Description
Monocyte chemoattractant protein-induced protein 1 (MCPIP1), also referred to as ZC3H12A and Regnase-1, is an endonuclease that cleaves and destabilizes mRNA and functions as a negative regulator of inflammation (1,2). MCPIP1 is encoded by the ZC3H12A gene as a protein of 599 amino acids (aa) in length with a theoretical molecular weight of approximately 66 kDa (3-5). Common structural features of the MCPIP1 protein are the ubiquitin-associated (UBA) domain (43-89 aa), two protein-rich regions (PRRs) (100-126 aa, 458-536 aa), the PilT N-terminal (PIN) domain (133-270 aa), the zinc-finger motif (305-325 aa), the natively disordered region (326-457 aa), and the C-terminal conserved region (CCR) (545-598 aa) (1,3-5). MCPIP1 functions as an anti-inflammatory protein with RNase activity that is known to degrade many cytokine mRNA transcripts including interleukin-1beta (IL-1beta), IL-6, and IL-17 (4,5). In addition to its regulation of inflammation through mRNA degradation, MCPIP1 also controls inflammation through ubiquitin-specific peptidase 10 (USP10)-mediated protein deubiquitination of TRAF6 which results in suppression of c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NFkappaB) transcription factors (1,2,5). Besides regulating inflammation, MCPIP1 is involved in several non-immune cellular processes including apoptosis, adipogenesis, angiogenesis, and proliferation (2,5). MCPIP1 has also been implicated in a number of autoimmune diseases and other pathologies including chronic obstructive pulmonary disease (COPD), diabetes, rheumatoid arthritis, and cancer (3,5). Additionally, MCPIP1/ZC3H12A has been shown to have anti-viral activity against RNA viruses such as Japanese encephalitis virus and human immunodeficiency virus (HIV)-1 (1,5).
References
1. Uehata, T., & Takeuchi, O. (2017). Regnase-1 Is an Endoribonuclease Essential for the Maintenance of Immune Homeostasis. Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research, 37(5), 220-229. https://doi.org/10.1089/jir.2017.0001
2. Miekus, K., Kotlinowski, J., Lichawska-Cieslar, A., Rys, J., & Jura, J. (2019). Activity of MCPIP1 RNase in tumor associated processes. Journal of experimental & clinical cancer research : CR, 38(1), 421. https://doi.org/10.1186/s13046-019-1430-6
3. Jura, J., Skalniak, L., & Koj, A. (2012). Monocyte chemotactic protein-1-induced protein-1 (MCPIP1) is a novel multifunctional modulator of inflammatory reactions. Biochimica et biophysica acta, 1823(10), 1905-1913. https://doi.org/10.1016/j.bbamcr.2012.06.029
4. Xu, J., Fu, S., Peng, W., & Rao, Z. (2012). MCP-1-induced protein-1, an immune regulator. Protein & cell, 3(12), 903-910. https://doi.org/10.1007/s13238-012-2075-9
5. Musson, R., Szukala, W., & Jura, J. (2020). MCPIP1 RNase and Its Multifaceted Role. International journal of molecular sciences, 21(19), 7183. https://doi.org/10.3390/ijms21197183
Bioinformatics
Entrez |
Human |
Uniprot |
Human Human |
Product By Gene ID |
80149 |
Alternate Names |
- Reg1
- Regnase-1
- zinc finger CCCH-type containing 12A
|