View source for 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 ==
C16orf95 is a ''Homo sapiens'' gene oriented on the minus strand of [[Chromosome 16 (human)|chromosome 16]]. It is located on the cytogenic band 16q24.2 and spans 14.62 kilobases.<ref name=":0">{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene?cmd=retrieve&list_uids=100506581|title=C16orf95 chromosome 16 open reading frame 95 [Homo sapiens (human)] - Gene - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2016-05-03}}</ref> The gene contains 6 introns and 7 [[exon]]s.<ref name=":0" />
[[File:Diagram of Chromosome 16.png|none|thumb|720x720px|Diagram showing the location of C16orf95 on chromosome 16.  Image retrieved from the GeneCards entry on C16orf95.<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=C16orf95&keywords=c16orf95|title=C16orf95 Gene|last=|first=|date=|website=GeneCards|publisher=Weizmann Institute of Science|access-date=May 8, 2016}}</ref>]]

== Homology ==

=== Paralogs ===
There are no known [[paralogs]] of C16orf95.

=== Orthologs ===
[[Orthologs]] of C16orf95 exist only in mammals (identified with BLAST).<ref>{{Cite web|url=https://blast.ncbi.nlm.nih.gov|title=BLAST: Basic Local Alignment Search Tool|website=blast.ncbi.nlm.nih.gov|access-date=2016-05-03}}</ref> The most distant orthologs are found in opossums and Tasmanian devils.
{| class="wikitable"
|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|thumb|444x444px|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.<ref>{{Cite web|url=http://timetree.org|title=TimeTree :: The Timescale of Life|website=timetree.org|access-date=2016-05-03}}</ref>|none]]
[[File:Time-calibrated phylogenetic tree of C16orf95 orthologs.png|thumb|500x500px|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.<ref name=":2">{{Cite web|url=http://workbench.sdsc.edu|title=SDSC Biology Workbench|website=workbench.sdsc.edu|access-date=2016-05-08}}</ref>|none]]

== mRNA ==

=== Alternative splicing ===
There are three [[Alternative splicing|splice variants]] of C16orf95.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/nuccore/?term=c16orf95|title=c16orf95 - Nucleotide - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2016-05-05}}</ref> The longest [[Transcription (genetics)|transcript]] contains 1156 base pairs and 7 exons.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/nuccore/NM_001195124.1|title=Homo sapiens chromosome 16 open reading frame 95 (C16orf95), transcrip - Nucleotide - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2016-05-05}}</ref> Compared to variant 1, the second transcript variant lacks exons 4 and 5.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/nuccore/NM_001195125.1|title=Homo sapiens chromosome 16 open reading frame 95 (C16orf95), transcrip - Nucleotide - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2016-05-07}}</ref> This alternative splicing results in a [[Translational frameshift|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]].<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/nuccore/NM_001256917.1|title=Homo sapiens chromosome 16 open reading frame 95 (C16orf95), transcrip - Nucleotide - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2016-05-07}}</ref> The resulting peptide has unique N- and C-termini compared to variant 1.
{| class="wikitable"
!
! colspan="3" |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|thumb|245x245px|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.<ref>{{Cite web|url=http://unafold.rna.albany.edu/?q=mfold/rna-folding-form|title=RNA Folding Form |website= The RNA Institute, College of Arts and Sciences, State University of New York at Albany.|access-date=2016-05-09}}</ref><ref>{{Cite web|url=http://rbpdb.ccbr.utoronto.ca|title=RBPDB: The database of RNA-binding specificities|website=rbpdb.ccbr.utoronto.ca|access-date=2016-05-09}}</ref>]]

=== Secondary structure ===
The [[Three prime untranslated region|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.<ref>{{Cite web|url=https://www.uniprot.org/uniprot/O75525|title=KHDRBS3 - KH domain-containing, RNA-binding, signal transduction-associated protein 3 - Homo sapiens (Human) - KHDRBS3 gene & protein|website=www.uniprot.org|access-date=2016-05-09}}</ref>

== 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.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi?uglist=Hs.729380|title=EST Profile - Hs.729380|website=www.ncbi.nlm.nih.gov|access-date=2016-05-08}}</ref>

== Protein ==

=== Structure ===

==== Primary ====
The longest isoform of the C16orf95 protein has 239 amino acids.<ref name=":1">{{Cite web|url=https://www.ncbi.nlm.nih.gov/protein/NP_001182053.1|title=uncharacterized protein C16orf95 isoform 1 [Homo sapiens] - Protein - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2016-05-08}}</ref> It has a conserved domain of unknown function spanning residues 76 to 239.<ref name=":1" /> C16orf95 has a calculated molecular weight of 26.5 kDa, and a predicted isoelectric point of 9.8.<ref name=":2" /> Compared to other human proteins, C16orf95 has more [[cysteine]], [[arginine]], and [[glutamine]] residues.<ref name=":2" /> It has fewer [[Aspartic acid|aspartate]], [[Glutamic acid|glutamate]], and [[asparagine]].<ref name=":2" /> 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 helix|alpha-helices]] in its C-terminus.<ref name=":2" /> 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|none|thumb|880x880px|PELE compiles secondary structure predictions from multiple programs based on the amino acid sequence.<ref>{{Cite web|url=http://workbench.sdsc.edu|title=SDSC Biology Workbench|website=workbench.sdsc.edu|access-date=2016-05-09}}</ref> 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.<ref>{{Cite web|url=http://www.expasy.org|title=ExPASy: SIB Bioinformatics Resource Portal - Home|website=www.expasy.org|access-date=2016-05-09}}</ref> 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.
{| class="wikitable"
!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<ref>{{Cite web|url=http://csspalm.biocuckoo.org|title=CSS-Palm - Palmitoylation Site Prediction|website=csspalm.biocuckoo.org|access-date=2016-05-09}}</ref>
|-
|[[Phosphorylation]]
|S6, S9, '''S53''', '''T57''', '''S68''',
S91, '''S111''', T122, '''S166'''
|'''S30''', '''S76''', S89, S120,

T134, S141
|S15, '''S35''', '''T39''', '''S153'''
|NetPhos 2.0<ref>{{Cite web|url=http://www.cbs.dtu.dk/services/NetPhos/|title=NetPhos 2.0 Server|website=www.cbs.dtu.dk|access-date=2016-05-09}}</ref>
|-
|[[O-Linked β-N-acetylglucosamine|O-β-GlcNAc]]
|S4, S6, S9, T57, S111
|None
|None
|NetOGlyc 4.0<ref>{{Cite web|url=http://www.cbs.dtu.dk/services/NetOGlyc/|title=NetOGlyc 4.0 Server|website=www.cbs.dtu.dk|access-date=2016-05-09}}</ref>
|}

=== 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|thumb|425x425px|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.<ref>{{Cite journal|last=Griffiths|first=Anthony JF|last2=Miller|first2=Jeffrey H.|last3=Suzuki|first3=David T.|last4=Lewontin|first4=Richard C.|last5=Gelbart|first5=William M.|date=2000-01-01|title=Rate of molecular evolution|url=https://www.ncbi.nlm.nih.gov/books/NBK21946/|language=en}}</ref>|none]]

== Interacting proteins ==
There are no proteins known to interact with C16orf95.

== Clinical significance ==
Deletions of C16orf95 have been associated with [[hydronephrosis]], [[microcephaly]], [[distichia]]sis, [[vesicoureteral reflux]], and intellectual impairment.<ref>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}}</ref><ref>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}}</ref> 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 ==
{{reflist|30em}}

[[Category:Genes on human chromosome 16]]
[[Category:Human proteins]]