Chromosome 20 open reading frame 144 (c20orf144) is a human protein-encoding gene. The human c20orf144 protein consists of 153 amino acids, with the first 150 amino acids being characterized as part of the Bcl-2 like protein of testis (Bclt) family (pfam 15318).
Gene The c20orf144 gene is located on the plus strand at 20q11.22 and spans 3,293 base pairs. The gene contains two exons. Of the plus strand, 572 nucleotides are antisense to parts of the human genes PXMP4 and NECAB3. Other gene neighbors include ACTL10 and CBFA2T2.
Transcript The encoded mRNA is 522 nucleotides in length (Accession: NM_080825) and there are no identified alternative splicings. Human c20orf144 mRNA expression is enriched in the testis, specifically in the early and late spermatids.
Protein The human c20orf144 gene encodes a protein of 153 amino acids in length, and there are three disordered regions (Accession: NP_543015.1). Amino acids 1-150 are a part of the Bclt protein family which is predicted to be involved in apoptosis. The molecular weight is 17.2kDa and the theoretical isoelectric point is 11.47. There are 21 more lysines and arginines, which are positively charged, than there are aspartates and glutamates, which are negatively charged. The tertiary protein structure, produced by AlphaFold, predicts the presence of 3 α helices, and the absence of β sheets in human c20orf144.
Cellular localization Analysis of the localization of human c20orf144 and many mammalian orthologs predicts localization of c20orf144 in the nucleus, with 78.3% confidence for the human protein.
Post translational modifications +Table 1. Predicted Post Translation Modifications of Human C20orf144ModificationModification Site in Human C20orf144N-Myristoylation2GProtein Kinase C Phosphorylation6SCasein Kinase 2 Phosphorylation87SNon-Specific Phosphorylation117SO-Glycosylation117SProtein Kinase C Phosphorylation123S
Evolution and orthologs
The evolutionary rate of C20orf144 is comparable to the high rate of evolution of fibrinogen alpha chain, suggesting the protein is evolving quickly.
Orthologs of the c20orf144 gene in Homo sapiens are found in many mammals excluding monotremes. As shown in Table 2, marsupials are the most distantly related organisms to humans in which proteins encoded by human c20orf144 gene orthologs are found, suggesting that C20orf144 first appeared approximately 160 million years ago.
+Table 2. Proteins encoded by the orthologs of the c20orf144 gene in humans.Genus and Species Common NameOrderProtein Accession #Median Date of Divergence (MYA)Sequence LengthSequence Identity (%)Sequence Similarity (%)Homo sapiensHumanPrimata NP_543015.10153100100Macaca mulattaRhesus MonkeyPrimata XP_001105397.1 28.915386.390.8Piliocolobus tephroscelesUgandan Red ColobusPrimata XP_023076213.128.914163.766.1Jaculus jaculusLesser Egyptian JerboaRodentiaXP_045011648.18717646.455.8Myodes glareolusBank VoleRodentiaXP_048287479.18719742.151.8Mus musculusHouse MouseRodentiaNP_083581.18719741.449.8Camelus ferusWild Bactrian CamelArtiodactylaXP_032318023.1 941745464.4Equus caballusDomestic HorsePerissodactylaXP_023482143.19417845.756Monodon monocerosNarwhalArtiodactylaXP_029075207.19418142.950.5Physeter catodonSperm WhaleArtiodactylaXP_023984368.1 9414840.848.4Prionailurus bengalensisLeopard CatCarnivora XP_043458511.1941795260.9Ursus arctosBrown BearCarnivora XP_026358671.19418451.661.4Eumetopias jubatusSteller Sea LionCarnivora XP_027974622.19418447.358.1Rousettus aegyptiacusEgyptian Fruit BatChiropteraXP_016017694.29417551.462.7Rhinolophus ferrumenquinumGreater Horseshoe BatChiropteraXP_032951343.1 9419140.251.5Pteropus vampyrusLarge Flying FoxChiropteraXP_023377960.1942094050.5Choloepus didactylusSouthern Two-Toed SlothPilosaXP_037668100.19918847.957.4Gracilinanus agilisAgile Gracile Mouse OpossumDidelphimorphiaXP_044517537.116016937.949.7Dromiciops gliroidesMonito del MonteMicrobiotheriaXP_043845608.11601703750.8Sarcophilus harrisiiTasmanian DevilDasyuromorphiaXP_031809718.116016036.450
Clinical significance In a study of 28 breast cancer patients, missense mutations in c20orf144 were found in approximately 33% of patients, suggesting a potential role for c20orf144 in the development of breast cancer. Furthermore, c20orf144 is listed in primary renal proximal tubule epithelial cells as a top candidate hit in an siRNA screen, which silences targeted genes. The silencing of c20orf144 in cells exposed to Shiga toxin resulted in metabolic activity that was greater than or equal to 90% of that in a typical cell.
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