Biology:SHLD1

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

SHLD1 or shieldin complex subunit 1 is a gene on chromosome 20.[1] The C20orf196 gene encodes an mRNA that is 1,763 base pairs long, and a protein that is 205 amino acids long.[1]

Function

C20orf196 is involved in the DNA repair network. Gupta et al. identified C20orf196 as part of a vertebrate-specific protein complex called shieldin.[2] 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.[2] Analysis indicates a sub-stoichiometric interaction or weaker interaction affinity of SHLD1 to the shieldin complex.[2]

Gene

Locus

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.[1] It contains 11 exons.[3]

Aliases

Its aliases are RINN3[2] and SHLD1.

Expression

mRNA

Alternative Splicing

C20orf196 produces 9 different mRNAs, with 7 alternatively spliced variants and 2 unspliced forms.[3] There are 3 probable alternative promoters, 3 non-overlapping alternative last exons, and 2 alternative polyadenylation sites.[3] 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.[3]

Isoforms

C20orf196 has six splice isoforms.[3]

Promoter

The promoter region is within bases 5749286 to 5750555, totaling 1270 base pairs.[1] The transcription start site is located within bases 5750382 and 5750409, totaling 28 base pairs.[1]

Expression

NCBI GEO Human Tissue Expression Profile for C20orf196.

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.[1] The highest C20orf196 mRNA levels were found in the lymph node, tonsil, thyroid, adrenal gland, prostate, pharynx, parathyroid, connective tissue, and bone marrow.[4]

C20orf196 was found to be expressed in soft tissue/muscle tissue tumors, lymphoma tumors, and pancreatic tumors.[5] C20orf196 representation was biased toward the fetal developmental stage.[5] EBI expression data showed high expression of C20orf196 in the diencephalon and cerebral cortex in the developing brain.[5]

Protein

General Features

The most common transcript encodes a protein that is 205 amino acids long with a molecular mass of 23 kDa.[6] It has a predicted isoelectric point of 4.72.[7] It is predicted to have a half-life around 30 hours.[8] C20orf196 contains 19 positive residues (9.3%), 32 negative residues (15.6%), and 46 hydrophobic residues (22.4%).[9]

Cellular Localization

C20orf196 is predicted to localize in the nucleus.[3]

Domains

C20orf196 contains one domain, DUF4521, which arose in Amniote.[1] DUF4521 spans from amino acid 3 to 201.[1] Several regions of this domain are conserved in c20orf196 orthologs found in mammals, amphibians, and fish. The proteins of this family are functionally uncharacterized.

Post-Translational Modifications

There are many phosphorylation sites targeted by unspecified serine kinases.[10] C20orf196 is predicted to have one SUMOylation site at amino acid 203 and one N-glycosylation site at amino acid 69.[11][12] C20orf196 is predicted to have two ubiquitination sites at amino acids 84 and 139.[13]

Secondary Structure

Several modeling programs predicted a secondary structure containing alpha helix, beta sheet, and coil regions.[14][15] CFSSP has predicted that C20orf196 secondary structure is 57.1% alpha helices, 48.8% beta strands, and 16.6% beta turns.[16]

Protein Interactions

Several databases citing yeast two-hybrid screenings have found C20orf196 to interact with PRMT1, QARS, MAD2L2, and CUL3.[17][18][19][20] C20orf196 functionally interacts with REV7, SHLD2, and SHLD3 in the shieldin complex within the DNA repair network.[2]

Homology and Evolution

Orthologs

C20orf196 gene orthologs are found in species including mammals, birds, reptiles, and amphibians.[2][21] C20orf196 has distant orthologs in bony fish and cartilaginous fish.[2][21] There are no invertebrate orthologs.[2] Orthologs are found in 163 organisms.[1]

Table of Orthologs for C20orf196
Class Species Common Name Date of Divergence (MYA) Accession Number Sequence Identity (%) Sequence Similarity (%)
Mammalia (Marsupialia) Sarcophilus harrisii Tasmanian devil 159 XP_012395605.1 55 68
Phascolarctos cinereus Koala 159 XP_020841153.1 54 67
Aves Gallus gallus Red junglefowl 312 XP_015139412.1 33 49
Aptenodytes forsteri Emperor penguin 312 XP_009280865.1 35 47
Reptilia Crocodylus porosus Saltwater crocodile 312 XP_019404613.1 36 50
Pogona vitticeps Central bearded dragon 312 XP_020649300.1 30 46
Thamnophis sirtalis Common garter snake 312 XP_013911941.1 33 51
Amphibia Nanorana parkeri High Himalaya frog 352 XP_018422019.1 39 57
Osteichthyes Monopterus albus Asian swamp eel 435 XP_020455013.1 46 73
Chondrichthyes Rhincodon typus Whale shark 473 XP_020391945.1 30 55

Paralogs

There are no paralogs in humans.[1]

Figure illustrating the evolution rate for C20orf196 in twenty orthologs as compared to the fast-evolving protein, fibrinogen, and slow-evolving protein, cytochrome C.

Rate of evolution

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.

Phenotype

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.[22]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 "C20orf196 chromosome 20 open reading frame 196 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/149840. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity". Cell 173 (4): 972–988.e23. May 2018. doi:10.1016/j.cell.2018.03.050. PMID 29656893. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Thierry-Mieg, Danielle; Thierry-Mieg, Jean. "AceView: Gene:C20orf196, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView.". https://www.ncbi.nlm.nih.gov/ieb/research/acembly/av.cgi?db=human&term=C20orf196&submit=Go. 
  4. ↑ "Proteomics. Tissue-based map of the human proteome". Science 347 (6220): 1260419. January 2015. doi:10.1126/science.1260419. PMID 25613900. 
  5. ↑ 5.0 5.1 5.2 "The European Bioinformatics Institute < EMBL-EBI". 2018. https://www.ebi.ac.uk/. 
  6. ↑ Database, GeneCards Human Gene. "C20orf196 Gene - GeneCards | CT196 Protein | CT196 Antibody". https://www.genecards.org/cgi-bin/carddisp.pl?gene=C20orf196. 
  7. ↑ "Compute pI/Mw". 2018. https://web.expasy.org/compute_pi/. 
  8. ↑ "In vivo half-life of a protein is a function of its amino-terminal residue". Science 234 (4773): 179–86. October 1986. doi:10.1126/science.3018930. PMID 3018930. Bibcode: 1986Sci...234..179B. 
  9. ↑ "Statistical Analysis of Protein Sequences". 2018. https://www.ebi.ac.uk/Tools/seqstats/saps/. 
  10. ↑ "Sequence and structure-based prediction of eukaryotic protein phosphorylation sites". Journal of Molecular Biology 294 (5): 1351–62. December 1999. doi:10.1006/jmbi.1999.3310. PMID 10600390. 
  11. ↑ "GPS-SUMO: a tool for the prediction of sumoylation sites and SUMO-interaction motifs". Nucleic Acids Research 42 (Web Server issue): W325-30. July 2014. doi:10.1093/nar/gku383. PMID 24880689. 
  12. ↑ "Prediction of N-glycosylation sites in human proteins". DTU Bioinformatics 46: 203–206. 
  13. ↑ "UbiSite: incorporating two-layered machine learning method with substrate motifs to predict ubiquitin-conjugation site on lysines". BMC Systems Biology 10 Suppl 1 (1): 6. January 2016. doi:10.1186/s12918-015-0246-z. PMID 26818456. 
  14. ↑ "I-TASSER server for protein 3D structure prediction". BMC Bioinformatics 9: 40. January 2008. doi:10.1186/1471-2105-9-40. PMID 18215316. 
  15. ↑ Raghava, G. P. S. (2000). "APSSP: Advanced Protein Secondary Structure Prediction Server". http://crdd.osdd.net/raghava/apssp/. 
  16. ↑ T, Ashok Kumar (2013-04-01). "CFSSP: Chou and Fasman Secondary Structure Prediction server". Zenodo 1 (9): 15–19. doi:10.5281/zenodo.50733. 
  17. ↑ "STRING v10: protein-protein interaction networks, integrated over the tree of life". Nucleic Acids Research 43 (Database issue): D447-52. January 2015. doi:10.1093/nar/gku1003. PMID 25352553. 
  18. ↑ "MINT, the molecular interaction database: 2012 update". Nucleic Acids Research 40 (Database issue): D857-61. January 2012. doi:10.1093/nar/gkr930. PMID 22096227. 
  19. ↑ "IntAct: an open source molecular interaction database". Nucleic Acids Research 32 (Database issue): D452-5. January 2004. doi:10.1093/nar/gkh052. PMID 14681455. 
  20. ↑ "mentha: a resource for browsing integrated protein-interaction networks". Nature Methods 10 (8): 690–1. August 2013. doi:10.1038/nmeth.2561. PMID 23900247. https://zenodo.org/record/924817. 
  21. ↑ 21.0 21.1 "Basic local alignment search tool". Journal of Molecular Biology 215 (3): 403–10. October 1990. doi:10.1016/s0022-2836(05)80360-2. PMID 2231712. 
  22. ↑ "GWAS Catalog". 2018. https://www.ebi.ac.uk/gwas/. 



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