TMEM19
{{Short description|Protein encoded by the TMEM19 gene}}
{{Infobox gene}}
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.{{cite journal | vauthors = Fu S, Liu J | title = Genome-wide association study identified genes associated with ammonia nitrogen tolerance in Litopenaeus vannamei | journal = Frontiers in Genetics | volume = 13 | pages = 961009 | date = 2022-08-22 | pmid = 36072655 | pmc = 9441690 | doi = 10.3389/fgene.2022.961009 | doi-access = free }} 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.{{cite journal | vauthors = Yu Y, Zuo X, He M, Gao J, Fu Y, Qin C, Meng L, Wang W, Song Y, Cheng Y, Zhou F, Chen G, Zheng X, Wang X, Liang B, Zhu Z, Fu X, Sheng Y, Hao J, Liu Z, Yan H, Mangold E, Ruczinski I, Liu J, Marazita ML, Ludwig KU, Beaty TH, Zhang X, Sun L, Bian Z | display-authors = 6 | title = Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity | journal = Nature Communications | volume = 8 | pages = 14364 | date = February 2017 | pmid = 28232668 | pmc = 5333091 | doi = 10.1038/ncomms14364 | bibcode = 2017NatCo...814364Y }} 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.{{cite journal | vauthors = Yu X, Guo Z, Fang Z, Yang K, Liu C, Dong Z, Liu C | title = Identification and validation of disulfidptosis-associated molecular clusters in non-alcoholic fatty liver disease | journal = Frontiers in Genetics | volume = 14 | pages = 1251999 | date = 2023-09-08 | pmid = 37745847 | pmc = 10514914 | doi = 10.3389/fgene.2023.1251999 | doi-access = free }}
File:TMEM19 - 5662 nucleotides Map.pdf|A conceptual translation of the human TMEM19 was made using data from NCBI{{Cite web |title=TMEM19 transmembrane protein 19 [Homo sapiens (human)] - Gene - NCBI |url=https://www.ncbi.nlm.nih.gov/gene/55266 |access-date=2023-12-16 |website=www.ncbi.nlm.nih.gov}} and translated using Six Frame Translations.{{Cite web |title=Six-Frame Translation |url=https://www.bioline.com/media/calculator/01_13.html |access-date=2023-12-16 |website=www.bioline.com}} Transmembrane regions are highlighted in gray, and highly conserved regions are bolded.
File:PT2 Map.pdf|A conceptual translation of the human TMEM19 was made using data from NCBI and translated using Six Frame Translations. Transmembrane regions are highlighted in gray, and highly conserved regions are bolded.
File:PT3 Map.pdf|A conceptual translation of the human TMEM19 was made using data from NCBI and translated using Six Frame Translations. 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.{{cite journal | vauthors = Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, Zhang J, Soden R, Hayakawa M, Kreiman G, Cooke MP, Walker JR, Hogenesch JB | display-authors = 6 | title = A gene atlas of the mouse and human protein-encoding transcriptomes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 16 | pages = 6062–6067 | date = April 2004 | pmid = 15075390 | pmc = 395923 | doi = 10.1073/pnas.0400782101 | doi-access = free | bibcode = 2004PNAS..101.6062S }} TMEM19 interacts with many proteins, most of these proteins are localized around membranes found in the cell.
File:TMEM19 Large-scale Analysis of the Human Transcriptome (HG-U133A).png
= Protein Interactions =
| class="wikitable"
|Protein |Full Name |Detection Method |Description |CV |
| MC4R
|Melanocortin 4 Receptor |Ubiquitin Reconstruction |Membrane-bound receptor and member of the melanocortin receptor family. Protein interacts with adrenocorticotropic and MSH hormones. Mediated by G proteins. (NCBI{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/4160 | title=MC4R melanocortin 4 receptor [Homo sapiens (Human)] - Gene - NCBI }}) |0.37 |
| BSCL2
|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{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/26580#summary | title=BSCL2 BSCL2 lipid droplet biogenesis associated, seipin [Homo sapiens (Human)] - Gene - NCBI }}) |0.67 |
| APOA5
|Apolipoprotein A5 |Two Hybrid |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{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/116519 | title=APOA5 apolipoprotein A5 [Homo sapiens (Human)] - Gene - NCBI }}) |0.56 |
| AQP6
|Aquaporin 6 |Two Hybrid |Functions as a water channel in cells. Specific to the kidney. (NCBI{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/363 | title=AQP6 aquaporin 6 [Homo sapiens (Human)] - Gene - NCBI }}) |0.56 |
| C10orf67
|Chromosome 10 open reading frame 67 |Two Hybrid |Predicted to be located in mitochondrion. Possible link to Crohn's and sarcoidosis. (NCBI{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/256815 | title=C10orf67 chromosome 10 open reading frame 67 [Homo sapiens (Human)] - Gene - NCBI }}) |0.56 |
| CD3G
|CD3 gamma subunit of T-cell receptor complex |Two Hybrid |Component of the T-cell receptor-CD3 complex. Mutations with this protein are associated with T cell immunodeficieny. (NCBI{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/917 | title=CD3G CD3 gamma subunit of T-cell receptor complex [Homo sapiens (Human)] - Gene - NCBI }}) |0.56 |
| CD79A
|CD79a molecule |Two Hybrid |The Ig-alpha protein of the B-cell antigen component. (NCBI{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/973 | title=CD79A CD79a molecule [Homo sapiens (Human)] - Gene - NCBI }}) |0.56 |
| CNR2
|Cannabinoid receptor 2 |Two Hybrid |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{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/1269 | title=CNR2 cannabinoid receptor 2 [Homo sapiens (Human)] - Gene - NCBI }}) |0.56 |
| CPLX4
|Complexin 4 |Two Hybrid |May be involved in synaptic vesicle exocytosis. (NCBI{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/339302#summary | title=CPLX4 complexin 4 [Homo sapiens (Human)] - Gene - NCBI }}) |0.56 |
| CREB3
|cAMP responsive element binding protein 3 |Two Hybrid |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{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/10488 | title=CREB3 cAMP responsive element binding protein 3 [Homo sapiens (Human)] - Gene - NCBI }}) |0.56 |
| CREB3L1
|cAMP responsive element binding protein 3 like 1 |Two Hybrid |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{{cite web | url=https://www.ncbi.nlm.nih.gov/gene/90993 | title=CREB3L1 cAMP responsive element binding protein 3 like 1 [Homo sapiens (Human)] - Gene - NCBI }}) |0.56 |
= Post translational modifications =
File:JPEG TMEM19 in Membrane with PTM.jpgUsing 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.{{Cite web |title=The CUCKOO Workgroup |url=https://biocuckoo.org/ |access-date=2023-12-07 |website=biocuckoo.org}}
| class="wikitable sortable"
|+Phosphorylation Sites |Position |Code |Kinase |Protein Sequence Pos. |Score |Cutoff |
| 197
|S |AGC |SEVGPVLSKSSPRLI |0.0559 |0.0197 |
| 214
|T |AGC |WEKVPVGTNGGVTVV |0.0568 |0.0197 |
| 187
|T |CK1 |LACSAGDTWASEVGP |0.0666 |0.0532 |
| 108
|S |AGC |LMFFLSSSKLTKWKG |0.1333 |0.0197 |
| 288
|T |CK1 |YTGLDESTGMVVNSP |0.1427 |0.0532 |
| 287
|S |CK1 |QYTGLDESTGMVVNS |0.1517 |0.0532 |
| 200
|S |GPVLSKSSPRLITTW |0.1546 |0.0403 |
| 296
|T |CK1 |GMVVNSPTNKARHIA |0.2926 |0.0532 |
| 125
|Y |TK |KKRLDSEYKEGGQRN |0.7851 |0.7641 |
| 167
|Y |TK |PVDFSKQYSASWMCL |0.8679 |0.7641 |
| 281
|Y |TK |YLGATMQYTGLDEST |0.9762 |0.7641 |
Evolutionary history
File:Sequence Divergence of TMEM19.pngTMEM19 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.
File:Strict Annotated Orthlog Alignment TMEM19.png|TMEM19 Strict Orthologs (Vertebrates) Multiple Sequence Alignment. Sequences were aligned using ClustalO,{{Cite web |title=Clustal Omega < Multiple Sequence Alignment < EMBL-EBI |url=https://www.ebi.ac.uk/Tools/msa/clustalo/ |access-date=2023-12-16 |website=www.ebi.ac.uk}} 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.
File:Strict Annotated Orthlog Alignment P2 TMEM19.png|TMEM19 Strict Orthologs (Vertebrates) Multiple Sequence Alignment. Sequences were aligned using ClustalO, 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.
File:Strict Annotated Orthlog Alignment P3 TMEM19.png|TMEM19 Strict Orthologs (Vertebrates) Multiple Sequence Alignment. Sequences were aligned using ClustalO, 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.
| class="wikitable sortable"
|+Orthologs of Human TMEM19 !Common Name !Class !Order !Genus and Species !Median Date of Divergence !Accession Number !Sequence Length !Sequence Identity to Humans % !Sequence Similarity to Humans % |
| Humans
|Mammal |Primates |Homo sapiens |0 |336 |100 |100 |
| Mouse
|Mammal |Rodentia |Mus musculus |87 |351 |87.46 |90.3 |
| Meerkat
|Mammal |Suricata suricatta |94 |336 |91.92 |96.4 |
| Jamaican Fruit Bat
|Mammal |Bats |Artibeus jamaicensis |94 |336 |90.45 |95.5 |
| Baiji Dolphin
|Mammal |Lipotes vexillifer |94 |358 |89.58 |90.8 |
| Leatherback Turtle
|Reptile |Dermochelys coriacea |319 |335 |82.26 |89.9 |
| Schlegal's Japanese Gecko
|Reptile |Gekko japonicus |319 |282 |81.23 |77.4 |
| Burmese Python
|Reptile |Python bivittatus |319 |371 |80.06 |80.1 |
| Viviparous Lizard
|Reptile |Zootoca vivipara |319 |336 |79.85 |88.3 |
| Emu
|Bird |Dromaius novaehollandiae |319 |336 |77.38 |89.3 |
| Black Legged Kittiwake
|Bird |Rissa tridactyla |319 |367 |77.31 |82.3 |
| Japanese Quail
|Bird |Coturnix japonica |319 |344 |76.13 |86.4 |
| California Condor
|Bird |Gymnogyps |Accipitriformes |319 |336 |77.4 |89.6 |
| African Clawed Frog
|Amphibian |Xenopus laevis |352 |336 |76.12 |89.3 |
| Two-Lined Caecillian
|Amphibian |Rhinatrema bivittatum |352 |336 |76.12 |89.3 |
| Asian Arowana
|Fish |Scleropages formosus |429 |336 |69.33 |84.5 |
| Pacific Halibut
|Fish |Hippoglossus stenolepis |429 |335 |67.87 |83 |
| Sea Lamprey
|Fish |Petromyzon marinus |563 |362 |63.35 |73 |
| Zebra Shark
|Fish |Stegostoma tigrinum |462 |354 |73.59 |80.5 |
| Pin Mould
|Fungi |Mucor mucedo |1275 |284 |32.8 |47.7 |
| Ascomycete Fungi
|Fungi |Lachnellula hyalina |1275 |383 |23.3 |35.9 |
| Thale Cress
|Plant |Arabidopsis thaliana |1598 |288 |34.6 |50 |