C5orf24

Last updated

C5orf24
Identifiers
Aliases C5orf24 , chromosome 5 open reading frame 24
External IDs MGI: 1925771; HomoloGene: 17572; GeneCards: C5orf24; OMA:C5orf24 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

134553

78521

Ensembl

ENSG00000181904

ENSMUSG00000045767

UniProt

Q7Z6I8

Q80X32

RefSeq (mRNA)

NM_001135586
NM_001300894
NM_152409

NM_181278

RefSeq (protein)

NP_001129058
NP_001287823
NP_689622

NP_851795

Location (UCSC) Chr 5: 134.85 – 134.86 Mb Chr 13: 55.84 – 55.85 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

C5orf24 (chromosome 5 open reading frame 24) is a protein encoded by the C5orf24 gene (5q31.1) in humans. [5] [6] C5orf24 is primarily localized to the nucleus and is highly conserved with orthologs in mammals, birds, reptiles, amphibians, and fish. [7] [8] [9]

Contents

Gene

Human C5orf24 is a protein-coding gene 26,133 base pairs long (chr5:134,833,603-134,859,735) composed of two exons and one intron at locus 5q31.1 oriented on the plus strand. [5] [10] [11] [12] Alternate names for the gene are FLJ37562 and LOC134553. [10] [13] [14] Genes neighboring C5orf24 include DDX46, RPL34P13, and TXNDC15. [5] Some transcription factors predicted to bind to conserved sites on the promoter region (GXP_7545710) are NRF1, E2F, ZF5, and AHR. [15]

Transcripts

Transcript VariantLength (nt)Protein IsoformLength (aa)
1 (NM_001135586.1)50831 (NP_001129058.1)188
2 (NM_152409.3)48961 (NP_689622.2)188
3 (NM_001300894.2)30542 (NP_001287823.1)155

The human C5orf24 gene has three mRNA transcript variants. [5] [11] Both transcript variant 1 and 2 encode protein isoform 1 which is 188 amino acids in length. [16] [17] Transcript variant 1 is the longest and highest quality transcript (5083 nucleotides) with transcript variant 2 (4896 nucleotides) having a smaller 5' UTR region. [16] [17] Transcript variant 3 lacks an internal segment resulting in an alternate translational stop codon making it is the shortest variant (3054 nucleotides) encoding the smaller protein isoform 2 which is 155 amino acids in length. [18]

Protein

Conceptual translation of the protein-coding region of the C5orf24 mRNA transcript variant 1 (NM_001135586.1) aligned with the corresponding protein sequence (NP_001129058.1). Conceptual Translation of C5orf24 Transcript Variant 1 Protein-Coding Sequence.jpg
Conceptual translation of the protein-coding region of the C5orf24 mRNA transcript variant 1 (NM_001135586.1) aligned with the corresponding protein sequence (NP_001129058.1).
C5orf24 protein isoform 1 cartoon including two disordered regions DR1 & DR2 (blue), nuclear localization signal (green), experimental phosphorylation sites (red), and a ubiquitination site (grey). C5orf24 Protein Cartoon.jpg
C5orf24 protein isoform 1 cartoon including two disordered regions DR1 & DR2 (blue), nuclear localization signal (green), experimental phosphorylation sites (red), and a ubiquitination site (grey).

Isoform 1 of the UPF0461 protein C5orf24 is 188 amino acids long encoded by exon 2. [6] It contains two disordered regions at the amino acid positions 1-20 and 79-142, respectively. [6] The second disordered region contains a series of internal repeats. [19] [20] The human precursor protein is predicted to be 20.1 kDa with an isoelectric point of approximately 10. [21] Immunoblotting demonstrated the experimental molecular-weight to be about 25 kDa. [22] Three experimental phosphorylation sites have been reported at Ser37, [23] Ser121, [24] and Ser180 [24] along with evidence for a ubiquitination site at Lys146. [25] [26] [6] [27] A conserved nuclear localization signal at amino acid positions 79 – 83 (KKKK) was corroborated by immunofluorescence experiments using anti-C5orf24 antibodies depicting localization to the nucleoplasm. [7] [8] [9] Affinity chromatography and anti tag coimmunoprecipitation experiments showed C5orf24 likely interacts with multiple other proteins including STK11, CAB39, LYK5, PKNOX1, and PBX1. [28] [29]

Evolutionary history

Orthologs

The C5orf24 protein is not present in plants or fungus but orthologs have been found in mammals, birds, reptiles, amphibians, as well as bony fish (Osteichthyes) and cartilaginous fish (Chondrichthyes). [7] There is evidence for an orthologous domain in jawless fishes (Agnatha) and invertebrates. [7] Comparison of m values (corrected rate of divergence) between C5orf24 (NP_001129058.1), Cytochrome c (NP_061820.1) which has a slow rate of evolution, [30] and Fibrinogen alpha (NP_000499.1) which has a fast rate of evolution [31] demonstrated this protein evolved at fairly slow rate especially when fish sequences are excluded. [6] [7] [32] [33] [34]

Rate of Molecular Evolution (m vs. Date of Divergence in Millions of Years Ago) of the C5orf24 protein (NP_001129058.1) compared to Cytochrome C (NP_061820.1) and Fibrinogen Alpha (NP_000499.1). Rate of Molecular Evolution of the C5orf24 Protein Compared to Cytochrome C and Fibrinogen alpha.jpg
Rate of Molecular Evolution (m vs. Date of Divergence in Millions of Years Ago) of the C5orf24 protein (NP_001129058.1) compared to Cytochrome C (NP_061820.1) and Fibrinogen Alpha (NP_000499.1).
C5orf24Scientific NameCommon NameTaxonomic GroupMedian Date of Divergence (MYA)Accession NumberSequence Length (aa)Query CoverSequence Identity
MammalsHomo sapiens Human Primates0NP_001129058.1188100%100%
Cavia porcellus Guinea Pig Rodentia89XP_005005246.1188100%98.4%
Ursus maritimus Polar Bear Carnivora94XP_008689817.1188100%97.9%
Trichechus manatus latirostris Florida Manatee Sirenia102XP_004384765.1188100%95.7%
Ornithorhynchus anatinus Platypus Monotremata180XP_007669207.1188100%82.4%
BirdsCalypte anna Anna's Hummingbird Apodiformes318XP_030314921.1188100%86.2%
Strigops habroptila Kākāpō Psittaciformes318XP_030360294.1188100%85.1%
ReptilesPelodiscus sinensis Chinese Softshell Turtle Testudines318XP_006116108.1188100%85.1%
Python bivittatus Burmese python Squamata318XP_007421938.1188100%78.7%
AmphibiansRhinatrema bivittatumTwo-Lined Caecilian Gymnophiona352XP_029439506.1188100%75.5%
Xenopus tropicalis Tropical Clawed Frog Anura352NP_001072358.1186100%70.7%
FishesEsox Lucius Northern Pike Osteichtyes433XP_019903474.2204100%56.5%
Scyliorhinus canicular Small-Spotted Catshark Chondrichthyes465XP_038651786.119396%53.8%

Paralogs

The C5orf24 gene has no paralogs. [7] [11]

Multiple sequence alignment of the highly conserved C5orf24 protein region containing internal repeats in mammals, birds, reptiles, amphibians, fish, and invertebrates. C5orf24 Conserved Region with Internal Repeats.jpg
Multiple sequence alignment of the highly conserved C5orf24 protein region containing internal repeats in mammals, birds, reptiles, amphibians, fish, and invertebrates.

Conservation

Multiple sequence alignments revealed the C5orf24 protein has been highly conserved and likely originated in cartilaginous fishes nearly 465 million years ago. [7] [32] [35] [36] A series of internal repeats in the second disordered region were additionally identified in proteins found within jawless fishes and invertebrates, suggesting an orthologous domain began even further back in evolutionary history. [7]

Clinical significance

Expression

C5orf24 is ubiquitously expressed with limited tissue variability. [5] [10] [37] Microarray-assessed tissue expression patterns show C5orf24 levels decreasing in pro-inflammatory environments such as in patients with tibial muscular dystrophy [38] and children with obesity. [39]

Genotype-phenotype correlations

While this gene has yet to be well understood by the scientific community, some genotype-phenotype correlations have been established including the upregulation of C5orf24 in individuals with PTSD and downregulation in those with improved symptoms, [40] a linear correlation between methylation levels of C5orf24 GC sites to negative affect scores in drug addicts, [41] as well as GWAS studies demonstrating SNPs in C5orf24 to be associated with Parkinson's disease in the Chinese Han population [42] and Crohn's disease. [43]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000181904 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000045767 – 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. 1 2 3 4 5 "C5orf24 chromosome 5 open reading frame 24 [ Homo sapiens (human) ]". NCBI Gene. Retrieved 25 September 2021.
  6. 1 2 3 4 5 "UPF0461 protein C5orf24 isoform 1 [Homo sapiens]". NCBI Protein. Archived from the original on 2021-10-17. Retrieved 16 December 2021.
  7. 1 2 3 4 5 6 7 8 "Standard Protein BLAST (Basic Local Alignment Search Tool)". NCBI. 2 October 2021. Archived from the original on 2011-04-08.
  8. 1 2 "C5orf24". PSORT II Prediction. Archived from the original on 2003-12-14. Retrieved 15 November 2021.
  9. 1 2 "Anti-C5orf24 antibody produced in rabbit". MilliporeSigma. Archived from the original on 2021-12-16.
  10. 1 2 3 "Homo sapiens gene C5orf24, encoding chromosome 5 open reading frame 24". NCBI AceView. Archived from the original on 2001-12-12. Retrieved 18 September 2021.
  11. 1 2 3 "C5orf24 (Homo sapiens chromosome 5 open reading frame 24) transcript variant 1 mRNA". UCSC Genome Browser. Archived from the original on 2002-02-07. Retrieved 16 September 2021.
  12. ↑ "C5orf24 Gene - GeneCards | CE024 Protein | CE024 Antibody". www.genecards.org. Retrieved 2021-12-18.
  13. ↑ "Gene: C5orf24 (ENSG00000181904) - Summary - Homo_sapiens - Ensembl genome browser 105". www.ensembl.org. Retrieved 2021-12-17.
  14. ↑ "Gene symbol report | HUGO Gene Nomenclature Committee". www.genenames.org. Retrieved 2021-12-17.
  15. ↑ "MatInspector: Search for transcription factor binding sites". genomatix. Archived from the original on 2002-08-12. Retrieved 20 November 2021.
  16. 1 2 "Homo sapiens chromosome 5 open reading frame 24 (C5orf24), transcript variant 1, mRNA". NCBI Gene. 18 June 2021.
  17. 1 2 "Homo sapiens chromosome 5 open reading frame 24 (C5orf24), transcript variant 2, mRNA". NCBI Gene. 18 June 2021.
  18. ↑ "Homo sapiens chromosome 5 open reading frame 24 (C5orf24), transcript variant 3, mRNA". NCBI Gene. 27 June 2021.
  19. ↑ "Dotlet JS". dotlet.vital-it.ch. Retrieved 2021-12-17.
  20. ↑ "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2021-12-17.
  21. ↑ "Compute pI/Mw tool". ExPASy. Archived from the original on 2011-07-04. Retrieved 2 December 2021.
  22. ↑ "Anti-C5orf24 (61-75) antibody produced in rabbit". MilliporeSigma. Archived from the original on 2021-12-16.
  23. ↑ Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, et al. (January 2013). "Toward a comprehensive characterization of a human cancer cell phosphoproteome". Journal of Proteome Research. 12 (1): 260–271. doi:10.1021/pr300630k. PMID   23186163.
  24. 1 2 Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER, Hurov KE, Luo J, et al. (May 2007). "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage". Science. 316 (5828): 1160–1166. Bibcode:2007Sci...316.1160M. doi:10.1126/science.1140321. PMID   17525332. S2CID   16648052.
  25. ↑ Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, et al. (October 2011). "A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles". Molecular & Cellular Proteomics. 10 (10) M111.013284. doi: 10.1074/mcp.M111.013284 . PMC   3205876 . PMID   21890473.
  26. ↑ Akimov V, Barrio-Hernandez I, Hansen SV, Hallenborg P, Pedersen AK, Bekker-Jensen DB, et al. (July 2018). "UbiSite approach for comprehensive mapping of lysine and N-terminal ubiquitination sites". Nature Structural & Molecular Biology. 25 (7): 631–640. doi:10.1038/s41594-018-0084-y. PMID   29967540. S2CID   49559977.
  27. ↑ "UPF0461 protein C5orf24". PhosphoSitePlus. Archived from the original on 2021-12-16. Retrieved 15 November 2021.
  28. ↑ Huttlin EL, Bruckner RJ, Paulo JA, Cannon JR, Ting L, Baltier K, et al. (May 2017). "Architecture of the human interactome defines protein communities and disease networks". Nature. 545 (7655): 505–509. Bibcode:2017Natur.545..505H. doi:10.1038/nature22366. PMC   5531611 . PMID   28514442.
  29. ↑ "C5orf24". STRING. Retrieved 20 September 2021.
  30. ↑ Pierron D, Wildman DE, Hüttemann M, Markondapatnaikuni GC, Aras S, Grossman LI (April 2012). "Cytochrome c oxidase: evolution of control via nuclear subunit addition". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1817 (4): 590–597. doi:10.1016/j.bbabio.2011.07.007. PMC   3923406 . PMID   21802404.
  31. ↑ O'Neil PB, Doolittle RF (1973). "Mammalian Phylogeny Based on Fibrinopeptide Amino Acid Sequences". Systematic Zoology. 22 (4): 590–595. doi:10.2307/2412963. JSTOR   2412963.
  32. 1 2 "TimeTree :: The Timescale of Life". www.timetree.org. Retrieved 2021-12-17.
  33. ↑ "cytochrome c [Homo sapiens]". NCBI Protein. Archived from the original on 2011-08-10. Retrieved 10 December 2020.
  34. ↑ "fibrinogen alpha chain isoform alpha-E preproprotein [Homo sapiens]". NCBI Protein. Archived from the original on 2016-08-26. Retrieved 10 December 2021.
  35. ↑ "EMBOSS Needle < Pairwise Sequence Alignment < EMBL-EBI". www.ebi.ac.uk. Retrieved 2021-12-17.
  36. ↑ "Vital-IT - Competence Centre in Bioinformatics and Computational Biology". www.vital-it.ch. Retrieved 2021-12-17.[ permanent dead link ]
  37. ↑ "UPF0461 protein C5orf24 homolog". GENEPAINT. Archived from the original on 2021-12-17.
  38. ↑ Screen M, Raheem O, Holmlund-Hampf J, Jonson PH, Huovinen S, Hackman P, et al. (2014). "Gene expression profiling in tibial muscular dystrophy reveals unfolded protein response and altered autophagy". PLOS ONE. 9 (3) e90819. Bibcode:2014PLoSO...990819S. doi: 10.1371/journal.pone.0090819 . PMC   3949689 . PMID   24618559.
  39. ↑ Aguilera CM, Gomez-Llorente C, Tofe I, Gil-Campos M, Cañete R, Gil Á (April 2015). "Genome-wide expression in visceral adipose tissue from obese prepubertal children". International Journal of Molecular Sciences. 16 (4): 7723–7737. doi: 10.3390/ijms16047723 . PMC   4425045 . PMID   25856673.
  40. ↑ Rusch HL, Robinson J, Yun S, Osier ND, Martin C, Brewin CR, et al. (August 2019). "Gene expression differences in PTSD are uniquely related to the intrusion symptom cluster: A transcriptome-wide analysis in military service members". Brain, Behavior, and Immunity. 80: 904–908. doi:10.1016/j.bbi.2019.04.039. PMC   6752960 . PMID   31039430.
  41. ↑ Lax E, Warhaftig G, Ohana D, Maayan R, Delayahu Y, Roska P, et al. (2018). "A DNA Methylation Signature of Addiction in T Cells and Its Reversal With DHEA Intervention". Frontiers in Molecular Neuroscience. 11: 322. doi: 10.3389/fnmol.2018.00322 . PMC   6139343 . PMID   30250424.
  42. ↑ Fan L, Shi C, Hu X, Zhang Z, Zheng H, Luo H, et al. (2021). "Analysis of 12 GWAS-Linked Loci With Parkinson's Disease in the Chinese Han Population". Frontiers in Neurology. 12 623913. doi: 10.3389/fneur.2021.623913 . PMC   8058430 . PMID   33897588.
  43. ↑ O'Donnell S, Borowski K, Espin-Garcia O, Milgrom R, Kabakchiev B, Stempak J, et al. (August 2019). "The Unsolved Link of Genetic Markers and Crohn's Disease Progression: A North American Cohort Experience". Inflammatory Bowel Diseases. 25 (9): 1541–1549. doi:10.1093/ibd/izz016. PMID   30801121.
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