Transmembrane protein 19 is a protein that in humans is encoded by the TMEM19 gene.
Gene
TMEM19 location on chromosome 12
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.[5] 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.[6] 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.[7]
A conceptual translation of the human TMEM19 was made using data from NCBI[8] and translated using Six Frame Translations.[9] Transmembrane regions are highlighted in gray, and highly conserved regions are bolded.
A conceptual translation of the human TMEM19 was made using data from NCBI[8] and translated using Six Frame Translations.[9] Transmembrane regions are highlighted in gray, and highly conserved regions are bolded.
A conceptual translation of the human TMEM19 was made using data from NCBI[8] and translated using Six Frame Translations.[9] Transmembrane regions are highlighted in gray, and highly conserved regions are bolded.
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.[10] TMEM19 interacts with many proteins, most of these proteins are localized around membranes found in the cell.
Data was obtained from a large-scale analysis of the human transcriptome on NCBI Geo.[10] The data contains expression patterns of TMEM19 in different tissues in the body. The value in red shows the amount of expression and the blue dot signifies the rank of expression compared to other protein expression in tissues.TMEM19 expression in Mus musculus brain. A sagittal slice of a mouse midbrain shows expression of TMEM19 shown in purple. The image was collected by the Allen Brain Map.[11]
Membrane-bound receptor and member of the melanocortin receptor family. Protein interacts with adrenocorticotropic and MSH hormones. Mediated by G proteins. (NCBI[12])
Bernardinelli-Seip Congenital Lipodystrophy Type 2 Protein
Two Hybrid
Also 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[13])
Plays 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[14])
G 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[19])
0.56
CPLX4
Complexin 4
Two Hybrid
May be involved in synaptic vesicle exocytosis. (NCBI[20])
Transcription 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[21])
Normally 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[22])
0.56
Post translational modifications
Visual predicted representation of TMEM19 in the cell membrane. In image A the transmembrane regions were selected using NCBI[8] and in image B the seventh predicted transmembrane region found from SOSUI analysis was added. Amino acids in red are sites of kinase phosphorylation.
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.[23]
Sequence Divergence of TMEM19. The sequence divergence of TMEM19 was compared alongside Cytochrome C and Fibrinogen alpha. Sequence identity of each protein was determined in order to find the sequence divergence. The sequence divergence was used to calculate the corrected divergence (M). A line of best fit was included to show the projected divergence.
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.
TMEM19 Strict Orthologs (Vertebrates) Multiple Sequence Alignment. Sequences were aligned using ClustalO,[24] transmembrane regions and exons were boxed. Consensus of amino acids are shown at 100% and 90%. Amino acids are colored based on their physicochemical properties.
TMEM19 Strict Orthologs (Vertebrates) Multiple Sequence Alignment. Sequences were aligned using ClustalO,[24] transmembrane regions and exons were boxed. Consensus of amino acids are shown at 100% and 90%. Amino acids are colored based on their physicochemical properties.
TMEM19 Strict Orthologs (Vertebrates) Multiple Sequence Alignment. Sequences were aligned using ClustalO,[24] transmembrane regions and exons were boxed. Consensus of amino acids are shown at 100% and 90%. Amino acids are colored based on their physicochemical properties.
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