ID   Q5NE14_DANRE            Unreviewed;       511 AA.
AC   Q5NE14; A2RRU6; F6NJL1;
DT   01-FEB-2005, integrated into UniProtKB/TrEMBL.
DT   01-FEB-2005, sequence version 1.
DT   27-MAR-2024, entry version 172.
DE   SubName: Full=Interferon-induced, double-stranded RNA-activated protein kinase {ECO:0000313|RefSeq:NP_001035466.1};
DE   SubName: Full=Protein kinase-containing Z-DNA-binding domains {ECO:0000313|EMBL:AAI31858.1, ECO:0000313|Ensembl:ENSDARP00000033668};
DE   SubName: Full=Z-DNA binding protein kinase {ECO:0000313|EMBL:CAH68526.1};
GN   Name=pkz {ECO:0000313|EMBL:AAI31858.1,
GN   ECO:0000313|Ensembl:ENSDARP00000033668,
GN   ECO:0000313|RefSeq:NP_001035466.1,
GN   ECO:0000313|ZFIN:ZDB-GENE-050301-2};
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955 {ECO:0000313|EMBL:AAI31858.1};
RN   [1] {ECO:0000313|EMBL:CAH68526.1, ECO:0000313|RefSeq:NP_001035466.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=15659550; DOI=10.1073/pnas.0408714102;
RA   Rothenburg S., Deigendesch N., Dittmar K., Koch-Nolte F., Haag F.,
RA   Lowenhaupt K., Rich A.;
RT   "A PKR-like eukaryotic initiation factor 2alpha kinase from zebrafish
RT   contains Z-DNA binding domains instead of dsRNA binding domains.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:1602-1607(2005).
RN   [2] {ECO:0000313|RefSeq:NP_001035466.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=16954046; DOI=10.1051/gse:2006021;
RA   Perelygin A.A., Lear T.L., Zharkikh A.A., Brinton M.A.;
RT   "Comparative analysis of vertebrate EIF2AK2 (PKR) genes and assignment of
RT   the equine gene to ECA15q24-q25 and the bovine gene to BTA11q12-q15.";
RL   Genet. Sel. Evol. 38:551-563(2006).
RN   [3] {ECO:0000313|EMBL:AAI31858.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney {ECO:0000313|EMBL:AAI31858.1}, and Whole
RC   {ECO:0000313|EMBL:AAI15216.1};
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (JAN-2007) to the EMBL/GenBank/DDBJ databases.
RN   [4] {ECO:0000313|RefSeq:NP_001035466.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=18312693;
RA   Rothenburg S., Deigendesch N., Dey M., Dever T.E., Tazi L.;
RT   "Double-stranded RNA-activated protein kinase PKR of fishes and amphibians:
RT   varying the number of double-stranded RNA binding domains and lineage-
RT   specific duplications.";
RL   BMC Biol. 6:12-12(2008).
RN   [5] {ECO:0000313|RefSeq:NP_001035466.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=19265122;
RA   Lopez-Munoz A., Roca F.J., Meseguer J., Mulero V.;
RT   "New insights into the evolution of IFNs: zebrafish group II IFNs induce a
RT   rapid and transient expression of IFN-dependent genes and display powerful
RT   antiviral activities.";
RL   J. Immunol. 182:3440-3449(2009).
RN   [6] {ECO:0000313|RefSeq:NP_001035466.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=19729206; DOI=10.1016/j.vetimm.2009.08.009;
RA   Zenke K., Nam Y.K., Kim K.H.;
RT   "Molecular cloning and expression analysis of double-stranded RNA-dependent
RT   protein kinase (PKR) in rock bream (Oplegnathus fasciatus).";
RL   Vet. Immunol. Immunopathol. 133:290-295(2010).
RN   [7] {ECO:0000313|Ensembl:ENSDARP00000033668}
RP   IDENTIFICATION.
RC   STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000033668};
RG   Ensembl;
RL   Submitted (FEB-2012) to UniProtKB.
RN   [8] {ECO:0000313|Ensembl:ENSDARP00000033668, ECO:0000313|Proteomes:UP000000437}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000033668};
RX   PubMed=23594743; DOI=10.1038/nature12111;
RG   Genome Reference Consortium Zebrafish;
RA   Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA   Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA   Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA   White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA   Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA   Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA   Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA   Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA   Clee C., Oliver K., Clark R., Riddle C., Elliot D., Eliott D.,
RA   Threadgold G., Harden G., Ware D., Begum S., Mortimore B., Mortimer B.,
RA   Kerry G., Heath P., Phillimore B., Tracey A., Corby N., Dunn M.,
RA   Johnson C., Wood J., Clark S., Pelan S., Griffiths G., Smith M.,
RA   Glithero R., Howden P., Barker N., Lloyd C., Stevens C., Harley J.,
RA   Holt K., Panagiotidis G., Lovell J., Beasley H., Henderson C., Gordon D.,
RA   Auger K., Wright D., Collins J., Raisen C., Dyer L., Leung K.,
RA   Robertson L., Ambridge K., Leongamornlert D., McGuire S., Gilderthorp R.,
RA   Griffiths C., Manthravadi D., Nichol S., Barker G., Whitehead S., Kay M.,
RA   Brown J., Murnane C., Gray E., Humphries M., Sycamore N., Barker D.,
RA   Saunders D., Wallis J., Babbage A., Hammond S., Mashreghi-Mohammadi M.,
RA   Barr L., Martin S., Wray P., Ellington A., Matthews N., Ellwood M.,
RA   Woodmansey R., Clark G., Cooper J., Cooper J., Tromans A., Grafham D.,
RA   Skuce C., Pandian R., Andrews R., Harrison E., Kimberley A., Garnett J.,
RA   Fosker N., Hall R., Garner P., Kelly D., Bird C., Palmer S., Gehring I.,
RA   Berger A., Dooley C.M., Ersan-Urun Z., Eser C., Geiger H., Geisler M.,
RA   Karotki L., Kirn A., Konantz J., Konantz M., Oberlander M.,
RA   Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G., Osoegawa K., Zhu B.,
RA   Rapp A., Widaa S., Langford C., Yang F., Schuster S.C., Carter N.P.,
RA   Harrow J., Ning Z., Herrero J., Searle S.M., Enright A., Geisler R.,
RA   Plasterk R.H., Lee C., Westerfield M., de Jong P.J., Zon L.I.,
RA   Postlethwait J.H., Nusslein-Volhard C., Hubbard T.J., Roest Crollius H.,
RA   Rogers J., Stemple D.L.;
RT   "The zebrafish reference genome sequence and its relationship to the human
RT   genome.";
RL   Nature 496:498-503(2013).
RN   [9] {ECO:0007829|PDB:4LB5, ECO:0007829|PDB:4LB6}
RP   X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 5-70.
RX   PubMed=23975196; DOI=10.1093/nar/gkt743;
RA   de Rosa M., Zacarias S., Athanasiadis A.;
RT   "Structural basis for Z-DNA binding and stabilization by the zebrafish Z-
RT   DNA dependent protein kinase PKZ.";
RL   Nucleic Acids Res. 41:9924-9933(2013).
RN   [10] {ECO:0000313|RefSeq:NP_001035466.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=27815423;
RA   Liu X., Cai X., Zhang D., Xu C., Xiao W.;
RT   "Zebrafish foxo3b Negatively Regulates Antiviral Response through
RT   Suppressing the Transactivity of irf3 and irf7.";
RL   J. Immunol. 197:4736-4749(2016).
RN   [11] {ECO:0000313|RefSeq:NP_001035466.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=27351838;
RA   Espin-Palazon R., Martinez-Lopez A., Roca F.J., Lopez-Munoz A.,
RA   Tyrkalska S.D., Candel S., Garcia-Moreno D., Falco A., Meseguer J.,
RA   Estepa A., Mulero V.;
RT   "TNFalpha Impairs Rhabdoviral Clearance by Inhibiting the Host Autophagic
RT   Antiviral Response.";
RL   PLoS Pathog. 12:e1005699-e1005699(2016).
RN   [12] {ECO:0000313|RefSeq:NP_001035466.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=27856245;
RA   Lee A.R., Seo Y.J., Choi S.R., Ryu K.S., Cheong H.K., Lee S.S.,
RA   Katahira M., Park C.J., Lee J.H.;
RT   "NMR elucidation of reduced B-Z transition activity of PKZ protein kinase
RT   at high NaCl concentration.";
RL   Biochem. Biophys. Res. Commun. 482:335-340(2017).
RN   [13] {ECO:0000313|RefSeq:NP_001035466.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=30273864;
RA   Zhang Y., Su G., Li M., Li S., Wang Q., Zhu G., Letcher R.J., Liu C.;
RT   "Chemical and biological transfer: Which one is responsible for the
RT   maternal transfer toxicity of tris(1,3-dichloro-2-propyl) phosphate in
RT   zebrafish?";
RL   Environ. Pollut. 243:1376-1382(2018).
RN   [14] {ECO:0000313|RefSeq:NP_001035466.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=29441066;
RA   Hu Y.W., Zhang J., Wu X.M., Cao L., Nie P., Chang M.X.;
RT   "TANK-Binding Kinase 1 (TBK1) Isoforms Negatively Regulate Type I
RT   Interferon Induction by Inhibiting TBK1-IRF3 Interaction and IRF3
RT   Phosphorylation.";
RL   Front. Immunol. 9:84-84(2018).
RN   [15] {ECO:0000313|RefSeq:NP_001035466.1}
RP   IDENTIFICATION.
RG   RefSeq;
RL   Submitted (NOV-2023) to UniProtKB.
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DR   EMBL; CU929278; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC115215; AAI15216.1; -; mRNA.
DR   EMBL; BC131857; AAI31858.1; -; mRNA.
DR   EMBL; BC162488; AAI62488.1; -; mRNA.
DR   EMBL; AJ852019; CAH68526.1; -; mRNA.
DR   RefSeq; NP_001035466.1; NM_001040376.2.
DR   PDB; 4LB5; X-ray; 2.00 A; A/B=5-70.
DR   PDB; 4LB6; X-ray; 1.80 A; B=5-70.
DR   PDBsum; 4LB5; -.
DR   PDBsum; 4LB6; -.
DR   STRING; 7955.ENSDARP00000033668; -.
DR   PaxDb; 7955-ENSDARP00000033668; -.
DR   Ensembl; ENSDART00000038391.8; ENSDARP00000033668.5; ENSDARG00000052396.7.
DR   GeneID; 503703; -.
DR   KEGG; dre:503703; -.
DR   AGR; ZFIN:ZDB-GENE-050301-2; -.
DR   CTD; 503703; -.
DR   ZFIN; ZDB-GENE-050301-2; pkz.
DR   eggNOG; KOG1033; Eukaryota.
DR   HOGENOM; CLU_049460_0_0_1; -.
DR   OMA; AVVIMEY; -.
DR   OrthoDB; 8734at2759; -.
DR   TreeFam; TF317576; -.
DR   Reactome; R-DRE-9833482; PKR-mediated signaling.
DR   Proteomes; UP000000437; Chromosome 13.
DR   Bgee; ENSDARG00000052396; Expressed in zone of skin and 17 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0003726; F:double-stranded RNA adenosine deaminase activity; IEA:InterPro.
DR   GO; GO:0004694; F:eukaryotic translation initiation factor 2alpha kinase activity; IBA:GO_Central.
DR   GO; GO:0003692; F:left-handed Z-DNA binding; IDA:ZFIN.
DR   GO; GO:0004672; F:protein kinase activity; IDA:ZFIN.
DR   GO; GO:0003723; F:RNA binding; IEA:InterPro.
DR   GO; GO:0048856; P:anatomical structure development; IEA:UniProt.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 2.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   InterPro; IPR036388; WH-like_DNA-bd_sf.
DR   InterPro; IPR036390; WH_DNA-bd_sf.
DR   InterPro; IPR042371; Z_dom.
DR   PANTHER; PTHR11042; EUKARYOTIC TRANSLATION INITIATION FACTOR 2-ALPHA KINASE EIF2-ALPHA KINASE -RELATED; 1.
DR   PANTHER; PTHR11042:SF163; INTERFERON-INDUCED, DOUBLE-STRANDED RNA-ACTIVATED PROTEIN KINASE; 1.
DR   Pfam; PF00069; Pkinase; 2.
DR   Pfam; PF02295; z-alpha; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SMART; SM00550; Zalpha; 2.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   SUPFAM; SSF46785; Winged helix' DNA-binding domain; 2.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   PROSITE; PS50139; Z_BINDING; 1.
PE   1: Evidence at protein level;
KW   3D-structure {ECO:0007829|PDB:4LB5, ECO:0007829|PDB:4LB6};
KW   ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PROSITE-
KW   ProRule:PRU10141};
KW   Kinase {ECO:0000313|EMBL:AAI31858.1, ECO:0000313|RefSeq:NP_001035466.1};
KW   Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741, ECO:0000256|PROSITE-
KW   ProRule:PRU10141}; Reference proteome {ECO:0000313|Proteomes:UP000000437};
KW   RNA-binding {ECO:0000256|ARBA:ARBA00022884};
KW   Transferase {ECO:0000313|EMBL:AAI31858.1,
KW   ECO:0000313|RefSeq:NP_001035466.1}.
FT   DOMAIN          4..69
FT                   /note="Z-binding"
FT                   /evidence="ECO:0000259|PROSITE:PS50139"
FT   DOMAIN          170..499
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000259|PROSITE:PS50011"
FT   REGION          237..281
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        237..256
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        259..281
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         199
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU10141"
SQ   SEQUENCE   511 AA;  58539 MW;  1E7E7695B63B9EEB CRC64;
     MAKMSAENEI EMRICDYLRR HGRSTVQDIF KELKLEKSTV NRHLYSLQAS KQVFKTVEDN
     KRPVWNLVES MNDEQKAKPE QIKPEMTRDA IEEKHVKDLL KSGGLKASHI ASKLGQQTQS
     TNKLLYGLME KGEVRKCSKS HMWTLKNDQE RNGSGSDRKL TSVSGMSQTF DVIEELGDGG
     YGFVCKVKHK IDDKIYAVKR VEFNSEAEPE VKALARLDHP NIVRYFTCWP DSDNWMSNQE
     TNEKSNTTGS STDTDDTNER SASDDDVADD EDDDDDDVSD DVTLGMESLT FTESTSAAKA
     SGQCDPTNHR TYLFIQMEFC EGGTLTSWIG ERNYGGKQRI PLEIHRIFYE ISSGVEYIHS
     NNLIHRDLKP DNILFNDGKV KIGDFGLVAA QKNPSGDPIE RSKRKGTPTY MSPEQENLRN
     YDEKTDIFPL GLMWFEMLWK ISSGMERAEI WTNLRNQKLP DQFCERYTAE NKFIEKMLSV
     TPEDRPHAKD IRLNLETFFS LHQNSLSQKT I
//