# C15orf61

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

Locus
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.

### 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 name | Function | Basis of identification | Subcellular location |
| CTLA4 (cytotoxic T-lymphocyte-associated protein 4) | 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) | 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) | 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) | 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 |

## 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 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

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.