# TMEM238

Transmembrane protein 238 is a transmembrane protein that in humans is encoded by the TMEM238 gene. 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.

## Gene
### Locus

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

### Gene neighborhood

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

## Protein

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

### Protein structure

The secondary structure of the protein has two transmembrane domains shown as dark blue alpha helices.
Protein topology within the membrane shows extracellular N- and C-terminals with a short intracellular domain between transmembrane domains.

## Gene level regulation
### Expression pattern

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

### 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.

## Protein level regulation
### Subcellular localization

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

### Lipid anchor attachment

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

### Phosphorylation

Six post-translational phosphorylation modification sites were found within the protein.$^,$$^,$ 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.
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 |

### Evolutionary history

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

### Function and biochemistry

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

### Interacting proteins

Several proteins interact with transmembrane protein 238, all located in the cell membrane.
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.
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.$^,$ DNA methylation in TMEM238 was identified as a mediator in the developmental BPA exposure and female-specific body weight phenotypes in mice. Upregulation of the TMEM238 gene is present in POEMS syndrome.