Biology:TMEM19

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Short description: Protein encoded by the TMEM19 gene


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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.[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]

  • A conceptual translation of the human TMEM19 was made using data from NCBI[4] and translated using Six Frame Translations.[5] 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[4] and translated using Six Frame Translations.[5] 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[4] and translated using Six Frame Translations.[5] 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.[6] 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.[6] 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[7].

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

Visual predicted representation of TMEM19 in the cell membrane. In image A the transmembrane regions were selected using NCBI[4] 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.[19]

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 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

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,[20] 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,[20] 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,[20] 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.

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 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

  1. ↑ 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. 
  2. ↑ 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. 
  3. ↑ 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. ↑ 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. ↑ 5.0 5.1 5.2 "Six-Frame Translation". https://www.bioline.com/media/calculator/01_13.html. 
  6. ↑ 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. 
  7. ↑ "Gene Detail :: Allen Brain Atlas: Mouse Brain". https://mouse.brain-map.org/gene/show/43069. 
  8. ↑ "MC4R melanocortin 4 receptor [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/4160. 
  9. ↑ "BSCL2 BSCL2 lipid droplet biogenesis associated, seipin [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/26580#summary. 
  10. ↑ https://www.ncbi.nlm.nih.gov/gene/116519
  11. ↑ "AQP6 aquaporin 6 [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/363. 
  12. ↑ https://www.ncbi.nlm.nih.gov/gene/256815
  13. ↑ "CD3G CD3 gamma subunit of T-cell receptor complex [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/917. 
  14. ↑ "CD79A CD79a molecule [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/973. 
  15. ↑ "CNR2 cannabinoid receptor 2 [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/1269. 
  16. ↑ "CPLX4 complexin 4 [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/339302#summary. 
  17. ↑ "CREB3 cAMP responsive element binding protein 3 [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/10488. 
  18. ↑ "CREB3L1 cAMP responsive element binding protein 3 like 1 [Homo sapiens (Human)] - Gene - NCBI". https://www.ncbi.nlm.nih.gov/gene/90993. 
  19. ↑ "The CUCKOO Workgroup". https://biocuckoo.org/. 
  20. ↑ 20.0 20.1 20.2 "Clustal Omega < Multiple Sequence Alignment < EMBL-EBI". https://www.ebi.ac.uk/Tools/msa/clustalo/. 
  21. ↑ "Transmembrane protein 19 [Homo sapiens] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/NP_060749.2/. 
  22. ↑ "Transmembrane protein 19 isoform 1 [Mus musculus] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/NP_001346399.1/. 
  23. ↑ "Transmembrane protein 19 [Suricata suricatta] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_029810978.1/. 
  24. ↑ "Transmembrane protein 19 [Artibeus jamaicensis] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_037017069.2/. 
  25. ↑ "PREDICTED: Transmembrane protein 19 [Lipotes vexillifer] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_007448836.1/. 
  26. ↑ "Transmembrane protein 19 isoform X1 [Dermochelys coriacea] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_038233118.1/. 
  27. ↑ "PREDICTED: Transmembrane protein 19, partial [Gekko japonicus] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_015261175.1/. 
  28. ↑ "Transmembrane protein 19 isoform X1 [Python bivittatus] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_007423004.1/. 
  29. ↑ "Transmembrane protein 19 isoform X2 [Zootoca vivipara] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_034984278.1/. 
  30. ↑ "Transmembrane protein 19 [Dromaius novaehollandiae] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_025956153.1/. 
  31. ↑ "Transmembrane protein 19 [Rissa tridactyla] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_054044439.1/. 
  32. ↑ "Transmembrane protein 19 [Coturnix japonica] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_015711317.1/. 
  33. ↑ "Transmembrane protein 19 [Gymnogyps californianus] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_050753817.1/. 
  34. ↑ "Transmembrane protein 19 [Xenopus laevis] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/NP_001085034.1/. 
  35. ↑ "Transmembrane protein 19 [Rhinatrema bivittatum] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_029453037.1/. 
  36. ↑ "Transmembrane protein 19 [Scleropages formosus] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_018611167.1/. 
  37. ↑ "Transmembrane protein 19 [Hippoglossus stenolepis] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_035003305.1/. 
  38. ↑ "Transmembrane protein 19 isoform X1 [Petromyzon marinus] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_032815808.1/. 
  39. ↑ "Transmembrane protein 19 isoform X1 [Stegostoma tigrinum] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_048404699.1/. 
  40. ↑ "Integral membrane protein DUF92-domain-containing protein [Mucor muced - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_051459555.1/. 
  41. ↑ "Transmembrane protein [Lachnellula hyalina] - Protein - NCBI". https://www.ncbi.nlm.nih.gov/protein/XP_031007997.1/. 
  42. ↑ "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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