Biology:Chromosome 4 open reading frame 54

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Short description: Chromosome 4 open reading frame 54 gene

Chromosome 4 open reading frame 54 is a protein that in humans is coded by the c4orf54 gene.[1][2] This gene is also known as FOPV (Familial Obliterative Portal Venopathy) and LOC285556. This protein is mostly expressed in the nucleus of muscle cells.[1] Orthologs are found in vertebrates but not invertebrates.

Gene

Human chromosome 4 open reading frame 54(c4orf54) is made up of 10451 nucleotides from chromosome 4, map 4q23(chr4:99,636,529-99,657,828), on the complement strand. The mRNA of c4orf54(NM_001354435) is made up of 3 exons.

Location of C4orf54 on human chromosome 4

Gene Expression

Human cells treated with c4orf54 rabbit antibodies. Green is target protein and blue is nucleus. Expression is intracellular, in the cytosol with pockets of concentrated expression in the nucleus.

Within cells, c4orf54 is primarily expressed in the nucleus with a.[3][4] An analysis of unknown type of human cells treated with an antibody for c4orf54 showed that there is some expression in the nucleus but is primarily in the cytoplasm.[4] C4orf54 is expressed in muscle cells such as biceps and bone, as well as some glands.[1]

Regulation of expression

On the 5'UTR of the c4orf54 gene, there are several transcription factors that have to do with leucine zippers and they bind to the same 11 nucleotides: FOS, BATF::JUN, BATF3, and BATF.

Transcript

Exon 2 is the only exon transcribed. There is also the X1 variant of this gene. The 5' UTR is shorter than the main variant.

Protein

Expression from four datasets for the human c4orf54 gene from sequencing RNA. The highest RNA expression is from skeletal muscle from all four sets but the results vary.
C4orf54 mRNA expression using microarray data on patients with normal tissues. The tissues with highest expression are from the cervix, lymph nodes, skin, and thyroid.
C4orf54 mRNA expression using microarray data on patient biceps with infantile-onset Pompe disease.The control samples have higher levels of expression than those with Pompe disease.
C4orf54 mRNA expression using microarray data on patient bone biopsies before and after surgery with Endogenous Cushing’s Syndrome. Expression is slightly increased overall post-surgery.
C4orf54 mRNA expression using microarray data on patients with SOX11 depletion. The control has significantly higher expression.

C4orf54 human protein is made up of 1793 amino acids. This unmodified form has a predicted molecular weight of approximately 190 kDal and a predicted isoelectric point of 9.11. This mass is concurrent with results from OMIM. The more enriched protein compared to other human proteins was serine(12.9%) and the pattern of serine then threonine was also highly enriched comparatively at 19.1%. This aligns with the results found from Motif Scan that the amino acid sequence is serine rich from amino acids 237 to 312. There is significant expression in smooth muscle tissue. There is a domain of unknown function.

Post-translational modifications

The c4orf54 protein is myristylated with over 20 predicted sites.[5] There is also significant phosphorylation with 2 experimentally proven sites and over 50 predicted sites.[2] One methylation site was found experimentally.

Structure

Alpha Fold Tertiary c4orf54 structure with high confidence zoomed in on. Color key for model confidence in lower right corner.

An analysis of the structure using Alpha Fold shows both alpha helices and beta sheets with 70% or more model confidence.[6] The alpha helices have an overall higher higher model confidence.

Function

FOPV has been found to interact with 3 other proteins: BTF3, CUL4A, and KRAS.[7] This protein may have lethal interactions with the Ras Oncogene.[8] There may be an association between mutations in the FOPV gene and Obliterative portal venopathy which is lesions in portal vein branches in the liver.[9]

Orthologs

C4orf54 was found in vertebrates but not invertebrates. The most distant species found using NCBI BLAST with protein c4orf54 was Petromyzon marinus, the sea lamprey, which had the last common ancestor with humans around 600 million years ago with a sequence identity of 26.3%. This is also an estimate of when the c4orf54 gene emerged. The closest non primate relative is from about 87 million years ago with a sequence identity similarity to the human protein of 86.6%.

c4orf54 Genus and Species Common Name Taxonomic Group Median Date of Divergence (MYA) Accession # Sequence Length (aa) Query Cover (%) Sequence Identity to Human Protein (%) Sequence Similarity to Human Protein (%) Corrected Divergence
Mammal Homo sapiens Human Primates 0 NP_001341364.1 1793 100 100 100.0 0.00
Mus musculus House Mouse Rodentia 87 NP_001357791.1 1786 96 86.94 86.6 14.25
Neosciurus carolinensis Eastern Grey Squirrel Rodentia 87 XP_047423506.1 1786 100 86.72 90.8 14.25
Felis catus House Cat Carnivora 94 XP_006931007.1 1801 100 84.71 89.8 16.59
Reptilia Trachemys scripta elegans Red-eared Slider Testudines 319 XP_034627307.1 1670 79 51.47 57.9 66.42
Terrapene carolina triunguis Three-toed Box Turtle Testudines 319 XP_024067528.1 1553 79 51.58 54.8 66.20
Pantherophis guttatus Corn Snake Squamata 319 XP_034298051.1 1505 66 51.45 49.1 66.46
Chelonia mydas Green Sea Turtle Testudines 319 XP_037752386.1 1553 79 51.10 54.4 67.14
Aves Catharus ustulatus Swainson's Thrush Passeriformes 319 XP_032915906.1 1472 79 47.05 51.4 75.40
Calypte anna Anna's hummingbird Apodiformes 319 XP_030306184.1 1540 79 46.95 51.7 75.61
Gallus gallus Red Junglefowl Galliformes 319 XP_040527126.1 1296 62 46.35 46.5 76.89
Amphibian Xenopus tropicalis Western Clawed Frog Anura 353 XP_004911157.2 1521 74 42.92 48.0 84.58
Rana temporaria Common Frog Ranidae 353 XP_040184421.1 1501 79 38.75 43.0 94.80
Geotrypetes seraphini Gaboon Caecilian Gymnophiona 353 XP_033813063.1 1303 58 38.15 43.0 96.36
Fish Chanos chanos Milkfish Gonorynchiformes 431 XP_030635043.1 1571 74 37.92 44.0 96.97
Megalops cyprinoides Oxeye Herring Elopiformes 431 XP_036406656.1 1612 79 37.82 45.1 97.23
Melanotaenia boesemani Boeseman's Rainbowfish Atheriniformes 431 XP_041840397.1 1505 73 35.83 43.1 102.64
Chiloscyllium plagiosum Whitespotted Bamboo Shark Orectolobiformes 464 XP_043530392.1 1237 52 48.25 37.3 72.88
Carcharodon carcharias Great White Shark Lamniformes 464 XP_041050558.1 1414 56 34.15 37.6 107.44
Petromyzon marinus Sea Lamprey Petromyzontiformes 599 XP_032825160.1 1482 27 31.20 26.3 116.48
Corrected Sequence Divergence v. Median Date of Divergence of c4orf54 orthologs.

References

  1. ↑ 1.0 1.1 1.2 "NCBI (National Center for Biotechnology Information) entry on C4orf54 chromosome 4 open reading frame 54 [ Homo sapiens (human)". https://www.ncbi.nlm.nih.gov/gene/285556. 
  2. ↑ 2.0 2.1 "NCBI (National Center for Biotechnology Information) entry on Homo sapiens chromosome 4 open reading frame 54 (C4orf54), mRNA". 8 June 2022. https://www.ncbi.nlm.nih.gov/nuccore/NM_001354435.2. 
  3. ↑ "Prediction of Protein sorting Signals and Localization Sites in Amino Acid Sequences(PSORT)". https://psort.hgc.jp/. 
  4. ↑ 4.0 4.1 "The Human Protein Atlas profile of c4orf54". https://www.proteinatlas.org/ENSG00000248713-C4orf54. 
  5. ↑ ExPasy Myristoylator [https://www.expasy.org/resources/myristoylator]
  6. ↑ "AlphaFold". https://alphafold.ebi.ac.uk/. 
  7. ↑ "NCBI (National Center for Biotechnology Information) entry on uncharacterized protein C4orf54 [Homo sapiens"]. https://www.ncbi.nlm.nih.gov/protein/1230839365. 
  8. ↑ Luo, J.; Emanuele, M. J.; Li, D.; Creighton, C. J.; Schlabach, M. R.; Westbrook, T. F.; Wong, K. K.; Elledge, S. J. (2009). "A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene". Cell 137 (5): 835–848. doi:10.1016/j.cell.2009.05.006. PMID 19490893. PMC 2768667. https://doi.org/10.1016/j.cell.2009.05.006. 
  9. ↑ Besmond, C; Valla, D; Hubert, L; Poirier, K; Grosse, B; Guettier, C; Bernard, O; Gonzales, E et al. (February 2018). "Mutations in the novel gene FOPV are associated with familial autosomal dominant and non-familial obliterative portal venopathy.". Liver International 38 (2): 358–364. doi:10.1111/liv.13547. PMID 28792652. https://doi.org/10.1111/liv.13547. 



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