{{short description|Human protein-encoding gene on chromosome 7}} {{Orphan|date=December 2022}}
'''c7orf26 (Chromosome 7, Open Reading Frame 26)''' is a gene in humans that encodes a protein known as c7orf26 (uncharacterized protein c7orf26). Based on properties of c7orf26 and its conservation over a long period of time, its suggested function is targeted for the cytoplasm and it is predicted to play a role in regulating transcription. thumb|Predicted tertiary structure of c7orf26 with leucine zipper elements highlighted in red, and dileucine components highlighted in green.
== Gene ==
=== Background === Chromosome 7 is one of the 23 pairs of chromosomes in the human body, and spans about 159 million base pairs and represents about 5-5.5% of the total DNA in cells.<ref>{{Cite web|url=https://medlineplus.gov/genetics/chromosome/7/|title=Chromosome 7|last=Reference|first=Genetics Home|website=Genetics Home Reference|language=en|access-date=2019-04-29}}</ref> Changes to the structure of chromosome 7 can result in a number of genetic abnormalities, including Williams Syndrome which causes structural and cosmetic changes to the human body, ultimately resulting in a shorter lifespan.<ref>{{Cite web|url=https://medlineplus.gov/genetics/condition/williams-syndrome/|title=Williams syndrome|last=Reference|first=Genetics Home|website=Genetics Home Reference|language=en|access-date=2019-05-02}}</ref> There are hundreds of known open reading frames (ORF) along the domain of chromosome 7, however there is not much known about the 26th reading frame, which is of considerable interest.
Currently, two isoforms of c7orf26 are known in ''Homo Sapiens'' and are referred to as isoforms 1 and 2, respectively.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/protein/NP_076972.2|title=uncharacterized protein C7orf26 isoform 1 [Homo sapiens] – Protein – NCBI|website=www.ncbi.nlm.nih.gov|access-date=2019-05-02}}</ref>
=== Location === thumb|alt=|center|485x485px|Location of c7orf26 on chromosome 7 c7orf26 (accession: NM_024067 / NP_076972; alias: MGC-2178) is located on the long arm of chromosome 7 (7p22.1), starting at 6590021 and ending at 6608726. The c7orf26 gene spans 2178 base pairs and is orientated on the + strand. The coding region is made up of a protein sequence measuring 449 amino acids long. It is divided into 6 transcripts containing a total of 24 exons on the forward strand and has 5952 unique Single Nucleotide Polymorphisms (SNPs).<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/79034|title=C7orf26 chromosome 7 open reading frame 26 [Homo sapiens (human)] – Gene – NCBI|website=www.ncbi.nlm.nih.gov|access-date=2019-05-02}}</ref>
=== Gene neighborhood === Genes ZDHHC4, ZNF853 and ZNF316 neighbor c7orf26 on chromosome 7.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/79034|title=C7orf26 chromosome 7 open reading frame 26 [Homo sapiens (human)] – Gene – NCBI|website=www.ncbi.nlm.nih.gov|access-date=2019-05-02}}</ref> Gene ZDHHC4 is a zinc-finger protein involved with cytochrome-c oxidase activity and protein-cysteine S-palmitoyltransferase activity and has overlapping regions with c7orf26.<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=ZDHHC4|website=www.genecards.org|access-date=2019-05-02|title=ZDHHC4 Gene - GeneCards | ZDHC4 Protein | ZDHC4 Antibody}}</ref> Gene GRID2IP lies upstream by >2000 bp of c7orf26, and is heavily involved with in synaptogenesis and synaptic plasticity.<ref>{{Cite web|url=https://www.google.com/search?q=GRID2IP|title=GRID2IP – Google Search|website=www.google.com|access-date=2019-05-02}}</ref>
=== Expression === center|thumb|550x550px|Diagram depicting the expression of c7orf26 in tissues throughout the body. c7orf26 is highly expressed in lymphatic, reproductive, and nervous tissue. These include the brain (frontal and occipital cortex), thymus glands, salivary glands, endometrium, cervix, and prostate. It is intermediately expressed in the lungs.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS1085:4306|title=GDS1085 / 4306|website=www.ncbi.nlm.nih.gov|access-date=2019-05-02}}</ref>
== Homology ==
=== Paralogs === No paralogs of c7orf26 have been found in the human genome, however, six unique isoforms have been identified. They are c7orf26 isoform (X1, X2, X3, X4) and isoform 2 (two sub-isoforms identified).<ref>{{Cite web|url=https://www.uniprot.org/uniprot/Q96N11|title=C7orf26 – Uncharacterized protein C7orf26 – Homo sapiens (Human) – C7orf26 gene & protein|website=www.uniprot.org|access-date=2019-05-02}}</ref>
=== Orthologs === Below is a table of a variety of orthologs of the human c7orf26. The table include closely, intermediately and distantly related orthologs.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/homologene/11445|archive-url=https://web.archive.org/web/20150803051036/http://www.ncbi.nlm.nih.gov/homologene/11445|archive-date=August 3, 2015|title=HomoloGene – NCBI|website=www.ncbi.nlm.nih.gov|access-date=2019-05-02}}</ref> Orthologs of the human protein c7orf26 are listed above in descending order of the date of divergence. c7orf26 is highly conserved throughout all orthologs, this is demonstrated with a 65% identity in the least similar ortholog. c7orf26 has evolved slowly and evenly over time. {| class="wikitable" |+
!Genus Species !Common name !Taxonomy !Date of Divergency (MYA) !Sequence length (# amino acids) !Sequence identity (%) !Sequence similarity |- |Lingula anatina |Lingulata |Invertebrata |916 |406 |72% |66% |- |Cryptotermes secundus |West Indian Drywood Termite |Invertebrata |797 |403 |77% |70% |- |Saccoglossus kowalevskii |Acorn Worm |Invertebrata |794 |407 |86% |81% |- |Python bivittatus |Burmese Python |Reptilia |286 |329 |72% |66% |- |Colius striatus |Speckled Mousebird |Aves |273 |309 |87% |83% |- |Callorhinchus milii |Australian Ghostshark |Chondrichthyes |177 |441 |70% |57% |- |Cynoglossus semilaevis |Tonguefish |Osteichthyes |128 |307 |67% |52% |- |Amphiprion ocellaris |Clownfish |Osteichthyes |117 |481 |65% |50% |- |Elephantulus edwardii |Cape Elephant Shrew |Mammalia |105 |445 |91% |88% |- |Piliocolobus tephrosceles |Ugandan Red Colobus |Mammalia |102 |449 |88% |84% |- |Theropithecus gelada |Bleeding Heart Monkey |Primate |43.6 |617 |91% |88% |- |Saimiri boliviensis boliviensis |Black Capped Squirrel Monkey |Primate |43.2 |585 |92% |90% |- |Homo Sapiens |Human |Primate |0 |449 |100% |100% |}
=== Phylogeny === Below is a phylogenetic tree showing the evolutionary history of c7orf26 and its nearest orthologs. center|thumb|580x580px|Phylogenetic Tree of nearest orthologs of c7orf26
== Protein ==
=== General properties === The molecular weight of c7orf26 is 50 kilodaltons. The isoelectric point is 7.61. The protein sequence is uniquely rich for leucine at 15.8% of its composition, this may indicate a leucine-zipper. Further analysis from PSORT indicates that a leucine-zipper region is found at amino acid 318 and lasts until position 340 (22 amino acids long). There are no extremes with regards to acidity and alkalinity. c7orf26 has a positive charge cluster from amino acid 245 – 275 and does not have any negative, or mixed charge clusters.<ref>{{Cite web|url=https://www.ebi.ac.uk/Tools/seqstats/saps/|title=SAPS < Sequence Statistics < EMBL-EBI|website=www.ebi.ac.uk|access-date=2019-05-04}}</ref>
=== Composition === An even distribution of amino acids compose c7orf26. The percent composition of each amino acid is fairly consistent throughout the orthologs of the protein. The most distant ortholog displays the most variance in amino acid composition. There is a higher percent composition of tyrosine, histidine and leucine and a lower composition of valine and alanine.
===Post-translational modifications=== c7orf26 is highly phosphorylated post modified. There are 66 predicted phosphorylated sites according to the NetPhos predictor of phosphorylation sites.<ref>{{Cite web|url=http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=5CCDFBEF000006F11AE22BBA&wait=20|title=NetPhos 3.1 Server – prediction results|website=www.cbs.dtu.dk|access-date=2019-05-04}}</ref> There are 4 unique sumoylation sites according to SUMOplot/SUMOsp programs.<ref>{{Cite web|url=https://www.abgent.com/sumoplot|title=SUMOplot™ Analysis Program {{!}} Abgent|website=www.abgent.com|access-date=2019-05-04|archive-date=2005-01-03|archive-url=https://web.archive.org/web/20050103221931/http://www.abgent.com/sumoplot}}</ref> Sumoylation sites are involved in a number of cellular processes, including nuclear-cytosolic transport, transcriptional regulation and protein stability.
According DAS-TMFilter Server,<ref>{{Cite web|url=http://www.enzim.hu/DAS/DAS.html|title=DAS-TMfilter server|website=www.enzim.hu|access-date=2019-05-05}}</ref> c7orf26 has zero predicted transmembrane sites or transmembrane protein coding regions, therefore, it can be inferred with certainty that c7orf26 is ''not'' a transmembrane protein.
===Secondary structure=== Using the GOR ('''G'''arnier-'''O'''sguthorpe-'''R'''obson)<ref>{{Cite web|url=https://npsa-prabi.ibcp.fr/NPSA/npsa_gor4.html|title=NPS@: GOR4 secondary structure prediction|website=npsa-prabi.ibcp.fr|access-date=2019-05-05}}</ref> method, it can be inferred that c7orf26 has unique secondary structure composed of alpha helices, random coil regions and extended strands. Random coil regions are most found in c7orf26, as they constitute 53.23% of the protein, while alpha helices constitute 34.30% and extended strands 12.47%.
=== Subcellular localization === According to PSORT, c7orf26 is predicted to be localized in the cytoplasm with 70.6% confidence.<ref>{{Cite web|url=https://psort.hgc.jp/form2.html|title=PSORT II Prediction|website=psort.hgc.jp|access-date=2019-05-05}}</ref>
=== Interacting proteins === c7orf26 interacts uniquely with 11 different proteins, according to the Mentha interactome browser.<ref>{{Cite web|url=https://mentha.uniroma2.it/|title=mentha: the interactome browser|website=mentha.uniroma2.it|access-date=2019-05-05}}</ref> In particular, c7orf26 interacts with the entire family of 'INTS' (Integrator Complex Subunit 1–7). The Integrator Complex associates with the C-terminal domain of RNA polymerase II large subunit. It is involved in the transcription and processing of their transcripts. INTS mediates recruitment of cytoplasmic dynein to the nuclear envelope.
Outside of the INTS gene family, c7orf26 interacts with AK5,<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=AK5|website=www.genecards.org|access-date=2019-05-05|title=AK5 Gene - GeneCards | KAD5 Protein | KAD5 Antibody}}</ref> HDGF, and ASUN.<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=INTS13|website=www.genecards.org|access-date=2019-05-05|title=INTS13 Gene - GeneCards | INT13 Protein | INT13 Antibody}}</ref>
== Clinical significance == According to Guirato et al. (2018), there may be some evidence that regions on chromosome 7 may be directly linked to a nuclear estrogen receptor (ESR2) that modulates cancer cell proliferation and tumor growth.<ref>{{cite journal |last1=Giurato |first1=Giorgio |last2=Nassa |first2=Giovanni |last3=Salvati |first3=Annamaria |last4=Alexandrova |first4=Elena |last5=Rizzo |first5=Francesca |last6=Nyman |first6=Tuula A. |last7=Weisz |first7=Alessandro |last8=Tarallo |first8=Roberta |title=Quantitative mapping of RNA-mediated nuclear estrogen receptor β interactome in human breast cancer cells |journal=Scientific Data |date=6 March 2018 |volume=5 |page=180031 |doi=10.1038/sdata.2018.31 |pmc=5839158 |pmid=29509190 |bibcode=2018NatSD...580031G }}</ref> In another journal article by Fu et al. (2014), there is further indication that regions along chromosome 7, located between open reading frames 20-30, directly correlate to cellular functions of a hepatoma-derived growth factor (HDGF), another way of expressing normal function in tumorigenesis.<ref>{{cite journal |last1=Fu |first1=Wenxian |last2=Farache |first2=Julia |last3=Clardy |first3=Susan M |last4=Hattori |first4=Kimie |last5=Mander |first5=Palwinder |last6=Lee |first6=Kevin |last7=Rioja |first7=Inmaculada |last8=Weissleder |first8=Ralph |last9=Prinjha |first9=Rab K |last10=Benoist |first10=Christophe |last11=Mathis |first11=Diane |title=Epigenetic modulation of type-1 diabetes via a dual effect on pancreatic macrophages and β cells |journal=eLife |date=19 November 2014 |volume=3 |article-number=e04631 |doi=10.7554/eLife.04631 |pmc=4270084 |pmid=25407682 |doi-access=free }}</ref>
== References == <references />
== Further reading ==
# {{cite journal |last1=Boeing |first1=Stefan |last2=Williamson |first2=Laura |last3=Encheva |first3=Vesela |last4=Gori |first4=Ilaria |last5=Saunders |first5=Rebecca E. |last6=Instrell |first6=Rachael |last7=Aygün |first7=Ozan |last8=Rodriguez-Martinez |first8=Marta |last9=Weems |first9=Juston C. |last10=Kelly |first10=Gavin P. |last11=Conaway |first11=Joan W. |last12=Conaway |first12=Ronald C. |last13=Stewart |first13=Aengus |last14=Howell |first14=Michael |last15=Snijders |first15=Ambrosius P. |last16=Svejstrup |first16=Jesper Q. |title=Multiomic Analysis of the UV-Induced DNA Damage Response |journal=Cell Reports |date=May 2016 |volume=15 |issue=7 |pages=1597–1610 |doi=10.1016/j.celrep.2016.04.047 |pmc=4893159 |pmid=27184836 }} # {{cite journal |last1=Goto |first1=Yusuke |last2=Kojima |first2=Satoko |last3=Kurozumi |first3=Akira |last4=Kato |first4=Mayuko |last5=Okato |first5=Atsushi |last6=Matsushita |first6=Ryosuke |last7=Ichikawa |first7=Tomohiko |last8=Seki |first8=Naohiko |title=Regulation of E3 ubiquitin ligase-1 (WWP1) by microRNA-452 inhibits cancer cell migration and invasion in prostate cancer |journal=British Journal of Cancer |date=12 April 2016 |volume=114 |issue=10 |pages=1135–1144 |doi=10.1038/bjc.2016.95 |pmc=865980 |pmid=27070713 }} # {{cite journal |last1=Subaran |first1=Ryan L. |last2=Odgerel |first2=Zagaa |last3=Swaminathan |first3=Rajeswari |last4=Glatt |first4=Charles E. |last5=Weissman |first5=Myrna M. |title=Novel variants in ZNF34 and other brain-expressed transcription factors are shared among early-onset MDD relatives |journal=American Journal of Medical Genetics Part B: Neuropsychiatric Genetics |date=April 2016 |volume=171 |issue=3 |pages=333–341 |doi=10.1002/ajmg.b.32408 |pmid=26823146 |pmc=5832964 }} # {{cite journal |last1=Stelzl |first1=Ulrich |last2=Worm |first2=Uwe |last3=Lalowski |first3=Maciej |last4=Haenig |first4=Christian |last5=Brembeck |first5=Felix H. |last6=Goehler |first6=Heike |last7=Stroedicke |first7=Martin |last8=Zenkner |first8=Martina |last9=Schoenherr |first9=Anke |last10=Koeppen |first10=Susanne |last11=Timm |first11=Jan |last12=Mintzlaff |first12=Sascha |last13=Abraham |first13=Claudia |last14=Bock |first14=Nicole |last15=Kietzmann |first15=Silvia |last16=Goedde |first16=Astrid |last17=Toksöz |first17=Engin |last18=Droege |first18=Anja |last19=Krobitsch |first19=Sylvia |last20=Korn |first20=Bernhard |last21=Birchmeier |first21=Walter |last22=Lehrach |first22=Hans |last23=Wanker |first23=Erich E. |title=A Human Protein-Protein Interaction Network: A Resource for Annotating the Proteome |journal=Cell |date=September 2005 |volume=122 |issue=6 |pages=957–968 |doi=10.1016/j.cell.2005.08.029 |pmid=16169070 |hdl=11858/00-001M-0000-0010-8592-0 |s2cid=8235923 |hdl-access=free }}
Category:Chromosomes Category:Genes on human chromosome 7 Category:Proteins