8.A.75.1.5 Transmembrane 4 L6 family member 5 of 197 aas and 4 TMSs, TM4SF5 It is also called Tetraspan transmembrane protein L6H. Lysosomal TM4SF5 senses and enables arginine efflux for mTORC1/S6K1 activation (Jung et al. 2019). TM4SF5 can be N-glycosylated and palmitoylated, enabling homophilic or heterophilic binding to diverse membrane proteins and receptors, including growth factor receptors, integrins, and tetraspanins. It promotes protein-protein complexes for the spatiotemporal regulation of the expression, stability, binding, and signaling activity of its binding partners (Jung et al. 2020). Chronic diseases such as liver diseases involve bidirectional communication between extracellular and intracellular spaces, resulting in immune-related metabolic effects during the development of pathological phenotypes. During the development of fibrosis and cancer, TM4SF5 forms protein-protein complexes with amino acid transporters, which can lead to the regulation of cystine uptake from the extracellular space to the cytosol and arginine export from the lysosomal lumen to the cytosol. Diverse amino acid transporters are precipitated with TM4SF5 (Jung et al. 2020). Tetraspanin TM4SF5 in hepatocytes negatively modulates SLC27A transporters during acute fatty acid supply (Park et al. 2021). Hepatic TM4SF5 modulates GLUT8 localization and activity through transient binding, leading to steatosis-related fructose uptake and lipogenesis. Thus, TM4SF5 and/or GLUT8 may be promising treatment targets against liver steatosis resulting from excessive fructose consumption (Lee et al. 2022). TM4SF5 interacts with and regulates many solute transporters for amino acids and sugars, and these may be indicative of liver diseases (Kim et al. 2022). Liver-originated small extracellular vesicles with TM4SF5 target brown adipose tissue for homeostatic glucose clearance (Jung et al. 2022). Glucose mediates mitochondrial reprogramming by cholesterol export at TM4SF5-enriched mitochondria-lysosome contact sites (Kim et al. 2024).
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Accession Number: | O14894 |
Protein Name: | Transmembrane 4 L6 family member 5 |
Length: | 197 |
Molecular Weight: | 20823.00 |
Species: | Homo sapiens (Human) [9606] |
Number of TMSs: | 4 |
Location1 / Topology2 / Orientation3: |
Membrane1 / Multi-pass membrane protein2 |
Substrate |
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1: MCTGKCARCV GLSLITLCLV CIVANALLLV PNGETSWTNT NHLSLQVWLM GGFIGGGLMV
61: LCPGIAAVRA GGKGCCGAGC CGNRCRMLRS VFSSAFGVLG AIYCLSVSGA GLRNGPRCLM
121: NGEWGYHFED TAGAYLLNRT LWDRCEAPPR VVPWNVTLFS LLVAASCLEI VLCGIQLVNA
181: TIGVFCGDCR KKQDTPH