C1orf159 Explained

C1orf159 is a protein that in human is encoded by the C1orf159 gene located on chromosome 1.[1] [2] This gene is also found to be an unfavorable prognosis marker for renal and liver cancer, and a favorable prognosis marker for urothelial cancer.[3]

Gene

The Homo sapiens C1orf159 gene (UniProt ID: Q96HA4) is a gene located on the short arm of chromosome 1 at locus 1p36.33. The gene is 34,247 base pairs in length, located at Chromosome 1 position 1,081,818 to 1,116,089 on the reverse strand.[4]

Transcript

The longest variant of human C1orf159 gene encodes an mRNA that is 2,432 nucleotides in length with 12 exons.[5] A promoter region was predicted using UCSC Genome Browser,[6] which is 762 nucleotides long, including a 434 nucleotide upstream of the transcriptional start site, exon 1, and a 298 nucleotide region of intron 1.

Protein

Isoforms

Alternative splicing of the gene creates 5 protein isoforms. The longest isoform is 380 amino acids in length with a molecular mass of 40.382 kDa.

Isoforms of human C1orf159 protein!Isoform!UniProt[7] ID!Length (aa)
1Q96HA4-1380
2Q96HA4-2185
3Q96HA4-3189
4Q96HA4-4198
5Q96HA4-5254

Composition

C1orf159 protein is a proline- and arginine-rich, and a lysine- and glutamic acid- poor protein. The isoelectric point of the human C1orf159 protein is 10.07,[8] which is more basic than the average human proteomic protein pI of 7.36.[9]

Domain

The human C1orf159 protein contains a domain of unknown function DUF4501. Although the exact function of the domain is not clear, it is thought to be a single pass-membrane protein with highly conserved cysteine residues.

The protein also contains a transmembrane domain at positions 144-169 and a signal peptide at positions 1-18.

Structure

Alphafold predicts the structure of human C1orf159 protein to be mainly composed of alpha-helices.[10]

Post-translational modification

The predicted post-translational modifications of the C1orf159 protein includes N-linked glycosylation on asparagine at positions 104, 111, and 128.[11]

Homology/evolution

Orthologs

Orthologs of human C1orf159 are found in vertebrates including mammals, birds, reptiles, amphibians, and fish[12] with the most distantly related group of organisms being cartilaginous fish, with a date of divergence of approximately 450 million years ago.[13] Orthologs are not found in jawless fish or invertebrates.

Species
GroupTaxonomicGroupNCBI Protein Accession NumberProtein SequenceSimilarity

(% Relative to Human Protein)

HumanMammalsPrimatesNP_001317235.1100.0
ChimpanzeePrimatesXP_024204744.198.4
BonoboPrimatesXP_008975653.288.9
House MouseRodentiaNP_796179.140.9
CattleArtiodactylaNP_001026925.136.6
Sunda Flying LemurDermopteraXP_008567908.139.4
Chinese Tree ShrewScandentiaXP_027622332.135.8
CougarCarnivoraXP_025768111.141.7
ChickenBirdsGalliformesXP_024998437.232.8
Rock PigeonColumbiformesXP_013226562.235.7
Hooded CrowPasseriformesXP_039420032.129.9
Golden-collared ManakinPasseriformesXP_017934783.136.5
GharialReptilesCrocodiliaXP_019367354.136.8
Leatherback Sea TurtleTestudinesXP_027584571.135.9
Chinese Softshell TurtleTestudinesXP_006127168.135.2
Western Clawed FrogAnuraNP_001039047.134.6
Two-lined CaecilianAmphibiansGymnophionaXP_029433955.133.9
Asiatic ToadAnuraXP_044137731.131.6
ZebrafishFishCypriniformesNP_001313355.126.4
SterletAcipenseriformesXP_034760226.132.8
ReedfishPolypteriformesXP_028663678.132.9
Small-spotted CatsharkCarcharhiniformesXP_038629468.128.0
Whale SharkOrectolobiformesXP_020381962.132.9

Evolutionary History

When compared with the evolution rate with cytochrome c and fibrinogen alpha, the C1orf159 protein has a similar evolutionary rate of change to the fast-evolving fibrinogen alpha protein, C1orf159 protein has a relatively fast evolution rate.

Clinical Significance

The Human Protein Atlas shows that C1orf159 is an unfavorable prognosis marker for renal and liver cancer, and a favorable prognosis marker for urothelial cancer, indicating that a high expression of C1orf159 is associated with a lower survival probability for patients with renal and liver cancer, and is associated with a higher survival probability for patients with urothelial cancer.

Notes and References

  1. Web site: C1orf159 Gene . GeneCards . 2022-06-20 .
  2. Web site: Gene symbol report . HUGO Gene Nomenclature Committee . 2022-06-20 .
  3. Web site: Expression of C1orf159 in cancer - Summary - The Human Protein Atlas . 2022-06-20 . www.proteinatlas.org.
  4. Web site: Gene: C1orf159 (ENSG00000131591) - Summary - Homo_sapiens - Ensembl genome browser 107 . 2022-07-27 . uswest.ensembl.org.
  5. Web site: 2022-04-17 . Homo sapiens chromosome 1 open reading frame 159 (C1orf159), transcript variant 1, mRNA . en-US.
  6. Web site: UCSC Genome Browser Home . 2022-07-28 . genome.ucsc.edu.
  7. Web site: UniProt . 2022-07-28 . www.uniprot.org.
  8. Web site: SIB Swiss Institute of Bioinformatics Expasy . 2022-07-28 . www.expasy.org.
  9. Kurotani A, Tokmakov AA, Sato KI, Stefanov VE, Yamada Y, Sakurai T . Localization-specific distributions of protein pI in human proteome are governed by local pH and membrane charge . BMC Molecular and Cell Biology . 20 . 1 . 36 . August 2019 . 31429701 . 6701068 . 10.1186/s12860-019-0221-4 . free .
  10. Web site: AlphaFold Protein Structure Database . 2022-07-28 . alphafold.ebi.ac.uk.
  11. Web site: C1orf159 - Proteomics . 2022-07-30 . www.nextprot.org.
  12. Web site: C1orf159 orthologs . 2022-07-28 . NCBI . en.
  13. Redmond AK, Macqueen DJ, Dooley H . Phylotranscriptomics suggests the jawed vertebrate ancestor could generate diverse helper and regulatory T cell subsets . BMC Evolutionary Biology . 18 . 1 . 169 . November 2018 . 30442091 . 10.1186/s12862-018-1290-2 . 6238376 . 2018BMCEE..18..169R . free .