Trinucleotide repeat containing 18

Source: Wikipedia, the free encyclopedia.
TNRC18
Identifiers
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000182095

ENSMUSG00000039477

UniProt

O15417

Q80WC3

RefSeq (mRNA)

NM_001013722
NM_001080495

NM_001122730
NM_178242

RefSeq (protein)

NP_001073964

NP_001116202
NP_839973

Location (UCSC)Chr 7: 5.31 – 5.43 MbChr 5: 142.72 – 142.82 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Trinucleotide repeat containing 18 is a protein that in humans is encoded by the TNRC18 gene.[5]

Function

The exact function of TNRC18 is not yet well understood by the scientific community. The protein sequence provided by the National Center for Biotechnology Information (NCBI) database includes a Bromo Adjacent Homology (BAH) Domain within TNRC18.[6] BAH domains are often found in chromatin-associated proteins and assist in the silencing of genes.[7]

Gene

According to the UCSC Genome Browser, TNRC18 is located within Chromosome 7 in humans (chr7: 5,306,800-5,423,546). There are 29 introns and 30 exons listed. Directly preceding TNRC18 is SLC29A4 and immediately following is AC092171.4.[8] SLC29A4 encodes the plasma membrane monoamine transporter in humans.

GeneCards lists five aliases for TNRC18, Long CAG Trinucleotide Repeat-Containing Gene 79 Protein, Trinucleotide Repeat-Containing Gene 18 Protein, CAGL79, KIAA1856, and TNRC18A. Additionally, TNRC18 has two paralogs, BAH Domain And Coiled-Coil Containing 1 (BAHCC1) and Bromo Adjacent Homology Domain Containing 1 (BAHD1).[9]

mRNA and Isoforms

The NCBI gene page for TNRC18 lists 9 different protein isoforms across 12 transcript variant mRNA sequences.[10] TNRC18 isoform X7 is encoded by mRNA transcript variants X7-X10. Additionally, isoforms X8 and X9 are produced by variants X11 and X12 respectively.

TNRC18 Isoform variations
Isoform mRNA Protein mRNA length (bp) Protein length (aa)
TNRC18 NM_001080495 NP_001073964 10586 2968
TNRC18 isoform X1 XM_017012728 XP_016868217 10902 2979
TNRC18 isoform X2 XM_017012730 XP_016868219 10424 2978
TNRC18 isoform X3 XM_017012731 XP_016868220 10299 2936
TNRC18 isoform X4 XM_017012732 XP_016868221 10296 2935
TNRC18 isoform X5 XM_017012733 XP_016868222 10284 2931
TNRC18 isoform X6 XM_017012734 XP_016868223 11319 2929
TNRC18 isoform X7 XM_017012735 XP_016868224 10312 2905
TNRC18 isoform X7 XM_017012736 XP_016868225 10899 2905
TNRC18 isoform X7 XM_017012737 XP_016868226 10472 2905
TNRC18 isoform X7 XM_017012738 XP_016868227 10194 2905
TNRC18 isoform X8 XM_017012739 XP_016868228 6816 2189
TNRC18 isoform X9 XM_017012740 XP_016868229 6839 2094

Protein

The protein sequence provided by NCBI lists human TNRC18 having a length of 2968

ExPASy[11] predicts the isoelectric point and molecular weight for the TNRC18 to be 8.88 and 315 kDa respectively. Additionally, the NCBI protein sequence for TNRC18 contains nine phosphorylation sites on TNRC18, eight phosphoserines and one phosphothreonine
. There is a large serine repeat upstream of the BAH site located from amino acid positions 2604–2670. The BAH site is located on position 2816–2960.

The predicted secondary structure for TNRC18 consists of 32.61% alpha helix, 6.74% extended strand, and 60.55% random coil. This was found using the GOR4 program available at PRABI-Lyon-Gerland with the NCBI protein sequence for TNRC18.[12][13]

Expression

RNA sequencing of TNRC18 tissue samples found ubiquitous gene expression. Most prominent expression was observed within the colon, kidney, and prostate tissue samples. In fetal human tissue samples, notable expression was found in the stomach, lung, and brain. RNA sequencing data was acquired though the TNRC18 gene expression page found on NCBI.[14]

The Human Protein Atlas shows highest RNA expression of TNRC18 in the brain, endocrine tissue, and muscle tissue. Additionally, the highest protein expression is observed in the brain, endocrine tissue, lung, gastrointestinal tract, and male and female specific tissues. Conversely, there is no protein expression in the eye or blood tissue, yet ubiquitous RNA expression for TNRC18.[15]

TNRC18 expression in mouse brain can be found below. Noteworthy expression is observed in the olfactory bulb, isocortex, and cerebellar cortex shown in color. This image and brain atlas information is provided by the Allen Institute Brain Atlas.[16][17]

Mus musculus brain. Expression is observed in the olfactory bulb, isocortex, and cerebellar cortex (see color). This image is provided by the Allen Institute Brain Atlas.[17]

Homology

NCBI Protein BLAST search for reference proteins lists the following orthologs for human TNRC18. The table is ordered first by increasing estimated date of divergence from humans in millions of years (MYA) and then by highest-to-lowest sequence identity with humans. Date of divergence information was acquired from TimeTree[18] and sequence identify and similarity percentages were found by a pairwise sequence alignment using the European Bioinformatics Institute (EMBL-EBI) EMBOSS Needle program.[19]

Orthologs for
Homo sapiens
 TNRC18 gene
Species Common name NCBI Protein Accession Date of Divergence (MYA) Sequence Identity with Humans (%) Sequence Similarity with Humans (%) Length (aa)
Homo Sapiens Human NP_001073964 0 100 100 2968
Pongo abelii Sumatran orangutan XP_024097037 15.76 98.6 98.9 2964
Nomascus leucogenys Northern white-cheeked gibbon XP_030652734 19.8 98.4 98.8 2965
Ictidomys tridecemlineatus Thirteen-lined ground squirrel XP_021575654 90 85.3 88.2 2924
Rattus norvegicus Brown Rat NP_001100593 90 81.4 85.6 2900
Acinonyx jubatus Cheetah XP_026898111 96 87.5 89.9 2972
Orcinus orca
 		Killer whale XP_012388176 96 87.3 89.8 2967
Lynx canadensis Canada lynx XP_030156810 96 87.3 89.8 2966
Enhydra lutris kenyoni Sea otter XP_022356606 96 86.8 89.6 2999
Odocoileus virginianus texanus White-tailed deer XP_020730376 96 86.2 89.1 2939
Ursus arctos horribilis Grizzy Bear XP_026371323 96 82.1 85 3111
Haliaeetus leucocephalus Bald Eagle XP_010568620 312 58.7 69.4 2928
Apteryx rowi Okarito kiwi XP_025939070 312 58.7 69.3 2932
Pogona vitticeps Central bearded dragon XP_020658091 312 54.7 65.7 2943
Python bivittatus Burmese python XP_015744874 312 53.6 65 2872
Perca flavescens Yellow perch XP_028454308 435 39.1 50.5 3044
Amphiprion ocellaris Ocellaris clownfish XP_023150301 435 39 50 3071
Branchiostoma belcheri Lancelet XP_019646059 684 25.6 36.5 2799
Saccoglossus kowalevskii Acorn worm XP_002738509 684 23.6 34.8 3174
Crassostrea virginica Eastern oyster XP_022319473 797 21 31.6 2200

Predicted post-translational modifications and motifs

The following post-translational modifications and motifs are predicted for TNRC18 and found on the ExPASy Proteomics page.[20] Exception to GPS-MSP methylation program which is found on The Cuckoo Workgroup site.[21] This list is not conclusive of the total post-translational modifications or motifs associated with TNRC18 and is solely based on software predictions.

Of the predicted post-translational modifications, there are 92 O-Linked β-N-acetylglucosamine (O-ß-GlcNAc) sites with a high scoring threshold (>=0.5), 23 Sumoylation sites, two palmitoylation sites, one methylation site, and 52 glycation sites. Additionally, GPS 5.0 predicted 22,317 phosphorylation sites on TNRC18. The program was used to confirm the nine phosphorylation sites found on the NCBI protein page for TNRC18.

Predicted post-translational modifications and motifs for TNRC18
Program Predicted post-translational modification Amino Acid location on protein
YinOYang
O-ß-GlcNAc
 80, 185, 199, 352, 416, 626, 627, 640, 788, 991, 995, 1033, 1038, 1533, 1753, 1956, 2023, 2368, 2404, 2510, 2557, 2559–2573, 2611, 2614–2667, 2721, 2892
GPS-SUMO (SUMOsp) Archived 2019-02-17 at the Wayback Machine Sumoylation 238-242, 467, 620, 652, 858–862, 1159, 1258, 1461, 1544, 1629, 1638, 1704, 1743, 1885–1889, 1893, 1898, 1899, 2098, 2213–2217, 2259–2263, 2463, 2542, 2964-2968
CSS-Palm Archived 2009-02-15 at the Wayback Machine Palmitoylation 284, 1196
GPS-MSP Methylation 2332
GPS 5.0 Phosphorylation Phosphorylation 263, 611, 1127, 1136, 1540, 1857, 1863, 2146, 2771
NetGlycate Glycation 156, 197, 270, 272, 429, 492, 548, 609, 652. 692, 749, 755, 938, 988, 1058, 1059, 1131, 1370, 1461, 1470, 1503, 1554, 1558, 1577, 1615, 1618, 1791, 1797, 1893, 1895,

1898, 1899, 1933, 1967, 1978, 2028, 2091, 2301, 2315, 2328, 2388, 2438, 2475, 2519, 2702, 2709, 2720, 2750, 2801, 2816, 2857, 2869

Eukaryotic Linear Motif (ELM) Coiled-Coil region 916-949, 1481-1516

Clinical significance

Shen et al. observed circTNRC18 inhibiting miR-762 activity within pre-eclampsia (PE) placenta tissue samples.[22] The inhibition of miR-762 by circTNRC18 resulted in elevated Grhl2 protein levels. PE placenta samples were observed to have lower miR-762 levels and higher Grhl2 levels which was attributed to overexpression of circTNRC18. Shen et al. conclude that circTNRC18 was upregulated in PE placentas when compared with normal pregnancy placentas.

Chu et al. found that from 19

ANKRD11, PQLC2, and PRPF8
. Chu et al. conclude that epigenetic variation may be associated with CKD.

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000182095 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000039477 – 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. ^ "Entrez Gene: Trinucleotide repeat containing 18". Retrieved 2016-10-22.
  6. ^ a b "trinucleotide repeat-containing gene 18 protein [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-05-01.
  7. ^ "InterPro". www.ebi.ac.uk. Retrieved 2020-05-01.
  8. ^ "Human hg38 chr7:5,306,800-5,423,546 UCSC Genome Browser v397". genome.ucsc.edu. Retrieved 2020-05-03.
  9. ^ "TNRC18 Gene - GeneCards | TNC18 Protein | TNC18 Antibody". www.genecards.org. Retrieved 2020-05-01.
  10. ^ "TNRC18 trinucleotide repeat containing 18 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-05-01.
  11. ^ "ExPASy - Compute pI/Mw tool". web.expasy.org. Retrieved 2020-05-01.
  12. ^ NPS@: Network Protein Sequence Analysis TIBS 2000 March Vol. 25, No 3 [291]:147-150 Combet C., Blanchet C., Geourjon C. and Deléage G.
  13. ^ "NPS@ : GOR4 secondary structure prediction". npsa-prabi.ibcp.fr. Retrieved 2020-05-03.
  14. ^ "TNRC18 Gene Expression - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-05-03.
  15. ^ "Tissue expression of TNRC18 - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2020-05-03.
  16. ^ "Interactive Atlas Viewer :: Atlas Viewer". atlas.brain-map.org. Retrieved 2020-05-03.
  17. ^ a b "Experiment 73424495 Tnrc18 - RP_051019_04_A01 - sagittal". Allen Institute Brain Atlas. © 2020 Allen Institute for Brain Science. Allen Human Brain Atlas. Available from: human.brain-map.org. Retrieved 3 May 2020.
  18. ^ "TimeTree :: The Timescale of Life". www.timetree.org. Retrieved 2020-05-03.
  19. ^ "EMBOSS Needle < Pairwise Sequence Alignment < EMBL-EBI". www.ebi.ac.uk. Retrieved 2020-05-03.
  20. ^ "ExPASy: SIB Bioinformatics Resource Portal - Categories". www.expasy.org. Retrieved 2020-05-03.
  21. ^ "GPS-MSP - Methyl-group Specific Predictor 1.0". msp.biocuckoo.org. Retrieved 2020-05-03.
  22. PMID 31354028
    .
  23. PMID 29097680
    .
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