ZBP1_HUMAN
ID ZBP1_HUMAN Reviewed; 429 AA.
AC Q9H171; A2A2F7; B3KVA1; F5GYT1; Q5JY39; Q9BYW4;
DT 25-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Z-DNA-binding protein 1 {ECO:0000303|PubMed:16876127};
DE AltName: Full=DNA-dependent activator of IFN-regulatory factors {ECO:0000303|PubMed:19095800};
DE Short=DAI {ECO:0000303|PubMed:19095800};
DE AltName: Full=Tumor stroma and activated macrophage protein DLM-1 {ECO:0000303|PubMed:11842111};
GN Name=ZBP1 {ECO:0000303|PubMed:16876127, ECO:0000312|HGNC:HGNC:16176};
GN Synonyms=C20orf183 {ECO:0000312|HGNC:HGNC:16176},
GN DLM1 {ECO:0000303|PubMed:11842111};
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 [MRNA], TISSUE SPECIFICITY, ALTERNATIVE SPLICING, AND
RP VARIANTS LYS-88 AND ARG-258.
RC TISSUE=Spleen;
RX PubMed=11842111; DOI=10.1093/nar/30.4.993;
RA Rothenburg S., Schwartz T., Koch-Nolte F., Haag F.;
RT "Complex regulation of the human gene for the Z-DNA binding protein DLM-
RT 1.";
RL Nucleic Acids Res. 30:993-1000(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6), AND VARIANT LYS-88.
RC TISSUE=T-cell;
RA Heil O., Ebert L., Hennig S., Henze S., Radelof U., Schneider D., Korn B.;
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7), AND VARIANT ARG-258.
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-258.
RA Mural R.J., Istrail S., Sutton 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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Blood;
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.
RX PubMed=16876127; DOI=10.1016/j.bbrc.2006.07.061;
RA Pham H.T., Park M.Y., Kim K.K., Kim Y.G., Ahn J.H.;
RT "Intracellular localization of human ZBP1: Differential regulation by the
RT Z-DNA binding domain, Zalpha, in splice variants.";
RL Biochem. Biophys. Res. Commun. 348:145-152(2006).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=16990255; DOI=10.1093/nar/gkl575;
RA Deigendesch N., Koch-Nolte F., Rothenburg S.;
RT "ZBP1 subcellular localization and association with stress granules is
RT controlled by its Z-DNA binding domains.";
RL Nucleic Acids Res. 34:5007-5020(2006).
RN [9]
RP INTERACTION WITH HUMAN HERPESVIRUS 1 ICP0 (MICROBIAL INFECTION).
RX PubMed=23283962; DOI=10.1128/jvi.02860-12;
RA Pham T.H., Kwon K.M., Kim Y.E., Kim K.K., Ahn J.H.;
RT "DNA sensing-independent inhibition of herpes simplex virus 1 replication
RT by DAI/ZBP1.";
RL J. Virol. 87:3076-3086(2013).
RN [10]
RP REVIEW.
RX PubMed=29236673; DOI=10.1016/j.it.2017.11.002;
RA Kuriakose T., Kanneganti T.D.;
RT "ZBP1: innate sensor regulating cell death and inflammation.";
RL Trends Immunol. 39:123-134(2018).
RN [11]
RP FUNCTION.
RX PubMed=32200799; DOI=10.1016/j.cell.2020.02.050;
RA Zhang T., Yin C., Boyd D.F., Quarato G., Ingram J.P., Shubina M.,
RA Ragan K.B., Ishizuka T., Crawford J.C., Tummers B., Rodriguez D.A., Xue J.,
RA Peri S., Kaiser W.J., Lopez C.B., Xu Y., Upton J.W., Thomas P.G.,
RA Green D.R., Balachandran S.;
RT "Influenza virus Z-RNAs induce ZBP1-mediated necroptosis.";
RL Cell 180:1115-1129(2020).
RN [12]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH HHV-1 PROTEIN RIR1
RP (MICROBIAL INFECTION), AND DOMAIN (MICROBIAL INFECTION).
RX PubMed=33348174; DOI=10.1016/j.bpc.2020.106524;
RA Shanmugam N., Baker M.O.D.G., Sanz-Hernandez M., Sierecki E., Gambin Y.,
RA Steain M., Pham C.L.L., Sunde M.;
RT "Herpes simplex virus encoded ICP6 protein forms functional amyloid
RT assemblies with necroptosis-associated host proteins.";
RL Biophys. Chem. 269:106524-106524(2021).
RN [13]
RP CRYSTALLIZATION.
RX PubMed=16448869; DOI=10.1016/j.bbapap.2005.12.012;
RA Ha S.C., Van Quyen D., Hwang H.Y., Oh D.B., Brown B.A. II, Lee S.M.,
RA Park H.J., Ahn J.H., Kim K.K., Kim Y.G.;
RT "Biochemical characterization and preliminary X-ray crystallographic study
RT of the domains of human ZBP1 bound to left-handed Z-DNA.";
RL Biochim. Biophys. Acta 1764:320-323(2006).
RN [14] {ECO:0007744|PDB:3EYI}
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 103-166, AND DNA-BINDING.
RX PubMed=19095800; DOI=10.1073/pnas.0810463106;
RA Ha S.C., Kim D., Hwang H.Y., Rich A., Kim Y.G., Kim K.K.;
RT "The crystal structure of the second Z-DNA binding domain of human DAI
RT (ZBP1) in complex with Z-DNA reveals an unusual binding mode to Z-DNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:20671-20676(2008).
RN [15] {ECO:0007744|PDB:2L4M}
RP STRUCTURE BY NMR OF 103-166.
RX PubMed=21471454; DOI=10.1073/pnas.1014898107;
RA Kim K., Khayrutdinov B.I., Lee C.K., Cheong H.K., Kang S.W., Park H.,
RA Lee S., Kim Y.G., Jee J., Rich A., Kim K.K., Jeon Y.H.;
RT "Solution structure of the Zbeta domain of human DNA-dependent activator of
RT IFN-regulatory factors and its binding modes to B- and Z-DNAs.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:6921-6926(2011).
RN [16] {ECO:0007744|PDB:2LNB}
RP STRUCTURE BY NMR OF 6-74.
RX PubMed=25173411; DOI=10.1007/s10858-014-9858-7;
RA Yang Y., Ramelot T.A., Lee H.W., Xiao R., Everett J.K., Montelione G.T.,
RA Prestegard J.H., Kennedy M.A.;
RT "Solution structure of the free Zalpha domain of human DLM-1 (ZBP1/DAI), a
RT Z-DNA binding domain.";
RL J. Biomol. NMR 60:189-195(2014).
CC -!- FUNCTION: Key innate sensor that recognizes and binds Z-RNA structures,
CC which are produced by a number of viruses, such as herpesvirus,
CC orthomyxovirus or flavivirus, and triggers different forms of cell
CC death (PubMed:32200799). ZBP1 acts as an essential mediator of
CC pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of
CC host defense against pathogens, by activating RIPK3, caspase-8 (CASP8),
CC and the NLRP3 inflammasome (By similarity). Key activator of
CC necroptosis, a programmed cell death process in response to death-
CC inducing TNF-alpha family members, via its ability to bind Z-RNA: once
CC activated upon Z-RNA-binding, ZBP1 interacts and stimulates RIPK3
CC kinase, which phosphorylates and activates MLKL, triggering execution
CC of programmed necrosis (By similarity). In addition to TNF-induced
CC necroptosis, necroptosis can also take place in the nucleus in response
CC to orthomyxoviruses infection: ZBP1 recognizes and binds Z-RNA
CC structures that are produced in infected nuclei by orthomyxoviruses,
CC such as the influenza A virus (IAV), leading to ZBP1 activation, RIPK3
CC stimulation and subsequent MLKL phosphorylation, triggering disruption
CC of the nuclear envelope and leakage of cellular DNA into the cytosol
CC (PubMed:32200799). ZBP1-dependent cell death in response to IAV
CC infection promotes interleukin-1 alpha (IL1A) induction in an NLRP3-
CC inflammasome-independent manner: IL1A expression is required for the
CC optimal interleukin-1 beta (IL1B) production, and together, these
CC cytokines promote infiltration of inflammatory neutrophils to the lung,
CC leading to the formation of neutrophil extracellular traps (By
CC similarity). In addition to its direct role in driving necroptosis via
CC its ability to sense Z-RNAs, also involved in PANoptosis triggered in
CC response to bacterial infection: component of the AIM2 PANoptosome
CC complex, a multiprotein complex that triggers PANoptosis (By
CC similarity). Also acts as the apical sensor of fungal infection
CC responsible for activating PANoptosis (By similarity). Involved in
CC CASP8-mediated cell death via its interaction with RIPK1 but
CC independently of its ability to sense Z-RNAs (By similarity). In some
CC cell types, also able to restrict viral replication by promoting cell
CC death-independent responses (By similarity). In response to Zika virus
CC infection in neurons, promotes a cell death-independent pathway that
CC restricts viral replication: together with RIPK3, promotes a death-
CC independent transcriptional program that modifies the cellular
CC metabolism via up-regulation expression of the enzyme ACOD1/IRG1 and
CC production of the metabolite itaconate (By similarity). Itaconate
CC inhibits the activity of succinate dehydrogenase, generating a
CC metabolic state in neurons that suppresses replication of viral genomes
CC (By similarity). {ECO:0000250|UniProtKB:Q9QY24,
CC ECO:0000269|PubMed:32200799}.
CC -!- FUNCTION: (Microbial infection) In case of herpes simplex virus 1/HHV-1
CC infection, forms hetero-amyloid structures with HHV-1 protein RIR1/ICP6
CC which may inhibit ZBP1-mediated necroptosis, thereby preventing host
CC cell death pathway and allowing viral evasion.
CC {ECO:0000269|PubMed:33348174}.
CC -!- ACTIVITY REGULATION: ZBP1-dependent necroptosis is normally inhibited
CC by RIPK1: RIPK1 inhibits the ZBP1-induced activation of RIPK3 via FADD-
CC mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-
CC induced necroptosis. {ECO:0000250|UniProtKB:Q9QY24}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts (via RIP homotypic
CC interaction motif) with RIPK3; leading to RIPK3 activation and
CC necroptosis; interaction is enhanced by CASP6 (By similarity).
CC Interacts (via RIP homotypic interaction motif) with RIPK1 (By
CC similarity). Component of the AIM2 PANoptosome complex, a multiprotein
CC complex that drives inflammatory cell death (PANoptosis) (By
CC similarity). {ECO:0000250|UniProtKB:Q9QY24}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via RIP homotypic interaction
CC motif/RHIM) with herpes simplex virus 1/HHV-1 protein RIR1/ICP6 (via
CC RHIM); this interaction may induce heteromeric amyloid assemblies and
CC prevent necroptosis activation (PubMed:33348174). Interacts with human
CC herpes simplex virus 1/HHV-1 protein ICP0 (Probable).
CC {ECO:0000269|PubMed:33348174, ECO:0000305|PubMed:23283962}.
CC -!- INTERACTION:
CC Q9H171; P42858: HTT; NbExp=6; IntAct=EBI-6264672, EBI-466029;
CC Q9H171; Q13601: KRR1; NbExp=3; IntAct=EBI-6264672, EBI-744525;
CC Q9H171; Q9Y572: RIPK3; NbExp=4; IntAct=EBI-6264672, EBI-298250;
CC Q9H171-1; Q9H171-1: ZBP1; NbExp=2; IntAct=EBI-15747763, EBI-15747763;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16876127,
CC ECO:0000269|PubMed:16990255}. Nucleus {ECO:0000269|PubMed:16876127,
CC ECO:0000269|PubMed:16990255}. Note=Mainly cytoplasmic (PubMed:16876127,
CC PubMed:16990255). Accumulates in the nucleus in response to influenza A
CC virus (IAV) infection: senses IAV defective viral genomes RNA in the
CC nucleus (By similarity). {ECO:0000250|UniProtKB:Q9QY24,
CC ECO:0000269|PubMed:16876127, ECO:0000269|PubMed:16990255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 7]: Cytoplasm
CC {ECO:0000269|PubMed:16876127, ECO:0000269|PubMed:16990255}. Nucleus
CC {ECO:0000269|PubMed:16876127, ECO:0000269|PubMed:16990255}.
CC Note=Compared to isoform 1, a higher proportion of this isoform is
CC localized in the nucleus. {ECO:0000269|PubMed:16876127,
CC ECO:0000269|PubMed:16990255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=Q9H171-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H171-2; Sequence=VSP_004081;
CC Name=3;
CC IsoId=Q9H171-3; Sequence=VSP_004082;
CC Name=4;
CC IsoId=Q9H171-4; Sequence=VSP_004078;
CC Name=5;
CC IsoId=Q9H171-5; Sequence=VSP_004079, VSP_004080;
CC Name=6;
CC IsoId=Q9H171-6; Sequence=VSP_045405, VSP_045406;
CC Name=7; Synonyms=Delta-exon-2 {ECO:0000303|PubMed:16876127},
CC Deltaexon-2 {ECO:0000303|PubMed:16876127}, Delta-Z-alpha
CC {ECO:0000303|PubMed:16990255}, DeltaZalpha
CC {ECO:0000303|PubMed:16990255};
CC IsoId=Q9H171-7; Sequence=VSP_046081;
CC -!- TISSUE SPECIFICITY: Highly expressed in lymphatic tissues including
CC lymph node, leukocytes, tonsil, bone marrow and spleen
CC (PubMed:11842111). Expressed to a lesser extent in thymus, lung and
CC liver (PubMed:11842111). {ECO:0000269|PubMed:11842111}.
CC -!- DOMAIN: The Z-binding domains recognize and bind left-handed double-
CC stranded Z-RNA structures, but not A-RNA, the right-handed double-
CC stranded RNAs that are structurally very different from Z-RNAs. The
CC second Z-binding domain (also named Zalpha2) acts as a molecular switch
CC regulating pyroptosis, necroptosis and apoptosis (PANoptosis). The
CC second Z-binding domain is essential for sensing influenza A virus
CC (IAV) Z-RNAs. {ECO:0000250|UniProtKB:Q9QY24}.
CC -!- DOMAIN: (Microbial infection) The RIP homotypic interaction motif
CC (RHIM) mediates interaction with the RHIM motif of the herpes simplex
CC virus 1/HHV-1 protein RIR1/ICP6 to form hetero-amyloid structures.
CC {ECO:0000269|PubMed:33348174}.
CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:Q9QY24}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Spotting patterns - Issue
CC 227 of August 2020;
CC URL="https://web.expasy.org/spotlight/back_issues/227/";
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DR EMBL; AJ300575; CAC18810.1; -; mRNA.
DR EMBL; CT002036; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK122761; BAG53713.1; -; mRNA.
DR EMBL; AL035541; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75511.1; -; Genomic_DNA.
DR EMBL; BC028218; AAH28218.1; -; mRNA.
DR CCDS; CCDS13461.1; -. [Q9H171-1]
DR CCDS; CCDS54477.1; -. [Q9H171-7]
DR CCDS; CCDS54478.1; -. [Q9H171-6]
DR RefSeq; NP_001153889.1; NM_001160417.1.
DR RefSeq; NP_001153890.1; NM_001160418.1. [Q9H171-7]
DR RefSeq; NP_001153891.1; NM_001160419.2. [Q9H171-6]
DR RefSeq; NP_001310895.1; NM_001323966.1.
DR RefSeq; NP_110403.2; NM_030776.2. [Q9H171-1]
DR PDB; 2L4M; NMR; -; A=103-166.
DR PDB; 2LNB; NMR; -; A=6-74.
DR PDB; 3EYI; X-ray; 1.45 A; A/B=103-166.
DR PDB; 4KA4; X-ray; 2.60 A; A/B/D/E=96-165.
DR PDBsum; 2L4M; -.
DR PDBsum; 2LNB; -.
DR PDBsum; 3EYI; -.
DR PDBsum; 4KA4; -.
DR AlphaFoldDB; Q9H171; -.
DR BMRB; Q9H171; -.
DR SMR; Q9H171; -.
DR BioGRID; 123349; 24.
DR DIP; DIP-44121N; -.
DR IntAct; Q9H171; 13.
DR MINT; Q9H171; -.
DR STRING; 9606.ENSP00000360215; -.
DR iPTMnet; Q9H171; -.
DR PhosphoSitePlus; Q9H171; -.
DR BioMuta; ZBP1; -.
DR DMDM; 71153189; -.
DR jPOST; Q9H171; -.
DR MassIVE; Q9H171; -.
DR PaxDb; Q9H171; -.
DR PeptideAtlas; Q9H171; -.
DR PRIDE; Q9H171; -.
DR ProteomicsDB; 199; -.
DR ProteomicsDB; 24833; -.
DR ProteomicsDB; 80370; -. [Q9H171-1]
DR ProteomicsDB; 80371; -. [Q9H171-2]
DR ProteomicsDB; 80372; -. [Q9H171-3]
DR ProteomicsDB; 80373; -. [Q9H171-4]
DR ProteomicsDB; 80374; -. [Q9H171-5]
DR Antibodypedia; 14231; 213 antibodies from 35 providers.
DR DNASU; 81030; -.
DR Ensembl; ENST00000371173.8; ENSP00000360215.3; ENSG00000124256.15. [Q9H171-1]
DR Ensembl; ENST00000395822.7; ENSP00000379167.3; ENSG00000124256.15. [Q9H171-7]
DR Ensembl; ENST00000541799.1; ENSP00000440552.1; ENSG00000124256.15. [Q9H171-6]
DR GeneID; 81030; -.
DR KEGG; hsa:81030; -.
DR MANE-Select; ENST00000371173.8; ENSP00000360215.3; NM_030776.3; NP_110403.2.
DR UCSC; uc002xyo.4; human. [Q9H171-1]
DR CTD; 81030; -.
DR DisGeNET; 81030; -.
DR GeneCards; ZBP1; -.
DR HGNC; HGNC:16176; ZBP1.
DR HPA; ENSG00000124256; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 606750; gene.
DR neXtProt; NX_Q9H171; -.
DR OpenTargets; ENSG00000124256; -.
DR PharmGKB; PA38094; -.
DR VEuPathDB; HostDB:ENSG00000124256; -.
DR eggNOG; ENOG502SRWE; Eukaryota.
DR GeneTree; ENSGT00390000002234; -.
DR HOGENOM; CLU_053260_0_0_1; -.
DR InParanoid; Q9H171; -.
DR OMA; ICQQGAN; -.
DR OrthoDB; 1138811at2759; -.
DR PhylomeDB; Q9H171; -.
DR TreeFam; TF337658; -.
DR PathwayCommons; Q9H171; -.
DR Reactome; R-HSA-1606322; ZBP1(DAI) mediated induction of type I IFNs.
DR Reactome; R-HSA-1606341; IRF3 mediated activation of type 1 IFN.
DR Reactome; R-HSA-1810476; RIP-mediated NFkB activation via ZBP1.
DR Reactome; R-HSA-3134975; Regulation of innate immune responses to cytosolic DNA.
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR SignaLink; Q9H171; -.
DR SIGNOR; Q9H171; -.
DR BioGRID-ORCS; 81030; 6 hits in 1071 CRISPR screens.
DR ChiTaRS; ZBP1; human.
DR EvolutionaryTrace; Q9H171; -.
DR GeneWiki; ZBP1; -.
DR GenomeRNAi; 81030; -.
DR Pharos; Q9H171; Tbio.
DR PRO; PR:Q9H171; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9H171; protein.
DR Bgee; ENSG00000124256; Expressed in granulocyte and 138 other tissues.
DR ExpressionAtlas; Q9H171; baseline and differential.
DR Genevisible; Q9H171; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0003726; F:double-stranded RNA adenosine deaminase activity; IEA:InterPro.
DR GO; GO:0003725; F:double-stranded RNA binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003692; F:left-handed Z-DNA binding; NAS:UniProtKB.
DR GO; GO:0002218; P:activation of innate immune response; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0050832; P:defense response to fungus; ISS:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0060545; P:positive regulation of necroptotic process; IMP:UniProtKB.
DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0070269; P:pyroptosis; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:2000659; P:regulation of interleukin-1-mediated signaling pathway; ISS:UniProtKB.
DR Gene3D; 1.10.10.10; -; 2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR InterPro; IPR042371; Z_dom.
DR InterPro; IPR042361; ZBP1.
DR PANTHER; PTHR14966; PTHR14966; 1.
DR Pfam; PF02295; z-alpha; 1.
DR SMART; SM00550; Zalpha; 2.
DR SUPFAM; SSF46785; SSF46785; 2.
DR PROSITE; PS50139; Z_BINDING; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Antiviral defense; Apoptosis;
KW Cytoplasm; DNA-binding; Host-virus interaction; Immunity; Innate immunity;
KW Necrosis; Nucleus; Reference proteome; Repeat; RNA-binding.
FT CHAIN 1..429
FT /note="Z-DNA-binding protein 1"
FT /id="PRO_0000066564"
FT DOMAIN 8..70
FT /note="Z-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00073"
FT DOMAIN 103..166
FT /note="Z-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00073"
FT REGION 68..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 277..299
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 339..429
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 195..219
FT /note="RIP homotypic interaction motif (RHIM) 1"
FT /evidence="ECO:0000250|UniProtKB:Q9QY24"
FT MOTIF 253..277
FT /note="RIP homotypic interaction motif (RHIM) 2"
FT /evidence="ECO:0000250|UniProtKB:Q9QY24"
FT COMPBIAS 360..374
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 386..400
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 12..86
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046081"
FT VAR_SEQ 87..149
FT /note="AERPQQHAATIPETPGPQFSQQREEDIYRFLKDNGPQRALVIAQALGMRTAK
FT DVNRDLYRMKS -> GNCHPGEAGLTLQGASWQWTSTDLSLGSNLNSATWELTGFLSLC
FT LGFFFWLMELTAGLLGRGC (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004079"
FT VAR_SEQ 87..109
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_004078"
FT VAR_SEQ 150..429
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004080"
FT VAR_SEQ 225..248
FT /note="SAGPRHLPSMAPGDSSTWGTLVDP -> KSPKRAQGGDLGGEPPDPLGGGKG
FT (in isoform 6)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_045405"
FT VAR_SEQ 249..429
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_045406"
FT VAR_SEQ 365..429
FT /note="GRRPADTQSRSHFPRDIGQPITPSHSKLTPKLETMTLGNRSHKAAEGSHYVD
FT EASHEGSWWGGGI -> VAAFTEVLNPSKSFMKFGINFFQTPVNVDSLTSSHESQMFLT
FT ACRLVIFSRRFSTYFAQIHLRNHSVLHLCPHKIYLLKNKK (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_004081"
FT VAR_SEQ 365..429
FT /note="GRRPADTQSRSHFPRDIGQPITPSHSKLTPKLETMTLGNRSHKAAEGSHYVD
FT EASHEGSWWGGGI -> GRRPADTQSRSFDGQE (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_004082"
FT VARIANT 17
FT /note="R -> I (in dbSNP:rs35813125)"
FT /id="VAR_057030"
FT VARIANT 53
FT /note="K -> R (in dbSNP:rs35895307)"
FT /id="VAR_061728"
FT VARIANT 70
FT /note="G -> R (in dbSNP:rs34964609)"
FT /id="VAR_057031"
FT VARIANT 88
FT /note="E -> K (in dbSNP:rs2073145)"
FT /evidence="ECO:0000269|PubMed:11842111, ECO:0000269|Ref.2"
FT /id="VAR_014316"
FT VARIANT 154
FT /note="D -> H (in dbSNP:rs16981187)"
FT /id="VAR_057032"
FT VARIANT 166
FT /note="R -> H (in dbSNP:rs34478944)"
FT /id="VAR_057033"
FT VARIANT 258
FT /note="Q -> R (in dbSNP:rs2865394)"
FT /evidence="ECO:0000269|PubMed:11842111,
FT ECO:0000269|PubMed:14702039, ECO:0000269|Ref.5"
FT /id="VAR_069138"
FT VARIANT 332
FT /note="A -> V (in dbSNP:rs41275648)"
FT /id="VAR_061729"
FT HELIX 10..25
FT /evidence="ECO:0007829|PDB:2LNB"
FT HELIX 31..38
FT /evidence="ECO:0007829|PDB:2LNB"
FT HELIX 42..54
FT /evidence="ECO:0007829|PDB:2LNB"
FT STRAND 57..62
FT /evidence="ECO:0007829|PDB:2LNB"
FT STRAND 65..72
FT /evidence="ECO:0007829|PDB:2LNB"
FT HELIX 108..120
FT /evidence="ECO:0007829|PDB:3EYI"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:3EYI"
FT HELIX 125..131
FT /evidence="ECO:0007829|PDB:3EYI"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:3EYI"
FT HELIX 141..149
FT /evidence="ECO:0007829|PDB:3EYI"
FT STRAND 152..155
FT /evidence="ECO:0007829|PDB:3EYI"
FT TURN 157..159
FT /evidence="ECO:0007829|PDB:3EYI"
FT STRAND 161..164
FT /evidence="ECO:0007829|PDB:3EYI"
SQ SEQUENCE 429 AA; 46343 MW; 2C9B195112822991 CRC64;
MAQAPADPGR EGHLEQRILQ VLTEAGSPVK LAQLVKECQA PKRELNQVLY RMKKELKVSL
TSPATWCLGG TDPEGEGPAE LALSSPAERP QQHAATIPET PGPQFSQQRE EDIYRFLKDN
GPQRALVIAQ ALGMRTAKDV NRDLYRMKSR HLLDMDEQSK AWTIYRPEDS GRRAKSASII
YQHNPINMIC QNGPNSWISI ANSEAIQIGH GNIITRQTVS REDGSAGPRH LPSMAPGDSS
TWGTLVDPWG PQDIHMEQSI LRRVQLGHSN EMRLHGVPSE GPAHIPPGSP PVSATAAGPE
ASFEARIPSP GTHPEGEAAQ RIHMKSCFLE DATIGNSNKM SISPGVAGPG GVAGSGEGEP
GEDAGRRPAD TQSRSHFPRD IGQPITPSHS KLTPKLETMT LGNRSHKAAE GSHYVDEASH
EGSWWGGGI
