# C10orf95

Chromosome 10 open reading frame 95 is a protein that in humans is encoded by the c10orf95 gene. The protein is involved in pre-mRNA splicing and is localized to the nucleus in most tissues.

## Gene

C10orf95 is located at 10q24.32. It has two exons and spans 1907 base pairs. No splice isoforms or variants are known.

### Gene neighborhood

The gene neighborhood of c10orf95 consists of c10orf95 antisense 1 (c10orf95-AS1), CUE domain containing 2 (CUEDC2), major facilitator superfamily domain containing 13A (MFSD13A), and actin related protein 1A (ACTR1A). The CUEDC2 gene enables ubiquitin binding activity and is involved in cytokine production in inflammatory responses. The MFSD13A gene is located in the plasma membrane but does not have a defined function. The ACTR1A gene encodes for a subunit of dynactin that binds to both microtubules and cytoplasmic dynein.

## Protein
### Structure

The c10orf95 protein structure consists of one alpha helix and five beta sheets. The alpha helix is in a region of the amino acid sequence that is conserved all the way from mammals to invertebrates, and it is exposed to the external environment for binding. No transmembrane domains exist. Compared to other human proteins, c10orf95 is arginine rich. Arginine rich regions allow for interactions with negatively charged molecules such as DNA or RNA, and arginine rich proteins have a significant role in pre-mRNA splicing.

### Properties

* Molecular Weight: 23.9kDal
* Interactions: NUS1, DDX39A
* Minus Strand

## Gene Level regulation
### Tissue Distribution

C10orf95 has moderate ubiquitous expression at low levels in most tissues. However, there is higher expression in lung tissue when compared to other tissues. The fetal heart at 10 weeks has moderately high expression that quickly decreases to almost no expression at 20 weeks gestation.

## Protein level regulation
### Subcellular localization

The c10orf95 protein is likely to be localized to the nucleus due to the presence of multiple nuclear localization signals within the amino acid sequence.

### Post translational modification

There is a signal peptide located from amino acid 1 to 37 and a cleavage site between amino acid 37 and 38. Five important phosphorylation sites exist due to their conservation among orthologs. Serine and threonine were the most commonly phosphorylated amino acids.

## Homology
### Orthologs

The table below shows ortholog sequences first sorted by increasing median date of divergence in millions of years ago (MYA) followed by percent sequence identity to the human protein. The most distantly related species to humans are invertebrates (excluding fungi, bacteria, plants) with the furthest median date of divergence being 686 MYA and the average sequence identity being 18.5%. Conversely, the closest related species to humans are other mammals with the closest date of divergence being 87 MYA and the average sequence identity being 57.8%. In between there are reptiles, birds, amphibians, and bony fish that are moderately related with average sequence identities being 34.25%, 31%, 29.67%, and 31.3% respectively. There are no known paralogs.
| Genus/Species | Common Name | Taxonomic Order | Date of Divergence (MYA) | Accession Number | Sequence Length (aa) | Sequence Identity | Sequence Similarity |
| Homo sapiens | Human | Primate | 0 | NP_001350509.1 | 213 | 100% | 100% |
| Oryctolagus cuniculus | European Rabbit | Lagomorpha | 87 | XP_051679518.1 | 217 | 65% | 70% |
| Tursiops truncatus | Common Bottlenose Dolphin | Artiodactyla | 94 | XP_033698270.1 | 219 | 61% | 65% |
| Prionailurus bengalensis | Leopard Cat | Carnivora | 94 | XP_043452052.1 | 219 | 62% | 66% |
| Diceros bicornis minor | South-central Black Rhinoceros | Perissodactyla | 94 | XP_058399863.1 | 211 | 66% | 71% |
| Phascolarctos cinereus | Koala | Diprotodontia | 160 | XP_020823116.1 | 212 | 33% | 47% |
| Tyto alba | Barn Owl | Strigiformes | 319 | XP_032844583.1 | 218 | 28% | 46% |
| Rhea pennata | Darwin's Rhea | Rheiformes | 319 | XP_062436384.1 | 224 | 31% | 48% |
| Melanerpes formicivorous | Acorn Woodpecker | Piciformes | 319 | XP_067995321.1 | 224 | 34% | 52% |
| Ahaetulla prasina | Asian Vine Snake | Squamata | 319 | XP_058044567 | 216 | 32% | 49% |
| Alligator mississippiensis | American Alligator | Crocodilia | 319 | XP_014451110.1 | 223 | 34% | 47% |
| Caretta caretta | Loggerhead Sea Turtle | Testudines | 319 | XP_048714142.1 | 223 | 35% | 49% |
| Eublepharis macularius | Leopard Gecko | Squamata | 319 | XP_054839650.1 | 214 | 36% | 48% |
| Rhinatrema bivittatum | Two-lined Caecilian | Caecilians | 352 | XP_029466125.1 | 215 | 29% | 46% |
| Pleurodeles waltl | Iberian Ribbed Newt | Urodela | 352 | KAJ1140798.1 | 187 | 29% | 44% |
| Hyperolius riggenbachi | Riggenbach's Reed Frog | Anura | 352 | XP_068115078.1 | 216 | 31% | 44% |
| Erpetoichthys calabaricus | Reedfish | Polypteriformes | 429 | XP_028651575.1 | 215 | 29% | 44% |
| Salvelinus fontinalis | Brook Trout | Salmoniformes | 429 | XP_055757593.1 | 221 | 30% | 45% |
| Mobula hypostoma | Lesser Devil Ray | Myliobatiformes | 462 | XP_062927344.1 | 201 | 35% | 49% |
| Branchiostoma lanceolatum | European Lancelet | Amphioxiformes | 581 | CAH1258412.1 | 287 | 16% | 26% |
| Physella acuta | Bladder Snail | Basommatophora | 686 | XP_059175428.1 | 289 | 21% | 29% |

### Rate of evolution

C10orf95 is estimated to have first appeared in invertebrates about 686 million years ago. Very limited invertebrates had the protein with it only being found in lancelets and a variety of snails. The most distantly related species to humans with c10orf95 is the bladder snail that has no isoforms. The c10orf95 gene appears to evolve fairly quickly based on similarity to fibrinogen alpha evolution.

## Interacting proteins

| Protein | Interaction Type | Detection Method | Interacting Protein Function | Score |
| DDX39A (DExD-box helicase 39A) | Physical Association | Anti-tag coimmunoprecipitation | ATP-dependent RNA helicase DDX39A; Involved in pre-mRNA splicing. Required for the export of mRNA out of the nucleus; Belongs to the DEAD box helicase family. DECD subfamily. | 0.292 |
| NUS1 (nuclear undecaprenyl pyrophosphate synthase 1) | Physical Association | Anti-tag coimmunoprecipitation | This gene encodes a type I single transmembrane domain receptor, which is a subunit of cis-prenyltransferase, and serves as a specific receptor for the neural and cardiovascular regulator Nogo-B. The encoded protein is essential for dolichol synthesis and protein glycosylation. | 0.292 |

## Clinical significance

One study done on asthma found that c10orf95 was downregulated in the peripheral blood of asthmatics. Additionally, c10orf95 was listed as a commonly downregulated gene between the severe versus normal asthma and severe versus mild groups. Another study has identified a SNP at position 39 as a variant connected to an increased risk of late onset Alzheimer's disease.