ZBP1_RAT
ID ZBP1_RAT Reviewed; 409 AA.
AC Q8VDA5;
DT 25-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 25-MAY-2022, entry version 113.
DE RecName: Full=Z-DNA-binding protein 1 {ECO:0000305};
DE AltName: Full=Tumor stroma and activated macrophage protein DLM-1 {ECO:0000303|PubMed:11842111};
GN Name=Zbp1 {ECO:0000312|RGD:619956};
GN Synonyms=Dlm1 {ECO:0000303|PubMed:11842111};
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].
RC STRAIN=Lewis; 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).
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. ZBP1 acts as an essential mediator of pyroptosis, necroptosis
CC and apoptosis (PANoptosis), an integral part of host defense against
CC pathogens, by activating RIPK3, caspase-8 (CASP8), and the NLRP3
CC inflammasome. Key activator of necroptosis, a programmed cell death
CC process in response to death-inducing TNF-alpha family members, via its
CC ability to bind Z-RNA: once activated upon Z-RNA-binding, ZBP1
CC interacts and stimulates RIPK3 kinase, which phosphorylates and
CC activates MLKL, triggering execution of programmed necrosis. In
CC addition to TNF-induced necroptosis, necroptosis can also take place in
CC the nucleus in response to orthomyxoviruses infection: ZBP1 recognizes
CC and binds Z-RNA structures that are produced in infected nuclei by
CC orthomyxoviruses, such as the influenza A virus (IAV), leading to ZBP1
CC activation, RIPK3 stimulation and subsequent MLKL phosphorylation,
CC triggering disruption of the nuclear envelope and leakage of cellular
CC DNA into the cytosol. 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. In addition
CC to its direct role in driving necroptosis via its ability to sense Z-
CC RNAs, also involved in PANoptosis triggered in response to bacterial
CC infection: component of the AIM2 PANoptosome complex, a multiprotein
CC complex that triggers PANoptosis. Also acts as the apical sensor of
CC fungal infection responsible for activating PANoptosis. Involved in
CC CASP8-mediated cell death via its interaction with RIPK1 but
CC independently of its ability to sense Z-RNAs. In some cell types, also
CC able to restrict viral replication by promoting cell death-independent
CC responses. In response to flavivirus infection in neurons, promotes a
CC cell death-independent pathway that restricts viral replication:
CC together with RIPK3, promotes a death-independent transcriptional
CC program that modifies the cellular metabolism via up-regulation
CC expression of the enzyme ACOD1/IRG1 and production of the metabolite
CC itaconate. Itaconate inhibits the activity of succinate dehydrogenase,
CC generating a metabolic state in neurons that suppresses replication of
CC viral genomes. {ECO:0000250|UniProtKB:Q9QY24}.
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. Interacts (via RIP homotypic interaction motif)
CC with RIPK3; leading to RIPK3 activation and necroptosis; interaction is
CC enhanced by CASP6. Interacts (via RIP homotypic interaction motif) with
CC RIPK1. Component of the AIM2 PANoptosome complex, a multiprotein
CC complex that drives inflammatory cell death (PANoptosis).
CC {ECO:0000250|UniProtKB:Q9QY24}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9QY24}. Nucleus
CC {ECO:0000250|UniProtKB:Q9QY24}. Note=Mainly cytoplasmic. Accumulates in
CC the nucleus in response to influenza A virus (IAV) infection: senses
CC IAV defective viral genomes RNA in the nucleus.
CC {ECO:0000250|UniProtKB:Q9QY24}.
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 -!- PTM: Ubiquitinated; polyubiquitinated following influenza A virus (IAV)
CC infection. {ECO:0000250|UniProtKB:Q9QY24}.
CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:Q9QY24}.
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; AJ302054; CAC83103.1; -; mRNA.
DR AlphaFoldDB; Q8VDA5; -.
DR SMR; Q8VDA5; -.
DR STRING; 10116.ENSRNOP00000008365; -.
DR iPTMnet; Q8VDA5; -.
DR PhosphoSitePlus; Q8VDA5; -.
DR PaxDb; Q8VDA5; -.
DR UCSC; RGD:619956; rat.
DR RGD; 619956; Zbp1.
DR eggNOG; ENOG502SRWE; Eukaryota.
DR InParanoid; Q8VDA5; -.
DR PhylomeDB; Q8VDA5; -.
DR PRO; PR:Q8VDA5; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
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:0003692; F:left-handed Z-DNA binding; ISO:RGD.
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; ISS: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; ISS:UniProtKB.
DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; ISO:RGD.
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; 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; PTHR14966; 1.
DR Pfam; PF12721; RHIM; 2.
DR Pfam; PF02295; z-alpha; 2.
DR SMART; SM00550; Zalpha; 2.
DR SUPFAM; SSF46785; SSF46785; 2.
DR PROSITE; PS50139; Z_BINDING; 2.
PE 2: Evidence at transcript level;
KW Antiviral defense; Apoptosis; Cytoplasm; DNA-binding;
KW Host-virus interaction; Immunity; Innate immunity; Isopeptide bond;
KW Necrosis; Nucleus; Reference proteome; Repeat; RNA-binding;
KW Ubl conjugation.
FT CHAIN 1..409
FT /note="Z-DNA-binding protein 1"
FT /id="PRO_0000066566"
FT DOMAIN 8..70
FT /note="Z-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00073"
FT DOMAIN 85..147
FT /note="Z-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00073"
FT REGION 59..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 269..307
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 323..369
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 183..207
FT /note="RIP homotypic interaction motif (RHIM) 1"
FT /evidence="ECO:0000250|UniProtKB:Q9QY24"
FT MOTIF 241..265
FT /note="RIP homotypic interaction motif (RHIM) 2"
FT /evidence="ECO:0000250|UniProtKB:Q9QY24"
FT COMPBIAS 274..291
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 333..350
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 351..369
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 17
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9QY24"
FT CROSSLNK 43
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9QY24"
SQ SEQUENCE 409 AA; 43918 MW; 9D41759124CF6130 CRC64;
MAEASVDLGT GDNLEQKILQ VLSDAGSPVQ IDQLLKKLQV PKKILNQVLY RLKKEGRVSS
PAPATWSLGG DGASGDGAPE IPEDSAAQPS LEERILRFLE TKGPQRALHI AKALGMTTAK
EVNPILYSMR NKHLLTVSDT QMWTIYRSSQ EGQERACSGV GQESPAVIYQ QNPINMICQQ
GPNSLISISN SKAIQIGHGN VMSRQTICGD PGPGTPHHAP LPVLEDAAAQ DTPPGTHGAQ
LIHLNKSMLR RVQLGHGNEM NLERDPVEHP IFSFSSSPPE STTTADPETA FNMQTPEPGP
HPEGGTTQIV HIKSCLLEDT TVGNNNKMTI HRRSKGGTKE SADSQELKED TGASSEATPP
RSCLHTPSDS TLLTSELTAM ALGDGSPQIT ESMLREDEVQ AAETCQTQD
