SHLD1

C20orf196 is involved in the DNA repair network. Gupta et al. identified C20orf196 as part of a vertebrate-specific protein complex called shieldin.{{cite journal | vauthors = Gupta R, Somyajit K, Narita T, Maskey E, Stanlie A, Kremer M, Typas D, Lammers M, Mailand N, Nussenzweig A, Lukas J, Choudhary C | title = DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity | journal = Cell | volume = 173 | issue = 4 | pages = 972–988.e23 | date = May 2018 | pmid = 29656893 | doi = 10.1016/j.cell.2018.03.050 | pmc = 8108093 | s2cid = 4886733 | doi-access = free }} Shieldin is recruited to double stranded breaks (DSB) to promote nonhomologous end joining-dependent repair (NHEJ), immunoglobulin class-switch recombination (CSR), and fusion of unprotected telomeres. Analysis indicates a sub-stoichiometric interaction or weaker interaction affinity of SHLD1 to the shieldin complex.

C20orf196 is located on the short arm of chromosome 20 at 20p12.3, from base pairs 5,750,286 to 5,864,407 on the direct strand. It contains 11 exons.{{cite web|url=https://www.ncbi.nlm.nih.gov/ieb/research/acembly/av.cgi?db=human&term=C20orf196&submit=Go|title=AceView: Gene:C20orf196, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView.|first1=Danielle|last1=Thierry-Mieg|first2=Jean|last2=Thierry-Mieg|website=www.ncbi.nlm.nih.gov|access-date=2018-02-05}}

Its aliases are RINN3 and SHLD1.

C20orf196 produces 9 different mRNAs, with 7 alternatively spliced variants and 2 unspliced forms. There are 3 probable alternative promoters, 3 non-overlapping alternative last exons, and 2 alternative polyadenylation sites. The mRNAs differ by the truncation of the 5' end, truncation of the 3' end, presence or absence of 2 cassette exons, and overlapping exons with different boundaries.

C20orf196 has six splice isoforms.

The promoter region is within bases 5749286 to 5750555, totaling 1270 base pairs. The transcription start site is located within bases 5750382 and 5750409, totaling 28 base pairs.

File:NCBI_GEO_Human_Tissue_Expression_Profile_for_C20orf196.png

RNA-Seq analysis has shown ubiquitous expression of c20orf196 in 26 human tissues: adrenal, appendix, bone marrow, brain, colon, duodenum, endometrium, esophagus, fat, gall bladder, heart, kidney, liver, lung, lymph node, ovary, pancreas, placenta, prostate, salivary gland, skin, small intestine, spleen, stomach, testis, thyroid, and urinary bladder. The highest C20orf196 mRNA levels were found in the lymph node, tonsil, thyroid, adrenal gland, prostate, pharynx, parathyroid, connective tissue, and bone marrow.{{cite journal | vauthors = Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson Å, Kampf C, Sjöstedt E, Asplund A, Olsson I, Edlund K, Lundberg E, Navani S, Szigyarto CA, Odeberg J, Djureinovic D, Takanen JO, Hober S, Alm T, Edqvist PH, Berling H, Tegel H, Mulder J, Rockberg J, Nilsson P, Schwenk JM, Hamsten M, von Feilitzen K, Forsberg M, Persson L, Johansson F, Zwahlen M, von Heijne G, Nielsen J, Pontén F | title = Proteomics. Tissue-based map of the human proteome | journal = Science | volume = 347 | issue = 6220 | pages = 1260419 | date = January 2015 | pmid = 25613900 | doi = 10.1126/science.1260419 | s2cid = 802377 }}

C20orf196 was found to be expressed in soft tissue/muscle tissue tumors, lymphoma tumors, and pancreatic tumors.{{cite web|url=https://www.ebi.ac.uk/|title=The European Bioinformatics Institute < EMBL-EBI|date=2018}} C20orf196 representation was biased toward the fetal developmental stage. EBI expression data showed high expression of C20orf196 in the diencephalon and cerebral cortex in the developing brain.

The most common transcript encodes a protein that is 205 amino acids long with a molecular mass of 23 kDa.{{cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=C20orf196|title=C20orf196 Gene - GeneCards {{!}} CT196 Protein {{!}} CT196 Antibody|last=Database|first=GeneCards Human Gene|website=www.genecards.org|access-date=2018-02-20}} It has a predicted isoelectric point of 4.72.{{cite web|url=https://web.expasy.org/compute_pi/|title=Compute pI/Mw|date=2018|website=ExPASy }} It is predicted to have a half-life around 30 hours.{{cite journal | vauthors = Bachmair A, Finley D, Varshavsky A | title = In vivo half-life of a protein is a function of its amino-terminal residue | journal = Science | volume = 234 | issue = 4773 | pages = 179–86 | date = October 1986 | pmid = 3018930 | doi = 10.1126/science.3018930 | bibcode = 1986Sci...234..179B }} C20orf196 contains 19 positive residues (9.3%), 32 negative residues (15.6%), and 46 hydrophobic residues (22.4%).{{cite web|url=https://www.ebi.ac.uk/Tools/seqstats/saps/|title=Statistical Analysis of Protein Sequences |date=2018 |website=EMBL-EBI }}

C20orf196 is predicted to localize in the nucleus.

C20orf196 contains one domain, DUF4521, which arose in Amniote. DUF4521 spans from amino acid 3 to 201. Several regions of this domain are conserved in c20orf196 orthologs found in mammals, amphibians, and fish. The proteins of this family are functionally uncharacterized.

There are many phosphorylation sites targeted by unspecified serine kinases.{{cite journal | vauthors = Blom N, Gammeltoft S, Brunak S | title = Sequence and structure-based prediction of eukaryotic protein phosphorylation sites | journal = Journal of Molecular Biology | volume = 294 | issue = 5 | pages = 1351–62 | date = December 1999 | pmid = 10600390 | doi = 10.1006/jmbi.1999.3310 }} C20orf196 is predicted to have one SUMOylation site at amino acid 203 and one N-glycosylation site at amino acid 69.{{cite journal | vauthors = Zhao Q, Xie Y, Zheng Y, Jiang S, Liu W, Mu W, Liu Z, Zhao Y, Xue Y, Ren J | title = GPS-SUMO: a tool for the prediction of sumoylation sites and SUMO-interaction motifs | journal = Nucleic Acids Research | volume = 42 | issue = Web Server issue | pages = W325-30 | date = July 2014 | pmid = 24880689 | pmc = 4086084 | doi = 10.1093/nar/gku383 }}{{cite journal| vauthors = Gupta R, Jung E, Brunak S |title=Prediction of N-glycosylation sites in human proteins |journal=DTU Bioinformatics|volume=46|pages=203–206 }} C20orf196 is predicted to have two ubiquitination sites at amino acids 84 and 139.{{cite journal | vauthors = Huang CH, Su MG, Kao HJ, Jhong JH, Weng SL, Lee TY | title = UbiSite: incorporating two-layered machine learning method with substrate motifs to predict ubiquitin-conjugation site on lysines | journal = BMC Systems Biology | volume = 10 Suppl 1 | issue = 1 | pages = 6 | date = January 2016 | pmid = 26818456 | pmc = 4895383 | doi = 10.1186/s12918-015-0246-z | doi-access = free }}

Several modeling programs predicted a secondary structure containing alpha helix, beta sheet, and coil regions.{{cite journal | vauthors = Zhang Y | title = I-TASSER server for protein 3D structure prediction | journal = BMC Bioinformatics | volume = 9 | pages = 40 | date = January 2008 | pmid = 18215316 | pmc = 2245901 | doi = 10.1186/1471-2105-9-40 | doi-access = free }}{{cite web|url=http://crdd.osdd.net/raghava/apssp/|title=APSSP: Advanced Protein Secondary Structure Prediction Server|last=Raghava|first=G. P. S.|date=2000}} CFSSP has predicted that C20orf196 secondary structure is 57.1% alpha helices, 48.8% beta strands, and 16.6% beta turns.{{cite journal|last=T|first=Ashok Kumar|date=2013-04-01|title=CFSSP: Chou and Fasman Secondary Structure Prediction server|journal=Zenodo|volume=1 |issue=9 |pages=15–19 |doi=10.5281/zenodo.50733}}

Several databases citing yeast two-hybrid screenings have found C20orf196 to interact with PRMT1, QARS, MAD2L2, and CUL3.{{cite journal | vauthors = Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, Kuhn M, Bork P, Jensen LJ, von Mering C | title = STRING v10: protein-protein interaction networks, integrated over the tree of life | journal = Nucleic Acids Research | volume = 43 | issue = Database issue | pages = D447-52 | date = January 2015 | pmid = 25352553 | pmc = 4383874 | doi = 10.1093/nar/gku1003 }}{{cite journal | vauthors = Licata L, Briganti L, Peluso D, Perfetto L, Iannuccelli M, Galeota E, Sacco F, Palma A, Nardozza AP, Santonico E, Castagnoli L, Cesareni G | title = MINT, the molecular interaction database: 2012 update | journal = Nucleic Acids Research | volume = 40 | issue = Database issue | pages = D857-61 | date = January 2012 | pmid = 22096227 | pmc = 3244991 | doi = 10.1093/nar/gkr930 }}{{cite journal | vauthors = Hermjakob H, Montecchi-Palazzi L, Lewington C, Mudali S, Kerrien S, Orchard S, Vingron M, Roechert B, Roepstorff P, Valencia A, Margalit H, Armstrong J, Bairoch A, Cesareni G, Sherman D, Apweiler R | title = IntAct: an open source molecular interaction database | journal = Nucleic Acids Research | volume = 32 | issue = Database issue | pages = D452-5 | date = January 2004 | pmid = 14681455 | pmc = 308786 | doi = 10.1093/nar/gkh052 | url = }}{{cite journal | vauthors = Calderone A, Castagnoli L, Cesareni G | title = mentha: a resource for browsing integrated protein-interaction networks | journal = Nature Methods | volume = 10 | issue = 8 | pages = 690–1 | date = August 2013 | pmid = 23900247 | doi = 10.1038/nmeth.2561 | s2cid = 9733108 | url = https://zenodo.org/record/924817 }} C20orf196 functionally interacts with REV7, SHLD2, and SHLD3 in the shieldin complex within the DNA repair network.

C20orf196 gene orthologs are found in species including mammals, birds, reptiles, and amphibians.{{cite journal | vauthors = Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ | title = Basic local alignment search tool | journal = Journal of Molecular Biology | volume = 215 | issue = 3 | pages = 403–10 | date = October 1990 | pmid = 2231712 | doi = 10.1016/s0022-2836(05)80360-2 | s2cid = 14441902 }} C20orf196 has distant orthologs in bony fish and cartilaginous fish. There are no invertebrate orthologs. Orthologs are found in 163 organisms.

There are no paralogs in humans. File:Rate of Evolution for C20orf196.png

C20orf196 has a high protein sequence divergence rate. It is a fast evolving protein. It evolves faster than fibrinogen, as seen in the figure to the right.

Genome-wide association studies have identified SNPs found in the C20orf196 gene that are associated with parental longevity, information processing speed, and breast carcinoma occurrence.{{cite web|url=https://www.ebi.ac.uk/gwas/|title=GWAS Catalog|date=2018}}{{clear}}

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Category:Genes on human chromosome 20