CCDC47

The CCDC47 gene itself is located on the minus strand of human chromosome 17 and contains 13 exon splice sites and 14 distinct introns. After removal of exons, the gene is 3445 base pairs in length. No evidence for micro RNA or pseudogenes has been found. The gene does not have various isoforms, only transcript variant 1X exists.

File:Chromosome 17 Diagram.jpg

The protein encoded by CCDC47 is 483 amino acids in length and contains both a signal peptide and transmembrane domain. It is rich in negatively charged amino acids such as aspartic acid and glutamic acid giving it an acidic isoelectric point of 4.56.{{cite web|title=SAPS Anaysis|url=http://workbench.sdsc.edu|publisher=SDSC Workbench|accessdate=14 April 2014}} The protein is also rich in methionine. In total, it weighs 55.9 kDal which is conserved through various orthologs. CCDC47 also contains the SEEEED superfamily and domain of unknown function 1682 (DUF1682). The SEEEED superfamily is a short, low complexity region which is composed mainly of serine. The family routinely lies on the clathrin adaptor complex 3 beta-1 subunit proteins.{{cite web|title=NCBI BLAST|url=http://blast.ncbi.nlm.hin.gov/Blast|publisher=National Center for Biotechnology Information|accessdate=7 March 2014}}{{Dead link|date=November 2018 |bot=InternetArchiveBot |fix-attempted=yes }} The exact function of DUF 1682 is unclear but one member of the family has been described as an adipocyte-specific protein.{{cite web|title=Genecards|url=https://www.genecards.org|publisher=The Human Gene Compendium|accessdate=7 March 2014}}

File:C Terminus CCDC47.png

There are two predicted disulfide bonds in the structure of CCDC47 at cysteines 209 to 214 and cysteines 215 to 283, respectively.{{cite web|title=Sulfinator|url=http://web.expasy.org/sulfinator|publisher=ExPASy|accessdate=7 April 2014}} The C-terminal portion of the protein is highly charged and its secondary structure is predicted to be that of an alpha helix region.{{cite web|title=PHYRE 2 Protein Recognition Software|url=http://www.sbg.bio.ic.ac.uk/phyre2/html/page.cgi?id-index|accessdate=14 April 2014}} This region also contains coiled coil domains which are structural motifs in which 2-7 alpha helices are coiled together and are subsequently involved in biological expression. These domains typically follow the pattern HxxHCxC where H is a hydrophobic amino acid, C is a charged amino acid and x is any amino acid.{{cite journal |vauthors = Mason JM, Arndt KM |title = Coiled coil domains: stability, specificity, and biological implications |journal = ChemBioChem |volume = 5 |issue = 2 |pages = 170–6 |year = 2004 |pmid = 14760737 |doi = 10.1002/cbic.200300781 |s2cid = 39252601 }} Many amino acid sequences following this pattern are seen in the C-terminal region of CCDC47 where the highest conservation through orthologs is represented.

File:CCDC47 Protein.jpg

CCDC47 is regulated by the promoter GXP43413.{{cite web|title=El Dorado|url=http://www.genomatix.de/cgi-bin//eldorado|publisher=Genomatix|accessdate=3 April 2014}}{{Dead link|date=November 2018 |bot=InternetArchiveBot |fix-attempted=yes }} The promoter is 819 base pairs in length and is highly conserved in mammals. Conserved binding sites in mammals which are located on this promoter include nuclear respiratory factor 1 (NRF1), cAMP response element-binding protein (CREB), PAR bZIP family and Sp4 transcription factor. NRF1 encodes a protein which homodimerizes and activates expression of key metabolic genes. CREB binds to cAMP response elements thereby increasing or decreasing the transcription of downstream genes{{cite web|title=Protein One|url=http://www.proteinone.com/products/proteins/transcription-factors/|publisher=Transcription Factors|accessdate=29 March 2014|archive-url=https://web.archive.org/web/20140605033608/http://www.proteinone.com/products/proteins/transcription-factors|archive-date=2014-06-05|url-status=dead}} while PAR bZIP family is involved in the regulation of circadian rhythms.{{cite web|title=Protein Spotlight, The PAR b ZIP Family|date=20 August 2004 |url=http://web.expasy.org/spotlight/snapshots/002/|accessdate=March 28, 2014}}

In regards to the mRNA, translation begins at base pair 337 and ends at 1728. There is a strong stem loop located in the 5' UTR from bases 289-318 which likely is involved in regulation of the mRNA due to its close proximity to the start codon.{{cite web|title=The mfold Web Server|url=http://mfold.rna.albany.edu/?q-mfold|accessdate=3 April 2014}}

The final protein is thought to be translated from the endoplasmic reticulum into the cytoplasm of the cell. The protein is anchored in the membrane of the ER at the transmembrane domain located from amino acid 137 to 165.{{cite web|title=DAS-TM Filter Server|url=http://mendel.imp.ac.at/sat/DAS/DAS.html|publisher=ExPASy|accessdate=17 April 2014|archive-date=5 February 2018|archive-url=https://web.archive.org/web/20180205151802/http://mendel.imp.ac.at/sat/DAS/DAS.html|url-status=dead}} The portion of the protein which extends into the cytosol is predicted to be highly phosphorylated as the protein's phosphorylation sites are conserved into the bony fish orthologs.{{cite web|title=NetPhos Server 2.0|url=http://www.cbs.dtu.dk/services/NetPhos|publisher=ExPASy|accessdate=20 April 2014}} Research has shown that CCDC47 is expressed in the response to an ER overload making this close proximity to the ER important.{{cite journal|last1=Viguerie|first1=Nathalie|last2=Picard|first2=Flora|last3=Hul|first3=Gabby|last4=Roussel|first4=Balbine|last5=Barbe|first5=Pierre|last6=Iacovoni|first6=Jason S.|last7=Valle|first7=Carine|last8=Langin|first8=Dominique|last9=Saris|first9=Wim H. M.|title=Multiple effects of a short-term dexamethasone treatment in human skeletal muscle and adipose tissue|journal=Physiological Genomics|volume=44|issue=2|year=2012|pages=141–151|issn=1094-8341|doi=10.1152/physiolgenomics.00032.2011|pmid=22108209}}

In addition to the high levels of phosphorylation seen in CCDC47, three sulfation sites are predicted and conserved in mammals, reptiles and birds but not in fish, amphibians or invertebrates.{{cite web|title=Sulfinator|url=http://web.expasy.org/sulfinator|publisher=ExPASy|accessdate=20 April 2014}} Five potential sumoylation sites are also seen and conserved back to the bony fish.{{cite web|title=SumoPLOT|url=http://www.abgent.com/sumplot|publisher=ExPASy|accessdate=20 April 2014}}{{Dead link|date=November 2018 |bot=InternetArchiveBot |fix-attempted=yes }} There is no glycosylation of the protein as it is not predicted to extend into the extracellular space.

Microarray tissue expression patterns from GEO were analyzed and showed that CCDC47 appears to be an ubiquitously expressed at moderate levels in many different human tissues.{{cite web|title=GEO Profiles|url=https://www.ncbi.nlm.nih.gov/geo|publisher=NCBI|accessdate=20 March 2014}} Although the protein is ubiquitously expressed, the highest levels of expression are seen in neuronal tissues such as the superior cervical ganglion, brain amygdala and ciliary ganglion. Elevated expression is also seen in the thyroid and CD34⁺ cells.

CCDC47 has no known paralogs through text based queries, BLAST and BLAT. The gene has many orthologs extending back to invertebrates such as C. elegans and is highly conserved in mammals with a percent identity greater than 95%. CCDC47 has been sequenced in a wide taxonomy of organisms including mammals, birds, reptiles, amphibians, bony fish and invertebrates. Percent identity of human CCDC47 to a specific ortholog declines with increasing years of divergence, as expected. Homologous genes of CCDC47 are also present in mosquitos, mushrooms, arabidopsis and Asian rice. These homologs contain the same DUF1682 which is found in CCDC47.

{{Reflist|33em}}

• {{UCSC gene info|CCDC47}}

Category:Genes on human chromosome 17

Category:Human proteins