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FLASH GENE
Symbol ZC3H12A contributors: mct - updated : 17-04-2013
HGNC name zinc finger CCCH-type containing 12A
HGNC id 26259
Location 1p34.3      Physical location : 37.940.118 - 37.949.976
Synonym name
  • MCP-1 treatment-induced protein
  • ribonuclease ZC3H12A
  • monocyte chemotactic protein-induced protein 1
  • Regulatory RNase 1
  • Regnase-1
  • Synonym symbol(s) FLJ23231, RP3-423B22.1, dJ423B22.1, MCPIP, MCPIP1
    EC.number 3.1.-.-
    DNA
    TYPE functioning gene
    STRUCTURE 9.86 kb     6 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 2737 66 599 - 2008 18178554
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiensAdult
    Digestivepharynx   highly
    Lymphoid/Immunespleen   highly Homo sapiensAdult
     thymus   highly
    Reproductivefemale systemplacenta  highly Homo sapiensAdult
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly Homo sapiensAdult
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunemacrophage
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a putative N-terminal nuclease domain, a PilT N-terminus-like RNase structure, further supporting the notion that it has RNase activity (PMID;
  • a CCCH-type zinc-finger motif, playing a part in the control of IL6 mRNA decay
  • two proline-rich domains at the N- and C-terminals, which may mediate interaction with Src homology 3 domain-containing proteins
  • a PIN-like RNase domain
  • HOMOLOGY
    Homologene
    FAMILY
  • CCCH-zinc finger protein family
  • ZC3H12 family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text mainly localized in the cytoplasm, rather than in the nucleus
    basic FUNCTION
  • causing cardiac myocyte apoptosis and ventricular dysfunction
  • regulating macrophage activation
  • negative regulator in macrophage activation and implicated in host immunity and inflammatory diseases
  • plays an important role in both physiological and pathological processes related to inflammation
  • essential RNase that prevents immune disorders by directly controlling the stability of a set of inflammatory genes
  • essential role for preventing the development of severe immune diseases characterized by an increase in immunoglobulin-producing plasma cells and the formation of granulomas
  • having a functional role of CCCH zinc finger genes in the regulation of macrophage activation
  • expression caused induction of a variety of genes known to be involved in cell death
  • acts as a DUB to negatively regulate JNK and NFKB1 signaling and macrophage inflammation
  • functions as a negative regulator of the cytokine-induced inflammatory responses in vascular endothelial cells
  • functions as a RNase to regulate mRNA degradation, and negatively regulates adhesion molecules gene expression by inhibition of their transcription (as VCAM1)
  • may inhibits cytokines-initiated NF-KB signaling and thus limits VCAM1 gene transcription
  • is an equilibrium gatekeeper that not only regulates its own inducers but also controls the regulation by degrading its own mRNA
  • critical regulator of the inflammatory response and immune homeostasis
  • coordinates stress granules formation and apoptosis during cellular stress and may play a critical role in immune homeostasis and resolution of macrophage inflammation
  • may promote cellular apoptosis by disassembling SGs and releasing apoptosis-inducing components
  • functions as a factor to coordinate formation and apoptosis during cellular stress, which may be implicated in the resolution of macrophage inflammation and immune homeostasis
  • potent regulator of innate immunity, which can be strongly engaged in the pathogenesis of acute and chronic infective diseases (PMISD: 22777400)
  • down-regulates IL2 via an ARE-independent pathway
  • destabilizes its own mRNA, thereby preventing excessive translation of Regnase-1 and degradation of cytokine-encoding mRNAs
  • possible involvement of ZC3H12A up-regulation in toxic properties of proteasome inhibition, which is an acknowledged approach to the treatment of several cancer types
  • prominent role in the control of inflammation and immune homeostasis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • TANK formed a complex with ZC3H12A and a deubiquitinase, USP10, which was essential for the USP10-dependent deubiquitination of TRAF6 and the resolution of genotoxic NFKB1 activation upon DNA damage
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • caused activation of JNK (c-Jun N-terminal kinase) and p38 and induction of TP53 and PUMA
  • potential antagonism between ZC3H12A and DICER1 function in human cancer
  • can act as an RNase to promote the mRNA degradation of some inflammatory cytokines, such as IL6 and IL1
  • can degrade IL6, IL12 and TNF mRNA by an ARE-independent pathway in the activation of macrophages
  • by mediating USP10-dependent deubiquitination of IKBKG, ZC3H12A induction serves as a negative feedback mechanism for attenuating genotoxic NFKB activation
  • cell & other
    REGULATION
    induced by dramatically induced by lipopolysaccharide (LPS) in macrophages
    stress in macrophages during the late period, which is associated with the decrease in phosphorylation of EIF2A
    by CCL2 and IL1 whose signals are transduced through the NFKB1 and MAPkinase pathways
    Other Regnase-1 protein expression is dynamically regulated during the course of inflammation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in atherosclerotic lesion, which underlines the importance of ZC3H12A in plaque progression
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target would be a potential therapeutic target for treatment of human inflammatory diseases such as atherosclerosis
    ANIMAL & CELL MODELS
  • Zc3h12a-/- mice suffered from severe anaemia, together with an increase in white blood cells and platelets
  • Mcpip1-deficient mice showed disorganization of lymphoid organs, including spleen, lymph nodes and thymus, and massive infiltration of lymphocytes, macrophages and neutrophils into many other non-lymphoid organs, primarily in lungs and liver
  • Regnase-1-/- mice developed severe systemic inflammation, characterized by production of autoantibodies