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Q9QY24

- ZBP1_MOUSE

UniProt

Q9QY24 - ZBP1_MOUSE

Protein

Z-DNA-binding protein 1

Gene

Zbp1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 110 (01 Oct 2014)
      Sequence version 1 (01 May 2000)
      Previous versions | rss
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    Functioni

    Participates in the detection by the host's innate immune system of DNA from viral, bacterial or even host origin. Plays a role in host defense against tumors and pathogens. Acts as a cytoplasmic DNA sensor which, when activated, induces the recruitment of TBK1 and IRF3 to its C-terminal region and activates the downstream interferon regulatory factor (IRF) and NF-kappa B transcription factors, leading to type-I interferon production. ZBP1-induced NF-kappaB activation probably involves the recruitment of the RHIM containing kinases RIPK1 and RIPK3.2 Publications

    GO - Molecular functioni

    1. DNA binding Source: MGI
    2. double-stranded RNA adenosine deaminase activity Source: InterPro
    3. left-handed Z-DNA binding Source: MGI
    4. RNA binding Source: InterPro

    GO - Biological processi

    1. defense response to virus Source: UniProtKB-KW
    2. innate immune response Source: UniProtKB-KW
    3. positive regulation of type I interferon-mediated signaling pathway Source: MGI
    4. viral process Source: UniProtKB-KW

    Keywords - Biological processi

    Antiviral defense, Host-virus interaction, Immunity, Innate immunity

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_196447. IRF3-mediated induction of type I IFN.
    REACT_196519. Regulation of innate immune responses to cytosolic DNA.
    REACT_198980. IRF3 mediated activation of type 1 IFN.
    REACT_222971. RIP-mediated NFkB activation via ZBP1.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Z-DNA-binding protein 1
    Alternative name(s):
    DNA-dependent activator of IFN-regulatory factors
    Short name:
    DAI
    Tumor stroma and activated macrophage protein DLM-1
    Gene namesi
    Name:Zbp1
    Synonyms:Dlm1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:1927449. Zbp1.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. cytosol Source: Reactome
    3. nucleus Source: MGI

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 411411Z-DNA-binding protein 1PRO_0000066565Add
    BLAST

    Proteomic databases

    MaxQBiQ9QY24.
    PaxDbiQ9QY24.
    PRIDEiQ9QY24.

    PTM databases

    PhosphoSiteiQ9QY24.

    Expressioni

    Tissue specificityi

    Expressed in lung, spleen and liver. Lower levels were seen in heart, kidney and testis. Expression is greatly up-regulated in tumor stromal cells and activated macrophages.

    Inductioni

    By interferon gamma and lipopolysaccharides (LPS).

    Gene expression databases

    ArrayExpressiQ9QY24.
    BgeeiQ9QY24.
    CleanExiMM_ZBP1.
    GenevestigatoriQ9QY24.

    Interactioni

    Subunit structurei

    Interacts (via RIP homotypic interaction motif) with murid herpesvirus 1 viral inhibitor of RIP activation (via RIP homotypic interaction motif); this interaction inhibits recruitment of RIPK1 and RIPK3 to ZBP1 and prevents ZBP1-induced NFkappa-B activation.1 Publication

    Protein-protein interaction databases

    DIPiDIP-29879N.
    STRINGi10090.ENSMUSP00000029018.

    Structurei

    Secondary structure

    1
    411
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi13 – 2513
    Helixi31 – 388
    Helixi42 – 5413
    Beta strandi57 – 626
    Beta strandi65 – 684

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1J75X-ray1.85A8-70[»]
    2HEOX-ray1.70A/D8-70[»]
    ProteinModelPortaliQ9QY24.
    SMRiQ9QY24. Positions 13-69, 92-144.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9QY24.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati6 – 7267DRADA 1Add
    BLAST
    Repeati82 – 14766DRADA 2Add
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi188 – 20518RIP homotypic interaction motif (RHIM) 1Add
    BLAST
    Motifi237 – 26125RIP homotypic interaction motif (RHIM) 2Add
    BLAST

    Sequence similaritiesi

    Contains 2 DRADA repeats.Curated

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG38978.
    GeneTreeiENSGT00390000002234.
    HOGENOMiHOG000230878.
    HOVERGENiHBG036279.
    InParanoidiQ9QY24.
    KOiK12965.
    OMAiPGCPRTH.
    PhylomeDBiQ9QY24.

    Family and domain databases

    Gene3Di1.10.10.10. 2 hits.
    InterProiIPR000607. dsRNA_A_deaminase.
    IPR025735. RHIM_dom.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view]
    PfamiPF12721. RHIM. 2 hits.
    PF02295. z-alpha. 2 hits.
    [Graphical view]
    SMARTiSM00550. Zalpha. 2 hits.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9QY24-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAEAPVDLST GDNLEQKILQ VLSDDGGPVK IGQLVKKCQV PKKTLNQVLY    50
    RLKKEDRVSS PEPATWSIGG AASGDGAPAI PENSSAQPSL DERILRFLEA 100
    NGPHRALHIA KALGMTTAKE VNPLLYSMRN KHLLSYDGQT WKIYHSRQEG 150
    QDIAHSGVTQ ESPAIICQHN PVNMICQQGA NSHISIANSN AIQIGHGNVI 200
    VREKACGEPG PRTSHPLPLA WDASAQDMPP VAHGAQYIYM DKSLLQQVQL 250
    GHHNEMSLVG DAGKHPSYSF SDSPPEVSTT TADPGASFNM QTFEPGPHPE 300
    GDTVQTVHIK SCFLEDATIG NGNKMTIHLR SKGEVMESGD SEEPKKEDTG 350
    TSSEATPPRS CQHTPSDSML PTSELRAMAL GDSSPQTTEP VLREHEVQDI 400
    ESSQDTGLSK Q 411
    Length:411
    Mass (Da):44,331
    Last modified:May 1, 2000 - v1
    Checksum:i6D5F7B526A7DAA40
    GO
    Isoform 2 (identifier: Q9QY24-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         154-187: AHSGVTQESPAIICQHNPVNMICQQGANSHISIA → VLPCSPGCPRTHHVDQAGLEPTEIFLLLPIKFWD
         188-411: Missing.

    Show »
    Length:187
    Mass (Da):20,569
    Checksum:i216A1996CDD858DC
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti67 – 671S → R in AAH20033. (PubMed:15489334)Curated
    Sequence conflicti83 – 831N → D in AAH20033. (PubMed:15489334)Curated
    Sequence conflicti197 – 1971G → R in AAH20033. (PubMed:15489334)Curated
    Sequence conflicti293 – 2931F → S in AAH20033. (PubMed:15489334)Curated
    Sequence conflicti403 – 4031S → T in AAH20033. (PubMed:15489334)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei154 – 18734AHSGV…HISIA → VLPCSPGCPRTHHVDQAGLE PTEIFLLLPIKFWD in isoform 2. 1 PublicationVSP_004083Add
    BLAST
    Alternative sequencei188 – 411224Missing in isoform 2. 1 PublicationVSP_004084Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF136520 mRNA. Translation: AAF17234.1.
    AK008179 mRNA. Translation: BAB25513.1.
    BC020033 mRNA. Translation: AAH20033.1.
    CCDSiCCDS17142.1. [Q9QY24-1]
    CCDS50813.1. [Q9QY24-2]
    RefSeqiNP_001132991.1. NM_001139519.1. [Q9QY24-2]
    UniGeneiMm.116687.

    Genome annotation databases

    EnsembliENSMUST00000109116; ENSMUSP00000104744; ENSMUSG00000027514. [Q9QY24-2]
    GeneIDi58203.
    KEGGimmu:58203.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF136520 mRNA. Translation: AAF17234.1 .
    AK008179 mRNA. Translation: BAB25513.1 .
    BC020033 mRNA. Translation: AAH20033.1 .
    CCDSi CCDS17142.1. [Q9QY24-1 ]
    CCDS50813.1. [Q9QY24-2 ]
    RefSeqi NP_001132991.1. NM_001139519.1. [Q9QY24-2 ]
    UniGenei Mm.116687.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1J75 X-ray 1.85 A 8-70 [» ]
    2HEO X-ray 1.70 A/D 8-70 [» ]
    ProteinModelPortali Q9QY24.
    SMRi Q9QY24. Positions 13-69, 92-144.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-29879N.
    STRINGi 10090.ENSMUSP00000029018.

    PTM databases

    PhosphoSitei Q9QY24.

    Proteomic databases

    MaxQBi Q9QY24.
    PaxDbi Q9QY24.
    PRIDEi Q9QY24.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000109116 ; ENSMUSP00000104744 ; ENSMUSG00000027514 . [Q9QY24-2 ]
    GeneIDi 58203.
    KEGGi mmu:58203.

    Organism-specific databases

    CTDi 81030.
    MGIi MGI:1927449. Zbp1.

    Phylogenomic databases

    eggNOGi NOG38978.
    GeneTreei ENSGT00390000002234.
    HOGENOMi HOG000230878.
    HOVERGENi HBG036279.
    InParanoidi Q9QY24.
    KOi K12965.
    OMAi PGCPRTH.
    PhylomeDBi Q9QY24.

    Enzyme and pathway databases

    Reactomei REACT_196447. IRF3-mediated induction of type I IFN.
    REACT_196519. Regulation of innate immune responses to cytosolic DNA.
    REACT_198980. IRF3 mediated activation of type 1 IFN.
    REACT_222971. RIP-mediated NFkB activation via ZBP1.

    Miscellaneous databases

    EvolutionaryTracei Q9QY24.
    NextBioi 314185.
    PROi Q9QY24.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9QY24.
    Bgeei Q9QY24.
    CleanExi MM_ZBP1.
    Genevestigatori Q9QY24.

    Family and domain databases

    Gene3Di 1.10.10.10. 2 hits.
    InterProi IPR000607. dsRNA_A_deaminase.
    IPR025735. RHIM_dom.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view ]
    Pfami PF12721. RHIM. 2 hits.
    PF02295. z-alpha. 2 hits.
    [Graphical view ]
    SMARTi SM00550. Zalpha. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning of DLM-1, a novel gene that is up-regulated in activated macrophages, using RNA differential display."
      Fu Y., Comella N., Tognazzi K., Brown L.F., Dvorak H.F., Kocher O.
      Gene 240:157-163(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Strain: C3Heb/FeJ.
      Tissue: Liver.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Strain: C57BL/6J.
      Tissue: Small intestine.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Mammary tumor.
    4. "DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response."
      Takaoka A., Wang Z., Choi M.K., Yanai H., Negishi H., Ban T., Lu Y., Miyagishi M., Kodama T., Honda K., Ohba Y., Taniguchi T.
      Nature 448:501-505(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    5. "DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB."
      Rebsamen M., Heinz L.X., Meylan E., Michallet M.C., Schroder K., Hofmann K., Vazquez J., Benedict C.A., Tschopp J.
      EMBO Rep. 10:916-922(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH RIPK1; RIPK3 AND MURID HERPESVIRUS 1 VIRAL INHIBITOR OF RIP ACTIVATION.
    6. "The phagosomal proteome in interferon-gamma-activated macrophages."
      Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
      Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    7. "Structure of the DLM-1-Z-DNA complex reveals a conserved family of Z-DNA-binding proteins."
      Schwartz T., Behlke J., Lowenhaupt K., Heinemann U., Rich A.
      Nat. Struct. Biol. 8:761-765(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 8-70, DNA-BINDING.

    Entry informationi

    Entry nameiZBP1_MOUSE
    AccessioniPrimary (citable) accession number: Q9QY24
    Secondary accession number(s): Q8VE02, Q9D8B9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 25, 2002
    Last sequence update: May 1, 2000
    Last modified: October 1, 2014
    This is version 110 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3