C16orf95

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Chromosome 16 open reading frame 95 (C16orf95) is a gene which in humans encodes the protein C16orf95. It has orthologs in mammals, and is expressed at a low level in many tissues. C16orf95 evolves quickly compared to other proteins.

Gene

C16orf95 is a Homo sapiens gene oriented on the minus strand of chromosome 16. It is located on the cytogenic band 16q24.2 and spans 14.62 kilobases.[1] The gene contains 6 introns and 7 exons.[1]

File:Diagram of Chromosome 16.png
Diagram showing the location of C16orf95 on chromosome 16. Image retrieved from the GeneCards entry on C16orf95.[2]

Homology

Paralogs

There are no known paralogs of C16orf95.

Orthologs

Orthologs of C16orf95 exist only in mammals (identified with BLAST).[3] The most distant orthologs are found in opossums and Tasmanian devils.

Genus and species Common name NCBI accession Date of divergence Sequence identity
Homo sapiens Human NP_001182053 0 mya 100%
Pan paniscus Bonobo XP_008972565 6.2 mya 92%
Gorilla gorilla gorilla Gorilla XP_004058157 8.3 mya 95%
Nomascus leucogenys White-cheeked gibbon XP_003272503 19.3 mya 88%
Mandrillus leucophaeus Drill XP_011827052 27.3 mya 78%
Propithecus coquereli Lemur XP_012513111 77.1 mya 62%
Tupaia chinensis Tree shrew XP_006152612 86.5 mya 58%
Oryctolagus cuniculus European rabbit XP_008250325 90.1 mya 56%
Mus musculus Mouse NP_083873 90.1 mya 54%
Rattus norvegicus Rat XP_006222844 90.1 mya 51%
Camelus bactrianus Camel XP_010966555 95 mya 63%
Canis lupus familiaris Dog XP_005620646 95 mya 63%
Equus caballus Horse XP_005608538 95 mya 60%
Felis catus Cat XP_011288582 95 mya 60%
Bos taurus Cattle XP_015331266 95 mya 60%
Lipotes vexillifer Yangtze river dolphin XP_007468528 95 mya 50%
Myotis lucifugus Brown bat XP_014318589 95 mya 56%
Trichechus manatus latirostris Manatee XP_004377854 102 mya 66%
Loxodonta africana Elephant XP_003418190 102 mya 59%
Orycteropus afer afer Aardvark XP_007937409 102 mya 54%
Monodelphis domestica Opossum XP_007477328 162.4 mya 42%
Sarcophilus harrisii Tasmanian devil XP_012395810 162.4 mya 41%
File:Percent identity versus approximate time of divergence..png
The percent identity of several sequences to the human C16orf95 protein were graphed with respect to approximate time of divergence. Data points are labeled with the appropriate species name. Median dates of divergence were found using TimeTree.[4]
File:Time-calibrated phylogenetic tree of C16orf95 orthologs.png
A time-calibrated phylogenetic tree showing the evolutionary relationships among a subset of orthologs. The primates, rodents, and carnivores are grouped together based on the similarity of their protein sequences. The unrooted tree was made using the ClustalW application in SDSC Biology Workbench.[5]

mRNA

Alternative splicing

There are three splice variants of C16orf95.[6] The longest transcript contains 1156 base pairs and 7 exons.[7] Compared to variant 1, the second transcript variant lacks exons 4 and 5.[8] This alternative splicing results in a frameshift of the 3' coding region, and a shorter, unique C-terminus. The third transcript variant lacks exons 4 and 5, and uses an alternate 5' exon and start codon.[9] The resulting peptide has unique N- and C-termini compared to variant 1.

Size (base pairs)
Exon # Variant 1 Variant 2 Variant 3
1 330 330 334
2 52 52 52
3 126 126 126
4 147 – –
5 37 – –
6 187 187 187
7 277 278 278
Total 1,156 973 977
File:Binding sites for KHDRBS3.png
The binding sites for KHDRBS3 in the 3' untranslated region (UTR) are highlighted in green. Secondary structure was predicted with the mfold Web Server, and likely sites for RNA-binding proteins were found with RBPDB.[10][11]

Secondary structure

The 3' untranslated region of the C16orf95 mRNA contains binding sites for KH domain-containing, RNA-binding, signal transduction-associated protein 3 (KHDRBS3) within an internal loop structure. KHDRBS3 regulates mRNA splicing and may act as a negative regulator of cell growth.[12]

Expression

The expression of C16orf95 is not well characterized. However, it has been detected at low levels in the following tissue types: bone, brain, ear, eye, intestine, kidney, lung, lymph nodes, prostate, testes, tonsils, skin, and uterus.[13]

Protein

Structure

Primary

The longest isoform of the C16orf95 protein has 239 amino acids.[14] It has a conserved domain of unknown function spanning residues 76 to 239.[14] C16orf95 has a calculated molecular weight of 26.5 kDa, and a predicted isoelectric point of 9.8.[5] Compared to other human proteins, C16orf95 has more cysteine, arginine, and glutamine residues.[5] It has fewer aspartate, glutamate, and asparagine.[5] The high ratio of basic to acidic amino acids contributes to the protein's higher isoelectric point.

Secondary

C16orf95 is predicted to have several alpha-helices in its C-terminus.[5] This is true for the human and mouse proteins. The N-terminus does not have significant cross-program consensus for secondary structure.

File:C16orf95 secondary structure prediction- human and mouse.png
PELE compiles secondary structure predictions from multiple programs based on the amino acid sequence.[15] Predictions for the C-termini of the human and mouse proteins are shown. There is cross-program consensus that C16orf95 has alpha-helices in its C-terminal tail. This is seen in both the human and mouse proteins.

Post-translational modifications

The tools available at ExPASy were used to predict post-translational modification sites on C16orf95.[16] The following modifications are predicted: palmitoylation, phosphorylation, and O-linked glycosylation. Bolded residues in the table indicate sites that are conserved in more than one species.

Predicted modification Sites - Homo sapiens Sites - Mus musculus Sites - Canis lupus familiaris Tool
Palmitoylation C77, C80, C126, C178,

C187

C24, C41, C90 C64, C113, C174 CSS-Palm[17]
Phosphorylation S6, S9, S53, T57, S68,

S91, S111, T122, S166

S30, S76, S89, S120,

T134, S141

S15, S35, T39, S153 NetPhos 2.0[18]
O-β-GlcNAc S4, S6, S9, T57, S111 None None NetOGlyc 4.0[19]

Evolution

C16orf95 has a large number of amino acid changes over time, indicating it is a quickly evolving protein.

File:Corrected number of amino acid changes versus approximate time of divergence..png
Graph of the corrected number of amino acid changes versus the approximate time of divergence. The corrected number of amino acid substitutions was calculated with the formula: – natural log (1 – observed number of substitutions) × 100. Data points are included for fibrinogen, a quickly evolving protein, and cytochrome c, a slowly evolving protein.[20]

Interacting proteins

There are no proteins known to interact with C16orf95.

Clinical significance

Deletions of C16orf95 have been associated with hydronephrosis, microcephaly, distichiasis, vesicoureteral reflux, and intellectual impairment.[21][22] However, the deletions included coding regions of the following genes: F-box Protein 31 (FBXO31), Microtubule-Associated Protein 1 Light Chain 3 Beta (MAP1LC3B), and Zinc Finger CCHC Type 14 (ZCCHC14). The contributions of each of these genes to the observed phenotypes has yet to be scientifically determined.

References

  1. ↑ 1.0 1.1 "C16orf95 chromosome 16 open reading frame 95 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-05-03.
  2. ↑ "C16orf95 Gene". GeneCards. Weizmann Institute of Science. Retrieved May 8, 2016.
  3. ↑ "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2016-05-03.
  4. ↑ "TimeTree :: The Timescale of Life". timetree.org. Retrieved 2016-05-03.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 "SDSC Biology Workbench". workbench.sdsc.edu. Retrieved 2016-05-08.
  6. ↑ "c16orf95 - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-05-05.
  7. ↑ "Homo sapiens chromosome 16 open reading frame 95 (C16orf95), transcrip - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-05-05.
  8. ↑ "Homo sapiens chromosome 16 open reading frame 95 (C16orf95), transcrip - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-05-07.
  9. ↑ "Homo sapiens chromosome 16 open reading frame 95 (C16orf95), transcrip - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-05-07.
  10. ↑ "RNA Folding Form". The RNA Institute, College of Arts and Sciences, State University of New York at Albany. Retrieved 2016-05-09.
  11. ↑ "RBPDB: The database of RNA-binding specificities". rbpdb.ccbr.utoronto.ca. Retrieved 2016-05-09.
  12. ↑ "KHDRBS3 - KH domain-containing, RNA-binding, signal transduction-associated protein 3 - Homo sapiens (Human) - KHDRBS3 gene & protein". www.uniprot.org. Retrieved 2016-05-09.
  13. ↑ "EST Profile - Hs.729380". www.ncbi.nlm.nih.gov. Retrieved 2016-05-08.
  14. ↑ 14.0 14.1 "uncharacterized protein C16orf95 isoform 1 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-05-08.
  15. ↑ "SDSC Biology Workbench". workbench.sdsc.edu. Retrieved 2016-05-09.
  16. ↑ "ExPASy: SIB Bioinformatics Resource Portal - Home". www.expasy.org. Retrieved 2016-05-09.
  17. ↑ "CSS-Palm - Palmitoylation Site Prediction". csspalm.biocuckoo.org. Retrieved 2016-05-09.
  18. ↑ "NetPhos 2.0 Server". www.cbs.dtu.dk. Retrieved 2016-05-09.
  19. ↑ "NetOGlyc 4.0 Server". www.cbs.dtu.dk. Retrieved 2016-05-09.
  20. ↑ Griffiths, Anthony JF; Miller, Jeffrey H.; Suzuki, David T.; Lewontin, Richard C.; Gelbart, William M. (2000-01-01). "Rate of molecular evolution".
  21. ↑ Handrigan, G. R., Chitayat, D., Lionel, A. C., Pinsk, M., Vaags, A. K., Marsall, C. R., ... Rosenblum, N. D. (2013). Deletions in 16q24.2 are associated with autism spectrum disorder, intellectual disability and congenital renal malformation. Journal of Medical Genetics, 50(4), 163-73. doi:10.1136/jmedgenet-2012-101288
  22. ↑ Butler, M. G., Dagenais, S. L., Garcia-Perez, J. L., Brouillard, P., Vikkula, M., Strouse, P., Innis, J. W., & Grover, T. W. (2012). Microcephaly, intellectual impairment, bilateral vesicoureteral reflux, distichiasis, and glomuvenous malformations associated with a 16q24.3 contiguous gene deletion and a Glomulin mutation. American Journal of Medical Genetics Part A, 158A(4), 839-49. doi:10.1002/ajmg.a.35229
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