C15orf54 (Chromosome 15 Open Reading Frame 54) is a protein in humans that is encoded by the C6orf54 gene. This gene is mostly conserved in mammals, primarily primates. While the function of the gene is currently unknown, the gene has shown high expression in the prostate, thymus, appendix, bone marrow, and lungs.[3]

LINC02915
Identifiers
AliasesLINC02915, chromosome 15 open reading frame 54, chromosome 15 open reading frame 54 (putative), chromosome 15 putative open reading frame 54, long intergenic non-protein coding RNA 2915, C15orf54
External IDsHomoloGene: 131352; GeneCards: LINC02915; OMA:LINC02915 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_207445
NM_001302797

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)Chr 15: 39.25 – 39.25 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Gene

edit

C15orf54 is located on chromosome 15 from 39542870 to 39547048 on the direct strand. This gene is 4,180 bases in length. The gene is otherwise known as LOC400360 or FLJ39531. The gene contains 2 distinct gt-ag introns and two exons with two alternatively spliced mRNAs, both encoding the same protein.[3] The NCBI accession number is NC_000015.10.[4]

 
Location of C15orf54 on chromosome 15

mRNA

edit

Isoforms

edit

C15orf54 has a total of 2 isoforms: variant 1 and variant 2. Variant 1 represents the longer transcript and variant 2 uses an alternate splice site in the 3' exon compared to variant 1.[3]

Variant 1

edit

The complete mRNA is 3095 bp long and contains 2 exons. The 5' UTR contains 383 bp with an in frame stop 48 bp before the Met. The 3' UTR contains 2160 bp followed by the polyA. The standard AATAAA polyadenylation signal is seen about 23 bp before the polyA. The predicted protein product has 183 aa.[3]

Protein

edit

General properties

edit

The sequence for the C15orf54 protein is as follows:[3]

MEVKFITGKHGGRRPQRAEPQRICRALWLTPWPSLILKLLSWIILSNLFLHLRATHHMTE

LPLRFLYIALSEMTFREQTSHQIIQQMSLSNKLEQNQLYGEVINKETDNPVISSGLTLLF

AQKPQSPGWKNMSSTKRVCTILADSCRAQAHAADRGERGHFGVQILHHFIEVFNVMAVRS

NPF

The dominant protein product is 183 amino acids long and has a predicted molecular weight of 21 kDa. The isoelectric point is 9.87.[3] C15orf54 has a relatively high frequency of leucine at 12.0% and a relatively low frequency of tyrosine at 1.1%.[5] The number of multiplets in this sequence is 12. There are no unusual spacings in this protein.[5]

Domains and Motifs

edit

Analysis of C15orf54 showed a globular domain with multiple motif functional sites. One site is the MAPK-docking motif, which consists of one or more basic and two to four hydrophobic residues in adjacent groups. These motifs regulate specific interactions in the MAPK cascade. Another such site is the LIR motif which is a part of the Atg8 protein family ligands and plays a role in selective autophagy by recruiting specific adaptors bound to ubiquitylated proteins, organelles, or pathogens for degradation.[6]

Post-translational modification

edit

C15orf54 is non-myristoylated. There was also no sulfinated sites found in this protein. One motif with a high probability of post translational modification sumoylation sites were found. Sumoylation sites are involved in nuclear-cytosolic transport, transcriptional regulation and protein stability.[7]

Secondary structure

edit

C15orf54 is composed of both alpha helices and beta sheets, as well as turns and some coils. Alpha helices constituted the majority of the protein.[8]

Sub-cellular Localization

edit

The membrane topology was determined to be type 1b with a cytoplasmic tail from 34 to 183, indicating that the C-terminal side will be inside. There was a transmembrane region located from 34 to 50. There were dileucine motifs found in the tail at 39 and 118.[9]

Interacting Proteins

edit

Two interacting proteins were found, lsd2_drome and npfr_drome. Lsd2_drome is a lipid storage droplet surface binding protein and npfr_drome is a neuropeptide F receptor.

Regulation

edit

Gene regulation

edit

Promoter

edit

C15orf54 has one predicted promoter sequence. GXP_6084 is located from 39249718 to 39250757 on the plus strand of chromosome 15 and is composed of 1040 bp.[10]

Transcription factor binding sites

edit

The following table displays the transcription factors most likely to bind to the GXP_6084 promoter for C15orf54.[10]

Matrix Family Detailed Family Information
TALE TG-interacting factor belonging to TALE class of homeodomain factors
CART Binding site for S8 type homeodomains
HAND T-cell acute lymphocytic leukemia 1, SCL
ZFHX AREB6 (Atp1a1 regulatory element binding factor 6)
TZAP Zinc finger and BTB domain containing 48
SAL4 Spalt like 4, DRRS, HSAL4, ZNF797
TEAF TEA domain family member 4, TEF-3
RUSH SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 3
EGRF Wilms Tumor Suppressor

Expression pattern

edit

The gene has shown high expression in the prostate, thymus, appendix, bone marrow, and lungs. NCBI AceView shows that the gene is moderately expressed.[3]

 
Diagram depicting the expression of C15orf54 in tissues throughout the body.[4]

Transcription regulation

edit

miRNA targeting

edit

TargetScan showed that miRNA hsa-miR-375 was highly conserved across various organisms. This miRNA is specifically expressed in the pancreatic islets, brain, and spinal cord. This miRNA has also been shown to be associated with different cancers, including breast and gastric cancer.[11]

Homology

edit

Rate of evolution

edit
 
Relative mutation rate of C15orf54 (blue) compared to fibrinogen alpha (grey) and cytochrome C (orange)

Paralogs

edit

No paralogs of C15orf54 have been detected in the human genome.

Orthologs

edit

Orthologs were primarily found in primates, although many different mammals also exhibited sizeable sequence similarity to the human C15orf54 sequence. Below is a table of selected orthologs sorted by date of divergence for the C15orf54 gene, including closely and distantly related orthologs.[12][13] C15orf54 was shown to evolve relatively quickly and evenly over time with a faster rate than both Cytochrome C and Fibrinogen Alpha.

Genus and species Common Name Taxonomic Group Date of Divergence - Est. Time (MYA) Accession Number Sequence length (aa) Sequence Identity (%) Sequence Similarity (%) n m
Homo sapiens Humans Primates 0 NP_001027544.1 803 100 100 0 0.0
Macaca mulatta Rhesus Macaque Primates 29.44 AFE75666.1 (extended) 767 91.9 93.9 8.1 8.4
Fukomys damarensis Damara Mole Rat Rodentia 90 XP_010621546.2 753 73.6 79.3 26.4 30.7
Camelus ferus Wild Bactrian Camel Artiodactyla 94 XP_006175095.2 802 81.8 88.6 18.2 20.1
Odobenus rosmarus divergens Pacific Walrus Carnivora 96 XP_012418040.1 806 84.5 90.3 15.5 16.8
Mirounga leonina Southern Elephant Seal Carnivora 96 XP_034842573.1 806 83.7 89.8 16.3 17.8
Manis javanica Malayan Pangolin Pholidota 96 XP_017502667.1 584 49.4 53.0 50.6 70.5
Echinops telfairi Lesser Hedgehog Tenrec Afrosoricida 102 XP_030742207.1 419 31.9 38.9 68.1 114.3
Denticeps clupeoides Denticle herring Actinoptergyii/Clupeiformes 435 XP_028809248.1 3037 12.4 16.7 87.6 208.7
Beroe forskalii Cigar comb jellies Ctenophora/Beroida 540 AHA51259.1 212 12.0 18.2 88.0 212.0
Araneus ventricosus Orb weaving Spider Araneae 736 GBN07005.1 543 30.2 38.9 69.8 119.7
Capitella teleta Segmented annelid worm Annelida 797 ELT92884.1 537 31.3 43.3 68.7 116.2
Thelazia callipaeda Parasitic nematode Nematoda/Rhabditida 797 VDN04867.1 418 25.2 32.9 74.8 137.8
Drosophila melanogaster Fruit flies Diptera 797 NP_650197.1 501 24.4 34.8 75.6 141.1
Octopus sinensis Common octopus Octopada/Mollusca 797 XP_029652221.1 5045 6.8 9.2 93.2 268.8
Nematostella vectensis Starlet Sea Anemone Cnidaria/Anthozoa 824 EDO31838.1 482 30.7 42.6 69.3 118.1
Macrostomum lignano Flatworm Platyhelminthes/Macrostomida 824 PAA81016.1 477 27.0 35.6 73.0 130.9
Salpingoeca rosetta Choanoflagellates Choanoflagelletes 1023 XP_004989424.1 480 20.5 28.3 79.5 158.5
Rhizophagus clarus Arbuscular mycorrhizal fungi Fungi/Glomerales 1105 GBB86324.1 717 30.1 41.8 69.9 120.1
Salmonella enterica Gram Negative Bacteria Salmonella/Enterobacterales 4290 EDQ2188565.1 310 12.8 18.2 87.2 205.6

Clinical significance

edit

C15orf54 was associated with hypertrophy-associated polymorphisms in heart failure risk[14] and Atherosclerosis risk.[15] C15orf54 was also positively correlated with higher survival rates in patients with gastric cancer.[16] It was also shown to be a locus of interest in determining the glomerular filtration rate in a pool of individuals with Mongolian ancestry[17]

References

edit
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000175746Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ a b c d e f g "AceView: Gene:C15orf54, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView". www.ncbi.nlm.nih.gov. Retrieved 2020-12-19.
  4. ^ a b "C15orf54 chromosome 15 putative open reading frame 54 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-12-19.
  5. ^ a b "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2020-12-19.
  6. ^ "Motif Scan". myhits.sib.swiss. Retrieved 2020-12-19.
  7. ^ "SIB Swiss Institute of Bioinformatics | Expasy". www.expasy.org. Retrieved 2020-12-19.
  8. ^ Prof. T. Ashok Kumar. "CFSSP: Chou & Fasman Secondary Structure Prediction Server". www.biogem.org. Retrieved 2020-12-19.
  9. ^ "PSORT II Prediction". psort.hgc.jp. Retrieved 2020-12-19.
  10. ^ a b "Genomatix" (in German). Archived from the original on 2001-02-24. Retrieved 2020-12-19.
  11. ^ "TargetScanHuman 7.2". www.targetscan.org. Retrieved 2020-12-19.
  12. ^ "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2020-12-19.
  13. ^ "TimeTree :: The Timescale of Life". www.timetree.org. Retrieved 2020-12-19.
  14. ^ Chamaria, Surbhi; Johnson, Kipp W.; Vengrenyuk, Yuliya; Baber, Usman; Shameer, Khader; Divaraniya, Aparna A.; Glicksberg, Benjamin S.; Li, Li; Bhatheja, Samit; Moreno, Pedro; Maehara, Akiko (2017-08-01). "Intracoronary Imaging, Cholesterol Efflux, and Transcriptomics after Intensive Statin Treatment in Diabetes". Scientific Reports. 7 (1): 7001. Bibcode:2017NatSR...7.7001C. doi:10.1038/s41598-017-07029-7. ISSN 2045-2322. PMC 5539108. PMID 28765529.
  15. ^ Yu, Bing (2013). Human metabolome and common complex diseases: A genetic and epidemiological study among African-Americans in the atherosclerosis risk in communities study (Thesis). ProQuest 1503137765.
  16. ^ Zhou, Li-Li; Jiao, Yan; Chen, Hong-Mei; Kang, Li-Hua; Yang, Qi; Li, Jing; Guan, Meng; Zhu, Ge; Liu, Fei-Qi; Wang, Shuang; Bai, Xue (2019-10-21). "Differentially expressed long noncoding RNAs and regulatory mechanism of LINC02407 in human gastric adenocarcinoma". World Journal of Gastroenterology. 25 (39): 5973–5990. doi:10.3748/wjg.v25.i39.5973. ISSN 1007-9327. PMC 6815795. PMID 31660034.
  17. ^ Park, Hansoo; Kim, Hyun-Jin; Lee, Seungbok; Yoo, Yun Joo; Ju, Young Seok; Lee, Jung Eun; Cho, Sung-Il; Sung, Joohon; Kim, Jong-Il; Seo, Jeong-Sun (2013-02-01). "A family-based association study after genome-wide linkage analysis identified two genetic loci for renal function in a Mongolian population". Kidney International. 83 (2): 285–292. doi:10.1038/ki.2012.389. hdl:10371/91067. ISSN 0085-2538. PMID 23254893.