C19orf67
UPF0575 protein C19orf67 is a
Gene
In humans, C19orf67 is located on the minus strand of
The following genes are found near C19orf67 on the positive strand:[1]
- MISP3
- Eukaryotic Translation Elongation Factor 1 Delta Pseudogene 1 (EEF1DP1)
- MicroRNA 1199 (MIR1199)
The following genes are found near C19orf67 on the minus strand:[1]
mRNA transcript
C19orf67 has three transcript variants, although the second and third variants are only predicted by an Ensembl analysis and not experimentally confirmed.[7] Only the first two variants are protein-coding transcripts.
The first transcript consists of 1447bp while the second and third have 751bp and 656bp respectively.[7] The mature mRNA of the longest isoform is made up from 6 exons.
Protein
The unmodified protein has 358 amino acids, predicted molecular weight of 40kDa, charge of -11, and isoelectric point of 5.[8][9] 44 prolines were found along the protein, making up 12.3% of the total amino acid sequence. The proline content by percentage was found to be higher in UPF0575 than 95% of comparable human proteins. However, the amount of asparagine the protein is less abundant when compared to the human proteome.[9]
Domains
Both isoforms contain DUF3314. Although the function is not yet well understood, conservation among numerous taxa indicate that it may be important to the function of the protein.[2][10] The first isoform has a non-repeating proline-rich region from amino acids 12 to 80.[11] The function of the region is not well understood but it may be involved in preventing helices from forming due to the rigid structure of proline.[12]
Secondary structure
A cross-program consensus predicted that UPF0575 protein C19orf67 forms four alpha helices and two beta sheets in the following locations in the amino acid sequence:[13][14]
Helix | 52-62 | 90-108 | 115-125 | 153-180 |
Sheet | 193-202 | 210-217 |
Post-translational modifications
Acetylation is likely to occur at the N-terminus while the C-terminus is unlikely to be modified.[15][16] O-Glycosylation is predicted to occur at amino acids 18 and 67. Several possible phosphorylation sites were identified along with the associated kinases:[17][18]
Location | Amino acid | Kinase |
---|---|---|
67 | Serine | cdk5 |
127 | Threonine | PKC |
169 | Threonine | PKC |
196 | Serine | cdc2
|
204 | Serine | PKA |
299 | Tyrosine | SRC |
346 | Serine | PKA/PKG |
Subcellular localization
UPF0575 protein C19orf67 is expected to be targeted in the nucleus, specifically the nucleolus.[19][20]
Expression and regulation
Regulation of gene expression
The promoter region is predicted to start 1,303 bp upstream from the 5' UTR and consist of 1,447 bp, causing 144 bp to overlap with the 5' UTR.[21]
A number of transcription factors such as FOXP1, SOX5, SOX6, SOX4, and MZF1 are likely to bind with the promoter, often acting to downregulate transcription. When regarding the expression of other genes, these transcription factors typically play a role in the development of various tissues such as the heart, lung, and also take part in the differentiation of early embryonic cells, and red blood cells.
Transcriptional regulation
It is suspected that the mature mRNA of C19orf67 forms a stem loop on the 3' UTR that spans from 1,296bp to 1,350bp of the transcript.[22]
Tissue expression
In humans, UPF0575 protein C19orf67 is highly expressed in the testis and breast tissue, although it is also expressed at low levels in the stomach, cerebral cortex, thyroid gland, and salivary gland.[8][4][5]
The protein product is less abundant than most of the human proteome in many tissues.[23]
Homology
Paralogs
There are no known
Orthologs
Orthologs of UPF0575 protein C19orf67 were found to be present among a wide variety of mammals with it being particularly well represented in rodentia and primates. Orthologs were also found in each reptilian order but were much more scarce in presence relative to mammals.[2][3] A high number and variety of ray-finned fishes were found to have orthologs while there were fewer cartilaginous fish found to have orthologs; no jawless fish could be found with orthologs.[2]
No orthologs are known to be present in birds or amphibians. No invertebrates, fungi, bacteria, or lower species have known orthologs.
BLAT and BLAST were used to create following table as a sample ortholog space for UPF0575 protein C19orf67.[2][3][24][25] This table is not a complete list of orthologs, it is meant to display the span in which there are orthologs and the diversity of those species.
Genus and species | Common name | Accession number | Order | Divergence (MYA) | Sequence length | Identity | Similarity |
---|---|---|---|---|---|---|---|
Homo sapiens | Human | NP_001264307 | Primate | 0 | 358 | -- | -- |
Galeopterus variegatus | Sunda Flying Lemur | XP_008564240.1 | Dermoptera | 82 | 358 | 85% | 89% |
Miniopterus natalensis | Long-fingered bat | XP_016077689.1 | Chiroptera | 94 | 356 | 84% | 89% |
Ursus maritimus | Polar bear | XP_008709937.1 | Carnivores | 94 | 358 | 85% | 89% |
Mus musculus | House mouse | NP_898920.2 | Rodentia | 88 | 300 | 71% | 74% |
Gekko japonicus | Gekko | XP_015270669.1 | Squamata | 320 | 331 | 49% | 63% |
Chelonia mydas | Green Turtle | XP_007069233.1 | Testudinata | 320 | 345 | 49% | 61% |
Alligator mississippiensis | American alligator | XP_019353135.1 | Crocodilia | 320 | 297 | 45% | 57% |
Latimeria chalumnae | West Indian Coelacanth | XP_005995930.1 | Coelacanthiformes | 440 | 414 | 37% | 50% |
Salmo salar | Atlantic Salmon | XP_013986580.1 | Salmoniformes | 432 | 336 | 35% | 45% |
Danio rerio | Zebrafish | NP_001083047.1 | Cypriniformes | 432 | 344 | 32% | 44% |
Pygocentrus nattereri | Red piranha | XP_017554468.1 | Characiformes | 432 | 348 | 32% | 43% |
Molecular evolution
UPF0575 protein C19orf67 consists of one family and there are no apparent duplications throughout the evolution of UPF0575 protein C19orf67.[2]
The DUF3314 region of the gene appears to have diverged at a slower rate relative to the rest of the gene, indicating that that region may have been undergoing purifying selection because that region played an important role in the protein.[2][24][25]
Clinical significance
In one case study, C19orf67 was one of 29 genes on chromosome 19 lost due to deletions caused by chromosomal rearrangements. The rearrangements resulted neural development issues and behavioral abnormalities, although it is not known whether C19orf67 played an active role in the resulting phenotypes.[26] In a different study, when a portion of chromosome 19 that also included C19orf67 was deleted, developmental issues such as Intrauterine growth restriction, premature birth, and muscular hypotonia, occurred.[27]
C19orf67, among many other genes, may be used as a possible marker to detect mature beta cells.[28]
References
- ^ a b c d "C19orf67 chromosome 19 open reading frame 67 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-03-02.
- ^ a b c d e f g h "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2017-03-02.
- ^ a b c d "Human BLAT Search". genome.ucsc.edu. Retrieved 2017-03-02.
- ^ a b github.com/gxa/atlas/graphs/contributors, EMBL-EBI Expression Atlas development team. "Expression Atlas < EMBL-EBI". www.ebi.ac.uk. Retrieved 2017-05-07.
{{cite web}}
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has generic name (help) - ^ a b "77903326 - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 7 May 2017.
- PMID 15057824.
- ^ a b c "Transcript: C19orf67-001 (ENST00000548523) - Domains & features - Homo sapiens - Ensembl genome browser 83". dec2015.archive.ensembl.org. Retrieved 2017-03-02.
- ^ a b "Tissue expression of C19orf67 - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2017-03-02.
- ^ PMID 1549558.
- ^ "Pfam: Family: DUF3314 (PF11771)". pfam.xfam.org. Retrieved 2017-03-02.
- ^ "Database of protein domains, families and functional sites". ExPASy. Retrieved 2017-02-27.
- PMID 8297327.
- PMID 27131380.
- PMID 4358940.
- ^ Charpilloz, Jean-Luc Falcone & Christophe. "TERMINUS - Welcome to terminus". terminus.unige.ch. Retrieved 2017-04-24.
- PMID 15691858.
- PMID 10600390.
- S2CID 18810164.
- ^ "PSORT II server - GenScript". www.genscript.com. Retrieved 2017-04-27.
- PMID 17993650.
- ^ "Genomatix - NGS Data Analysis & Personalized Medicine". www.genomatix.de. Archived from the original on 24 February 2001. Retrieved 7 May 2017.
- ^ "The Mfold Web Server | mfold.rit.albany.edu". unafold.rna.albany.edu. Retrieved 2017-05-07.
- ^ "C19orf67 protein abundance in PaxDb". pax-db.org. Retrieved 2017-04-30.
- ^ a b EMBL-EBI. "EMBOSS Needle < Pairwise Sequence Alignment < EMBL-EBI". www.ebi.ac.uk. Retrieved 2017-03-02.
- ^ a b "TimeTree :: The Timescale of Life". www.timetree.org. Retrieved 2 March 2017.
- PMID 22419660.
- PMID 20466091.
- ^ US 20140329704, Melton, Douglas A. & Hrvatin, Sinisa, "Markers for mature beta-cells and methods of using the same", published Nov 6, 2014