Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Bifunctional endoribonuclease and deubiquitinase ZC3H12A

Gene

ZC3H12A

Organism
Homo sapiens (Human)
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: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). Functions as a deubiquitinase that affects the overall ubiquitination of cellular proteins (By similarity). 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 (By similarity). Deubiquitinates also the transcription factor HIF1A, probably leading to its stabilization and nuclear import, thereby positively regulating the expression of proangiogenic HIF1A-targeted genes (PubMed:24048733). Prevents stress granule (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 (By similarity). 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 (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).By similarity9 Publications
(Microbial infection) Exhibits broad antiviral activity by cleaving viral RNAs (PubMed:23355615). Binds to Japanese encephalitis virus (JEV) and dengue virus (DEN) RNAs (PubMed:23355615). Exhibits antiviral activity against HIV-1 in lymphocytes by decreasing the abundance of HIV-1 viral RNA species (PubMed:24191027).2 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).By similarity

Cofactori

Mg2+1 PublicationNote: Mg2+ is required for RNase activity (PubMed:22561375).1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi226 – 2261Magnesium1 Publication

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: UniProtKB
  • ribonuclease activity Source: UniProtKB
  • ribosome binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • RNA stem-loop binding Source: UniProtKB
  • thiol-dependent ubiquitinyl hydrolase activity Source: UniProtKB-EC

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Angiogenesis, Antiviral defense, Apoptosis, Differentiation, Immunity, Inflammatory response, Neurogenesis, Stress response, Transcription, Transcription regulation, 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:3.4.19.12By similarity)
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:
Reg1By similarity
Zinc finger CCCH domain-containing protein 12AImported
Gene namesi
Name:ZC3H12AImported
Synonyms:MCPIP1 Publication, MCPIP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:26259. 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: HPA
  • nucleus Source: UniProtKB
  • plasma membrane Source: HPA
  • 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).

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi141 – 1411D → N: Abolishes RNase activity. 1 Publication
Mutagenesisi141 – 1411D → N: Loss of pre-miRNA RNase activity. Attenuates strongly miRNA silencing activity. Loss of interleukin IL17A and IL6 mRNA instabilities. Reduces angiogenic differentiation. No loss of deubiquitinase activity. Loss of RNase activity on JEV and DEN viral RNAs and antiviral effects. Loss of HIV-1 antiviral activity. Loss of IL1B mRNA instability; when associated with A-226. 7 Publications
Mutagenesisi144 – 1441N → A: No change in RNase activity. 1 Publication
Mutagenesisi157 – 1571C → A: Loss of deubiquitinating activity. Does not inhibit antiviral effects. 1 Publication
Mutagenesisi214 – 2141R → A: Abolishes RNase activity. 1 Publication
Mutagenesisi225 – 2251D → A: Loss of pre-miRNA RNase activity, IL17A mRNA instability and antiviral effects; when associated with A-226. 3 Publications
Mutagenesisi226 – 2261D → A: Loss of pre-miRNA RNase activity, IL17A mRNA instability and antiviral effects; when associated with A-225. Loss of IL1B mRNA instability; when associated with N-141. 4 Publications
Mutagenesisi306 – 3061C → R: Loss of interleukin IL17A mRNA instability. Reduces weakly pre-miRNA RNase activity. Attenuates miRNA silencing activity. Does not inhibits binding to Japanese encephalitis virus (JEV) and dengue virus (DEN) RNAs and weakly attenuates antiviral effects. Loss of HIV-1 antiviral activity. 4 Publications
Mutagenesisi311 – 3111K → G: Inhibits transcriptional activity; when associated with G-312. 1 Publication
Mutagenesisi312 – 3121C → G: Inhibits transcriptional activity; when associated with G-311. 1 Publication
Mutagenesisi317 – 3171K → G: Inhibits transcriptional activity; when associated with G-318. 1 Publication
Mutagenesisi318 – 3181C → G: Inhibits transcriptional activity; when associated with G-317. 1 Publication

Organism-specific databases

PharmGKBiPA142670537.

Polymorphism and mutation databases

BioMutaiZC3H12A.
DMDMi190479827.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 599599Bifunctional endoribonuclease and deubiquitinase ZC3H12APRO_0000341512Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei438 – 4381PhosphoserineBy similarity
Modified residuei442 – 4421PhosphoserineBy similarity

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 (By similarity).By similarity
Phosphorylated by IRAK1; phosphorylation is necessary for subsequent phosphorylation by the I-kappa-B-kinase (IKK) complex. Phosphorylated by I-kappa-B-kinase (IKK) subunits IKBKB/IKKB and CHUK/IKKA at Ser-438 and Ser-442; these phosphorylations promote ubiquitin proteasome-mediated degradation of ZC3H12A and hence facilitates rapid and robust production of IL-6 mRNA in response to toll-like receptor (TLR) or IL-1 receptor stimuli (By similarity).By similarity
(Microbial infection) Rapidly degraded in activated T-cells in response to phorbol 13-acetate 12-myristate (PMA) during HIV-1 viral infection (PubMed:24191027).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 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ5D1E8.
MaxQBiQ5D1E8.
PaxDbiQ5D1E8.
PRIDEiQ5D1E8.

PTM databases

iPTMnetiQ5D1E8.
PhosphoSiteiQ5D1E8.

Expressioni

Tissue specificityi

Expressed in heart, placenta, spleen, kidney, liver and lung (PubMed:19909337). Expressed in leukocytes (PubMed:19909337). Expressed in monocyte (PubMed:16574901).2 Publications

Inductioni

Up-regulated by the transcription factor ELK1 in a interleukin IL1B-dependent manner through activation of the NF-kappa-B and ERK signaling pathways (PubMed:19747262, PubMed:20137095, PubMed:22037600). Up-regulated by chemokine CCL2 in endothelial cells and in peripheral blood monocytes (PubMed:16574901, PubMed:18364357). Up-regulated in activated T lymphocytes (PubMed:23185455). Up-regulated by phorbol 12-myristate 13-acetate (PMA) in primary T lymphocytes (PubMed:19909337, PubMed:23185455). Up-regulated by interleukin IL17 in keratinocytes (PubMed:26320658). Up-regulated by lipopolysaccharide (LPS) (PubMed:19909337). Up-regulated by tumor necrosis factor TNF-alpha and interleukin IL1 in acute monocytic leukemia cell line THP-1 cells (PubMed:18178554, PubMed:19909337). Up-regulated by amyloid precursor protein (APP) (PubMed:19185603).10 Publications
(Microbial infection) Up-regulated in response to Japanese encephalitis virus (JEV) and dengue virus (DEN) infections (PubMed:23355615).1 Publication

Gene expression databases

BgeeiQ5D1E8.
CleanExiHS_ZC3H12A.
ExpressionAtlasiQ5D1E8. baseline and differential.
GenevisibleiQ5D1E8. HS.

Organism-specific databases

HPAiHPA032052.
HPA032053.

Interactioni

Subunit structurei

Oligomer (PubMed:22055188, PubMed:23355615). Interacts with ZC3H12D (PubMed:26134560). Interacts with TNRC6A (PubMed:26134560). Interacts with IKBKB/IKKB (PubMed:22037600). Interacts with IKBKB/IKKB. Interacts with BTRC; the interaction occurs when ZC3H12A is phosphorylated in a IKBKB/IKKB-dependent manner (By similarity). Interacts with IRAK1; this interaction increases the interaction between ZC3H12A and IKBKB/IKKB (By similarity). 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 (By similarity). Associates with ribosomes (By similarity). Interacts with ubiquitin (By similarity).By similarity4 Publications
(Microbial infection) Oligomerization is necessary for antiviral activity (PubMed:23355615).1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
AHSPQ9NZD44EBI-747793,EBI-720250
BTRCQ9Y2973EBI-747793,EBI-307461
IKBKGQ9Y6K92EBI-747793,EBI-81279
IRAK2O431872EBI-747793,EBI-447733
P4HA3Q7Z4N83EBI-747793,EBI-10181968
SMAD3P840222EBI-747793,EBI-347161
USP10Q146945EBI-747793,EBI-2510389

Protein-protein interaction databases

BioGridi123141. 16 interactions.
IntActiQ5D1E8. 14 interactions.
MINTiMINT-6776367.
STRINGi9606.ENSP00000362174.

Structurei

Secondary structure

1
599
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi138 – 1414Combined sources
Helixi142 – 1498Combined sources
Turni150 – 1534Combined sources
Beta strandi154 – 1563Combined sources
Helixi157 – 16913Combined sources
Beta strandi175 – 1806Combined sources
Helixi181 – 1844Combined sources
Beta strandi193 – 1953Combined sources
Helixi197 – 2048Combined sources
Beta strandi208 – 2114Combined sources
Beta strandi213 – 2164Combined sources
Beta strandi219 – 2224Combined sources
Helixi225 – 23511Combined sources
Beta strandi239 – 2413Combined sources
Helixi247 – 2526Combined sources
Helixi254 – 26310Combined sources
Beta strandi268 – 2703Combined sources
Beta strandi273 – 2753Combined sources
Turni280 – 2834Combined sources
Helixi288 – 2914Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3V32X-ray2.00A/B112-296[»]
3V33X-ray2.00A/B112-334[»]
3V34X-ray2.00A/B112-296[»]
ProteinModelPortaliQ5D1E8.
SMRiQ5D1E8. Positions 134-296.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 6363Deubiquitinase activityBy similarityAdd
BLAST
Regioni42 – 8746Ubiquitin association domainBy similarityAdd
BLAST
Regioni112 – 297186RNase1 PublicationAdd
BLAST
Regioni214 – 2207RNA binding1 Publication
Regioni301 – 457157Necessary for interaction with ZC3H12D1 PublicationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi458 – 53679Pro-richSequence analysisAdd
BLAST

Domaini

The C3H1-type zinc finger domain and C-terminal region are necessary for pre-miRNA binding (PubMed:22055188). The C-terminal region and proline-rich domain are necessary for oligomerization (PubMed:22055188).1 Publication
(Microbial infection) The C3H1-type zinc finger domain is necessary for JEV and DEN viral RNA-binding and antiviral activity (PubMed:23355615).1 Publication

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.
InParanoidiQ5D1E8.
KOiK18668.
OMAiFPPREYW.
OrthoDBiEOG7NSB2F.
PhylomeDBiQ5D1E8.
TreeFamiTF315783.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

Q5D1E8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGPCGEKPV LEASPTMSLW EFEDSHSRQG TPRPGQELAA EEASALELQM
60 70 80 90 100
KVDFFRKLGY SSTEIHSVLQ KLGVQADTNT VLGELVKHGT ATERERQTSP
110 120 130 140 150
DPCPQLPLVP RGGGTPKAPN LEPPLPEEEK EGSDLRPVVI DGSNVAMSHG
160 170 180 190 200
NKEVFSCRGI LLAVNWFLER GHTDITVFVP SWRKEQPRPD VPITDQHILR
210 220 230 240 250
ELEKKKILVF TPSRRVGGKR VVCYDDRFIV KLAYESDGIV VSNDTYRDLQ
260 270 280 290 300
GERQEWKRFI EERLLMYSFV NDKFMPPDDP LGRHGPSLDN FLRKKPLTLE
310 320 330 340 350
HRKQPCPYGR KCTYGIKCRF FHPERPSCPQ RSVADELRAN ALLSPPRAPS
360 370 380 390 400
KDKNGRRPSP SSQSSSLLTE SEQCSLDGKK LGAQASPGSR QEGLTQTYAP
410 420 430 440 450
SGRSLAPSGG SGSSFGPTDW LPQTLDSLPY VSQDCLDSGI GSLESQMSEL
460 470 480 490 500
WGVRGGGPGE PGPPRAPYTG YSPYGSELPA TAAFSAFGRA MGAGHFSVPA
510 520 530 540 550
DYPPAPPAFP PREYWSEPYP LPPPTSVLQE PPVQSPGAGR SPWGRAGSLA
560 570 580 590
KEQASVYTKL CGVFPPHLVE AVMGRFPQLL DPQQLAAEIL SYKSQHPSE
Length:599
Mass (Da):65,699
Last modified:February 5, 2008 - v1
Checksum:i9213139FA7DCA443
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti248 – 2481D → G in CAG33645 (Ref. 3) Curated
Sequence conflicti599 – 5991E → D in CAG33645 (Ref. 3) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti240 – 2401V → M.
Corresponds to variant rs16824179 [ dbSNP | Ensembl ].
VAR_052968
Natural varianti547 – 5471G → D.3 Publications
Corresponds to variant rs17849897 [ dbSNP | Ensembl ].
VAR_044082

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY920403 mRNA. Translation: AAX14017.1.
AK026884 mRNA. Translation: BAB15581.1.
CR457364 mRNA. Translation: CAG33645.1.
AL034379, AL449284 Genomic DNA. Translation: CAI20551.1.
AL449284, AL034379 Genomic DNA. Translation: CAH73689.1.
CH471059 Genomic DNA. Translation: EAX07346.1.
CH471059 Genomic DNA. Translation: EAX07347.1.
BC005001 mRNA. Translation: AAH05001.1.
CCDSiCCDS417.1.
RefSeqiNP_079355.2. NM_025079.2.
UniGeneiHs.656294.

Genome annotation databases

EnsembliENST00000373087; ENSP00000362179; ENSG00000163874.
GeneIDi80149.
KEGGihsa:80149.
UCSCiuc001cbb.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY920403 mRNA. Translation: AAX14017.1.
AK026884 mRNA. Translation: BAB15581.1.
CR457364 mRNA. Translation: CAG33645.1.
AL034379, AL449284 Genomic DNA. Translation: CAI20551.1.
AL449284, AL034379 Genomic DNA. Translation: CAH73689.1.
CH471059 Genomic DNA. Translation: EAX07346.1.
CH471059 Genomic DNA. Translation: EAX07347.1.
BC005001 mRNA. Translation: AAH05001.1.
CCDSiCCDS417.1.
RefSeqiNP_079355.2. NM_025079.2.
UniGeneiHs.656294.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3V32X-ray2.00A/B112-296[»]
3V33X-ray2.00A/B112-334[»]
3V34X-ray2.00A/B112-296[»]
ProteinModelPortaliQ5D1E8.
SMRiQ5D1E8. Positions 134-296.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123141. 16 interactions.
IntActiQ5D1E8. 14 interactions.
MINTiMINT-6776367.
STRINGi9606.ENSP00000362174.

PTM databases

iPTMnetiQ5D1E8.
PhosphoSiteiQ5D1E8.

Polymorphism and mutation databases

BioMutaiZC3H12A.
DMDMi190479827.

Proteomic databases

EPDiQ5D1E8.
MaxQBiQ5D1E8.
PaxDbiQ5D1E8.
PRIDEiQ5D1E8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000373087; ENSP00000362179; ENSG00000163874.
GeneIDi80149.
KEGGihsa:80149.
UCSCiuc001cbb.5. human.

Organism-specific databases

CTDi80149.
GeneCardsiZC3H12A.
HGNCiHGNC:26259. ZC3H12A.
HPAiHPA032052.
HPA032053.
MIMi610562. gene.
neXtProtiNX_Q5D1E8.
PharmGKBiPA142670537.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3777. Eukaryota.
ENOG410ZNK1. LUCA.
GeneTreeiENSGT00750000117218.
HOGENOMiHOG000060218.
HOVERGENiHBG108758.
InParanoidiQ5D1E8.
KOiK18668.
OMAiFPPREYW.
OrthoDBiEOG7NSB2F.
PhylomeDBiQ5D1E8.
TreeFamiTF315783.

Miscellaneous databases

ChiTaRSiZC3H12A. human.
GenomeRNAii80149.
PROiQ5D1E8.
SOURCEiSearch...

Gene expression databases

BgeeiQ5D1E8.
CleanExiHS_ZC3H12A.
ExpressionAtlasiQ5D1E8. baseline and differential.
GenevisibleiQ5D1E8. HS.

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], FUNCTION AS A TRANSCRIPTION FACTOR, SUBCELLULAR LOCATION, INDUCTION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-311; CYS-312; LYS-317 AND CYS-318, POSSIBLE INVOLVEMENT IN ISCHEMIC HEART DISEASE.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASP-547.
    Tissue: ArteryImported.
  3. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASP-547.
  4. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "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], VARIANT ASP-547.
    Tissue: KidneyImported.
  7. "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: SUBCELLULAR LOCATION, INDUCTION.
  8. "Monocyte chemotactic protein (MCP)-1 promotes angiogenesis via a novel transcription factor, MCP-1-induced protein (MCPIP)."
    Niu J., Azfer A., Zhelyabovska O., Fatma S., Kolattukudy P.E.
    J. Biol. Chem. 283:14542-14551(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS A TRANSCRIPTION FACTOR, INDUCTION, CHROMATIN BINDING, DNA-BINDING.
  9. "MCP-1 involvement in glial differentiation of neuroprogenitor cells through APP signaling."
    Vrotsos E.G., Kolattukudy P.E., Sugaya K.
    Brain Res. Bull. 79:97-103(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION.
  10. "Regulatory feedback loop between NF-kappaB and MCP-1-induced protein 1 RNase."
    Skalniak L., Mizgalska D., Zarebski A., Wyrzykowska P., Koj A., Jura J.
    FEBS J. 276:5892-5905(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  11. "Interleukin-1-inducible MCPIP protein has structural and functional properties of RNase and participates in degradation of IL-1beta mRNA."
    Mizgalska D., Wegrzyn P., Murzyn K., Kasza A., Koj A., Jura J., Jarzab B., Jura J.
    FEBS J. 276:7386-7399(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AN ENDORIBONUCLEASE, SUBCELLULAR LOCATION, INDUCTION, TISSUE SPECIFICITY, MUTAGENESIS OF ASP-141 AND ASP-226.
  12. "Transcription factors Elk-1 and SRF are engaged in IL1-dependent regulation of ZC3H12A expression."
    Kasza A., Wyrzykowska P., Horwacik I., Tymoszuk P., Mizgalska D., Palmer K., Rokita H., Sharrocks A.D., Jura J.
    BMC Mol. Biol. 11:14-14(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  13. "MCPIP1 ribonuclease antagonizes dicer and terminates microRNA biogenesis through precursor microRNA degradation."
    Suzuki H.I., Arase M., Matsuyama H., Choi Y.L., Ueno T., Mano H., Sugimoto K., Miyazono K.
    Mol. Cell 44:424-436(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AN ENDORIBONUCLEASE, CATALYTIC ACTIVITY, SUBUNIT, RNA-BINDING, SUBCELLULAR LOCATION, DOMAIN, MUTAGENESIS OF ASP-141 AND CYS-306.
  14. "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: INTERACTION WITH IKBKB, INDUCTION.
  15. "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: INDUCTION.
  16. "Antidicer RNase activity of monocyte chemotactic protein-induced protein-1 is critical for inducing angiogenesis."
    Roy A., Zhang M., Saad Y., Kolattukudy P.E.
    Am. J. Physiol. 305:C1021-C1032(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AN ENDORIBONUCLEASE AND AS A DEUBIQUITINASE, MUTAGENESIS OF ASP-141.
  17. "mRNA degradation by the endoribonuclease Regnase-1/ZC3H12a/MCPIP-1."
    Uehata T., Akira S.
    Biochim. Biophys. Acta 1829:708-713(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  18. "MCPIP1 ribonuclease exhibits broad-spectrum antiviral effects through viral RNA binding and degradation."
    Lin R.J., Chien H.L., Lin S.Y., Chang B.L., Yu H.P., Tang W.C., Lin Y.L.
    Nucleic Acids Res. 41:3314-3326(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AN ENDORIBONUCLEASE (MICROBIAL INFECTION), SUBUNIT (MICROBIAL INFECTION), RNA-BINDING, DOMAIN (MICROBIAL INFECTION), INDUCTION (MICROBIAL INFECTION), MUTAGENESIS OF ASP-141; CYS-157; ASP-225; ASP-226 AND CYS-306.
  19. "MCPIP1 restricts HIV infection and is rapidly degraded in activated CD4+ T cells."
    Liu S., Qiu C., Miao R., Zhou J., Lee A., Liu B., Lester S.N., Fu W., Zhu L., Zhang L., Xu J., Fan D., Li K., Fu M., Wang T.
    Proc. Natl. Acad. Sci. U.S.A. 110:19083-19088(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AN ENDORIBONUCLEASE (MICROBIAL INFECTION), DEGRADATION (MICROBIAL INFECTION), MUTAGENESIS OF ASP-141; ASP-225; ASP-226 AND CYS-306.
  20. Cited for: FUNCTION AS AN ENDORIBONUCLEASE IN INFLAMMATION, INDUCTION, MUTAGENESIS OF ASP-141; ASP-225; ASP-226 AND CYS-306.
  21. "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, INTERACTION WITH TNRC6A AND ZC3H12D, SUBCELLULAR LOCATION, DOMAIN, MUTAGENESIS OF ASP-141.
  22. "Structural study of MCPIP1 N-terminal conserved domain reveals a PIN-like RNase."
    Xu J., Peng W., Sun Y., Wang X., Xu Y., Li X., Gao G., Rao Z.
    Nucleic Acids Res. 40:6957-6965(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 112-334, FUNCTION AS AN ENDORIBONUCLEASE, CATALYTIC REGION, COFACTOR, DOMAIN, MUTAGENESIS OF ASP-141; ASN-144 AND ARG-214, MAGNESIUM-BINDING SITE.

Entry informationi

Entry nameiZC12A_HUMAN
AccessioniPrimary (citable) accession number: Q5D1E8
Secondary accession number(s): D3DPT0, Q6I9Z1, Q9H5P1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 10, 2008
Last sequence update: February 5, 2008
Last modified: June 8, 2016
This is version 74 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

Was originally proposed to bind to DNA and act as transcription factor.1 Publication

Keywords - Technical termi

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

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.