C9orf135

Last updated
CFAP95
Identifiers
Aliases CFAP95 , chromosome 9 open reading frame 135, C9orf135, cilia and flagella associated protein 95
External IDs MGI: 1914733; HomoloGene: 49850; GeneCards: CFAP95; OMA:CFAP95 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001010940
NM_001308084
NM_001308085
NM_001308086

Contents

NM_026188

RefSeq (protein)

NP_001010940
NP_001295013
NP_001295014
NP_001295015

NP_080464

Location (UCSC) Chr 9: 69.82 – 69.91 Mb Chr 19: 23.54 – 23.63 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

C9orf135 is a gene that encodes a 229 amino acid protein. It is located on Chromosome 9 of the Homo sapiens genome at 9q12.21. [5] The protein has a transmembrane domain from amino acids 124-140 and a glycosylation site at amino acid 75. C9orf135 is part of the GRCh37 gene on Chromosome 9 and is contained within the domain of unknown function superfamily 4572. [6] Also, c9orf135 is known by the name of LOC138255 which is a description of the gene location on Chromosome 9.1. [7]

c9orf135 location on chromosome 9 and the neighboring genes. C9orf135 Gene Location.gif
c9orf135 location on chromosome 9 and the neighboring genes.

There is some evidence associating the c9orf135 gene with premature ovarian failure. [8] In affected women, an autosomal recessive microduplication occurs which may be linked to premature ovarian failure. A Single Nucleotide Polymorphism (SNP) the c9orf135 gene has been linked to Parkinson's disease; a statistically significant mutation has been seen on a Manhattan plot. [9] Further research is required to establish whether c9orf135 relates to Parkinson's disease. [9]

mRNA

Splice Variants of c9orf135 based on NCBI AceView Slice variants.png
Splice Variants of c9orf135 based on NCBI AceView

The mRNA of c9orf135 is 906 nucleotides in length. [10] The 5' and 3' Untranslated regions (UTR) contain hairpin loops. [11] The 3' UTR comprises 123 nucleotides and the 5' UTR comprises 18 nucleotides. The mRNA encodes a protein with a secondary structure composed of both beta-sheets and alpha-helices. [12]

Protein

Properties of c9orf135

It is likely that c9orf135 is a nuclear protein because it has properties that match attributes of nuclear proteins rather than secretory pathways. [13] [14] Furthermore, there is a nuclear localization signal (PEKVKKL) from amino acid 67 to 73 on c9orf135. [15] C9orf135 is soluble with an average hydrophobicity of -0.772. The negative hydrophobicity value is due to its slightly acidic properties. [16]

Post-translational modifications

Serine phosphorylation sites were seen at amino acid positions 7, 50, 86, 98, and 194. Threonine phosphorylation occurs at 34, 129, 155, and 201. Tyrosine phosphorylation sites occur at 78, 160, 177, and 209. Also, a N-terminal acetylation site is present at amino acid 3. A Signal cleavage site is present between amino acids 11 and 12. [17]

Protein Interaction

PB2 interacts with c9orf135 which was found from a two-hybrid yeast assay. The information provided about PB2 (Polymerase Basic Protein 2) is that it is a viral protein that is involved with the influenza A virus. It is primarily involved in Cap stealing in which it binds the pre-mRNA cap an ultimately cleaves 10-13 nucleotides off. PB2 is also important for starting the replication of viral genomes. PB2 is also known to inhibit type 1 interferon by inhibiting the mitochondrial antiviral signalling protein MAVS. [18]

Mutations

Eleven different common DNA genome variants of the human c9orf135 gene have been identified. All of the mutations within those genome variants have been compiled into the following table. [19] Mutations that were present at levels of 0.01 frequency or higher have been incorporated into the table; synonymous mutations were excluded.

LocationAmino Acid PositionMutationFrequency
5' UTR57N/A0.386
5' UTR93N/A0.047
5' UTR138N/A0.018
Exon169 Missense K30T0.018
Exon237 Missense R53K0.047
Exon456 Missense E126K0.01

Gene Expression

c9orf135 is expressed in connective tissue and testicular tissue at high levels. [20] It is likely that the expression of c9orf135 is expressed at low levels throughout human cells. It was also found that c9orf135 is found at significantly higher levels in the adult human umbilical cord versus the foetal human umbilical cord. [21] Furthermore, in women with ovarian adenocarcinoma the expression of c9orf135 is much higher in the epithelial cells within the ovaries. [22] Women with polycystic ovarian syndrome have a lower expression of c9orf135 than those people who do not have the condition. [23]

Amino Acid Quantity

A comparison between the c9orf135 from Mus musculus (House Mouse) and Pteropus alecto (Black Flying Fox) is described here. There were no significant amino acids that differed in c9orf135 from the rest of the mouse body. However, in the Black Flying Fox, it was valine poor and tryptophan rich. As seen from the human results, the Black Flying fox only shared the tryptophan surplus results. The House Mouse and Black Flying Fox were both used because they shared 64% and 79% similarity in the c9orf135 genome respectively. Analysis demonstrates that alanine and tyrosine could predict points of interest because they both contained results differing from the rest of the human gene averages. [16]

Amino Acid of InterestCompositional Percentage

Compared to normal protein amounts in H. sapiens

Alanine3.1%Less than Average
Tyrosine5.2%More than Average
Tryptophan3.1%More than average

Homology

c9orf135 is conserved through eukaryotes, ranging from mammals, reptiles and Annelida.

Orthologs

The orthologs of c9orf135 were sequenced in BLAST and 20 orthologs were picked. The orthologs were all multicellular organisms and were limited to aquatic animals, reptiles, amphibians, and warm-blooded animals. Also, protists, bacteria, archea, and fungi did not have orthologs. However, no paralogs were found when c9orf135 was sequenced in BLAST. Please refer to the spreadsheet for the complete list of orthologs to c9orf135. Time tree was a program that was used to find the evolutionary branching shown in MYA [24] There were no paralogs found for c9orf135.

Genus/SpeciesCommon nameDivergence from Humans (MYA)Accession numberAmino Acid LengthSequence identitySequence similarity
Homo sapiens Human--Q5VTT2229----
Pongo abelii Sumatran Orangutan15.8XP_00281990420686%87%
Rhinopithecus roxellana Golden Snub-Nosed Monkey29.1XP_01036125022993%95%
Mus musculus House Mouse90.9EDL4160422864%73%
Pteropus alecto Black Flying Fox97.5XP_78596423079%86%
Equus przewalskii Przewalski's horse97.5XP_00850480618377%86%
Panthera tigris altaica Siberian Tiger97.5XP_00707753718773%83%
Ovis aries Sheep97.5XP_01494867020769%77%
Elephantulus edwardii Cape Elephant Shrew105XP_00689448525472%82%
Pelodiscus sinensis Chinese Softshell Turtle320.5XP_00613790221755%68%
Gekko japonicusGekko320.5XP_01527599922152%64%
Alligator mississippiensis American Alligator320.5XP_01446414421251%64%
Ophiophagus hannah King Cobra320.5ETE6172021543%59%
Salmo salar Atlantic Salmon429.6XP_0139988409934%55%
Esox lucius Northern Pike429.6XP_01090169115430%47%
Branchiostoma floridae Lancelet733XP_00259178622145%59%
Strongylocentrotus purpuratus Sea Urchin747.8XP_78596424147%62%
Saccoglossus kowalevskii Acorn Worm747.8XP_00273341015338%58%
Lingula anatina Ocean Clam847XP_01339860522043%59%
Crassostrea gigas Pacific Oyster847XP_01142694421540%57%
Helobdella robusta Leech847XP_00901986125629%44%

Divergence of c9orf135

A divergence comparison of c9orf135 with fast diverging cytochrome C, and slow diverging fibrinogen is shown in the chart. Overall, c9orf135 has diverged significantly quicker than fibrinogen and slightly slower than cytochrome C.

C9orf135 Divergence.png

Related Research Articles

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References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000204711 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000033053 Ensembl, May 2017
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  7. Result Filters. (n.d.). Retrieved February 07, 2016, from https://www.ncbi.nlm.nih.gov/protein/Q5VTT2.1 Archived 2018-06-23 at the Wayback Machine
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  18. "1 binary interaction found for search term C9orf135". IntAct Molecular Interaction Database. EMBL-EBI. Archived from the original on 2018-08-25. Retrieved 2018-08-25.
  19. NCBI SNP Geneview https://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?geneId=138255&ctg=NT_008470.20&mrna=XM_011518232.1&prot=XP_011516534.1&orien=forward Archived 2018-06-23 at the Wayback Machine
  20. EST profile, NCBI, https://www.ncbi.nlm.nih.gov/nuccore/NM_001308086.1 Archived 2016-09-16 at the Wayback Machine
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Further reading

Chromosome 9