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Protein

Z-DNA-binding protein 1

Gene

ZBP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 (By similarity).By similarity

GO - Molecular functioni

  • DNA binding Source: MGI
  • double-stranded RNA adenosine deaminase activity Source: InterPro
  • left-handed Z-DNA binding Source: UniProtKB
  • RNA binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Immunity, Innate immunity

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000124256-MONOMER.
ReactomeiR-HSA-1606322. ZBP1(DAI) mediated induction of type I IFNs.
R-HSA-1606341. IRF3 mediated activation of type 1 IFN.
R-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-3134975. Regulation of innate immune responses to cytosolic DNA.
R-HSA-3270619. IRF3-mediated induction of type I IFN.

Names & Taxonomyi

Protein namesi
Recommended name:
Z-DNA-binding protein 1
Alternative name(s):
Tumor stroma and activated macrophage protein DLM-1
Gene namesi
Name:ZBP1
Synonyms:C20orf183, DLM1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:16176. ZBP1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytosol Source: MGI
  • nucleus Source: MGI
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi81030.
OpenTargetsiENSG00000124256.
PharmGKBiPA38094.

Polymorphism and mutation databases

BioMutaiZBP1.
DMDMi71153189.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000665641 – 429Z-DNA-binding protein 1Add BLAST429

Proteomic databases

PaxDbiQ9H171.
PeptideAtlasiQ9H171.
PRIDEiQ9H171.

PTM databases

iPTMnetiQ9H171.
PhosphoSitePlusiQ9H171.

Expressioni

Tissue specificityi

Highly expressed in lymphatic tissues including lymph node, leukocytes, tonsil, bone marrow and spleen. Expressed to a lesser extent in thymus, lung and liver.

Gene expression databases

BgeeiENSG00000124256.
CleanExiHS_ZBP1.
ExpressionAtlasiQ9H171. baseline and differential.
GenevisibleiQ9H171. HS.

Organism-specific databases

HPAiHPA041256.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
KRR1Q136013EBI-6264672,EBI-744525
RIPK3Q9Y5724EBI-6264672,EBI-298250

Protein-protein interaction databases

BioGridi123349. 13 interactors.
DIPiDIP-44121N.
IntActiQ9H171. 6 interactors.
MINTiMINT-6167522.
STRINGi9606.ENSP00000360215.

Structurei

Secondary structure

1429
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi10 – 25Combined sources16
Helixi31 – 38Combined sources8
Helixi42 – 54Combined sources13
Beta strandi57 – 62Combined sources6
Beta strandi65 – 72Combined sources8
Helixi108 – 120Combined sources13
Beta strandi122 – 124Combined sources3
Helixi125 – 131Combined sources7
Helixi137 – 139Combined sources3
Helixi141 – 149Combined sources9
Beta strandi152 – 155Combined sources4
Turni157 – 159Combined sources3
Beta strandi161 – 164Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L4MNMR-A103-166[»]
2LNBNMR-A6-74[»]
3EYIX-ray1.45A/B103-166[»]
4KA4X-ray2.60A/B/D/E96-165[»]
ProteinModelPortaliQ9H171.
SMRiQ9H171.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H171.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati6 – 72DRADA 1Add BLAST67
Repeati103 – 168DRADA 2Add BLAST66

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi195 – 219RIP homotypic interaction motif (RHIM) 1Add BLAST25
Motifi253 – 277RIP homotypic interaction motif (RHIM) 2Add BLAST25

Sequence similaritiesi

Contains 2 DRADA repeats.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410J2S4. Eukaryota.
ENOG411196S. LUCA.
GeneTreeiENSGT00390000002234.
HOGENOMiHOG000230878.
HOVERGENiHBG036279.
InParanoidiQ9H171.
KOiK12965.
OMAiIGHGNVI.
OrthoDBiEOG091G0L53.
PhylomeDBiQ9H171.
TreeFamiTF337658.

Family and domain databases

Gene3Di1.10.10.10. 2 hits.
InterProiIPR000607. dsRNA_A_deaminase.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF02295. z-alpha. 1 hit.
[Graphical view]
SMARTiSM00550. Zalpha. 2 hits.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 2 hits.

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q9H171-1) [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

        10         20         30         40         50
MAQAPADPGR EGHLEQRILQ VLTEAGSPVK LAQLVKECQA PKRELNQVLY
60 70 80 90 100
RMKKELKVSL TSPATWCLGG TDPEGEGPAE LALSSPAERP QQHAATIPET
110 120 130 140 150
PGPQFSQQRE EDIYRFLKDN GPQRALVIAQ ALGMRTAKDV NRDLYRMKSR
160 170 180 190 200
HLLDMDEQSK AWTIYRPEDS GRRAKSASII YQHNPINMIC QNGPNSWISI
210 220 230 240 250
ANSEAIQIGH GNIITRQTVS REDGSAGPRH LPSMAPGDSS TWGTLVDPWG
260 270 280 290 300
PQDIHMEQSI LRRVQLGHSN EMRLHGVPSE GPAHIPPGSP PVSATAAGPE
310 320 330 340 350
ASFEARIPSP GTHPEGEAAQ RIHMKSCFLE DATIGNSNKM SISPGVAGPG
360 370 380 390 400
GVAGSGEGEP GEDAGRRPAD TQSRSHFPRD IGQPITPSHS KLTPKLETMT
410 420
LGNRSHKAAE GSHYVDEASH EGSWWGGGI
Length:429
Mass (Da):46,343
Last modified:July 19, 2005 - v2
Checksum:i2C9B195112822991
GO
Isoform 2 (identifier: Q9H171-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     365-429: GRRPADTQSR...HEGSWWGGGI → VAAFTEVLNP...HKIYLLKNKK

Show »
Length:446
Mass (Da):48,754
Checksum:iAB6807A7F1397076
GO
Isoform 3 (identifier: Q9H171-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     365-429: GRRPADTQSR...HEGSWWGGGI → GRRPADTQSRSFDGQE

Show »
Length:380
Mass (Da):41,028
Checksum:i247472C6F85CEB36
GO
Isoform 4 (identifier: Q9H171-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     87-109: Missing.

Show »
Length:406
Mass (Da):43,786
Checksum:i709506D06777E8F2
GO
Isoform 5 (identifier: Q9H171-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     87-149: AERPQQHAAT...VNRDLYRMKS → GNCHPGEAGL...LTAGLLGRGC
     150-429: Missing.

Show »
Length:149
Mass (Da):15,985
Checksum:i1D948BB00599314B
GO
Isoform 6 (identifier: Q9H171-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     225-248: SAGPRHLPSMAPGDSSTWGTLVDP → KSPKRAQGGDLGGEPPDPLGGGKG
     249-429: Missing.

Note: No experimental confirmation available.
Show »
Length:248
Mass (Da):27,218
Checksum:iE79D75F5D4FE665C
GO
Isoform 7 (identifier: Q9H171-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     12-86: Missing.

Note: No experimental confirmation available.
Show »
Length:354
Mass (Da):38,220
Checksum:i162A79FBD15B1B0F
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05703017R → I.Corresponds to variant rs35813125dbSNPEnsembl.1
Natural variantiVAR_06172853K → R.Corresponds to variant rs35895307dbSNPEnsembl.1
Natural variantiVAR_05703170G → R.Corresponds to variant rs34964609dbSNPEnsembl.1
Natural variantiVAR_01431688E → K.2 PublicationsCorresponds to variant rs2073145dbSNPEnsembl.1
Natural variantiVAR_057032154D → H.Corresponds to variant rs16981187dbSNPEnsembl.1
Natural variantiVAR_057033166R → H.Corresponds to variant rs34478944dbSNPEnsembl.1
Natural variantiVAR_069138258Q → R.3 PublicationsCorresponds to variant rs2865394dbSNPEnsembl.1
Natural variantiVAR_061729332A → V.Corresponds to variant rs41275648dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04608112 – 86Missing in isoform 7. 1 PublicationAdd BLAST75
Alternative sequenceiVSP_00407987 – 149AERPQ…YRMKS → GNCHPGEAGLTLQGASWQWT STDLSLGSNLNSATWELTGF LSLCLGFFFWLMELTAGLLG RGC in isoform 5. 1 PublicationAdd BLAST63
Alternative sequenceiVSP_00407887 – 109Missing in isoform 4. CuratedAdd BLAST23
Alternative sequenceiVSP_004080150 – 429Missing in isoform 5. 1 PublicationAdd BLAST280
Alternative sequenceiVSP_045405225 – 248SAGPR…TLVDP → KSPKRAQGGDLGGEPPDPLG GGKG in isoform 6. 1 PublicationAdd BLAST24
Alternative sequenceiVSP_045406249 – 429Missing in isoform 6. 1 PublicationAdd BLAST181
Alternative sequenceiVSP_004081365 – 429GRRPA…WGGGI → VAAFTEVLNPSKSFMKFGIN FFQTPVNVDSLTSSHESQMF LTACRLVIFSRRFSTYFAQI HLRNHSVLHLCPHKIYLLKN KK in isoform 2. CuratedAdd BLAST65
Alternative sequenceiVSP_004082365 – 429GRRPA…WGGGI → GRRPADTQSRSFDGQE in isoform 3. CuratedAdd BLAST65

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ300575 mRNA. Translation: CAC18810.1.
CT002036 mRNA. No translation available.
AK122761 mRNA. Translation: BAG53713.1.
AL035541 Genomic DNA. Translation: CAI23107.1.
AL035541 Genomic DNA. Translation: CAM28299.1.
CH471077 Genomic DNA. Translation: EAW75511.1.
BC028218 mRNA. Translation: AAH28218.1.
CCDSiCCDS13461.1. [Q9H171-1]
CCDS54477.1. [Q9H171-7]
CCDS54478.1. [Q9H171-6]
RefSeqiNP_001153889.1. NM_001160417.1.
NP_001153890.1. NM_001160418.1. [Q9H171-7]
NP_001153891.1. NM_001160419.2. [Q9H171-6]
NP_001310895.1. NM_001323966.1.
NP_110403.2. NM_030776.2. [Q9H171-1]
UniGeneiHs.302123.

Genome annotation databases

EnsembliENST00000371173; ENSP00000360215; ENSG00000124256. [Q9H171-1]
ENST00000395822; ENSP00000379167; ENSG00000124256. [Q9H171-7]
ENST00000541799; ENSP00000440552; ENSG00000124256. [Q9H171-6]
GeneIDi81030.
KEGGihsa:81030.
UCSCiuc002xyo.4. human. [Q9H171-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ300575 mRNA. Translation: CAC18810.1.
CT002036 mRNA. No translation available.
AK122761 mRNA. Translation: BAG53713.1.
AL035541 Genomic DNA. Translation: CAI23107.1.
AL035541 Genomic DNA. Translation: CAM28299.1.
CH471077 Genomic DNA. Translation: EAW75511.1.
BC028218 mRNA. Translation: AAH28218.1.
CCDSiCCDS13461.1. [Q9H171-1]
CCDS54477.1. [Q9H171-7]
CCDS54478.1. [Q9H171-6]
RefSeqiNP_001153889.1. NM_001160417.1.
NP_001153890.1. NM_001160418.1. [Q9H171-7]
NP_001153891.1. NM_001160419.2. [Q9H171-6]
NP_001310895.1. NM_001323966.1.
NP_110403.2. NM_030776.2. [Q9H171-1]
UniGeneiHs.302123.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L4MNMR-A103-166[»]
2LNBNMR-A6-74[»]
3EYIX-ray1.45A/B103-166[»]
4KA4X-ray2.60A/B/D/E96-165[»]
ProteinModelPortaliQ9H171.
SMRiQ9H171.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123349. 13 interactors.
DIPiDIP-44121N.
IntActiQ9H171. 6 interactors.
MINTiMINT-6167522.
STRINGi9606.ENSP00000360215.

PTM databases

iPTMnetiQ9H171.
PhosphoSitePlusiQ9H171.

Polymorphism and mutation databases

BioMutaiZBP1.
DMDMi71153189.

Proteomic databases

PaxDbiQ9H171.
PeptideAtlasiQ9H171.
PRIDEiQ9H171.

Protocols and materials databases

DNASUi81030.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000371173; ENSP00000360215; ENSG00000124256. [Q9H171-1]
ENST00000395822; ENSP00000379167; ENSG00000124256. [Q9H171-7]
ENST00000541799; ENSP00000440552; ENSG00000124256. [Q9H171-6]
GeneIDi81030.
KEGGihsa:81030.
UCSCiuc002xyo.4. human. [Q9H171-1]

Organism-specific databases

CTDi81030.
DisGeNETi81030.
GeneCardsiZBP1.
H-InvDBHIX0203057.
HGNCiHGNC:16176. ZBP1.
HPAiHPA041256.
MIMi606750. gene.
neXtProtiNX_Q9H171.
OpenTargetsiENSG00000124256.
PharmGKBiPA38094.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J2S4. Eukaryota.
ENOG411196S. LUCA.
GeneTreeiENSGT00390000002234.
HOGENOMiHOG000230878.
HOVERGENiHBG036279.
InParanoidiQ9H171.
KOiK12965.
OMAiIGHGNVI.
OrthoDBiEOG091G0L53.
PhylomeDBiQ9H171.
TreeFamiTF337658.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000124256-MONOMER.
ReactomeiR-HSA-1606322. ZBP1(DAI) mediated induction of type I IFNs.
R-HSA-1606341. IRF3 mediated activation of type 1 IFN.
R-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-3134975. Regulation of innate immune responses to cytosolic DNA.
R-HSA-3270619. IRF3-mediated induction of type I IFN.

Miscellaneous databases

EvolutionaryTraceiQ9H171.
GeneWikiiZBP1.
GenomeRNAii81030.
PROiQ9H171.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000124256.
CleanExiHS_ZBP1.
ExpressionAtlasiQ9H171. baseline and differential.
GenevisibleiQ9H171. HS.

Family and domain databases

Gene3Di1.10.10.10. 2 hits.
InterProiIPR000607. dsRNA_A_deaminase.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF02295. z-alpha. 1 hit.
[Graphical view]
SMARTiSM00550. Zalpha. 2 hits.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiZBP1_HUMAN
AccessioniPrimary (citable) accession number: Q9H171
Secondary accession number(s): A2A2F7
, B3KVA1, F5GYT1, Q5JY39, Q9BYW4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 25, 2002
Last sequence update: July 19, 2005
Last modified: November 2, 2016
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.