Biology:TMEM238

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

Transmembrane protein 238 is a transmembrane protein that in humans is encoded by the TMEM238 gene.[1] The Homo sapiens TMEM238 gene is related to Bardet-Biedl Syndrome 2 and may play a role in amino acid transport, primarily showing expression in stomach and colon tissues.[1][2][3]

Gene

Locus

TMEM238 in Homo sapiens spans 5,049 base pairs and has two exons.[1] TMEM238 in humans is located at 19q13.42 near the end of the long arm, minus strand of the chromosome.[2] No splice isoforms or variants are known.

The general position of TMEM238 on human chromosome 19 marked by a red line from GeneCards.[2]

Gene neighborhood

TMEM238 is chromosomally located between the transmembrane protein 190 (TMEM190) gene and ribosomal protein L28 (RPL28) gene.[4] TMEM190 is involved in protein self-association and hematopoietic progenitor cell differentiation.[5] RPL28 encodes a ribosomal protein that is part of the large 60S subunit.[6]

TMEM238 human gene neighbors diagram from UCSC Genome Browser.[4]

Protein

Transmembrane protein 238 is composed of 176 amino acids, weighing approximately 18.0 kDa.[2] It has a basal isoelectric point of approximately 11.5.[7] The protein is rich in alanine, arginine, and small amino acids, with a greater preponderance of basic amino acids.

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TMEM238 protein folding structuve via AlphaFold[8]
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TMEM238 protein topology in the membrane visualized via Protter[9]

Protein structure

The secondary structure of the protein has two transmembrane domains shown as dark blue alpha helices.[8]

Protein topology within the membrane shows extracellular N- and C-terminals with a short intracellular domain between transmembrane domains.[9]

Gene level regulation

Expression pattern

TMEM238 shows higher expression in colon and stomach tissues, but variable ubiquitous expression in all other tissues.[1]

In situ hybridization

TMEM238 gene expression in the mouse brain shows higher expression in the pons and medulla as indicated by white arrows in the sagittal plane view.[10]

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TMEM238 gene expression in the Mus musculus brain in the sagittal plane from the Allen Brain Atlas. Increased expression was found in the pons and medulla as indicated by the yellow fluorescence and white arrows.

Protein level regulation

Subcellular localization

The presence of two transmembrane domains within the protein confirm its presence in the plasma membrane.[11]

Lipid anchor attachment

The protein is not glycosylphosphatidylinositol (GPI) anchored, instead relying on hydrophobic transmembrane domains.[12]

Phosphorylation

Six post-translational phosphorylation modification sites were found within the protein.[13][14][15] Presence of such sites indicate that both the N-terminus and C-terminus of the protein are located in the cytosol.

Homology

Orthologs can be found in vertebrates dating back to 563 million years ago from human divergence but not in any invertebrates.[16]

TMEM238 Ortholog Table
Taxonomic Class Genus and Species Common name Date of Divergence from Humans (MYA) Accession number Sequence length Sequence identity Sequence similarity
Mammalia Homo sapiens Human 0 NP_001177693.1 176 100.0 100.0
Mammalia Mus musculus Rodentia 87 NP_083660.1 176 85.2 86.9
Mammalia Eschrichtius robustus Gray Whale 94 XP_068384946.1 178 87.1 91.0
Mammalia Trichosurus vulpecula Common Brushtail Possum 160 XP_036599039.1 168 65.8 70.7
Reptilia Alligator mississippiensis American Alligator 319 XP_019356415.1 131 48.9 55.0
Reptilia Malaclemys terrapin pileata Mississippi Diamondback Terrapin Turtle 319 XP_053865811.1 123 43.2 54.0
Reptilia Pantherophis guttatus Corn Snake 319 XP_034292043.1 158 33.0 42.0
Aves Gallus gallus Red Junglefowl Chicken 319 XP_040503607.1 135 33.3 41.4
Aves Sylvia atricapilla Eurasian Blackcap Bird 319 XP_066185702.1 131 33.0 39.5
Amphibia Xenopus laevis African Clawed Frog 352 XP_018083581.1 160 39.7 51.3
Amphibia Bufotes viridis European Green Toad 352 CAK8623525.1 137 36.5 48.6
Dipnoi Protopterus annectens West African Lungfish 408 XP_043937488.1 138 36.4 50.0
Coelacanthi Latimeria chalumnae West Indian Ocean Coelacanth 415 XP_006010124.1 143 41.1 53.3
Ray-Finned Fishes Nothobranchius furzeri Turquoise Killifish 429 XP_015830691.2 104 29.0 40.3
Ray-Finned Fishes Danio rerio Zebrafish 429 NP_001076543.1 105 26.4 37.4
Ray-Finned Fishes Nerophis ophidion Straightnose Pipefish 429 XP_061764902.1 191 26.1 42.4
Ray-Finned Fishes Hippocampus zosterae Dwarf Seahorse 429 XP_051927990.1 185 25.6 33.8
Cartilaginous Fishes Callorhinchus milii Australian Ghostshark 462 XP_007905786.1 144 38.8 52.5
Cartilaginous Fishes Chiloscyllium plagiosum Whitespotted Bamboo Shark 462 XP_043571155.1 155 27.2 37.6
Hyperoartia Lethenteron reissneri Asiatic Brook Lamprey 563 XP_061425829.1 210 27.3 34.3
Hyperoartia Petromyzon marinus Sea Lamprey 563 XP_032832039.1 158 25.3 38.7
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TMEM238 evolutionary history in humans compared to the rates of cytochrome c and fibrinogen alpha

Evolutionary history

TMEM238 is evolving moderately quickly in history with a rate faster than cytochrome c but slower than fibrinogen alpha.[17]

Function and biochemistry

The TMEM238 protein is predicted to be an integral component of the membrane and play a role in amino acid transport.[3]

Interacting proteins

Several proteins interact with transmembrane protein 238, all located in the cell membrane.[18][19]

Protein Interactions
Abbreviated Name Full Name Statistical Measures Compartment of the Cell Protein Function
KRTCAP3 Keratinocyte Associated Protein 3 0.4504 Cell Membrane Adiposity
TMEM30B Transmembrane Protein 30B 0.4512 Cell Membrane, Golgi, ER Aminophospholipid transport, regulate protein exit from ER
TMEM223 Transmembrane Protein 223 0.524 Cell Membrane Nervous System Development
CATSPERB Cation Channel Sperm-Associated Protein Subunit Beta 0.573 Cell Membrane, Cilium Sperm cell hyperactivation, motility, spermatogenesis

Clinical significance

The Homo sapiens TMEM238 gene is related to Bardet-Biedl Syndrome 2, a ciliopathic human genetic disorder.[2]

Expression of the TMEM238 protein was also shown to increase in several disease states including asthma and low invasive breast cancers as found in various microarray experiments.[20][21] DNA methylation in TMEM238 was identified as a mediator in the developmental BPA exposure and female-specific body weight phenotypes in mice.[3] Upregulation of the TMEM238 gene is present in POEMS syndrome.[22]

References

  1. ↑ 1.0 1.1 1.2 1.3 "NCBI TMEM238 Transmembrane Protein 238 [Homo sapiens (human)"]. https://www.ncbi.nlm.nih.gov/gene/388564/. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 "GeneCards TMEM 238 gene - Transmembrane Protein 238". https://www.genecards.org/cgi-bin/carddisp.pl?gene=TMEM238. 
  3. ↑ 3.0 3.1 3.2 "Novel Epigenetic Biomarkers Mediating Bisphenol A Exposure and Metabolic Phenotypes in Female Mice". Endocrinology 158 (1): 31–40. January 2017. doi:10.1210/en.2016-1441. PMID 27824486. 
  4. ↑ 4.0 4.1 "UCSC Genome Browser on Human (GRCh38/hg38)". https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=chr19%3A55373247%2D55390288&hgsid=2355005599_fmBo7R0GIwp4k9FiEjiHASabWuEC. 
  5. ↑ "TMEM190 transmembrane protein 190 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/147744. 
  6. ↑ Database, GeneCards Human Gene. "RPL28 Gene - GeneCards | RL28 Protein | RL28 Antibody" (in en). https://www.genecards.org/cgi-bin/carddisp.pl?gene=RPL28. 
  7. ↑ "TMEM238 (human)". https://www.phosphosite.org/proteinAction.action?id=2830203&showAllSites=true. 
  8. ↑ 8.0 8.1 "iCn3D: Web-based 3D Structure Viewer". https://www.ncbi.nlm.nih.gov/Structure/icn3d/?mmdbafid=C9JI98&bu=1. 
  9. ↑ 9.0 9.1 "Protter open-source visualization tool of proteoforms". https://wlab.ethz.ch/protter/start/. 
  10. ↑ "Gene Detail :: Allen Brain Atlas: Mouse Brain". https://mouse.brain-map.org/gene/show/159388. 
  11. ↑ "DeepLoc 2.0 - DTU Health Tech - Bioinformatic Services" (in en). https://services.healthtech.dtu.dk/services/DeepLoc-2.0/. 
  12. ↑ "NetGPI 1.1 - DTU Health Tech - Bioinformatic Services" (in en). https://services.healthtech.dtu.dk/services/NetGPI-1.1/. 
  13. ↑ "NetPhos 3.1 - DTU Health Tech - Bioinformatic Services". https://services.healthtech.dtu.dk/services/NetPhos-3.1/. 
  14. ↑ "NetPhospan 1.0 - DTU Health Tech - Bioinformatic Services" (in en). https://services.healthtech.dtu.dk/services/NetPhospan-1.0/. 
  15. ↑ "GPS 6.0 - Kinase-specific Phosphorylation Site Prediction". http://gps.biocuckoo.cn/online.php. 
  16. ↑ "BLAST: Basic Local Alignment Search Tool". https://blast.ncbi.nlm.nih.gov/Blast.cgi. 
  17. ↑ "Gene - NCBI - Cytochrome C and Fibrinogen Alpha". https://www.ncbi.nlm.nih.gov/gene. 
  18. ↑ "TMEM238 protein (human) - STRING interaction network". https://string-db.org/network/9606.ENSP00000416154. 
  19. ↑ "TMEM238 Result Summary | BioGRID". https://thebiogrid.org/132746. 
  20. ↑ "GDS5343 / A_51_P359122". https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS5343:A_51_P359122. 
  21. ↑ "GDS5801 / ILMN_1748827". https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS5801:ILMN_1748827. 
  22. ↑ He, Haiyan; Chen, Xi; Hou, Nan (August 2023). "P845: Deciphering Plasma Cell Heterogeneity and Transcriptome Features in POEMS Syndrome Using Single Cell RNA-Sequencing". HemaSphere 7 (3): e6511991. doi:10.1097/01.HS9.0000970284.65119.91. 



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