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FLASH GENE
Symbol ZC3H12A contributors: mct - updated : 07-04-2021
HGNC name zinc finger CCCH-type containing 12A
HGNC id 26259
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
6 - 2737 66 599 - 2020 32548715
6 - 2738 - 325 - 2020 32548715
6 - 2651 - 599 - 2020 32548715
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly Homo sapiensAdult
Lymphoid/Immunespleen   highly Homo sapiensAdult
 thymus   highly
Nervousbrain   highly Homo sapiensFetal
Reproductivefemale systemplacenta  highly Homo sapiensAdult
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow  highly Homo sapiensAdult
cells
SystemCellPubmedSpeciesStageRna symbol
Lymphoid/Immunemacrophage
Nervousneuron Homo sapiensFetal
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,cytoskeleton
    intracellular,nucleus,nucleoplasm,nuclear bodies
    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
  • MCPIP1 endoribonuclease activity negatively regulates IL17-mediated signaling and inflammation
  • plays a crucial anti-inflammatory role not only in myeloid cells but also in epithelial cells
  • plays an important role in early cortical neurogenesis but also reveal an unexpected link between neocortical development, immune regulators, and epigenetic modification
  • contributes to the clear cell renal cell carcinoma (ccRCC) development (28197812)
  • is a master RNA regulator in macrophages and T cells that degrades cellular and viral RNA upon NFKB1 signaling
  • ZC3H12A, like ZC3H12C, is an RNase essential for immune homeostasis but has diverged as key regulator in the IFN pathway in macrophages
  • 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