TMEM175
Description
The TMEM175 (transmembrane protein 175) is a protein-coding gene located on chromosome 4.
TMEM175 is a proton-activated proton channel that plays a crucial role in maintaining pH homeostasis within endosomes and lysosomes. It facilitates proton efflux from these organelles, particularly at acidic pH (below 4.6), by acting as a selective mediator of lysosomal proton release. This proton leak counterbalances the activity of V-ATPase, contributing to the stabilization of lumenal pH. Maintaining pH stability is essential for proper autophagosome-lysosome fusion. Furthermore, TMEM175 can also function as a potassium channel at higher pH levels, regulating potassium conductance in endosomes and lysosomes. It forms the pore-forming subunit of the lysoK(GF) complex, which is activated by extracellular growth factors. This complex is composed of TMEM175 and AKT (AKT1, AKT2, or AKT3), a major target of growth factor receptors. Conformational changes in AKT within the complex lead to the opening of the TMEM175 channel and its activation. The lysoK(GF) complex is crucial for protecting neurons against stress-induced damage.
TMEM175 is also known as hTMEM175.
Associated Diseases
- Parkinson disease
- late-onset Parkinson disease
- Griscelli syndrome type 3
- ringed hair disease
- uncombable hair syndrome
- microcephaly-albinism-digital anomalies syndrome
- oculocutaneous albinism type 3
- pili bifurcati
