C16orf71

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Uncharacterized protein Chromosome 16 Open Reading Frame 71 is a protein in humans, encoded by the C16orf71 gene.[1] The gene is expressed in epithelial tissue of the respiratory system, adipose tissue, and the testes.[2] Predicted associated biological processes of the gene include regulation of the cell cycle, cell proliferation, apoptosis, and cell differentiation in those tissue types.[3] 1357 bp of the gene are antisense to spliced genes ZNF500 and ANKS3, indicating possibility of regulated alternate expression.[4]

Gene

Locus

The gene is located on the short arm of chromosome 16 at 16p13.1.[5] Its genomic sequence begins on the plus strand at 4,734,242 bp and ends at 4,749,396 bp.[1]

File:C16orf71 Gene Neighborhood.gif
A diagram of C16orf71 and nearby genes on human chromosome 16.[6]

mRNA

Alternative Splicing

Three different protein encoding transcript variants, or isoforms, have been identified for C16orf7.[7] One non-protein coding transcript variant was identified for the gene.[8]

Name Length (bp) Protein (aa) Mass (kDa) Biotype
Uncharacterized protein C16orf71 (primary assembly)[7] 2716 520 55.7 Protein coding
Uncharacterized protein C16orf71 isoform X2[9] 2324 136 14.6 Protein coding
Uncharacterized protein C16orf71 isoform X3[10] 2435 156 16.8 Protein coding
Uncharacterized protein C16orf71 isoform X1[11] 2562 537 57.5 Protein coding
Uncharacterized protein C16orf71 Transcript-003[8] 3705 No protein Retained intron

Protein

General properties

The primary encoded protein consists of 520 amino acid residues, 11 total exons, and is 15.14 kb long, with a molecular weight of approximately 55.68 kDa.[1] The predicted isoelectric point was reported to be 4.81, indicating it is relatively unstable.[13] The gene was reported to be well expressed, at 1.1 times the average gene level.[4]

Composition

Alanine was the most abundant amino acid, contributing to 11.54% of the molecular weight of the protein.[13] Serine was the second most abundant, contributing 10.19% to the overall molecular weight.[13] The average Alanine frequency in vertebrate proteins is approximately 7.4% and the average Serine frequency is approximately 8.1%.[14]

Domains

C16orf71 has one identified domain of unknown function, DUF4701, that is conserved in all mammals and some species of reptiles and birds.[1] DUF4701 spans from amino acid residue 21 to 520 in the protein.[1]

Post-translational modifications

C16orf71 is predicted to undergo multiple post-translational modifications such as phosphorylation, N-glycosylation, and amidation.

Protein Interactions

Experimentally proven interactions

Experimentation with C16orf71 has revealed interactions with four other proteins, ARHGAP1, ZNFX1, PLVAP, and MBTPS1.[15] ARHGAP1, ZNFX1, and MBTPS1 are associated with regulation in signaling and metabolism while PLVAP is associated with the formation of small lipid rafts in the plasma membrane of vertebrate endothelial and adipose cells.[3]

Predicted interactions

The majority of the predicted interactions involved with the protein related to regulation of mitotic processes, cellular differentiation, proliferation, metabolism, and signaling.[3] Additional related processes included the formation and differentiation of B cells, T cells, endothelial cells, endoderm, and endocrine glands.[3]

Interactor[3] Function[3]
CREB1 (cAMP responsive element binding protein 1) Induction of growth, differentiation, migration, adhesion, and cell survival in epidermal cells

Mediation of growth, differentiation, survival, and migration in early developmental stages

Mediation of metabolic functions, tissue repair, and regeneration in mature adult tissue

TYK2 (tyrosine kinase 2) Cellular differentiation, migration, and proliferation in immune cells
TNIP2 (TNPAIP3 interacting protein 2) Negative regulation of apoptosis for endothelial cells
OBSL1 (obscurin-like 1) Mitotic regulation, cytoskeleton and microtubule organization and assembly
DUSP3 (dual specificity phosphatase 3) Negative regulation of multiple enzymatic cascades and signaling pathways

Positive regulation of the mitotic cell cycle

FGFRL1 (fibroblast growth factor receptor-like 1) Fibroblast growth activity
GNPAT (glyceronephosphate O-acyltransferase) Involved in multiple metabolic and biosynthesis processes for cellular lipids, ether lipids,

glycerophospholipids, phosphatidic acid, and phospholipids

AURKA (aurora kinase A) Regulation for G2/M transition, nuclear division, mitotic spindle organization, the centrosome

cycle, cytokinesis, and spindle stabilization

NAMPT (nicotinamide phosphoribosyltransferase) Adipose tissue development, regulation of nicotinamide metabolism, signal transduction,

cell-cell signaling, and vitamin metabolism.

Subcellular localization

C16orf71 was observed in nuclear speckles of the nucleus through experimental protocols involving fluorescent in situ hybridization with antibodies.[2] Nuclear speckles, also known as interchromatin granule clusters, are enriched in pre-mRNA splicing factors.[16] These highly dynamic structures are located in interchromatin regions of the nucleoplasm in mammalian cells and have been observed to cycle throughout various nuclear regions and active transcription sites.[16]

Structure

File:Secondary Structure Prediction of C16orf71.png
Predicted secondary structure for C16orf71 by I-TASSER.

The secondary structure of C16orf71 is predicted to consist primarily of coils, with small regions of alpha helices and two segments of beta sheets throughout the span of the protein.[13][17]

Protein sequences of the gene's mammalian orthologs were analyzed to reveal similar results, while distant reptilian and avian ortholog sequences predicted more regions of beta sheets.[18][19]

File:C16orf71 Predicted Secondary Structure.jpg
Plot indicating the predicted secondary structure of the protein generated by I-TASSER.[17]

Expression

File:Expression of C16orf71 in obese omental adipose tissue.png
Expression levels of C16orf71 from microarray analysis in obese omental adipose tissue.[20]

Tissue expression pattern

Human expression for the gene has been observed primarily in respiratory epithelial tissue, specifically the trachea, larynx, nasopharynx, and bronchus.[2] C16orf71 is also moderately expressed in adipose tissue and testes.[2]

DNA microarray experimental data

DNA microarray analysis from various experiments provided information on the expression levels of C16orf71 in unique, varying conditions.

The gene appears to have higher levels of expression in the omental adipose tissue of obese subjects compared to non-obese subjects.[20]

File:Expression level of C16orf71 in deletions of HIFs.png
Expression levels of C16orf71 in the occurrence of HIF-1 alpha/HIF-2 alpha depletion.[21]
File:Expression Levels of C16orf71 in Teratozoospermia .png
Expression levels of C16orf71 in sperm with teratozoospermia.[22]

C16orf71 was also observed to have decreased expression when there was a depletion of HIF-1 alpha, HIF-2 beta, or both. HIF, or hypoxia-inducible factors, are responsible for the mediation of hypoxia effects within the body.[23] In addition, HIFs promote clotting and restoration of various epithelial tissues and are vital in the development of mammalian embryos, sperm, and ova.[24]

Data from an experiment also indicated noticeably lower expression of the gene in sperm affected with teratozoospermia, a condition where sperm have abnormal morphology affecting the fertility in males, compared to normal sperm.[22]

C16orf71 was observed to be present in all stages of development, with similar levels of expression throughout.[25]

Toxicogenomics experimental data

Three chemicals, bisphenol A, butyraldehyde, and polychlorinated biphenyls, have been experimentally tested with C16orf71 for evidence of interaction.[26]

Bisphenol A is suspected to cause impairment in male reproduction.[27] An experiment utilizing seminiferous tubule culture was conducted to observe the effects on meiosis and potential germ-line abnormalities.[27] Gene expression analysis revealed decrease expression for C16orf71 when exposed to the chemical.[27]

Butyraldehyde has been observed to affect inflammatory responses in bronchial airway tissue on a genetic level.[28] Microarray analysis was used to determine levels of expression in human alveolar epithelial cells after exposure to the compound.[28] Results indicated decreased expression for C16orf71 when exposed to the chemical.[28]

Polychlorinated biphenyl was used in an experiment to determine its effects on external male genital development.[29] Human fetal corpora cavernosa cells were used as the model tissue.[29] Toxicogenomic analysis indicated the chemical affected all genes involved with genitourinary development and revealed lowered expression levels for C16orf71.[29]

Regulation of expression

1357 bp of the gene are antisense to spliced genes ZNF500 and ANKS3, indicating possibility of regulated alternate expression.[4] A ZNF500 transcription factor binding domain was found on the minus strand within the promoter region of the gene.[30] ZNF500 is predicted to play a role in gene regulation, transcription, and cellular differentiation.[31]

The beginning of the promoter region was predicted to be 117 bp upstream from the 5' UTR of C16orf71 and is 1371 bp long.[30] The region was analyzed for predicted transcription factors and regulatory elements. Predicted transcription factors in the promoter region related to the regulation of the cell cycle, proliferation, apoptosis, and differentiation of sperm and epithelial tissue components.[3]

Predicted transcription factors

Transcription factor[30] Associated functions[30]
Ascl1 (Mammaliam achaete scute homolog 1) B-cell differentiation, maturation, and development

Negative regulation of transcription and apoptosis

Positive regulation of cell cycle and cellular differentiation

Response to hypoxia and epidermal growth factor

Regulation of epithelial cell differentiation

ZNF500 (Zinc finger with KRAB and SCAN domains 3) Cartilage development

Negative regulation of gene expression and cellular senescence

T-cell and stem cell differentiation

Positive regulation of transcription

SMAD4 transcription factor involved in TGF-beta signaling Regulation of apoptosis, T-cell and endothelial cell activation

Endoderm formation and development

Negative regulation of cell growth and death

Response to hypoxia

Thyroid gland development

Tissue morphogenesis

Cysteine-serine-rich nuclear protein 1 TGF-beta induced apoptosis

Regulation of early development and differentiation

Extracellular matrix formation

Homology

Paralogs

No human paralogs for the gene were found.[32]

Orthologs

Orthologs have been identified in most mammals for which complete genome data is available.[32] C16orf71 and its domain of unknown function, DUF4701, was present in mammals.[32] The most distant orthologs identified were reptilian.[32][33]

Molecular evolution

The m value, or number of corrected amino acid changes per 100 residues, for the gene C16orf71 was plotted against the divergence of species in millions of years. When compared to the data of hemoglobin, fibrinopeptides, and cytochrome C, it was determined that the gene has the closest progression to fibrinopeptides, suggesting a relatively rapid pace of evolution. M values for C16orf71 were derived from percentage of identity of species mRNA sequences compared to the human sequence using the formula derived from the Molecular Clock Hypothesis.

References

  1. 1.0 1.1 1.2 1.3 1.4 Database, GeneCards Human Gene. "C16orf71 Gene - GeneCards | CP071 Protein | CP071 Antibody". www.genecards.org. Retrieved 2017-02-19.
  2. 2.0 2.1 2.2 2.3 "Tissue expression of C16orf71 - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2017-04-23.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 "C16orf71 protein (Homo sapiens) - STRING network view". string-db.org. Retrieved 2017-05-05.
  4. 4.0 4.1 4.2 mieg@ncbi.nlm.nih.gov, Danielle Thierry-Mieg and Jean Thierry-Mieg, NCBI/NLM/NIH,. "AceView: Gene:C16orf71, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
  5. "C16orf71 Symbol Report | HUGO Gene Nomenclature Committee". www.genenames.org. Retrieved 2017-02-19.
  6. "C16orf71 chromosome 16 open reading frame 71 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-04-27.
  7. 7.0 7.1 "C16orf71 chromosome 16 open reading frame 71 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-04-23.
  8. 8.0 8.1 "Transcript: C16orf71-003 (ENST00000586256.1) - Summary - Homo sapiens - Ensembl genome browser 88". www.ensembl.org. Retrieved 2017-05-02.
  9. "PREDICTED: Homo sapiens chromosome 16 open reading frame 71 (C16orf71) - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-04-27.
  10. "PREDICTED: Homo sapiens chromosome 16 open reading frame 71 (C16orf71) - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-04-27.
  11. "PREDICTED: Homo sapiens chromosome 16 open reading frame 71 (C16orf71) - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-04-27.
  12. "Cell atlas - C16orf71 - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2017-04-27.
  13. 13.0 13.1 13.2 13.3 Workbench, NCSA Biology. "SDSC Biology Workbench". seqtool.sdsc.edu. Archived from the original on 2003-08-11. Retrieved 2017-04-23.
  14. "AMINO ACID FREQUENCY". www.tiem.utk.edu. Retrieved 2017-04-30.
  15. Aungier, S. P. M.; Roche, J. F.; Duffy, P.; Scully, S.; Crowe, M. A. (2015-03-01). "The relationship between activity clusters detected by an automatic activity monitor and endocrine changes during the periestrous period in lactating dairy cows". Journal of Dairy Science. 98 (3): 1666–1684. doi:10.3168/jds.2013-7405. ISSN 0022-0302. PMID 25529424.
  16. 16.0 16.1 Spector, David L.; Lamond, Angus I. (2011-02-01). "Nuclear Speckles". Cold Spring Harbor Perspectives in Biology. 3 (2): a000646. doi:10.1101/cshperspect.a000646. ISSN 1943-0264. PMC 3039535. PMID 20926517.
  17. 17.0 17.1 "I-TASSER server for protein structure and function prediction". zhanglab.ccmb.med.umich.edu. Retrieved 2017-04-23.
  18. "Redirecting to Phyre2". www.sbg.bio.ic.ac.uk. Retrieved 2017-05-06.
  19. "NucPred - Home". www.sbc.su.se. Retrieved 2017-05-06.
  20. 20.0 20.1 "GDS3688 / 222089_s_at". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
  21. "GDS2761 / GI_21040258-S". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
  22. 22.0 22.1 "GDS2696 / GI_21040258-S". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
  23. "GDS2761 / GI_21040258-S". www.ncbi.nlm.nih.gov. Retrieved 2017-05-06.
  24. Semenza, Gregg (February 2012). "Hypoxia-Inducible Factors in Physiology and Medicine". Cell. 148: 399–408.
  25. "Home - EST - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-04-23.
  26. "C16ORF71 - Chemical Interactions | CTD". ctd.mdibl.org. Retrieved 2017-05-06.
  27. 27.0 27.1 27.2 Ali, Sazan; Steinmetz, Gérard; Montillet, Guillaume; Perrard, Marie-Hélène; Loundou, Anderson; Durand, Philippe; Guichaoua, Marie-Roberte; Prat, Odette (2014-09-02). "Exposure to Low-Dose Bisphenol A Impairs Meiosis in the Rat Seminiferous Tubule Culture Model: A Physiotoxicogenomic Approach". PLOS ONE. 9 (9): e106245. doi:10.1371/journal.pone.0106245. ISSN 1932-6203. PMC 4152015. PMID 25181051.
  28. 28.0 28.1 28.2 Song, Mi-Kyung; Lee, Hyo-Sun; Ryu, Jae-Chun. "Integrated analysis of microRNA and mRNA expression profiles highlights aldehyde-induced inflammatory responses in cells relevant for lung toxicity". Toxicology. 334: 111–121. doi:10.1016/j.tox.2015.06.007.
  29. 29.0 29.1 29.2 Tait, Sabrina; La Rocca, Cinzia; Mantovani, Alberto (2011-07-01). "Exposure of human fetal penile cells to different PCB mixtures: transcriptome analysis points to diverse modes of interference on external genitalia programming". Reproductive Toxicology. 32 (1): 1–14. doi:10.1016/j.reprotox.2011.02.001.
  30. 30.0 30.1 30.2 30.3 "Genomatix - NGS Data Analysis & Personalized Medicine". www.genomatix.de. Retrieved 2017-04-23.
  31. Database, GeneCards Human Gene. "ZNF500 Gene - GeneCards | ZN500 Protein | ZN500 Antibody". www.genecards.org. Retrieved 2017-05-06.
  32. 32.0 32.1 32.2 32.3 "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2017-04-23.
  33. "Human BLAT Search". genome.ucsc.edu. Retrieved 2017-04-23.

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