C19Orf81

C19Orf81 is a protein which in humans is encoded by the gene C19Orf81. It is a rarely expressed protein found mainly in the testes, cerebellum and cerebral cortex.Uhlén, M., Fagerberg, L., Hallström, B. M., Lindskog, C., Oksvold, P., Mardinoglu, A., Sivertsson, Å., Kampf, C., Sjöstedt, E., Asplund, A., Olsson, I., Edlund, K., Lundberg, E., Navani, S., Szigyarto, C. A., Odeberg, J., Djureinovic, D., Takanen, J. O., Hober, S., Alm, T., … Pontén, F. (2015). Proteomics. Tissue-based map of the human proteome. Science, 347(6220), 1260419. https://doi.org/10.1126/science.1260419proteinatlas.org

Aliases Other names for C19Orf81 include chromosome 19 open reading frame 81 and C9J6K1.The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses (PMID 27322403; Citations: 2,595) Stelzer G, Rosen R, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, Iny Stein T, Nudel R, Lieder I, Mazor Y, Kaplan S, Dahary, D, Warshawsky D, Guan - Golan Y, Kohn A, Rappaport N, Safran M, and Lancet D Current Protocols in Bioinformatics(2016), 54:1.30.1 - 1.30.33.doi: 10.1002 / cpbi.5 [PDF]

Gene The gene C19Orf81 is found on chromosome 19 at site 19q13.33 from and is 9862 base pairs in length.Gene [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004 – [cited 2023 12 15]. Available from: https://www.ncbi.nlm.nih.gov/gene?LinkName=protein_gene&from_uid=304307731 It runs in the positive direction. 5 exons compose the 761 base pair (bp) coding sequence of the gene.Nucleotide [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004 – [cited 2023 12 15]. Available from: https://www.ncbi.nlm.nih.gov/nuccore/NM_001195076.2 One isoform gene exists for C19Orf81 that is 951 bp in length (XM_054320844.1).

mRNA expression Tissue expression of C19Orf81 mRNA is found in the testes. mRNA expression may be regulated by the KMT2D transcription factor, a histone methyltransferase, due to a decrease in C19Orf81 expression when KMT2D is down regulated.Jefri, M., Zhang, X., Stumpf, P. S., Zhang, L., Peng, H., Hettige, N., Theroux, J. F., Aouabed, Z., Wilson, K., Deshmukh, S., Antonyan, L., Ni, A., Alsuwaidi, S., Zhang, Y., Jabado, N., Garcia, B. A., Schuppert, A., Bjornsson, H. T., & Ernst, C. (2022). Kabuki syndrome stem cell models reveal locus specificity of histone methyltransferase 2D (KMT2D/MLL4). Human molecular genetics, 31(21), 3715–3728. https://doi.org/10.1093/hmg/ddac121

Protein The protein, C19Orf81, is 198 amino acids in length and has a molecular weight of 22.4 kDa.The UniProt Consortium UniProt: the Universal Protein Knowledgebase in 2023 Nucleic Acids Res. 51:D523–D531 (2023) uniprot.org It contains one domain of unknown function, DUF4732, that spans from Gly23 to Leu181.Protein [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004 – [cited 2023 12 15]. Available from: https://www.ncbi.nlm.nih.gov/protein/304307731 Using DeepLoc 2.0,DeepLoc 2.0: multi-label subcellular localization prediction using protein language models. Vineet Thumuluri, Jose Juan Almagro Armenteros, Alexander Rosenberg Johansen, Henrik Nielsen, Ole Winther. Nucleic Acids Research, Web server issue 2022. DeepLoc 2.0 C19Orf81 has cytoplasm and nuclear localization. Predicted post-translational modifications (PTMs) of the protein, shown below, could indicate intercellular location and activity.

Post-translational modifications PTMs predicted using Motif Scan and DTU Health TecSequence- and structure-based prediction of eukaryotic protein phosphorylation sites. Blom, N., Gammeltoft, S., and Brunak, S. Journal of Molecular Biology: 294(5): 1351-1362, 1999.PMID 10600390 DTU Bioinformatic Tools bioinformatic tools.

Phosphorylation Casein kinase 2 (CK2): Thr31, Thr86, Thr93

Protein kinase C (PKC): Ser46, Ser111, Ser116, Ser154

Casein kinases, specifically CK2, have been shown to play a role in major cell events such as survival metabolism, growth, protein synthesis, proliferation and DNA repair.Pepperkok, R., Lorenz, P., Ansorge, W., & Pyerin, W. (1994). Casein kinase II is required for transition of G0/G1, early G1, and G1/S phases of the cell cycle. The Journal of biological chemistry, 269(9), 6986–6991. In an oncogenic setting, CK2 promotes the cancer cell’s growth due to its interference with apoptotic pathways.Litchfield D. W. (2003). Protein kinase CK2: structure, regulation and role in cellular decisions of life and death. The Biochemical journal, 369(Pt 1), 1–15. https://doi.org/10.1042/BJ20021469 CK2 also plays a role in spermatogenesis and germ cell growth.Xu, X., Toselli, P., Russell, L. et al. Globozoospermia in mice lacking the casein kinase II α′ catalytic subunit. Nat Genet 23, 118–121 (1999). https://doi.org/10.1038/12729

Amidation An amidation site on C19Orf81 is positioned at Arg129 in the snippet ARGG. Amidation of a protein is and important modification necessary for signaling and protein interactions.

Structure Secondary structure prediction by CFSSPAshok Kumar, T. (2013). CFSSP: Chou and Fasman Secondary Structure Prediction server. WIDE SPECTRUM: Research Journal. 1(9):15-19. method displays multiple α-helices and a few β-sheets. A similar pattern seen in the tertiary structure of C19Orf81 by AlphaFold,Jumper, J et al. Highly accurate protein structure prediction with AlphaFold. Nature (2021).Varadi, M et al. AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Research (2021). is shown below

Function Given C19Orf81’s appearance in early stage spermatogonia cells and lower levels in other stages of spermatogenesis, as shown by expression summaries from the Human Protein Atlas, phosphorylation by CK2 could indicate a role for C19Orf81 in spermatogonial stem cell differentiation and growth.Guo, J., Grow, E.J., Mlcochova, H. et al. The adult human testis transcriptional cell atlas. Cell Res 28, 1141–1157 (2018). https://doi.org/10.1038/s41422-018-0099-2

Phylogeny

Based on data found in the NCBI database and using NCBI BLAST,BLAST [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004 – [cited 2023 12 15]. Available from: C19Orf81 has orthologs in all vertebrates except birds.

Orthologs Below is a table of ortholog genes of the human C19Orf81 gene found by using NCBI Blast. Sequence similarities were calculated using Emboss Needle Alignment ToolNeedleman SB, Wunsch CD. A general method applicable to the search for similarities in the amino acid sequence of two proteins. Journal of Molecular Biology. 1970 Mar;48(3):443-453. DOI: 10.1016/0022-2836(70)90057-4. PMID 5420325. and median date of divergence (million years ago) was retrieved from TimeTreeKumar S, Suleski M, Craig JM, Kasprowicz AE, Sanderford M, Li M, Stecher G, Hedges SB (2022) TimeTree 5: An Expanded Resource for Species Divergence Times. Mol Biol Evol doi.org/10.1093/molbev/msac174

+ Summary of 19 Orthologs for C19Orf81 Genus Species Common name Taxonomic Order Median Date of Divergence (MYA) Sequence length (aa) Sequence identity% to Human ! !Sequence similarity% to Human Accession # Homo sapiens Human Primate 0 198 100 100 NP_001182005.1 Rhinopithecus roxellana Golden Snub-Nosed Monkey Primate 28.8 198 96 98 XP_010367863.1 Piliocolobus tephrosceles Ugandan Red Colobus Primate 28.8 198 95.5 97.5 XP_023038374.1 Mus musculus Mouse Rodentia 87 196 78.3 88.9 NP_081325.1 Orcinus orca Orca Artiodactyle 94 198 84.3 91.4 XP_049559498.1 Eumetopias jubatus Steller Sea Lion Carnivora 94 198 81.8 89.9 XP_027947235.1 Echinops telfairi Lesser Hedgehog Tenrec Afrosoricida 99 198 83.3 90.4 XP_012862141.2 Hyla sarda Sardinian Tree Frog Anura 352 219 33.2 47.5 XP_056398596.1 Bufo gargarizans Asiatic Toad Anura 352 254 28.8 42 XP_044133453.1 Microcaecilia unicolor Microcaecilia Unicolor Gymnophiona 352 212 41.7 56.6 XP_030051298.1 Rhinatrema bivittatum Two-lined Caecilian Gymnophiona 352 216 40.6 55.2 XP_029441218.1 Protopterus annectens Western African Lungfish Lepidosireniformes 408 205 37.8 59 XP_043915129.1 Latimeria chalumnae West Indian Ocean Coelacanth Coelacathiformes 415 219 40.3 61.5 XP_014341008.1 Acipenser ruthenus Sterlet Aceripensiformes 429 210 40.6 57.5 XP_058875337.1 Amblyraja radiata Thorny Skate Rajiformes 462 197 38.8 53.3 XP_032872447.1 Leucoraja erinacea Little Skate Rajiformes 462 197 38.8 52.9 XP_055521580.1 Carcharodon carcharias Great White Shark Lamniformes 462 198 42.3 61.4 XP_041033413.1 Scyliorhinus canicula Small Spotted Catshark Carcharhiniformes 462 198 38.6 55.7 XP_038639721.1 Chiloscyllium plagiosum White Spotted Bamboo Shark Orectolobiformes 462 158 36.6 54.6 XP_043535241.1 Rhincodon typus Whale Shark Orectolobiformes 462 176 39.5 60 XP_020365855.2

References