ZC12A_HUMAN
ID ZC12A_HUMAN Reviewed; 599 AA.
AC Q5D1E8; D3DPT0; Q6I9Z1; Q9H5P1;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Endoribonuclease ZC3H12A {ECO:0000305};
DE EC=3.1.-.- {ECO:0000269|PubMed:22055188};
DE AltName: Full=Monocyte chemotactic protein-induced protein 1 {ECO:0000303|PubMed:16574901};
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:22037600};
DE Short=Reg1 {ECO:0000250|UniProtKB:Q5D1E7};
DE AltName: Full=Zinc finger CCCH domain-containing protein 12A {ECO:0000312|HGNC:HGNC:26259};
GN Name=ZC3H12A {ECO:0000312|HGNC:HGNC:26259};
GN Synonyms=MCPIP {ECO:0000303|PubMed:16574901}, MCPIP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAX14017.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION AS A TRANSCRIPTION FACTOR, SUBCELLULAR
RP LOCATION, INDUCTION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-311; CYS-312;
RP LYS-317 AND CYS-318, AND POSSIBLE INVOLVEMENT IN ISCHEMIC HEART DISEASE.
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:0000305, ECO:0000312|EMBL:BAB15581.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-547.
RC TISSUE=Artery {ECO:0000312|EMBL:BAB15581.1};
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3] {ECO:0000305, ECO:0000312|EMBL:CAG33645.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-547.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000312|EMBL:AL449284}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5] {ECO:0000305, ECO:0000312|EMBL:CAG33645.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000305, ECO:0000312|EMBL:AAH05001.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-547.
RC TISSUE=Kidney {ECO:0000312|EMBL:AAH05001.1};
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 [7]
RP SUBCELLULAR LOCATION, 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 [8] {ECO:0000305}
RP FUNCTION AS A TRANSCRIPTION FACTOR, INDUCTION, CHROMATIN BINDING, AND
RP DNA-BINDING.
RX PubMed=18364357; DOI=10.1074/jbc.m802139200;
RA Niu J., Azfer A., Zhelyabovska O., Fatma S., Kolattukudy P.E.;
RT "Monocyte chemotactic protein (MCP)-1 promotes angiogenesis via a novel
RT transcription factor, MCP-1-induced protein (MCPIP).";
RL J. Biol. Chem. 283:14542-14551(2008).
RN [9]
RP FUNCTION, AND INDUCTION.
RX PubMed=19185603; DOI=10.1016/j.brainresbull.2009.01.004;
RA Vrotsos E.G., Kolattukudy P.E., Sugaya K.;
RT "MCP-1 involvement in glial differentiation of neuroprogenitor cells
RT through APP signaling.";
RL Brain Res. Bull. 79:97-103(2009).
RN [10]
RP INDUCTION.
RX PubMed=19747262; DOI=10.1111/j.1742-4658.2009.07273.x;
RA Skalniak L., Mizgalska D., Zarebski A., Wyrzykowska P., Koj A., Jura J.;
RT "Regulatory feedback loop between NF-kappaB and MCP-1-induced protein 1
RT RNase.";
RL FEBS J. 276:5892-5905(2009).
RN [11]
RP FUNCTION AS AN ENDORIBONUCLEASE, SUBCELLULAR LOCATION, INDUCTION, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF ASP-141 AND ASP-226.
RX PubMed=19909337; DOI=10.1111/j.1742-4658.2009.07452.x;
RA Mizgalska D., Wegrzyn P., Murzyn K., Kasza A., Koj A., Jura J., Jarzab B.,
RA Jura J.;
RT "Interleukin-1-inducible MCPIP protein has structural and functional
RT properties of RNase and participates in degradation of IL-1beta mRNA.";
RL FEBS J. 276:7386-7399(2009).
RN [12]
RP INDUCTION.
RX PubMed=20137095; DOI=10.1186/1471-2199-11-14;
RA Kasza A., Wyrzykowska P., Horwacik I., Tymoszuk P., Mizgalska D.,
RA Palmer K., Rokita H., Sharrocks A.D., Jura J.;
RT "Transcription factors Elk-1 and SRF are engaged in IL1-dependent
RT regulation of ZC3H12A expression.";
RL BMC Mol. Biol. 11:14-14(2010).
RN [13]
RP FUNCTION AS AN ENDORIBONUCLEASE, CATALYTIC ACTIVITY, SUBUNIT, RNA-BINDING,
RP SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF ASP-141 AND CYS-306.
RX PubMed=22055188; DOI=10.1016/j.molcel.2011.09.012;
RA Suzuki H.I., Arase M., Matsuyama H., Choi Y.L., Ueno T., Mano H.,
RA Sugimoto K., Miyazono K.;
RT "MCPIP1 ribonuclease antagonizes dicer and terminates microRNA biogenesis
RT through precursor microRNA degradation.";
RL Mol. Cell 44:424-436(2011).
RN [14]
RP INTERACTION WITH IKBKB, AND INDUCTION.
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 [15]
RP 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 [16]
RP FUNCTION AS AN ENDORIBONUCLEASE.
RX PubMed=24048733; DOI=10.1152/ajpcell.00203.2013;
RA Roy A., Zhang M., Saad Y., Kolattukudy P.E.;
RT "Antidicer RNase activity of monocyte chemotactic protein-induced protein-1
RT is critical for inducing angiogenesis.";
RL Am. J. Physiol. 305:C1021-C1032(2013).
RN [17]
RP REVIEW.
RX PubMed=23500036; DOI=10.1016/j.bbagrm.2013.03.001;
RA Uehata T., Akira S.;
RT "mRNA degradation by the endoribonuclease Regnase-1/ZC3H12a/MCPIP-1.";
RL Biochim. Biophys. Acta 1829:708-713(2013).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99 AND SER-344, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [19]
RP FUNCTION AS AN ENDORIBONUCLEASE (MICROBIAL INFECTION), SUBUNIT (MICROBIAL
RP INFECTION), RNA-BINDING, DOMAIN (MICROBIAL INFECTION), INDUCTION (MICROBIAL
RP INFECTION), AND MUTAGENESIS OF ASP-141; CYS-157; ASP-225; ASP-226 AND
RP CYS-306.
RX PubMed=23355615; DOI=10.1093/nar/gkt019;
RA Lin R.J., Chien H.L., Lin S.Y., Chang B.L., Yu H.P., Tang W.C., Lin Y.L.;
RT "MCPIP1 ribonuclease exhibits broad-spectrum antiviral effects through
RT viral RNA binding and degradation.";
RL Nucleic Acids Res. 41:3314-3326(2013).
RN [20]
RP FUNCTION AS AN ENDORIBONUCLEASE (MICROBIAL INFECTION), DEGRADATION
RP (MICROBIAL INFECTION), AND MUTAGENESIS OF ASP-141; ASP-225; ASP-226 AND
RP CYS-306.
RX PubMed=24191027; DOI=10.1073/pnas.1316208110;
RA Liu S., Qiu C., Miao R., Zhou J., Lee A., Liu B., Lester S.N., Fu W.,
RA Zhu L., Zhang L., Xu J., Fan D., Li K., Fu M., Wang T.;
RT "MCPIP1 restricts HIV infection and is rapidly degraded in activated CD4+ T
RT cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:19083-19088(2013).
RN [21]
RP FUNCTION AS AN ENDORIBONUCLEASE IN INFLAMMATION, INDUCTION, AND MUTAGENESIS
RP OF ASP-141; ASP-225; ASP-226 AND CYS-306.
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 [22]
RP FUNCTION, IDENTIFICATION IN A DEUBIQUITINATION COMPLEX WITH TANK AND USP10,
RP AND INTERACTION WITH IKBKG; TANK; TRAF6 AND USP10.
RX PubMed=25861989; DOI=10.1074/jbc.m115.643767;
RA Wang W., Huang X., Xin H.B., Fu M., Xue A., Wu Z.H.;
RT "TRAF family member-associated NF-kappaB activator (TANK) inhibits
RT genotoxic nuclear factor kappaB activation by facilitating deubiquitinase
RT USP10-dependent deubiquitination of TRAF6 ligase.";
RL J. Biol. Chem. 290:13372-13385(2015).
RN [23]
RP FUNCTION AS AN ENDORIBONUCLEASE, INTERACTION WITH TNRC6A AND ZC3H12D,
RP SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF ASP-141.
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 [24]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 112-334, FUNCTION AS AN
RP ENDORIBONUCLEASE, CATALYTIC REGION, COFACTOR, DOMAIN, MUTAGENESIS OF
RP ASP-141; ASN-144 AND ARG-214, AND MAGNESIUM-BINDING SITE.
RX PubMed=22561375; DOI=10.1093/nar/gks359;
RA Xu J., Peng W., Sun Y., Wang X., Xu Y., Li X., Gao G., Rao Z.;
RT "Structural study of MCPIP1 N-terminal conserved domain reveals a PIN-like
RT RNase.";
RL Nucleic Acids Res. 40:6957-6965(2012).
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:19909337). 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:26320658).
CC Prevents aberrant T-cell-mediated immune reaction by degradation of
CC multiple mRNAs controlling T-cell activation, such as those encoding
CC cytokines (IL6 and IL2), cell surface receptors (ICOS, TNFRSF4 and
CC TNFR2) and transcription factor (REL) (By similarity). 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 (By
CC similarity). Together with RC3H1, destabilizes TNFRSF4/OX40 mRNA by
CC binding to the conserved stem loop structure in its 3'UTR (By
CC similarity). Self regulates by destabilizing its own mRNA (By
CC similarity). Cleaves mRNA harboring a stem-loop (SL), often located in
CC their 3'-UTRs, during the early phase of inflammation in a helicase
CC UPF1-dependent manner (PubMed:19909337, PubMed:26320658,
CC PubMed:26134560, PubMed:22561375). Plays a role in the inhibition of
CC microRNAs (miRNAs) biogenesis (PubMed:22055188). Cleaves the terminal
CC loop of a set of precursor miRNAs (pre-miRNAs) important for the
CC regulation of the inflammatory response leading to their degradation,
CC and thus preventing the biosynthesis of mature miRNAs
CC (PubMed:22055188). Also plays a role in promoting angiogenesis in
CC response to inflammatory cytokines by inhibiting the production of
CC antiangiogenic microRNAs via its anti-dicer RNase activity
CC (PubMed:24048733). Affects the overall ubiquitination of cellular
CC proteins (By similarity). Positively regulates deubiquitinase activity
CC promoting the cleavage at 'Lys-48'- and 'Lys-63'-linked polyubiquitin
CC chains on TNF receptor-associated factors (TRAFs), preventing JNK and
CC NF-kappa-B signaling pathway activation, and hence negatively
CC regulating macrophage-mediated inflammatory response and immune
CC homeostasis (By similarity). Induces also deubiquitination of the
CC transcription factor HIF1A, probably leading to its stabilization and
CC nuclear import, thereby positively regulating the expression of
CC proangiogenic HIF1A-targeted genes (PubMed:24048733). Involved in a
CC TANK-dependent negative feedback response to attenuate NF-kappaB
CC activation through the deubiquitination of IKBKG or TRAF6 in response
CC to interleukin-1-beta (IL1B) stimulation or upon DNA damage
CC (PubMed:25861989). Prevents stress granule (SGs) formation and promotes
CC macrophage apoptosis under stress conditions, including arsenite-
CC induced oxidative stress, heat shock and energy deprivation (By
CC similarity). Plays a role in the regulation of macrophage polarization;
CC promotes IL4-induced polarization of macrophages M1 into anti-
CC inflammatory M2 state (By similarity). May also act as a transcription
CC factor that regulates the expression of multiple genes involved in
CC inflammatory response, angiogenesis, adipogenesis and apoptosis
CC (PubMed:16574901, PubMed:18364357). Functions as a positive regulator
CC of glial differentiation of neuroprogenitor cells through an amyloid
CC precursor protein (APP)-dependent signaling pathway (PubMed:19185603).
CC Attenuates septic myocardial contractile dysfunction in response to
CC lipopolysaccharide (LPS) by reducing I-kappa-B-kinase (IKK)-mediated
CC NF-kappa-B activation, and hence myocardial pro-inflammatory cytokine
CC production (By similarity). {ECO:0000250|UniProtKB:Q5D1E7,
CC ECO:0000269|PubMed:16574901, ECO:0000269|PubMed:18364357,
CC ECO:0000269|PubMed:19185603, ECO:0000269|PubMed:19909337,
CC ECO:0000269|PubMed:22055188, ECO:0000269|PubMed:22561375,
CC ECO:0000269|PubMed:24048733, ECO:0000269|PubMed:25861989,
CC ECO:0000269|PubMed:26134560, ECO:0000269|PubMed:26320658}.
CC -!- FUNCTION: (Microbial infection) Binds to Japanese encephalitis virus
CC (JEV) and Dengue virus (DEN) RNAs. {ECO:0000269|PubMed:23355615}.
CC -!- FUNCTION: (Microbial infection) Exhibits antiviral activity against
CC HIV-1 in lymphocytes by decreasing the abundance of HIV-1 viral RNA
CC species. {ECO:0000269|PubMed:24191027}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:22561375};
CC Note=Mg(2+) is required for RNase activity (PubMed:22561375).
CC {ECO:0000269|PubMed:22561375};
CC -!- SUBUNIT: Oligomer (PubMed:22055188, PubMed:23355615). Found in a
CC deubiquitination complex with TANK, USP10 and ZC3H12A; this complex
CC inhibits genotoxic stress- or interleukin-1-beta-mediated NF-kappaB
CC activation by promoting IKBKG or TRAF6 deubiquitination
CC (PubMed:25861989). Interacts with IKBKG; this interaction increases in
CC response to DNA damage (PubMed:25861989). Interacts with TANK; 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 (PubMed:25861989). Interacts with TRAF6; this interaction increases in
CC response to DNA damage and is stimulated by TANK (PubMed:25861989).
CC Interacts with USP10; this interaction increases in response to DNA
CC damage and serves as a bridge to anchor both TANK and USP10 into a
CC deubiquitinating complex (PubMed:25861989). Interacts with ZC3H12D
CC (PubMed:26134560). Interacts with TNRC6A (PubMed:26134560). Interacts
CC with IKBKB/IKKB (PubMed:22037600). Interacts with IKBKB/IKKB. Interacts
CC with BTRC; the interaction occurs when ZC3H12A is phosphorylated in a
CC IKBKB/IKKB-dependent manner (By similarity). Interacts with IRAK1; this
CC interaction increases the interaction between ZC3H12A and IKBKB/IKKB
CC (By similarity). Interacts with UPF1; this interaction occurs in a mRNA
CC translationally active- and termination-dependent manner and is
CC essential for ZC3H12A-mediated degradation of target mRNAs (By
CC similarity). Associates with ribosomes (By similarity). Interacts with
CC ubiquitin (By similarity). {ECO:0000250|UniProtKB:Q5D1E7,
CC ECO:0000269|PubMed:22037600, ECO:0000269|PubMed:22055188,
CC ECO:0000269|PubMed:23355615, ECO:0000269|PubMed:25861989,
CC ECO:0000269|PubMed:26134560}.
CC -!- SUBUNIT: (Microbial infection) Oligomerization is necessary for
CC antiviral activity (PubMed:23355615). {ECO:0000269|PubMed:23355615}.
CC -!- INTERACTION:
CC Q5D1E8; Q9NZD4: AHSP; NbExp=4; IntAct=EBI-747793, EBI-720250;
CC Q5D1E8; Q9Y297: BTRC; NbExp=3; IntAct=EBI-747793, EBI-307461;
CC Q5D1E8; P59910: DNAJB13; NbExp=3; IntAct=EBI-747793, EBI-11514233;
CC Q5D1E8; Q9Y6K9: IKBKG; NbExp=2; IntAct=EBI-747793, EBI-81279;
CC Q5D1E8; O43187: IRAK2; NbExp=2; IntAct=EBI-747793, EBI-447733;
CC Q5D1E8; Q7Z4N8: P4HA3; NbExp=6; IntAct=EBI-747793, EBI-10181968;
CC Q5D1E8; P84022: SMAD3; NbExp=2; IntAct=EBI-747793, EBI-347161;
CC Q5D1E8; Q14694: USP10; NbExp=5; IntAct=EBI-747793, EBI-2510389;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16574901}. Cytoplasm
CC {ECO:0000269|PubMed:18178554, ECO:0000269|PubMed:19909337,
CC ECO:0000269|PubMed:22055188}. Cytoplasm, P-body
CC {ECO:0000269|PubMed:22055188, ECO:0000269|PubMed:26134560}. Rough
CC endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q5D1E7};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q5D1E7}; Cytoplasmic
CC side {ECO:0000250|UniProtKB:Q5D1E7}. Cytoplasmic granule
CC {ECO:0000250|UniProtKB:Q5D1E7}. Note=Predominantly localized in the
CC cytoplasm. Colocalizes with GW182 on many granule-like structures,
CC probably corresponding to cytoplasmic GW bodies (GWBs), also called
CC processing bodies (P bodies). Colocalizes with calnexin on the surface
CC of the rough endoplasmic reticulum (RER) membrane and with
CC translationally active polysomes (By similarity). Colocalizes with
CC ZC3H12D in cytoplasmic mRNA processing P-body, also known as GW bodies
CC (GWBs) (PubMed:22055188, PubMed:26134560).
CC {ECO:0000269|PubMed:22055188, ECO:0000269|PubMed:26134560}.
CC -!- TISSUE SPECIFICITY: Expressed in heart, placenta, spleen, kidney, liver
CC and lung (PubMed:19909337). Expressed in leukocytes (PubMed:19909337).
CC Expressed in monocyte (PubMed:16574901). {ECO:0000269|PubMed:16574901,
CC ECO:0000269|PubMed:19909337}.
CC -!- INDUCTION: Up-regulated by the transcription factor ELK1 in a
CC interleukin IL1B-dependent manner through activation of the NF-kappa-B
CC and ERK signaling pathways (PubMed:19747262, PubMed:20137095,
CC PubMed:22037600). Up-regulated by chemokine CCL2 in endothelial cells
CC and in peripheral blood monocytes (PubMed:16574901, PubMed:18364357).
CC Up-regulated in activated T lymphocytes (PubMed:23185455). Up-regulated
CC by phorbol 12-myristate 13-acetate (PMA) in primary T lymphocytes
CC (PubMed:19909337, PubMed:23185455). Up-regulated by interleukin IL17 in
CC keratinocytes (PubMed:26320658). Up-regulated by lipopolysaccharide
CC (LPS) (PubMed:19909337). Up-regulated by tumor necrosis factor TNF-
CC alpha and interleukin IL1 in acute monocytic leukemia cell line THP-1
CC cells (PubMed:18178554, PubMed:19909337). Up-regulated by amyloid
CC precursor protein (APP) (PubMed:19185603).
CC {ECO:0000269|PubMed:16574901, ECO:0000269|PubMed:18178554,
CC ECO:0000269|PubMed:18364357, ECO:0000269|PubMed:19185603,
CC ECO:0000269|PubMed:19747262, ECO:0000269|PubMed:19909337,
CC ECO:0000269|PubMed:20137095, ECO:0000269|PubMed:22037600,
CC ECO:0000269|PubMed:23185455, ECO:0000269|PubMed:26320658}.
CC -!- INDUCTION: (Microbial infection) Up-regulated in response to Japanese
CC encephalitis virus (JEV) and dengue virus (DEN) infections
CC (PubMed:23355615). {ECO:0000269|PubMed:23355615}.
CC -!- DOMAIN: The C3H1-type zinc finger domain and C-terminal region are
CC necessary for pre-miRNA binding (PubMed:22055188). The C-terminal
CC region and proline-rich domain are necessary for oligomerization
CC (PubMed:22055188). {ECO:0000269|PubMed:22055188}.
CC -!- DOMAIN: (Microbial infection) The C3H1-type zinc finger domain is
CC necessary for JEV and DEN viral RNA-binding and antiviral activity
CC (PubMed:23355615). {ECO:0000269|PubMed:23355615}.
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-kinase (IKK) subunits IKBKB/IKKB and
CC CHUK/IKKA at Ser-438 and Ser-442; these phosphorylations promote
CC ubiquitin proteasome-mediated degradation of ZC3H12A and hence
CC facilitates rapid and robust production of IL-6 mRNA in response to
CC toll-like receptor (TLR) or IL-1 receptor stimuli (By similarity).
CC {ECO:0000250|UniProtKB:Q5D1E7}.
CC -!- PTM: (Microbial infection) Rapidly degraded in activated T-cells in
CC response to phorbol 13-acetate 12-myristate (PMA) during HIV-1 viral
CC infection (PubMed:24191027). {ECO:0000269|PubMed:24191027}.
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 (By similarity).
CC {ECO:0000250|UniProtKB:Q5D1E7}.
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:0000250|UniProtKB:Q5D1E7}.
CC -!- DISEASE: Note=Increased expression of ZC3H12A is associated with
CC ischemic heart disease (PubMed:16574901).
CC {ECO:0000269|PubMed:16574901}.
CC -!- SIMILARITY: Belongs to the ZC3H12 family. {ECO:0000305}.
CC -!- CAUTION: Was originally proposed to bind to DNA and act as
CC transcription factor. {ECO:0000305|PubMed:18364357}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY920403; AAX14017.1; -; mRNA.
DR EMBL; AK026884; BAB15581.1; -; mRNA.
DR EMBL; CR457364; CAG33645.1; -; mRNA.
DR EMBL; AL034379; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL449284; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07346.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07347.1; -; Genomic_DNA.
DR EMBL; BC005001; AAH05001.1; -; mRNA.
DR CCDS; CCDS417.1; -.
DR RefSeq; NP_001310479.1; NM_001323550.1.
DR RefSeq; NP_079355.2; NM_025079.2.
DR PDB; 3V32; X-ray; 2.00 A; A/B=112-296.
DR PDB; 3V33; X-ray; 2.00 A; A/B=112-334.
DR PDB; 3V34; X-ray; 2.00 A; A/B=112-296.
DR PDBsum; 3V32; -.
DR PDBsum; 3V33; -.
DR PDBsum; 3V34; -.
DR AlphaFoldDB; Q5D1E8; -.
DR SMR; Q5D1E8; -.
DR BioGRID; 123141; 37.
DR CORUM; Q5D1E8; -.
DR IntAct; Q5D1E8; 17.
DR MINT; Q5D1E8; -.
DR STRING; 9606.ENSP00000362179; -.
DR iPTMnet; Q5D1E8; -.
DR PhosphoSitePlus; Q5D1E8; -.
DR BioMuta; ZC3H12A; -.
DR DMDM; 190479827; -.
DR EPD; Q5D1E8; -.
DR jPOST; Q5D1E8; -.
DR MassIVE; Q5D1E8; -.
DR MaxQB; Q5D1E8; -.
DR PaxDb; Q5D1E8; -.
DR PeptideAtlas; Q5D1E8; -.
DR PRIDE; Q5D1E8; -.
DR ProteomicsDB; 62741; -.
DR Antibodypedia; 31721; 207 antibodies from 34 providers.
DR DNASU; 80149; -.
DR Ensembl; ENST00000373087.7; ENSP00000362179.5; ENSG00000163874.11.
DR GeneID; 80149; -.
DR KEGG; hsa:80149; -.
DR MANE-Select; ENST00000373087.7; ENSP00000362179.5; NM_025079.3; NP_079355.2.
DR UCSC; uc001cbb.5; human.
DR CTD; 80149; -.
DR DisGeNET; 80149; -.
DR GeneCards; ZC3H12A; -.
DR HGNC; HGNC:26259; ZC3H12A.
DR HPA; ENSG00000163874; Tissue enhanced (bone).
DR MIM; 610562; gene.
DR neXtProt; NX_Q5D1E8; -.
DR OpenTargets; ENSG00000163874; -.
DR PharmGKB; PA142670537; -.
DR VEuPathDB; HostDB:ENSG00000163874; -.
DR eggNOG; KOG3777; Eukaryota.
DR GeneTree; ENSGT00940000155107; -.
DR HOGENOM; CLU_013020_2_1_1; -.
DR InParanoid; Q5D1E8; -.
DR OMA; CGIFHPH; -.
DR OrthoDB; 771251at2759; -.
DR PhylomeDB; Q5D1E8; -.
DR TreeFam; TF315783; -.
DR PathwayCommons; Q5D1E8; -.
DR SignaLink; Q5D1E8; -.
DR SIGNOR; Q5D1E8; -.
DR BioGRID-ORCS; 80149; 12 hits in 1088 CRISPR screens.
DR ChiTaRS; ZC3H12A; human.
DR GenomeRNAi; 80149; -.
DR Pharos; Q5D1E8; Tbio.
DR PRO; PR:Q5D1E8; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5D1E8; protein.
DR Bgee; ENSG00000163874; Expressed in gall bladder and 125 other tissues.
DR ExpressionAtlas; Q5D1E8; baseline and differential.
DR Genevisible; Q5D1E8; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB.
DR GO; GO:0042406; C:extrinsic component of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0005791; C:rough endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0030867; C:rough endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0004521; F:endoribonuclease activity; ISS:UniProtKB.
DR GO; GO:0004532; F:exoribonuclease activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035198; F:miRNA binding; IDA:UniProtKB.
DR GO; GO:0035925; F:mRNA 3'-UTR AU-rich region binding; ISS:UniProtKB.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; ISS:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0004540; F:ribonuclease activity; IDA:UniProtKB.
DR GO; GO:0043022; F:ribosome binding; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0035613; F:RNA stem-loop binding; ISS: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; IMP:UniProtKB.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; ISS:UniProtKB.
DR GO; GO:1904637; P:cellular response to ionomycin; ISS:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:1903936; P:cellular response to sodium arsenite; ISS:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB.
DR GO; GO:0098586; P:cellular response to virus; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0002757; P:immune response-activating signal transduction; IDA:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0010587; P:miRNA catabolic process; IDA:GO_Central.
DR GO; GO:0044828; P:negative regulation by host of viral genome replication; IDA:UniProtKB.
DR GO; GO:0055118; P:negative regulation of cardiac muscle contraction; ISS:UniProtKB.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; ISS:UniProtKB.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IDA:BHF-UCL.
DR GO; GO:0043031; P:negative regulation of macrophage activation; IC:BHF-UCL.
DR GO; GO:1903799; P:negative regulation of miRNA maturation; IDA:UniProtKB.
DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:BHF-UCL.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:2000320; P:negative regulation of T-helper 17 cell differentiation; ISS:UniProtKB.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IDA:BHF-UCL.
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; ISS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IDA:BHF-UCL.
DR GO; GO:0010942; P:positive regulation of cell death; IDA:UniProtKB.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IDA:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:UniProtKB.
DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; ISS:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IDA:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0010884; P:positive regulation of lipid storage; IDA:BHF-UCL.
DR GO; GO:2000627; P:positive regulation of miRNA catabolic process; IDA:UniProtKB.
DR GO; GO:0061014; P:positive regulation of mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; IDA:UniProtKB.
DR GO; GO:1903003; P:positive regulation of protein deubiquitination; IMP:UniProtKB.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IDA:UniProtKB.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IDA: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; IDA:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0090501; P:RNA phosphodiester bond hydrolysis; ISS:UniProtKB.
DR GO; GO:0090502; P:RNA phosphodiester bond hydrolysis, endonucleolytic; IBA:GO_Central.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISS:UniProtKB.
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; Antiviral defense; Apoptosis; Cytoplasm;
KW Developmental protein; Differentiation; DNA damage; DNA-binding;
KW Endonuclease; Endoplasmic reticulum; Host-virus interaction; Hydrolase;
KW Immunity; Inflammatory response; Magnesium; Membrane; Metal-binding;
KW Neurogenesis; Nuclease; Nucleus; Phosphoprotein; Reference proteome;
KW Repressor; RNA-binding; Stress response; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..599
FT /note="Endoribonuclease ZC3H12A"
FT /id="PRO_0000341512"
FT DOMAIN 135..290
FT /note="RNase NYN"
FT /evidence="ECO:0000255"
FT ZN_FING 301..324
FT /note="C3H1-type"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 42..87
FT /note="Ubiquitin association domain"
FT /evidence="ECO:0000250|UniProtKB:Q5D1E7"
FT REGION 81..150
FT /note="Necessary for interaction with TANK"
FT /evidence="ECO:0000269|PubMed:25861989"
FT REGION 90..133
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 112..297
FT /note="RNase"
FT /evidence="ECO:0000305|PubMed:22561375"
FT REGION 214..220
FT /note="RNA binding"
FT /evidence="ECO:0000305|PubMed:22561375"
FT REGION 301..457
FT /note="Necessary for interaction with ZC3H12D"
FT /evidence="ECO:0000269|PubMed:26134560"
FT REGION 343..420
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 522..546
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 355..373
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 388..420
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 226
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:22561375"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 344
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 438
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5D1E7"
FT MOD_RES 442
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5D1E7"
FT VARIANT 240
FT /note="V -> M (in dbSNP:rs16824179)"
FT /id="VAR_052968"
FT VARIANT 547
FT /note="G -> D (in dbSNP:rs17849897)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3"
FT /id="VAR_044082"
FT MUTAGEN 141
FT /note="D->N: Abolishes RNase activity."
FT /evidence="ECO:0000269|PubMed:22561375"
FT MUTAGEN 141
FT /note="D->N: Loss of pre-miRNA RNase activity. Attenuates
FT strongly miRNA silencing activity. Loss of interleukin
FT IL17A and IL6 mRNA instabilities. Reduces angiogenic
FT differentiation. Loss of RNase activity on JEV and DEN
FT viral RNAs and antiviral effects. Loss of HIV-1 antiviral
FT activity. Loss of IL1B mRNA instability; when associated
FT with A-226."
FT /evidence="ECO:0000269|PubMed:19909337,
FT ECO:0000269|PubMed:22055188, ECO:0000269|PubMed:23355615,
FT ECO:0000269|PubMed:24191027, ECO:0000269|PubMed:26134560,
FT ECO:0000269|PubMed:26320658"
FT MUTAGEN 144
FT /note="N->A: No change in RNase activity."
FT /evidence="ECO:0000269|PubMed:22561375"
FT MUTAGEN 157
FT /note="C->A: Does not inhibit antiviral effects."
FT /evidence="ECO:0000269|PubMed:23355615"
FT MUTAGEN 214
FT /note="R->A: Abolishes RNase activity."
FT /evidence="ECO:0000269|PubMed:22561375"
FT MUTAGEN 225
FT /note="D->A: Loss of pre-miRNA RNase activity, IL17A mRNA
FT instability and antiviral effects; when associated with A-
FT 226."
FT /evidence="ECO:0000269|PubMed:23355615,
FT ECO:0000269|PubMed:24191027, ECO:0000269|PubMed:26320658"
FT MUTAGEN 226
FT /note="D->A: Loss of pre-miRNA RNase activity, IL17A mRNA
FT instability and antiviral effects; when associated with A-
FT 225. Loss of IL1B mRNA instability; when associated with N-
FT 141."
FT /evidence="ECO:0000269|PubMed:19909337,
FT ECO:0000269|PubMed:23355615, ECO:0000269|PubMed:24191027,
FT ECO:0000269|PubMed:26320658"
FT MUTAGEN 306
FT /note="C->R: Loss of interleukin IL17A mRNA instability.
FT Reduces weakly pre-miRNA RNase activity. Attenuates miRNA
FT silencing activity. Does not inhibits binding to Japanese
FT encephalitis virus (JEV) and dengue virus (DEN) RNAs and
FT weakly attenuates antiviral effects. Loss of HIV-1
FT antiviral activity."
FT /evidence="ECO:0000269|PubMed:22055188,
FT ECO:0000269|PubMed:23355615, ECO:0000269|PubMed:24191027,
FT ECO:0000269|PubMed:26320658"
FT MUTAGEN 311
FT /note="K->G: Inhibits transcriptional activity; when
FT associated with G-312."
FT /evidence="ECO:0000269|PubMed:16574901"
FT MUTAGEN 312
FT /note="C->G: Inhibits transcriptional activity; when
FT associated with G-311."
FT /evidence="ECO:0000269|PubMed:16574901"
FT MUTAGEN 317
FT /note="K->G: Inhibits transcriptional activity; when
FT associated with G-318."
FT /evidence="ECO:0000269|PubMed:16574901"
FT MUTAGEN 318
FT /note="C->G: Inhibits transcriptional activity; when
FT associated with G-317."
FT /evidence="ECO:0000269|PubMed:16574901"
FT CONFLICT 248
FT /note="D -> G (in Ref. 3; CAG33645)"
FT /evidence="ECO:0000305"
FT CONFLICT 599
FT /note="E -> D (in Ref. 3; CAG33645)"
FT /evidence="ECO:0000305"
FT STRAND 138..141
FT /evidence="ECO:0007829|PDB:3V32"
FT HELIX 142..149
FT /evidence="ECO:0007829|PDB:3V32"
FT TURN 150..153
FT /evidence="ECO:0007829|PDB:3V32"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:3V32"
FT HELIX 157..169
FT /evidence="ECO:0007829|PDB:3V32"
FT STRAND 175..180
FT /evidence="ECO:0007829|PDB:3V32"
FT HELIX 181..184
FT /evidence="ECO:0007829|PDB:3V32"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:3V33"
FT HELIX 197..204
FT /evidence="ECO:0007829|PDB:3V32"
FT STRAND 208..211
FT /evidence="ECO:0007829|PDB:3V32"
FT STRAND 213..216
FT /evidence="ECO:0007829|PDB:3V33"
FT STRAND 219..222
FT /evidence="ECO:0007829|PDB:3V33"
FT HELIX 225..235
FT /evidence="ECO:0007829|PDB:3V32"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:3V32"
FT HELIX 247..252
FT /evidence="ECO:0007829|PDB:3V32"
FT HELIX 254..263
FT /evidence="ECO:0007829|PDB:3V32"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:3V32"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:3V32"
FT TURN 280..283
FT /evidence="ECO:0007829|PDB:3V32"
FT HELIX 288..291
FT /evidence="ECO:0007829|PDB:3V32"
SQ SEQUENCE 599 AA; 65699 MW; 9213139FA7DCA443 CRC64;
MSGPCGEKPV LEASPTMSLW EFEDSHSRQG TPRPGQELAA EEASALELQM KVDFFRKLGY
SSTEIHSVLQ KLGVQADTNT VLGELVKHGT ATERERQTSP DPCPQLPLVP RGGGTPKAPN
LEPPLPEEEK EGSDLRPVVI DGSNVAMSHG NKEVFSCRGI LLAVNWFLER GHTDITVFVP
SWRKEQPRPD VPITDQHILR ELEKKKILVF TPSRRVGGKR VVCYDDRFIV KLAYESDGIV
VSNDTYRDLQ GERQEWKRFI EERLLMYSFV NDKFMPPDDP LGRHGPSLDN FLRKKPLTLE
HRKQPCPYGR KCTYGIKCRF FHPERPSCPQ RSVADELRAN ALLSPPRAPS KDKNGRRPSP
SSQSSSLLTE SEQCSLDGKK LGAQASPGSR QEGLTQTYAP SGRSLAPSGG SGSSFGPTDW
LPQTLDSLPY VSQDCLDSGI GSLESQMSEL WGVRGGGPGE PGPPRAPYTG YSPYGSELPA
TAAFSAFGRA MGAGHFSVPA DYPPAPPAFP PREYWSEPYP LPPPTSVLQE PPVQSPGAGR
SPWGRAGSLA KEQASVYTKL CGVFPPHLVE AVMGRFPQLL DPQQLAAEIL SYKSQHPSE
