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/SpeciesCommon nameTaxonomic OrderDate of Divergence (MYA)Accession numberSequence length (aa)Sequence identitySequence similarityHomo sapiensHumanPrimate0NP_001350509.1213100%100%Oryctolagus cuniculusEuropean RabbitLagomorpha87XP_051679518.121765%70%Tursiops truncatusCommon Bottlenose DolphinArtiodactyla94XP_033698270.121961%65%Prionailurus bengalensisLeopard CatCarnivora94XP_043452052.121962%66%Diceros bicornis minorSouth-central Black RhinocerosPerissodactyla94XP_058399863.121166%71%Phascolarctos cinereusKoalaDiprotodontia160XP_020823116.121233%47%Tyto albaBarn OwlStrigiformes319XP_032844583.121828%46%Rhea pennataDarwin's RheaRheiformes319XP_062436384.122431%48%Melanerpes formicivorousAcorn WoodpeckerPiciformes319XP_067995321.122434%52%Ahaetulla prasinaAsian Vine SnakeSquamata319XP_05804456721632%49%Alligator mississippiensisAmerican AlligatorCrocodilia319XP_014451110.122334%47%Caretta carettaLoggerhead Sea TurtleTestudines319XP_048714142.122335%49%Eublepharis maculariusLeopard GeckoSquamata319XP_054839650.121436%48%Rhinatrema bivittatumTwo-lined CaecilianCaecilians352XP_029466125.121529%46%Pleurodeles waltlIberian Ribbed NewtUrodela352KAJ1140798.118729%44%Hyperolius riggenbachiRiggenbach's Reed FrogAnura352XP_068115078.121631%44%Erpetoichthys calabaricusReedfishPolypteriformes429XP_028651575.121529%44%Salvelinus fontinalisBrook TroutSalmoniformes429XP_055757593.122130%45%Mobula hypostomaLesser Devil RayMyliobatiformes462XP_062927344.120135%49%Branchiostoma lanceolatumEuropean LanceletAmphioxiformes581CAH1258412.128716%26%Physella acutaBladder SnailBasommatophora686XP_059175428.128921%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 ProteinInteraction TypeDetection MethodInteracting Protein FunctionScoreDDX39A
(DExD-box helicase 39A)Physical AssociationAnti-tag coimmunoprecipitationATP-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.0.292NUS1
(nuclear undecaprenyl pyrophosphate synthase 1)Physical AssociationAnti-tag coimmunoprecipitationThis 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.
References