C4orf36

C4orf36 (also referred to as MGC26744, LOC132989, spostobu, fersnyby, and forsnyby){{Cite web|title=AceView: Gene:C4orf36, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView.|url=https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&q=C4orf36|access-date=2021-12-18|website=www.ncbi.nlm.nih.gov}} is located on chromosome 4 at band 4q21.3 on the minus strand. The gene is 21,052 base pairs long (chr4: 86,876,205-86,897,256){{Cite web | date=2021-11-22|title=Homo sapiens chromosome 4, GRCh38.p13 Primary Assembly|url=http://www.ncbi.nlm.nih.gov/nuccore/NC_000004.12|language=en-US}} and contains 8 exons. Its gene neighborhood includes AFF1-AS1, RPL6P13, SLC10A6, LOC260422, and AFF1.{{Cite web|title=Gene neighbors for Gene (Select 132989) - Gene - NCBI|url=https://www.ncbi.nlm.nih.gov/gene?LinkName=gene_gene_neighbors&from_uid=132989|access-date=2021-12-18|website=www.ncbi.nlm.nih.gov}} No human paralogs for c4orf36 have been identified.

RNA-seq and microarray data indicate that the c4orf36 gene is most highly expressed in the placenta, thyroid, ovary, and skin.{{Cite web|title=48992692 - GEO Profiles - NCBI|url=https://www.ncbi.nlm.nih.gov/geoprofiles/48992692|access-date=2021-12-18|website=www.ncbi.nlm.nih.gov}}{{Cite web|title=69554904 - GEO Profiles - NCBI|url=https://www.ncbi.nlm.nih.gov/geoprofiles/?term=c4orf36,+GDS3834|access-date=2021-12-18|website=www.ncbi.nlm.nih.gov}} It is also expressed in the lungs during fetal development, most highly at 17 weeks into development.

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C4orf36 encodes 24 different mRNA transcripts, including 20 alternatively spliced variants and 4 unspliced forms. The transcript variant 1 (NM_144645.4), the subject of this article, is 908 nucleotides long and contains 5 exons.{{Cite web |date=2020-12-12|title=Homo sapiens chromosome 4 open reading frame 36 (C4orf36), transcript variant 1, mRNA|url=http://www.ncbi.nlm.nih.gov/nuccore/NM_144645.4|language=en-US}} The promoter for transcript variant 1 (GXP_263623) spans the base pairs 86892213-86893422 on chromosome 4.{{Cite web|title=Genomatix: ElDorado|url=https://www.genomatix.de/cgi-bin/eldorado/eldorado.pl?s=a691e18792b81bb3a3ac1430949e9770;RESULT=C4orf36_1|website=Genomatix}}

C4orf36 encodes a 117 amino acid protein{{Cite web|title=uncharacterized protein C4orf36 [Homo sapiens] - Protein - NCBI|url=https://www.ncbi.nlm.nih.gov/protein/1519312833|access-date=2021-12-18|website=www.ncbi.nlm.nih.gov}} with a molecular weight of 13.28 kDa and an isoelectric point of 9.54.{{Cite web|title=ExPASy: get PI/Mw|url=https://www.expasy.org/resources/compute-pi-mw|url-status=live|website=ExPASy|archive-url=https://web.archive.org/web/20201022094419/https://www.expasy.org/resources/compute-pi-mw |archive-date=2020-10-22 }} It contains a divalent cation tolerance protein CutA motif from amino acids 57-88.{{Cite web|title=GenomeNet MOTIF Search|url=https://www.genome.jp/tools/motif/|url-status=live|website=GenomeNet|archive-url=https://web.archive.org/web/20110817163817/http://www.genome.jp/tools/motif/ |archive-date=2011-08-17 }} No transmembrane domains or N-terminal signal peptides have been identified for c4orf36.{{Cite web|title=PSORTII Prediction|url=https://psort.hgc.jp/form2.html|url-status=live|website=PSORTII|archive-url=https://web.archive.org/web/20031214095645/http://psort.hgc.jp:80/form2.html |archive-date=2003-12-14 }} The protein is predicted to undergo several post-translational modifications, including myristoylation and phosphorylation.{{Cite web|title=ScanProsite|url=https://prosite.expasy.org/scanprosite/|access-date=2021-12-19|website=prosite.expasy.org}}{{Cite web|title=MyHits - SIB Swiss Institute of Bioinformatics {{!}} Expasy|url=https://www.expasy.org/resources/myhits|access-date=2021-12-19|website=www.expasy.org}}

Immunohistochemistry experiments have shown that the c4orf36 protein is localized to the cytosol and focal adhesion sites in the human U2-OS cell line, cultivated from the bone tissue of an osteosarcoma patient.{{Cite web|title=C4orf36 Antibody (NBP2-31678): Novus Biologicals|url=https://www.novusbio.com/products/c4orf36-antibody_nbp2-31678#datasheet|url-status=live|website=Novus Biologicals|archive-url=https://web.archive.org/web/20211219004334/https://www.novusbio.com/products/c4orf36-antibody_nbp2-31678 |archive-date=2021-12-19 }}{{Cite web|title=U-2 OS {{!}} ATCC|url=https://www.atcc.org/products/htb-96|access-date=2021-12-19|website=www.atcc.org}} Staining in human kidney tissue showed strong cytoplasmic and membranous expression within cells of tubules and moderate expression in glomeruli.{{Cite web|title=C4orf36 Antibody (PA5-63441)|url=https://www.thermofisher.com/antibody/product/C4orf36-Antibody-Polyclonal/PA5-63441|access-date=2021-12-19|website=www.thermofisher.com}} Data from Human Protein Atlas also indicates that the protein is enriched in several regions of the brain, including the basal ganglia, cerebral cortex, pons, medulla, and in the hippocampus during its formation.{{Cite web|title=C4orf36 protein expression summary - The Human Protein Atlas|url=https://www.proteinatlas.org/ENSG00000163633-C4orf36|access-date=2021-12-19|website=www.proteinatlas.org}}

C4orf36 orthologs are found in mammals and turtles. The gene is not found in other reptiles, birds, amphibians, fish, invertebrates, or outside of Kingdom Animalia. The gene likely first appeared around 318 million years ago, when mammals diverged from birds and reptiles.

The following table presents a diverse subset of c4orf36 orthologs found using BLAST searches.{{Cite web|title=BLAST: Basic Local Alignment Search Tool|url=https://blast.ncbi.nlm.nih.gov/Blast.cgi|access-date=2021-12-19|website=blast.ncbi.nlm.nih.gov}} Within mammals, the sequence identity of the selected orthologs ranges from 99.1% to 47%. Within turtles, the sequence identity ranges from 34.8% to 32.2%.

C4orf36 is predicted to evolve more rapidly than other common human proteins, including cytochrome C and fibrinogen alpha.

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Immunostaining of c4orf36 in syncytiotrophoblast cells (STBs) of mid-gestation human embryos showed a dense punctate pattern consistent with that of c4orf36’s fungal protein analog, dynein light chain, which is involved in intracellular cargo transport and other cellular processes.{{cite journal | vauthors = Gormley M, Oliverio O, Kapidzic M, Ona K, Hall S, Fisher SJ | title = RNA profiling of laser microdissected human trophoblast subtypes at mid-gestation reveals a role for cannabinoid signaling in invasion | journal = Development | volume = 148 | issue = 20 | pages = dev199626 | date = October 2021 | pmid = 34557907 | pmc = 8572005 | doi = 10.1242/dev.199626 }} In another study, ovarian cancer (OVCA) cell lines were treated with gemcitabine. Higher c4orf36 expression was associated with in vitro chemoresistance to the drug, indicating that increased c4orf36 expression may be related to decreased OCVA patient survival.{{cite journal | vauthors = Bou Zgheib N, Xiong Y, Marchion DC, Bicaku E, Chon HS, Stickles XB, Sawah EA, Judson PL, Hakam A, Gonzalez-Bosquet J, Wenham RM, Apte SM, Cubitt CL, Chen DT, Lancaster JM | display-authors = 6 | title = The O-glycan pathway is associated with in vitro sensitivity to gemcitabine and overall survival from ovarian cancer | journal = International Journal of Oncology | volume = 41 | issue = 1 | pages = 179–188 | date = July 2012 | pmid = 22552627 | pmc = 4017641 | doi = 10.3892/ijo.2012.1451 }} Furthermore, microarray data suggests that C4orf36 expression levels are higher in the saliva of pre-treatment pancreatic cancer patients than that of healthy controls.{{Cite web|title=GDS4100 / 1552919_at|url=https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS4100:1552919_at|access-date=2021-12-19|website=www.ncbi.nlm.nih.gov}}

In one study on adaptogenic plants, neuroglia cell lines were treated with Rhaponticum carthamoides (RC), which promotes non-specific stress resistance and may mitigate the onset of senescence. C4orf36 was significantly deregulated in neuroglia cell lines after RC treatment, indicating that tighter c4orf36 regulation may play a role in the development of age-related disorders.{{Cite journal| vauthors = Panossian A, Seo EJ, Efferth T |date=2018-12-01|title=Synergy assessments of plant extracts used in the treatment of stress and aging-related disorders |journal=Synergy|language=en|volume=7|pages=39–48|doi=10.1016/j.synres.2018.10.001|s2cid=92541197|issn=2213-7130}} A study on chondrogenesis found that c4orf36 has an oscillatory expression pattern coupled to that of ATP, indicating a potential link to skeletal development during embryogenesis.{{cite journal | vauthors = Kwon HJ, Kurono S, Kaneko Y, Ohmiya Y, Yasuda K | title = Analysis of proteins showing differential changes during ATP oscillations in chondrogenesis | journal = Cell Biochemistry and Function | volume = 32 | issue = 5 | pages = 429–437 | date = July 2014 | pmid = 24578328 | doi = 10.1002/cbf.3033 | s2cid = 21018808 }}

Chemically significant amino acid changes in conserved regions of the c4orf36 protein were found with NCBI SNPGeneView.{{Cite web|title=SNP linked to Gene (geneID:132989) Via Contig Annotation|url=https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?locusId=132989|access-date=2021-12-19|website=www.ncbi.nlm.nih.gov}}

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Category:Genes on human chromosome 4