C9orf85


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 C9orf85
  • MGC61599
  • RP11-364E17.2
  • LOC138241
  • OTTHUMP00000021461

Isoforms

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.
Genus speciesCommon nameTaxonomic groupDate of Divergence Accession numberLength IdentitySimilarity
Homo 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%

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 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, 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. 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. 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.

Promoter

C9orf85 has 3 predicted promoters for the gene. 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'
Transcription factorDetailed matrix informationMatrix Score
CLOXTranscriptional repressor CDP0.962
KLFSGut-enriched Krueppel-like factor1.000
CAATNuclear factor Y 0.940
HIFFAryl hydrocarbon receptor nuclear translocator-like, homodimer1.000
MZF1Myeloid zinc finger protein0.992
STATSTAT5: signal transducer and activator of transcription 50.944
ETSFETS-like gene 1 0.958
CREBTax/CREB complex0.834
P53FTumor suppressor p53 0.921
TCFFTCF11/LCP-F1/Nrf1 homodimers1.000
FKHDFork head homologous X binds DNA with a dual sequence specificity 0.870
MIRFZinc finger protein 7680.819
BCL6B-cell CLL/lymphoma 6, member B 0.878
AP2FTranscription factor AP-2, alpha0.931
EBOXMYC associated factor X0.926
GCMFGlial 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, 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.