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Description

Transmembrane protein 100 (UniProt: Q9CQG9, also known as TMEM100) is encoded by the Tmem100 gene (Gene ID: 67888) in murine species. TMEM100 is a multi-pass membrane protein that is shown to be involved in renal development, vasculogenesis and lung cancer invasiveness. It plays a role during embryonic arterial endothelium differentiation and vascular morphogenesis through the ACVRL1 receptor-dependent signaling pathway upon stimulation by bone morphogenetic proteins, such as GDF2/BMP9 and BMP10. TMEM100 is also involved in the regulation of nociception by forming a complex with TRPA1 and TRPV1 and act as a modulator of their interaction in dorsal root ganglia (DRG) neurons. It is reported to weaken TRPA1 and TRPV1 interaction, thereby releasing the inhibition of TRPA1 by TRPV1 and increasing the single-channel open probability of the TRPA1-TRPV1 complex. TMEM100-deficient mice show a reduction in inflammatory mechanical hyperalgesia and TRPA1- but not TRPV1-mediated pain. A mutation involving aa 117-119 KRR to QQQ is shown to abolish TMEM100 interaction with TRPA1, but increases interaction with TRPV1. Mutations is Tmem100 gene can lead to embryonic lethality due to impaired differentiation of arterial endothelium and defects of vascular morphogenesis. (Ref.: Weng, H-J., et al. (2015). Neuron 85(4), 833-846).