Biology:TMEM19
![]() Generic protein structure example |
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.[1] 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.[2] 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.[3]
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.[6] TMEM19 interacts with many proteins, most of these proteins are localized around membranes found in the cell.
![](https://upload.wikimedia.org/wikipedia/commons/thumb/0/09/TMEM19_Large-scale_Analysis_of_the_Human_Transcriptome_%28HG-U133A%29.png/250px-TMEM19_Large-scale_Analysis_of_the_Human_Transcriptome_%28HG-U133A%29.png)
![](https://upload.wikimedia.org/wikipedia/commons/thumb/5/58/AllenBrainAtlas_TMEM19_expression_in_Mouse_Brain.png/250px-AllenBrainAtlas_TMEM19_expression_in_Mouse_Brain.png)
Protein Interactions
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[8]) | 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[9]) | 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[10]) | 0.56 |
AQP6 | Aquaporin 6 | Two Hybrid | Functions as a water channel in cells. Specific to the kidney. (NCBI[11]) | 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[12]) | 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[13]) | 0.56 |
CD79A | CD79a molecule | Two Hybrid | The Ig-alpha protein of the B-cell antigen component. (NCBI[14]) | 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[15]) | 0.56 |
CPLX4 | Complexin 4 | Two Hybrid | May be involved in synaptic vesicle exocytosis. (NCBI[16]) | 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 supression, and ER stress-associated protein degradation. (NCBI[17]) | 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[18]) | 0.56 |
Post translational modifications
![](https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/JPEG_TMEM19_in_Membrane_with_PTM.jpg/250px-JPEG_TMEM19_in_Membrane_with_PTM.jpg)
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.[19]
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 | CDK, MAPK,
GSK, CLK |
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
![](https://upload.wikimedia.org/wikipedia/commons/thumb/5/5c/Sequence_Divergence_of_TMEM19.png/250px-Sequence_Divergence_of_TMEM19.png)
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.
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 | NP_060749.2[21] | 336 | 100 | 100 |
Mouse | Mammal | Rodentia | Mus musculus | 87 | NP_001346399.1[22] | 351 | 87.46 | 90.3 |
Meerkat | Mammal | Carnivora | Suricata suricatta | 94 | XP_029810978.1[23] | 336 | 91.92 | 96.4 |
Jamaican Fruit Bat | Mammal | Bats | Artibeus jamaicensis | 94 | XP_037017069.2[24] | 336 | 90.45 | 95.5 |
Baiji Dolphin | Mammal | Artiodactyla | Lipotes vexillifer | 94 | XP_007448836.1[25] | 358 | 89.58 | 90.8 |
Leatherback Turtle | Reptile | Testudines | Dermochelys coriacea | 319 | XP_038233118.1[26] | 335 | 82.26 | 89.9 |
Schlegal's Japanese Gecko | Reptile | Squamata | Gekko japonicus | 319 | XP_015261175.1[27] | 282 | 81.23 | 77.4 |
Burmese Python | Reptile | Squamata | Python bivittatus | 319 | XP_007423004.1[28] | 371 | 80.06 | 80.1 |
Viviparous Lizard | Reptile | Squamata | Zootoca vivipara | 319 | XP_034984278.1[29] | 336 | 79.85 | 88.3 |
Emu | Bird | Casuariiformes | Dromaius novaehollandiae | 319 | XP_025956153.1[30] | 336 | 77.38 | 89.3 |
Black Legged Kittiwake | Bird | Charadriiformes | Rissa tridactyla | 319 | XP_054044439.1[31] | 367 | 77.31 | 82.3 |
Japanese Quail | Bird | Galliformes | Coturnix japonica | 319 | XP_015711317.1[32] | 344 | 76.13 | 86.4 |
California Condor | Bird | Gymnogyps | Accipitriformes | 319 | XP_050753817.1[33] | 336 | 77.4 | 89.6 |
African Clawed Frog | Amphibian | Anura | Xenopus laevis | 352 | NP_001085034.1[34] | 336 | 76.12 | 89.3 |
Two-Lined Caecillian | Amphibian | Gymnophiona | Rhinatrema bivittatum | 352 | XP_029453037.1[35] | 336 | 76.12 | 89.3 |
Asian Arowana | Fish | Osteoglossiformes | Scleropages formosus | 429 | XP_018611167.1[36] | 336 | 69.33 | 84.5 |
Pacific Halibut | Fish | Pleuronectiformes | Hippoglossus stenolepis | 429 | XP_035003305.1[37] | 335 | 67.87 | 83 |
Sea Lamprey | Fish | Petromyzontiformes | Petromyzon marinus | 563 | XP_032815808.1[38] | 362 | 63.35 | 73 |
Zebra Shark | Fish | Orectolobiformes | Stegostoma tigrinum | 462 | XP_048404699.1[39] | 354 | 73.59 | 80.5 |
Pin Mould | Fungi | Mucorales | Mucor mucedo | 1275 | XP_051459555.1[40] | 284 | 32.8 | 47.7 |
Ascomycete Fungi | Fungi | Helotiales | Lachnellula hyalina | 1275 | XP_031007997.1[41] | 383 | 23.3 | 35.9 |
Thale Cress | Plant | Brassicales | Arabidopsis thaliana | 1598 | NP_001190343.1[42] | 288 | 34.6 | 50 |
References
- ↑ Fu, Shuo; Liu, Jianyong (2022-08-22). "Genome-wide association study identified genes associated with ammonia nitrogen tolerance in Litopenaeus vannamei". Frontiers in Genetics 13: 961009. doi:10.3389/fgene.2022.961009. ISSN 1664-8021. PMID 36072655.
- ↑ Yu, Yanqin; Zuo, Xianbo; He, Miao; Gao, Jinping; Fu, Yuchuan; Qin, Chuanqi; Meng, Liuyan; Wang, Wenjun et al. (2017-02-24). "Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity". Nature Communications 8: 14364. doi:10.1038/ncomms14364. ISSN 2041-1723. PMID 28232668. PMC 5333091. Bibcode: 2017NatCo...814364Y. https://pure.johnshopkins.edu/en/publications/genome-wide-analyses-of-non-syndromic-cleft-lip-with-palate-ident.
- ↑ Yu, Xiaoxiao; Guo, Zihao; Fang, Zhihao; Yang, Kai; Liu, Changxu; Dong, Zhichao; Liu, Chang (2023-09-08). "Identification and validation of disulfidptosis-associated molecular clusters in non-alcoholic fatty liver disease". Frontiers in Genetics 14: 1251999. doi:10.3389/fgene.2023.1251999. ISSN 1664-8021. PMID 37745847.
- ↑ 4.0 4.1 4.2 4.3 "TMEM19 transmembrane protein 19 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/55266.
- ↑ 5.0 5.1 5.2 "Six-Frame Translation". https://www.bioline.com/media/calculator/01_13.html.
- ↑ 6.0 6.1 Su, Andrew I.; Wiltshire, Tim; Batalov, Serge; Lapp, Hilmar; Ching, Keith A.; Block, David; Zhang, Jie; Soden, Richard et al. (2004-04-20). "A gene atlas of the mouse and human protein-encoding transcriptomes" (in en). Proceedings of the National Academy of Sciences 101 (16): 6062–6067. doi:10.1073/pnas.0400782101. ISSN 0027-8424. PMID 15075390. Bibcode: 2004PNAS..101.6062S.
- ↑ "Gene Detail :: Allen Brain Atlas: Mouse Brain". https://mouse.brain-map.org/gene/show/43069.
- ↑ "MC4R melanocortin 4 receptor [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/4160.
- ↑ "BSCL2 BSCL2 lipid droplet biogenesis associated, seipin [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/26580#summary.
- ↑ https://www.ncbi.nlm.nih.gov/gene/116519
- ↑ "AQP6 aquaporin 6 [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/363.
- ↑ https://www.ncbi.nlm.nih.gov/gene/256815
- ↑ "CD3G CD3 gamma subunit of T-cell receptor complex [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/917.
- ↑ "CD79A CD79a molecule [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/973.
- ↑ "CNR2 cannabinoid receptor 2 [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/1269.
- ↑ "CPLX4 complexin 4 [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/339302#summary.
- ↑ "CREB3 cAMP responsive element binding protein 3 [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/10488.
- ↑ "CREB3L1 cAMP responsive element binding protein 3 like 1 [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/90993.
- ↑ "The CUCKOO Workgroup". https://biocuckoo.org/.
- ↑ 20.0 20.1 20.2 "Clustal Omega < Multiple Sequence Alignment < EMBL-EBI". https://www.ebi.ac.uk/Tools/msa/clustalo/.
- ↑ "Transmembrane protein 19 [Homo sapiens] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/NP_060749.2/.
- ↑ "Transmembrane protein 19 isoform 1 [Mus musculus] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/NP_001346399.1/.
- ↑ "Transmembrane protein 19 [Suricata suricatta] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_029810978.1/.
- ↑ "Transmembrane protein 19 [Artibeus jamaicensis] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_037017069.2/.
- ↑ "PREDICTED: Transmembrane protein 19 [Lipotes vexillifer] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_007448836.1/.
- ↑ "Transmembrane protein 19 isoform X1 [Dermochelys coriacea] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_038233118.1/.
- ↑ "PREDICTED: Transmembrane protein 19, partial [Gekko japonicus] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_015261175.1/.
- ↑ "Transmembrane protein 19 isoform X1 [Python bivittatus] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_007423004.1/.
- ↑ "Transmembrane protein 19 isoform X2 [Zootoca vivipara] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_034984278.1/.
- ↑ "Transmembrane protein 19 [Dromaius novaehollandiae] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_025956153.1/.
- ↑ "Transmembrane protein 19 [Rissa tridactyla] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_054044439.1/.
- ↑ "Transmembrane protein 19 [Coturnix japonica] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_015711317.1/.
- ↑ "Transmembrane protein 19 [Gymnogyps californianus] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_050753817.1/.
- ↑ "Transmembrane protein 19 [Xenopus laevis] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/NP_001085034.1/.
- ↑ "Transmembrane protein 19 [Rhinatrema bivittatum] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_029453037.1/.
- ↑ "Transmembrane protein 19 [Scleropages formosus] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_018611167.1/.
- ↑ "Transmembrane protein 19 [Hippoglossus stenolepis] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_035003305.1/.
- ↑ "Transmembrane protein 19 isoform X1 [Petromyzon marinus] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_032815808.1/.
- ↑ "Transmembrane protein 19 isoform X1 [Stegostoma tigrinum] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_048404699.1/.
- ↑ "Integral membrane protein DUF92-domain-containing protein [Mucor muced - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_051459555.1/.
- ↑ "Transmembrane protein [Lachnellula hyalina] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_031007997.1/.
- ↑ "Integral membrane protein (Protein of unknown function DUF92, transmem - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/NP_001190343.1/.
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![]() | Original source: https://en.wikipedia.org/wiki/TMEM19.
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