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. C15orf61 is evolutionarily conserved and has orthologs in various species, including mammals, birds, reptiles, amphibians, fishes, and invertebrates.
Gene
LocusC15orf61 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.
Expression
C15orf61 is ubiquitously expressed across human tissues with moderate variability. Expression of c15orf61 is highest in skeletal muscle, fat, and cerebellum brain tissues.
mRNA C15orf61 contains 4,193 nucleotides. There are no known isoforms for c15orf61.
Protein The protein encoded by c15orf61 is 157 amino acids long. The theoretical molecular weight is 18.1kDa and the predicted isoelectric point is 9.9. The isoelectric point of c15orf61 is higher than the average human protein.
Domains and motifs C15orf61 is part of the conserved protein domain family DUF4528. A L27 domain, associated with protein-protein interactions was also identified. C15orf61 is rich in histidine, arginine and tryptophan, and deficient in aspartate compared to other human proteins.
Subcellular localization and topology The protein encoded by c15orf61 has a signal peptide consisting of amino acids 1-19. There is also one transmembrane region. 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. The high isoelectric point of 9.9, which would suggest mitochondrial localization due to the high pH of the mitochondrial matrix.
Post-translational modifications 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 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 +Protein nameFunctionBasis of identificationSubcellular locationCTLA4 (cytotoxic T-lymphocyte-associated protein 4)Member of the immunoglobulin superfamily and encodes a protein which transmits an inhibitory signal to T cellsCo-immuno precipitationGolgi apparatusTNIP2 (TNFAIP3 interacting protein 2)Encodes a protein which acts as an inhibitor of NFkappaB activation. The encoded protein is also involved in MAP/ERK signaling pathwayCo-immuno precipitationCytosolVIPR2 (vasoactive intestinal peptide receptor 2)Receptor for VIP as well as PACAP-38 and -27, the activity of this receptor is mediated by G proteins which activate adenylyl cyclaseCo-immuno precipitationCytosolORF7B (SARS-CoV-2 accessory protein 7B)Interferes with the host’s innate immune response by targeting and suppressing TOM70, part of the mitochondrial antiviral-signaling protein (MAVS) pathwayCo-immuno precipitationHost mitochondria
Homology and evolution
Orthologs 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 typeSpecies nameCommon nameTaxonomic groupDate of divergence (MYA)Percent identitySeq similarityAccession numberMammalHomo sapiensHumanMammalia0100%100.0%NP_001137408MammalGaleopterus variegatusSunda flying lemurDermoptera7995.5%96.8%XP_008581098MammalMus musculusHouse mouseRodentia8792.3%95.5%NP_081366MammalAiluropoda melanoleucaGiant pandaCarnivora9494.9%95.5%XP_034516667BirdGallus gallusChickenGalliformes31974.5%82.2%NP_001269258ReptileEuleptes europaeaEuropean leaf-toed geckoSquamata31970.7%80.9%XP_056721932AmphibianXenopus laevisAfrican clawed frogAnura35269.4%80.9%XP_018108803FishBetta splendensSiamese fighting fish Perciformes42964.6%74.7%XP_029010739FishPeriophthalmus magnuspinnatusKorean giant-fin mudskipperGobiiformes42963.9%74.1%XP_033824044FishDanio rerioZebrafishCyprinidae42963.3%70.9%NP_001076422FishHypanus sabinusAntlatic stingrayMyliobatiformes46248.2%59.4%XP_059808977FishPetromyzon marinusSea lampreyAgnathans53659.2%71.3%XP_032804365InvertebrateSaccoglossus kowalevskiiAcorn wormEnteropneusta61954.1%67.2%XP_002740887InvertebrateBombus impatiensCommon eastern bumblebeeInsecta68653.5%70.4%XP_012237208InvertebratePenaeus indicusIndian prawnDecapoda68648.5%62.0%XP_063605333InvertebrateLimulus polyphemusAntlantic horseshoe crabXiphosura68645.9%56.4%XP_013780284InvertebrateDrosophila melanogasterFruit flyInsecta68644.7%57.9%NP_788708InvertebrateArtemia franciscanaBrine shrimpBranchiopoda68649.1%67.9%XP_065579866InvertebrateIschnura elegansBlue-tailed damselflyInsecta68647.8%66.0%XP_046398922InvertebrateFasciolopsis buskiGiant intestinal flukeTrematoda68636.9%52.9%KAA0199948InvertebrateMacrostomum lignanoFlatwormMacrostomida68644.3%62.0%PAA50735.1InvertebrateParalvinella palmiformisPalm wormTerebellida68639.9%48.7%KAK2159949
Evolution
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.
Clinical significance Disease association
C15ord61 has been implicated to be involved in mitochondrial function, having shown significant negative correlation between c15orf61 and mitochondrial respiratory conductance. 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.
References