ZC3H12A [The Human Chemical-Genetic Interaction Map Project]

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======= ZC3H12A =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: ZC3H12A
  * **<color #00a2e8>Official Name</color>**: zinc finger CCCH-type containing 12A
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=80149|80149]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q5D1E8|Q5D1E8]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=ZC3H12A&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20ZC3H12A|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/610562|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  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). 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). {ECO:0000250|UniProtKB:Q5D1E7, ECO:0000269|PubMed:16574901, ECO:0000269|PubMed:18364357, ECO:0000269|PubMed:19185603, ECO:0000269|PubMed:19909337, ECO:0000269|PubMed:22055188, ECO:0000269|PubMed:22561375, ECO:0000269|PubMed:24048733, ECO:0000269|PubMed:25861989, ECO:0000269|PubMed:26134560, ECO:0000269|PubMed:26320658}. (Microbial infection) Exhibits antiviral activity against HIV-1 in lymphocytes by decreasing the abundance of HIV-1 viral RNA species. {ECO:0000269|PubMed:24191027}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|RNase Zc3h12a|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|nuclear-transcribed mRNA catabolic process, endonucleolytic cleavage-dependent decay|
|positive regulation of miRNA catabolic process|
|regulation of miRNA catabolic process|
|negative regulation of interferon-gamma secretion|
|cellular response to ionomycin|
|response to ionomycin|
|positive regulation of miRNA metabolic process|
|cellular response to sodium arsenite|
|cellular response to ether|
|negative regulation of cardiac muscle contraction|
|negative regulation by host of viral genome replication|
|response to sodium arsenite|
|extrinsic component of endoplasmic reticulum membrane|
|positive regulation of protein deubiquitination|
|cellular response to salt|
|negative regulation of striated muscle contraction|
|negative regulation of T-helper 17 cell differentiation|
|rough endoplasmic reticulum membrane|
|negative regulation of tumor necrosis factor secretion|
|negative regulation of production of miRNAs involved in gene silencing by miRNA|
|regulation of miRNA metabolic process|
|negative regulation of T-helper 17 type immune response|
|negative regulation of interleukin-6 secretion|
|negative regulation by host of viral process|
|regulation of interferon-gamma secretion|
|regulation of protein deubiquitination|
|response to ether|
|response to herbicide|
|negative regulation of gene silencing by miRNA|
|modulation by host of viral genome replication|
|exoribonuclease activity|
|negative regulation of nitric oxide metabolic process|
|negative regulation of nitric oxide biosynthetic process|
|positive regulation of execution phase of apoptosis|
|negative regulation of interleukin-1 beta secretion|
|negative regulation of posttranscriptional gene silencing|
|negative regulation of T-helper cell differentiation|
|negative regulation of macrophage activation|
|negative regulation of gene silencing by RNA|
|3-UTR-mediated mRNA destabilization|
|response to insecticide|
|negative regulation of cytokine production involved in inflammatory response|
|regulation of T-helper 17 cell differentiation|
|negative regulation of interleukin-1 secretion|
|regulation of production of miRNAs involved in gene silencing by miRNA|
|cellular response to arsenic-containing substance|
|response to salt|
|regulation of production of small RNA involved in gene silencing by RNA|
|negative regulation of CD4-positive, alpha-beta T cell differentiation|
|regulation of T-helper 17 type immune response|
|positive regulation of lipid storage|
|ribonuclease activity|
|RNA stem-loop binding|
|negative regulation of NIK/NF-kappaB signaling|
|negative regulation of muscle contraction|
|negative regulation of alpha-beta T cell differentiation|
|negative regulation of heart contraction|
|mRNA 3-UTR AU-rich region binding|
|positive regulation of defense response to virus by host|
|negative regulation of interleukin-1 beta production|
|endoribonuclease activity|
|positive regulation of p38MAPK cascade|
|negative regulation of reactive oxygen species biosynthetic process|
|modulation by host of viral process|
|negative regulation of CD4-positive, alpha-beta T cell activation|
|regulation of tumor necrosis factor secretion|
|mRNA destabilization|
|miRNA binding|
|cellular response to virus|
|RNA destabilization|
|response to arsenic-containing substance|
|negative regulation of interleukin-1 production|
|negative regulation of blood circulation|
|negative regulation of interferon-gamma production|
|regulation of T-helper cell differentiation|
|negative regulation of gene silencing|
|regulation of defense response to virus by host|
|negative regulation of muscle cell apoptotic process|
|positive regulation of protein import into nucleus|
|negative regulation of alpha-beta T cell activation|
|positive regulation of protein import|
|regulation of cytokine production involved in inflammatory response|
|negative regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|regulation of p38MAPK cascade|
|regulation of execution phase of apoptosis|
|cellular response to glucose starvation|
|RNA phosphodiester bond hydrolysis, exonucleolytic|
|negative regulation of interleukin-6 production|
|negative regulation of T cell differentiation|
|negative regulation of I-kappaB kinase/NF-kappaB signaling|
|negative regulation of adaptive immune response|
|regulation of lipid storage|
|regulation of CD4-positive, alpha-beta T cell differentiation|
|regulation of interleukin-1 beta secretion|
|positive regulation of mRNA catabolic process|
|regulation of macrophage activation|
|negative regulation of lymphocyte differentiation|
|negative regulation of reactive oxygen species metabolic process|
|regulation of interleukin-1 secretion|
|cellular response to fatty acid|
|regulation of protein import into nucleus|
|ribosome binding|
|regulation of nitric oxide biosynthetic process|
|negative regulation of viral genome replication|
|regulation of protein import|
|negative regulation of tumor necrosis factor production|
|regulation of CD4-positive, alpha-beta T cell activation|
|rough endoplasmic reticulum|
|negative regulation of tumor necrosis factor superfamily cytokine production|
|positive regulation of fat cell differentiation|
|regulation of alpha-beta T cell differentiation|
|positive regulation of nucleocytoplasmic transport|
|cytoplasmic ribonucleoprotein granule|
|negative regulation of cytokine secretion|
|regulation of muscle cell apoptotic process|
|modification by host of symbiont morphology or physiology|
|regulation of defense response to virus|
|positive regulation of protein localization to nucleus|
|mRNA 3-UTR binding|
|interaction with symbiont|
|regulation of cardiac muscle contraction|
|positive regulation of mRNA metabolic process|
|negative regulation of viral life cycle|
|RNA phosphodiester bond hydrolysis, endonucleolytic|
|regulation of interleukin-1 beta production|
|positive regulation of lipid localization|
|negative regulation of NF-kappaB transcription factor activity|
|response to fatty acid|
|regulation of reactive oxygen species biosynthetic process|
|P-body|
|regulation of gene silencing by miRNA|
|response to chemokine|
|cellular response to chemokine|
|regulation of gene silencing by RNA|
|regulation of posttranscriptional gene silencing|
|regulation of striated muscle contraction|
|regulation of alpha-beta T cell activation|
|regulation of viral genome replication|
|regulation of interleukin-1 production|
|response to antineoplastic agent|
|positive regulation of reactive oxygen species metabolic process|
|negative regulation of viral process|
|regulation of interferon-gamma production|
|positive regulation of endothelial cell migration|
|negative regulation of leukocyte differentiation|
|regulation of nucleocytoplasmic transport|
|thiol-dependent ubiquitin-specific protease activity|
|regulation of NIK/NF-kappaB signaling|
|negative regulation of T cell activation|
|modification of morphology or physiology of other organism involved in symbiotic interaction|
|regulation of protein localization to nucleus|
|cellular response to antibiotic|
|negative regulation of immune effector process|
|positive regulation of autophagy|
|negative regulation of leukocyte cell-cell adhesion|
|regulation of fat cell differentiation|
|regulation of gene silencing|
|negative regulation of translation|
|negative regulation of protein secretion|
|positive regulation of protein modification by small protein conjugation or removal|
|negative regulation of hemopoiesis|
|negative regulation of inflammatory response|
|regulation of T cell differentiation|
|regulation of lipid localization|
|negative regulation of peptide secretion|
|regulation of interleukin-6 production|
|positive regulation of epithelial cell migration|
|regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|negative regulation of lymphocyte activation|
|regulation of viral life cycle|
|negative regulation of cellular amide metabolic process|
|negative regulation of immune response|
|regulation of tumor necrosis factor production|
|cellular response to starvation|
|regulation of tumor necrosis factor superfamily cytokine production|
|positive regulation of intracellular protein transport|
|modification of morphology or physiology of other organism|
|regulation of endothelial cell migration|
|RNA phosphodiester bond hydrolysis|
|negative regulation of DNA-binding transcription factor activity|
|regulation of muscle contraction|
|regulation of adaptive immune response|
|mRNA binding|
|positive regulation of angiogenesis|
|positive regulation of stress-activated MAPK cascade|
|regulation of lymphocyte differentiation|
|positive regulation of stress-activated protein kinase signaling cascade|
|cellular response to interleukin-1|
|negative regulation of leukocyte activation|
|negative regulation of cell-cell adhesion|
|T cell receptor signaling pathway|
|regulation of mRNA stability|
|regulation of reactive oxygen species metabolic process|
|negative regulation of protein transport|
|positive regulation of vasculature development|
|cellular response to lipopolysaccharide|
|regulation of RNA stability|
|negative regulation of establishment of protein localization|
|defense response to virus|
|cellular response to molecule of bacterial origin|
|response to starvation|
|negative regulation of cell activation|
|nuclear-transcribed mRNA catabolic process|
|response to interleukin-1|
|regulation of mRNA catabolic process|
|negative regulation of secretion by cell|
|regulation of cytokine secretion|
|regulation of viral process|
|negative regulation of defense response|
|positive regulation of intracellular transport|
|cellular response to acid chemical|
|cellular response to toxic substance|
|negative regulation of multi-organism process|
|cellular response to biotic stimulus|
|mRNA catabolic process|
|regulation of epithelial cell migration|
|regulation of symbiosis, encompassing mutualism through parasitism|
|regulation of protein modification by small protein conjugation or removal|
|regulation of intracellular protein transport|
|negative regulation of secretion|
|cellular response to nutrient levels|
|regulation of stress-activated MAPK cascade|
|regulation of muscle system process|
|regulation of I-kappaB kinase/NF-kappaB signaling|
|regulation of stress-activated protein kinase signaling cascade|
|cellular response to oxidative stress|
|cellular response to tumor necrosis factor|
|regulation of heart contraction|
|RNA catabolic process|
|response to tumor necrosis factor|
|cellular response to extracellular stimulus|
|regulation of leukocyte differentiation|
|negative regulation of cell adhesion|
|negative regulation of cytokine production|
|response to virus|
|protein deubiquitination|
|regulation of angiogenesis|
|regulation of blood circulation|
|antigen receptor-mediated signaling pathway|
|regulation of leukocyte cell-cell adhesion|
|protein modification by small protein removal|
|nucleic acid phosphodiester bond hydrolysis|
|response to antibiotic|
|response to lipopolysaccharide|
|regulation of T cell activation|
|angiogenesis|
|regulation of vasculature development|
|positive regulation of cellular protein localization|
|response to molecule of bacterial origin|
|regulation of mRNA metabolic process|
|regulation of autophagy|
|cellular response to external stimulus|
|regulation of inflammatory response|
|response to acid chemical|
|regulation of intracellular transport|
|regulation of translation|
|regulation of neurotransmitter levels|
|positive regulation of proteolysis|
|positive regulation of cellular catabolic process|
|negative regulation of response to external stimulus|
|cytoskeleton|
|nucleobase-containing compound catabolic process|
|response to oxidative stress|
|chromatin binding|
|regulation of cell-cell adhesion|
|cellular response to drug|
|regulation of cellular amide metabolic process|
|negative regulation of protein phosphorylation|
|blood vessel morphogenesis|
|positive regulation of protein transport|
|regulation of DNA-binding transcription factor activity|
|positive regulation of catabolic process|
|heterocycle catabolic process|
|cellular nitrogen compound catabolic process|
|negative regulation of immune system process|
|aromatic compound catabolic process|
|negative regulation of phosphorylation|
|immune response-activating cell surface receptor signaling pathway|
|regulation of hemopoiesis|
|positive regulation of establishment of protein localization|
|regulation of protein secretion|
|regulation of immune effector process|
|organic cyclic compound catabolic process|
|immune response-regulating cell surface receptor signaling pathway|
|negative regulation of transport|
|blood vessel development|
|regulation of peptide secretion|
|inflammatory response|
|response to nutrient levels|
|positive regulation of cell migration|
|response to toxic substance|
|negative regulation of intracellular signal transduction|
|vasculature development|
|regulation of lymphocyte activation|
|cardiovascular system development|
|protein complex oligomerization|
|cellular response to lipid|
|regulation of response to biotic stimulus|
|positive regulation of cell motility|
|posttranscriptional regulation of gene expression|
|response to extracellular stimulus|
|response to inorganic substance|
|positive regulation of cellular component movement|
|regulation of cellular protein localization|
|cellular response to organic cyclic compound|
|positive regulation of MAPK cascade|
|positive regulation of locomotion|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|immune response-activating signal transduction|
|regulation of system process|
|negative regulation of protein modification process|
|protein-containing complex|
|immune response-regulating signaling pathway|
|regulation of leukocyte activation|
|activation of immune response|
|regulation of cell activation|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|tube morphogenesis|
|regulation of cell adhesion|
|response to bacterium|
|mRNA metabolic process|
|regulation of cytokine production|
|positive regulation of cell death|
|regulation of protein transport|
|negative regulation of cell differentiation|
|regulation of proteolysis|
|regulation of cellular response to stress|
|regulation of peptide transport|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|regulation of MAPK cascade|
|regulation of defense response|
|regulation of multi-organism process|
|cellular response to DNA damage stimulus|
|symbiotic process|
|regulation of secretion|
|interspecies interaction between organisms|
|regulation of cellular catabolic process|
|tube development|
|regulation of cell migration|
|response to lipid|
|positive regulation of immune response|
|circulatory system development|
|negative regulation of apoptotic process|
|anatomical structure formation involved in morphogenesis|
|cellular macromolecule catabolic process|
|negative regulation of programmed cell death|
|regulation of cell motility|
|regulation of cellular localization|
|response to organic cyclic compound|
|apoptotic process|
|negative regulation of developmental process|
|defense response to other organism|
|positive regulation of cell differentiation|
|regulation of locomotion|
|protein modification by small protein conjugation or removal|
|positive regulation of transport|
|regulation of cellular component movement|
|negative regulation of cell death|
|regulation of catabolic process|
|cellular response to cytokine stimulus|
|positive regulation of protein phosphorylation|
|response to drug|
|positive regulation of intracellular signal transduction|
|regulation of protein localization|
|negative regulation of cellular protein metabolic process|
|macromolecule catabolic process|
|programmed cell death|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|regulation of anatomical structure morphogenesis|
|cell death|
|immune effector process|
|regulation of response to external stimulus|
|response to cytokine|
|negative regulation of protein metabolic process|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|negative regulation of molecular function|
|regulation of immune response|
|positive regulation of immune system process|
|negative regulation of multicellular organismal process|
|positive regulation of transcription by RNA polymerase II|
|positive regulation of protein modification process|
|negative regulation of signal transduction|
|proteolysis|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|negative regulation of RNA metabolic process|
|defense response|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|negative regulation of cellular macromolecule biosynthetic process|
|RNA binding|
|negative regulation of nucleobase-containing compound metabolic process|
|regulation of protein phosphorylation|
|DNA binding|
|negative regulation of macromolecule biosynthetic process|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|positive regulation of transcription, DNA-templated|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|negative regulation of response to stimulus|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|positive regulation of signal transduction|
|regulation of immune system process|
|RNA metabolic process|
|regulation of cell death|
|cellular response to stress|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|organic substance catabolic process|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|cellular catabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|regulation of transport|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp129|Isonicotinamide 500μM R03 exp129]]|2.86|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 6964
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 2.68 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='ZC3H12A Expression in NALM6 Cells: 2.68'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>