TMEM198 (Transmembrane Protein 198) is a protein in humans encoded by the TMEM198 gene, also known as TMEM198A. TMEM198 is known to promote LRP6 phosphorylation by casein kinases. Furthermore, a knockdown of TMEM198 in Vero cells significantly reduces the production of PEDV and SADS. Porcine Epidemic Diarrhea Virus (PEDV) and Swine Acute Diarrhea Syndrome Coronavirus (SADS) are both coronaviruses that infect pigs.
Gene TMEM198 gene is located on chromosome 2 (2q35), with a plus orientation.
TMEM198 has 5 exons and spans 6,568 bp, with the coding region 1,083 bp. The fifth exon is hard to discern, which is due to being too small to detect and/or located near the UTR regions. TMEM198 is principally observed in the Brain ( expressed at 2.52), Ovary (4.71), and testes (2.19). The overexpression of TMEM198 promotes tumor growth, which leads to cancers such as Rectosigmoid Cancer.
In the gene neighborhood of the human gene TMEM198, there are notable genes located such as: Acid-sensing ion channel 4 (ASIC4), inhibin subunit alpha (INHA), and GDP-Mannose Pyrophosphorylase A (GMPPA) are all upstream of TMEM198. While Chondroitin Polymerizing Factor (CHPF), ODS1, and ASIC4 Antisense RNA 1 (ASCIC4-AS1) are all downstream.
Protein TMEM198 is 360 amino acids long, with long untranslated regions (UTRs). The conceptual translation of TMEM198 depicts multiple transmembrane regions as well as phosphorylation sites.
The first 3 labeled missense mutations do not affect major proteins. This was determined with multiple sequence alignment to identify the most conserved proteins among multiple vertebrates. However, the last two missense mutations affect a protein that is highly conserved within all tested vertebrates, highlighting its importance.
In humans, TMEM198 has a molecular weight of 39.3kDa and a theoretical pI of approximately 10.0. TMEM198 is predicted to be positively charged at physiological pH. TMEM198 also has a high Leu% (16.7%), thus making TMEM198 hydrophobic.
Structure TMEM198 has 15 alternate splice variants and 3 distinct transcript variants. The 3 main transcript variants encode the same protein, NP_001005209.1, thus making TMEM198 only have one protein isoform.
The structure of TMEM198 can be noted to have alpha helices as the area with main confidence, while the beta sheets are of lower confidence in the true structure.
There are 6 transmembrane helices (hydrophobic alpha helices). This is to be considered as more evidence shows that TMEM198 has 7 transmembrane helices, with the seventh one having a lower probability of appearing as compared to the first 6.
Dis1 and Dis2 are regions with no fixed 3d structure. It’s located at the C-terminus end of the protein, in the cytoplasm, thus making it the protein's signaling end. UniProt does note that the protein is involved in Wnt signalling via LRP6. The first 35 amino acids at the N- terminal of TMEM198 are necessary for viral replication as well as the formation of DMVs (Double-Membrane Vesicles)
Homologs
Ortholog table The following table provides a few details on orthologs of the human version of TMEM198. To save space, not all of these orthologs are included in the multiple sequence alignment. Only the listed vertebrates were included. These orthologs were identified through TimeTree and BLAST searches. The table is categorized by increasing date of divergence from the human lineage, with Hazel plant being the furthest known ortholog of TMEM198.
A major trend of the Ortholog table is that as the date of divergence from the human lineage increases, so does the sequence length. There are a few outliers to this trend, but it is otherwise notable.
TMEM198 has no known paralog in the human genome.
Genus and speciesCommon nametaxonomic group
(order)date of divergence from the human lineage
(MYA)accession numbersequence length (aa)sequence identity to a human protein mammalsHomo sapienshumansPrimates0NP_001005209.1360100%Cercocebus atyssooty-mangabeyCercopithecidae 28.8 XP_032133956.1 36099.4%Mesoplodon densirostrisBlainville's beaked whale Cetacea 94 XP_059962316.136097.5%Vulpes lagopusArctic foxCarnivora 94XP_041593119 36098.33%Birds Aptenodytes forsteriemperor penguin Sphenisciformes319XP_009273195.1 36762.81%Cygnus atratusblack swan atratus 319XP_03539271536561.79%Aphelocoma coerulescensscrub jayPasseriformes 319 XP_068876958.140263.09%AmphibianXenupus laevisAfrican clawed frogAnura352XP_018091162.136062.71%Ambystoma mexicanum axolotlCaudata 353XP_06947304636759.51%Pleurodeles waltlIberian ribbed newtCaudata. 353XP_069083303.136660.22%Leptodactylus fuscusRufuos frogAnura360 XP_07514066936062.71%FishPangasianodon hypophthalmusStriped catfishSiluriformes429 XP_02676833538452.97%Barbatula barbatulaStone loachCypriniformes429 XP_079321182 38055.09%Anguilla rostrataAmerican eelAnguilliformes 429 XP_064185487.1 36058.33%Conger congerEuropean congerAnguilliformes429 XP_06109151236558.49%CnidraMontipora capricornisStony coralsScleractinia 685XP_068749306.1 34231.01%Insects Homalodisca vitripennisGlassy-winged sharpshooterHemiptera 686 XP_046670335.134741.7% Planococcus citri citrus mealybug Hemiptera 686 XP_065218741.1 39733.22%Lampyridae fireflyColeoptera 686XP_031343369.1 34937.94%Reduviidae Assassin bugHemiptera 686KAK9500599.1 30134%plantsCorylus avellana Hazel Fagales 1530 XP_059433272.1 77331.94%
Multiple sequence alignment The multiple sequence alignment (MSA) box-frame format. It demonstrates that TMEM198 is highly conserved across a wide range of vertebrate species, including mammals, fish, amphibians, and a bird (long-tailed hermit used as an outlier). (The American eel may not be a true TMEM198 ortholog given its FASTA header mislabeling). The consistency score of 96 indicates high confidence in the alignment, meaning the residue positions are strongly supported across pairwise comparisons.
Phylogenetic tree The Phylogenetic tree depicts the evolutionary relationships among 15 vertebrate species from the Ortholog table, excluding Hazel, as it will exaggerate the results. The furthest relative in this phylogenetic tree is Anguilla rostrata.
References