ID   ZBP1_HUMAN              Reviewed;         429 AA.
AC   Q9H171; Q5JY39; Q9BYW4;
DT   25-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2005, sequence version 2.
DT   25-JAN-2012, entry version 93.
DE   RecName: Full=Z-DNA-binding protein 1;
DE   AltName: Full=Tumor stroma and activated macrophage protein DLM-1;
GN   Name=ZBP1; Synonyms=C20orf183, DLM1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, AND VARIANT LYS-88.
RC   TISSUE=Spleen;
RX   MEDLINE=21831095; 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 GENOMIC DNA].
RX   MEDLINE=21638749; 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.,
RA   Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA   Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA   Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA   Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA   Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA   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.,
RA   Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA   Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA   Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA   Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA   Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA   Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA   Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [3]
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
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-
RT   DNA.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:20671-20676(2008).
CC   -!- FUNCTION: Participates in the detection by the host's innate
CC       immune system of DNA from viral, bacterial or even host origin.
CC       Plays a role in host defense against tumors and pathogens. Acts as
CC       a cytoplasmic DNA sensor which, when activated, induces the
CC       recruitment of TBK1 and IRF3 to its C-terminal region and
CC       activates the downstream interferon regulatory factor (IRF) and
CC       NF-kappa B transcription factors, leading to type-I interferon
CC       production. ZBP1-induced NF-kappaB activation probably involves
CC       the recruitment of the RHIM containing kinases RIPK1 and RIPK3 (By
CC       similarity).
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
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   -!- TISSUE SPECIFICITY: Highly expressed in lymphatic tissues
CC       including lymph node, leukocytes, tonsil, bone marrow and spleen.
CC       Expressed to a lesser extent in thymus, lung and liver.
CC   -!- SIMILARITY: Contains 2 DRADA repeats.
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DR   EMBL; AJ300575; CAC18810.1; -; mRNA.
DR   EMBL; AL035541; CAI23107.1; -; Genomic_DNA.
DR   EMBL; BC028218; AAH28218.1; -; mRNA.
DR   IPI; IPI00006512; -.
DR   IPI; IPI00181608; -.
DR   IPI; IPI00219702; -.
DR   IPI; IPI00219704; -.
DR   IPI; IPI00334653; -.
DR   RefSeq; NP_001153889.1; NM_001160417.1.
DR   RefSeq; NP_001153890.1; NM_001160418.1.
DR   RefSeq; NP_110403.2; NM_030776.2.
DR   UniGene; Hs.302123; -.
DR   PDB; 2L4M; NMR; -; A=103-166.
DR   PDB; 3EYI; X-ray; 1.45 A; A/B=103-166.
DR   PDBsum; 2L4M; -.
DR   PDBsum; 3EYI; -.
DR   ProteinModelPortal; Q9H171; -.
DR   SMR; Q9H171; 13-69, 103-166.
DR   DIP; DIP-44121N; -.
DR   MINT; MINT-6167522; -.
DR   STRING; Q9H171; -.
DR   DMDM; 71153189; -.
DR   PRIDE; Q9H171; -.
DR   Ensembl; ENST00000371173; ENSP00000360215; ENSG00000124256.
DR   GeneID; 81030; -.
DR   KEGG; hsa:81030; -.
DR   UCSC; uc002xyo.1; human.
DR   CTD; 81030; -.
DR   GeneCards; GC20M056178; -.
DR   H-InvDB; HIX0203057; -.
DR   HGNC; HGNC:16176; ZBP1.
DR   MIM; 606750; gene.
DR   neXtProt; NX_Q9H171; -.
DR   GeneTree; ENSGT00390000002234; -.
DR   HOVERGEN; HBG036279; -.
DR   OMA; IRSCFLE; -.
DR   OrthoDB; EOG4QZ7KZ; -.
DR   NextBio; 71358; -.
DR   ArrayExpress; Q9H171; -.
DR   Bgee; Q9H171; -.
DR   CleanEx; HS_ZBP1; -.
DR   Genevestigator; Q9H171; -.
DR   GermOnline; ENSG00000124256; Homo sapiens.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0003726; F:double-stranded RNA adenosine deaminase activity; IEA:InterPro.
DR   GO; GO:0003692; F:left-handed Z-DNA binding; NAS:UniProtKB.
DR   GO; GO:0003723; F:RNA binding; IEA:InterPro.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   InterPro; IPR000607; dsRNA_A_deaminase.
DR   InterPro; IPR011991; WHTH_trsnscrt_rep_DNA-bd.
DR   Gene3D; G3DSA:1.10.10.10; Wing_hlx_DNA_bd; 2.
DR   KO; K12965; -.
DR   Pfam; PF02295; z-alpha; 2.
DR   PROSITE; PS50139; DRADA_REPEAT; FALSE_NEG.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Complete proteome; DNA-binding;
KW   Immunity; Innate immunity; Polymorphism; Reference proteome; Repeat.
FT   CHAIN         1    429       Z-DNA-binding protein 1.
FT                                /FTId=PRO_0000066564.
FT   REPEAT        6     72       DRADA 1.
FT   REPEAT      103    168       DRADA 2.
FT   MOTIF       195    219       RIP homotypic interaction motif (RHIM) 1.
FT   MOTIF       253    277       RIP homotypic interaction motif (RHIM) 2.
FT   VAR_SEQ      87    149       AERPQQHAATIPETPGPQFSQQREEDIYRFLKDNGPQRALV
FT                                IAQALGMRTAKDVNRDLYRMKS -> GNCHPGEAGLTLQGA
FT                                SWQWTSTDLSLGSNLNSATWELTGFLSLCLGFFFWLMELTA
FT                                GLLGRGC (in isoform 5).
FT                                /FTId=VSP_004079.
FT   VAR_SEQ      87    109       Missing (in isoform 4).
FT                                /FTId=VSP_004078.
FT   VAR_SEQ     150    429       Missing (in isoform 5).
FT                                /FTId=VSP_004080.
FT   VAR_SEQ     365    429       GRRPADTQSRSHFPRDIGQPITPSHSKLTPKLETMTLGNRS
FT                                HKAAEGSHYVDEASHEGSWWGGGI -> VAAFTEVLNPSKS
FT                                FMKFGINFFQTPVNVDSLTSSHESQMFLTACRLVIFSRRFS
FT                                TYFAQIHLRNHSVLHLCPHKIYLLKNKK (in isoform
FT                                2).
FT                                /FTId=VSP_004081.
FT   VAR_SEQ     365    429       GRRPADTQSRSHFPRDIGQPITPSHSKLTPKLETMTLGNRS
FT                                HKAAEGSHYVDEASHEGSWWGGGI -> GRRPADTQSRSFD
FT                                GQE (in isoform 3).
FT                                /FTId=VSP_004082.
FT   VARIANT      17     17       R -> I (in dbSNP:rs35813125).
FT                                /FTId=VAR_057030.
FT   VARIANT      53     53       K -> R (in dbSNP:rs35895307).
FT                                /FTId=VAR_061728.
FT   VARIANT      70     70       G -> R (in dbSNP:rs34964609).
FT                                /FTId=VAR_057031.
FT   VARIANT      88     88       E -> K (in dbSNP:rs2073145).
FT                                /FTId=VAR_014316.
FT   VARIANT     154    154       D -> H (in dbSNP:rs16981187).
FT                                /FTId=VAR_057032.
FT   VARIANT     166    166       R -> H (in dbSNP:rs34478944).
FT                                /FTId=VAR_057033.
FT   VARIANT     332    332       A -> V (in dbSNP:rs41275648).
FT                                /FTId=VAR_061729.
FT   CONFLICT    258    258       Q -> R (in Ref. 1; CAC18810).
FT   HELIX       108    119
FT   HELIX       125    131
FT   HELIX       137    139
FT   HELIX       141    149
FT   STRAND      152    155
FT   TURN        157    159
FT   STRAND      161    164
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
//