View source for CFAP206

{{Short description|Protein-coding gene in humans}}
{{Infobox_gene}}
'''Cilia And Flagella Associated Protein 206''' (CFAP206) is a [[gene]] that in humans encodes a [[protein]] “DUF3508”. This protein has a function that is not currently very well understood.<ref name="NCBI(National Center for Biotechnology Information)">{{cite web | title = Entrez Gene: C6orf165| date=17 July 2006 | url = https://www.ncbi.nlm.nih.gov/nuccore/34191365?report=genbank| accessdate = 2014-03-01}}</ref><ref name="Nature genetics">{{cite journal |vauthors=Mungall AJ, Palmer SA, Sims SK, Edwards CA | title = The DNA sequence and analysis of human chromosome 6.| journal = Nature | volume = 425 | issue = 6960 | pages = 40–45 |date=Oct 2003| pmid=14574404 | doi=10.1038/nature02055| bibcode = 2003Natur.425..805M|display-authors=etal| doi-access=free }}</ref> Other known aliases are “dJ382I10.1, UPF0704 Protein C6orf165.”<ref name="genecards">{{cite web | title = GeneCards: C6orf165 Gene| url = https://www.genecards.org/cgi-bin/carddisp.pl?gene=C6orf165| accessdate = 2014-02-28}}</ref> In humans, the gene coding sequence is 56,501 base pairs long, with an mRNA of 2,215 base pairs, and a protein sequence of 622 amino acids. The C6orf165 gene is conserved in chimpanzee, rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, mosquito, frog, and more<ref name="gene summary">{{cite web |title = NCBI gene: C6orf165 Gene|url=https://www.ncbi.nlm.nih.gov/gene?linkname=protein_gene&from_uid=72534780|accessdate=April 27, 2014}}</ref>
C6orf165 is rarely expressed in humans, with relatively high expression in brain, lungs (trachea) and testis.<ref name="EST File">{{cite web |title = NCBI EST: C6orf165 Gene|url=https://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi?uglist=Hs.82921|accessdate=April 27, 2014}}</ref> The molecular weight of UPF0704 is 71,193 Da <ref name="PhosphoSitePlus">{{cite web|title=PhosphoSitePlus|url=http://www.phosphosite.org/proteinAction.do?id=21671&showAllSites=true|accessdate=2014-05-08}}</ref> and the PI is 6.38<ref name="PhosphoSitePlus"/>
== Gene Locus ==
The CFAP206 gene is located at Chromosome 6 from 88119558 to 88173965(6q15).<ref name="NCBI Gene">{{cite web | title = NCBI: C6orf165 Gene| url = https://www.ncbi.nlm.nih.gov/gene/154313| accessdate = 2014-03-09}}</ref> It contains 12 [[exons]].<ref name="UCSC">{{cite web | title = UCSC: C6orf165| url =http://genome.ucsc.edu/cgi-bin/hgc?hgsid=365752405&g=htcUserAli&i=..%2Ftrash%2FhgSs%2FhgSs_genome_496d_cd8300.pslx+..%2Ftrash%2FhgSs%2FhgSs_genome_496d_cd8300.fa+NP_001026913.1&c=chr6&l=88119557&r=88173965&o=88119557&aliTable=user&table=hgUserPsl| accessdate = 2014-02-28}}</ref>
The genomic DNA is 54,407 [[base pair]]s long, while the longest mRNA that it produces is 2,215 bp long.<ref name="UCSC"/>
== Homology and Evolution ==
=== Orthologs ===
This protein is well conserved through a series of distantly related organisms including mammals, birds, amphibians, tunicates, bony fish, lancelets, insects, and sea urchins. The list of organisms in which orthologs have been found is shown below.
{| class="wikitable" style="width: 60%;"
! scientific name
! common name
! divergence from human lineage (MYA)
! accession number
! sequence length (aa)
! sequence identity to human protein
|-
| ''Homo sapiens''||[[Human]]||0||NP_001026913.1|622||100%||
|-
| ''Macaca mulatta''||[[Rhesus macaque]]||92.3||XP_001089007.2||658||98%||
|-
| ''Rattus norvegicus''||[[Brown rat]]||92.3||NP_001073169.1||622||81%||
|-
| ''Felis catus''||[[Cat]]||94.2||XP_003986405.2||629||85%||
|-
| ''Chrysochloris asiatica''||[[Cape golden mole]]||98.7||XP_006870694.1||622||85%||
|-
| ''Elephantulus edwardii''||[[Cape elephant shrew]]||98.7||XP_006902101.1||608||79%||
|-
| ''[[Anolis carolinensis]]''||Arboreal lizard||296||XP_003215583.1||621||70%||
|-
| ''Gallus gallus''||[[Chicken]]||296||XP_004940450.1||621||58%||
|-
| ''Xenopus (Silurana) tropicalis''||[[Western clawed frog]]||371.2||XP_002938343.1||635||65%||
|-
| ''Danio rerio''||[[Zebrafish]]||400.1||NP_991180||624||55%||
|-
| ''[[Branchiostoma floridae]]''||Lancelet||713.2||XP_002603798.1||626||63%||
|-
| ''[[Oikopleura dioica]]''||''Oikopleura dioica''||722.5||CBY12373.1||631||44%||
|-
| ''[[Ciona intestinalis]]''||Sea squirt||722.5||XP_002128218.1||624||60%||
|-
| ''[[Helobdella]]''||Leech||725.5||ESO10267.1||620||37%||
|-
| ''[[Aedes aegypti]]''||Mosquito||725.5||XP_001659130.1|630||30%||
|-
| ''[[Crassostrea gigas]]''||Japanese oyster||782.7||EKC36332.1||624||61%||
|-
| ''[[Anopheles gambiae]]''||Str. PEST||782.7||XP_001689194.1|642||28%||
|-
| ''[[Albugo laibachii]]''||Oomycetes||1317.5||CCA20014.1|642||26.8%||
|}
=== Paralogs ===
C6orf165 has no [[paralog]].
=== Phylogeny ===
The rooted phylogeny tree is shown below<ref name="ensembel.org">{{cite web |url= http://useast.ensembl.org/Homo_sapiens/Gene/Compara_Tree?collapse=none;db=core;g=ENSG00000272514;r=6:88117731-88145775;t=ENST00000296885|date= |work= SDSC Biology Workbench|publisher= |accessdate=27 April 2014|title=Gene: C6ORF165 ENSG00000272514}}</ref>
<!-- Deleted image removed: [[File:EnsEMBL Web Component Gene ComparaTree-Homo sapiens-Gene-Compara Tree-75-ENSG00000272514-10.png|thumb|none|800px|Gene tree for c6orf165 gene]] -->
== Protein ==
The protein that is produced by the C6orf165 gene is termed DUF3508 and is 622 [[amino acids]] long.<ref name = "NCBI Protein">{{cite web | title =NCBI Protein: protein DUF3508 C6orf165| url = https://www.ncbi.nlm.nih.gov/protein/72534780?report=genpept| accessdate = 2013-03-09}}</ref> The protein has a predicated molecular weight of 71.20 kDa and isoelectric point of 6.38.<ref name="Compute pI/Mw">{{cite web| title = Compute pI/Mw| url = http://web.expasy.org/cgi-bin/compute_pi/pi_tool| accessdate = 2014-03-09}}{{dead link|date=August 2017 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>
=== Domains ===
The C6orf165 gene protein product contains a well conserved domain  DUF3508<ref name="NCBI Gene"/>  This presumed domain is functionally uncharacterized. This domain is found in eukaryotes. This domain is about 280 amino acids in length.<ref name="NCBI conserved domain">{{cite web | title = C6orf165 chromosome 6 open reading frame 165 [ Homo sapiens (human) ] | url = https://www.ncbi.nlm.nih.gov/gene/154313| accessdate = 2014-03-09}}</ref>
=== Motifs ===
This domain has two conserved sequence motifs: GFC and GLL.<ref name="NCBI conserved domain 2">{{cite web | title = Conserved domains on [ Homo sapiens (human) ]| url = https://www.ncbi.nlm.nih.gov/gene/154313| accessdate = 2014-03-09}}</ref>
=== Post-translational modifications ===
The only predicted [[post-translational modification]] this protein undergo is phosphorylation after trying all tools under post translational modification category on expasy.org.<ref name="Expasy">{{cite web| title = post-translational_modification| url = http://www.expasy.org/proteomics/post-translational_modification3| accessdate = 2014-05-06}}{{Dead link|date=June 2019 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Three phosphorylation site is predicted with score over 0.8.
Phosphorylation on Ser 176, Thr 232 and Ser 310 are notified on the conceptual translation.
<!-- Commented out because image was deleted: [[File:Phos.jpg|thumb|none|631px|Phosphorylation sites in UPF0704 predicted by NetPhosK 1.0.<ref name = "netPhosK">{{cite journal |author=Blom N, Gammeltoft S, Sicheritz-Ponten T, Brunak S |title=Prediction of post-translational glycosylation and phosphorylation of proteins from amino acid sequence|journal=Proteomics |volume=4 |issue=6 |pages=1633–49 |url=http://www.cbs.dtu.dk/services/NetPhosK/|pmid=15174133|year=2004|last2=Sicheritz-Pontén|last3=Gupta|last4=Gammeltoft|last5=Brunak|doi=10.1002/pmic.200300771}}</ref>]] -->
=== Secondary structure ===
The consensus of the prediction software PELE<ref name="PELE">{{cite web|url=http://seqtool.sdsc.edu/CGI/BW.cgi#! |title=PELE |date= |work=SDSC Biology Workbench |publisher= |accessdate=27 April 2014 }}{{dead link|date=November 2016 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> predicts that protein UPF0704 is dominated by alpha helices with interspersed regions of random coil.
<!-- Commented out because image was deleted: [[File:Concensus PELE.jpg|thumb|none|317px|Secondary protein structure predicted by PELE tool<ref name="PELE">{{cite web |url= http://seqtool.sdsc.edu/CGI/BW.cgi#!|title= PELE|date= |work= SDSC Biology Workbench|publisher= |accessdate=27 April 2014}}</ref>]] --> PSORT II analysis<ref name="PSORT II server">{{cite web| title = PSORT II: Results of Subprograms| url = http://psort.hgc.jp/cgi-bin/runpsort.pl| accessdate = 2014-05-08}}{{dead link|date=August 2017 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> predicts that there is a coiled_coil_region from 88 to 117 with sequence MNYTNRVEFLEEHHRVLESRLGSVTREITD.
=== Location ===
PSORT II analysis<ref name="PSORT II server"/> trained on yeast data predicts that the subcellular location of this protein is most likely in the cytoplasm (56%). Less likely possibilities are in the mitochondria (21%) or in the nucleus (17%) or in vacuoles (4%).
== Gene expression ==
=== Gene expression data ===
From the EST file of Unigene, the gene expression in human is not strong, the gene EST/EST in pool is really low, even low than 0.01%. These little expression is in brain, connective tissue, kidney, lungs, parathyroid, pharynx, placenta, testis and trachea.  In mouse, the gene expression of C6orf165 is even lower, the gene is only expressed in two body parts, ovary and testis. In chicken, the weak expressions are in two body part, brain and testis. In zebra fish, gene expression is still low, the very weak expressions are in eye, kidney and reproductive system. In sea squirt, the expressions are in gonad, heart and neural complex.
In summary, c6orf165 is expressed conservatively in testis across the species and partially conservatively in brain or neural complex.<ref name="Unigene">{{cite web |url= https://www.ncbi.nlm.nih.gov/unigene|title= Unigene|date= |work= National Center for Biotechnology Information|publisher= |accessdate=April 27, 2014}}</ref>
=== Promoter ===
The promoter region for human c6orf165 is identified by ElDorado (at Genomatix).<ref name="Genomatix">{{cite web|url= http://www.genomatix.de/|title= Eldorado|accessdate= April 27, 2014|archive-date= December 2, 2021|archive-url= https://web.archive.org/web/20211202010908/https://www.genomatix.de/|url-status= dead}}</ref>
<!-- Commented out because image was deleted: [[File:Promoter C6orf165.jpg|thumb|none|600px|The promoter of the human C6orf165 gene.The labeled regions are transcription factor with  best matrix scores which express in testis at the same time and also TATA box binding factors, RNA polymerase II transcription factor II B and CCAAT/enhancer binding protein beta]] -->
In addition to this, the start codon is at the second exon of the mRNA and this indicate the first exon is spliced during the modification.
=== Transcript variants ===
In humans, the c6orf165 gene produces 4 different transcripts, 2 of which form a protein product (one undergoes nonsense mediated decay ang the other is  retained intron). The main transcript in humans is transcript ID  ENST00000369562, or C6ORF165-001; it has 13 exons and 12 coding exons; the translation length is 622 residues<ref name="Ensembl">{{cite web |url=http://useast.ensembl.org/Homo_sapiens/Transcript/Summary?db=core;g=ENSG00000272514;r=6:88117731-88145775;t=ENST00000369562|title= Ensemble: gene c6orf165|date= |work= Ensembl|publisher= |accessdate=April 27, 2014}}</ref>
<!-- Commented out because image was deleted: [[File:EnsEMBL Web Component Transcript TranscriptImage-Homo sapiens-Transcript-Summary-75-ENST00000369562-5.png|thumb|none|631px|Main transcript of C6orf165 gene,12 coding exons,622 amino acids<ref name="Ensembl 2">{{cite web |url=http://useast.ensembl.org/Homo_sapiens/Transcript/Summary?db=core;g=ENSG00000272514;r=6:88117731-88145775;t=ENST00000369562|title= Ensemble: gene c6orf165|date= |work= Ensembl|publisher= |accessdate=April 27, 2014}}</ref>]] -->
The second protein coding transcript in human is transcript ID ENST00000480123 or C6ORF165-002;it contains 7 exons and only 6 exons are protein coding; the translation length is 252 residues<ref name="Ensembl 3">{{cite web |url=http://useast.ensembl.org/Homo_sapiens/Transcript/Summary?db=core;g=ENSG00000272514;r=6:88117731-88145775;t=ENST00000480123|title= Ensemble: gene c6orf165|date= |work= Ensembl|publisher= |accessdate=April 27, 2014}}</ref>
<!-- Deleted image removed: [[File:EnsEMBL Web Component Transcript TranscriptImage-Homo sapiens-Transcript-Summary-75-ENST00000480123-5.png|thumb|none|631px|second protein coding transcript of C6orf165 gene,6 coding exons,252 amino acids<ref name="Ensembl 2" /> -->
== Interactions ==
Two-hybrid experiments revealed interacting proteins such as Myogenic repressor I-mf.<ref name="Rual, Jean-François 2005">Rual, Jean-François, et al. "Towards a proteome-scale map of the human protein–protein interaction network." Nature 437.7062 (2005): 1173-1178.</ref> This repressor is highly expressed in sclerotome. It inhibits the transactivation activity of the MyoD family and represses myogenesis.<ref>Chen, C-M. Amy, et al. "I-mf, a novel myogenic repressor, interacts with members of the MyoD family." Cell 86.5 (1996): 731-741.</ref>
Protein complex co-immunoprecipitation ([[Co-IP]]) experiments revealed interacting protein [[NRF1]] nuclear respiratory factor 1<ref>Satoh, Jun-ichi, Natsuki Kawana, and Yoji Yamamoto. "pathway Analysis of chIp-seq-Based nRF1 Target Genes suggests a Logical Hypothesis of their Involvement in the pathogenesis of neurodegenerative Diseases." Gene regulation and systems biology 7 (2013): 139.</ref> This gene encodes a protein that [[homodimerization|homodimerizes]] and functions as a [[transcription factor]] which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication.
Two-hybrid experiments revealed interacting protein RNF138 (ring finger protein 138),<ref name="Rual, Jean-François 2005"/> an E3 ubiquitin protein ligase.
Affinity Capture-Western reveal an interaction protein called TP73 tumor protein [[p73]],<ref>Lunardi, Andrea, et al. "A genome-scale protein interaction profile of Drosophila p53 uncovers additional nodes of the human p53 network." Proceedings of the National Academy of Sciences 107.14 (2010): 6322-6327.</ref> which is a protein related to the [[p53]] tumor protein.
== Clinical significance ==
C6orf165 has no currently known disease associations or mutations.
== References ==
{{reflist|35em}}
[[Category:Uncharacterized proteins]]