Percent Similarity
Homo sapiens	Human	NP_149079	837	-	-
Pongo abelii	Sumatran orangutan	XP_002810520	837	99.6%	100%
Sus scrofa	Pig	XP_003125904	837	98.8%	100%
Equus caballus	Horse	XP_001493762	837	98.8%	100%
Mus musculus	Mouse	NP_705791	837	98%	100%
Rattus norvegicus	Rat	XP_001068288	837	97.8%	100%
Monodelphis domestica	Gray short-tailed opossum	XP_001372588	843	95.4%	100%
Danio rerio	Zebra fish	XP_001918929	813	83.4%	98%
Canis lupus familiaris	Dog	From BLAT	812	96.1%	100%
Ailuropoda melanoleuca	Panda	From BLAT	823	$96.2	100%
Oryzias latipes	Medaka	From BLAT	751	78.4%	96%
Xenopus (Silurana) tropicalis	Western clawed frog	NP_001027483	819	86.4%	96%
Aedes aegypti	Yellow-fever mosquito	XP_001658692	829	51.2%	97%
Tribolium castaneum	Red flour beetle	XP_001815164	817	57.4%	97%
Hydra magnipapillata	Hydra hydrozoan	XP_002164866	830	44%	97%
Ciona intestinalis	Sea squirt	XP_002130558	867	46.4%	97%
Pediculus humanus corporis	Human lice	XP_002425964	808	52.7%	97%
Nasonia vitripennis	Jewel wasp	XP_001603859	802	52.7%	97%
Drosophila erecta	Fruit fly	XP_001971743	882	45.2%	97%
Saccharomyces cerevisiae	Bakers yeast	NP_014272	953	18.9%	97%

Expression

FAM40A is expressed in high levels during the blastocyst, eight-cell stage, and fetal stages of development.^[15] FAM40A has also been shown to be expressed in high levels in the mammary glands, brain, thymus, mouth and the testes.^[16] It has also been shown to be expressed in high levels in mammary gland tumors, leukemia cells, and germ cell tumors.

Transcription Regulation

FAM40A is predicted to have a promoter region 789 base pairs upstream of the start of transcription.^[17] The SOX transcription factors are predicted to bind to the promoter region of the FAM40A gene, possibly indicating a role in sex determination.

Interactions

FAM40A has been shown to interact with RP6-213H19.1,^[18] STRN,^[18] PDCD10,^[18] TRAF3IP3,^[18] STRN3,^[18] PPP2R1A,^[18] MOBKL3,^[18] CTTNBP2NL,^[18] STK24^{[18] [19]} and PPP2CA.^[18]

Further reading

• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . etal. 2002PNAS...9916899M . free .
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Beausoleil SA, Jedrychowski M, Schwartz D . Large-scale characterization of HeLa cell nuclear phosphoproteins. . Proc. Natl. Acad. Sci. U.S.A. . 101 . 33 . 12130–5 . 2004 . 15302935 . 10.1073/pnas.0404720101 . 514446 . etal. 2004PNAS..10112130B . free .
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Gregory SG, Barlow KF, McLay KE . The DNA sequence and biological annotation of human chromosome 1. . Nature . 441 . 7091 . 315–21 . 2006 . 16710414 . 10.1038/nature04727 . etal. 2006Natur.441..315G . free .
• Beausoleil SA, Villén J, Gerber SA . A probability-based approach for high-throughput protein phosphorylation analysis and site localization. . Nat. Biotechnol. . 24 . 10 . 1285–92 . 2006 . 16964243 . 10.1038/nbt1240 . 14294292 . etal.
• Olsen JV, Blagoev B, Gnad F . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. . Cell . 127 . 3 . 635–48 . 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . etal. free .
• Ewing RM, Chu P, Elisma F . Large-scale mapping of human protein-protein interactions by mass spectrometry. . Mol. Syst. Biol. . 3 . 1. 89 . 2007 . 17353931 . 10.1038/msb4100134 . 1847948 . etal.

Notes and References

1. Nagase T, Kikuno R, Hattori A, Kondo Y, Okumura K, Ohara O . Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Res . 7 . 6 . 347–55 . Feb 2001 . 11214970 . 10.1093/dnares/7.6.347 . free .
2. Kemp HA, ((Sprague GF Jr)) . Far3 and five interacting proteins prevent premature recovery from pheromone arrest in the budding yeast Saccharomyces cerevisiae . Mol Cell Biol . 23 . 5 . 1750–63 . Feb 2003 . 12588993 . 151714 . 10.1128/MCB.23.5.1750-1763.2003 .
3. Web site: Entrez Gene: FAM40A family with sequence similarity 40, member A.
4. http://ca.expasy.org/tools/pi_tool.html pI/MW Tool
5. https://web.archive.org/web/20040320214259/http://bp.nuap.nagoya-u.ac.jp/sosui/sosui_submit.html Transmembrane domain prediction
6. http://www.cbs.dtu.dk/services/SignalP/ SignalP 3.0 Server
7. https://web.archive.org/web/20040320214259/http://bp.nuap.nagoya-u.ac.jp/sosui/sosui_submit.html SOSUI System
8. http://www.sbg,bio.ic.ac.uk Phyre v. 2.0
9. Web site: RNA Folding Form . 2019-04-29 . https://web.archive.org/web/20150818021243/http://mfold.rna.albany.edu/ . 2015-08-18 . dead .
10. http://www.mirbase.org miRBase
11. https://www.yeastgenome.org/locus/FAR11 Yeast Gene FAR11 from Saccharomyces Genome Database
12. https://www.ncbi.nlm.nih.gov/protein/56790935?from=1&to=837&report=gpwithparts National Center for Biotechnology Information (NCBI) Protein
13. http://blast.ncbi.nlm.nih.gov/Blast.cgi NCBI BLAST: Basic Local Alignment Search Tool
14. http://genome.brc.mcw.edu/cgi-bin/hgBlat BLAT Search Genome
15. https://archive.today/20121222223443/http://www.ebi.ac.uk/s4/eyeresult/?node=expression&species=Homo_sapiens&term=FAM40A&tid=nameOrgENSMUSG00000014601 European Bioinformatics Institute
16. https://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi?uglist=Hs.584996 EST Profile for FAM40A
17. Web site: Genomatix . 2011-05-10 . 2021-12-02 . https://web.archive.org/web/20211202010908/https://www.genomatix.de/ . dead .
18. Goudreault . Marilyn . D'Ambrosio Lisa M . Kean Michelle J . Mullin Michael J . Larsen Brett G . Sanchez Amy . Chaudhry Sidharth . Chen Ginny I . Sicheri Frank . Nesvizhskii Alexey I . Aebersold Ruedi . Raught Brian . Gingras Anne-Claude . Jan 2009 . A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein . Mol. Cell. Proteomics . 8 . 1 . 157–71 . 18782753 . 10.1074/mcp.M800266-MCP200 . free . 2621004 .
19. Ewing . Rob M . Chu Peter . Elisma Fred . Li Hongyan . Taylor Paul . Climie Shane . McBroom-Cerajewski Linda . Robinson Mark D . O'Connor Liam . Li Michael . Taylor Rod . Dharsee Moyez . Ho Yuen . Heilbut Adrian . Moore Lynda . Zhang Shudong . Ornatsky Olga . Bukhman Yury V . Ethier Martin . Sheng Yinglun . Vasilescu Julian . Abu-Farha Mohamed . Lambert Jean-Philippe . Duewel Henry S . Stewart Ian I . Kuehl Bonnie . Hogue Kelly . Colwill Karen . Gladwish Katharine . Muskat Brenda . Kinach Robert . Adams Sally-Lin . Moran Michael F . Morin Gregg B . Topaloglou Thodoros . Figeys Daniel . 2007. Large-scale mapping of human protein-protein interactions by mass spectrometry . Mol. Syst. Biol. . 3 . 1. 89 . 17353931 . 10.1038/msb4100134 . 1847948 .