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Coiled-coil domain containing 74a

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CCDC74A
Identifiers
AliasesCCDC74A, coiled-coil domain containing 74A
External IDsGeneCards: CCDC74A; OMA:CCDC74A - orthologs
Orthologs
SpeciesHumanMouse
Entrez

90557

n/a

Ensembl

ENSG00000163040

n/a

UniProt

Q96AQ1

n/a

RefSeq (mRNA)

n/a

RefSeq (protein)

n/a

Location (UCSC)Chr 2: 131.53 – 131.53 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Coiled-coil domain containing 74A is a protein that in humans is encoded by the CCDC74A gene.[3] The protein is most highly expressed in the testis and may play a role in developmental pathways.[4] The gene has undergone duplication in the primate lineage within the last 9 million years, and its only true ortholog is found in Pan troglodytes.

Gene

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The gene locus is located on the long arm of chromosome 2 at 2q21.1, and spans 5991 base pairs.[5] A common alternative alias is LOC90557.[6]

Transcript

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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.[7]

Protein

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The longest CCDC74A peptide product, isoform 6, is 420 amino acids in length.[8] This protein has a predicted molecular weight of 45.9kD and a predicted isoelectric point of 10.65.[9] 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.[10] 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.[11]

Secondary structure

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This diagram summarizes the locations of predicted alpha helix secondary structures for the human protein CCDC74A.

Predicted secondary structure for CCDC74A consists of 4 alpha helix regions, which are summarized in the table below and the diagram to the right.[12]

Structure Start End
Alpha Helix 1 47 81
Alpha Helix 2 315 330
Alpha Helix 3 371 378
Alpha Helix 4 384 417
This diagram summarizes the conserved domains, signal peptides, and predicted post-translational modifications for the human protein CCDC74A.

Post-translational modification

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A threonine residue (T395) which is highly conserved across Animalia orthologs may serve as a phosphorylation site by PKG kinase.[13] Additionally, SUMOylation, methylation, and acetylation sites are predicted within highly conserved regions and may play a part in regulation.[14][15] These predicted post-translational modifications and conserved domains are summarized in the diagram to the right.

Homology

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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.

Function

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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.

Expression

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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.[16]

Interactions

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Consistent with predicted post-translational methylation, CCDC74A has been shown to interact with the lysine demethylase KDM1A through a yeast 2-hybrid assay.[17] Additionally, through a yeast 2-hybrid assay, CCDC74A has been shown to interact with the lymphocyte activation molecule associated protein SH2D1A.[18]

Clinical significance

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In a study on androgen-independent prostate cancer, knockout of CCDC74A in androgen-dependent prostate cancer inhibited cell proliferation.[19] Experiments in genital fibroblast cells have shown that CCDC74A expression significantly increases upon exposure to dihydrotestosterone.[20]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000163040 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ "Entrez Gene: Coiled-coil domain containing 74A". Retrieved 2018-02-20.
  4. ^ "NCBI GEO Profiles GDS 3113/119241".
  5. ^ "CCDC74A". NCBI Gene. NCBI. Retrieved 5 February 2018.
  6. ^ "CCDC74A". AceView. NCBI. Retrieved 5 February 2018.
  7. ^ "NCBI Gene CCDC74A".
  8. ^ "NCBI Gene CCDC74A".
  9. ^ Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S (March 1992). "Methods and algorithms for statistical analysis of protein sequences". Proceedings of the National Academy of Sciences of the United States of America. 89 (6): 2002–6. Bibcode:1992PNAS...89.2002B. doi:10.1073/pnas.89.6.2002. PMC 48584. PMID 1549558.
  10. ^ Finn RD, Attwood TK, Babbitt PC, Bateman A, Bork P, Bridge AJ, et al. (January 2017). "InterPro in 2017-beyond protein family and domain annotations". Nucleic Acids Research. 45 (D1): D190–D199. doi:10.1093/nar/gkw1107. PMC 5210578. PMID 27899635.
  11. ^ Briesemeister S, Rahnenführer J, Kohlbacher O (May 2010). "Going from where to why--interpretable prediction of protein subcellular localization". Bioinformatics. 26 (9): 1232–8. doi:10.1093/bioinformatics/btq115. PMC 2859129. PMID 20299325.
  12. ^ Madadkar-Sobhani A, Guallar V (July 2013). "PELE web server: atomistic study of biomolecular systems at your fingertips". Nucleic Acids Research. 41 (Web Server issue): W322-8. doi:10.1093/nar/gkt454. PMC 3692087. PMID 23729469.
  13. ^ Blom N, Sicheritz-Pontén T, Gupta R, Gammeltoft S, Brunak S (June 2004). "Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence". Proteomics. 4 (6): 1633–49. doi:10.1002/pmic.200300771. PMID 15174133. S2CID 18810164.
  14. ^ Deng W, Wang C, Zhang Y, Xu Y, Zhang S, Liu Z, Xue Y (December 2016). "GPS-PAIL: prediction of lysine acetyltransferase-specific modification sites from protein sequences". Scientific Reports. 6: 39787. Bibcode:2016NatSR...639787D. doi:10.1038/srep39787. PMC 5177928. PMID 28004786.
  15. ^ Drazic A, Myklebust LM, Ree R, Arnesen T (October 2016). "The world of protein acetylation". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1864 (10): 1372–401. doi:10.1016/j.bbapap.2016.06.007. PMID 27296530.
  16. ^ "NCBI GEO Profiles GDS 3113/119241".
  17. ^ Weimann M, Grossmann A, Woodsmith J, Özkan Z, Birth P, Meierhofer D, Benlasfer N, Valovka T, Timmermann B, Wanker EE, Sauer S, Stelzl U (April 2013). "A Y2H-seq approach defines the human protein methyltransferase interactome". Nature Methods. 10 (4): 339–42. doi:10.1038/nmeth.2397. hdl:11858/00-001M-0000-0019-0F4F-2. PMID 23455924. S2CID 30202708.
  18. ^ Grossmann A, Benlasfer N, Birth P, Hegele A, Wachsmuth F, Apelt L, Stelzl U (March 2015). "Phospho-tyrosine dependent protein-protein interaction network". Molecular Systems Biology. 11 (3): 794. doi:10.15252/msb.20145968. PMC 4380928. PMID 25814554.
  19. ^ Chen M, Akinola O, Carkner R, Mian B, Buttyan R (April 2011). "High-throughput screen for genes that selectively promote growth of androgen independent prostate cancer cells". The Journal of Urology. 185 (4): e164. doi:10.1016/j.juro.2011.02.495.
  20. ^ "NCBI GEO Profiles GDS1836/22724".

Further reading

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