TMEM100 Membrane Protein Introduction

Introduction of TMEM100

Transmembrane protein 100 (TMEM100) is a transmembrane protein encoded by the TMEM100 gene located at 17q32. It consists of 134 amino acids (aa) and contains two transmembrane domains (amino acids 53-75, 85-107). TMEM100 is highly conserved in vertebrates and not structurally related to any known family of proteins in any species. It is expressed in various organs, such as the brain, heart, skeletal muscles and gastrointestinal tract, but mainly in the lungs. TMEM100 expression has not been reported in adult mammalian tissues, but appears in the ventral neural tube of mouse embryos and plays a role in signaling pathways in the development of the enteric nervous system. TRPA1 and TRPV1 are key pain mediators, TMEM100 is identified as a potentiating regulator of the TRPA1-V1 complex and as a candidate for the modulation of the TRPA1-V1 complex in the nociceptive pathway.

The Function of TMEM100 Membrane Protein

TMEM100 is involved in renal development, cardiovascular morphogenesis, pain signaling in the dorsal root ganglia, and reduction of the invasiveness of lung and liver cancer cells. TMEM100 is considered to be a marker of enteric nerves and is used to identify neuronal structures in the gastrointestinal tract. The expression of TMEM100 in the enteric nervous system can reflect the role of transforming growth factor beta, bone morphogenetic protein (BMP) or related signaling pathways in cell development and differentiation. TMEM100 knockout mice have been reported to exhibit embryonic lethality with abnormal vascular differentiation and heart morphogenesis. In addition, TMEM100 is involved in the development and progression of tumors, including invasion, migration and proliferation. TMEM100 is down-regulated in lung cancer and inhibits proliferation and metastasis of lung cancer cells by inhibiting TNF signaling pathway, which may be a potential prognostic biomarker and therapeutic target for non-small cell lung carcinoma. Moreover, it is also an independent risk factor for overall survival and disease-free survival in hepatocellular carcinoma (HCC) patients, suggesting that TMEM100 may act as a tumor suppressor in HCC metastasis and proliferation.

Fig.1 The structure of the TEME100. TEME100 is a two-transmembrane protein with a TRPA1 binding site (KRR) at its C terminus. Both the N and C termini are intracellular, while the loop region is extracellular. PM, plasma membrane. (Weng, 2015)

Application of TMEM100 Membrane Protein in Literature

1. Mizuta K., et al. TMEM100: A Novel Intracellular Transmembrane Protein Essential for Vascular Development and Cardiac Morphogenesis. Etiology and Morphogenesis of Congenital Heart Disease. 2016, 9-170. PubMed ID: 29787135
   
   

   This article shows that TMEM100 is a new intracellular protein with two transmembrane domains whose amino acid sequence is highly conserved from fish to humans.

2. Ren D., et al. BMP7 plays a critical role in TMEM100-inhibited cell proliferation and apoptosis in mouse metanephric mesenchymal cells in vitro. In Vitro Cellular & Developmental Biology-Animal. 2018, 54(2):111-119. PubMed ID: 29247399
   
   

   This study demonstrates the important role of BMP7 in Tmem100-mediated cell proliferation and apoptosis and reveals a complicated regulation network among Tmem100, BMP7, and BMPR-II in mouse embryonic kidney-derived cells.

3. Kuboyama A., et al. The expression of Transmembrane Protein 100 is regulated by alterations in calcium signaling rather than endoplasmic reticulum stress. Bioscience Biotechnology & Biochemistry. 2018, 82(8):1377-1383. PubMed ID: 29690857
   
   

   This article suggests that TMEM100 performs various functions in response to changes in calcium signaling in addition to responding to endoplasmic reticulum stress.

4. Han Z., et al. Low-expression of TMEM100 is associated with poor prognosis in non-small-cell lung cancer. American Journal of Translational Research. 2017, 9(5):2567-2578. PubMed ID: 28560005
   
   

   This article finds that TMEM100 acts as a tumor suppressor gene by inhibiting the TNF signaling pathway and may prove to be a potential prognostic biomarker and therapeutic target for non-small-cell lung carcinoma.

5. Ou D., et al. Novel roles of TMEM100: inhibition metastasis and proliferation of hepatocellular carcinoma. Oncotarget. 2015, 6(19):17379-90. PubMed ID: 25978032
   
   

   The results of this study suggest that TMEM100 acts as a tumor suppressor in hepatocellular carcinoma metastasis and proliferation.

TMEM100 Preparation Options

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Reference

1. Weng H J, et al. (2015). Tmem100 Is a Regulator of TRPA1-TRPV1 Complex and Contributes to Persistent Pain. Neuron. 85(4):833.

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