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GBP1 (guanylate binding protein 1, interferon-inducible, 67kDa)

Written2009-10Nathalie Britzen-Laurent, Michael Stürzl
Division of Molecular, Experimental Surgery, Department of Surgery, Friedrich-Alexander University, Schwabachanlage 10, 91054 Erlangen, Germany

(Note : for Links provided by Atlas : click)

Identity

Alias_namesguanylate binding protein 1, interferon-inducible, 67kDa
guanylate binding protein 1, interferon-inducible
Other aliasGBP-1
HuGBP-1
HGNC (Hugo) GBP1
LocusID (NCBI) 2633
Atlas_Id 50147
Location 1p22.2  [Link to chromosome band 1p22]
Location_base_pair Starts at 89517987 and ends at 89531043 bp from pter ( according to hg19-Feb_2009)  [Mapping GBP1.png]
Local_order Chromosome 1; starts at 89,290,575 bp from pter and ends 89,303,631 bp from pter; size= 13,056 base pairs; orientation: minus strand (according to hg18-Mar_2006). The family of guanylate binding proteins (GBP) consists of 7 members. All seven genes are located in 1p22.2. The human GBP1 gene is telomeric to GBP2 and centromeric to GBP3.
Fusion genes
(updated 2016)
SIK3 (11q23.3) / GBP1 (1p22.2)

DNA/RNA

Description The GBP1 gene consists of 11 exons (ranging from 102 to 1164 bp) and 10 introns. The coding sequence starts in the second exon.
Transcription Only one variant mRNA has been described for GBP-1 (Accession Number: NM_002053). This mRNA is 3050 bp long with a coding sequence of 1779 bp. Four polymorphisms have been described for GBP-1: c.232A>G (codon 78 Ile>Val), c.498G>C (codon 166 Glu>Asp), c.1046C>G (codon 349 Thr>Ser), c.1226C>G (codon 409 Ala>Gly).
Pseudogene A pseudogene has been identified for GBP1 (LOC400759 alias FLJ17004) on chromosome 1 (1p22.2, chro 1: 89645826-89663081, according to hg18-Mar_2006). Two pseudogenes have also been described in the mouse (pseudomGbp1 and pseudomGbp2).

Protein

 
  A schematic representation of the domain structure and the three-dimensional structure of GBP-1. GBP-1 consists of a globular domain (residues 1 to 278), which contains the GTP binding and hydrolysis domains, and of a helical domain (residues 279 to 593) terminated by a polybasic sequence and an isoprenylation motif (CAAX). C= Cysteine, A= aliphatic acid, X= any amino-acid (here a serine, specifically recognized by a farnesyl-transferase).
Description GBP-1 belongs to the class of large GTPases that contains, in addition to the GBPs, three further groups of proteins, which share structural and biochemical properties: the dynamins, the Mx proteins and the atlastins. GBP-1 has a molecular weight of 67 kDa and its crystal structure has revealed the presence of two domains: (1) a N-terminal globular alpha/beta domain harbouring the GTPase activity and (2) a long C-terminal part organized in an index finger-like domain composed exclusively of seven alpha-helices (alpha7 - alpha13). The domains are connected by a short intermediate region consisting of one alpha-helix and a short two-stranded beta-sheet. In addition, GBP-1 harbours a C-terminal CAAX isoprenylation motif. GTPases typically harbour three classical GTP-binding domains: the phosphate-binding P-loop GXXXXGK(S/T), the phosphate- and Mg2+-binding DXXG motif (G, glycine; K, lysine; S, serine; D, aspartic acid; T, threonine; and X, any amino acid) and the guanine nucleotide-specificity providing (N/T)KXD motif (N, asparagine). In GBP-1 the classical (N/T)KXD motif is substituted by a conserved arginine-aspartic acid (RD)-motif (TLRD, with L, leucine and R, arginine).
Expression GBP-1 was initially shown to be among the most highly induced proteins in human fibroblasts exposed to interferon (IFN)-gamma. Subsequently, it was reported that in vitro hGBP-1 expression can be induced by IFN-gamma in many different cell types including endothelial cells, fibroblasts, keratinocytes, B-cells, T-cells or peripheral blood mononuclear cells. In vivo expression of hGBP-1 has been predominantly detected in inflammatory tissues and has been found to be associated almost exclusively with endothelial cells and monocytes. It has been shown subsequently that hGBP-1 expression in endothelial cells is also induced by other pro-inflammatory cytokines such as IFNalpha, TNFalpha and IL1alpha/IL1beta. Many other cytokines (IL-4, IL-6, IL-10, IL-18), chemokines (MCP-1, PF4) or growth factors (angiopoietin-2, PDGF B/B) tested did not affect GBP-1 expression in these cells. Interestingly, the two major angiogenic growth factors (AGF: bFGF, VEGF) are able to inhibit the expression of GBP-1 induced by inflammatory cytokines.
Localisation The localization of GBP-1 is primarily cytosolic and its distribution is granular. Plasma membrane association at the level of tight junctions has also been described. In addition, GBP-1 has been shown to be secreted from IFN-gamma-stimulated endothelial cells through a non-classical secretion pathway.
Function GTPase activity
GBP-1 can bind the three nucleotides GTP, GDP and GMP with a relative low affinity (Kd mant-GMP=0,53 μM, Kd mant-GDP=2,4 μM, Kdmant-GppNHp=1,1 μM). GBP-1 has however the ability to hydrolyse GTP to both GDP and GMP with a high hydrolysis rate (max 95 min-1). At physiological temperature GMP is the major product (90%) of hGBP1. On the contrary to small GTPases like Ras, GBP-1 does not require the presence of GEF (GTP exchange factor) or GAP (GTPase activating protein) proteins for its GTPase activity. In the case of GBP-1, the GTP hydrolysis is self-stimulated by oligomerization of the protein.
GBP-1 is involved in IFN-gamma response, either in infection or in inflammation.
Homology The human GBP family comprises 7 highly homologous members, all located on the chromosome 1. GBP-1 is to 77% similar to GBP-2, 88% to GBP-3, 56% to GBP-4, 68% to GBP-5, 54% to GBP-6 and 56% to GBP-7. Homologues have been found in various species like zebrafish, chimpanzee (99% homology), rat, dog or mouse. GBP-1 shares 59% of homology with murine GBP-1 and murine GBP-2.

Mutations

Note No somatic or germline mutations have yet been reported for human GBP-1.

Implicated in

Note
  
Entity Infection
Note GBP-1 exhibits antiviral activity against vesicular stomatitis virus and encephalomyocarditis virus. The expression of GBP-1 is also elevated in the blood of patients with a chronic active Epstein-Barr Virus infection. Furthermore GBP-1 and GBP-2 can potentiate the inhibitory effects of IFN-gamma on Chlamydia trachomatis growth. Finally, elevated concentrations of GBP-1 have been detected in the cerebrospinal fluid of patients with bacterial meningitis.
  
  
Entity Inflammation
Note As GBP-1 is mainly expressed in endothelial cells in vivo in a context of inflammation, its effects have been extensively studied in these cells. It has been showed in endothelial cells that GBP-1 mediates the effects of inflammatory cytokines and inhibits proliferation, spreading, migration or invasion. GBP-1 is also involved in the regulation of apoptosis and senescence in endothelial cells stimulated with IFN-alpha. Evidence for an implication in cancer has been found for GBP-1 (see below).
  
  
Entity Colorectal carcinomas
Note GBP-1 protein is strongly expressed in the stroma of about one third of colorectal carcinomas in association with an IFN-gamma dominated Th-1-like angiostatic immune response.
Prognosis This expression correlates with an increased cancer-related 5-year survival.
  

Bibliography

Interferon-induced guanylate binding protein-1 (GBP-1) mediates an antiviral effect against vesicular stomatitis virus and encephalomyocarditis virus.
Anderson SL, Carton JM, Lou J, Xing L, Rubin BY.
Virology. 1999 Mar 30;256(1):8-14.
PMID 10087221
 
Affinity purification of an interferon-induced human guanylate-binding protein and its characterization.
Cheng YS, Becker-Manley MF, Chow TP, Horan DC.
J Biol Chem. 1985 Dec 15;260(29):15834-9.
PMID 3934165
 
Interferon induction of fibroblast proteins with guanylate binding activity.
Cheng YS, Colonno RJ, Yin FH.
J Biol Chem. 1983 Jun 25;258(12):7746-50.
PMID 6305951
 
Extensive characterization of IFN-induced GTPases mGBP1 to mGBP10 involved in host defense.
Degrandi D, Konermann C, Beuter-Gunia C, Kresse A, Wurthner J, Kurig S, Beer S, Pfeffer K.
J Immunol. 2007 Dec 1;179(11):7729-40.
PMID 18025219
 
How guanylate-binding proteins achieve assembly-stimulated processive cleavage of GTP to GMP.
Ghosh A, Praefcke GJ, Renault L, Wittinghofer A, Herrmann C.
Nature. 2006 Mar 2;440(7080):101-4.
PMID 16511497
 
The guanylate binding protein-1 GTPase controls the invasive and angiogenic capability of endothelial cells through inhibition of MMP-1 expression.
Guenzi E, Topolt K, Lubeseder-Martellato C, Jorg A, Naschberger E, Benelli R, Albini A, Sturzl M.
EMBO J. 2003 Aug 1;22(15):3772-82.
PMID 12881412
 
Oligonucleotide microarray analysis of gene expression profiles followed by real-time reverse-transcriptase polymerase chain reaction assay in chronic active Epstein-Barr virus infection.
Ito Y, Shibata-Watanabe Y, Ushijima Y, Kawada J, Nishiyama Y, Kojima S, Kimura H.
J Infect Dis. 2008 Mar 1;197(5):663-6.
PMID 18260761
 
Guanylate-binding protein-1 expression is selectively induced by inflammatory cytokines and is an activation marker of endothelial cells during inflammatory diseases.
Lubeseder-Martellato C, Guenzi E, Jorg A, Topolt K, Naschberger E, Kremmer E, Zietz C, Tschachler E, Hutzler P, Schwemmle M, Matzen K, Grimm T, Ensoli B, Sturzl M.
Am J Pathol. 2002 Nov;161(5):1749-59.
PMID 12414522
 
Golgi targeting of human guanylate-binding protein-1 requires nucleotide binding, isoprenylation, and an IFN-gamma-inducible cofactor.
Modiano N, Lu YE, Cresswell P.
Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8680-5. Epub 2005 Jun 3.
PMID 15937107
 
Prenylation of an interferon-gamma-induced GTP-binding protein: the human guanylate binding protein, huGBP1.
Nantais DE, Schwemmle M, Stickney JT, Vestal DJ, Buss JE.
J Leukoc Biol. 1996 Sep;60(3):423-31.
PMID 8830800
 
Angiostatic immune reaction in colorectal carcinoma: Impact on survival and perspectives for antiangiogenic therapy.
Naschberger E, Croner RS, Merkel S, Dimmler A, Tripal P, Amann KU, Kremmer E, Brueckl WM, Papadopoulos T, Hohenadl C, Hohenberger W, Sturzl M.
Int J Cancer. 2008 Nov 1;123(9):2120-9.
PMID 18697200
 
In silico genomic analysis of the human and murine guanylate-binding protein (GBP) gene clusters.
Olszewski MA, Gray J, Vestal DJ.
J Interferon Cytokine Res. 2006 May;26(5):328-52.
PMID 16689661
 
Interferon-alpha prevents apoptosis of endothelial cells after short-term exposure but induces replicative senescence after continuous stimulation.
Pammer J, Reinisch C, Birner P, Pogoda K, Sturzl M, Tschachler E.
Lab Invest. 2006 Oct;86(10):997-1007. Epub 2006 Aug 7.
PMID 16894355
 
Identification of residues in the human guanylate-binding protein 1 critical for nucleotide binding and cooperative GTP hydrolysis.
Praefcke GJ, Kloep S, Benscheid U, Lilie H, Prakash B, Herrmann C.
J Mol Biol. 2004 Nov 12;344(1):257-69.
PMID 15504415
 
Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins.
Prakash B, Praefcke GJ, Renault L, Wittinghofer A, Herrmann C.
Nature. 2000 Feb 3;403(6769):567-71.
PMID 10676968
 
Triphosphate structure of guanylate-binding protein 1 and implications for nucleotide binding and GTPase mechanism.
Prakash B, Renault L, Praefcke GJ, Herrmann C, Wittinghofer A.
EMBO J. 2000 Sep 1;19(17):4555-64.
PMID 10970849
 
Guanylate-binding protein-1 is expressed at tight junctions of intestinal epithelial cells in response to interferon-gamma and regulates barrier function through effects on apoptosis.
Schnoor M, Betanzos A, Weber DA, Parkos CA.
Mucosal Immunol. 2009 Jan;2(1):33-42. Epub 2008 Sep 17.
PMID 19079332
 
The interferon-induced 67-kDa guanylate-binding protein (hGBP1) is a GTPase that converts GTP to GMP.
Schwemmle M, Staeheli P.
J Biol Chem. 1994 Apr 15;269(15):11299-305.
PMID 7512561
 
Human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-gamma.
Tietzel I, El-Haibi C, Carabeo RA.
PLoS One. 2009 Aug 4;4(8):e6499.
PMID 19652711
 
Unique features of different members of the human guanylate-binding protein family.
Tripal P, Bauer M, Naschberger E, Mortinger T, Hohenadl C, Cornali E, Thurau M, Sturzl M.
J Interferon Cytokine Res. 2007 Jan;27(1):44-52.
PMID 17266443
 
The guanylate-binding proteins (GBPs): proinflammatory cytokine-induced members of the dynamin superfamily with unique GTPase activity.
Vestal DJ.
J Interferon Cytokine Res. 2005 Aug;25(8):435-43. (REVIEW)
PMID 16108726
 
Guanylate binding protein-1 inhibits spreading and migration of endothelial cells through induction of integrin alpha4 expression.
Weinlander K, Naschberger E, Lehmann MH, Tripal P, Paster W, Stockinger H, Hohenadl C, Sturzl M.
FASEB J. 2008 Dec;22(12):4168-78. Epub 2008 Aug 12.
PMID 18697840
 

Citation

This paper should be referenced as such :
Britzen-Laurent, N ; Störzl, M
GBP1 (guanylate binding protein 1, interferon-inducible, 67kDa)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(8):761-764.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/GBP1ID50147ch1p22.html


External links

Nomenclature
HGNC (Hugo)GBP1   4182
Cards
AtlasGBP1ID50147ch1p22
Entrez_Gene (NCBI)GBP1  2633  guanylate binding protein 1
Aliases
GeneCards (Weizmann)GBP1
Ensembl hg19 (Hinxton)ENSG00000117228 [Gene_View]  chr1:89517987-89531043 [Contig_View]  GBP1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000117228 [Gene_View]  chr1:89517987-89531043 [Contig_View]  GBP1 [Vega]
ICGC DataPortalENSG00000117228
TCGA cBioPortalGBP1
AceView (NCBI)GBP1
Genatlas (Paris)GBP1
WikiGenes2633
SOURCE (Princeton)GBP1
Genetics Home Reference (NIH)GBP1
Genomic and cartography
GoldenPath hg19 (UCSC)GBP1  -     chr1:89517987-89531043 -  1p22.2   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)GBP1  -     1p22.2   [Description]    (hg38-Dec_2013)
EnsemblGBP1 - 1p22.2 [CytoView hg19]  GBP1 - 1p22.2 [CytoView hg38]
Mapping of homologs : NCBIGBP1 [Mapview hg19]  GBP1 [Mapview hg38]
OMIM600411   
Gene and transcription
Genbank (Entrez)AB208912 AK291783 AK298032 AK303893 AY920436
RefSeq transcript (Entrez)NM_002053
RefSeq genomic (Entrez)NC_000001 NC_018912 NT_032977 NW_004929290
Consensus coding sequences : CCDS (NCBI)GBP1
Cluster EST : UnigeneHs.62661 [ NCBI ]
CGAP (NCI)Hs.62661
Alternative Splicing GalleryENSG00000117228
Gene ExpressionGBP1 [ NCBI-GEO ]   GBP1 [ EBI - ARRAY_EXPRESS ]   GBP1 [ SEEK ]   GBP1 [ MEM ]
Gene Expression Viewer (FireBrowse)GBP1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)2633
GTEX Portal (Tissue expression)GBP1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP32455   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP32455  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP32455
Splice isoforms : SwissVarP32455
PhosPhoSitePlusP32455
Domaine pattern : Prosite (Expaxy)G_GB1_RHD3 (PS51715)   
Domains : Interpro (EBI)G_GB1_RHD3_dom    Guanylate-bd_C    Guanylate-bd_N    P-loop_NTPase   
Domain families : Pfam (Sanger)GBP (PF02263)    GBP_C (PF02841)   
Domain families : Pfam (NCBI)pfam02263    pfam02841   
Conserved Domain (NCBI)GBP1
DMDM Disease mutations2633
Blocks (Seattle)GBP1
PDB (SRS)1DG3    1F5N    2B8W    2B92    2BC9    2D4H   
PDB (PDBSum)1DG3    1F5N    2B8W    2B92    2BC9    2D4H   
PDB (IMB)1DG3    1F5N    2B8W    2B92    2BC9    2D4H   
PDB (RSDB)1DG3    1F5N    2B8W    2B92    2BC9    2D4H   
Structural Biology KnowledgeBase1DG3    1F5N    2B8W    2B92    2BC9    2D4H   
SCOP (Structural Classification of Proteins)1DG3    1F5N    2B8W    2B92    2BC9    2D4H   
CATH (Classification of proteins structures)1DG3    1F5N    2B8W    2B92    2BC9    2D4H   
SuperfamilyP32455
Human Protein AtlasENSG00000117228
Peptide AtlasP32455
HPRD02681
IPIIPI00028564   IPI00909555   IPI01015897   IPI00556028   
Protein Interaction databases
DIP (DOE-UCLA)P32455
IntAct (EBI)P32455
FunCoupENSG00000117228
BioGRIDGBP1
STRING (EMBL)GBP1
ZODIACGBP1
Ontologies - Pathways
QuickGOP32455
Ontology : AmiGOGolgi membrane  actin binding  GTPase activity  protein binding  GTP binding  extracellular region  cytosol  cytosol  plasma membrane  metabolic process  enzyme binding  cytokine binding  spectrin binding  identical protein binding  regulation of calcium-mediated signaling  negative regulation of T cell receptor signaling pathway  defense response to virus  Hsp90 protein binding  interferon-gamma-mediated signaling pathway  negative regulation of ERK1 and ERK2 cascade  negative regulation of substrate adhesion-dependent cell spreading  negative regulation of interleukin-2 secretion  regulation of protein localization to plasma membrane  negative regulation of protein localization to plasma membrane  
Ontology : EGO-EBIGolgi membrane  actin binding  GTPase activity  protein binding  GTP binding  extracellular region  cytosol  cytosol  plasma membrane  metabolic process  enzyme binding  cytokine binding  spectrin binding  identical protein binding  regulation of calcium-mediated signaling  negative regulation of T cell receptor signaling pathway  defense response to virus  Hsp90 protein binding  interferon-gamma-mediated signaling pathway  negative regulation of ERK1 and ERK2 cascade  negative regulation of substrate adhesion-dependent cell spreading  negative regulation of interleukin-2 secretion  regulation of protein localization to plasma membrane  negative regulation of protein localization to plasma membrane  
REACTOMEP32455 [protein]
REACTOME Pathways877300 [pathway]   
NDEx NetworkGBP1
Atlas of Cancer Signalling NetworkGBP1
Wikipedia pathwaysGBP1
Orthology - Evolution
OrthoDB2633
GeneTree (enSembl)ENSG00000117228
Phylogenetic Trees/Animal Genes : TreeFamGBP1
HOVERGENP32455
HOGENOMP32455
Homologs : HomoloGeneGBP1
Homology/Alignments : Family Browser (UCSC)GBP1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerGBP1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)GBP1
dbVarGBP1
ClinVarGBP1
1000_GenomesGBP1 
Exome Variant ServerGBP1
ExAC (Exome Aggregation Consortium)GBP1 (select the gene name)
Genetic variants : HAPMAP2633
Genomic Variants (DGV)GBP1 [DGVbeta]
DECIPHER (Syndromes)1:89517987-89531043  ENSG00000117228
CONAN: Copy Number AnalysisGBP1 
Mutations
ICGC Data PortalGBP1 
TCGA Data PortalGBP1 
Broad Tumor PortalGBP1
OASIS PortalGBP1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICGBP1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDGBP1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch GBP1
DgiDB (Drug Gene Interaction Database)GBP1
DoCM (Curated mutations)GBP1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)GBP1 (select a term)
intoGenGBP1
NCG5 (London)GBP1
Cancer3DGBP1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM600411   
Orphanet
MedgenGBP1
Genetic Testing Registry GBP1
NextProtP32455 [Medical]
TSGene2633
GENETestsGBP1
Huge Navigator GBP1 [HugePedia]
snp3D : Map Gene to Disease2633
BioCentury BCIQGBP1
ClinGenGBP1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD2633
Chemical/Pharm GKB GenePA28596
Clinical trialGBP1
Miscellaneous
canSAR (ICR)GBP1 (select the gene name)
Probes
Litterature
PubMed57 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineGBP1
EVEXGBP1
GoPubMedGBP1
iHOPGBP1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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