Table 1.
Summary of the distribution and functions of human selenoproteins
| Selenoprotein | Subcellular location | †RNA expression in immune cells | †Expression in tissues and organs | Function |
|---|---|---|---|---|
| *GPX1 (cGPX) | cytoplasm; mitochondrial membrane |
unclear | ubiquitous expression; high in kidney and liver | antioxidant; cardioprotective and anti-angiogenic (Galasso et al. 2006; Thu et al. 2010) |
| GPX2 (GI-GPX) | cytoplasm | NK cell > intermediate monocyte > neutrophil > naïve B cell > classical monocyte | gastrointestinal epithelium | antioxidant; dual role in carcinogenesis ((Brigelius-Flohe and Kipp 2012; Krehl et al. 2012; Muller MF et al. 2013; Emmink et al. 2014) |
| GPX3 (pGPX) | secreted abundantly in plasma | neutrophil > classical monocyte > myeloid DC > intermediate monocyte > total PBMC | plasma, kidney, thyroid gland | antioxidant; tumor suppressor (Barrett et al. 2013) |
| **GPX4 (PHGPX) | cytoplasm mitochondria and nuclei |
total PBMC > eosinophil > classical monocyte > basophil > non-classical monocyte | ubiquitous expression | antioxidant; regulation of ferroptosis and phospholipid hydroperoxide levels (Seiler et al. 2008); involved in spermiogenesis (Ursini et al. 1999) |
| GPX6 | Secreted protein | neutrophil > eosinophil > non-classical monocyte > intermediate monocyte | olfactory epithelium and embryonic tissues; secreted in male reproductive system |
antioxidant (Kryukov et al. 2003) |
| **Txnrd1 (TrxR1) | cytoplasm nucleoplasm |
neutrophil > basophil > eosinophil > non-classical monocyte > myeloid DC | ubiquitous expression | antioxidant; embryonic development (Conrad et al. 2004; Jakupoglu et al. 2005) |
| Txnrd2 (TrxR3) | cytoplasm Mitochondrial membrane |
classical monocyte > intermediate monocyte > myeloid DC > non-classical monocyte > eosinophil | ubiquitous expression | antioxidant; embryonic development (Conrad et al. 2004; Jakupoglu et al. 2005) |
| **Txnrd3 (TGR/TrxR2) | cytoplasm nucleoplasm |
naïve CD4 T cell > naïve CD8 T cell > classical monocyte > NK cell > intermediate monocyte | testis-specific expression | antioxidant; involved in spermiogenesis (Su et al. 2005) |
| DIO1 | plasma membrane | myeloid DC > classical monocyte > naïve CD4 T cell > intermediate monocyte > memory CD4 T-cell | thyroid gland, kidney, liver | regulation of the circulating thyroid hormone levels (St Germain and Galton 1997) |
| DIO2 | ER membrane | neutrophil > basophil > classical monocyte > plasmacytoid DC > eosinophil | thyroid gland, cervix, uterine | regulation of muscular thyroid hormone levels (St Germain and Galton 1997) |
| DIO3 | plasma membrane | not detected | thyroid gland, cervix, uterine, placenta | Inactivating thyroid hormone (St Germain and Galton 1997) |
| *SelenoH | nucleoplasm and nucleoli | plasmacytoid DC > classical monocyte > total PBMC > myeloid DC > intermediate monocyte | ubiquitous expression | antioxidant (Martin-Romero et al. 2001; Kryukov et al. 2003) |
| SelenoI | plasma membrane | memory B cell > naïve CD8 T cell > Treg > naïve CD4 T cell > plasmacytoid DC | ubiquitous expression | catalyzing the synthesis of phosphatidylethanolamine (Kryukov et al. 2003) |
| SelenoK | ER membrane | basophil > eosinophil > neutrophil > total PBMC > γδT cell | mainly expressed in heart and skeletal muscle; also present in other organs such as pancreas, liver, placenta | involved in ERAD and protein palmitoylation (Shchedrina et al. 2011; Fredericks et al. 2014) |
| SelenoM | ER membrane | naïve CD4 T cell > memory CD4 T cell > Treg > memory B cell > naïve CD8 T cell | expression is the highest in brain; also present in thyroid, heart, lung, kidney, uterus, placenta | the exact function remains unknown; possibly involved in neurodegeneration (Korotkov et al. 2002) |
| SelenoN | ER membrane | basophil > eosinophil > classical monocyte > intermediate monocyte > naïve CD4 T cell | ubiquitous expression | regulating the muscular regeneration (Moghadaszadeh et al. 2001) |
| SelenoO | mitochondrial membrane | eosinophil > classical monocyte > myeloid DC >MAIT cell > memory CD8 T cell | ubiquitous expression | the exact function remains unknow; possibly involved in redox regulation (Kryukov et al. 2003) |
| SelenoP (SEPP1) | secreted protein in plasma | plasmacytoid DC > NK cell > MAIT cell > naïve CD4 T cell > neutrophil | secreted to plasma by liver; but also seen in all tissues (Hill KE et al. 2003; Schomburg et al. 2003) | transporting Se to peripheral tissues |
| *SelenoR (MsrB1) | cytoplasm nucleoplasm |
neutrophil > eosinophil > classical monocyte > basophil > total PBMC | ubiquitous, mainly enriched in liver and kidney | antioxidant; regulation of actin polymerization (Lee et al. 2013) |
| SelenoS (SEPS1) | ER membrane | plasmacytoid DC > basophil > memory CD8 T cell > γδT cell > MAIT cell | ubiquitous expression | involved in ERAD and inflammation as well as immune response (Turanov et al. 2014) |
| SelenoT | ER membrane Golgi complex |
total PBMC > neutrophil > classical monocyte > MAIT cell > basophil | ubiquitous expression; abundant in brain at embryonic stages; but undetectable in the adult; persistently high expression in adult endocrine organs | possibly involved in redox regulation (Ursini et al. 1999) |
| SelenoV | unclear | neutrophil > classical monocyte > MAIT cell > naïve CD4 T cell > plasmacytoid DC | testes-specific expression | possibly involved in redox regulation (Kryukov et al. 2003) |
| *SelenoW | cytoplasm, a small fraction is bound to the cell membrane | eosinophil > Treg > total PBMC > naïve CD4 T cell > memory CD4 T cell | highly expressed in skeletal muscle, heart, and brain | antioxidant; possibly involved in muscle growth and differentiation (Vendeland et al. 1995) |
| SPS2 | nucleoplasm | NK cell > eosinophil > naïve CD4 T cell > MAIT cell > memory CD8 T cell | ubiquitous expression | autoregulation and synthesis of selenoproteins (Low et al. 1995; Guimaraes et al. 1996) |
| *Sep15 (SelenoF) | ER membrane | naïve B cell > plasmacytoid DC > memory B cell > total PBMC > basophil | Brain, prostate, testis, liver, and kidney | possibly implicated in cancer etiology (Kumaraswamy et al. 2000; Ferguson et al. 2006) |
*
Stress-responsive selenoproteins;
**
Housekeeping selenoproteins;
†
Data were extracted from “The Human Protein Atlas” (https://www.proteinatlas.org)
ER: endoplasmic reticulum; ERAD: ER-associated degradation; GI: gastrointestinal; MAIT: mucosal associated invariant T cell; PBMC: peripheral blood mononuclear cell; PHGPX: phospholipid hydroperoxide GPX