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Protein

Guanylate-binding protein 5

Gene

Gbp5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

As an activator of NLRP3 inflammasome assembly, plays a role in innate immunity and inflammation. Promotes selective NLRP3 inflammasome assembly in response to microbial and soluble, but not crystalline, inflammasome activating agents (PubMed:22461501). Hydrolyzes GTP, but in contrast to other family members, such as GBP1 and GBP2, does not produce GMP (By similarity).By similarity1 Publication

Catalytic activityi

GTP + H2O = GDP + phosphate.By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi45 – 528GTPBy similarity
Nucleotide bindingi67 – 693GTPBy similarity
Nucleotide bindingi97 – 1015GTPBy similarity

GO - Molecular functioni

GO - Biological processi

  • cellular response to interferon-gamma Source: MGI
  • inflammatory response Source: UniProtKB-KW
  • interleukin-18 secretion Source: UniProtKB
  • interleukin-1 beta secretion Source: UniProtKB
  • positive regulation of cytokine production involved in inflammatory response Source: UniProtKB
  • positive regulation of innate immune response Source: UniProtKB
  • positive regulation of NLRP3 inflammasome complex assembly Source: UniProtKB
  • protein homotetramerization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Antimicrobial, Hydrolase

Keywords - Biological processi

Immunity, Inflammatory response

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Guanylate-binding protein 5 (EC:3.6.5.-By similarity)
Alternative name(s):
GTP-binding protein 5
Short name:
GBP-5
Short name:
MuGBP-5
Guanine nucleotide-binding protein 5
Gene namesi
Name:Gbp5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:2429943. Gbp5.

Subcellular locationi

  • Cytoplasm By similarity
  • Golgi apparatus membrane By similarity; Lipid-anchor By similarity

GO - Cellular componenti

  • cytoplasmic vesicle Source: MGI
  • Golgi membrane Source: UniProtKB-SubCell
  • membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Golgi apparatus, Membrane

Pathology & Biotechi

Disruption phenotypei

Mutant mice exhibit impaired host defense and NLRP3-dependent inflammatory responses. During LPS-induced sepsis, knockout animals show 60 to 75% reduction in IL1B and IL-18 serum levels compared to wild-type mice. Orogastric challenge with Listeria monocytogenes leads to higher bacterial burdens, discernible weight loss, and 50 to 80% fewer leukocytes expressing active CASP1 in mesenteric lymph nodes compared to wild-type counterparts.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 587587Guanylate-binding protein 5PRO_0000190970Add
BLAST
Propeptidei588 – 5903Removed in mature formSequence analysisPRO_0000370786

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei587 – 5871Cysteine methyl esterSequence analysis
Lipidationi587 – 5871S-geranylgeranyl cysteineBy similarity

Post-translational modificationi

Isoprenylation is required for proper subcellular location.By similarity

Keywords - PTMi

Lipoprotein, Methylation, Prenylation

Proteomic databases

EPDiQ8CFB4.
MaxQBiQ8CFB4.
PaxDbiQ8CFB4.
PRIDEiQ8CFB4.

PTM databases

iPTMnetiQ8CFB4.
PhosphoSiteiQ8CFB4.

Expressioni

Tissue specificityi

Low expression, if any, in many tissues in the absence of stimulation.1 Publication

Inductioni

Strongly up-regulated by IFNG and, at lower levels, by LPS. The LPS-induced increase is attenuated in the presence of dexamethasone. Up-regulated by TNF in certain strains. Up-regulation by a combination of IFNG and TNF is synergistic, even in strains that do not respond to TNF alone.1 Publication

Gene expression databases

BgeeiQ8CFB4.
CleanExiMM_GBP5.
ExpressionAtlasiQ8CFB4. baseline and differential.

Interactioni

Subunit structurei

Homodimer. Heterodimer with other family members, including GBP1, GBP2, GBP3 and GBP4 (By similarity). Dimerization is nucleotide-dependent (By similarity). Dimerization regulates subcellular location. May also form tetramers (dimer of dimers) in the presence of GTP (By similarity). Interacts with NLRP3, possibly in its tetrameric form, and promotes PYCARD/ASC polymerization (PubMed:22461501).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

MINTiMINT-4997709.
STRINGi10090.ENSMUSP00000087587.

Structurei

3D structure databases

ProteinModelPortaliQ8CFB4.
SMRiQ8CFB4. Positions 2-575.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini35 – 277243GB1/RHD3-type GAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 310310GTPase domain (Globular)By similarityAdd
BLAST
Regioni1 – 306306NLRP3-bindingBy similarityAdd
BLAST
Regioni529 – 59062Required for tetramerization, but not for dimerizationBy similarityAdd
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2037. Eukaryota.
ENOG410XR6Z. LUCA.
GeneTreeiENSGT00550000074475.
HOGENOMiHOG000266974.
HOVERGENiHBG001979.
InParanoidiQ8CFB4.
OrthoDBiEOG7BW0J3.
TreeFamiTF331602.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR030386. G_GB1_RHD3_dom.
IPR003191. Guanylate-bd_C.
IPR015894. Guanylate-bd_N.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF02263. GBP. 1 hit.
PF02841. GBP_C. 1 hit.
[Graphical view]
SUPFAMiSSF48340. SSF48340. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS51715. G_GB1_RHD3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8CFB4-1) [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
MAPEIHMPEP LCLIGSTEGH LVTNQEALKI LSAITQPVVV VAIVGLYRTG
60 70 80 90 100
KSYLMNKLAG KEKGFSVGST VQSHTKGIWM WCVPHPQKPD HTLVLLDTEG
110 120 130 140 150
LGDVEKDDKK NDTQIFALAI LLSSTFVYNT MNKIDQGAID LLHNVTELTD
160 170 180 190 200
LLRTRNSSDS NQTEGEGPAD MSFFPDLVWT LRDFFLDLQA NGHAITSDEY
210 220 230 240 250
LENSLKLKQG SDERTQTFNL PRLCIQKFFP VKKCFVFDAP ALGSKLSQLP
260 270 280 290 300
TLSNEELNSD FVQDLSEFCS HIFTQSKTKT LPGGIQVNGP RLESLVLTYV
310 320 330 340 350
DAINSGALPS IENTVVTLAR RENSAAVQKA IGHYDQLMSE KVQLPTETLQ
360 370 380 390 400
ELLDLHRTCE REAIEIFRKH SFKDEGEFFQ KELESLLSAK QDEICKKNAD
410 420 430 440 450
ASAALCSTLL GSIFKPLEQE VAQEFYHKPG GHKLFLQRME QLKANYRQQP
460 470 480 490 500
GKGTQAEEVL QTYLNAKETV SRTILQTDQV LTDKEIQSKA EQERAEAARL
510 520 530 540 550
EAQRLEAIRI QEEQRKAEME RQHQEQLRQI ALEKARVAQE QQWILKQRAQ
560 570 580 590
EEADRIKAEQ EAQLRALQQQ LQHMREMNHH RRHHHDCVIS
Length:590
Mass (Da):66,930
Last modified:July 27, 2011 - v2
Checksum:iCEBC9CD65F183436
GO
Isoform 2 (identifier: Q8CFB4-2) [UniParc]FASTAAdd to basket

Also known as: GBP-5a

The sequence of this isoform differs from the canonical sequence as follows:
     64-175: Missing.
     551-590: EEADRIKAEQ...RRHHHDCVIS → GRCPVIWCLD...ALTRKVAGCL

Show »
Length:612
Mass (Da):68,036
Checksum:i9CA68C1BD7FF433E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti488 – 4903SKA → T in AAN46362 (Ref. 2) Curated
Sequence conflicti488 – 4881S → K in AAN31451 (PubMed:12396730).Curated
Sequence conflicti488 – 4881S → K in AAN52282 (PubMed:12396730).Curated
Sequence conflicti488 – 4881S → K in AAH58555 (PubMed:15489334).Curated
Sequence conflicti501 – 5011E → K in AAN31451 (PubMed:12396730).Curated
Sequence conflicti501 – 5011E → K in AAN52282 (PubMed:12396730).Curated
Sequence conflicti501 – 5011E → K in AAH58555 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei64 – 175112Missing in isoform 2. VSP_057889Add
BLAST
Alternative sequencei551 – 59040EEADR…DCVIS → GRCPVIWCLDLLLAEDEGPK QDLSQKLCCFGQEGGRLSGA EDGAASEALWISPFPETAGL CIPHCHPSNLPSVESRSQGG SRRGLRHKPLRPGGPLCTHQ EGARLSGAEDGTASEALWLS PVLETVGLFIPHPHPCSLPS TDSRSEGGSRRGLRQKPLGL VDPCALTRKVAGCL in isoform 2. VSP_057890Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF422243 mRNA. Translation: AAN31451.1.
AF487898 mRNA. Translation: AAN52282.1.
AY128412 Genomic DNA. Translation: AAN46362.1.
AC102108 Genomic DNA. No translation available.
BC058555 mRNA. Translation: AAH58555.1.
CCDSiCCDS17877.1. [Q8CFB4-1]
RefSeqiNP_705792.2. NM_153564.2. [Q8CFB4-1]
UniGeneiMm.459245.

Genome annotation databases

EnsembliENSMUST00000090127; ENSMUSP00000087587; ENSMUSG00000105504. [Q8CFB4-1]
ENSMUST00000197459; ENSMUSP00000142938; ENSMUSG00000105504. [Q8CFB4-2]
GeneIDi229898.
KEGGimmu:229898.
UCSCiuc008rop.1. mouse. [Q8CFB4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF422243 mRNA. Translation: AAN31451.1.
AF487898 mRNA. Translation: AAN52282.1.
AY128412 Genomic DNA. Translation: AAN46362.1.
AC102108 Genomic DNA. No translation available.
BC058555 mRNA. Translation: AAH58555.1.
CCDSiCCDS17877.1. [Q8CFB4-1]
RefSeqiNP_705792.2. NM_153564.2. [Q8CFB4-1]
UniGeneiMm.459245.

3D structure databases

ProteinModelPortaliQ8CFB4.
SMRiQ8CFB4. Positions 2-575.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-4997709.
STRINGi10090.ENSMUSP00000087587.

PTM databases

iPTMnetiQ8CFB4.
PhosphoSiteiQ8CFB4.

Proteomic databases

EPDiQ8CFB4.
MaxQBiQ8CFB4.
PaxDbiQ8CFB4.
PRIDEiQ8CFB4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000090127; ENSMUSP00000087587; ENSMUSG00000105504. [Q8CFB4-1]
ENSMUST00000197459; ENSMUSP00000142938; ENSMUSG00000105504. [Q8CFB4-2]
GeneIDi229898.
KEGGimmu:229898.
UCSCiuc008rop.1. mouse. [Q8CFB4-1]

Organism-specific databases

CTDi115362.
MGIiMGI:2429943. Gbp5.

Phylogenomic databases

eggNOGiKOG2037. Eukaryota.
ENOG410XR6Z. LUCA.
GeneTreeiENSGT00550000074475.
HOGENOMiHOG000266974.
HOVERGENiHBG001979.
InParanoidiQ8CFB4.
OrthoDBiEOG7BW0J3.
TreeFamiTF331602.

Miscellaneous databases

ChiTaRSiGbp5. mouse.
PROiQ8CFB4.
SOURCEiSearch...

Gene expression databases

BgeeiQ8CFB4.
CleanExiMM_GBP5.
ExpressionAtlasiQ8CFB4. baseline and differential.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR030386. G_GB1_RHD3_dom.
IPR003191. Guanylate-bd_C.
IPR015894. Guanylate-bd_N.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF02263. GBP. 1 hit.
PF02841. GBP_C. 1 hit.
[Graphical view]
SUPFAMiSSF48340. SSF48340. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS51715. G_GB1_RHD3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Murine GBP-5, a new member of the murine guanylate-binding protein family, is coordinately regulated with other GBPs in vivo and in vitro."
    Nguyen T.T., Hu Y., Widney D.P., Mar R.C., Smith J.B.
    J. Interferon Cytokine Res. 22:899-909(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, INDUCTION BY IFNG; LPS AND TNF.
    Strain: Swiss Webster.
    Tissue: Lung.
  2. Adams M., Mural R.
    Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. "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).
    Strain: NMRI.
    Tissue: Mammary tumor.
  5. "GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals."
    Shenoy A.R., Wellington D.A., Kumar P., Kassa H., Booth C.J., Cresswell P., MacMicking J.D.
    Science 336:481-485(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH NLRP3.

Entry informationi

Entry nameiGBP5_MOUSE
AccessioniPrimary (citable) accession number: Q8CFB4
Secondary accession number(s): E9QJR4, Q8CFA4, Q8CFA8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 24, 2003
Last sequence update: July 27, 2011
Last modified: June 8, 2016
This is version 111 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.