Biology:C14orf119

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

C14orf119 is a protein that in humans is encoded by the c14orf119 gene. The c14orf119 protein is predicted to be localized in the nucleus.[1] Additionally, c14orf119 expression is decreased in individuals with systemic lupus erythematosus (SLE) when compared with healthy individual and is increased in individuals with various types of lymphomas when compared to healthy individuals.[2][3]

Gene

The common aliases of c14orf119 are chromosome open reading frame 119 and My028.[4] The gene is located on chromosome 14, with the specific location of 14q11.2.[5] It contains two exons and covers 5.76 kb, from 23563900 to 23569660 on the forward strand.[6] The span of the c14orf119 gene, from the start of transcription to the polyA site, is 4951 basepairs in length.[7]

Transcripts

The c14orf119 mRNA is composed of 2914 basepairs.[5] C14orf119 has two isoforms, shown in the table below.

C14orf119 Isoforms[8]
Name Accession Number[9] Transcript ID Length
C14orf119-201 NM_017924.4 ENST00000319074.6 2914 nt
C14orf119-202 XM_017021390.2 ENST00000554203.1 725 nt

Protein

The c14orf119 protein is composed of 140 amino acids.[10] The molecular weight of the c14orf119 protein is approximately 16 kDa and the basal isoelectric point is 4.86.[11] There is a long section of hydrophobic amino acids at the start of the protein.[12] There are no additional significant compositional features of the c14orf119 protein, including charge clusters, charge runs, patterns, repetitive structures or multiplets.[13] The primary sequence of the c14orf119 protein is as follows,

MPLESSSSMP LSFPSLLPSV PHNTNPSPPL MSYITSQEMK CILHWFANWS GPQRERFLED LVAKAVPEKL

QPLLDSLEQL SVSGADRPPS IFECQLHLWD QWFRGWAEQE RNEFVRQLEF SEPDFVAKFY QAVAATAGKD[14]

There are two known c14orf119 protein isoforms, as shown in the table below.

C14orf119 Protein Isoforms[15]
Name Accession Number Size Domain Inclusion
Uncharacterized c14orf119 protein NP_060394.1 140 aa DUF4508
Uncharacterized c14orf119 protein isoform X1 XP_016876879.1 140 aa DUF4508

Domains and motifs

There is a domain of unknown function (DUF) found in the c14orf119 protein: DUF4508 (with an E-value of 6.3e-36).[16] This DUF is a part of a family of proteins that is found in eukaryotes and is typically between 117 and 253 amino acids in length.[17] Additionally, there are three predicted CK2 phosphorylation sites (at positions 36, 83, and 121) within the c14orf119 protein.[18]

Figure 1. Phyre2 predicted secondary structure of the c14orf119 protein.[19]

Secondary structure

The predicted secondary structure of the c14orf119 protein is largely alpha helical in content. The specific makeup of the secondary structure is as follows, alpha helices make up 38.57% of the protein (54 amino acids), extended strands make up 23.57% of the protein (33 amino acids), and random coils make up 37.86% of the protein (53 amino acids).[20] Phryre2, a program for protein modeling, prediction, and analysis, was used to determine and model the predicted structure of the c14orf119 protein.[21] Shown in Figure 1, Phyre2 created a model for the predicted structure of 106 (out of a total of 140) residues of the c14orf119 protein, with 79.7% confidence and 76% coverage.[21]

Tertiary and quaternary structures

With only two cysteines, 52 amino acids apart, found in the c14orf119 protein sequence, there were no predicted disulfide bonds in the c14orf119 protein.[22][13] There are no predicted transmembrane regions or signal peptides in the c14orf119 protein.[23][24][25]

Gene level regulation

Promoter

The predicted promoter sequence associated with c14orf119 is 3332 bases in length.[26] This promoter sequence has one CpG island associated with it, with a CpG count of 78[26] Additionally, there are a number of transcription factor binding sites associated with this promoter sequence, such as RB1, HNF4A, ETS1, and RBL2.[27]

Expression pattern

C14orf119 is expressed in 203 organs.[28] The c14orf119 gene is expressed in a number of tissues and has the highest expression rates in cultured fibroblast cells, with a TPM of 75.63.[29] There is notable decreased expression of c14orf119 in the following tissues, pancreas, bone marrow, brain, salivary glands, and the liver.[15][30] Additionally, there is notable increased expression of c14orf119 in the adrenal gland, kidney, lung, prostate, thymus, white blood cells, lymph node, and thyroid.[15] Finally, expression levels of c14orf119 decrease with the development of the kidney and increases with development of the stomach.[15]

Transcript level regulation

There were no predicted enhancers associated with c14orf119.[27] There were a number of stem loop formation predictions in both the 5' UTR and 3' UTR of c14orf119.[31]

miRNA targeting

The miRNA binding sites found in the 3' UTR of c14orf119 include miR-489, miR-1872, and miR-4778-3p; however, there were no miRNA binding sites found in the 5' UTR of c14orf119.[32]

Protein level regulation

Subcellular localization

The c14orf119 protein is predicted to be located in the nucleus, with a reliability score of 55.5.[1] However, the protein has a 7.9% basic residue content and a nuclear localization signal (NLS) score of -0.47.[33] Additionally, there was a predicted ER retention motif at positions 136-139 of the protein.[33] Finally, there were no N-terminal signal peptides, no cleavage sites for mitochondria, no actinin-type actin-binding motifs, and no N-myristolyation pattern.[1]

Figure 2. Conceptual translation of c14orf119, which reveals predicted post-translational modifications.[34][35][36][37][38][39]

Post-translational modifications

There are a number of post-translational modifications of the c14orf119 protein, all of which are shown on the conceptual translation of c14orf119 in Figure 2.

There are predicted ubiquitination sites at lysine residues at positions 128 and 139.[40]

There are predicted kinase-specific phosphorylation sites at serines at the following position in the c14orf119 protein sequence, 15, 19, 27, 32, 36, 81, 83, 90, and 121.[39][41] Protein phosphorylation at serine residues can play critical roles in the regulation of protein function and the transmission of signals throughout the cell.[42]

There are two N-glycosylation sites at positions 25-27 and 48–50.[38] This type of post-translational modification plays important roles in both the structure and function of some eukaryotic proteins.

Additionally, there are predicted glycation of epsilon amino groups of lysines at the following positions, 40, 64, 69, and 139.[37] Glycation is a process in which proteins react with reducing sugar molecules, which ultimately impairs the function and changes the characteristics of the protein.[43]

There are also predicted mammalian mucin type GalNAc-O-glycosylation sites at the following positions, 5, 6, 7, 12, 15, 19, and 24.[36] GalNAc-type-O-glycosylation is the attachment of a sugar molecule to the oxygen atom of serine or threonine residues in a protein.[44] O-glycans or the sugars added to the serine or threonine, have various functions, including allowing recognition of foreign material, providing cartilage and tendon flexibility, controlling cell metabolism, and trafficking cells in the immune system.[45]

There is a predicted SUMOylation sites at the lysine at position 139.[35] SUMOylation is involved in transcriptional regulation, protein stability, apoptosis, nuclear-cytosolic transport, progression through the cell cycle, and response to stress.[46]

Finally, there are predicted O-GlcNAc sites at the serines at the following position in the c14orf119 protein, 5, 6, 7, 8, and 83.[34] This post-translational modification can play various critical roles such as, progression through the cell cycle, response to cellular stress, protein turnover, and protein stability.[47]

Regulation of expression

Epigenetic

There are varying levels of H3K27ac, H3K4me1, and H3K4me3 throughout the c14orf119 gene.[27] H3K4me1 has variation in signal strength among different cell lines, which may reflect differences of epigenetic landscapes in these cell lines.[27] Additionally, there is a strong signal of H3K27ac across the majority of cell lines along the predicted promoter region.[27] Finally, there is also a strong signal of H3K4me3 across the majority of the cell types along the predicted promoter region, with no signal variation across cell types.[27]

Figure 3. Date of divergence graph for c14orf119, with comparison to hemoglobin, fibrinogen alpha chain, and cytochrome c.

Homology/evolution

C14orf119 is conserved in both vertebrates and invertebrates, however, it is not conserved in bacteria, archaea, trichoplax, plants or fungi.[48] The c14orf119 gene is highly conserved in the mammalian orthologs, however, within the non-mammalian orthologs, there are various insertions, especially at the beginning and end of the gene.[48] This gene does not contain any paralogs or paralogous domains.[48]

As shown in Figure 3, the c14orf119 gene has evolved moderately quickly when compared to cytochrome c, fibrinogen alpha chain, and hemoglobin. It has evolved faster than both hemoglobin and cytochrome c, but slower than fibrinogen alpha chain.

The table below reveals the various orthologs of the c14orf119 protein. This table includes the date of divergence (DoD) from humans, in million years ago (MYA), accession number, and percent identity and similarity to humans for each ortholog.

C14orf119 Orthologs
Genus and Species Common Name Taxonomy - Class Taxonomy - Order DoD (MYA) Accession Number Sequence Length (aa) Percent Identity Percent Similarity
Homo sapiens Human Mammalia Primates 0 NP_060394.1 140 100 100
Mus musculus Mouse Mammalia Rodentia 89 NP_067412.1 142 83.1 90.1
Myotis brandtii Brandt's Bat Mammalia Chiroptera 94 XP_005852873.1 141 86.5 90.8
Callorhinus ursinus Northern Fur Seal Mammalia Carnivora 94 XP_025726115.1 142 88 91.5
Bos taurus Cattle Mammalia Artiodactyla 94 XP_002690553.1 142 88 92.3
Orycteropus afer afer Aardvark Mammalia Tubulidentata 102 XP_007949377.1 140 85.1 89.4
Python bivittatus Burmese Python Reptilia Squamata 318 XP_007441564.1 156 47.8 60.2
Podarcia muralis Common Wall Lizard Reptilia Squamata 318 XP_028559108.1 115 51.8 63.8
Nanorana parkeri High Himalaya Frog Amphibia Anura 351.7 XP_018411628.1 115 45.7 60.7
Larimichthys crocea Marine Fish Actinopterygii Perciformes 433 XP_010740478.3 201 34.5 44.3
Aethina tumida Small Hive Beetle Insecta Coleoptera 736 XP_019869014.1 124 18.6 39.7
Bombus terrestris Buff-Tailed Bumblebee Insecta Hymenoptera 736 XP_020718687.1 125 19 36.1
Photinus pyraliis Common Eastern Firefly Insecta Coleoptera 736 XP_031358233.1 128 19.9 40.4
Pieris rapae Cabbage White Butterfly Insecta Lepidoptera 736 XP_022116245.1 180 20 38.4
Nasonia vitripennis Small Parasitoid Wasp Insecta Hymenoptera 736 XP_031785555.1 121 22.4 42.1
Biomphalaria glabrata Freshwater Snail Gastropoda Basommatophora 736 XP_013090201.1 113 31.7 46.2
Aplysia californica California Seahorse Gastropoda Anaspidea 736 XP_005112416.1 112 32.6 47.9

Function/biochemistry

The function of the c14orf119 protein is not yet well understood by the scientific community.

Interacting proteins

There are a number predicted interacting proteins found in Y2H screens, such as exportin 1 (XPO1), ras homolog family member U (RHOU), deoxyhypusine hydroxylase/monooxygenase (DOHH), hepatocyte nuclear factor 4, alpha (HNF4A), leukocyte receptor cluster member 1 (LENG1), and ubiquitin C (UBC).[49][50][51]

Clinical significance

Disease association

Expression of c14orf119 is decreased in individuals with systemic lupus erythematosus (SLE) when compared with healthy individuals.[2] Furthermore, expression of c14orf119 is increased in individuals with various types of lymphomas when compared to healthy individuals.[3]

References

  1. ↑ 1.0 1.1 1.2 "PSORT II page for c14orf119". https://psort.hgc.jp/cgi-bin/runpsort.pl. [yes|permanent dead link|dead link}}]
  2. ↑ 2.0 2.1 "NCBI GEO Profile for record GDS4889, c14orf119". https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS4889:223060_at. 
  3. ↑ 3.0 3.1 "NCBI GEO Profile for record GDS3516, c14orf119.". https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS3516:223060_at. 
  4. ↑ "C14orf119 Gene (Protein Coding)". https://www.genecards.org/cgi-bin/carddisp.pl?gene=C14orf119#transcripts. 
  5. ↑ 5.0 5.1 "C14orf119 chromosome 14 open reading frame 119 [ Homo sapiens (human) "]. https://www.ncbi.nlm.nih.gov/gene/55017. 
  6. ↑ "Homo sapiens gene C14orf119, encoding chromosome 14 open reading frame 119". https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=c14orf119&submit=Go. 
  7. ↑ "Genome Data Viewer". https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=55017. 
  8. ↑ "Gene: C14orf119 ENSG00000179933". http://useast.ensembl.org/Homo_sapiens/Gene/Splice?db=core;g=ENSG00000179933;r=14:23095505-23100456. 
  9. ↑ "NC_000014.9 Chromosome 14 Reference GRCh38.p13 Primary Assembly". https://www.ncbi.nlm.nih.gov/gene/55017. 
  10. ↑ "uncharacterized protein C14orf119 [Homo sapiens - Protein - NCBI"]. https://www.ncbi.nlm.nih.gov/protein/NP_060394.1. 
  11. ↑ "Uncharacterized protein C14orf119". https://www.phosphosite.org/proteinAction?id=14198&showAllSites=true#appletMsg. 
  12. ↑ "Statistical Analysis of Protein Sequences, Compositional Analysis - c14orf119". https://www.ebi.ac.uk/Tools/services/web/toolresult.ebi?jobId=saps-I20200331-144354-0169-6968840-p1m. 
  13. ↑ 13.0 13.1 "Statistical Analysis of Protein Sequences, Compositional Analysis, c14orf119.". https://www.ebi.ac.uk/Tools/services/web/toolresult.ebi?jobId=saps-I20200331-144354-0169-6968840-p1m. 
  14. ↑ "uncharacterized protein C14orf119 [Homo sapiens"]. https://www.ncbi.nlm.nih.gov/protein/NP_060394.1?report=fasta. 
  15. ↑ 15.0 15.1 15.2 15.3 "C14orf119 chromosome 14 open reading frame 119 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/55017. 
  16. ↑ "MotifFinder page for c14orf119 protein". https://www.genome.jp/tools-bin/search_motif_lib. 
  17. ↑ "Pfam: DUF4508". https://www.genome.jp/dbget-bin/www_bget?pfam:DUF4508. 
  18. ↑ "MyHits Motif Scan page for c14orf119 protein.". https://myhits.isb-sib.ch/cgi-bin/motif_scan. 
  19. ↑ "Phyre 2 Results for c14orf119". http://www.sbg.bio.ic.ac.uk/phyre2/phyre2_output/3d7e0d6c7ae74052/summary.html. 
  20. ↑ "GOR page for c14orf119 protein.". https://npsa-prabi.ibcp.fr/cgi-bin/secpred_gor4.pl. 
  21. ↑ 21.0 21.1 "Phyre 2 Results for c14orf119". http://www.sbg.bio.ic.ac.uk/phyre2/phyre2_output/3d7e0d6c7ae74052/summary.html. 
  22. ↑ "DISULFIND - Cysteines Disulfide Bonding State and Connectivity Predictor". http://disulfind.dsi.unifi.it/monitor.php?query=f5jIqy. 
  23. ↑ "CCTOP - c14orf119 protein". http://cctop.enzim.ttk.mta.hu/?_=/jobs/result/786fcd53236503ac626ea64b7d33e376. 
  24. ↑ "DAS-TMfilter prediction results". http://mendel.imp.ac.at/sat/DAS/cgi-bin/das.cgi. 
  25. ↑ "SignalP-5.0". http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=5EADC3D40000794ABA9A52B9&wait=20. 
  26. ↑ 26.0 26.1 "Human hg38 chr14:23,093,525-23,098,476 UCSC Genome Browser v397". https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=chr14:23093525-23098476&hgsid=823331693_9u117hzsmpcdEEInN0IaJJIIUj44. 
  27. ↑ 27.0 27.1 27.2 27.3 27.4 27.5 "UCSC Genome Browser page for c14orf119". https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=chr14%3A23093525%2D23098476&hgsid=823331693_9u117hzsmpcdEEInN0IaJJIIUj44. 
  28. ↑ [1]. "Uncharacterized Protein c14orf119"]. https://www.uniprot.org/uniprot/Q9NWQ9].. 
  29. ↑ [2]. "Gene Expression for c14orf119"]. https://gtexportal.org/home/gene/C14ORF119].. 
  30. ↑ "GDS3113 / 161646". https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS3113:161646. 
  31. ↑ "Sfold - Software for Statistical Folding and Studies of Regulatory RNAs". http://sfold.wadsworth.org/cgi-bin/index.pl. 
  32. ↑ "miRDB - MicroRNA Target Prediction Database". http://mirdb.org/. 
  33. ↑ 33.0 33.1 "PSORT II - c14orf119". https://psort.hgc.jp/cgi-bin/runpsort.pl. [yes|permanent dead link|dead link}}]
  34. ↑ 34.0 34.1 "YinOYang page for c14orf119 protein". http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=5E8F5AFB000004AC7D078BFC&wait=20. 
  35. ↑ 35.0 35.1 "SUMOsp page for c14orf119 protein.". http://sumosp.biocuckoo.org/showResult.php. 
  36. ↑ 36.0 36.1 "NetOGlyc page for c14orf119 protein". http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=5E8F282400002281D099295D&wait=20. 
  37. ↑ 37.0 37.1 "NetGlycate page for c14orf119 protein". http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=5E8F258E00000BC611D5F9C1&wait=20. 
  38. ↑ 38.0 38.1 "NetNGlyc - c14orf119". http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=5EA885390000399B26EB3FB0&wait=20. 
  39. ↑ 39.0 39.1 "GPS page for the c14orf119 protein". http://gps.biocuckoo.cn/wsresult.php. 
  40. ↑ "Proteins for C14orf119 Gene". https://www.genecards.org/cgi-bin/carddisp.pl?gene=C14orf119#transcripts. 
  41. ↑ "NetPhos - c14orf119". http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=5E8F2BDC00001D5E85044D1C&wait=20. 
  42. ↑ "Sequence and structure-based prediction of eukaryotic protein phosphorylation sites". Journal of Molecular Biology 294 (5): 1351–1362. December 1999. doi:10.1006/jmbi.1999.3310. PMID 10600390. 
  43. ↑ "Analysis and prediction of mammalian protein glycation". Glycobiology 16 (9): 844–853. September 2006. doi:10.1093/glycob/cwl009. PMID 16762979. 
  44. ↑ "Precision mapping of the human O-GalNAc glycoproteome through SimpleCell technology". The EMBO Journal 32 (10): 1478–1488. May 2013. doi:10.1038/emboj.2013.79. PMID 23584533. 
  45. ↑ "O-linked protein glycosylation structure and function". Glycoconjugate Journal 13 (1): 19–26. February 1996. doi:10.1007/BF01049675. PMID 8785483. 
  46. ↑ "SUMO: a history of modification". Molecular Cell 18 (1): 1–12. April 2005. doi:10.1016/j.molcel.2005.03.012. PMID 15808504. 
  47. ↑ "Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease". Annual Review of Biochemistry 80 (1): 825–858. July 7, 2011. doi:10.1146/annurev-biochem-060608-102511. PMID 21391816. 
  48. ↑ 48.0 48.1 48.2 "BLAST: Basic Local Alignment Search Tool". https://blast.ncbi.nlm.nih.gov/Blast.cgi. 
  49. ↑ "C14orf119 (My028) Result Summary | BioGRID". https://thebiogrid.org/120349/summary/homo-sapiens/c14orf119.html. 
  50. ↑ al, David Lynn et. "InnateDB: Systems Biology of the Innate Immune Response". https://www.innatedb.com/interactionSearch.do?listType=interaction&participantField=idphysical_molecule&participantKeyword=3095. 
  51. ↑ "Results - mentha: the interactome browser". http://mentha.uniroma2.it/result.php#c14orf119. 



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