C5orf24: Difference between revisions
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[[File:Conceptual_Translation_of_C5orf24_Transcript_Variant_1_Protein-Coding_Sequence.jpg|thumb|207x207px|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).]] |
[[File:Conceptual_Translation_of_C5orf24_Transcript_Variant_1_Protein-Coding_Sequence.jpg|thumb|207x207px|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).]] |
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[[File:C5orf24_Protein_Cartoon.jpg|thumb|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).]] |
[[File:C5orf24_Protein_Cartoon.jpg|thumb|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).]] |
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Isoform 1 of the UPF0461 protein C5orf24 is 188 amino acids long encoded by exon 2.<ref name=":3" /> It contains two disordered regions at the amino acid positions 1-20 and 79-142, respectively.<ref name=":3" /> The second disordered region contains a series of internal repeats.<ref>{{Cite web|title=Dotlet JS|url=https://dotlet.vital-it.ch/|access-date=2021-12-17|website=dotlet.vital-it.ch}}</ref><ref>{{Cite web|title=SAPS < Sequence Statistics < EMBL-EBI|url=https://www.ebi.ac.uk/Tools/seqstats/saps/|access-date=2021-12-17|website=www.ebi.ac.uk}}</ref> The human precursor protein is predicted to be 20.1 kDa with an [[isoelectric point]] of approximately 10.<ref name=":7">{{Cite web|title=Compute pI/Mw tool|url=https://web.expasy.org/compute_pi/|url-status=live|access-date=2 December 2021|website=ExPASy}}</ref> [[Immunoblotting]] demonstrated the experimental [[molecular-weight]] to be about 25 kDa.<ref>{{Cite web|title=Anti-C5orf24 (61-75) antibody produced in rabbit|url=https://www.sigmaaldrich.com/US/en/product/sigma/sab1103592|url-status=live|website=MilliporeSigma}}</ref> Three experimental [[phosphorylation]] sites have been reported at Ser37,<ref> |
Isoform 1 of the UPF0461 protein C5orf24 is 188 amino acids long encoded by exon 2.<ref name=":3" /> It contains two disordered regions at the amino acid positions 1-20 and 79-142, respectively.<ref name=":3" /> The second disordered region contains a series of internal repeats.<ref>{{Cite web|title=Dotlet JS|url=https://dotlet.vital-it.ch/|access-date=2021-12-17|website=dotlet.vital-it.ch}}</ref><ref>{{Cite web|title=SAPS < Sequence Statistics < EMBL-EBI|url=https://www.ebi.ac.uk/Tools/seqstats/saps/|access-date=2021-12-17|website=www.ebi.ac.uk}}</ref> The human precursor protein is predicted to be 20.1 kDa with an [[isoelectric point]] of approximately 10.<ref name=":7">{{Cite web|title=Compute pI/Mw tool|url=https://web.expasy.org/compute_pi/|url-status=live|access-date=2 December 2021|website=ExPASy}}</ref> [[Immunoblotting]] demonstrated the experimental [[molecular-weight]] to be about 25 kDa.<ref>{{Cite web|title=Anti-C5orf24 (61-75) antibody produced in rabbit|url=https://www.sigmaaldrich.com/US/en/product/sigma/sab1103592|url-status=live|website=MilliporeSigma}}</ref> Three experimental [[phosphorylation]] sites have been reported at Ser37,<ref>{{doi|10.1021/pr300630k}}</ref> Ser121,<ref name=":14">{{doi|10.1126/science.1140321}}</ref> and Ser180<ref name=":14" /> along with evidence for a [[ubiquitination]] site at Lys146.<ref>{{doi|10.1074/mcp.M111.013284}}</ref><ref>{{doi|10.1038/s41594-018-0084-y}}</ref><ref name=":3" /><ref name=":8">{{Cite web|title=UPF0461 protein C5orf24|url=https://www.phosphosite.org/proteinAction.action?id=11980&showAllSites=true|url-status=live|access-date=15 November 2021|website=PhosphoSitePlus}}</ref> A conserved [[Nuclear localization sequence|nuclear localization signal]] at amino acid positions 79 – 83 (KKKK) was corroborated by [[immunofluorescence]] experiments using anti-C5orf24 [[antibodies]] depicting localization to the [[nucleoplasm]].<ref name=":9">{{Cite web|date=2 October 2021|title=Standard Protein BLAST (Basic Local Alignment Search Tool)|url=https://blast.ncbi.nlm.nih.gov/Blast.cgi?PAGE=Proteins|url-status=live|website=NCBI}}</ref><ref name=":12" /><ref name=":13">{{Cite web|title=Anti-C5orf24 antibody produced in rabbit|url=https://www.sigmaaldrich.com/US/en/product/sigma/hpa062502|url-status=live|website=MilliporeSigma}}</ref> [[Affinity chromatography]] and anti tag [[coimmunoprecipitation]] experiments showed C5orf24 likely interacts with multiple other proteins including [[STK11]], [[CAB39]], [[LYK5]], [[PKNOX1]], and [[PBX1]].<ref>{{doi|10.1038/nature22366}}</ref><ref>{{Cite web|title=C5orf24|url=https://string-db.org/cgi/network?taskId=bug5kAKXPkoB&sessionId=bukF9iucuDX7|url-status=live|access-date=20 September 2021|website=STRING}}</ref> |
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== Evolutionary history == |
== Evolutionary history == |
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=== Orthologs === |
=== Orthologs === |
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The C5orf24 protein is not present in [[plant]]s or [[fungus]] but orthologs have been found in mammals, birds, reptiles, amphibians, as well as bony fish ([[Osteichthyes]]) and cartilaginous fish ([[Chondrichthyes]]).<ref name=":9" /> There is evidence for an orthologous domain in jawless fishes ([[Agnatha]]) and [[invertebrate]]s.<ref name=":9" /> Comparison of m values (corrected rate of divergence) between C5orf24 ([https://www.ncbi.nlm.nih.gov/protein/NP_001129058.1 NP_001129058.1]), [[Cytochrome c]] [https://www.ncbi.nlm.nih.gov/protein/NP_061820.1 (NP_061820.1]) which has a slow rate of [[evolution]],<ref> |
The C5orf24 protein is not present in [[plant]]s or [[fungus]] but orthologs have been found in mammals, birds, reptiles, amphibians, as well as bony fish ([[Osteichthyes]]) and cartilaginous fish ([[Chondrichthyes]]).<ref name=":9" /> There is evidence for an orthologous domain in jawless fishes ([[Agnatha]]) and [[invertebrate]]s.<ref name=":9" /> Comparison of m values (corrected rate of divergence) between C5orf24 ([https://www.ncbi.nlm.nih.gov/protein/NP_001129058.1 NP_001129058.1]), [[Cytochrome c]] [https://www.ncbi.nlm.nih.gov/protein/NP_061820.1 (NP_061820.1]) which has a slow rate of [[evolution]],<ref>{{doi|10.1016/j.bbabio.2011.07.007}}</ref> and [[Fibrinogen alpha chain|Fibrinogen alpha]] ([https://www.ncbi.nlm.nih.gov/protein/NP_000499 NP_000499.1]) which has a fast rate of evolution<ref>{{doi|10.2307/2412963}}</ref> demonstrated this protein evolved at fairly slow rate especially when fish sequences are excluded.<ref name=":3" /><ref name=":9" /><ref name=":11">{{Cite web|title=TimeTree :: The Timescale of Life|url=http://www.timetree.org/|access-date=2021-12-17|website=www.timetree.org}}</ref><ref>{{Cite web|title=cytochrome c [Homo sapiens]|url=https://www.ncbi.nlm.nih.gov/protein/NP_061820.1|url-status=live|access-date=10 December 2020|website=NCBI Protein}}</ref><ref>{{Cite web|title=fibrinogen alpha chain isoform alpha-E preproprotein [Homo sapiens]|url=https://www.ncbi.nlm.nih.gov/protein/NP_000499|url-status=live|access-date=10 December 2021|website=NCBI Protein}}</ref> |
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[[File:Rate_of_Molecular_Evolution_of_the_C5orf24_Protein_Compared_to_Cytochrome_C_and_Fibrinogen_alpha.jpg|thumb|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).|260x260px]] |
[[File:Rate_of_Molecular_Evolution_of_the_C5orf24_Protein_Compared_to_Cytochrome_C_and_Fibrinogen_alpha.jpg|thumb|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).|260x260px]] |
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=== Expression === |
=== Expression === |
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''C5orf24'' is ubiquitously expressed with limited [[Tissue (biology)|tissue]] variability.<ref name=":0" /><ref name=":2" /><ref>{{Cite web|title=UPF0461 protein C5orf24 homolog|url=https://gp3.mpg.de/results/c5orf24|url-status=live|website=GENEPAINT}}</ref> [[Microarray]]-assessed tissue [[Gene expression|expression]] patterns show ''C5orf24'' levels decreasing in pro-[[Inflammation|inflammatory]] environments such as in patients with tibial [[muscular dystrophy]]<ref> |
''C5orf24'' is ubiquitously expressed with limited [[Tissue (biology)|tissue]] variability.<ref name=":0" /><ref name=":2" /><ref>{{Cite web|title=UPF0461 protein C5orf24 homolog|url=https://gp3.mpg.de/results/c5orf24|url-status=live|website=GENEPAINT}}</ref> [[Microarray]]-assessed tissue [[Gene expression|expression]] patterns show ''C5orf24'' levels decreasing in pro-[[Inflammation|inflammatory]] environments such as in patients with tibial [[muscular dystrophy]]<ref>{{doi|10.1371/journal.pone.0090819}}</ref> and children with [[obesity]].<ref>{{doi|10.3390/ijms16047723}}</ref> |
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===Genotype-phenotype correlations=== |
===Genotype-phenotype correlations=== |
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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 [[Post-traumatic stress disorder|PTSD]] and downregulation in those with improved symptoms,<ref> |
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 [[Post-traumatic stress disorder|PTSD]] and downregulation in those with improved symptoms,<ref>{{doi|10.1016/j.bbi.2019.04.039}}</ref> a linear correlation between [[methylation]] levels of ''C5orf24'' GC sites to negative affect scores in [[drug addicts]],<ref>{{doi|10.3389/fnmol.2018.00322}}</ref> as well as [[Genome-wide association study|GWAS]] studies demonstrating [[Single-nucleotide polymorphism|SNPs]] in ''C5orf24'' to be associated with [[Parkinson's disease]] in the [[Han Chinese|Chinese Han population]]<ref>{{doi|10.3389/fneur.2021.623913}}</ref> and [[Crohn's disease]].<ref>{{doi|10.1093/ibd/izz016}}</ref> |
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==References== |
==References== |
Revision as of 16:28, 22 December 2021
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Aliases | C5orf24, chromosome 5 open reading frame 24 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | MGI: 1925771; HomoloGene: 17572; GeneCards: C5orf24; OMA:C5orf24 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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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
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]
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]
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
- ^ a b c GRCh38: Ensembl release 89: ENSG00000181904 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000045767 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d e "C5orf24 chromosome 5 open reading frame 24 [ Homo sapiens (human) ]". NCBI Gene. Retrieved 25 September 2021.
- ^ a b c d e "UPF0461 protein C5orf24 isoform 1 [Homo sapiens]". NCBI Protein. Retrieved 16 December 2021.
{{cite web}}
: CS1 maint: url-status (link) - ^ a b c d e f g h "Standard Protein BLAST (Basic Local Alignment Search Tool)". NCBI. 2 October 2021.
{{cite web}}
: CS1 maint: url-status (link) - ^ a b "C5orf24". PSORT II Prediction. Retrieved 15 November 2021.
{{cite web}}
: CS1 maint: url-status (link) - ^ a b "Anti-C5orf24 antibody produced in rabbit". MilliporeSigma.
{{cite web}}
: CS1 maint: url-status (link) - ^ a b c "Homo sapiens gene C5orf24, encoding chromosome 5 open reading frame 24". NCBI AceView. Retrieved 18 September 2021.
{{cite web}}
: CS1 maint: url-status (link) - ^ a b c "C5orf24 (Homo sapiens chromosome 5 open reading frame 24) transcript variant 1 mRNA". UCSC Genome Browser. Retrieved 16 September 2021.
{{cite web}}
: CS1 maint: url-status (link) - ^ "C5orf24 Gene - GeneCards | CE024 Protein | CE024 Antibody". www.genecards.org. Retrieved 2021-12-18.
- ^ "Gene: C5orf24 (ENSG00000181904) - Summary - Homo_sapiens - Ensembl genome browser 105". www.ensembl.org. Retrieved 2021-12-17.
- ^ "Gene symbol report | HUGO Gene Nomenclature Committee". www.genenames.org. Retrieved 2021-12-17.
- ^ "MatInspector: Search for transcription factor binding sites". genomatix. Retrieved 20 November 2021.
{{cite web}}
: CS1 maint: url-status (link) - ^ a b "Homo sapiens chromosome 5 open reading frame 24 (C5orf24), transcript variant 1, mRNA". NCBI Gene. 18 June 2021.
{{cite journal}}
: CS1 maint: url-status (link) - ^ a b "Homo sapiens chromosome 5 open reading frame 24 (C5orf24), transcript variant 2, mRNA". NCBI Gene. 18 June 2021.
{{cite journal}}
: CS1 maint: url-status (link) - ^ "Homo sapiens chromosome 5 open reading frame 24 (C5orf24), transcript variant 3, mRNA". NCBI Gene. 27 June 2021.
{{cite journal}}
: CS1 maint: url-status (link) - ^ "Dotlet JS". dotlet.vital-it.ch. Retrieved 2021-12-17.
- ^ "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2021-12-17.
- ^ "Compute pI/Mw tool". ExPASy. Retrieved 2 December 2021.
{{cite web}}
: CS1 maint: url-status (link) - ^ "Anti-C5orf24 (61-75) antibody produced in rabbit". MilliporeSigma.
{{cite web}}
: CS1 maint: url-status (link) - ^ doi:10.1021/pr300630k
- ^ a b doi:10.1126/science.1140321
- ^ doi:10.1074/mcp.M111.013284
- ^ doi:10.1038/s41594-018-0084-y
- ^ "UPF0461 protein C5orf24". PhosphoSitePlus. Retrieved 15 November 2021.
{{cite web}}
: CS1 maint: url-status (link) - ^ doi:10.1038/nature22366
- ^ "C5orf24". STRING. Retrieved 20 September 2021.
{{cite web}}
: CS1 maint: url-status (link) - ^ doi:10.1016/j.bbabio.2011.07.007
- ^ doi:10.2307/2412963
- ^ a b "TimeTree :: The Timescale of Life". www.timetree.org. Retrieved 2021-12-17.
- ^ "cytochrome c [Homo sapiens]". NCBI Protein. Retrieved 10 December 2020.
{{cite web}}
: CS1 maint: url-status (link) - ^ "fibrinogen alpha chain isoform alpha-E preproprotein [Homo sapiens]". NCBI Protein. Retrieved 10 December 2021.
{{cite web}}
: CS1 maint: url-status (link) - ^ "EMBOSS Needle < Pairwise Sequence Alignment < EMBL-EBI". www.ebi.ac.uk. Retrieved 2021-12-17.
- ^ "Vital-IT - Competence Centre in Bioinformatics and Computational Biology". www.vital-it.ch. Retrieved 2021-12-17.
- ^ "UPF0461 protein C5orf24 homolog". GENEPAINT.
{{cite web}}
: CS1 maint: url-status (link) - ^ doi:10.1371/journal.pone.0090819
- ^ doi:10.3390/ijms16047723
- ^ doi:10.1016/j.bbi.2019.04.039
- ^ doi:10.3389/fnmol.2018.00322
- ^ doi:10.3389/fneur.2021.623913
- ^ doi:10.1093/ibd/izz016