Wikipedia

METTL26

METTL26, previously designated C16orf13, is a protein-coding gene for Methyltransferase Like 26, also known as JFP2.[5] Though the function of this gene is unknown, various data have revealed that it is expressed at high levels in various cancerous tissues.[6][7] Underexpression of this gene has also been linked to disease consequences in humans.[8]

METTL26
Identifiers
AliasesMETTL26, C16orf13, JFP2, Chromosome 16 open reading frame 13, methyltransferase like 26
External IDsMGI: 1915597; HomoloGene: 16917; GeneCards: METTL26; OMA:METTL26 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

84326

68347

Ensembl

ENSG00000130731

ENSMUSG00000025731

UniProt

Q96S19

Q9DCS2

RefSeq (mRNA)

NM_026686

RefSeq (protein)

NP_080962

Location (UCSC)Chr 16: 0.63 – 0.64 MbChr 17: 26.09 – 26.1 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Gene

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Exon breakdown of C16orf13 transcript variant 1. The AdoMet-MTase domain is also included in the diagram.

METTL26 is located on the short arm of chromosome 16 in humans, in the thirteenth open reading frame.[9] There are five transcript variants of this gene, named 1, 2, 3, 4, and 7. The longest cDNA transcript (transcript variant 1) contains 854 base pairs.[10] This transcript is composed of six exons, all of which contribute to the major superfamily included in the protein, the methyltransferases superfamily.[11] The primary transcript of this gene is 1,919 base pairs long.[12]

Species distribution

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Dot plot showing sequence similarity at the 5' and 3' ends of the Human gene and its Chimpanzee ortholog.

Using the Dotlet program, a dot plot was constructed comparing the Human gene with its Chimpanzee ortholog.

The plot indicates sequence conservation at the beginning and end of the gene, suggesting conservation and similarity in the 5' and 3' untranslated regions.

This sequence similarity in the 5’ UTR and 3’ UTR does not extend past mammalian species, and shows almost no similarity in a Dot Plot of the Human gene with distantly related species, such as Xenopus tropicalis.

A multiple sequence alignment conducted using the SDSC Biology Workbench [13] reveals little sequence similarity among species more distantly related than primates in the upstream region of the gene. Near the start of transcription site in the human C16orf13 gene, there is high conservation among the primates in which upstream data was available, specifically the human, orangutan, and rhesus monkey C16orf13 gene orthologs. High sequence similarity among primates is evident throughout the promoter region, the 5' UTR, and the C16orf13 gene.

The graph below shows selected gene orthologs for C16orf13 transcript variant 1. These data are collected from NCBI BLAST.[14]

Species Organism Common name Gene Common name NCBI accession number Sequence identity Expected value Sequence length (bp) Time since split from humans, MYA (Data from TimeTree.org)
Homo sapiens Human C16orf13 NM_032366.3 100% 0 854 0
Pan troglodytes Chimpanzee LOC467858 NM_032366.3 98% 0 784 6.4
Canis lupus familiaris Dog C6H16orf13 XM_547214.3 88% 0 865 94.4
Mus musculus Mouse 0610011F06Rik NM_026686.2 86% 0 825 92.4
Xenopus (Silurana) tropicalis Western clawed frog c16orf13 NM_001039734.1 BLAST search found no significant similarity BLAST search found no significant similarity 993 371.2

Tissue distribution

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The human expression profile from NCBI UniGene suggests that this gene has widespread expression in many different tissues in the body.[15] This expression profile suggests that this gene is a “housekeeping gene,” one that has important effects in all cells, regardless of tissue. The highest levels of expression appear to be in the adrenal gland, lung, and parathyroid.[15] There are many additional sites besides these highest three where the gene is expressed in high levels. There seems to be no real similarity in the few tissues where the gene is not expressed. This expression data does not seem to give any clues into specific function, except to suggest that the gene is involved in a “housekeeping” function of nearly all cells.

Gene neighborhood

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Approximate location of the C16orf13 gene on Chromosome 16
 
Gene neighborhood of C16orf13

The C16orf13 gene is located near the end of chromosome 16, potentially subject to deletion mutations.

The surrounding genes of the C16orf13 gene include hypothetical protein LOC100287175 and LOC100138285 to the right and RAB40C and WFIKKN1 to the left. This gene is located on the minus strand, along with LOC100138285. The other surrounding genes are oriented in the opposite way on the plus strand. The gene neighborhood is represented in the schematic below, originally from NCBI Gene.

Protein

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The protein that this gene codes for is known as UPF0585, where UPF signals unknown protein function. There are five isoforms of this protein, corresponding to the five splice variants of the gene.[16] The isoforms are named a, b, c, d, and g[16] As mentioned above, the conserved domain detected in a BLAST search of this amino acid sequence is a methyltransferase superfamily.

Conservation

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A multiple sequence alignment conducted using the protein tools in the SDSC Biology Workbench [13] reveals some sequence similarity among distantly related protein orthologs, as far back as archaea, in the region known to code for the methyltransferase domain. The methyltransferase superfamily portion of the protein appears more highly conserved among many of the more closely related orthologous proteins in a diverse array of species.

Species distribution

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The C16orf13 has homologs in many species, including distant orthologs in fungi and plants.[17][18] There are no known paralogs of this protein[19][20] This gene and its protein are very highly conserved in primates and mammals, particularly in the functional methyltransferase domain.

The graph below shows selected protein orthologs for C16orf13 transcript variant 1. These data are collected from NCBI BLAST.

Species Organism Common name Protein Common name NCBI accession number Sequence identity Expected value Sequence length (aa) Time since split from humans, MYA (Data from TimeTree.org)
Homo sapiens Human UPF0585, isoform a NP_115742.3 100% 0 204 0
Pan troglodytes Chimpanzee LOC467858 XP_001154838.1 98% 1E-150 204 6.4
Canis lupus familiaris Dog LOC490093 XP_547214.3 91% 4E-141 204 94.4
Mus musculus Mouse 0610011F06Rik NP_080962.1 87% 5E-134 204 92.4
Xenopus (Silurana) tropicalis Western clawed frog UPF0585 protein C16orf13 homolog NP_001034823.2 58% 1E-82 203 371.2

Predicted properties

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Predicted secondary structure of the protein based on results obtained using CHOFAS, GOR4, and PELE programs on SDSC Biology Workbench. The most confident areas (those that appeared in multiple programs) are boxed in addition to highlighted. The dashes in the sequences represent exon splice sites.

The protein secondary structure can be predicted using algorithms to predict the occurrence of alpha helices and beta sheets within the protein. An analysis of the protein structure was conducted using the CHOFAS, GOR4, and PELE algorithms in the SDSC Biology Workbench.[21] The analyses were combined and included in the adjacent diagram. Only structures that appeared in more than one output were included.

Interactions

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There are few known interactions for this protein. No interactions were found in the GeneCards database[9] or in the MINT database.[22] A STRING search resulted in two gene outputs.[23] These two gene interactions, though, are both in the evidence category of gene neighborhood, which does not necessarily suggest that these genes are interacting in any meaningful way, or are even expressed at the same time. There is no strong evidence, currently, for interactions with this protein.

Disease linkage

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Data from microarray experiments has linked over expression of this gene to cancer in various tissues, particularly breast and gastric cancer. In addition, under expression of this gene is also linked to disease, particularly connective tissue disease, nutritional and metabolic disorders, and digestive disorders. The canSAR Workbench database reveals microarray data that may link over or under expression of the C16orf13 gene to various carcinomas [24]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000130731 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025731 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "C16orf13 - UPF0585 protein C16orf13 - human protein (Identifiers)". Nextprot.org. Retrieved 2012-05-18.
  6. ^ "Breast Cancer Database". Itb.cnr.it. Retrieved 2012-05-18.
  7. ^ Oh JH, Yang JO, Hahn Y, Kim MR, Byun SS, Jeon YJ, Kim JM, Song KS, Noh SM, Kim S, Yoo HS, Kim YS, Kim NS (December 2005). "Transcriptome analysis of human gastric cancer". Mamm. Genome. 16 (12): 942–54. doi:10.1007/s00335-005-0075-2. PMID 16341674. S2CID 69278.
  8. ^ "C16orf13 Disease Atlas". NextBio. Retrieved 2012-05-18.[permanent dead link]
  9. ^ a b GeneCards Human Gene Database. "C16orf13 Gene - GeneCards | CP013 Protein | CP013 Antibody". GeneCards. Retrieved 2012-05-18.
  10. ^ "Homo sapiens chromosome 16 open reading frame 13 (C16orf13), transcrip - Nucleotide - NCBI". Ncbi.nlm.nih.gov. 2012-04-04. Retrieved 2012-05-18.
  11. ^ "Homo sapiens chromosome 16 open reading frame 13 (C16orf13), transcrip - Nucleotide - NCBI". Ncbi.nlm.nih.gov. 2012-04-04. Retrieved 2012-05-18.
  12. ^ "Homo sapiens chromosome 16, GRCh37.p5 Primary Assembly - Nucleotide - NCBI". Ncbi.nlm.nih.gov. 2012-04-04. Retrieved 2012-05-18.
  13. ^ a b "SDSC Biology Workbench". Workbench.sdsc.edu. Retrieved 2012-05-18.
  14. ^ "BLAST: Basic Local Alignment Search Tool".
  15. ^ a b "EST Profile - Hs.239500". Ncbi.nlm.nih.gov. Retrieved 2012-05-18.[permanent dead link]
  16. ^ a b "C16orf13 chromosome 16 open reading frame 13 [Homo sapiens] - Gene - NCBI". Ncbi.nlm.nih.gov. Retrieved 2012-05-18.
  17. ^ GeneCards Human Gene Database. "C16orf13 Gene - GeneCards | CP013 Protein | CP013 Antibody". GeneCards. Retrieved 2012-05-18.
  18. ^ "Ensembl genome browser 67: Homo sapiens - Orthologues - Gene: C16orf13 (ENSG00000130731)". Useast.ensembl.org. Retrieved 2012-05-18.
  19. ^ GeneCards Human Gene Database. "C16orf13 Gene - GeneCards | CP013 Protein | CP013 Antibody". GeneCards. Retrieved 2012-05-18.
  20. ^ "Ensembl genome browser 67: Homo sapiens - Comparative Genomics - Gene: C16orf13 (ENSG00000130731)". Useast.ensembl.org. Retrieved 2012-05-18.
  21. ^ Chou PY; Fasman GD (2006). "Advances in Enzymology and Related Areas of Molecular Biology". Advances in Enzymology - and Related Areas of Molecular Biology. pp. 45–148. doi:10.1002/9780470122921.ch2. ISBN 9780470122921. PMID 364941.[permanent dead link]
  22. ^ "HomoMINT database". Mint.bio.uniroma2.it. Retrieved 2012-05-18.[permanent dead link]
  23. ^ "STRING: functional protein association networks". String-db.org. Retrieved 2012-05-18.
  24. ^ "Gene Q96S19 | Protein METTL26 - Gene expression | canSAR Black".
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