ZCHC3_MOUSE
ID ZCHC3_MOUSE Reviewed; 400 AA.
AC Q8BPK2;
DT 16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Zinc finger CCHC domain-containing protein 3 {ECO:0000305};
GN Name=Zcchc3 {ECO:0000312|MGI:MGI:1915167};
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30193849; DOI=10.1016/j.immuni.2018.08.014;
RA Lian H., Zang R., Wei J., Ye W., Hu M.M., Chen Y.D., Zhang X.N., Guo Y.,
RA Lei C.Q., Yang Q., Luo W.W., Li S., Shu H.B.;
RT "The zinc-finger protein ZCCHC3 binds RNA and facilitates viral RNA sensing
RT and activation of the RIG-I-like receptors.";
RL Immunity 49:438-448(2018).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30135424; DOI=10.1038/s41467-018-05559-w;
RA Lian H., Wei J., Zang R., Ye W., Yang Q., Zhang X.N., Chen Y.D., Fu Y.Z.,
RA Hu M.M., Lei C.Q., Luo W.W., Li S., Shu H.B.;
RT "ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune
RT response.";
RL Nat. Commun. 9:3349-3349(2018).
CC -!- FUNCTION: Nucleic acid-binding protein involved in innate immune
CC response to DNA and RNA viruses (PubMed:30193849, PubMed:30135424).
CC Binds DNA and RNA in the cytoplasm and acts by promoting recognition of
CC viral nucleic acids by virus sensors, such as DDX58/RIG-I, IFIH1/MDA5
CC and CGAS (PubMed:30193849, PubMed:30135424). Acts as a co-sensor for
CC recognition of double-stranded DNA (dsDNA) by cGAS in the cytoplasm,
CC thereby playing a role in innate immune response to cytosolic dsDNA and
CC DNA virus (By similarity). Binds dsDNA and probably acts by promoting
CC sensing of dsDNA by CGAS, leading to enhance CGAS oligomerization and
CC activation (By similarity). Promotes sensing of viral RNA by RIG-I-like
CC receptors proteins DDX58/RIG-I and IFIH1/MDA5 via two mechanisms: binds
CC double-stranded RNA (dsRNA), enhancing the binding of DDX58/RIG-I and
CC IFIH1/MDA5 to dsRNA and promotes 'Lys-63'-linked ubiquitination and
CC subsequent activation of DDX58/RIG-I and IFIH1/MDA5 (By similarity).
CC {ECO:0000250|UniProtKB:Q9NUD5, ECO:0000269|PubMed:30135424,
CC ECO:0000269|PubMed:30193849}.
CC -!- SUBUNIT: Interacts with CGAS (By similarity). Interacts with DDX58/RIG-
CC I (By similarity). Interacts with IFIH1/MDA5 (By similarity).
CC {ECO:0000250|UniProtKB:Q9NUD5}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9NUD5}.
CC -!- DISRUPTION PHENOTYPE: Mice were born at the Mendelian ratio and do not
CC show defects in development and immune cell differentiation
CC (PubMed:30193849). Mice are however more susceptible to DNA and RNA
CC virus infection (PubMed:30193849, PubMed:30135424).
CC {ECO:0000269|PubMed:30135424, ECO:0000269|PubMed:30193849}.
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DR EMBL; AK053859; BAC35560.1; -; mRNA.
DR EMBL; AL928568; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC055755; AAH55755.1; -; mRNA.
DR CCDS; CCDS16884.1; -.
DR RefSeq; NP_780335.1; NM_175126.4.
DR AlphaFoldDB; Q8BPK2; -.
DR STRING; 10090.ENSMUSP00000096813; -.
DR iPTMnet; Q8BPK2; -.
DR PhosphoSitePlus; Q8BPK2; -.
DR MaxQB; Q8BPK2; -.
DR PaxDb; Q8BPK2; -.
DR PeptideAtlas; Q8BPK2; -.
DR PRIDE; Q8BPK2; -.
DR ProteomicsDB; 342707; -.
DR Antibodypedia; 72721; 66 antibodies from 20 providers.
DR DNASU; 67917; -.
DR Ensembl; ENSMUST00000099207; ENSMUSP00000096813; ENSMUSG00000074682.
DR GeneID; 67917; -.
DR KEGG; mmu:67917; -.
DR UCSC; uc008nfj.2; mouse.
DR CTD; 85364; -.
DR MGI; MGI:1915167; Zcchc3.
DR VEuPathDB; HostDB:ENSMUSG00000074682; -.
DR eggNOG; KOG4400; Eukaryota.
DR GeneTree; ENSGT00530000063983; -.
DR HOGENOM; CLU_723532_0_0_1; -.
DR InParanoid; Q8BPK2; -.
DR OMA; QGDESAC; -.
DR OrthoDB; 1535084at2759; -.
DR PhylomeDB; Q8BPK2; -.
DR TreeFam; TF334042; -.
DR BioGRID-ORCS; 67917; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Zcchc3; mouse.
DR PRO; PR:Q8BPK2; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8BPK2; protein.
DR Bgee; ENSMUSG00000074682; Expressed in animal zygote and 259 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0002218; P:activation of innate immune response; IMP:UniProtKB.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; IMP:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB.
DR GO; GO:0009597; P:detection of virus; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:1900246; P:positive regulation of RIG-I signaling pathway; ISS:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IMP:UniProtKB.
DR InterPro; IPR042509; ZCCHC3.
DR InterPro; IPR001878; Znf_CCHC.
DR InterPro; IPR036875; Znf_CCHC_sf.
DR PANTHER; PTHR22639; PTHR22639; 1.
DR Pfam; PF00098; zf-CCHC; 1.
DR SMART; SM00343; ZnF_C2HC; 3.
DR SUPFAM; SSF57756; SSF57756; 1.
DR PROSITE; PS50158; ZF_CCHC; 2.
PE 2: Evidence at transcript level;
KW Antiviral defense; Cytoplasm; DNA-binding; Immunity; Innate immunity;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; RNA-binding;
KW Zinc; Zinc-finger.
FT CHAIN 1..400
FT /note="Zinc finger CCHC domain-containing protein 3"
FT /id="PRO_0000446169"
FT ZN_FING 349..365
FT /note="CCHC-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT ZN_FING 369..384
FT /note="CCHC-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT REGION 1..157
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..63
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 90..106
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 198
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9NUD5"
SQ SEQUENCE 400 AA; 43771 MW; 710B3CCFB03DA391 CRC64;
MATGGGAEEE SQRGRPQLPL PARPVARVEE PEGVREKMGW AQVVKNLAEK KGDFREPRRR
DETGSGASGG LGSPGGLATP NPGDFPPAAR GDPKGRRRDP TGEASDAYRK KSASGAGDPS
RRKKAEVTAA MATPARPGTT EDATERPLQD EPPAAGPGKG RFLVRICFQG DESACPTRDF
VVGALILRSI GMDPDDIYAV IQIPGSREFD VSFRSAEKLA LFLRVYEEKR ELEDCWENFV
VLGRSRSSLK TLFILFRNET VDVEDIVTWL KRHCDVLAVP VKVTDRFGIW TGEYKCEIEL
RQGEGGVRHL PGAFFLGAER GYSWYKGQPK TCFKCGSRTH MSGTCTQDRC FRCGEEGHLS
PYCRKVIVCN LCGKRGHAFA QCPKAVHNSV TAQLTSVAGH
