ZCHC3_HUMAN
ID ZCHC3_HUMAN Reviewed; 403 AA.
AC Q9NUD5; Q3B7J3; Q6NT79;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 07-NOV-2018, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Zinc finger CCHC domain-containing protein 3 {ECO:0000305};
GN Name=ZCCHC3 {ECO:0000312|HGNC:HGNC:16230};
GN Synonyms=C20orf99 {ECO:0000312|HGNC:HGNC:16230};
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Liver;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-201, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [5]
RP FUNCTION, AND INTERACTION WITH IFIH1 AND DDX58.
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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CGAS.
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 (PubMed:30135424). Binds dsDNA and probably acts by promoting
CC sensing of dsDNA by CGAS, leading to enhance CGAS oligomerization and
CC activation (PubMed:30135424). Promotes sensing of viral RNA by RIG-I-
CC like receptors proteins DDX58/RIG-I and IFIH1/MDA5 via two mechanisms:
CC binds double-stranded RNA (dsRNA), enhancing the binding of DDX58/RIG-I
CC and IFIH1/MDA5 to dsRNA and promotes 'Lys-63'-linked ubiquitination and
CC subsequent activation of DDX58/RIG-I and IFIH1/MDA5 (PubMed:30193849).
CC {ECO:0000269|PubMed:30135424, ECO:0000269|PubMed:30193849}.
CC -!- SUBUNIT: Interacts with CGAS (PubMed:30135424). Interacts with
CC DDX58/RIG-I (PubMed:30193849). Interacts with IFIH1/MDA5
CC (PubMed:30193849). {ECO:0000269|PubMed:30135424,
CC ECO:0000269|PubMed:30193849}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:30135424}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NUD5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NUD5-2; Sequence=VSP_055996;
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; AL034548; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069238; AAH69238.1; -; mRNA.
DR EMBL; BC107584; AAI07585.1; -; mRNA.
DR CCDS; CCDS42844.1; -. [Q9NUD5-1]
DR RefSeq; NP_149080.2; NM_033089.6. [Q9NUD5-1]
DR AlphaFoldDB; Q9NUD5; -.
DR BioGRID; 124492; 157.
DR IntAct; Q9NUD5; 42.
DR STRING; 9606.ENSP00000484056; -.
DR iPTMnet; Q9NUD5; -.
DR PhosphoSitePlus; Q9NUD5; -.
DR BioMuta; ZCCHC3; -.
DR DMDM; 23396534; -.
DR EPD; Q9NUD5; -.
DR jPOST; Q9NUD5; -.
DR MassIVE; Q9NUD5; -.
DR PaxDb; Q9NUD5; -.
DR PeptideAtlas; Q9NUD5; -.
DR PRIDE; Q9NUD5; -.
DR ProteomicsDB; 82664; -. [Q9NUD5-1]
DR Antibodypedia; 72721; 66 antibodies from 20 providers.
DR DNASU; 85364; -.
DR Ensembl; ENST00000500893.4; ENSP00000484056.1; ENSG00000247315.4. [Q9NUD5-1]
DR GeneID; 85364; -.
DR KEGG; hsa:85364; -.
DR MANE-Select; ENST00000500893.4; ENSP00000484056.1; NM_033089.7; NP_149080.2.
DR UCSC; uc032oxz.2; human. [Q9NUD5-1]
DR CTD; 85364; -.
DR DisGeNET; 85364; -.
DR GeneCards; ZCCHC3; -.
DR HGNC; HGNC:16230; ZCCHC3.
DR HPA; ENSG00000247315; Low tissue specificity.
DR MIM; 618326; gene.
DR neXtProt; NX_Q9NUD5; -.
DR OpenTargets; ENSG00000247315; -.
DR PharmGKB; PA25806; -.
DR VEuPathDB; HostDB:ENSG00000247315; -.
DR eggNOG; KOG4400; Eukaryota.
DR GeneTree; ENSGT00530000063983; -.
DR HOGENOM; CLU_723532_0_0_1; -.
DR InParanoid; Q9NUD5; -.
DR OMA; QGDESAC; -.
DR OrthoDB; 1535084at2759; -.
DR PhylomeDB; Q9NUD5; -.
DR TreeFam; TF334042; -.
DR PathwayCommons; Q9NUD5; -.
DR SignaLink; Q9NUD5; -.
DR BioGRID-ORCS; 85364; 17 hits in 1082 CRISPR screens.
DR ChiTaRS; ZCCHC3; human.
DR GenomeRNAi; 85364; -.
DR Pharos; Q9NUD5; Tdark.
DR PRO; PR:Q9NUD5; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9NUD5; protein.
DR Bgee; ENSG00000247315; Expressed in ileal mucosa and 179 other tissues.
DR Genevisible; Q9NUD5; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0002218; P:activation of innate immune response; IDA:UniProtKB.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; IMP:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IBA:GO_Central.
DR GO; GO:0009597; P:detection of virus; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:1900246; P:positive regulation of RIG-I signaling pathway; IDA:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IBA:GO_Central.
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 1: Evidence at protein level;
KW Alternative splicing; Antiviral defense; Cytoplasm; DNA-binding; Immunity;
KW Innate immunity; Metal-binding; Phosphoprotein; Reference proteome; Repeat;
KW RNA-binding; Zinc; Zinc-finger.
FT CHAIN 1..403
FT /note="Zinc finger CCHC domain-containing protein 3"
FT /id="PRO_0000150951"
FT ZN_FING 335..350
FT /note="CCHC-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT ZN_FING 352..368
FT /note="CCHC-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT ZN_FING 372..387
FT /note="CCHC-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT REGION 1..158
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..17
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..65
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 94..126
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 201
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT VAR_SEQ 49..212
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055996"
FT CONFLICT 262
FT /note="E -> D (in Ref. 2; AAI07585)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 403 AA; 43547 MW; 692792D8A7BC00E8 CRC64;
MATGGGAEEE RKRGRPQLLP PARPAARGEE ADGGREKMGW AQVVKNLAEK KGEFREPRPP
RREEESGGGG GSAGLGGPAG LAAPDLGDFP PAGRGDPKGR RRDPAGEAVD PRKKKGAAEA
GRRKKAEAAA AAMATPARPG EAEDAAERPL QDEPAAAAGP GKGRFLVRIC FQGDEGACPT
RDFVVGALIL RSIGMDPSDI YAVIQIPGSR EFDVSFRSAE KLALFLRVYE EKREQEDCWE
NFVVLGRSKS SLKTLFILFR NETVDVEDIV TWLKRHCDVL AVPVKVTDRF GIWTGEYKCE
IELRQGEGGV RHLPGAFFLG AERGYSWYKG QPKTCFKCGS RTHMSGSCTQ DRCFRCGEEG
HLSPYCRKGI VCNLCGKRGH AFAQCPKAVH NSVAAQLTGV AGH
