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C15orf61

From Wikipedia, the free encyclopedia
C15orf61
Identifiers
AliasesC15orf61, chromosome 15 open reading frame 61
External IDsMGI: 1916728; HomoloGene: 19058; GeneCards: C15orf61; OMA:C15orf61 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

145853

69478

Ensembl

ENSG00000189227

ENSMUSG00000032403

UniProt

A6NNL5

Q0VG49

RefSeq (mRNA)

NM_001143936

NM_027090

RefSeq (protein)

NP_001137408

NP_081366

Location (UCSC)Chr 15: 67.52 – 67.53 MbChr 9: 63.3 – 63.31 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Chromosome 15 open reading frame 61 (c15orf61) is a uncharacterized, human-protein coding gene. This gene encodes a 157-amino-acid protein with a molecular weight of 18.1kDa.[5] C15orf61 is evolutionarily conserved and has orthologs in various species, including mammals, birds, reptiles, amphibians, fishes, and invertebrates.

Gene

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Locus

Microarray of tissue expression of c15orf61 in humans

C15orf61 is composed of two exons and spans from base pair 67,521,131 to 67,530,146 on the plus strand. C15orf61 is flanked by the gene IQCH upstream and the gene MAP2K5 downstream.[5]

C15orf61 Ideogram. C15orf61 is located at position 15q23.[6]

Expression

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C15orf61 is ubiquitously expressed across human tissues with moderate variability. Expression of c15orf61 is highest in skeletal muscle, fat, and cerebellum brain tissues.[5][7]

mRNA

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C15orf61 contains 4,193 nucleotides. There are no known isoforms for c15orf61.[5]

Protein

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The protein encoded by c15orf61 is 157 amino acids long.[8] The theoretical molecular weight is 18.1kDa and the predicted isoelectric point is 9.9.[9] The isoelectric point of c15orf61 is higher than the average human protein.[10]

Illustration of protein encoded by c15orf61, including the signal peptide and transmembrane region.[11]
Tertiary structure of c15orf61 protein

Domains and motifs

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C15orf61 is part of the conserved protein domain family DUF4528.[6] A L27 domain, associated with protein-protein interactions was also identified.[12] C15orf61 is rich in histidine, arginine and tryptophan, and deficient in aspartate compared to other human proteins.[9]

Subcellular localization and topology

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The protein encoded by c15orf61 has a signal peptide consisting of amino acids 1-19. There is also one transmembrane region.[13] The protein is predicted to be localized in the mitochondria with a 95% confidence. However, it is also predicted at a lower confidence (30.4%) to be cytoplasmic.[14] The high isoelectric point of 9.9, which would suggest mitochondrial localization due to the high pH of the mitochondrial matrix.

Post-translational modifications

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The protein encoded by c15orf61 has been shown to be phosphorylated at position 31-34 by Casein Kinase II. A tyrosine kinase phosphorylation was identified at positions 150-157. There is also a cleavage site to cleave the 19 amino acid N-terminal signal peptide.

Secondary and tertiary structure

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The structure of the protein encoded by c15orf61 consists of alpha helices and beta strands. A predicted tertiary structure of the protein encoded by c15orf61 is shown to the right.

Protein Interactions

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Protein name Function Basis of identification Subcellular location
CTLA4 (cytotoxic T-lymphocyte-associated protein 4)[15] Member of the immunoglobulin superfamily and encodes a protein which transmits an inhibitory signal to T cells Co-immuno

precipitation

Golgi apparatus
TNIP2 (TNFAIP3 interacting protein 2)[16] Encodes a protein which acts as an inhibitor of NFkappaB activation. The encoded protein is also involved in MAP/ERK signaling pathway Co-immuno

precipitation

Cytosol
VIPR2 (vasoactive intestinal peptide receptor 2)[17] Receptor for VIP as well as PACAP-38 and -27, the activity of this receptor is mediated by G proteins which activate adenylyl cyclase Co-immuno

precipitation

Cytosol
ORF7B (SARS-CoV-2 accessory protein 7B)[18] Interferes with the host’s innate immune response by targeting and suppressing TOM70, part of the mitochondrial antiviral-signaling protein (MAVS) pathway Co-immuno

precipitation

Host mitochondria
Phylogenetic tree of c15orf61 in humans and orthologs, identified by species name abbreviations.

Homology and evolution

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Orthologs

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C15orf61 shows high sequence identity in mammals, with human and mouse proteins sharing over 92% identity. The protein length is consistent across most species, though some invertebrates, such as worms and flukes, show significantly lower sequence identity (ranging from 36.9% to 54.1%) and longer evolutionary divergence.

Phylogenetic analysis indicates that the corrected sequence divergence increases with taxonomic distance, reflecting the evolutionary history and functional conservation of the protein.

Below is a table of a variety of orthologs for human c15orf61. Table includes closely, moderately, and distantly related orthologs, listed in descending order of the date of divergence.

Animal type Species name Common name Taxonomic group Date of divergence (MYA) Percent identity Seq similarity Accession number
Mammal Homo sapiens Human Mammalia 0 100% 100.0% NP_001137408
Mammal Galeopterus variegatus Sunda flying lemur Dermoptera 79 95.5% 96.8% XP_008581098
Mammal Mus musculus House mouse Rodentia 87 92.3% 95.5% NP_081366
Mammal Ailuropoda melanoleuca Giant panda Carnivora 94 94.9% 95.5% XP_034516667
Bird Gallus gallus Chicken Galliformes 319 74.5% 82.2% NP_001269258
Reptile Euleptes europaea European leaf-toed gecko Squamata 319 70.7% 80.9% XP_056721932
Amphibian Xenopus laevis African clawed frog Anura 352 69.4% 80.9% XP_018108803
Fish Betta splendens Siamese fighting fish Perciformes 429 64.6% 74.7% XP_029010739
Fish Periophthalmus magnuspinnatus Korean giant-fin mudskipper Gobiiformes 429 63.9% 74.1% XP_033824044
Fish Danio rerio Zebrafish Cyprinidae 429 63.3% 70.9% NP_001076422
Fish Hypanus sabinus Antlatic stingray Myliobatiformes 462 48.2% 59.4% XP_059808977
Fish Petromyzon marinus Sea lamprey Agnathans 536 59.2% 71.3% XP_032804365
Invertebrate Saccoglossus kowalevskii Acorn worm Enteropneusta 619 54.1% 67.2% XP_002740887
Invertebrate Bombus impatiens Common eastern bumblebee Insecta 686 53.5% 70.4% XP_012237208
Invertebrate Penaeus indicus Indian prawn Decapoda 686 48.5% 62.0% XP_063605333
Invertebrate Limulus polyphemus Antlantic horseshoe crab Xiphosura 686 45.9% 56.4% XP_013780284
Invertebrate Drosophila melanogaster Fruit fly Insecta 686 44.7% 57.9% NP_788708
Invertebrate Artemia franciscana Brine shrimp Branchiopoda 686 49.1% 67.9% XP_065579866
Invertebrate Ischnura elegans Blue-tailed damselfly Insecta 686 47.8% 66.0% XP_046398922
Invertebrate Fasciolopsis buski Giant intestinal fluke Trematoda 686 36.9% 52.9% KAA0199948
Invertebrate Macrostomum lignano Flatworm Macrostomida 686 44.3% 62.0% PAA50735.1
Invertebrate Paralvinella palmiformis Palm worm Terebellida 686 39.9% 48.7% KAK2159949

Evolution

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Divergence graph of c15orf61, fibrinogen, and cytochrome c

The rate of evolution of c15orf61 was compared to that of cytochrome c and fibrinogen. C15orf61 appears to be evolving at a moderate pace, slower than fibrinogen alpha chain but faster than cytochrome c. This suggests that C15orf61 is not under intense evolutionary pressure to evolve rapidly, but is in a complex that has the ability to mutate over time.[citation needed]

Clinical significance

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Disease association

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C15ord61 has been implicated to be involved in mitochondrial function, having shown significant negative correlation between c15orf61 and mitochondrial respiratory conductance.[19] Research has also suggested C15orf61 potentially influences transcriptional regulation in immune and neuronal tissues, having significantly different levels of expression in tissues taken from patients with autoimmune disorders such as rheumatoid arthritis, diabetes, and multiple sclerosis.[20][21][22][23]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000189227 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032403 – 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. ^ a b c d "C15orf61 chromosome 15 open reading frame 61 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-12.
  6. ^ a b "C15orf61 Gene - Chromosome 15 Open Reading Frame 61". GeneCards.
  7. ^ "2906311 - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-13.
  8. ^ "uncharacterized protein C15orf61 precursor [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-12.
  9. ^ a b www.ebi.ac.uk https://www.ebi.ac.uk/jdispatcher/seqstats/saps/summary?jobId=saps-I20241127-002927-0657-9290132-p1m&js=pass. Retrieved 2024-12-13. {{cite web}}: Missing or empty |title= (help)
  10. ^ Kozlowski, Lukasz P. "Proteome-pI - Proteome Isoelectric Point Database statistics". isoelectricpointdb.org. Retrieved 2024-12-12.
  11. ^ "Protter - interactive protein feature visualization". wlab.ethz.ch. Archived from the original on 2024-05-07. Retrieved 2024-12-12.
  12. ^ "Motif Scan". myhits.sib.swiss. Retrieved 2024-12-13.
  13. ^ "SOSUIsignal: Result". harrier.nagahama-i-bio.ac.jp. Retrieved 2024-12-13.
  14. ^ "WoLF PSORT: Protein Subcellular Localization Prediction". wolfpsort.hgc.jp. Retrieved 2024-12-13.
  15. ^ "CTLA4 gene: Cytotoxic T-lymphocyte associated protein 4". GeneCards.
  16. ^ "TNIP2 gene: TNFAIP3 interacting protein 2". GeneCards.
  17. ^ "VIPR2 gene: Vasoactive intestinal peptide receptor 2". GeneCards.
  18. ^ Schaecher, Scott R.; Mackenzie, Jason M.; Pekosz, Andrew (January 2007). "The ORF7b protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is expressed in virus-infected cells and incorporated into SARS-CoV particles". Journal of Virology. 81 (2): 718–731. doi:10.1128/JVI.01691-06. ISSN 0022-538X. PMC 1797472. PMID 17079322.
  19. ^ McLaughlin, Kelsey L.; Kew, Kimberly A.; McClung, Joseph M.; Fisher-Wellman, Kelsey H. (2020-02-27). "Subcellular proteomics combined with bioenergetic phenotyping reveals protein biomarkers of respiratory insufficiency in the setting of proofreading-deficient mitochondrial polymerase". Scientific Reports. 10 (1): 3603. Bibcode:2020NatSR..10.3603M. doi:10.1038/s41598-020-60536-y. ISSN 2045-2322. PMC 7046634. PMID 32107436.
  20. ^ Kusaoi, Makio; Yamaji, Ken; Murayama, Go; Yasui, Misa; Yamada, Risa; Hishinuma, Ruka; Nemoto, Takuya; Hohtatsu, Katsura; Kageyama, Michiaki; Kawamoto, Toshio; Sugimoto, Kaoru; Sekiya, Fumio; Kon, Takayuki; Ogasawara, Michihiro; Kempe, Kazuo (2012). "Gene Expression Analysis Using a High-Resolution DNA Microarray of Peripheral Whole Blood Immediately Before and After Leukocytapheresis for Rheumatoid Arthritis". Therapeutic Apheresis and Dialysis. 16 (5): 456–466. doi:10.1111/j.1744-9987.2012.01111.x. ISSN 1744-9987. PMID 23046371.
  21. ^ "90448097 - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-12.
  22. ^ "116168218 - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-12.
  23. ^ "21210695 - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-12-12.
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