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C15orf39

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C15orf39
Chromosome 15
Identifiers
SymbolC15orf39
NCBI gene56905
HGNC24497
RefSeqNP_056307.2
UniProtQ6ZRI6
Search for
StructuresSwiss-model
DomainsInterPro

C15orf39 is a protein that in humans is encoded by the Chromosome 15 open reading frame 15 (C15orf39) gene.

Gene

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Location

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C15orf39 is located on chromosome 15 (15q24.2), spanning 16.53kb from 75487985 to 75504515 on the plus DNA strand.[1] C15orf39 has three exons, and seven introns.[1][2]

Location of C15orf39 on chromosome 15.[3]

mRNA

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Isoforms

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The coding sequence for the C15orf39 mRNA is 4443 base pairs long.[4] The C15orf39 gene produces seven mRNA transcripts, with the longest coding isoform being 1047 amino acids long, and the shortest being 27 amino acids which has a truncated 3' end.[5]

Expression

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Expression of C15orf39 in human tissues.[6]

C15orf39 is highly expressed in the trigeminal ganglion, superior cervical ganglion, whole blood, and the heart. Low expression levels of C15orf39 were found in the occipital lobe and PB-CD19+ B-cells.[6]

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In-situ hybridization of C15orf39 in fetal and adult reticulocytes.[7]

C15orf39 expression levels in fetal and adult reticulocytes showed significantly different levels of expression (P < 0.0001), with adult reticulocytes expressing more C15orf39 than fetal cells.[7]

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Protein

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General Properties

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C15orf39 has an unmodified molecular mass of 110.6 kDA.[2][8] The modified molecular mass is 110.7 kDA.[9] C15orf39 is composed of an above average level of proline (≈17%), and is deficient in isoleucine (≈1%) and asparagine (≈1%).[10] Both close (Thirteen-lined ground squirrel) and distant (Crested-Ibis) orthologs contained above average levels of proline, and low levels of isoleucine, and asparagine.

Domains and Motifs

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Domains of C15orf39. P = Phosphorylation, A = Acetylation, SUMO = Sumoylation, O = O-glycosylation.

C15orf39 has four predicted domains. Two of which, are the proline rich and alanine rich domains. The large tegument protein UL36 domain is important in the regulation of the viral cycle of Human Herpes Virus 1 (HHV-1), including transporting the viral capsid to the nuclear pore complex, and linking the inner and outer viral tegument capsids together.[11] Lastly, the WH2 domain, WASP-homology domain 2, is approximately 18 amino acids long, and serves as an actin binding domain.[12] WH2 binds actin monomers enabling the production of actin filaments.

Post-Translational Modifications

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The predicted post-translational modifications for C15orf39 include phosphorylation, acetylation, sumoylation, and o-glycosylation. An amino acid of importance is K17, which has an acetyl and sumo-group covalently attached.[2][13] Also, T970, which is phosphorylated and has an o-glycosyl group attached.[14][15] All predicted post-translational modifications were conserved in distant and strict orthologs.

Conceptual translation of C15orf39 C-terminal showing predicted PTM and secondary structure.
PTM Amino Acid Location
Phosphorylation[14] S208, S322, S467, S496, S497, T970
Acetylation[2] K17
Sumoylation[13] K17, K57, K154, K358, K569, K975
Sumoylation Interaction[13] 462-466
O-Glycosylation[15] S497, T970

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Structure

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Alpha helices predicted in the C15orf39 protein are colored red, and random coils are represented as tan. No beta sheets were predicted to be part of the secondary structure for C15orf39. The amino acids not modeled were predicted to be random coils.[16]

Predicted tertiary structure for C-terminal end of C15orf39.[17]

Sub-cellular Localization

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C15orf39 is predicted to be located in the cytosol of the cell.[18]

Protein Interactions

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Protein interaction screenings have showed C15orf39 to interact with many proteins, including RPLP1 and EIF4ENIF1. C15orf39 was discovered to interact with RPLP1 (Large Ribosomal Subunit Protein P1), a cytoplasmic protein, in a high-output yeast two-hybrid screening. RPLP1 is an acidic ribosomal subunit that is important in the elongation step of transcription.[19][20] EIF4ENIF1 (Eukaryotic Translation Initiation Factor 4E Transporter), is a nucleocytoplasmic protein that shuttles the translation initiation factor eIF4E between the nucleus and cytoplasm.[21] The protein interaction between C15orf39 and EIF4ENIF1 was discovered through affinity capture.[22]

Homology

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Paralogs

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There are no known paralogs for the human C15orf39 gene.[23]

Orthologs

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The ortholog space for C15orf39 includes relatives as distant as the cartilaginous fish like Rhincodon typus (whale shark), and as strict as closely related mammals like the Gorilla, which has 99% sequence identity to the human protein.[24][25] The phylogenetic tree below, shows the evolutionary relationship of the C15orf39 protein sequence in its orthologs.[26]

Phylogenetic tree for select C15orf39 orthologs.[26]
Scientific Name Common Name MYA Protein Accession # Length (AA) % Identity
Homo sapiens Human 0 NP_056307 1,047 100
Gorilla gorilla gorilla Gorilla 9.06 XP_004056588.1 1,047 99
Ictidomys tridecemlineatus Thirteen-lined ground squirrel 90 XP_005316869.1 1,032 80
Equus caballus Horse 96 XP_023509136.1 1,033 79
Delphinapterus leucas Beluga Whale 96 XP_022435768.1 1,041 78
Loxodonta africana African Bush Elephant 105 XP_003413993.1 1,072 75
Omithorhynchus anatinus Platypus 177 XP_007656779.1 1,119 37
Gekko japonicus Gekko Japonicus 312 XP_015267003.1 1,387 51
Nipponia Nippon Crested Ibis 312 XP_009468021.1 1,046 32
Xenopus laevis African Clawed Frog 352 XP_018111022.1 1,475 40
Rhincodon typus Whale Shark 473 XP_020392571.1 1,491 31

Divergence

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Rate of sequence divergence for C15orf39, Fibrinogen, and Cytochrome C in orthologs.[27]

The graph displays that the C15orf39 protein is quickly evolving. C15orf39's sequence has diverged at a quicker rate than the quickly evolving fibrinogen protein in humans.[27]

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.References

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  1. ^ a b Thierry-Mieg, Danielle; Thierry-Mieg, Jean. "AceView: Gene:C15orf39, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView". www.ncbi.nlm.nih.gov. Retrieved 2018-02-19.
  2. ^ a b c d "uncharacterized protein C15orf39 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-02-19.
  3. ^ "C15orf39 chromosome 15 open reading frame 39 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-05-05.
  4. ^ "Homo sapiens chromosome 15 open reading frame 39 (C15orf39), mRNA - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-05-05.
  5. ^ "Gene: C15orf39 (ENSG00000167173) - Summary - Homo sapiens - Ensembl genome browser 92". useast.ensembl.org. Retrieved 2018-05-05.
  6. ^ a b "GDS596 / 204495_s_at". www.ncbi.nlm.nih.gov. Retrieved 2018-05-05.
  7. ^ a b "GDS2655 / 204494_s_at". www.ncbi.nlm.nih.gov. Retrieved 2018-05-05.
  8. ^ "C15orf39 Gene". www.genecards.org. Retrieved 2018-02-19.
  9. ^ "C15orf39 - Antibodies - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2018-05-05.
  10. ^ "PSORT II Prediction". psort.hgc.jp. Retrieved 2018-05-05.
  11. ^ "UL36 - Large tegument protein deneddylase - Human herpesvirus 1 (strain 17) (HHV-1) - UL36 gene & protein". www.uniprot.org. Retrieved 2018-05-05.
  12. ^ "ELM - search the eukaryotic linear motif resource". elm.eu.org. Retrieved 2018-05-05.
  13. ^ a b c "GPS-SUMO Online Service". GPS. April 20, 2018.[permanent dead link‍]
  14. ^ a b "GPS 3.0 - Kinase-specific Phosphorylation Site Prediction". gps.biocuckoo.org. Archived from the original on 2018-05-06. Retrieved 2018-05-05.
  15. ^ a b "5ADC962700006D04C7682FA1 expired". www.cbs.dtu.dk. Retrieved 2018-05-05.
  16. ^ "NPS@ : GOR4 secondary structure prediction". npsa-prabi.ibcp.fr. Retrieved 2018-05-06.
  17. ^ "Submit a Prediction Job". raptorx.uchicago.edu. Retrieved 2018-05-05.
  18. ^ "C15orf39 - Uncharacterized protein C15orf39 - Homo sapiens (Human) - C15orf39 gene & protein". www.uniprot.org. Retrieved 2018-02-19.
  19. ^ "RPLP1 Gene". www.genecards.org. Retrieved 2018-05-06.
  20. ^ Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070.
  21. ^ "EIF4ENIF1 Gene". www.genecards.org. Retrieved 2018-05-06.
  22. ^ Boldt K, van Reeuwijk J, Lu Q, Koutroumpas K, Nguyen TM, Texier Y, et al. (May 2016). "An organelle-specific protein landscape identifies novel diseases and molecular mechanisms". Nature Communications. 7: 11491. Bibcode:2016NatCo...711491B. doi:10.1038/ncomms11491. PMC 4869170. PMID 27173435.
  23. ^ "Gene: C15orf39 (ENSG00000167173) - Summary - Homo sapiens - Ensembl genome browser 91". useast.ensembl.org. Retrieved 2018-02-26.
  24. ^ "uncharacterized protein C15orf39 homolog isoform X1 [Rhincodon typus] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-05-06.
  25. ^ "PREDICTED: uncharacterized protein C15orf39 homolog [Gorilla gorilla g - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-05-06.
  26. ^ a b "Multiple Sequence Alignment - CLUSTALW". www.genome.jp. Retrieved 2018-05-06.
  27. ^ a b "TimeTree :: The Timescale of Life". www.timetree.org. Retrieved 2018-05-06.
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