Chromosome 9 open reading frame 85, commonly known as C9orf85, is a protein in Homo sapiens encoded by the C9orf85 gene. The gene is located at 9q21.13. When spliced, four different isoforms are formed. C9orf85 has a predicted molecular weight of 20.17 kdal. Isoelectric point was found to be 9.54. The function of the gene has not yet been confirmed, however it has been found to show high levels of expression in cells of high differentiation.
Background
Protein Sequence The sequence for C9orf85 isoform 1 in Homo sapiens, derived from NCBI: MSSQKGNVARSRPQKHQNTFSFKNDKFDKSVQTKKINAKLHDGVCQRCKEVLEWRVKYSKYKPLSKPKKCVKCLQKTVKDSYHIMCRPCACELEVCAKCGKKEDIVIPWSLPLLPRLECSGRILAHHNLRLPCSSDSPAS ASRVAGTTGAHHHAQLIFVFLVEMGFHYVGQAGLELLTS
Aliases Uncharacterized Protein C9orf85C9orf85 - Uncharacterized protein C9orf85 - Homo sapiens (Human) - C9orf85 gene & protein. (2020). Uniprot.Org. https://www.uniprot.org/uniprot/Q96MD7 MGC61599(2020). Genenames.Org. https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/28784 RP11-364E17.2 LOC138241 OTTHUMP00000021461
Isoforms +Table Showcasing the Lengths of all C9orf85 IsoformsIsoform #mRNA Length (bp)Amino Acid Length (aa)1382117921185157313161384370769 Isoform 1 is the major form of the gene used. This isoform contains 4 exons. It's accession number is NM_001365053.2.
Homology
Orthologs The C9orf85 gene was found in all species type including vertebrate to bacteria. However no type of protist was found as an ortholog for the human gene except for plasmodium. +A List of 20 Orthologs for the gene C9orf85 in Homo sapiensGenus speciesCommon nameTaxonomic groupDate of Divergence (MYA)Accession numberLength (aa)IdentitySimilarityHomo sapiensHumanChordata0NP_001351982179100%100%Meriones unguiculatusMongolian gerbilRodentia90XP_02151463815474%84%Gallus gallusChickenChordata312XP_00123382116678.70%60%Terrapene carolina triunguisThree-toed box turtleChordata312XP_02406679217185.45%61%Chelonia mydasGreen sea turtleChordata312XP_00706567617884.31%61%Calidris pugnaxRuff birdChordata312XP_01481398516677.78%60%Microcaecilia unicolorTiny cayenne caecilianChordata351.8XP_03004972317876.15%60%Xenopus tropicalisWestern clawed frogChordata351.8KAE863308513378.18%61%Electrophorus electricusElectric eelChordata435XP_02688615815655.13%87%Oncorhynchus mykissRainbow troutChordata435XP_02146115617760.77%72%Acanthaster planciCrown-of-thorns starfishEchinodermata684XP_02209625419756.76%62%Photinus pyralisBig dipper fireflyArthropoda797XP_03134672618358.04%62%Pomacea canaliculataGolden apple snailMollusca797XP_02507710120847.33%73%Drosophila melanogasterFruit FlyArthropoda797NP_57320923449.58%65%Acropora milleporaCoralCnidaria824XP_02918751719057.14%62%Salpingoeca rosettaChoanoflagellateChoanoflagellate1023XP_00499570028641.67%60%Apophysomyces ossiformisFungiMucoromycota1105KAF772513918140%72%Ricinus communisCaster oil plantSpermatophyta1496XP_00253099722734.21%78%Plasmodium ovale wallikeriMalarian protistApicomplexa1768SBT5695468068.75%17%Bacillus cereusBacteriaFirmicutes4290KXI725398373.61%39%
Paralogs +5 Possible Paralogs for the gene C9orf85 in Homo sapiensParalogAccession numberLength (aa)IdentitySimilarityLocationCCDC198XP_00526786329044.38%89%Chromosome 14RetbidinEAW8431622460%51%Chromosome 19hCG2038446EAX1146013568.54%49%Chromosome 2hCG1820974EAW9421514372.58%41%Chromosome 17O-phosphoseryl-tRNA(Sec) selenium transferase isoform X1XP_01686376658670.67%41%Chromosome 4
Rate of Molecular Evolution
A rate of divergence can be calculated using the molecular clock hypothesis. As observed by the graph, C9orf85 lies between Cytochrome C and Fibrinogen Alpha with a slope leaning more towards Cytochrome C. Therefore, C9orf85 is possibly evolving at a slower rate than most proteins.
Conservation
Multiple Sequence Alignment A multiple sequence alignment (MSA) was done between the top 15 closely related orthologs to the Homo sapiens C9orf85. 20 amino acids were discovered to be conserved among all 15 sequences at the beginning of the protein sequence; within the first three exons.
In a MSA between distantly related homologs, 5 amino acids were observed to be conserved between exons two and three.
Yet, when running a multiple sequence alignment between Homo sapiens and the extremely distant Bacillus cereus, 53 amino acids are observed to be conserved primarily in the fourth exon.
Cysteine
The amino acid cysteine appears the most throughout the protein sequence as a conserved amino acids; 8 out of 20 instances. Cysteine 48, 70, 89, 96, and Tryptophan 54 are amino acids conserved in all species type – including vertebrate, invertebrate, fungi, plants, and protists – besides bacteria.
Using the Statistical Analysis of Protein Sequences tool,EMBL-EBI. (2020). SAPS Results. Ebi.Ac.Uk. https://www.ebi.ac.uk/Tools/services/web/toolresult.ebi?jobId=saps-I20201219-191317-0344-54841082-p1m SAPS, 5 spacings of cysteine were found. Four with the pattern of C-X-X-C—at amino acids 45, 70, 86, and 96—and the fifth spacing at amino acid 89 (CAC). The C-X-X-C pattern is known to be present in metal-binding proteins and oxidoreductases. Additionally, three of the five cysteine spacings were also the top conserved amino acids throughout the most closely related orthologs; C70, C89, and C96.
Localization
Gene Localization in Humans C9orf85 has been found to be expressed highly in epithelial cells.GENEVESTIGATOR Team at Nebion AG. (2020). Genevisible. Genevisible.com; genevisible. https://genevisible.com/tissues/HS/UniProt/Q96MD7 of the pancreas. Additionally, high levels of expression have been established in the urinary bladder and thymus of the adult human, while expression levels were significant in the intestine of a 20-week-old fetus.
Subcellular Localization k-NN results predict C9orf85 to be 78.3% nuclear, 8.7% mitochondrial, 8.7% cytoplasmic, and 4.3% vacuolar.PSORT II Prediction. (2020). Psort.Hgc.Jp. https://psort.hgc.jp/form2.html
Promoter C9orf85 has 3 predicted promoters for the gene.Genomatix: Gene2Promoter Result. (2020). Genomatix.De. https://www.genomatix.de/cgi-bin/c2p/c2p.pl?s=c5402bf929e4d6000dfc7ce8c56fa1e6;TASK=c2p;SHOW=TempSeq_kd0ZKohP.html The choice promoter was GXG_18858 on the plus strand. Chosen for its large quantity of CAGE tags and its position being furthest upstream. Its start position is 71909780 and its end position is 71911841. It includes 2062 base pairs and has 13 transcripts. The last 500 base pairs of the double stranded promoter is featured below: 5' GCAGGAGGCGGGGATTGCGGAAAAGAAGAACCAATAGGAACAAAGGTTCC 3' 3' CGTCCTCCGCCCCTAACGCCTTTTCTTCTTGGTTATCCTTGTTTCCAAGG 5'
5' CCGCCCCTTTGATTTGATGGACTACACATTCGGGCCAATGGGGGAATTCT 3' 3' GGCGGGGAAACTAAACTACCTGATGTGTAAGCCCGGTTACCCCCTTAAGA 5'
5' CATTTCGAAGAAAGTGGGACTTGTTCTCCGGGTTTGAGAAAGAGGCTGCG 3' 3' GTAAAGCTTCTTTCACCCTGAACAAGAGGCCCAAACTCTTTCTCCGACGC 5'
5' CGGAGCCGGAGGGGTCGAGGCTGCGCCGCGTGGAGTGGCTTGGCTTAACA 3' 3' GCCTCGGCCTCCCCAGCTCCGACGCGGCGCACCTCACCGAACCGAATTGT 5'
5' GCAGGGAGGGCAGAGCGATGCTCTTTGACCTCCCAGAAGAGTCACGTGGG 3' 3' CGTCCCTCCCGTCTCGCTACGAGAAACTGGAGGGTCTTCTCAGTGCACCC 5'
5' CTGACCCAGAGCCGGGGCGGAAAGGCTGCGTTTGTTTCTTCCGGGTCATT 3' 3' GACTGGGTCTCGGCCCCGCCTTTCCGACGCAAACAAAGAAGGCCCAGTAA 5'
5' GACAGAAGCGTCAATTCCTGGGAGTAGTTCGTTGGTTTTCTTTCCCCTCA 3' 3' CTGTCTTCGCAGTTAAGGACCCTCATCAAGCAACCAAAAGAAAGGGGAGT 5'
5' TCCTTTTGCCTGCTCCCGGCGAGGGGTGGCTTTGATTTCGGCGATGAGCT 3' 3' AGGAAAACGGACGAGGGCCGCTCCCCACCGAAACTAAAGCCGCTACTCGA 5'
5' CCCAGAAAGGCAACGTGGCTCGTTCCAGACCTCAGAAGCACCAGAATACG 3' 3' GGGTCTTTCCGTTGCACCGAGCAAGGTCTGGAGTCTTCGTGGTCTTATGC 5'
5' TTTAGCTTCAAAAATGACAAGTTCGATAAAAGTGTGCAGACCAAGGTAGG 3' 3' AAATCGAAGTTTTTACTGTTCAAGCTATTTTCACACGTCTGGTTCCATCC 5' +A Table of 16 Possible Transcription Factors Predicted to Bind to the PromoterGenomatix: MatInspector Result. (2019). Genomatix.De. https://www.genomatix.de/cgi-bin/eldorado/eldorado.pl?s=c5402bf929e4d6000dfc7ce8c56fa1e6;PROM_ID=GXP_18858;GROUP=vertebrates;GROUP=others;ELDORADO_VERSION=E35R1911Transcription factorDetailed matrix informationMatrix ScoreCLOXTranscriptional repressor CDP0.962KLFSGut-enriched Krueppel-like factor1.000CAATNuclear factor Y (Y-box binding factor)0.940HIFFAryl hydrocarbon receptor nuclear translocator-like, homodimer1.000MZF1Myeloid zinc finger protein0.992STATSTAT5: signal transducer and activator of transcription 50.944ETSFETS-like gene 1 (ELK-1)0.958CREBTax/CREB complex0.834P53FTumor suppressor p53 (3' half site)0.921TCFFTCF11/LCP-F1/Nrf1 homodimers1.000FKHDFork head homologous X binds DNA with a dual sequence specificity (FHXA and FHXB)0.870MIRFZinc finger protein 7680.819BCL6B-cell CLL/lymphoma 6, member B (BCL6B)0.878AP2FTranscription factor AP-2, alpha0.931EBOXMYC associated factor X0.926GCMFGlial cells missing homolog 1, chorion-specific transcription factor GCMa0.942
Regulation
Transmembrane Domain Though there is a presence of hydrophobic regions in the protein sequence,TMPred results. (2020). Vital-It.Ch. https://embnet.vital-it.ch/cgi-bin/TMPRED_form_parser there have been no confirmed transmembrane domains present
Phosphorylation A protein kinase C phosphorylation site is predicted at amino acid 3-5. There is also a possible CK2 phosphorylation site at amino acid 77-80
SUMOylating There is one predicted SUMO site at position 23. The result is significant with a p-value of 0.041.
Function Through the level of expression in various tissue samples, the C9orf85 protein is a regulated gene rather than a constitutive gene.
Additionally, urinary bladder epithelial cells function by altering the immune system of an infection. The thymus is a primary lymphoid organ of the immune system, composed of T cells and epithelial cells. Research has found that the thymus has an increasing role in the development of intestinal immunity Both are an element of the immune system, designed to ensure proper function of the immune system.
References