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 ClassGenus and SpeciesCommon nameDate of Divergence from Humans (MYA)Accession numberSequence lengthSequence identitySequence similarityMammaliaHomo sapiensHuman0NP_001177693.1176100.0100.0MammaliaMus musculusRodentia87NP_083660.117685.286.9MammaliaEschrichtius robustusGray Whale94XP_068384946.117887.191.0MammaliaTrichosurus vulpeculaCommon Brushtail Possum160XP_036599039.116865.870.7ReptiliaAlligator mississippiensisAmerican Alligator319XP_019356415.113148.955.0ReptiliaMalaclemys terrapin pileataMississippi Diamondback Terrapin Turtle319XP_053865811.112343.254.0ReptiliaPantherophis guttatusCorn Snake319XP_034292043.115833.042.0AvesGallus gallusRed Junglefowl Chicken319XP_040503607.113533.341.4AvesSylvia atricapillaEurasian Blackcap Bird319XP_066185702.113133.039.5AmphibiaXenopus laevisAfrican Clawed Frog352XP_018083581.116039.751.3AmphibiaBufotes viridisEuropean Green Toad352CAK8623525.113736.548.6DipnoiProtopterus annectensWest African Lungfish408XP_043937488.113836.450.0CoelacanthiLatimeria chalumnaeWest Indian Ocean Coelacanth415XP_006010124.114341.153.3Ray-Finned FishesNothobranchius furzeriTurquoise Killifish429XP_015830691.210429.040.3Ray-Finned FishesDanio rerioZebrafish429NP_001076543.110526.437.4Ray-Finned FishesNerophis ophidionStraightnose Pipefish429XP_061764902.119126.142.4Ray-Finned FishesHippocampus zosteraeDwarf Seahorse429XP_051927990.118525.633.8Cartilaginous FishesCallorhinchus miliiAustralian Ghostshark462XP_007905786.114438.852.5Cartilaginous FishesChiloscyllium plagiosumWhitespotted Bamboo Shark462XP_043571155.115527.237.6HyperoartiaLethenteron reissneriAsiatic Brook Lamprey563XP_061425829.121027.334.3HyperoartiaPetromyzon marinus Sea Lamprey563XP_032832039.115825.338.7 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 InteractionsAbbreviated NameFull NameStatistical MeasuresCompartment of the CellProtein FunctionKRTCAP3Keratinocyte Associated Protein 30.4504Cell MembraneAdiposityTMEM30BTransmembrane Protein 30B0.4512Cell Membrane, Golgi, ERAminophospholipid transport, regulate protein exit from ERTMEM223Transmembrane Protein 2230.524Cell MembraneNervous System DevelopmentCATSPERBCation Channel Sperm-Associated Protein Subunit Beta0.573Cell Membrane, CiliumSperm 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.
References