TMEM19

Last updated
TMEM19
Identifiers
Aliases TMEM19 , transmembrane protein 19
External IDs MGI: 1914476 HomoloGene: 10107 GeneCards: TMEM19
Orthologs
SpeciesHumanMouse
Entrez

55266

67226

Ensembl

ENSG00000139291

ENSMUSG00000069520

UniProt

Q96HH6

Q91W52

RefSeq (mRNA)

NM_018279

NM_133683
NM_001359470
NM_001359471
NM_001359472

RefSeq (protein)

NP_060749

NP_598444
NP_001346399
NP_001346400
NP_001346401

Location (UCSC) Chr 12: 71.69 – 71.71 Mb Chr 10: 115.18 – 115.2 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Transmembrane protein 19 is a protein that in humans is encoded by the TMEM19 gene.

Contents

Gene

TMEM19 location on chromosome 12 TMEM19-gene.png
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]

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. 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 Large-scale Analysis of the Human Transcriptome (HG-U133A).png
Data was obtained from a large-scale analysis of the human transcriptome on NCBI Geo. 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 . AllenBrainAtlas TMEM19 expression in Mouse Brain.png
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 .

Protein Interactions

ProteinFull NameDetection MethodDescriptionCV
MC4R Melanocortin 4 ReceptorUbiquitin ReconstructionMembrane-bound receptor and member of the melanocortin receptor family. Protein interacts with adrenocorticotropic and MSH hormones. Mediated by G proteins. (NCBI [12] )0.37
BSCL2 Bernardinelli-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 [13] )0.67
APOA5 Apolipoprotein 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 [14] )0.56
AQP6 Aquaporin 6Two HybridFunctions as a water channel in cells. Specific to the kidney. (NCBI [15] )0.56
C10orf67 Chromosome 10 open reading frame 67Two HybridPredicted to be located in mitochondrion. Possible link to Crohn's and sarcoidosis. (NCBI [16] )0.56
CD3G CD3 gamma subunit of T-cell receptor complexTwo HybridComponent of the T-cell receptor-CD3 complex. Mutations with this protein are associated with T cell immunodeficieny. (NCBI [17] )0.56
CD79A CD79a moleculeTwo HybridThe Ig-alpha protein of the B-cell antigen component. (NCBI [18] )0.56
CNR2 Cannabinoid 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 [19] )0.56
CPLX4Complexin 4Two HybridMay be involved in synaptic vesicle exocytosis. (NCBI [20] )0.56
CREB3 cAMP 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 supression, and ER stress-associated protein degradation. (NCBI [21] )0.56
CREB3L1 cAMP 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 [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 and in image B the seventh predicted transmembrane region found from SOSUI analysis was added. Amino acids in red are sites of kinase phosphorylation. JPEG TMEM19 in Membrane with PTM.jpg
Visual predicted representation of TMEM19 in the cell membrane. In image A the transmembrane regions were selected using NCBI 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]

Phosphorylation Sites
PositionCodeKinaseProtein Sequence Pos.ScoreCutoff
197S AGC SEVGPVLSKSSPRLI0.05590.0197
214T AGC WEKVPVGTNGGVTVV0.05680.0197
187T CK1 LACSAGDTWASEVGP0.06660.0532
108S AGC LMFFLSSSKLTKWKG0.13330.0197
288T CK1 YTGLDESTGMVVNSP0.14270.0532
287S CK1 QYTGLDESTGMVVNS0.15170.0532
200S CDK, MAPK,

GSK, CLK

GPVLSKSSPRLITTW0.15460.0403
296T CK1 GMVVNSPTNKARHIA0.29260.0532
125Y TK KKRLDSEYKEGGQRN0.78510.7641
167Y TK PVDFSKQYSASWMCL0.86790.7641
281Y TK YLGATMQYTGLDEST0.97620.7641

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. Sequence Divergence of TMEM19.png
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.

Orthologs of Human TMEM19
Common NameClassOrderGenus and SpeciesMedian Date of DivergenceAccession NumberSequence LengthSequence Identity to Humans %Sequence Similarity to Humans %
Humans Mammal Primates Homo sapiens0NP_060749.2 [25] 336100100
Mouse Mammal Rodentia Mus musculus87NP_001346399.1 [26] 35187.4690.3
Meerkat Mammal Carnivora Suricata suricatta94XP_029810978.1 [27] 33691.9296.4
Jamaican Fruit Bat Mammal Bats Artibeus jamaicensis94XP_037017069.2 [28] 33690.4595.5
Baiji Dolphin Mammal Artiodactyla Lipotes vexillifer94XP_007448836.1 [29] 35889.5890.8
Leatherback Turtle Reptile Testudines Dermochelys coriacea319XP_038233118.1 [30] 33582.2689.9
Schlegal's Japanese Gecko Reptile Squamata Gekko japonicus319XP_015261175.1 [31] 28281.2377.4
Burmese Python Reptile Squamata Python bivittatus319XP_007423004.1 [32] 37180.0680.1
Viviparous Lizard Reptile Squamata Zootoca vivipara319XP_034984278.1 [33] 33679.8588.3
Emu Bird Casuariiformes Dromaius novaehollandiae319XP_025956153.1 [34] 33677.3889.3
Black Legged Kittiwake Bird Charadriiformes Rissa tridactyla319XP_054044439.1 [35] 36777.3182.3
Japanese Quail Bird Galliformes Coturnix japonica319XP_015711317.1 [36] 34476.1386.4
California Condor BirdGymnogypsAccipitriformes319XP_050753817.1 [37] 33677.489.6
African Clawed Frog Amphibian Anura Xenopus laevis352NP_001085034.1 [38] 33676.1289.3
Two-Lined Caecillian Amphibian Gymnophiona Rhinatrema bivittatum352XP_029453037.1 [39] 33676.1289.3
Asian Arowana Fish Osteoglossiformes Scleropages formosus429XP_018611167.1 [40] 33669.3384.5
Pacific Halibut Fish Pleuronectiformes Hippoglossus stenolepis429XP_035003305.1 [41] 33567.8783
Sea Lamprey Fish Petromyzontiformes Petromyzon marinus563XP_032815808.1 [42] 36263.3573
Zebra Shark Fish Orectolobiformes Stegostoma tigrinum462XP_048404699.1 [43] 35473.5980.5
Pin Mould Fungi Mucorales Mucor mucedo1275XP_051459555.1 [44] 28432.847.7
Ascomycete Fungi Fungi Helotiales Lachnellula hyalina1275XP_031007997.1 [45] 38323.335.9
Thale Cress Plant Brassicales Arabidopsis thaliana1598NP_001190343.1 [46] 28834.650

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References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000139291 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000069520 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Fu S, Liu J (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 . PMC   9441690 . PMID   36072655.
  6. ↑ Yu Y, Zuo X, He M, Gao J, Fu Y, Qin C, et al. (February 2017). "Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity". Nature Communications. 8: 14364. Bibcode:2017NatCo...814364Y. doi:10.1038/ncomms14364. PMC   5333091 . PMID   28232668.
  7. ↑ Yu X, Guo Z, Fang Z, Yang K, Liu C, Dong Z, Liu C (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 . PMC   10514914 . PMID   37745847.
  8. 1 2 3 4 "TMEM19 transmembrane protein 19 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-16.
  9. 1 2 3 "Six-Frame Translation". www.bioline.com. Retrieved 2023-12-16.
  10. 1 2 Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, et al. (April 2004). "A gene atlas of the mouse and human protein-encoding transcriptomes". Proceedings of the National Academy of Sciences of the United States of America. 101 (16): 6062–6067. Bibcode:2004PNAS..101.6062S. doi: 10.1073/pnas.0400782101 . PMC   395923 . PMID   15075390.
  11. ↑ "Gene Detail :: Allen Brain Atlas: Mouse Brain". mouse.brain-map.org. Retrieved 2023-12-16.
  12. ↑ "MC4R melanocortin 4 receptor [Homo sapiens (Human)] - Gene - NCBI".
  13. ↑ "BSCL2 BSCL2 lipid droplet biogenesis associated, seipin [Homo sapiens (Human)] - Gene - NCBI".
  14. ↑ https://www.ncbi.nlm.nih.gov/gene/116519
  15. ↑ "AQP6 aquaporin 6 [Homo sapiens (Human)] - Gene - NCBI".
  16. ↑ https://www.ncbi.nlm.nih.gov/gene/256815
  17. ↑ "CD3G CD3 gamma subunit of T-cell receptor complex [Homo sapiens (Human)] - Gene - NCBI".
  18. ↑ "CD79A CD79a molecule [Homo sapiens (Human)] - Gene - NCBI".
  19. ↑ "CNR2 cannabinoid receptor 2 [Homo sapiens (Human)] - Gene - NCBI".
  20. ↑ "CPLX4 complexin 4 [Homo sapiens (Human)] - Gene - NCBI".
  21. ↑ "CREB3 cAMP responsive element binding protein 3 [Homo sapiens (Human)] - Gene - NCBI".
  22. ↑ "CREB3L1 cAMP responsive element binding protein 3 like 1 [Homo sapiens (Human)] - Gene - NCBI".
  23. ↑ "The CUCKOO Workgroup". biocuckoo.org. Retrieved 2023-12-07.
  24. 1 2 3 "Clustal Omega < Multiple Sequence Alignment < EMBL-EBI". www.ebi.ac.uk. Retrieved 2023-12-16.
  25. ↑ "Transmembrane protein 19 [Homo sapiens] - Protein - NCBI".
  26. ↑ "Transmembrane protein 19 isoform 1 [Mus musculus] - Protein - NCBI".
  27. ↑ "Transmembrane protein 19 [Suricata suricatta] - Protein - NCBI".
  28. ↑ "Transmembrane protein 19 [Artibeus jamaicensis] - Protein - NCBI".
  29. ↑ "PREDICTED: Transmembrane protein 19 [Lipotes vexillifer] - Protein - NCBI".
  30. ↑ "Transmembrane protein 19 isoform X1 [Dermochelys coriacea] - Protein - NCBI".
  31. ↑ "PREDICTED: Transmembrane protein 19, partial [Gekko japonicus] - Protein - NCBI".
  32. ↑ "Transmembrane protein 19 isoform X1 [Python bivittatus] - Protein - NCBI".
  33. ↑ "Transmembrane protein 19 isoform X2 [Zootoca vivipara] - Protein - NCBI".
  34. ↑ "Transmembrane protein 19 [Dromaius novaehollandiae] - Protein - NCBI".
  35. ↑ "Transmembrane protein 19 [Rissa tridactyla] - Protein - NCBI".
  36. ↑ "Transmembrane protein 19 [Coturnix japonica] - Protein - NCBI".
  37. ↑ "Transmembrane protein 19 [Gymnogyps californianus] - Protein - NCBI".
  38. ↑ "Transmembrane protein 19 [Xenopus laevis] - Protein - NCBI".
  39. ↑ "Transmembrane protein 19 [Rhinatrema bivittatum] - Protein - NCBI".
  40. ↑ "Transmembrane protein 19 [Scleropages formosus] - Protein - NCBI".
  41. ↑ "Transmembrane protein 19 [Hippoglossus stenolepis] - Protein - NCBI".
  42. ↑ "Transmembrane protein 19 isoform X1 [Petromyzon marinus] - Protein - NCBI".
  43. ↑ "Transmembrane protein 19 isoform X1 [Stegostoma tigrinum] - Protein - NCBI".
  44. ↑ "Integral membrane protein DUF92-domain-containing protein [Mucor muced - Protein - NCBI".
  45. ↑ "Transmembrane protein [Lachnellula hyalina] - Protein - NCBI".
  46. ↑ "Integral membrane protein (Protein of unknown function DUF92, transmem - Protein - NCBI".
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