Coiled-coil domain containing 74a

The gene locus is located on the long arm of chromosome 2 at 2q21.1, and spans 5991 base pairs.{{cite web|title=CCDC74A|url=https://www.ncbi.nlm.nih.gov/gene/90557|website=NCBI Gene|publisher=NCBI|access-date=5 February 2018}}

A common alternative alias is LOC90557.{{cite web|title=CCDC74A|url=https://www.ncbi.nlm.nih.gov/ieb/research/acembly/av.cgi?db=human&term=CCDC74A&submit=Go|website=AceView|publisher=NCBI|access-date=5 February 2018}}

The mRNA encoding the largest peptide product, isoform 6, contains 8 exons and 9 introns. It is 1842bps in length. Altogether, 11 protein isoforms have been characterized as a result of alternative splicing.{{cite web|title=NCBI Gene CCDC74A|url=https://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=full_report&list_uids=90557}}

The longest CCDC74A peptide product, isoform 6, is 420 amino acids in length.{{cite web|title=NCBI Gene CCDC74A|url=https://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=full_report&list_uids=90557}} This protein has a predicted molecular weight of 45.9kD and a predicted isoelectric point of 10.65.{{cite journal | vauthors = Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S | title = Methods and algorithms for statistical analysis of protein sequences | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 6 | pages = 2002–6 | date = March 1992 | pmid = 1549558 | doi = 10.1073/pnas.89.6.2002 | pmc = 48584 | bibcode = 1992PNAS...89.2002B | doi-access = free }} The entire length of the protein is evenly enriched in lysine and arginine residues. The protein contains 2 eukaryotic coiled-coil domains of unknown function, CCDC92 and CCDC74C.{{cite journal | vauthors = Finn RD, Attwood TK, Babbitt PC, Bateman A, Bork P, Bridge AJ, Chang HY, Dosztányi Z, El-Gebali S, Fraser M, Gough J, Haft D, Holliday GL, Huang H, Huang X, Letunic I, Lopez R, Lu S, Marchler-Bauer A, Mi H, Mistry J, Natale DA, Necci M, Nuka G, Orengo CA, Park Y, Pesseat S, Piovesan D, Potter SC, Rawlings ND, Redaschi N, Richardson L, Rivoire C, Sangrador-Vegas A, Sigrist C, Sillitoe I, Smithers B, Squizzato S, Sutton G, Thanki N, Thomas PD, Tosatto SC, Wu CH, Xenarios I, Yeh LS, Young SY, Mitchell AL | display-authors = 6 | title = InterPro in 2017-beyond protein family and domain annotations | journal = Nucleic Acids Research | volume = 45 | issue = D1 | pages = D190–D199 | date = January 2017 | pmid = 27899635 | doi = 10.1093/nar/gkw1107 | pmc = 5210578 }} Its predicted localization is to the nucleus, but the protein may shuttle between the nucleus and the cytoplasm due to the presence of both a nuclear localization signal and a nuclear export signal.{{cite journal | vauthors = Briesemeister S, Rahnenführer J, Kohlbacher O | title = Going from where to why--interpretable prediction of protein subcellular localization | journal = Bioinformatics | volume = 26 | issue = 9 | pages = 1232–8 | date = May 2010 | pmid = 20299325 | doi = 10.1093/bioinformatics/btq115 | pmc = 2859129 }}

File:Secondary Structure Prediction for CCDC74A.png

Predicted secondary structure for CCDC74A consists of 4 alpha helix regions, which are summarized in the table below and the diagram to the right.{{cite journal | vauthors = Madadkar-Sobhani A, Guallar V | title = PELE web server: atomistic study of biomolecular systems at your fingertips | journal = Nucleic Acids Research | volume = 41 | issue = Web Server issue | pages = W322-8 | date = July 2013 | pmid = 23729469 | doi = 10.1093/nar/gkt454 | pmc=3692087}}

File:CCDC74A Domains and PTMs.png

A threonine residue (T395) which is highly conserved across Animalia orthologs may serve as a phosphorylation site by PKG kinase.{{cite journal | vauthors = Blom N, Sicheritz-Pontén T, Gupta R, Gammeltoft S, Brunak S | title = Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence | journal = Proteomics | volume = 4 | issue = 6 | pages = 1633–49 | date = June 2004 | pmid = 15174133 | doi = 10.1002/pmic.200300771 | s2cid = 18810164 }} Additionally, SUMOylation, methylation, and acetylation sites are predicted within highly conserved regions and may play a part in regulation.{{cite journal | vauthors = Deng W, Wang C, Zhang Y, Xu Y, Zhang S, Liu Z, Xue Y | title = GPS-PAIL: prediction of lysine acetyltransferase-specific modification sites from protein sequences | journal = Scientific Reports | volume = 6 | pages = 39787 | date = December 2016 | pmid = 28004786 | doi = 10.1038/srep39787 | pmc=5177928| bibcode = 2016NatSR...639787D }}{{cite journal | vauthors = Drazic A, Myklebust LM, Ree R, Arnesen T | title = The world of protein acetylation | journal = Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics | volume = 1864 | issue = 10 | pages = 1372–401 | date = October 2016 | pmid = 27296530 | doi = 10.1016/j.bbapap.2016.06.007 | doi-access = free }} These predicted post-translational modifications and conserved domains are summarized in the diagram to the right.

In humans, CCDC74A has one important paralog, CCDC74B. Gene duplication is estimated to have occurred approximately 7 million years ago (MYA). As such, the only true ortholog of CCDC74A is found in Pan troglodytes, and is not found in Gorilla gorilla. However, distant orthologs prior to gene duplication are conserved in species that diverged from humans between 92-797 MYA. This includes species as distant as Cnidaria, but excludes Porifera or species outside of the kingdom Animalia.

CCDC74A localization, expression, and interactions suggest that the protein may play a role in the expression of genes related to developmental and differentiation pathways, particularly during spermatogenesis.

The protein has been found most highly expressed in the testes and trachea. It is also expressed at moderate levels in the lung, brain, prostate, spinal cord, bone marrow, ovary, thymus, and thyroid gland.{{cite web|title=NCBI GEO Profiles GDS 3113/119241|url=https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS3113:119241}}

Consistent with predicted post-translational methylation, CCDC74A has been shown to interact with the lysine demethylase KDM1A through a yeast 2-hybrid assay.{{cite journal | vauthors = Weimann M, Grossmann A, Woodsmith J, Özkan Z, Birth P, Meierhofer D, Benlasfer N, Valovka T, Timmermann B, Wanker EE, Sauer S, Stelzl U | title = A Y2H-seq approach defines the human protein methyltransferase interactome | journal = Nature Methods | volume = 10 | issue = 4 | pages = 339–42 | date = April 2013 | pmid = 23455924 | doi = 10.1038/nmeth.2397 | hdl = 11858/00-001M-0000-0019-0F4F-2 | s2cid = 30202708 | hdl-access = free }} Additionally, through a yeast 2-hybrid assay, CCDC74A has been shown to interact with the lymphocyte activation molecule associated protein SH2D1A.{{cite journal | vauthors = Grossmann A, Benlasfer N, Birth P, Hegele A, Wachsmuth F, Apelt L, Stelzl U | title = Phospho-tyrosine dependent protein-protein interaction network | journal = Molecular Systems Biology | volume = 11 | issue = 3 | pages = 794 | date = March 2015 | pmid = 25814554 | doi=10.15252/msb.20145968 | pmc=4380928}}

In a study on androgen-independent prostate cancer, knockout of CCDC74A in androgen-dependent prostate cancer inhibited cell proliferation.{{cite journal |last1=Chen |first1=Mengqian |last2=Akinola |first2=Oluwaseun |last3=Carkner |first3=Richard |last4=Mian |first4=Badar |last5=Buttyan |first5=Ralph | name-list-style = vanc |title= High-throughput screen for genes that selectively promote growth of androgen independent prostate cancer cells |journal=The Journal of Urology |date=April 2011 |volume=185 |issue=4 |pages=e164 |doi=10.1016/j.juro.2011.02.495}} Experiments in genital fibroblast cells have shown that CCDC74A expression significantly increases upon exposure to dihydrotestosterone.{{cite web|url=https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS1836:22724|title=NCBI GEO Profiles GDS1836/22724}}

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