C16orf95
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
[edit]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]
![](http://upload.wikimedia.org/wikipedia/commons/5/52/Diagram_of_Chromosome_16.png)
Homology
[edit]Paralogs
[edit]There are no known paralogs of C16orf95.
Orthologs
[edit]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% |
![](http://upload.wikimedia.org/wikipedia/commons/thumb/1/11/Percent_identity_versus_approximate_time_of_divergence..png/444px-Percent_identity_versus_approximate_time_of_divergence..png)
![](http://upload.wikimedia.org/wikipedia/commons/thumb/7/79/Time-calibrated_phylogenetic_tree_of_C16orf95_orthologs.png/447px-Time-calibrated_phylogenetic_tree_of_C16orf95_orthologs.png)
mRNA
[edit]Alternative splicing
[edit]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 |
![](http://upload.wikimedia.org/wikipedia/commons/thumb/9/99/Binding_sites_for_KHDRBS3.png/245px-Binding_sites_for_KHDRBS3.png)
Secondary structure
[edit]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
[edit]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
[edit]Structure
[edit]Primary
[edit]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
[edit]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.
![](http://upload.wikimedia.org/wikipedia/commons/thumb/3/36/C16orf95_secondary_structure_prediction-_human_and_mouse.png/880px-C16orf95_secondary_structure_prediction-_human_and_mouse.png)
Post-translational modifications
[edit]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
[edit]C16orf95 has a large number of amino acid changes over time, indicating it is a quickly evolving protein.
![](http://upload.wikimedia.org/wikipedia/commons/thumb/9/93/Corrected_number_of_amino_acid_changes_versus_approximate_time_of_divergence..png/425px-Corrected_number_of_amino_acid_changes_versus_approximate_time_of_divergence..png)
Interacting proteins
[edit]There are no proteins known to interact with C16orf95.
Clinical significance
[edit]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
[edit]- ^ a b "C16orf95 chromosome 16 open reading frame 95 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-05-03.
- ^ "C16orf95 Gene". GeneCards. Weizmann Institute of Science. Retrieved May 8, 2016.
- ^ "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2016-05-03.
- ^ "TimeTree :: The Timescale of Life". timetree.org. Retrieved 2016-05-03.
- ^ a b c d e "SDSC Biology Workbench". workbench.sdsc.edu. Retrieved 2016-05-08.
- ^ "c16orf95 - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-05-05.
- ^ "Homo sapiens chromosome 16 open reading frame 95 (C16orf95), transcrip - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-05-05.
- ^ "Homo sapiens chromosome 16 open reading frame 95 (C16orf95), transcrip - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-05-07.
- ^ "Homo sapiens chromosome 16 open reading frame 95 (C16orf95), transcrip - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-05-07.
- ^ "RNA Folding Form". The RNA Institute, College of Arts and Sciences, State University of New York at Albany. Retrieved 2016-05-09.
- ^ "RBPDB: The database of RNA-binding specificities". rbpdb.ccbr.utoronto.ca. Retrieved 2016-05-09.
- ^ "KHDRBS3 - KH domain-containing, RNA-binding, signal transduction-associated protein 3 - Homo sapiens (Human) - KHDRBS3 gene & protein". www.uniprot.org. Retrieved 2016-05-09.
- ^ "EST Profile - Hs.729380". www.ncbi.nlm.nih.gov. Retrieved 2016-05-08.
- ^ a b "uncharacterized protein C16orf95 isoform 1 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-05-08.
- ^ "SDSC Biology Workbench". workbench.sdsc.edu. Retrieved 2016-05-09.
- ^ "ExPASy: SIB Bioinformatics Resource Portal - Home". www.expasy.org. Retrieved 2016-05-09.
- ^ "CSS-Palm - Palmitoylation Site Prediction". csspalm.biocuckoo.org. Archived from the original on 2009-02-15. Retrieved 2016-05-09.
- ^ "NetPhos 2.0 Server". www.cbs.dtu.dk. Retrieved 2016-05-09.
- ^ "NetOGlyc 4.0 Server". www.cbs.dtu.dk. Retrieved 2016-05-09.
- ^ Griffiths, Anthony JF; Miller, Jeffrey H.; Suzuki, David T.; Lewontin, Richard C.; Gelbart, William M. (2000-01-01). "Rate of molecular evolution".
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(help) - ^ 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
- ^ 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