GBP5_MOUSE
ID GBP5_MOUSE Reviewed; 590 AA.
AC Q8CFB4; E9QJR4; Q8CFA4; Q8CFA8;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Guanylate-binding protein 5;
DE EC=3.6.5.- {ECO:0000250|UniProtKB:Q96PP8};
DE AltName: Full=GTP-binding protein 5;
DE Short=GBP-5;
DE Short=MuGBP-5;
DE AltName: Full=Guanine nucleotide-binding protein 5;
DE Flags: Precursor;
GN Name=Gbp5;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND
RP INDUCTION BY IFNG; LPS AND TNF.
RC STRAIN=Swiss Webster; TISSUE=Lung;
RX PubMed=12396730; DOI=10.1089/107999002760274926;
RA Nguyen T.T., Hu Y., Widney D.P., Mar R.C., Smith J.B.;
RT "Murine GBP-5, a new member of the murine guanylate-binding protein family,
RT is coordinately regulated with other GBPs in vivo and in vitro.";
RL J. Interferon Cytokine Res. 22:899-909(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Adams M., Mural R.;
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=NMRI; TISSUE=Mammary tumor;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18025219; DOI=10.4049/jimmunol.179.11.7729;
RA Degrandi D., Konermann C., Beuter-Gunia C., Kresse A., Wurthner J.,
RA Kurig S., Beer S., Pfeffer K.;
RT "Extensive characterization of IFN-induced GTPases mGBP1 to mGBP10 involved
RT in host defense.";
RL J. Immunol. 179:7729-7740(2007).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH NLRP3.
RX PubMed=22461501; DOI=10.1126/science.1217141;
RA Shenoy A.R., Wellington D.A., Kumar P., Kassa H., Booth C.J., Cresswell P.,
RA MacMicking J.D.;
RT "GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals.";
RL Science 336:481-485(2012).
CC -!- FUNCTION: As an activator of NLRP3 inflammasome assembly, plays a role
CC in innate immunity and inflammation. Promotes selective NLRP3
CC inflammasome assembly in response to microbial and soluble, but not
CC crystalline, inflammasome activating agents (PubMed:22461501).
CC Hydrolyzes GTP, but in contrast to other family members, such as GBP1
CC and GBP2, does not produce GMP (By similarity).
CC {ECO:0000250|UniProtKB:Q96PP8, ECO:0000269|PubMed:22461501}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189;
CC Evidence={ECO:0000250|UniProtKB:Q96PP8};
CC -!- SUBUNIT: Homodimer. Heterodimer with other family members, including
CC GBP1, GBP2, GBP3 and GBP4 (By similarity). Dimerization is nucleotide-
CC dependent (By similarity). Dimerization regulates subcellular location.
CC May also form tetramers (dimer of dimers) in the presence of GTP (By
CC similarity). Interacts with NLRP3, possibly in its tetrameric form, and
CC promotes PYCARD/ASC polymerization (PubMed:22461501).
CC {ECO:0000250|UniProtKB:Q96PP8, ECO:0000269|PubMed:22461501}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96PP8}. Golgi
CC apparatus membrane {ECO:0000250|UniProtKB:Q96PP8}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q96PP8}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:18025219}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8CFB4-1; Sequence=Displayed;
CC Name=2; Synonyms=GBP-5a;
CC IsoId=Q8CFB4-2; Sequence=VSP_057889, VSP_057890;
CC -!- TISSUE SPECIFICITY: Low expression, if any, in many tissues in the
CC absence of stimulation. {ECO:0000269|PubMed:12396730}.
CC -!- INDUCTION: Strongly up-regulated by IFNG and, at lower levels, by LPS.
CC The LPS-induced increase is attenuated in the presence of
CC dexamethasone. Up-regulated by TNF in certain strains. Up-regulation by
CC a combination of IFNG and TNF is synergistic, even in strains that do
CC not respond to TNF alone. {ECO:0000269|PubMed:12396730,
CC ECO:0000269|PubMed:18025219}.
CC -!- PTM: Isoprenylation is required for proper subcellular location.
CC {ECO:0000250|UniProtKB:Q96PP8}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice exhibit impaired host defense and
CC NLRP3-dependent inflammatory responses. During LPS-induced sepsis,
CC knockout animals show 60 to 75% reduction in IL1B and IL-18 serum
CC levels compared to wild-type mice. Orogastric challenge with Listeria
CC monocytogenes leads to higher bacterial burdens, discernible weight
CC loss, and 50 to 80% fewer leukocytes expressing active CASP1 in
CC mesenteric lymph nodes compared to wild-type counterparts.
CC {ECO:0000269|PubMed:22461501}.
CC -!- SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase
CC superfamily. GB1/RHD3 GTPase family. GB1 subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01052}.
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; AF422243; AAN31451.1; -; mRNA.
DR EMBL; AF487898; AAN52282.1; -; mRNA.
DR EMBL; AY128412; AAN46362.1; -; Genomic_DNA.
DR EMBL; AC102108; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC058555; AAH58555.1; -; mRNA.
DR CCDS; CCDS17877.1; -. [Q8CFB4-1]
DR RefSeq; NP_705792.2; NM_153564.2. [Q8CFB4-1]
DR AlphaFoldDB; Q8CFB4; -.
DR SMR; Q8CFB4; -.
DR BioGRID; 230914; 2.
DR iPTMnet; Q8CFB4; -.
DR PhosphoSitePlus; Q8CFB4; -.
DR SwissPalm; Q8CFB4; -.
DR EPD; Q8CFB4; -.
DR MaxQB; Q8CFB4; -.
DR PaxDb; Q8CFB4; -.
DR PRIDE; Q8CFB4; -.
DR ProteomicsDB; 267770; -. [Q8CFB4-1]
DR ProteomicsDB; 267771; -. [Q8CFB4-2]
DR Antibodypedia; 33615; 330 antibodies from 32 providers.
DR DNASU; 229898; -.
DR Ensembl; ENSMUST00000090127; ENSMUSP00000087587; ENSMUSG00000105504. [Q8CFB4-1]
DR Ensembl; ENSMUST00000197459; ENSMUSP00000142938; ENSMUSG00000105504. [Q8CFB4-2]
DR GeneID; 229898; -.
DR KEGG; mmu:229898; -.
DR UCSC; uc008rop.1; mouse. [Q8CFB4-1]
DR CTD; 115362; -.
DR MGI; MGI:2429943; Gbp5.
DR VEuPathDB; HostDB:ENSMUSG00000105504; -.
DR GeneTree; ENSGT00940000162684; -.
DR HOGENOM; CLU_018608_2_2_1; -.
DR InParanoid; Q8CFB4; -.
DR OMA; PRKGMQA; -.
DR PhylomeDB; Q8CFB4; -.
DR TreeFam; TF331602; -.
DR BioGRID-ORCS; 229898; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Gbp5; mouse.
DR PRO; PR:Q8CFB4; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q8CFB4; protein.
DR Bgee; ENSMUSG00000105504; Expressed in spleen and 47 other tissues.
DR ExpressionAtlas; Q8CFB4; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IDA:MGI.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; IMP:UniProtKB.
DR GO; GO:0045089; P:positive regulation of innate immune response; IMP:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IMP:UniProtKB.
DR GO; GO:0032741; P:positive regulation of interleukin-18 production; IMP:UniProtKB.
DR GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0034067; P:protein localization to Golgi apparatus; ISO:MGI.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR CDD; cd16269; GBP_C; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR030386; G_GB1_RHD3_dom.
DR InterPro; IPR037684; GBP_C.
DR InterPro; IPR003191; Guanylate-bd/ATL_C.
DR InterPro; IPR036543; Guanylate-bd_C_sf.
DR InterPro; IPR015894; Guanylate-bd_N.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF02263; GBP; 1.
DR Pfam; PF02841; GBP_C; 1.
DR SUPFAM; SSF48340; SSF48340; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51715; G_GB1_RHD3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Antimicrobial; Cytoplasm; Cytoplasmic vesicle;
KW Golgi apparatus; GTP-binding; Hydrolase; Immunity; Inflammatory response;
KW Lipoprotein; Membrane; Methylation; Nucleotide-binding; Prenylation;
KW Reference proteome.
FT CHAIN 1..587
FT /note="Guanylate-binding protein 5"
FT /id="PRO_0000190970"
FT PROPEP 588..590
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000370786"
FT DOMAIN 35..277
FT /note="GB1/RHD3-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01052"
FT REGION 1..310
FT /note="GTPase domain (Globular)"
FT /evidence="ECO:0000250|UniProtKB:P32455"
FT REGION 1..306
FT /note="NLRP3-binding"
FT /evidence="ECO:0000250|UniProtKB:Q96PP8"
FT REGION 529..590
FT /note="Required for tetramerization, but not for
FT dimerization"
FT /evidence="ECO:0000250|UniProtKB:Q96PP8"
FT BINDING 45..52
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P32455"
FT BINDING 67..69
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P32455"
FT BINDING 97..101
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P32455"
FT MOD_RES 587
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000255"
FT LIPID 587
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q96PP8"
FT VAR_SEQ 64..175
FT /note="Missing (in isoform 2)"
FT /id="VSP_057889"
FT VAR_SEQ 551..590
FT /note="EEADRIKAEQEAQLRALQQQLQHMREMNHHRRHHHDCVIS -> GRCPVIWC
FT LDLLLAEDEGPKQDLSQKLCCFGQEGGRLSGAEDGAASEALWISPFPETAGLCIPHCHP
FT SNLPSVESRSQGGSRRGLRHKPLRPGGPLCTHQEGARLSGAEDGTASEALWLSPVLETV
FT GLFIPHPHPCSLPSTDSRSEGGSRRGLRQKPLGLVDPCALTRKVAGCL (in
FT isoform 2)"
FT /id="VSP_057890"
FT CONFLICT 488..490
FT /note="SKA -> T (in Ref. 2; AAN46362)"
FT /evidence="ECO:0000305"
FT CONFLICT 488
FT /note="S -> K (in Ref. 1; AAN31451/AAN52282 and 4;
FT AAH58555)"
FT /evidence="ECO:0000305"
FT CONFLICT 501
FT /note="E -> K (in Ref. 1; AAN31451/AAN52282 and 4;
FT AAH58555)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 590 AA; 66930 MW; CEBC9CD65F183436 CRC64;
MAPEIHMPEP LCLIGSTEGH LVTNQEALKI LSAITQPVVV VAIVGLYRTG KSYLMNKLAG
KEKGFSVGST VQSHTKGIWM WCVPHPQKPD HTLVLLDTEG LGDVEKDDKK NDTQIFALAI
LLSSTFVYNT MNKIDQGAID LLHNVTELTD LLRTRNSSDS NQTEGEGPAD MSFFPDLVWT
LRDFFLDLQA NGHAITSDEY LENSLKLKQG SDERTQTFNL PRLCIQKFFP VKKCFVFDAP
ALGSKLSQLP TLSNEELNSD FVQDLSEFCS HIFTQSKTKT LPGGIQVNGP RLESLVLTYV
DAINSGALPS IENTVVTLAR RENSAAVQKA IGHYDQLMSE KVQLPTETLQ ELLDLHRTCE
REAIEIFRKH SFKDEGEFFQ KELESLLSAK QDEICKKNAD ASAALCSTLL GSIFKPLEQE
VAQEFYHKPG GHKLFLQRME QLKANYRQQP GKGTQAEEVL QTYLNAKETV SRTILQTDQV
LTDKEIQSKA EQERAEAARL EAQRLEAIRI QEEQRKAEME RQHQEQLRQI ALEKARVAQE
QQWILKQRAQ EEADRIKAEQ EAQLRALQQQ LQHMREMNHH RRHHHDCVIS
