ZCCHV_RAT
ID ZCCHV_RAT Reviewed; 776 AA.
AC Q8K3Y6;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 25-MAY-2022, entry version 112.
DE RecName: Full=Zinc finger CCCH-type antiviral protein 1;
DE AltName: Full=ADP-ribosyltransferase diphtheria toxin-like 13;
DE Short=ARTD13;
DE AltName: Full=Inactive Poly [ADP-ribose] polymerase 13 {ECO:0000305};
DE Short=PARP13;
DE AltName: Full=Zinc finger antiviral protein;
DE Short=ZAP;
DE Short=rZAP;
GN Name=Zc3hav1; Synonyms=Zap;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12215647; DOI=10.1126/science.1074276;
RA Gao G., Guo X., Goff S.P.;
RT "Inhibition of retroviral RNA production by ZAP, a CCCH-type zinc finger
RT protein.";
RL Science 297:1703-1706(2002).
RN [2]
RP PROTEIN SEQUENCE OF 227-238; 341-349; 359-371 AND 548-562, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Lubec G., Kang S.U., Lubec S.;
RL Submitted (SEP-2007) to UniProtKB.
RN [3]
RP FUNCTION.
RX PubMed=14557641; DOI=10.1128/jvi.77.21.11555-11562.2003;
RA Bick M.J., Carroll J.W., Gao G., Goff S.P., Rice C.M., McDonald M.R.;
RT "Expression of the zinc-finger antiviral protein inhibits alphavirus
RT replication.";
RL J. Virol. 77:11555-11562(2003).
RN [4]
RP SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, AND NUCLEAR EXPORT
RP SIGNAL.
RX PubMed=15358138; DOI=10.1016/j.bbrc.2004.06.174;
RA Liu L., Chen G., Ji X., Gao G.;
RT "ZAP is a CRM1-dependent nucleocytoplasmic shuttling protein.";
RL Biochem. Biophys. Res. Commun. 321:517-523(2004).
RN [5]
RP RNA-BINDING.
RX PubMed=15542630; DOI=10.1128/jvi.78.23.12781-12787.2004;
RA Guo X., Carroll J.-W., McDonald M.R., Goff S.P., Gao G.;
RT "The zinc finger antiviral protein directly binds to specific viral mRNAs
RT through the CCCH zinc finger motifs.";
RL J. Virol. 78:12781-12787(2004).
RN [6]
RP FUNCTION.
RX PubMed=17182693; DOI=10.1128/jvi.01601-06;
RA Mueller S., Moeller P., Bick M.J., Wurr S., Becker S., Guenther S.,
RA Kuemmerer B.M.;
RT "Inhibition of filovirus replication by the zinc finger antiviral
RT protein.";
RL J. Virol. 81:2391-2400(2007).
RN [7]
RP FUNCTION, AND INTERACTION WITH EXOSC5.
RX PubMed=17185417; DOI=10.1073/pnas.0607063104;
RA Guo X., Ma J., Sun J., Gao G.;
RT "The zinc-finger antiviral protein recruits the RNA processing exosome to
RT degrade the target mRNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:151-156(2007).
RN [8]
RP FUNCTION, INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17928353; DOI=10.1128/jvi.00402-07;
RA MacDonald M.R., Machlin E.S., Albin O.R., Levy D.E.;
RT "The zinc finger antiviral protein acts synergistically with an interferon-
RT induced factor for maximal activity against alphaviruses.";
RL J. Virol. 81:13509-13518(2007).
RN [9]
RP FUNCTION.
RX PubMed=18225958; DOI=10.1371/journal.pgen.0040021;
RA Kerns J.A., Emerman M., Malik H.S.;
RT "Positive selection and increased antiviral activity associated with the
RT PARP-containing isoform of human zinc-finger antiviral protein.";
RL PLoS Genet. 4:E21-E21(2008).
RN [10]
RP INTERACTION WITH DDX17.
RX PubMed=18334637; DOI=10.1073/pnas.0712276105;
RA Chen G., Guo X., Lv F., Xu Y., Gao G.;
RT "p72 DEAD box RNA helicase is required for optimal function of the zinc-
RT finger antiviral protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:4352-4357(2008).
RN [11]
RP SUBUNIT, AND MUTAGENESIS OF CYS-88.
RX PubMed=20181706; DOI=10.1128/jvi.02018-09;
RA Law L.M., Albin O.R., Carroll J.W., Jones C.T., Rice C.M., Macdonald M.R.;
RT "Identification of a dominant negative inhibitor of human zinc finger
RT antiviral protein reveals a functional endogenous pool and critical
RT homotypic interactions.";
RL J. Virol. 84:4504-4512(2010).
RN [12]
RP INTERACTION WITH DHX30.
RX PubMed=21204022; DOI=10.1007/s13238-010-0117-8;
RA Ye P., Liu S., Zhu Y., Chen G., Gao G.;
RT "DEXH-Box protein DHX30 is required for optimal function of the zinc-finger
RT antiviral protein.";
RL Protein Cell 1:956-964(2010).
RN [13]
RP FUNCTION, AND INTERACTION WITH EXOSC5.
RX PubMed=21876179; DOI=10.1073/pnas.1101676108;
RA Zhu Y., Chen G., Lv F., Wang X., Ji X., Xu Y., Sun J., Wu L., Zheng Y.T.,
RA Gao G.;
RT "Zinc-finger antiviral protein inhibits HIV-1 infection by selectively
RT targeting multiply spliced viral mRNAs for degradation.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:15834-15839(2011).
RN [14]
RP PHOSPHORYLATION AT SER-257; SER-262; SER-266; SER-270 AND SER-274.
RX PubMed=22514281; DOI=10.1074/jbc.m111.306373;
RA Sun L., Lv F., Guo X., Gao G.;
RT "Glycogen synthase kinase 3? (GSK3?) modulates antiviral activity of zinc-
RT finger antiviral protein (ZAP).";
RL J. Biol. Chem. 287:22882-22888(2012).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266; SER-270; SER-274 AND
RP SER-325, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-225, SUBUNIT, RNA-BINDING, AND
RP DOMAIN N-TERMINAL.
RX PubMed=22407013; DOI=10.1038/nsmb.2243;
RA Chen S., Xu Y., Zhang K., Wang X., Sun J., Gao G., Liu Y.;
RT "Structure of N-terminal domain of ZAP indicates how a zinc-finger protein
RT recognizes complex RNA.";
RL Nat. Struct. Mol. Biol. 19:430-435(2012).
CC -!- FUNCTION: Antiviral protein which inhibits the replication of viruses
CC by recruiting the cellular RNA degradation machineries to degrade the
CC viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the
CC target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN
CC to remove the poly(A) tail, and the 3'-5' exoribonuclease complex
CC exosome to degrade the RNA body from the 3'-end. It also recruits the
CC decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove
CC the cap structure of the viral mRNA to initiate its degradation from
CC the 5'-end. Its target viruses belong to families which include
CC retroviridae: human immunodeficiency virus type 1 (HIV-1) and moloney
CC and murine leukemia virus (MoMLV), filoviridae: ebola virus (EBOV) and
CC marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river
CC virus (RRV). Specifically targets the multiply spliced but not
CC unspliced or singly spliced HIV-1 mRNAs for degradation.
CC {ECO:0000269|PubMed:12215647, ECO:0000269|PubMed:14557641,
CC ECO:0000269|PubMed:17182693, ECO:0000269|PubMed:17185417,
CC ECO:0000269|PubMed:17928353, ECO:0000269|PubMed:18225958,
CC ECO:0000269|PubMed:21876179}.
CC -!- SUBUNIT: Homodimer or homooligomer. Homooligomerization is essential
CC for its antiviral activity. Interacts with EXOSC5. Interacts with
CC EXOSC3, EXOSC7, DCP2 and DCP1A (By similarity). Interacts with PARN in
CC an RNA-independent manner (By similarity). Interacts with XRN1 in an
CC RNA-dependent manner (By similarity). Interacts (via N-terminal domain)
CC with DHX30 (via N-terminus) in an RNA-independent manner. Interacts
CC (via N-terminal domain) with DDX17 in an RNA-independent manner.
CC {ECO:0000250, ECO:0000269|PubMed:17185417, ECO:0000269|PubMed:18334637,
CC ECO:0000269|PubMed:20181706, ECO:0000269|PubMed:21204022,
CC ECO:0000269|PubMed:21876179, ECO:0000269|PubMed:22407013}.
CC -!- INTERACTION:
CC Q8K3Y6; Q8K3Y6: Zc3hav1; NbExp=3; IntAct=EBI-8860250, EBI-8860250;
CC Q8K3Y6; Q92841: DDX17; Xeno; NbExp=6; IntAct=EBI-8860250, EBI-746012;
CC Q8K3Y6; Q9NQT5: EXOSC3; Xeno; NbExp=3; IntAct=EBI-8860250, EBI-371866;
CC Q8K3Y6; Q9NQT4: EXOSC5; Xeno; NbExp=6; IntAct=EBI-8860250, EBI-371876;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15358138,
CC ECO:0000269|PubMed:17928353}. Nucleus {ECO:0000269|PubMed:15358138}.
CC Note=Localizes in the cytoplasm at steady state, but shuttles between
CC nucleus and cytoplasm in a XPO1-dependent manner.
CC {ECO:0000269|PubMed:15358138}.
CC -!- TISSUE SPECIFICITY: Expressed in the kidney and liver.
CC {ECO:0000269|PubMed:12215647}.
CC -!- INDUCTION: By type I interferon (IFN) and viruses.
CC {ECO:0000269|PubMed:17928353}.
CC -!- DOMAIN: The N-terminal domain is sufficient to bind to viral RNAs and
CC promote their degradation. The second and fourth zinc fingers are
CC involved in binding to specific viral RNAs. Contains a divergent PARP
CC homology ADP-ribosyltransferase domain which lacks the structural
CC requirements for NAD[+] binding. It is therefore inactive.
CC {ECO:0000250|UniProtKB:Q7Z2W4}.
CC -!- PTM: Phosphorylation at Ser-274 is essential for sequential
CC phosphorylation of Ser-270, Ser-266, Ser-262 and Ser-257 by GSK3-beta.
CC Phosphorylation by GSK3-beta enhances its antiviral activity.
CC {ECO:0000269|PubMed:22514281}.
CC -!- SIMILARITY: Belongs to the ARTD/PARP family. {ECO:0000305}.
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DR EMBL; AF521008; AAM75358.1; -; mRNA.
DR PDB; 3U9G; X-ray; 1.80 A; A=1-225.
DR PDBsum; 3U9G; -.
DR AlphaFoldDB; Q8K3Y6; -.
DR SMR; Q8K3Y6; -.
DR DIP; DIP-29842N; -.
DR IntAct; Q8K3Y6; 7.
DR STRING; 10116.ENSRNOP00000018782; -.
DR iPTMnet; Q8K3Y6; -.
DR PhosphoSitePlus; Q8K3Y6; -.
DR jPOST; Q8K3Y6; -.
DR PaxDb; Q8K3Y6; -.
DR PRIDE; Q8K3Y6; -.
DR UCSC; RGD:628694; rat.
DR RGD; 628694; Zc3hav1.
DR eggNOG; ENOG502QSC4; Eukaryota.
DR InParanoid; Q8K3Y6; -.
DR PhylomeDB; Q8K3Y6; -.
DR PRO; PR:Q8K3Y6; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IDA:RGD.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; ISO:RGD.
DR GO; GO:0098586; P:cellular response to virus; IMP:RGD.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0045071; P:negative regulation of viral genome replication; IDA:UniProtKB.
DR GO; GO:0061014; P:positive regulation of mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; ISO:RGD.
DR GO; GO:0050691; P:regulation of defense response to virus by host; IDA:RGD.
DR GO; GO:0009615; P:response to virus; IDA:UniProtKB.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.30.720.50; -; 1.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR004170; WWE-dom.
DR InterPro; IPR037197; WWE_dom_sf.
DR InterPro; IPR041360; ZAP_HTH.
DR InterPro; IPR040954; Znf-CCCH_8.
DR InterPro; IPR000571; Znf_CCCH.
DR Pfam; PF18606; HTH_53; 1.
DR Pfam; PF02825; WWE; 1.
DR Pfam; PF18633; zf-CCCH_8; 1.
DR SUPFAM; SSF117839; SSF117839; 1.
DR PROSITE; PS50918; WWE; 1.
DR PROSITE; PS50103; ZF_C3H1; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Antiviral defense; Cytoplasm;
KW Direct protein sequencing; Immunity; Innate immunity; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; RNA-binding; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2W4"
FT CHAIN 2..776
FT /note="Zinc finger CCCH-type antiviral protein 1"
FT /id="PRO_0000211344"
FT DOMAIN 671..758
FT /note="WWE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT ZN_FING 73..86
FT /note="C3H1-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 88..110
FT /note="C3H1-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 150..172
FT /note="C3H1-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 169..193
FT /note="C3H1-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT REGION 2..254
FT /note="N-terminal domain"
FT REGION 221..249
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 224..254
FT /note="Binding to EXOSC5"
FT REGION 308..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 457..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 512..562
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 69..76
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:15358138"
FT MOTIF 284..291
FT /note="Nuclear export signal"
FT MOTIF 405..406
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 228..245
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 308..328
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 339..354
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2W4"
FT MOD_RES 257
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000269|PubMed:22514281"
FT MOD_RES 262
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000269|PubMed:22514281"
FT MOD_RES 266
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000269|PubMed:22514281,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 270
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000269|PubMed:22514281,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22514281,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 278
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q3UPF5"
FT MOD_RES 283
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2W4"
FT MOD_RES 325
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 351
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2W4"
FT MOD_RES 398
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2W4"
FT MOD_RES 501
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q3UPF5"
FT MOD_RES 544
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UPF5"
FT MOD_RES 667
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2W4"
FT MUTAGEN 88
FT /note="C->R: Results in a non-functional protein with a
FT dominant negative phenotype."
FT /evidence="ECO:0000269|PubMed:20181706"
FT HELIX 9..16
FT /evidence="ECO:0007829|PDB:3U9G"
FT TURN 17..19
FT /evidence="ECO:0007829|PDB:3U9G"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:3U9G"
FT HELIX 23..30
FT /evidence="ECO:0007829|PDB:3U9G"
FT HELIX 34..44
FT /evidence="ECO:0007829|PDB:3U9G"
FT TURN 46..48
FT /evidence="ECO:0007829|PDB:3U9G"
FT STRAND 49..53
FT /evidence="ECO:0007829|PDB:3U9G"
FT STRAND 62..66
FT /evidence="ECO:0007829|PDB:3U9G"
FT HELIX 89..92
FT /evidence="ECO:0007829|PDB:3U9G"
FT HELIX 97..99
FT /evidence="ECO:0007829|PDB:3U9G"
FT HELIX 115..123
FT /evidence="ECO:0007829|PDB:3U9G"
FT HELIX 131..139
FT /evidence="ECO:0007829|PDB:3U9G"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:3U9G"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:3U9G"
FT STRAND 163..166
FT /evidence="ECO:0007829|PDB:3U9G"
FT HELIX 175..178
FT /evidence="ECO:0007829|PDB:3U9G"
FT HELIX 196..205
FT /evidence="ECO:0007829|PDB:3U9G"
FT HELIX 209..223
FT /evidence="ECO:0007829|PDB:3U9G"
SQ SEQUENCE 776 AA; 86771 MW; D13F61A9F8E5B552 CRC64;
MADPGVCCFI TKILCAHGGR MTLEELLGEI RLPEAQLYEL LETAGPDRFV LLETGGQAGI
TRSVVATTRA RVCRRKYCQR PCDSLHLCKL NLLGRCHYAQ SQRNLCKYSH DVLSEQNFQI
LKNHELSGLN QEELACLLVQ SDPFFLPEIC KSYKGEGRKQ TCGQPQPCER LHICEHFTRG
NCSYLNCLRS HNLMDRKVLT IMREHGLSPD VVQNIQDICN NKHARRNPPG TRAAHPHRRG
GAHRDRSKSR DRFLHNSLEF LSPVVSPLGS GPPSPDVTSC KDSLEDVSVD VTQKFKYLGT
HDRAQLSPVS SKAAGVQGPS QMRASQEFSE DGNLDDIFSR NRSDSSSSRA SAAKVAQRNE
AVAMKMGMEV KGKKEAPDID RVPFLNSYID GVTMEKASVS GIPGKKFTAN DLENLLLLND
TWKNVAKPQD LQTTGRITDS GQDKAFLQNK YGGNPVWASA STHNAPNGSS QIMDETPNVS
KSSTSGFAIK PAIAGGKEAV YSGVQSPRSQ VLAVPGEATT PVQSNRLPQS PLSSSSHRAA
ASGSPGKNST HTSVSPAIES SRMTSDPDEY LLRYILNPLF RMDNHGPKEI CQDHLYKGCQ
QSHCDRSHFH LPYRWQMFVY TTWRDFQDME SIEQAYCDPH VELILIENHQ INFQKMTCDS
YPIRRLSTPS YEEKPLSAVF ATKWIWYWKN EFNEYIQYGN ESPGHTSSDI NSAYLESFFQ
SCPRGVLPFQ AGSQKYELSF QGMIQTNIAS KTQRHVVRRP VFVSSNDVEQ KRRGPE
