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Identification
HMDB Protein ID HMDBP13852
Secondary Accession Numbers None
Name Endoribonuclease ZC3H12A
Synonyms
  1. Monocyte chemotactic protein-induced protein 1
  2. Regnase-1
  3. Zinc finger CCCH domain-containing protein 12A
  4. MCP-induced protein 1
  5. MCPIP-1
  6. Reg1
Gene Name ZC3H12A
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Endoribonuclease involved in various biological functions such as cellular inflammatory response and immune homeostasis, glial differentiation of neuroprogenitor cells, cell death of cardiomyocytes, adipogenesis and angiogenesis. Functions as an endoribonuclease involved in mRNA decay (PubMed:19909337). Modulates the inflammatory response by promoting the degradation of a set of translationally active cytokine-induced inflammation-related mRNAs, such as IL6 and IL12B, during the early phase of inflammation (PubMed:26320658). Prevents aberrant T-cell-mediated immune reaction by degradation of multiple mRNAs controlling T-cell activation, such as those encoding cytokines (IL6 and IL2), cell surface receptors (ICOS, TNFRSF4 and TNFR2) and transcription factor (REL) (By similarity). Inhibits cooperatively with ZC3H12A the differentiation of helper T cells Th17 in lungs. They repress target mRNA encoding the Th17 cell-promoting factors IL6, ICOS, REL, IRF4, NFKBID and NFKBIZ. The cooperation requires RNA-binding by RC3H1 and the nuclease activity of ZC3H12A (By similarity). Together with RC3H1, destabilizes TNFRSF4/OX40 mRNA by binding to the conserved stem loop structure in its 3'UTR (By similarity). Self regulates by destabilizing its own mRNA (By similarity). Cleaves mRNA harboring a stem-loop (SL), often located in their 3'-UTRs, during the early phase of inflammation in a helicase UPF1-dependent manner (PubMed:19909337, PubMed:26320658, PubMed:26134560, PubMed:22561375). Plays a role in the inhibition of microRNAs (miRNAs) biogenesis (PubMed:22055188). Cleaves the terminal loop of a set of precursor miRNAs (pre-miRNAs) important for the regulation of the inflammatory response leading to their degradation, and thus preventing the biosynthesis of mature miRNAs (PubMed:22055188). Plays also a role in promoting angiogenesis in response to inflammatory cytokines by inhibiting the production of antiangiogenic microRNAs via its anti-dicer RNase activity (PubMed:24048733). Affects the overall ubiquitination of cellular proteins (By similarity). Positively regulates deubiquitinase activity promoting the cleavage at 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains on TNF receptor-associated factors (TRAFs), preventing JNK and NF-kappa-B signaling pathway activation, and hence negatively regulating macrophage-mediated inflammatory response and immune homeostasis (By similarity). Induces also deubiquitination of the transcription factor HIF1A, probably leading to its stabilization and nuclear import, thereby positively regulating the expression of proangiogenic HIF1A-targeted genes (PubMed:24048733). Involved in a TANK-dependent negative feedback response to attenuate NF-kappaB activation through the deubiquitination of IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Prevents stress granule (SGs) formation and promotes macrophage apoptosis under stress conditions, including arsenite-induced oxidative stress, heat shock and energy deprivation (By similarity). Plays a role in the regulation of macrophage polarization; promotes IL4-induced polarization of macrophages M1 into anti-inflammatory M2 state (By similarity). May also act as a transcription factor that regulates the expression of multiple genes involved in inflammatory response, angiogenesis, adipogenesis and apoptosis (PubMed:16574901, PubMed:18364357). Functions as a positive regulator of glial differentiation of neuroprogenitor cells through an amyloid precursor protein (APP)-dependent signaling pathway (PubMed:19185603). Attenuates septic myocardial contractile dysfunction in response to lipopolysaccharide (LPS) by reducing I-kappa-B-kinase (IKK)-mediated NF-kappa-B activation, and hence myocardial proinflammatory cytokine production (By similarity).(Microbial infection) Binds to Japanese encephalitis virus (JEV) and Dengue virus (DEN) RNAs.(Microbial infection) Exhibits antiviral activity against HIV-1 in lymphocytes by decreasing the abundance of HIV-1 viral RNA species.
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
negative regulation of cytokine production involved in inflammatory response
negative regulation by host of viral genome replication
protein deubiquitination
positive regulation of reactive oxygen species metabolic process
positive regulation of execution phase of apoptosis
3'-UTR-mediated mRNA destabilization
negative regulation of interferon-gamma production
cellular response to glucose starvation
positive regulation of cell death
apoptotic process
positive regulation of protein import into nucleus
positive regulation of autophagy
negative regulation of I-kappaB kinase/NF-kappaB cascade
negative regulation of interleukin-1 beta production
inflammatory response
negative regulation of tumor necrosis factor production
cellular response to tumor necrosis factor
cellular response to virus
response to DNA damage stimulus
positive regulation of endothelial cell migration
negative regulation of nitric oxide biosynthetic process
cellular response to chemokine
cellular response to ionomycin
cellular response to sodium arsenite
immune response-activating signal transduction
negative regulation of macrophage activation
negative regulation of muscle cell apoptotic process
negative regulation of NIK/NF-kappaB signaling
negative regulation of production of miRNAs involved in gene silencing by miRNA
negative regulation of T-helper 17 cell differentiation
nuclear-transcribed mRNA catabolic process, endonucleolytic cleavage-dependent decay
positive regulation of protein deubiquitination
RNA phosphodiester bond hydrolysis
RNA phosphodiester bond hydrolysis, endonucleolytic
cellular response to lipopolysaccharide
cellular response to interleukin-1
T cell receptor signaling pathway
angiogenesis
positive regulation of angiogenesis
protein oligomerization
negative regulation of protein phosphorylation
nervous system development
positive regulation of lipid storage
defense response to virus
negative regulation of NF-kappaB transcription factor activity
positive regulation of defense response to virus by host
viral reproduction
positive regulation of transcription from RNA polymerase II promoter
cell differentiation
positive regulation of miRNA catabolic process
positive regulation of mRNA catabolic process
negative regulation of interleukin-6 production
positive regulation of fat cell differentiation
positive regulation of p38MAPK cascade
regulation of gene expression
positive regulation of gene expression
negative regulation of cardiac muscle contraction
negative regulation of gene expression
cellular response to oxidative stress
Cellular Component
cytoplasmic mRNA processing body
cytoskeleton
rough endoplasmic reticulum membrane
protein-containing complex
cytoplasm
nucleus
nucleoplasm
cytoplasmic ribonucleoprotein granule
extrinsic component of endoplasmic reticulum membrane
rough endoplasmic reticulum
Molecular Function
ribosome binding
mRNA 3'-UTR AU-rich region binding
metal ion binding
RNA stem-loop binding
endoribonuclease activity
exoribonuclease activity
ribonuclease activity
RNA binding
chromatin binding
miRNA binding
DNA binding
mRNA binding
mRNA 3'-UTR binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 599
Molecular Weight 65698.56
Theoretical pI 6.938
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q5D1E8
UniProtKB/Swiss-Prot Entry Name ZC12A_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  4. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [PubMed:23186163 ]
  5. Zhou L, Azfer A, Niu J, Graham S, Choudhury M, Adamski FM, Younce C, Binkley PF, Kolattukudy PE: Monocyte chemoattractant protein-1 induces a novel transcription factor that causes cardiac myocyte apoptosis and ventricular dysfunction. Circ Res. 2006 May 12;98(9):1177-85. doi: 10.1161/01.RES.0000220106.64661.71. Epub 2006 Mar 30. [PubMed:16574901 ]
  6. Liang J, Wang J, Azfer A, Song W, Tromp G, Kolattukudy PE, Fu M: A novel CCCH-zinc finger protein family regulates proinflammatory activation of macrophages. J Biol Chem. 2008 Mar 7;283(10):6337-46. doi: 10.1074/jbc.M707861200. Epub 2008 Jan 4. [PubMed:18178554 ]
  7. Niu J, Azfer A, Zhelyabovska O, Fatma S, Kolattukudy PE: Monocyte chemotactic protein (MCP)-1 promotes angiogenesis via a novel transcription factor, MCP-1-induced protein (MCPIP). J Biol Chem. 2008 May 23;283(21):14542-51. doi: 10.1074/jbc.M802139200. Epub 2008 Mar 24. [PubMed:18364357 ]
  8. Vrotsos EG, Kolattukudy PE, Sugaya K: MCP-1 involvement in glial differentiation of neuroprogenitor cells through APP signaling. Brain Res Bull. 2009 Apr 29;79(2):97-103. doi: 10.1016/j.brainresbull.2009.01.004. Epub 2009 Jan 29. [PubMed:19185603 ]
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  12. Suzuki HI, Arase M, Matsuyama H, Choi YL, Ueno T, Mano H, Sugimoto K, Miyazono K: MCPIP1 ribonuclease antagonizes dicer and terminates microRNA biogenesis through precursor microRNA degradation. Mol Cell. 2011 Nov 4;44(3):424-36. doi: 10.1016/j.molcel.2011.09.012. [PubMed:22055188 ]
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  15. Uehata T, Akira S: mRNA degradation by the endoribonuclease Regnase-1/ZC3H12a/MCPIP-1. Biochim Biophys Acta. 2013 Jun-Jul;1829(6-7):708-13. doi: 10.1016/j.bbagrm.2013.03.001. Epub 2013 Mar 13. [PubMed:23500036 ]
  16. Lin RJ, Chien HL, Lin SY, Chang BL, Yu HP, Tang WC, Lin YL: MCPIP1 ribonuclease exhibits broad-spectrum antiviral effects through viral RNA binding and degradation. Nucleic Acids Res. 2013 Mar 1;41(5):3314-26. doi: 10.1093/nar/gkt019. Epub 2013 Jan 25. [PubMed:23355615 ]
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  19. Huang S, Liu S, Fu JJ, Tony Wang T, Yao X, Kumar A, Liu G, Fu M: Monocyte Chemotactic Protein-induced Protein 1 and 4 Form a Complex but Act Independently in Regulation of Interleukin-6 mRNA Degradation. J Biol Chem. 2015 Aug 21;290(34):20782-20792. doi: 10.1074/jbc.M114.635870. Epub 2015 Jul 1. [PubMed:26134560 ]
  20. Xu J, Peng W, Sun Y, Wang X, Xu Y, Li X, Gao G, Rao Z: Structural study of MCPIP1 N-terminal conserved domain reveals a PIN-like RNase. Nucleic Acids Res. 2012 Aug;40(14):6957-65. doi: 10.1093/nar/gks359. Epub 2012 May 4. [PubMed:22561375 ]