TMEM184A Membrane Protein Introduction

Introduction of TMEM184A

Transmembrane protein 184A (TMEM184A) is a transmembrane protein composed of 413 amino acids with seven transmembrane domains. TMEM184A is encoded by the TMEM184A gene, which spans the 9.3 kb region on chromosome 5 and was originally identified in mouse cDNA library screen. Mouse TMEM184A has orthologs with many mammalian species, including humans, chimpanzees, dogs and rats, with homology among these homologs exceeding 80%. TMEM184A is predicted to have kinase activity; however, its amino acid sequence does not align to any known domains. Predictive analysis of the TMEM184A protein sequence reveals that the C-terminal region is rich in basic amino acids that can participate in heparin binding. In other regions of the TMEM184A protein, although there are no multiple basic residues in the transmembrane segment, it may also be involved in heparin binding.

The Function of TMEM184A Membrane Protein

TMEM184A is present in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) and is recently identified as the heparin receptor in vascular ECs and VSMCs. In VSMCs, TMEM184A is required for potent anti-proliferative and anti-inflammatory signaling cascades induced by heparin. Heparin binds specifically to TMEM184A and decreases growth-factor-induced MAPK signaling and proliferation. In ECs, TMEM184A is required for heparin-induced expression of dual specificity phosphatase-1 (DUSP1) and subsequent downregulation of MAPK signaling. Heparin-binding results in elevated levels of DUSP1 protein and decreased ERK activity. Therefore, TMEM184A is a heparin receptor that is involved in heparin-induced signaling transduction and mediates the anti-inflammatory response of ECs and VSMCs. The response of VSMC and ECs to heparin includes cell proliferation, ERK pathway activity, and reduction in activation of specific transcription factors. In addition, Furthermore, expression of TMEM184A is specifically upregulated during mouse development and in the Sertoli cells of the testis. Thus, it may mediate signaling events between germ cells and Sertoli cells or between other somatic and Sertoli cells, or mediate regulatory pathways that control the compartmentalization of testicular structures.

Fig.1 Signaling pathway for heparin receptors. Heparin interacts with TMEM184A and leads to an increase in DUSP1 and a decrease in ERK activation. (Pugh, 2016)

Application of TMEM184A Membrane Protein in Literature

1. Farwell S.L.N., et al. Novel Heparin Receptor Transmembrane Protein 184a Regulates Angiogenesis in the Adult Zebrafish Caudal Fin. Frontiers in Physiology. 2017, 8:671. PubMed ID: 28936181
   
   

   The study demonstrates that Tmem184a is a novel angiogenesis regulator using the adult zebrafish regenerating caudal fin as an in vivo model.

2. Farwell S.L., et al. Using a GFP-tagged TMEM184A Construct for Confirmation of Heparin Receptor Identity. Journal of Visualized Experiments. 2017, 17:(120). PubMed ID: 28287514
   
   

   This report presents a series of experimental protocols based on GFP-TMEM184A constructs expressed in vascular cells that can be easily adapted to other new proteins.

3. Pugh R.J., et al. Transmembrane Protein 184A Is a Receptor Required for Vascular Smooth Muscle Cell Responses to Heparin. Journal of Biological Chemistry. 2016, 291(10):5326-41. PubMed ID: 26769966
   
   

   The data from this study support the discovery that TMEM184A is a heparin receptor in vascular cells.

4. Svingen T., et al. Sex-specific expression of a novel gene Tmem184a during mouse testis differentiation. Reproduction. 2007, 133(5):983-9. PubMed ID: 17616727
   
   

   The results of this study suggest that Tmem184a is expressed only in the Sertoli cells of the developing testicular cord, which mediates gender-specific signals during Sertoli cell differentiation.

5. Farwell S.L.N., et al. Heparin Decreases in Tumor Necrosis Factor α (TNFα)-induced Endothelial Stress Responses Require Transmembrane Protein 184A and Induction of Dual Specificity Phosphatase 1. Journal of Biological Chemistry. 2016, 291(10):5342-54. PubMed ID: 26769965
   
   

   This article demonstrates that TMEM184A acts as a heparin receptor and mediates anti-inflammatory responses in endothelial cells, including reduced JNK and p38 activity.

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Reference

1. Pugh R J, et al. (2016). Transmembrane Protein 184A Is a Receptor Required for Vascular Smooth Muscle Cell Responses to Heparin. Journal of Biological Chemistry. 291(10):5326-41.

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