Transmembrane protein 19 is a protein that in humans is encoded by the TMEM19 gene.
Gene
The TMEM19 gene is located on chromosome 12(12q21.1) spanning 18,966 base pairs on the + strand. The gene has a total of 6 exon regions.
Studies have found that after using single nucleotide polymorphism (SNP) genotyping array method the TMEM19 gene was identified to be associated with ammonia nitrogen tolerance. Using a genome-wide association study of individuals with non-syndromic cleft lip with palate (NSCLP) to identify loci that are at risk for the birth defect. From this they were able to identify the loci of TMEM19 as a risk for this birth defect, along with 25 other loci.
Transcript The mRNA transcript of TMEM19 is 5662 base pairs. The TMEM19 transcript was found to be expressed in most tissues but has increased expression in duodenum, kidney, skin, small intestine, and urinary bladder. in a non-alcoholic fatty liver disease (NAFLD) model in cells that were subjected to glucose deficiency or oxidative stress. This results in cell death due to excessive disulfide formation in actin cytoskeleton and actin filament called disulfidptosis.
Protein TMEM19 is a protein spanning 336 amino acids. It has 6 transmembrane regions. The protein is found at moderate levels in the body, with the highest expression found in superior cervical ganglia and cardiac myocytes. TMEM19 interacts with many proteins, most of these proteins are localized around membranes found in the cell.
Protein Interactions ProteinFull NameDetection MethodDescriptionCVMC4RMelanocortin 4 ReceptorUbiquitin ReconstructionMembrane-bound receptor and member of the melanocortin receptor family. Protein interacts with adrenocorticotropic and MSH hormones. Mediated by G proteins. (NCBI)0.37BSCL2Bernardinelli-Seip Congenital Lipodystrophy Type 2 ProteinTwo HybridAlso known as Seipin, a multi-pass transmembrane protein. Localized in the ER and is predicted to be associated with lipid droplet morphology. Mutations of this gene leads to Berardinelli-Seip syndrome which results in absence of adipose tissue and severe insulin resistance. (NCBI)0.67APOA5Apolipoprotein A5Two HybridPlays a role in regulating the plasma triglyceride levels, a major risk factor of CAD. Is a component of high-density lipoprotein, similar to a rat protein that is upregulated in response to liver injury. Mutations in the gene are associated with hypertriglyceridemia and hyperlipoproteinemia type 5. (NCBI)0.56AQP6Aquaporin 6Two HybridFunctions as a water channel in cells. Specific to the kidney. (NCBI)0.56C10orf67Chromosome 10 open reading frame 67Two HybridPredicted to be located in mitochondrion. Possible link to Crohn's and sarcoidosis. (NCBI)0.56CD3GCD3 gamma subunit of T-cell receptor complexTwo HybridComponent of the T-cell receptor-CD3 complex. Mutations with this protein are associated with T cell immunodeficiency. (NCBI)0.56CD79ACD79a moleculeTwo HybridThe Ig-alpha protein of the B-cell antigen component. (NCBI)0.56CNR2Cannabinoid receptor 2Two HybridG protein-coupled receptor from cannabinoid family. Related to CB1 which is responsible for the efficacy of THC. Mainly expressed in cells of the immune system. (NCBI)0.56CPLX4Complexin 4Two HybridMay be involved in synaptic vesicle exocytosis. (NCBI)0.56CREB3cAMP responsive element binding protein 3Two HybridTranscription factor that bind to cAMP-response element and regulates cell proliferation. Also plays a role in leukocyte migration, tumor suppression, and ER stress-associated protein degradation. (NCBI)0.56CREB3L1cAMP responsive element binding protein 3 like 1Two HybridNormally found in the membrane of ER. Upon stress to ER the protein is cleaved and released into the cytoplasm where is translocated to the nucleus. It then activates the transcription of target genes by binding to box-B elements. (NCBI)0.56
Post translational modifications Using BioCuckoo, TMEM19 was analyzed for phosphorylation sites in the protein sequence. The program was run on a medium threshold and scanned for every kinase available. Phosphorylation sites are in order of decreasing score. AGC represents protein kinase A, protein kinase G, and protein kinase C. +Phosphorylation SitesPositionCodeKinaseProtein Sequence Pos.ScoreCutoff197SAGCSEVGPVLSKSSPRLI0.05590.0197214TAGCWEKVPVGTNGGVTVV0.05680.0197187TCK1LACSAGDTWASEVGP0.06660.0532108SAGCLMFFLSSSKLTKWKG0.13330.0197288TCK1YTGLDESTGMVVNSP0.14270.0532287SCK1QYTGLDESTGMVVNS0.15170.0532200SCDK, MAPK, GSK, CLKGPVLSKSSPRLITTW0.15460.0403296TCK1GMVVNSPTNKARHIA0.29260.0532125YTKKKRLDSEYKEGGQRN0.78510.7641167YTKPVDFSKQYSASWMCL0.86790.7641281YTKYLGATMQYTGLDEST0.97620.7641
Evolutionary history TMEM19 Orthologs were sorted by the median date of divergence. TMEM19 has a median date of divergence greater than 1598 MYA which is found in Thale cress. TMEM19 does not have any paralogs, this was determined after running TMEM19 through BLAST. The human TMEM19 protein is closely related to vertebrates and moderately related to fungi/plants. TMEM19 evolves at a rate that is related to cytochrome c. +Orthologs of Human TMEM19Common nameClassOrderGenus and speciesMedian Date of DivergenceAccession numberSequence lengthSequence identity to Humans %Sequence similarity to Humans %HumansMammalPrimatesHomo sapiens0NP_060749.2336100100MouseMammalRodentiaMus musculus87NP_001346399.135187.4690.3MeerkatMammalCarnivoraSuricata suricatta94XP_029810978.133691.9296.4Jamaican Fruit BatMammalBatsArtibeus jamaicensis94XP_037017069.233690.4595.5Baiji DolphinMammalArtiodactylaLipotes vexillifer94XP_007448836.135889.5890.8Leatherback TurtleReptileTestudinesDermochelys coriacea319XP_038233118.133582.2689.9Schlegal's Japanese GeckoReptileSquamataGekko japonicus319XP_015261175.128281.2377.4Burmese PythonReptileSquamataPython bivittatus319XP_007423004.137180.0680.1Viviparous LizardReptileSquamataZootoca vivipara319XP_034984278.133679.8588.3EmuBirdCasuariiformesDromaius novaehollandiae319XP_025956153.133677.3889.3Black Legged KittiwakeBirdCharadriiformesRissa tridactyla319XP_054044439.136777.3182.3Japanese QuailBirdGalliformesCoturnix japonica319XP_015711317.134476.1386.4California CondorBirdGymnogypsAccipitriformes319XP_050753817.133677.489.6African Clawed FrogAmphibianAnuraXenopus laevis352NP_001085034.133676.1289.3Two-Lined CaecillianAmphibianGymnophionaRhinatrema bivittatum352XP_029453037.133676.1289.3Asian ArowanaFishOsteoglossiformesScleropages formosus429XP_018611167.133669.3384.5Pacific HalibutFishPleuronectiformesHippoglossus stenolepis429XP_035003305.133567.8783Sea LampreyFishPetromyzontiformesPetromyzon marinus563XP_032815808.136263.3573Zebra SharkFishOrectolobiformesStegostoma tigrinum462XP_048404699.135473.5980.5Pin MouldFungiMucoralesMucor mucedo1275XP_051459555.128432.847.7Ascomycete FungiFungiHelotialesLachnellula hyalina1275XP_031007997.138323.335.9Thale CressPlantBrassicalesArabidopsis thaliana1598NP_001190343.128834.650
References