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 27-MAR-2024, entry version 182. 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}, DLM1 GN {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 RT DLM-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/"; 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; 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; 40. 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; 9606-ENSP00000360215; -. DR PeptideAtlas; 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; 228 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 AGR; HGNC:16176; -. 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; PATWCLA; -. DR OrthoDB; 5266205at2759; -. 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; 7 hits in 1149 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 139 other cell types or tissues. DR ExpressionAtlas; Q9H171; baseline and differential. 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:0003723; F:RNA binding; IDA:UniProt. DR GO; GO:0002218; P:activation of innate immune response; ISS:UniProtKB. DR GO; GO:0140374; P:antiviral innate immune response; IDA:UniProt. 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: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; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 2. DR InterPro; IPR025735; RHIM_dom. 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; Z-DNA-BINDING PROTEIN 1; 1. DR PANTHER; PTHR14966:SF0; Z-DNA-BINDING PROTEIN 1; 1. DR Pfam; PF12721; RHIM; 1. DR Pfam; PF02295; z-alpha; 1. DR SMART; SM00550; Zalpha; 2. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 2. DR PROSITE; PS50139; Z_BINDING; 2. DR Genevisible; Q9H171; HS. 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 //