ZC12A_MOUSE
ID ZC12A_MOUSE Reviewed; 596 AA.
AC Q5D1E7; Q3U8J3; Q3UE76; Q8JZW9; Q922T4;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 2.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Endoribonuclease ZC3H12A {ECO:0000305};
DE EC=3.1.-.- {ECO:0000269|PubMed:19322177};
DE AltName: Full=Monocyte chemotactic protein-induced protein 1 {ECO:0000303|PubMed:21115689};
DE Short=MCP-induced protein 1 {ECO:0000303|PubMed:16574901};
DE Short=MCPIP-1 {ECO:0000303|PubMed:16574901};
DE AltName: Full=Regnase-1 {ECO:0000303|PubMed:26000482};
DE Short=Reg1 {ECO:0000303|PubMed:23706741};
DE AltName: Full=Zinc finger CCCH domain-containing protein 12A {ECO:0000312|MGI:MGI:2385891};
GN Name=Zc3h12a {ECO:0000303|PubMed:19322177, ECO:0000312|MGI:MGI:2385891};
GN Synonyms=Mcpip {ECO:0000303|PubMed:16574901},
GN Mcpip1 {ECO:0000303|PubMed:19666473};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAX14018.1}
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP POSSIBLE INVOLVEMENT IN ISCHEMIC HEART DISEASE.
RC STRAIN=FVB/NJ {ECO:0000312|EMBL:AAX14018.1};
RX PubMed=16574901; DOI=10.1161/01.res.0000220106.64661.71;
RA Zhou L., Azfer A., Niu J., Graham S., Choudhury M., Adamski F.M.,
RA Younce C., Binkley P.F., Kolattukudy P.E.;
RT "Monocyte chemoattractant protein-1 induces a novel transcription factor
RT that causes cardiac myocyte apoptosis and ventricular dysfunction.";
RL Circ. Res. 98:1177-1185(2006).
RN [2] {ECO:0000312|EMBL:BAE25089.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE25089.1}, and
RC NOD {ECO:0000312|EMBL:BAE42965.1};
RC TISSUE=Bone marrow macrophage {ECO:0000312|EMBL:BAE31025.1},
RC Embryonic stomach {ECO:0000312|EMBL:BAE25089.1},
RC Skin {ECO:0000312|EMBL:BAE36216.1}, and
RC Spleen {ECO:0000312|EMBL:BAE42965.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4] {ECO:0000312|EMBL:AAH36563.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II {ECO:0000312|EMBL:AAH36563.1}, and
RC FVB/N {ECO:0000312|EMBL:AAH06817.1};
RC TISSUE=Lung {ECO:0000312|EMBL:AAH36563.1}, and
RC Mammary gland {ECO:0000312|EMBL:AAH06817.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION IN INFLAMMATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=18178554; DOI=10.1074/jbc.m707861200;
RA Liang J., Wang J., Azfer A., Song W., Tromp G., Kolattukudy P.E., Fu M.;
RT "A novel CCCH-zinc finger protein family regulates proinflammatory
RT activation of macrophages.";
RL J. Biol. Chem. 283:6337-6346(2008).
RN [6]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=18682727; DOI=10.1371/journal.pone.0002880;
RA Liang J., Song W., Tromp G., Kolattukudy P.E., Fu M.;
RT "Genome-wide survey and expression profiling of CCCH-zinc finger family
RT reveals a functional module in macrophage activation.";
RL PLoS ONE 3:E2880-E2880(2008).
RN [7]
RP FUNCTION AS A TRANSCRIPTION FACTOR IN ADIPOGENESIS, AND INDUCTION.
RX PubMed=19666473; DOI=10.1074/jbc.m109.025320;
RA Younce C.W., Azfer A., Kolattukudy P.E.;
RT "MCP-1 (monocyte chemotactic protein-1)-induced protein, a recently
RT identified zinc finger protein, induces adipogenesis in 3T3-L1 pre-
RT adipocytes without peroxisome proliferator-activated receptor gamma.";
RL J. Biol. Chem. 284:27620-27628(2009).
RN [8]
RP FUNCTION AS AN ENDORIBONUCLEASE, CATALYTIC ACTIVITY, COFACTOR, RNA-BINDING,
RP SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-141 AND CYS-306, INDUCTION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=19322177; DOI=10.1038/nature07924;
RA Matsushita K., Takeuchi O., Standley D.M., Kumagai Y., Kawagoe T.,
RA Miyake T., Satoh T., Kato H., Tsujimura T., Nakamura H., Akira S.;
RT "Zc3h12a is an RNase essential for controlling immune responses by
RT regulating mRNA decay.";
RL Nature 458:1185-1190(2009).
RN [9]
RP FUNCTION IN INFLAMMATION, CATALYTIC ACTIVITY, INTERACTION WITH UBIQUITIN,
RP DOMAIN, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ASP-141; CYS-157; ASP-278;
RP ASP-279 AND CYS-306.
RX PubMed=21115689; DOI=10.1084/jem.20092641;
RA Liang J., Saad Y., Lei T., Wang J., Qi D., Yang Q., Kolattukudy P.E.,
RA Fu M.;
RT "MCP-induced protein 1 deubiquitinates TRAF proteins and negatively
RT regulates JNK and NF-kappaB signaling.";
RL J. Exp. Med. 207:2959-2973(2010).
RN [10]
RP FUNCTION IN STRESS GRANULE FORMATION, SUBCELLULAR LOCATION, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF ASP-141; CYS-157; ASP-225 AND ASP-226.
RX PubMed=21971051; DOI=10.1074/jbc.m111.276006;
RA Qi D., Huang S., Miao R., She Z.G., Quinn T., Chang Y., Liu J., Fan D.,
RA Chen Y.E., Fu M.;
RT "Monocyte chemotactic protein-induced protein 1 (MCPIP1) suppresses stress
RT granule formation and determines apoptosis under stress.";
RL J. Biol. Chem. 286:41692-41700(2011).
RN [11]
RP FUNCTION IN INFLAMMATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=21616078; DOI=10.1016/j.yjmcc.2011.04.018;
RA Niu J., Wang K., Graham S., Azfer A., Kolattukudy P.E.;
RT "MCP-1-induced protein attenuates endotoxin-induced myocardial dysfunction
RT by suppressing cardiac NF-kappaB activation via inhibition of IkappaB
RT kinase activation.";
RL J. Mol. Cell. Cardiol. 51:177-186(2011).
RN [12]
RP FUNCTION AS AN ENDORIBONUCLEASE, INTERACTION WITH BTRC; IKBKB AND IRAK1,
RP PHOSPHORYLATION AT SER-435 AND SER-439, TISSUE SPECIFICITY, AND MUTAGENESIS
RP OF SER-435 AND SER-439.
RX PubMed=22037600; DOI=10.1038/ni.2137;
RA Iwasaki H., Takeuchi O., Teraguchi S., Matsushita K., Uehata T.,
RA Kuniyoshi K., Satoh T., Saitoh T., Matsushita M., Standley D.M., Akira S.;
RT "The IkappaB kinase complex regulates the stability of cytokine-encoding
RT mRNA induced by TLR-IL-1R by controlling degradation of regnase-1.";
RL Nat. Immunol. 12:1167-1175(2011).
RN [13]
RP FUNCTION IN ADIPOGENESIS.
RX PubMed=22739135; DOI=10.1159/000339066;
RA Younce C., Kolattukudy P.;
RT "MCP-1 induced protein promotes adipogenesis via oxidative stress,
RT endoplasmic reticulum stress and autophagy.";
RL Cell. Physiol. Biochem. 30:307-320(2012).
RN [14]
RP FUNCTION AS AN ENDORIBONUCLEASE, AND INDUCTION.
RX PubMed=23185455; DOI=10.1371/journal.pone.0049841;
RA Li M., Cao W., Liu H., Zhang W., Liu X., Cai Z., Guo J., Wang X., Hui Z.,
RA Zhang H., Wang J., Wang L.;
RT "MCPIP1 down-regulates IL-2 expression through an ARE-independent
RT pathway.";
RL PLoS ONE 7:E49841-E49841(2012).
RN [15]
RP FUNCTION IN T-CELL ACTIVATION, PROTEOLYTIC CLEAVAGE, DISRUPTION PHENOTYPE,
RP CONDITIONAL KNOCKOUT, AND MUTAGENESIS OF ARG-111; ARG-130; ARG-136;
RP ASP-141; ARG-158 AND ARG-214.
RX PubMed=23706741; DOI=10.1016/j.cell.2013.04.034;
RA Uehata T., Iwasaki H., Vandenbon A., Matsushita K., Hernandez-Cuellar E.,
RA Kuniyoshi K., Satoh T., Mino T., Suzuki Y., Standley D.M., Tsujimura T.,
RA Rakugi H., Isaka Y., Takeuchi O., Akira S.;
RT "Malt1-induced cleavage of regnase-1 in CD4(+) helper T cells regulates
RT immune activation.";
RL Cell 153:1036-1049(2013).
RN [16]
RP PROTEOLYTIC CLEAVAGE, MUTAGENESIS OF ASP-141; CYS-157 AND 225-ASP-ASP-226,
RP AND FUNCTION.
RX PubMed=25282160; DOI=10.1038/ni.3008;
RA Jeltsch K.M., Hu D., Brenner S., Zoeller J., Heinz G.A., Nagel D.,
RA Vogel K.U., Rehage N., Warth S.C., Edelmann S.L., Gloury R., Martin N.,
RA Lohs C., Lech M., Stehklein J.E., Geerlof A., Kremmer E., Weber A.,
RA Anders H.J., Schmitz I., Schmidt-Supprian M., Fu M., Holtmann H.,
RA Krappmann D., Ruland J., Kallies A., Heikenwalder M., Heissmeyer V.;
RT "Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their
RT cooperatively repressed targets to promote T(H)17 differentiation.";
RL Nat. Immunol. 15:1079-1089(2014).
RN [17]
RP FUNCTION AS AN ENDORIBONUCLEASE IN INFLAMMATION, INTERACTION WITH UPF1,
RP ASSOCIATION WITH RIBOSOMES, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE,
RP CONDITIONAL KNOCKOUT, AND MUTAGENESIS OF ASP-141.
RX PubMed=26000482; DOI=10.1016/j.cell.2015.04.029;
RA Mino T., Murakawa Y., Fukao A., Vandenbon A., Wessels H.H., Ori D.,
RA Uehata T., Tartey S., Akira S., Suzuki Y., Vinuesa C.G., Ohler U.,
RA Standley D.M., Landthaler M., Fujiwara T., Takeuchi O.;
RT "Regnase-1 and Roquin regulate a common element in inflammatory mRNAs by
RT spatiotemporally distinct mechanisms.";
RL Cell 161:1058-1073(2015).
RN [18]
RP DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=26320658; DOI=10.1016/j.immuni.2015.07.021;
RA Garg A.V., Amatya N., Chen K., Cruz J.A., Grover P., Whibley N.,
RA Conti H.R., Hernandez Mir G., Sirakova T., Childs E.C., Smithgall T.E.,
RA Biswas P.S., Kolls J.K., McGeachy M.J., Kolattukudy P.E., Gaffen S.L.;
RT "MCPIP1 endoribonuclease activity negatively regulates interleukin-17-
RT mediated signaling and inflammation.";
RL Immunity 43:475-487(2015).
RN [19]
RP FUNCTION AS AN ENDORIBONUCLEASE.
RX PubMed=26134560; DOI=10.1074/jbc.m114.635870;
RA Huang S., Liu S., Fu J.J., Tony Wang T., Yao X., Kumar A., Liu G., Fu M.;
RT "Monocyte chemotactic protein-induced protein 1 and 4 form a complex but
RT act independently in regulation of interleukin-6 mRNA degradation.";
RL J. Biol. Chem. 290:20782-20792(2015).
RN [20]
RP FUNCTION AS A ENDORIBONUCLEASE IN MACROPHAGE POLARIZATION, DISRUPTION
RP PHENOTYPE, CONDITIONAL KNOCKOUT, INDUCTION, DOMAIN, AND MUTAGENESIS OF
RP ASP-141.
RX PubMed=25934862; DOI=10.4049/jimmunol.1402797;
RA Kapoor N., Niu J., Saad Y., Kumar S., Sirakova T., Becerra E., Li X.,
RA Kolattukudy P.E.;
RT "Transcription factors STAT6 and KLF4 implement macrophage polarization via
RT the dual catalytic powers of MCPIP.";
RL J. Immunol. 194:6011-6023(2015).
RN [21]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=29244194; DOI=10.1002/eji.201747109;
RA Hanieh H., Masuda K., Metwally H., Chalise J.P., Mohamed M., Nyati K.K.,
RA Standley D.M., Li S., Higa M., Zaman M.M., Kishimoto T.;
RT "Arid5a stabilizes OX40 mRNA in murine CD4+ T cells by recognizing a stem-
RT loop structure in its 3'UTR.";
RL Eur. J. Immunol. 48:593-604(2018).
CC -!- FUNCTION: Endoribonuclease involved in various biological functions
CC such as cellular inflammatory response and immune homeostasis, glial
CC differentiation of neuroprogenitor cells, cell death of cardiomyocytes,
CC adipogenesis and angiogenesis. Functions as an endoribonuclease
CC involved in mRNA decay (PubMed:26000482). Modulates the inflammatory
CC response by promoting the degradation of a set of translationally
CC active cytokine-induced inflammation-related mRNAs, such as IL6 and
CC IL12B, during the early phase of inflammation (PubMed:19322177,
CC PubMed:21115689, PubMed:23185455, PubMed:26000482). Prevents aberrant
CC T-cell-mediated immune reaction by degradation of multiple mRNAs
CC controlling T-cell activation, such as those encoding cytokines (IL6
CC and IL2), cell surface receptors (ICOS, TNFRSF4 and TNFR2) and
CC transcription factor (REL) (PubMed:23706741, PubMed:26000482,
CC PubMed:19322177, PubMed:21115689, PubMed:23185455). Inhibits
CC cooperatively with ZC3H12A the differentiation of helper T cells Th17
CC in lungs. They repress target mRNA encoding the Th17 cell-promoting
CC factors IL6, ICOS, REL, IRF4, NFKBID and NFKBIZ. The cooperation
CC requires RNA-binding by RC3H1 and the nuclease activity of ZC3H12A
CC (PubMed:25282160). Together with RC3H1, destabilizes TNFRSF4/OX40 mRNA
CC by binding to the conserved stem loop structure in its 3'UTR
CC (PubMed:29244194). Self regulates by destabilizing its own mRNA
CC (PubMed:22037600). Cleaves mRNA harboring a stem-loop (SL), often
CC located in their 3'-UTRs, during the early phase of inflammation in a
CC helicase UPF1-dependent manner (PubMed:19322177, PubMed:23185455,
CC PubMed:23706741, PubMed:26000482, PubMed:26134560). Plays a role in the
CC inhibition of microRNAs (miRNAs) biogenesis (By similarity). Cleaves
CC the terminal loop of a set of precursor miRNAs (pre-miRNAs) important
CC for the regulation of the inflammatory response leading to their
CC degradation, and thus preventing the biosynthesis of mature miRNAs (By
CC similarity). Also plays a role in promoting angiogenesis in response to
CC inflammatory cytokines by inhibiting the production of antiangiogenic
CC microRNAs via its anti-dicer RNase activity (By similarity). Affects
CC the overall ubiquitination of cellular proteins (PubMed:21115689).
CC Positively regulates deubiquitinase activity promoting the cleavage at
CC 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains on TNF receptor-
CC associated factors (TRAFs), preventing JNK and NF-kappa-B signaling
CC pathway activation, and hence negatively regulating macrophage-mediated
CC inflammatory response and immune homeostasis (PubMed:21115689). Induces
CC also deubiquitination of the transcription factor HIF1A, probably
CC leading to its stabilization and nuclear import, thereby positively
CC regulating the expression of proangiogenic HIF1A-targeted genes.
CC Involved in a TANK-dependent negative feedback response to attenuate
CC NF-kappaB activation through the deubiquitination of IKBKG or TRAF6 in
CC response to interleukin-1-beta (IL1B) stimulation or upon DNA damage
CC (By similarity). Prevents stress granules (SGs) formation and promotes
CC macrophage apoptosis under stress conditions, including arsenite-
CC induced oxidative stress, heat shock, and energy deprivation
CC (PubMed:21971051). Plays a role in the regulation of macrophage
CC polarization; promotes IL4-induced polarization of macrophages M1 into
CC anti-inflammatory M2 state (PubMed:25934862). May also act as a
CC transcription factor that regulates the expression of multiple genes
CC involved in inflammatory response, angiogenesis, adipogenesis and
CC apoptosis (PubMed:18178554, PubMed:19666473, PubMed:22739135).
CC Functions as a positive regulator of glial differentiation of
CC neuroprogenitor cells through an amyloid precursor protein (APP)-
CC dependent signaling pathway (By similarity). Attenuates septic
CC myocardial contractile dysfunction in response to lipopolysaccharide
CC (LPS) by reducing I-kappa-B-kinase (IKK)-mediated NF-kappa-B
CC activation, and hence myocardial pro-inflammatory cytokine production
CC (PubMed:21616078). {ECO:0000250|UniProtKB:Q5D1E8,
CC ECO:0000269|PubMed:18178554, ECO:0000269|PubMed:19322177,
CC ECO:0000269|PubMed:19666473, ECO:0000269|PubMed:21115689,
CC ECO:0000269|PubMed:21616078, ECO:0000269|PubMed:21971051,
CC ECO:0000269|PubMed:22037600, ECO:0000269|PubMed:22739135,
CC ECO:0000269|PubMed:23185455, ECO:0000269|PubMed:23706741,
CC ECO:0000269|PubMed:25282160, ECO:0000269|PubMed:25934862,
CC ECO:0000269|PubMed:26000482, ECO:0000269|PubMed:26134560,
CC ECO:0000269|PubMed:29244194}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:19322177};
CC Note=Mg(2+) is required for RNase activity (PubMed:19322177).
CC {ECO:0000269|PubMed:19322177};
CC -!- SUBUNIT: Oligomer (By similarity). Found in a deubiquitination complex
CC with TANK, USP10 and ZC3H12A; this complex inhibits genotoxic
CC stress- or interleukin-1-beta-mediated NF-kappaB activation by
CC promoting IKBKG or TRAF6 deubiquitination. Interacts with IKBKG; this
CC interaction increases in response to DNA damage. Interacts with TANK;
CC this interaction increases in response to DNA damage and serves as a
CC bridge to anchor both TANK and USP10 into a deubiquitinating complex.
CC Interacts with TRAF6; this interaction increases in response to DNA
CC damage and is stimulated by TANK. Interacts with USP10; this
CC interaction increases in response to DNA damage and serves as a bridge
CC to anchor both TANK and USP10 into a deubiquitinating complex.
CC Interacts with ZC3H12D. Interacts with TNRC6A. Interacts with
CC IKBKB/IKKB. Interacts with IKBKB/IKKB (By similarity). Interacts with
CC IKBKB/IKKB (PubMed:22037600). Interacts with BTRC; the interaction
CC occurs when ZC3H12A is phosphorylated in a IKBKB/IKKB-dependent manner
CC (PubMed:22037600). Interacts with IRAK1; this interaction increases the
CC interaction between ZC3H12A and IKBKB/IKKB (PubMed:22037600). Interacts
CC with UPF1; this interaction occurs in a mRNA translationally
CC active- and termination-dependent manner and is essential for ZC3H12A-
CC mediated degradation of target mRNAs (PubMed:26000482). Associates with
CC ribosomes (PubMed:26000482). Interacts with ubiquitin
CC (PubMed:21115689). {ECO:0000250|UniProtKB:Q5D1E8,
CC ECO:0000269|PubMed:21115689, ECO:0000269|PubMed:22037600,
CC ECO:0000269|PubMed:26000482}.
CC -!- INTERACTION:
CC Q5D1E7; O14920: IKBKB; Xeno; NbExp=4; IntAct=EBI-5326026, EBI-81266;
CC Q5D1E7; P51617: IRAK1; Xeno; NbExp=3; IntAct=EBI-5326026, EBI-358664;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16574901,
CC ECO:0000269|PubMed:19322177}. Cytoplasm {ECO:0000269|PubMed:19322177,
CC ECO:0000269|PubMed:21971051, ECO:0000269|PubMed:26000482}. Rough
CC endoplasmic reticulum membrane {ECO:0000269|PubMed:26000482};
CC Peripheral membrane protein {ECO:0000269|PubMed:26000482}; Cytoplasmic
CC side {ECO:0000269|PubMed:26000482}. Cytoplasmic granule
CC {ECO:0000269|PubMed:21971051}. Cytoplasm, P-body
CC {ECO:0000250|UniProtKB:Q5D1E8}. Note=Predominantly localized in the
CC cytoplasm (PubMed:19322177). Colocalizes with GW182 on many granule-
CC like structures, probably corresponding to cytoplasmic GW bodies
CC (GWBs), also called processing bodies (P bodies) (PubMed:21971051).
CC Colocalizes with calnexin on the surface of the rough endoplasmic
CC reticulum (RER) membrane and with translationally active polysomes
CC (PubMed:26000482). Colocalizes with ZC3H12D in cytoplasmic mRNA
CC processing P-body, also known as GW bodies (GWBs) (By similarity).
CC {ECO:0000250|UniProtKB:Q5D1E8, ECO:0000269|PubMed:19322177,
CC ECO:0000269|PubMed:21971051, ECO:0000269|PubMed:26000482}.
CC -!- TISSUE SPECIFICITY: Expressed in CD4(+) helper T-cells (at protein
CC level) (PubMed:29244194). Highly expressed in macrophages
CC (PubMed:18178554). Expressed in lung, lymph nodes, spleen and thymus
CC (PubMed:22037600). Expressed weakly in heart (PubMed:21616078).
CC Expressed weakly in cardiomyocytes (at protein level)
CC (PubMed:16574901). Expressed in spleen, lung, intestine, brown adipose
CC tissue and thymus (PubMed:18682727). Weakly expressed in the heart
CC (PubMed:16574901). Weakly expressed in cardiomyocytes
CC (PubMed:16574901). {ECO:0000269|PubMed:16574901,
CC ECO:0000269|PubMed:18178554, ECO:0000269|PubMed:18682727,
CC ECO:0000269|PubMed:21616078, ECO:0000269|PubMed:22037600,
CC ECO:0000269|PubMed:29244194}.
CC -!- INDUCTION: Up-regulated by the transcription factor KLF4 in a
CC interleukin IL4-dependent manner in macrophage (PubMed:25934862). Up-
CC regulated by lipopolysaccharide (LPS) (at protein level)
CC (PubMed:21616078). Up-regulated by chemokine CCL2 during adipocytes
CC differentiation (PubMed:19666473). Up-regulated in activated T
CC lymphocytes (PubMed:23185455). Up-regulated in response to
CC lipopolysaccharide (LPS) in a MyD88-dependent manner in macrophages
CC (PubMed:18178554, PubMed:18682727, PubMed:19322177). Up-regulated by
CC phorbol 13-acetate 12-myristate (PMA) in primary T lymphocytes
CC (PubMed:23185455). Up-regulated by interleukin IL17 in keratinocytes
CC (PubMed:26320658). {ECO:0000269|PubMed:18178554,
CC ECO:0000269|PubMed:18682727, ECO:0000269|PubMed:19322177,
CC ECO:0000269|PubMed:19666473, ECO:0000269|PubMed:21616078,
CC ECO:0000269|PubMed:23185455, ECO:0000269|PubMed:25934862,
CC ECO:0000269|PubMed:26320658}.
CC -!- DOMAIN: The C3H1-type zinc finger domain and C-terminal region are
CC necessary for pre-miRNA binding (By similarity). The C-terminal region
CC and proline-rich domain are necessary for oligomerization (By
CC similarity). {ECO:0000250|UniProtKB:Q5D1E8}.
CC -!- PTM: Proteolytically cleaved between Arg-111 and Arg-214 by MALT1 in
CC activated T-cells; cleavage at Arg-111 is critical for promoting
CC ZC3H12A degradation in response to T-cell receptor (TCR) stimulation,
CC and hence is necessary for prolonging the stability of a set of mRNAs
CC controlling T-cell activation and Th17 cell differentiation.
CC {ECO:0000269|PubMed:23706741, ECO:0000269|PubMed:25282160}.
CC -!- PTM: Phosphorylated by IRAK1; phosphorylation is necessary for
CC subsequent phosphorylation by the I-kappa-B-kinase (IKK) complex.
CC Phosphorylated by I-kappa-B-kinases (IKKs) at Ser-435 and Ser-439 upon
CC lipopolysaccharide (LPS) or IL1B stimulation in macrophages through the
CC MyD88-dependent signaling pathway; these phosphorylations promote rapid
CC ubiquitin proteasome-mediated degradation of ZC3H12A in macrophages and
CC hence allows its target mRNAs, such as IL6, to escape from degradation
CC and accumulate during the inflammatory response (PubMed:22037600).
CC {ECO:0000269|PubMed:22037600}.
CC -!- PTM: Ubiquitinated; ubiquitination is induced in response to
CC interleukin IL1 receptor stimuli in a IKBKB/IKKB and IRAK1-dependent
CC manner, leading to proteasome-mediated degradation (PubMed:22037600).
CC {ECO:0000269|PubMed:22037600}.
CC -!- DISEASE: Note=Increased expression of ZC3H12A is associated with
CC ischemic heart disease (PubMed:16574901).
CC {ECO:0000269|PubMed:16574901}.
CC -!- DISRUPTION PHENOTYPE: Most mice die within the first 12 weeks
CC (PubMed:21115689). Show severe inflammatory syndromes, including growth
CC retardation, splenomegaly and lymphoadenopathy (PubMed:19322177,
CC PubMed:21115689). show systemic inflammation characterized by T-cell
CC and B-cell activation (PubMed:23706741). Exhibit greatly increased
CC levels of plasma cells and infiltration of plasma cells into the lungs
CC (PubMed:19322177, PubMed:21115689). Show elevated serum immunoglobulin
CC levels and produce anti-nuclear autoantibodies (PubMed:19322177,
CC PubMed:23706741). Mice show increased production of pro-inflammatory
CC cytokine mRNAs and secreted protein levels, such as IL6, TNF and PTGS2
CC expression upon lipopolysaccharide (LPS) stimulation in bone marrow
CC macrophages (BBMs) or embryonic fibroblasts, particularly in the early
CC phase of the inflammatory response (PubMed:21115689, PubMed:26000482).
CC Show impaired degradation of IL6 mRNA (PubMed:19322177,
CC PubMed:21115689). Show an increased in both JNK and NF-kappa-B
CC signaling pathway activations upon LPS stimulation (PubMed:21115689).
CC Show an increase in global ubiquitinated protein level in splenocytes
CC (PubMed:21115689). Display a drastic increase in both basal and LPS- or
CC TNF-induced ubiquitination of TRAF2, TRAF3 and TRAF6 in splenocytes
CC (PubMed:21115689). Splenocytes show spontaneously formed aggregation of
CC stress granules (SGs) and were resistant to stress-induced apoptosis
CC (PubMed:21971051). Heterozygous knockout mice display IL-17-dependent
CC enhanced resistance to disseminated Candida albicans infection compared
CC to wild-type mice (PubMed:26320658). Double knockout of ZC3H12A and
CC RC3H1 result in embryonic developmental arrest and death; embryonic
CC fibroblasts from these mice show a higher increase in IL6, TNF and
CC PTGS2 expression upon LPS stimulation, both in early and late phases of
CC the responses, compared to single knockout of either ZC3H12A or RC3H1
CC (PubMed:26000482). T-cell specific conditional knockout mice die within
CC the first 8 to 17 weeks after birth with the development of severe
CC splenomegaly and the development of a severe autoimmune inflammatory
CC disease (PubMed:23706741). Show massive increase in effector/memory T-
CC cells with elevated production of interferon IFNG, interleukins IL17A
CC and IL4 in response to phorbol 13-acetate 12-myristate (PMA)
CC (PubMed:23706741). Proteolytic cleavage is inhibited in T-cells in
CC response to antigen stimulation (PubMed:23706741). Conditional knockout
CC in myeloid cells show impairment in IL4-induced macrophage M2
CC polarization (PubMed:25934862). {ECO:0000269|PubMed:19322177,
CC ECO:0000269|PubMed:21115689, ECO:0000269|PubMed:21971051,
CC ECO:0000269|PubMed:23706741, ECO:0000269|PubMed:25934862,
CC ECO:0000269|PubMed:26000482, ECO:0000269|PubMed:26320658}.
CC -!- SIMILARITY: Belongs to the ZC3H12 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; AY920404; AAX14018.1; -; mRNA.
DR EMBL; AK142501; BAE25089.1; -; mRNA.
DR EMBL; AK149698; BAE29035.1; -; mRNA.
DR EMBL; AK152196; BAE31025.1; -; mRNA.
DR EMBL; AK161150; BAE36216.1; -; mRNA.
DR EMBL; AK172357; BAE42965.1; -; mRNA.
DR EMBL; AL626775; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006817; AAH06817.1; -; mRNA.
DR EMBL; BC036563; AAH36563.1; -; mRNA.
DR CCDS; CCDS18638.1; -.
DR RefSeq; NP_694799.1; NM_153159.2.
DR PDB; 2N5J; NMR; -; A=45-89.
DR PDB; 2N5K; NMR; -; A=299-327.
DR PDB; 2N5L; NMR; -; A=544-596.
DR PDB; 5H9V; X-ray; 2.75 A; A/B/C/D=134-339.
DR PDB; 5H9W; X-ray; 2.60 A; A/B=134-339.
DR PDBsum; 2N5J; -.
DR PDBsum; 2N5K; -.
DR PDBsum; 2N5L; -.
DR PDBsum; 5H9V; -.
DR PDBsum; 5H9W; -.
DR AlphaFoldDB; Q5D1E7; -.
DR SMR; Q5D1E7; -.
DR BioGRID; 231011; 2.
DR IntAct; Q5D1E7; 4.
DR MINT; Q5D1E7; -.
DR STRING; 10090.ENSMUSP00000037172; -.
DR iPTMnet; Q5D1E7; -.
DR PhosphoSitePlus; Q5D1E7; -.
DR EPD; Q5D1E7; -.
DR jPOST; Q5D1E7; -.
DR MaxQB; Q5D1E7; -.
DR PaxDb; Q5D1E7; -.
DR PRIDE; Q5D1E7; -.
DR ProteomicsDB; 302041; -.
DR Antibodypedia; 31721; 207 antibodies from 34 providers.
DR Ensembl; ENSMUST00000036188; ENSMUSP00000037172; ENSMUSG00000042677.
DR GeneID; 230738; -.
DR KEGG; mmu:230738; -.
DR UCSC; uc008urw.2; mouse.
DR CTD; 80149; -.
DR MGI; MGI:2385891; Zc3h12a.
DR VEuPathDB; HostDB:ENSMUSG00000042677; -.
DR eggNOG; KOG3777; Eukaryota.
DR GeneTree; ENSGT00940000155107; -.
DR HOGENOM; CLU_013020_2_1_1; -.
DR InParanoid; Q5D1E7; -.
DR OMA; CGIFHPH; -.
DR OrthoDB; 771251at2759; -.
DR PhylomeDB; Q5D1E7; -.
DR TreeFam; TF315783; -.
DR BioGRID-ORCS; 230738; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Zc3h12a; mouse.
DR PRO; PR:Q5D1E7; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q5D1E7; protein.
DR Bgee; ENSMUSG00000042677; Expressed in granulocyte and 84 other tissues.
DR Genevisible; Q5D1E7; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; ISO:MGI.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0042406; C:extrinsic component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0030867; C:rough endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0004521; F:endoribonuclease activity; IDA:UniProtKB.
DR GO; GO:0004532; F:exoribonuclease activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035198; F:miRNA binding; ISS:UniProtKB.
DR GO; GO:0035925; F:mRNA 3'-UTR AU-rich region binding; IDA:UniProtKB.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; IDA:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; ISO:MGI.
DR GO; GO:0004518; F:nuclease activity; IMP:UniProtKB.
DR GO; GO:0004540; F:ribonuclease activity; ISO:MGI.
DR GO; GO:0043022; F:ribosome binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; ISO:MGI.
DR GO; GO:0035613; F:RNA stem-loop binding; IDA:UniProtKB.
DR GO; GO:0061158; P:3'-UTR-mediated mRNA destabilization; IDA:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:1990869; P:cellular response to chemokine; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0042149; P:cellular response to glucose starvation; IDA:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; IDA:UniProtKB.
DR GO; GO:1904637; P:cellular response to ionomycin; IDA:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:UniProtKB.
DR GO; GO:1903936; P:cellular response to sodium arsenite; IDA:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
DR GO; GO:0098586; P:cellular response to virus; ISO:MGI.
DR GO; GO:0002757; P:immune response-activating signal transduction; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0010587; P:miRNA catabolic process; ISS:UniProtKB.
DR GO; GO:0044828; P:negative regulation by host of viral genome replication; ISO:MGI.
DR GO; GO:0055118; P:negative regulation of cardiac muscle contraction; IDA:UniProtKB.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; IDA:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IDA:UniProtKB.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IDA:UniProtKB.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IDA:UniProtKB.
DR GO; GO:1903799; P:negative regulation of miRNA maturation; ISS:UniProtKB.
DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; IDA:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:BHF-UCL.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IDA:UniProtKB.
DR GO; GO:2000320; P:negative regulation of T-helper 17 cell differentiation; IMP:UniProtKB.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0000294; P:nuclear-transcribed mRNA catabolic process, endonucleolytic cleavage-dependent decay; IDA:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:BHF-UCL.
DR GO; GO:0010942; P:positive regulation of cell death; ISS:UniProtKB.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; ISO:MGI.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISS:UniProtKB.
DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; IDA:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:BHF-UCL.
DR GO; GO:0010884; P:positive regulation of lipid storage; IMP:BHF-UCL.
DR GO; GO:2000627; P:positive regulation of miRNA catabolic process; ISO:MGI.
DR GO; GO:0061014; P:positive regulation of mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISS:UniProtKB.
DR GO; GO:1903003; P:positive regulation of protein deubiquitination; ISS:UniProtKB.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISS:UniProtKB.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISS:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0051259; P:protein complex oligomerization; ISS:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; ISO:MGI.
DR GO; GO:0090501; P:RNA phosphodiester bond hydrolysis; IDA:UniProtKB.
DR GO; GO:0090502; P:RNA phosphodiester bond hydrolysis, endonucleolytic; IDA:UniProtKB.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IDA:UniProtKB.
DR DisProt; DP02871; -.
DR InterPro; IPR040546; Rege-1_UBA-like.
DR InterPro; IPR040757; Regnase_1/ZC3H12_C.
DR InterPro; IPR021869; RNase_Zc3h12_NYN.
DR Pfam; PF18561; Regnase_1_C; 1.
DR Pfam; PF11977; RNase_Zc3h12a; 1.
DR Pfam; PF18039; UBA_6; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Angiogenesis; Apoptosis; Cytoplasm; Developmental protein;
KW Differentiation; DNA damage; DNA-binding; Endonuclease;
KW Endoplasmic reticulum; Hydrolase; Immunity; Inflammatory response;
KW Magnesium; Membrane; Metal-binding; Neurogenesis; Nuclease; Nucleus;
KW Phosphoprotein; Reference proteome; RNA-binding; Stress response;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..596
FT /note="Endoribonuclease ZC3H12A"
FT /id="PRO_0000341513"
FT DOMAIN 135..290
FT /note="RNase NYN"
FT /evidence="ECO:0000255"
FT ZN_FING 301..324
FT /note="C3H1-type"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 42..87
FT /note="Ubiquitin association domain"
FT /evidence="ECO:0000305|PubMed:21115689"
FT REGION 81..150
FT /note="Necessary for interaction with TANK"
FT /evidence="ECO:0000250|UniProtKB:Q5D1E8"
FT REGION 97..134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 112..281
FT /note="RNase"
FT /evidence="ECO:0000250|UniProtKB:Q5D1E8"
FT REGION 214..220
FT /note="RNA binding"
FT /evidence="ECO:0000250|UniProtKB:Q5D1E8"
FT REGION 278..306
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 301..454
FT /note="Necessary for interaction with ZC3H12D"
FT /evidence="ECO:0000250|UniProtKB:Q5D1E8"
FT REGION 340..417
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 511..543
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..27
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 288..306
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 349..371
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 511..528
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 226
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q5D1E8"
FT MOD_RES 344
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5D1E8"
FT MOD_RES 435
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22037600"
FT MOD_RES 439
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22037600"
FT MUTAGEN 111
FT /note="R->A: Loss of MALT1-dependent cleavage and
FT degradation in T-cells."
FT /evidence="ECO:0000269|PubMed:23706741"
FT MUTAGEN 130
FT /note="R->A: Reduces MALT1-dependent cleavage and
FT degradation in T-cells."
FT /evidence="ECO:0000269|PubMed:23706741"
FT MUTAGEN 136
FT /note="R->A: Reduces MALT1-dependent cleavage and
FT degradation in T-cells."
FT /evidence="ECO:0000269|PubMed:23706741"
FT MUTAGEN 141
FT /note="D->N: Loss of RNase activity. Loss of mRNAs and
FT miRNAs degradation. Loss of protein deubiquitination and
FT suppression of inhibition on JNK and NF-kappa-B signaling
FT pathway activation. Inhibits induction of angiogenesis and
FT macrophage M2 polarization. Mislocalized in stress granule
FT (SG). Loss of the ability to inhibit SG formation under
FT stress. Does not inhibit binding to IL6 mRNA. Increases
FT ICOS surface expression."
FT /evidence="ECO:0000269|PubMed:19322177,
FT ECO:0000269|PubMed:21115689, ECO:0000269|PubMed:21971051,
FT ECO:0000269|PubMed:23706741, ECO:0000269|PubMed:25282160,
FT ECO:0000269|PubMed:25934862, ECO:0000269|PubMed:26000482"
FT MUTAGEN 157
FT /note="C->A: Loss of protein deubiquitination and
FT suppression of inhibition on JNK and NF-kappa-B signaling
FT pathway activation. Loss of the ability to inhibit stress
FT granule (SG) formation. No loss of RNase activity. No
FT effect on ICOS surface expression."
FT /evidence="ECO:0000269|PubMed:21115689,
FT ECO:0000269|PubMed:21971051, ECO:0000269|PubMed:25282160"
FT MUTAGEN 158
FT /note="R->A: Reduces MALT1-dependent cleavage and
FT degradation in T-cells."
FT /evidence="ECO:0000269|PubMed:23706741"
FT MUTAGEN 214
FT /note="R->A: Reduces MALT1-dependent cleavage and
FT degradation in T-cells."
FT /evidence="ECO:0000269|PubMed:23706741"
FT MUTAGEN 225..226
FT /note="DD->AA: Increases ICOS surface expression."
FT /evidence="ECO:0000269|PubMed:25282160"
FT MUTAGEN 225
FT /note="D->A: Loss of RNase activity, no loss of protein
FT deubiquitination and ability to inhibit stress granule (SG)
FT formation under stress; when associated with A-226."
FT /evidence="ECO:0000269|PubMed:21971051"
FT MUTAGEN 226
FT /note="D->A: Loss of RNase activity and no loss of protein
FT deubiquitination; when associated with A-226."
FT /evidence="ECO:0000269|PubMed:21971051"
FT MUTAGEN 278
FT /note="D->A: Loss of inhibition on JNK and NF-kappa-B
FT signaling pathway activation; when associated with A-279."
FT /evidence="ECO:0000269|PubMed:21115689"
FT MUTAGEN 279
FT /note="D->A: Loss of inhibition on JNK and NF-kappa-B
FT signaling pathway activation; when associated with A-278."
FT /evidence="ECO:0000269|PubMed:21115689"
FT MUTAGEN 306
FT /note="C->R: Loss of protein deubiquitination and
FT suppression of inhibition on JNK and NF-kappa-B signaling
FT pathway activations. No loss of RNase activity."
FT /evidence="ECO:0000269|PubMed:19322177,
FT ECO:0000269|PubMed:21115689"
FT MUTAGEN 435
FT /note="S->A: Reduces its phosphorylation status, does not
FT interact with IKBKB/IKKB and BTRC, inhibits IL6 mRNA
FT instability and IKK-mediated degradation of ZC3H12A; when
FT associated with A-439."
FT /evidence="ECO:0000269|PubMed:22037600"
FT MUTAGEN 439
FT /note="S->A: Reduces its phosphorylation status, does not
FT interact with IKBKB/IKKB and BTRC, inhibits IL6 mRNA
FT instability and IKK-mediated degradation of ZC3H12A; when
FT associated with A-435."
FT CONFLICT 280
FT /note="P -> H (in Ref. 2; BAE29035)"
FT /evidence="ECO:0000305"
FT CONFLICT 315
FT /note="G -> E (in Ref. 1; AAX14018)"
FT /evidence="ECO:0000305"
FT HELIX 47..58
FT /evidence="ECO:0007829|PDB:2N5J"
FT HELIX 62..72
FT /evidence="ECO:0007829|PDB:2N5J"
FT HELIX 78..88
FT /evidence="ECO:0007829|PDB:2N5J"
FT STRAND 138..141
FT /evidence="ECO:0007829|PDB:5H9W"
FT HELIX 142..148
FT /evidence="ECO:0007829|PDB:5H9W"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:5H9W"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:5H9W"
FT HELIX 157..169
FT /evidence="ECO:0007829|PDB:5H9W"
FT STRAND 175..180
FT /evidence="ECO:0007829|PDB:5H9W"
FT HELIX 181..184
FT /evidence="ECO:0007829|PDB:5H9W"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:5H9W"
FT HELIX 198..204
FT /evidence="ECO:0007829|PDB:5H9W"
FT STRAND 208..211
FT /evidence="ECO:0007829|PDB:5H9W"
FT STRAND 213..216
FT /evidence="ECO:0007829|PDB:5H9W"
FT STRAND 219..222
FT /evidence="ECO:0007829|PDB:5H9W"
FT HELIX 225..236
FT /evidence="ECO:0007829|PDB:5H9W"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:5H9W"
FT HELIX 247..252
FT /evidence="ECO:0007829|PDB:5H9W"
FT HELIX 254..263
FT /evidence="ECO:0007829|PDB:5H9W"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:5H9W"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:5H9W"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:5H9W"
FT HELIX 288..291
FT /evidence="ECO:0007829|PDB:5H9W"
FT STRAND 301..304
FT /evidence="ECO:0007829|PDB:2N5K"
FT STRAND 323..325
FT /evidence="ECO:0007829|PDB:2N5K"
FT HELIX 546..557
FT /evidence="ECO:0007829|PDB:2N5L"
FT TURN 558..560
FT /evidence="ECO:0007829|PDB:2N5L"
FT HELIX 563..572
FT /evidence="ECO:0007829|PDB:2N5L"
FT HELIX 581..592
FT /evidence="ECO:0007829|PDB:2N5L"
SQ SEQUENCE 596 AA; 65598 MW; 420E116564B70212 CRC64;
MSDPCGTKPV QESNPTMSLW SLEDRHSSQG RPQPDQDPVA KEAPTSELQM KVDFFRKLGY
SSSEIHSVLQ KLGVQADTNT VLGELVKHGS ATERECQALT APSPQPPLVP RGGSTPKPST
LEPSLPEEDR EGSDLRPVVI DGSNVAMSHG NKEVFSCRGI LLAVNWFLER GHTDITVFVP
SWRKEQPRPD VPITDQHILR ELEKKKILVF TPSRRVGGKR VVCYDDRFIV KLAFESDGVV
VSNDTYRDLQ GERQEWKRFI EERLLMYSFV NDKFMPPDDP LGRHGPSLDN FLRKKPLPSE
HRKQPCPYGK KCTYGIKCRF FHPERPSRPQ RSVADELRAN ALLSPPRTPV KDKSSQRPSP
ASQSSSVSLE AEPGSLDGKK LGARSSPGPH REGSPQTCAP AGRSLPVSGG SFGPTEWLAH
TQDSLPYTSQ ECLDSGIGSL ESQMSELWGV RGGSPGESGP TRGPYAGYHS YGSKVPAAPS
FSPFRPAMGA GHFSVPTDYV PPPPTYPSRE YWSEPYPLPP PTPVLQEPQR PSPGAGGGPW
GRVGDLAKER AGVYTKLCGV FPPHLVEAVM RRFPQLLDPQ QLAAEILSYK SQHLSE
