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Protein

Bifunctional endoribonuclease and deubiquitinase ZC3H12A

Gene

Zc3h12a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Bifunctional enzyme with both endoribonuclease and deubiquitinase activities 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:26000482). 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:19322177, PubMed:21115689, PubMed:23185455, PubMed:26000482). 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) (PubMed:23706741). Self regulates by destabilizing its own mRNA (PubMed:22037600). 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:19322177, PubMed:23185455, PubMed:23706741, PubMed:26000482, PubMed:26134560). Plays a role in the inhibition of microRNAs (miRNAs) biogenesis (By similarity). 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 (By similarity). 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 (By similarity). Functions as a deubiquitinase that affects the overall ubiquitination of cellular proteins (PubMed:21115689). Possesses deubiquitinase activity that specifically cleaves '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 regulates macrophage-mediated inflammatory response and immune homeostasis (PubMed:21115689). Deubiquitinates also the transcription factor HIF1A, probably leading to its stabilization and nuclear import, thereby positively regulating the expression of proangiogenic HIF1A-targeted genes (By similarity). Prevents stress granules (SGs) formation and promotes macrophage apoptosis under stress conditions, including arsenite-induced oxidative stress, heat shock, and energy deprivation, which may be dependent on its deubiquitinase activity (PubMed:21971051). Plays a role in the regulation of macrophage polarization; promotes IL4-induced polarization of macrophages M1 into anti-inflammatory M2 state, depending on both endoribonuclease and deubiquitinase activities (PubMed:25934862). May also act as a transcription factor that regulates the expression of multiple genes involved in inflammatory response, angiogenesis, adipogenesis and apoptosis (PubMed:18178554, PubMed:19666473, PubMed:22739135). Functions as a positive regulator of glial differentiation of neuroprogenitor cells through an amyloid precursor protein (APP)-dependent signaling pathway (By similarity). 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 (PubMed:21616078).By similarity13 Publications

Catalytic activityi

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).1 Publication

Cofactori

Mg2+1 PublicationNote: Mg2+ is required for RNase activity (PubMed:19322177).1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi226 – 2261MagnesiumBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri301 – 32424C3H1-typeAdd
BLAST

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • DNA binding Source: UniProtKB
  • endoribonuclease activity Source: UniProtKB
  • exoribonuclease activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • miRNA binding Source: UniProtKB
  • mRNA 3'-UTR AU-rich region binding Source: UniProtKB
  • mRNA 3'-UTR binding Source: UniProtKB
  • mRNA binding Source: MGI
  • ribonuclease activity Source: MGI
  • ribosome binding Source: UniProtKB
  • RNA binding Source: MGI
  • RNA stem-loop binding Source: UniProtKB
  • thiol-dependent ubiquitinyl hydrolase activity Source: UniProtKB-EC

GO - Biological processi

  • 3'-UTR-mediated mRNA destabilization Source: UniProtKB
  • angiogenesis Source: UniProtKB-KW
  • apoptotic process Source: UniProtKB-KW
  • cell differentiation Source: UniProtKB-KW
  • cellular response to chemokine Source: UniProtKB
  • cellular response to glucose starvation Source: UniProtKB
  • cellular response to interleukin-1 Source: UniProtKB
  • cellular response to ionomycin Source: UniProtKB
  • cellular response to lipopolysaccharide Source: UniProtKB
  • cellular response to oxidative stress Source: UniProtKB
  • cellular response to phorbol 13-acetate 12-myristate Source: UniProtKB
  • cellular response to sodium arsenite Source: UniProtKB
  • cellular response to tumor necrosis factor Source: UniProtKB
  • cellular response to virus Source: MGI
  • immune system process Source: UniProtKB-KW
  • inflammatory response Source: UniProtKB-KW
  • negative regulation by host of viral genome replication Source: MGI
  • negative regulation of cardiac muscle contraction Source: UniProtKB
  • negative regulation of cytokine production involved in inflammatory response Source: UniProtKB
  • negative regulation of gene expression Source: BHF-UCL
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • negative regulation of interferon-gamma secretion Source: UniProtKB
  • negative regulation of interleukin-1 beta secretion Source: UniProtKB
  • negative regulation of interleukin-6 production Source: BHF-UCL
  • negative regulation of interleukin-6 secretion Source: UniProtKB
  • negative regulation of muscle cell apoptotic process Source: UniProtKB
  • negative regulation of NF-kappaB import into nucleus Source: UniProtKB
  • negative regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  • negative regulation of nitric oxide biosynthetic process Source: UniProtKB
  • negative regulation of production of miRNAs involved in gene silencing by miRNA Source: UniProtKB
  • negative regulation of protein phosphorylation Source: UniProtKB
  • negative regulation of tumor necrosis factor production Source: BHF-UCL
  • negative regulation of tumor necrosis factor secretion Source: UniProtKB
  • nervous system development Source: UniProtKB-KW
  • nuclear-transcribed mRNA catabolic process, endonucleolytic cleavage-dependent decay Source: UniProtKB
  • positive regulation of angiogenesis Source: UniProtKB
  • positive regulation of autophagy Source: BHF-UCL
  • positive regulation of cell death Source: UniProtKB
  • positive regulation of defense response to virus by host Source: MGI
  • positive regulation of endothelial cell migration Source: UniProtKB
  • positive regulation of execution phase of apoptosis Source: UniProtKB
  • positive regulation of fat cell differentiation Source: UniProtKB
  • positive regulation of gene expression Source: BHF-UCL
  • positive regulation of lipid storage Source: BHF-UCL
  • positive regulation of miRNA catabolic process Source: UniProtKB
  • positive regulation of mRNA catabolic process Source: UniProtKB
  • positive regulation of p38MAPK cascade Source: UniProtKB
  • positive regulation of protein import into nucleus Source: UniProtKB
  • positive regulation of reactive oxygen species metabolic process Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • protein deubiquitination Source: UniProtKB
  • protein oligomerization Source: UniProtKB
  • regulation of gene expression Source: MGI
  • RNA phosphodiester bond hydrolysis Source: UniProtKB
  • RNA phosphodiester bond hydrolysis, endonucleolytic Source: UniProtKB
  • RNA phosphodiester bond hydrolysis, exonucleolytic Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Endonuclease, Hydrolase, Nuclease, Protease, Thiol protease

Keywords - Biological processi

Angiogenesis, Apoptosis, Differentiation, Immunity, Inflammatory response, Neurogenesis, Stress response, Ubl conjugation pathway

Keywords - Ligandi

DNA-binding, Magnesium, Metal-binding, RNA-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional endoribonuclease and deubiquitinase ZC3H12ACurated
Including the following 2 domains:
Endoribonuclease ZC3H12ACurated (EC:3.1.-.-1 Publication)
Deubiquitinase ZC3H12ACurated (EC:3.4.19.121 Publication)
Alternative name(s):
Monocyte chemotactic protein-induced protein 11 Publication
Short name:
MCP-induced protein 11 Publication
Short name:
MCPIP-11 Publication
Regnase-11 Publication
Short name:
Reg11 Publication
Zinc finger CCCH domain-containing protein 12AImported
Gene namesi
Name:Zc3h12a1 PublicationImported
Synonyms:Mcpip1 Publication, Mcpip11 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:2385891. Zc3h12a.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytoplasmic mRNA processing body Source: UniProtKB
  • cytoskeleton Source: UniProtKB
  • extrinsic component of endoplasmic reticulum membrane Source: UniProtKB
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
  • plasma membrane Source: MGI
  • rough endoplasmic reticulum Source: UniProtKB
  • rough endoplasmic reticulum membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Increased expression of ZC3H12A is associated with ischemic heart disease (PubMed:16574901).

Disruption phenotypei

Most mice die within the first 12 weeks (PubMed:21115689). Show severe inflammatory syndromes, including growth retardation, splenomegaly and lymphoadenopathy (PubMed:19322177, PubMed:21115689). show systemic inflammation characterized by T-cell and B-cell activation (PubMed:23706741). Exhibit greatly increased levels of plasma cells and infiltration of plasma cells into the lungs (PubMed:19322177, PubMed:21115689). Show elevated serum immunoglobulin levels and produce anti-nuclear autoantibodies (PubMed:19322177, PubMed:23706741). Mice show increased production of proinflammatory cytokine mRNAs and secreted protein levels, such as IL6, TNF and PTGS2 expression upon lipopolysaccharide (LPS) stimulation in bone marrow macrophages (BBMs) or embryonic fibroblasts, particularly in the early phase of the inflammatory response (PubMed:21115689, PubMed:26000482). Show impaired degradation of IL6 mRNA (PubMed:19322177, PubMed:21115689). Show an increased in both JNK and NF-kappa-B signaling pathway activations upon LPS stimulation (PubMed:21115689). Show an increase in global ubiquitinated protein level in splenocytes (PubMed:21115689). Display a drastic increase in both basal and LPS- or TNF-induced ubiquitination of TRAF2, TRAF3 and TRAF6 in splenocytes (PubMed:21115689). Splenocytes show spontaneously formed aggregation of stress granules (SGs) and were resistant to stress-induced apoptosis (PubMed:21971051). Heterozygous knockout mice display IL-17-dependent enhanced resistance to disseminated Candida albicans infection compared to wild-type mice (PubMed:26320658). Double knockout of ZC3H12A and RC3H1 result in embryonic developmental arrest and death; embryonic fibroblasts from these mice show a higher increase in IL6, TNF and PTGS2 expression upon LPS stimulation, both in early and late phases of the responses, compared to single knockout of either ZC3H12A or RC3H1 (PubMed:26000482). T-cell specific conditional knockout mice die within the first 8 to 17 weeks after birth with the development of severe splenomegaly and the development of a severe autoimmune inflammatory disease (PubMed:23706741). Show massive increase in effector/memory T-cells with elevated production of interferon IFNG, interleukins IL17A and IL4 in response to phorbol 13-acetate 12-myristate (PMA) (PubMed:23706741). Proteolytic cleavage is inhibited in T-cells in response to antigen stimulation (PubMed:23706741). Conditional knockout in myeloid cells show impairment in IL4-induced macrophage M2 polarization (PubMed:25934862).7 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi111 – 1111R → A: Loss of MALT1-dependent cleavage and degradation in T-cells. 1 Publication
Mutagenesisi130 – 1301R → A: Reduces MALT1-dependent cleavage and degradation in T-cells. 1 Publication
Mutagenesisi136 – 1361R → A: Reduces MALT1-dependent cleavage and degradation in T-cells. 1 Publication
Mutagenesisi141 – 1411D → N: Loss of RNase activity. Loss of mRNAs and miRNAs degradation. Loss of deubiquitinase activity and suppression of inhibition on JNK and NF-kappa-B signaling pathway activation. Inhibits induction of angiogenesis and macrophage M2 polarization. Mislocalized in stress granule (SG). Loss of the ability to inhibit SG formation under stress. Does not inhibit binding to IL6 mRNA. 6 Publications
Mutagenesisi157 – 1571C → A: Loss of deubiquitinase activity and suppression of inhibition on JNK and NF-kappa-B signaling pathway activation. Loss of the ability to inhibit stress granule (SG) formation. No loss of RNase activity. 2 Publications
Mutagenesisi158 – 1581R → A: Reduces MALT1-dependent cleavage and degradation in T-cells. 1 Publication
Mutagenesisi214 – 2141R → A: Reduces MALT1-dependent cleavage and degradation in T-cells. 1 Publication
Mutagenesisi225 – 2251D → A: Loss of RNase activity, no loss of deubiquitinase activity and ability to inhibit stress granule (SG) formation under stress; when associated with A-226. 1 Publication
Mutagenesisi226 – 2261D → A: Loss of RNase activity and no loss of deubiquitinase activity; when associated with A-226. 1 Publication
Mutagenesisi278 – 2781D → A: Loss of inhibition on JNK and NF-kappa-B signaling pathway activation; when associated with A-279. 1 Publication
Mutagenesisi279 – 2791D → A: Loss of inhibition on JNK and NF-kappa-B signaling pathway activation; when associated with A-278. 1 Publication
Mutagenesisi306 – 3061C → R: Loss of deubiquitinase activity and suppression of inhibition on JNK and NF-kappa-B signaling pathway activations. No loss of RNase activity. 2 Publications
Mutagenesisi435 – 4351S → A: Reduces its phosphorylation status, does not interact with IKBKB/IKKB and BTRC, inhibits IL6 mRNA instability and IKK-mediated degradation of ZC3H12A; when associated with A-439. 1 Publication
Mutagenesisi439 – 4391S → A: Reduces its phosphorylation status, does not interact with IKBKB/IKKB and BTRC, inhibits IL6 mRNA instability and IKK-mediated degradation of ZC3H12A; when associated with A-435.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 596596Bifunctional endoribonuclease and deubiquitinase ZC3H12APRO_0000341513Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei435 – 4351Phosphoserine1 Publication
Modified residuei439 – 4391Phosphoserine1 Publication

Post-translational modificationi

Proteolytically cleaved between Arg-111 and Arg-214 by MALT1 in activated T-cells; cleavage at Arg-111 is critical for promoting ZC3H12A degradation in response to T-cell receptor (TCR) stimulation, and hence is necessary for prolonging the stability of a set of mRNAs controlling T-cell activation (PubMed:23706741).1 Publication
Phosphorylated by IRAK1; phosphorylation is necessary for subsequent phosphorylation by the I-kappa-B-kinase (IKK) complex. Phosphorylated by I-kappa-B-kinases (IKKs) at Ser-435 and Ser-439 upon lipopolysaccharide (LPS) or IL1B stimulation in macrophages through the MyD88-dependent signaling pathway; these phosphorylations promote rapid ubiquitin proteasome-mediated degradation of ZC3H12A in macrophages and hence allows its target mRNAs, such as IL6, to escape from degradation and accumulate during the inflammatory response (PubMed:22037600).1 Publication
Ubiquitinated; ubiquitination is induced in response to interleukin IL1 receptor stimuli in a IKBKB/IKKB and IRAK1-dependent manner, leading to proteasome-mediated degradation (PubMed:22037600).1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ5D1E7.
MaxQBiQ5D1E7.
PaxDbiQ5D1E7.
PRIDEiQ5D1E7.

PTM databases

iPTMnetiQ5D1E7.
PhosphoSiteiQ5D1E7.

Expressioni

Tissue specificityi

Highly expressed in macrophages (PubMed:18178554). Expressed in lung, lymph nodes, spleen and thymus (PubMed:22037600). Expressed weakly in heart (PubMed:21616078). Expressed weakly in cardiomyocytes (at protein level) (PubMed:16574901). Expressed in spleen, lung, intestine, brown adipose tissue and thymus (PubMed:18682727). Weakly expressed in the heart (PubMed:16574901). Weakly expressed in cardiomyocytes (PubMed:16574901).5 Publications

Inductioni

Up-regulated by the transcription factor KLF4 in a interleukin IL4-dependent manner in macrophage (PubMed:25934862). Up-regulated by lipopolysaccharide (LPS) (at protein level) (PubMed:21616078). Up-regulated by chemokine CCL2 during adipocytes differentiation (PubMed:19666473). Up-regulated in activated T lymphocytes (PubMed:23185455). Up-regulated in response to lipopolysaccharide (LPS) in a MyD88-dependent manner in macrophages (PubMed:18178554, PubMed:18682727, PubMed:19322177). Up-regulated by phorbol 13-acetate 12-myristate (PMA) in primary T lymphocytes (PubMed:23185455). Up-regulated by interleukin IL17 in keratinocytes (PubMed:26320658).8 Publications

Gene expression databases

BgeeiQ5D1E7.
GenevisibleiQ5D1E7. MM.

Interactioni

Subunit structurei

Oligomer (By similarity). Interacts with ZC3H12D (By similarity). Interacts with TNRC6A (By similarity). Interacts with IKBKB/IKKB (By similarity). Interacts with IKBKB/IKKB (By similarity). Interacts with IKBKB/IKKB (PubMed:22037600). Interacts with BTRC; the interaction occurs when ZC3H12A is phosphorylated in a IKBKB/IKKB-dependent manner (PubMed:22037600). Interacts with IRAK1; this interaction increases the interaction between ZC3H12A and IKBKB/IKKB (PubMed:22037600). Interacts with UPF1; this interaction occurs in a mRNA translationally active- and termination-dependent manner and is essential for ZC3H12A-mediated degradation of target mRNAs (PubMed:26000482). Associates with ribosomes (PubMed:26000482). Interacts with ubiquitin (PubMed:21115689).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
IKBKBO149204EBI-5326026,EBI-81266From a different organism.
IRAK1P516173EBI-5326026,EBI-358664From a different organism.

Protein-protein interaction databases

IntActiQ5D1E7. 4 interactions.
STRINGi10090.ENSMUSP00000037172.

Structurei

Secondary structure

1
596
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi47 – 5812Combined sources
Helixi62 – 7211Combined sources
Helixi78 – 8811Combined sources
Beta strandi138 – 1414Combined sources
Helixi142 – 1487Combined sources
Beta strandi149 – 1513Combined sources
Beta strandi154 – 1563Combined sources
Helixi157 – 16913Combined sources
Beta strandi175 – 1806Combined sources
Helixi181 – 1844Combined sources
Beta strandi193 – 1953Combined sources
Helixi198 – 2047Combined sources
Beta strandi208 – 2114Combined sources
Beta strandi213 – 2164Combined sources
Beta strandi219 – 2224Combined sources
Helixi225 – 23612Combined sources
Beta strandi239 – 2413Combined sources
Helixi247 – 2526Combined sources
Helixi254 – 26310Combined sources
Beta strandi268 – 2703Combined sources
Beta strandi273 – 2753Combined sources
Beta strandi283 – 2853Combined sources
Helixi288 – 2914Combined sources
Beta strandi301 – 3044Combined sources
Beta strandi323 – 3253Combined sources
Helixi546 – 55712Combined sources
Turni558 – 5603Combined sources
Helixi563 – 57210Combined sources
Helixi581 – 59212Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2N5JNMR-A45-89[»]
2N5KNMR-A299-327[»]
2N5LNMR-A544-596[»]
5H9VX-ray2.75A/B/C/D134-339[»]
5H9WX-ray2.60A/B134-339[»]
ProteinModelPortaliQ5D1E7.
SMRiQ5D1E7. Positions 134-296.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 6363Deubiquitinase activity1 PublicationAdd
BLAST
Regioni42 – 8746Ubiquitin association domain1 PublicationAdd
BLAST
Regioni112 – 281170RNaseBy similarityAdd
BLAST
Regioni214 – 2207RNA bindingBy similarity
Regioni301 – 454154Necessary for interaction with ZC3H12DBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi476 – 53358Pro-richSequence analysisAdd
BLAST

Domaini

The C3H1-type zinc finger domain and C-terminal region are necessary for pre-miRNA binding (By similarity). The C-terminal region and proline-rich domain are necessary for oligomerization (By similarity).By similarity

Sequence similaritiesi

Belongs to the ZC3H12 family.Curated
Contains 1 C3H1-type zinc finger.By similarity

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri301 – 32424C3H1-typeAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3777. Eukaryota.
ENOG410ZNK1. LUCA.
GeneTreeiENSGT00750000117218.
HOGENOMiHOG000060218.
HOVERGENiHBG108758.
InParanoidiQ5D1E7.
KOiK18668.
OMAiFPPREYW.
OrthoDBiEOG7NSB2F.
PhylomeDBiQ5D1E7.
TreeFamiTF315783.

Family and domain databases

InterProiIPR021869. RNase_Zc3h12_NYN.
[Graphical view]
PfamiPF11977. RNase_Zc3h12a. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q5D1E7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSDPCGTKPV QESNPTMSLW SLEDRHSSQG RPQPDQDPVA KEAPTSELQM
60 70 80 90 100
KVDFFRKLGY SSSEIHSVLQ KLGVQADTNT VLGELVKHGS ATERECQALT
110 120 130 140 150
APSPQPPLVP RGGSTPKPST LEPSLPEEDR EGSDLRPVVI DGSNVAMSHG
160 170 180 190 200
NKEVFSCRGI LLAVNWFLER GHTDITVFVP SWRKEQPRPD VPITDQHILR
210 220 230 240 250
ELEKKKILVF TPSRRVGGKR VVCYDDRFIV KLAFESDGVV VSNDTYRDLQ
260 270 280 290 300
GERQEWKRFI EERLLMYSFV NDKFMPPDDP LGRHGPSLDN FLRKKPLPSE
310 320 330 340 350
HRKQPCPYGK KCTYGIKCRF FHPERPSRPQ RSVADELRAN ALLSPPRTPV
360 370 380 390 400
KDKSSQRPSP ASQSSSVSLE AEPGSLDGKK LGARSSPGPH REGSPQTCAP
410 420 430 440 450
AGRSLPVSGG SFGPTEWLAH TQDSLPYTSQ ECLDSGIGSL ESQMSELWGV
460 470 480 490 500
RGGSPGESGP TRGPYAGYHS YGSKVPAAPS FSPFRPAMGA GHFSVPTDYV
510 520 530 540 550
PPPPTYPSRE YWSEPYPLPP PTPVLQEPQR PSPGAGGGPW GRVGDLAKER
560 570 580 590
AGVYTKLCGV FPPHLVEAVM RRFPQLLDPQ QLAAEILSYK SQHLSE
Length:596
Mass (Da):65,598
Last modified:June 10, 2008 - v2
Checksum:i420E116564B70212
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti280 – 2801P → H in BAE29035 (PubMed:16141072).Curated
Sequence conflicti315 – 3151G → E in AAX14018 (PubMed:16574901).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY920404 mRNA. Translation: AAX14018.1.
AK142501 mRNA. Translation: BAE25089.1.
AK149698 mRNA. Translation: BAE29035.1.
AK152196 mRNA. Translation: BAE31025.1.
AK161150 mRNA. Translation: BAE36216.1.
AK172357 mRNA. Translation: BAE42965.1.
AL626775 Genomic DNA. Translation: CAM20905.1.
BC006817 mRNA. Translation: AAH06817.1.
BC036563 mRNA. Translation: AAH36563.1.
CCDSiCCDS18638.1.
RefSeqiNP_694799.1. NM_153159.2.
UniGeneiMm.402.

Genome annotation databases

EnsembliENSMUST00000036188; ENSMUSP00000037172; ENSMUSG00000042677.
GeneIDi230738.
KEGGimmu:230738.
UCSCiuc008urw.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY920404 mRNA. Translation: AAX14018.1.
AK142501 mRNA. Translation: BAE25089.1.
AK149698 mRNA. Translation: BAE29035.1.
AK152196 mRNA. Translation: BAE31025.1.
AK161150 mRNA. Translation: BAE36216.1.
AK172357 mRNA. Translation: BAE42965.1.
AL626775 Genomic DNA. Translation: CAM20905.1.
BC006817 mRNA. Translation: AAH06817.1.
BC036563 mRNA. Translation: AAH36563.1.
CCDSiCCDS18638.1.
RefSeqiNP_694799.1. NM_153159.2.
UniGeneiMm.402.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2N5JNMR-A45-89[»]
2N5KNMR-A299-327[»]
2N5LNMR-A544-596[»]
5H9VX-ray2.75A/B/C/D134-339[»]
5H9WX-ray2.60A/B134-339[»]
ProteinModelPortaliQ5D1E7.
SMRiQ5D1E7. Positions 134-296.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ5D1E7. 4 interactions.
STRINGi10090.ENSMUSP00000037172.

PTM databases

iPTMnetiQ5D1E7.
PhosphoSiteiQ5D1E7.

Proteomic databases

EPDiQ5D1E7.
MaxQBiQ5D1E7.
PaxDbiQ5D1E7.
PRIDEiQ5D1E7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000036188; ENSMUSP00000037172; ENSMUSG00000042677.
GeneIDi230738.
KEGGimmu:230738.
UCSCiuc008urw.2. mouse.

Organism-specific databases

CTDi80149.
MGIiMGI:2385891. Zc3h12a.

Phylogenomic databases

eggNOGiKOG3777. Eukaryota.
ENOG410ZNK1. LUCA.
GeneTreeiENSGT00750000117218.
HOGENOMiHOG000060218.
HOVERGENiHBG108758.
InParanoidiQ5D1E7.
KOiK18668.
OMAiFPPREYW.
OrthoDBiEOG7NSB2F.
PhylomeDBiQ5D1E7.
TreeFamiTF315783.

Miscellaneous databases

PROiQ5D1E7.
SOURCEiSearch...

Gene expression databases

BgeeiQ5D1E7.
GenevisibleiQ5D1E7. MM.

Family and domain databases

InterProiIPR021869. RNase_Zc3h12_NYN.
[Graphical view]
PfamiPF11977. RNase_Zc3h12a. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Monocyte chemoattractant protein-1 induces a novel transcription factor that causes cardiac myocyte apoptosis and ventricular dysfunction."
    Zhou L., Azfer A., Niu J., Graham S., Choudhury M., Adamski F.M., Younce C., Binkley P.F., Kolattukudy P.E.
    Circ. Res. 98:1177-1185(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, POSSIBLE INVOLVEMENT IN ISCHEMIC HEART DISEASE.
    Strain: FVB/NJImported.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6JImported and NODImported.
    Tissue: Bone marrow macrophageImported, Embryonic stomachImported, SkinImported and SpleenImported.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Czech IIImported and FVB/NImported.
    Tissue: LungImported and Mammary glandImported.
  5. "A novel CCCH-zinc finger protein family regulates proinflammatory activation of macrophages."
    Liang J., Wang J., Azfer A., Song W., Tromp G., Kolattukudy P.E., Fu M.
    J. Biol. Chem. 283:6337-6346(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN INFLAMMATION, TISSUE SPECIFICITY, INDUCTION.
  6. "Genome-wide survey and expression profiling of CCCH-zinc finger family reveals a functional module in macrophage activation."
    Liang J., Song W., Tromp G., Kolattukudy P.E., Fu M.
    PLoS ONE 3:E2880-E2880(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, INDUCTION.
  7. "MCP-1 (monocyte chemotactic protein-1)-induced protein, a recently identified zinc finger protein, induces adipogenesis in 3T3-L1 pre-adipocytes without peroxisome proliferator-activated receptor gamma."
    Younce C.W., Azfer A., Kolattukudy P.E.
    J. Biol. Chem. 284:27620-27628(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS A TRANSCRIPTION FACTOR IN ADIPOGENESIS, INDUCTION.
  8. "Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decay."
    Matsushita K., Takeuchi O., Standley D.M., Kumagai Y., Kawagoe T., Miyake T., Satoh T., Kato H., Tsujimura T., Nakamura H., Akira S.
    Nature 458:1185-1190(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AN ENDORIBONUCLEASE, CATALYTIC ACTIVITY, COFACTOR, RNA-BINDING, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-141 AND CYS-306, INDUCTION, DISRUPTION PHENOTYPE.
  9. "MCP-induced protein 1 deubiquitinates TRAF proteins and negatively regulates JNK and NF-kappaB signaling."
    Liang J., Saad Y., Lei T., Wang J., Qi D., Yang Q., Kolattukudy P.E., Fu M.
    J. Exp. Med. 207:2959-2973(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS A DEUBIQUITINASE IN INFLAMMATION, CATALYTIC ACTIVITY, INTERACTION WITH UBIQUITIN, DOMAIN, DISRUPTION PHENOTYPE, MUTAGENESIS OF ASP-141; CYS-157; ASP-278; ASP-279 AND CYS-306.
  10. "Monocyte chemotactic protein-induced protein 1 (MCPIP1) suppresses stress granule formation and determines apoptosis under stress."
    Qi D., Huang S., Miao R., She Z.G., Quinn T., Chang Y., Liu J., Fan D., Chen Y.E., Fu M.
    J. Biol. Chem. 286:41692-41700(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN STRESS GRANULE FORMATION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, MUTAGENESIS OF ASP-141; CYS-157; ASP-225 AND ASP-226.
  11. "MCP-1-induced protein attenuates endotoxin-induced myocardial dysfunction by suppressing cardiac NF-kappaB activation via inhibition of IkappaB kinase activation."
    Niu J., Wang K., Graham S., Azfer A., Kolattukudy P.E.
    J. Mol. Cell. Cardiol. 51:177-186(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN INFLAMMATION, TISSUE SPECIFICITY, INDUCTION.
  12. "The IkappaB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1."
    Iwasaki H., Takeuchi O., Teraguchi S., Matsushita K., Uehata T., Kuniyoshi K., Satoh T., Saitoh T., Matsushita M., Standley D.M., Akira S.
    Nat. Immunol. 12:1167-1175(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AN ENDORIBONUCLEASE, INTERACTION WITH BTRC; IKBKB AND IRAK1, PHOSPHORYLATION AT SER-435 AND SER-439, TISSUE SPECIFICITY, MUTAGENESIS OF SER-435 AND SER-439.
  13. "MCP-1 induced protein promotes adipogenesis via oxidative stress, endoplasmic reticulum stress and autophagy."
    Younce C., Kolattukudy P.
    Cell. Physiol. Biochem. 30:307-320(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN ADIPOGENESIS.
  14. "MCPIP1 down-regulates IL-2 expression through an ARE-independent pathway."
    Li M., Cao W., Liu H., Zhang W., Liu X., Cai Z., Guo J., Wang X., Hui Z., Zhang H., Wang J., Wang L.
    PLoS ONE 7:E49841-E49841(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AN ENDORIBONUCLEASE, INDUCTION.
  15. Cited for: FUNCTION IN T-CELL ACTIVATION, PROTEOLYTIC CLEAVAGE, DISRUPTION PHENOTYPE, CONDITIONAL KNOCKOUT, MUTAGENESIS OF ARG-111; ARG-130; ARG-136; ASP-141; ARG-158 AND ARG-214.
  16. "Regnase-1 and Roquin regulate a common element in inflammatory mRNAs by spatiotemporally distinct mechanisms."
    Mino T., Murakawa Y., Fukao A., Vandenbon A., Wessels H.H., Ori D., Uehata T., Tartey S., Akira S., Suzuki Y., Vinuesa C.G., Ohler U., Standley D.M., Landthaler M., Fujiwara T., Takeuchi O.
    Cell 161:1058-1073(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AN ENDORIBONUCLEASE IN INFLAMMATION, INTERACTION WITH UPF1, ASSOCIATION WITH RIBOSOMES, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, CONDITIONAL KNOCKOUT, MUTAGENESIS OF ASP-141.
  17. Cited for: DISRUPTION PHENOTYPE, INDUCTION.
  18. "Monocyte chemotactic protein-induced protein 1 and 4 form a complex but act independently in regulation of interleukin-6 mRNA degradation."
    Huang S., Liu S., Fu J.J., Tony Wang T., Yao X., Kumar A., Liu G., Fu M.
    J. Biol. Chem. 290:20782-20792(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AN ENDORIBONUCLEASE.
  19. "Transcription factors STAT6 and KLF4 implement macrophage polarization via the dual catalytic powers of MCPIP."
    Kapoor N., Niu J., Saad Y., Kumar S., Sirakova T., Becerra E., Li X., Kolattukudy P.E.
    J. Immunol. 194:6011-6023(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS A ENDORIBONUCLEASE AND DEUBIQUITINASE IN MACROPHAGE POLARIZATION, DISRUPTION PHENOTYPE, CONDITIONAL KNOCKOUT, INDUCTION, DOMAIN, MUTAGENESIS OF ASP-141.

Entry informationi

Entry nameiZC12A_MOUSE
AccessioniPrimary (citable) accession number: Q5D1E7
Secondary accession number(s): Q3U8J3
, Q3UE76, Q8JZW9, Q922T4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 10, 2008
Last sequence update: June 10, 2008
Last modified: June 8, 2016
This is version 69 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.