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C5orf24

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C5orf24
Identifiers
AliasesC5orf24, chromosome 5 open reading frame 24
External IDsMGI: 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 MbChr 13: 55.84 – 55.85 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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]

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 Variant Length (nt) Protein Isoform Length (aa)
1 (NM_001135586.1) 5083 1 (NP_001129058.1) 188
2 (NM_152409.3) 4896 1 (NP_689622.2) 188
3 (NM_001300894.2) 3054 2 (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).
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).
C5orf24 Scientific Name Common Name Taxonomic Group Median Date of Divergence (MYA) Accession Number Sequence Length (aa) Query Cover Sequence Identity
Mammals Homo sapiens Human Primates 0 NP_001129058.1 188 100% 100%
Cavia porcellus Guinea Pig Rodentia 89 XP_005005246.1 188 100% 98.4%
Ursus maritimus Polar Bear Carnivora 94 XP_008689817.1 188 100% 97.9%
Trichechus manatus latirostris Florida Manatee Sirenia 102 XP_004384765.1 188 100% 95.7%
Ornithorhynchus anatinus Platypus Monotremata 180 XP_007669207.1 188 100% 82.4%
Birds Calypte anna Anna's Hummingbird Apodiformes 318 XP_030314921.1 188 100% 86.2%
Strigops habroptila Kākāpō Psittaciformes 318 XP_030360294.1 188 100% 85.1%
Reptiles Pelodiscus sinensis Chinese Softshell Turtle Testudines 318 XP_006116108.1 188 100% 85.1%
Python bivittatus Burmese python Squamata 318 XP_007421938.1 188 100% 78.7%
Amphibians Rhinatrema bivittatum Two-Lined Caecilian Gymnophiona 352 XP_029439506.1 188 100% 75.5%
Xenopus tropicalis Tropical Clawed Frog Anura 352 NP_001072358.1 186 100% 70.7%
Fishes Esox Lucius Northern Pike Osteichtyes 433 XP_019903474.2 204 100% 56.5%
Scyliorhinus canicular Small-Spotted Catshark Chondrichthyes 465 XP_038651786.1 193 96% 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.

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

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  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000045767 – Ensembl, May 2017
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  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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