Chromosome 1 open reading frame 185, also known as C1orf185, is a protein that in humans is encoded by the C1orf185 gene. In humans, C1orf185 is a lowly expressed protein that has been found to be occasionally expressed in the circulatory system.
Gene C1orf185 is located on chromosome 1 in humans on the positive strand between bases 51,102,221 and 51,148,086. There are 5 exons in the main splice isoform, however the number and selection of exons varies based on the isoform
mRNA and Protein Isoforms C1orf185 has 5 different splice isoforms in humans. +C1orf185 TranscriptsIsoformmRNA AccessionProtein AccessionTranscript Length (bp)Protein Length (AA)uncharacterized protein C1orf185NM_001136508.2 NP_001129980.1921199uncharacterized protein C1orf185 isoform X1XM_011541282.2XP_011539584.1 787195uncharacterized protein C1orf185 isoform X2XM_024446525.1XP_024302293.1586116uncharacterized protein C1orf185 isoform X3XM_024446528.1XP_024302296.1420116uncharacterized protein C1orf185 isoform X4XM_024446529.1XP_024302297.1367107
Protein C1orf185 is a member of the pfam15842 protein family, containing a domain of unknown function, DUF4718. This family of proteins is between 130 and 224 amino acids long, and is found only in eukaryotes..
The main splice isoform of C1orf185 has a molecular weight of 22.4 kDa and an isoelectric point of 7.67. It contains a transmembrane domain spanning from positions 15 to 37. There is also a conserved serine-rich region from S123 to S142, which could possibly indicate function as a "splicing activator".
C1orf185 contains 3 primary subcellular domains: an extracellular domain which spans the amino acids from positions 1 to 14, a transmembrane domain from positions 15–37, and a large intracellular domain from positions 38–199.
Below are predicted secondary and tertiary structures of C1orf185, modeled using the Chou-Fasman secondary structure prediction tool and the I-TASSER protein structure and function prediction tool. Chou-Fasman predicts a mixture of α-helices, β-sheets, and other structural turns and coils, which can be seen modeled on the I-TASSER prediction.
Regulation of expression
Gene level regulation Below is a diagram showing the locations of predicted transcription factor binding sites in the C1orf185 promoter, along with a table describing the attributes of each individual binding site. The transcription factors were found and analyzed using the ElDorado tool from Genomatix.
+Transcription Factor Binding Sites within the C1orf185 PromoterTranscription FactorDetailed matrix infoMatrix similaritySequence+/-VTATA.02Mammalian C-type LTR TATA box0.91tgtcaTAAAaacattcc+NKX25.05Homeodomain factor Nkx-2.5/Csx0.986tttttTGAGtgaagtcttg-CDX1.01Intestine specific homeodomain factor CDX-10.988ttgccctTTTAtgaaaaaa+VTATA.02Mammalian C-type LTR TATA box0.914tacttTAAAaataagca-ERG.02v-ets erythroblastosis virus E26 oncogene homolog0.942gtctcaaaGGAAaataaaaag-SPI1.02SPI-1 proto-oncogene; hematopoietic transcription factor PU.10.992attaaagaGGAAgtctcaaag-FHXB.01Fork head homologous X binds DNA with a dual sequence specificity (FHXA and FHXB)0.831ttctaaATAAcacattt-TGIF.01TG-interacting factor belonging to TALE class of homeodomain factors1tctataaatGTCAatta+ZNF219.01Kruppel-like zinc finger protein 2190.913ctccaCCCCcgtcagcccaaagg+ZBP89.01Zinc finger transcription factor ZBP-890.956catctccaCCCCcgtcagcccaa+CREB.02cAMP-responsive element binding protein0.922cctttgggcTGACgggggtgg-FOXP1_ES.01Alternative splicing variant of FOXP1, activated in ESCs1tcataaaAACAttccag-VTATA.02Mammalian C-type LTR TATA box0.895tgtcaTAAAaacattcc-CREB1.02cAMP-responsive element binding protein 10.949tggaaGTGAtgtcataaaaac-SPI1.02SPI-1 proto-oncogene; hematopoietic transcription factor PU.10.979atttgagtGGAAgtgatgtca-NKX25.05Homeodomain factor Nkx-2.5/Csx0.994gaattTGAGtggaagtgat-MESP1_2.01Mesoderm posterior 1 and 20.917cagtCATAtggct+MESP1_2.01Mesoderm posterior 1 and 20.929aagcCATAtgact-DELTAEF1.01deltaEF10.99gcttcACCTaaag+ERG.02v-ets erythroblastosis virus E26 oncogene homolog0.93gaagaagaGGAAaatatattt+ Matrix similarity correlates to the confidence in the prediction for each individual binding sites. +/- correlates to presence on either the positive or negative strand. The transcription factors are listed in order of appearance from beginning to end of the promoter.
C1orf185 has a very low expression pattern, with the only site in the body showing any signs of expression being the circulatory system. Two NCBI GEO profiles have shown that C1orf185 was consistently overexpressed in whole blood samples within a group of postmenopausal women, as well as being somewhat overexpressed in the peripheral blood of Parkinson's patients compared to controls.
Transcript level regulation Below is a figure produced by showing predicted mRNA structure of the 3' UTR of C1orf185.
C1orf185 has one conserved miRNA binding site of type 7mer-A1 among several orthologs. The presence of a 7mer-A1 binding site indicates that C1orf185 is likely to be post-transcriptionally repressed.
Protein level regulation Below is a figure and table showing predicted post-translational modification sites for C1orf185.
+Table of Post-Translational Modifications for C1orf185Type of ModificationToolPositions in Homo sapiensPhosphorylationNetPhosS61, S69, S104, S130, S142, S147, S165, S186GlycationNetGlycate, NetNGlycK5, K50, K98, K113O-GlcNAcYinOYangT121, S122, S130 The presence of multiple leucine glycation sites indicate that there may be ways to deter the function of the protein, as glycation has been associated with the loss of protein function in blood vessels
Clinical significance C1orf185 has been shown to play a role in the circulatory system, likely in a more reactive role, as it is lowly expressed across many species. It appears in studies surrounding atrial fibrillation and abnormal QRS duration, which implies it may play a role in those circulatory diseases.
Homology Below is a table showing C1orf185 orthologs across a variety of conserved species. Orthologs were found using NCBI BLAST, the dates of divergence were found using TimeTree, and the global sequence identities and similarities were found using the Clustal Omega multiple sequence alignment tool.
+Ortholog Table for C1orf185.Genus and speciesCommon nameTaxonomic groupDate of Divergence (MYA)Accession numberSequence length (aa)Sequence identity (Global)Sequence similarity (Global) Homo sapiensHumanPrimates0NP_001129980.1199100%100%Pongo abeliiSumatran orangutanPrimates15.76PNJ53823.119593.50%95.50%Cebus capucinus imitatorCapuchinPrimates43.2XP_017404303.122977.00%79.60%Galeopterus variegatusSunda flying lemurDermoptera76XP_008578352.120373.70%77.90%Oryctolagus cuniculusRabbitLagomorpha90XP_008263491.122569.90%76.40%Dipodomys ordiiOrd's kangaroo ratRodentia90XP_012877642.118852.20%59.40%Mastomys couchaSouthern multimammate mouseRodentia90XP_03123403726351.50%61.50%Mus musculusHouse mouseRodentia90NP_001186019.122647.40%59.50%Peromyscus leucopusWhite-footed mouseRodentia90XP_028745885.129541%48.20%Phyllostomus discolorPale spear-nosed batChiroptera96XP_028367083.119173.40%80.40%Myotis davidiiDavid's myotisChiroptera96XP_006768446.119671.40%78.40%Equus caballusHorsePerissodactyla96XP_023485921.124363.80%68.30%Muntiacus muntjakIndian muntjacArtiodactyla96KAB0362285.120059.40%65.90%Hipposideros armigerGreat roundleaf batChiroptera96XP_019487867.115754.90%59.20%Tursiops truncatusBottlenose dolphinArtiodactyla96XP_033708766.118954.10%59.00%Sarcophilus harrisiiTasmanian devilDasyuromorhpia159XP_031825005.133318.20%27.70%Ornithorhynchus anatinusPlatypusMonotremata180XP_02890227130926.80%37.40%Pelodiscus sinensisChinese softshell turtleReptilia312XP_025042106.18907.40%11.40%Gopherus evgoodeiSinaloan thornscrub tortoiseReptilia312XP_030429802.17774.00%6.30%Chrysemys picta belliiWestern painted turtleReptilia312XP_023960730.17483.70%5.80% Compared to other genes, C1orf185 appears to be evolving and changing relatively quickly, as it is only conserved in mammals and a few turtles, and more distant mammals have quite distant similarities. Primates are the only taxonomic group that heavily conserves this gene with regards to the human sequence, while other mammals and turtles only heavily conserve the transmembrane domain (positions 15–37). As primates and mammals are warm-blooded, this may further support the evidence showing a possible role in the circulatory system.
References