GBP1

Summary

GBP1 (guanylate binding protein 1, HGNC:4182) is a protein-coding gene on chromosome 1p22.2, encoding Guanylate-binding protein 1 (P32455). Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens.

Guanylate binding protein expression is induced by interferon. Guanylate binding proteins are characterized by their ability to specifically bind guanine nucleotides (GMP, GDP, and GTP) and are distinguished from the GTP-binding proteins by the presence of 2 binding motifs rather than 3.

Source: NCBI Gene 2633 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 111 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_002053

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4182
Approved symbol	GBP1
Name	guanylate binding protein 1
Location	1p22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000117228
Ensembl biotype	protein_coding
OMIM	600411
Entrez	2633

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 7 retained_intron

ENST00000370473, ENST00000459831, ENST00000468959, ENST00000469194, ENST00000479889, ENST00000484970, ENST00000493139, ENST00000495131, ENST00000681280, ENST00000872735, ENST00000872736, ENST00000872737, ENST00000872738, ENST00000872739, ENST00000958149, ENST00000958150

RefSeq mRNA: 1 — MANE Select: NM_002053 NM_002053

CCDS: CCDS718

Canonical transcript exons

ENST00000370473 — 11 exons

Exon	Start	End
ENSE00000776340	89058841	89059043
ENSE00001452808	89063045	89063253
ENSE00001452810	89065160	89065208
ENSE00001650939	89056016	89056228
ENSE00001675983	89055113	89055215
ENSE00001676167	89060197	89060324
ENSE00001681134	89059317	89059426
ENSE00001753781	89057992	89058234
ENSE00001797851	89056854	89057134
ENSE00001883245	89052319	89053468
ENSE00003549548	89054682	89054875

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 98.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 56.3010 / max 6768.7358, expressed in 1296 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13142	46.0925	1009
13145	3.6270	1036
13144	3.1717	922
13143	1.9313	448
13137	0.8665	230
13146	0.3290	158
13147	0.2222	98
13141	0.0607	21

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pericardium	UBERON:0002407	98.90	gold quality
trigeminal ganglion	UBERON:0001675	98.38	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.23	gold quality
lower lobe of lung	UBERON:0008949	97.96	gold quality
superficial temporal artery	UBERON:0001614	97.58	gold quality
vermiform appendix	UBERON:0001154	97.50	gold quality
gall bladder	UBERON:0002110	97.14	gold quality
monocyte	CL:0000576	96.83	gold quality
caecum	UBERON:0001153	96.70	gold quality
mononuclear cell	CL:0000842	96.62	gold quality
cauda epididymis	UBERON:0004360	96.59	gold quality
leukocyte	CL:0000738	96.52	gold quality
epithelium of nasopharynx	UBERON:0001951	96.48	gold quality
vena cava	UBERON:0004087	96.14	gold quality
lymph node	UBERON:0000029	95.88	gold quality
penis	UBERON:0000989	95.87	gold quality
body of uterus	UBERON:0009853	95.85	gold quality
pylorus	UBERON:0001166	95.53	gold quality
granulocyte	CL:0000094	95.09	gold quality
mammary duct	UBERON:0001765	94.94	gold quality
myometrium	UBERON:0001296	94.92	gold quality
germinal epithelium of ovary	UBERON:0001304	94.87	gold quality
saphenous vein	UBERON:0007318	94.68	gold quality
smooth muscle tissue	UBERON:0001135	94.63	gold quality
decidua	UBERON:0002450	94.57	gold quality
ectocervix	UBERON:0012249	94.31	gold quality
urethra	UBERON:0000057	94.23	gold quality
left uterine tube	UBERON:0001303	94.16	gold quality
parietal pleura	UBERON:0002400	94.14	gold quality
sural nerve	UBERON:0015488	94.02	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	1813.45
E-CURD-114	yes	534.75
E-MTAB-2983	no	667.87
E-GEOD-110499	no	285.31
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, NFKB1, NFKB, REL, RELA, STAT1, TP53, YY1

miRNA regulators (miRDB)

56 targeting GBP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-183-3P	99.41	69.41	1598

Literature-anchored findings (GeneRIF, showing 40)

• The helical domain of GBP-1 mediates the inhibition of endothelial cell proliferation by inflammatory cytokines. (PMID:11598000)
• GBP-1 expression is selectively induced by inflammatory cytokines and is an activation marker of endothelial cells during inflammatory diseases. (PMID:12414522)
• The GBP-1 GTPase controls the invasive and angiogenic capability of endothelial cells through inhibition of MMP-1 expression. (PMID:12881412)
• NF-kappaB motif and ISRE co-operate in the activation of GBP-1 expression by inflammatory cytokines in endothelial cells. (PMID:14741045)
• designed point mutants in the phosphate-binding loop (P-loop) as well as in the switch I and switch II regions. These mutant proteins were analysed for their interaction with guanine nucleotides and for their ability to hydrolyse GTP. (PMID:15504415)
• Golgi targeting of human guanylate-binding protein-1 requires nucleotide binding, isoprenylation, and an IFN-gamma-inducible cofactor. (PMID:15937107)
• GBP-1 regulates anti-proliferative effect of inflammatory cytokines. It also mediates inhibition of endothelial cell invasiveness by down regulation of MMP-1[review] (PMID:16005050)
• crystal structures of the N-terminal G domain trapped at successive steps along the reaction pathway and biochemical data reveal the molecular basis for nucleotide-dependent homodimerization and cleavage of GTP (PMID:16511497)
• kinetic investigation of GTP hydrolysis catalyzed by interferon-gamma-induced hGBP1 (PMID:16873363)
• Interferon-alpha upregulates GBP1 in cultured human vascular endothelial cells. (PMID:16894355)
• Human guanylate binding protein-1 may be a useful surrogate marker for diagnosis of bacterial meningitis (PMID:16936281)
• 3 genes were upregulated in patients with chronic EBV infection: guanylate binding protein 1, tumor necrosis factor-induced protein 6, and guanylate binding protein 5; they may be associated with the inflammatory reaction or with cell proliferation. (PMID:18260761)
• GBP-1 may be a novel biomarker and an active component of a Th-1-like angiostatic immune reaction in colorectal carcinoma. (PMID:18697200)
• Inhibition of endothelial cell spreading and migration by inflammatory cytokines is mediated by GBP-1 through induction of ITGA4 expression. (PMID:18697840)
• GBP-1 is a novel marker of intestinal mucosal inflammation that may protect against epithelial apoptosis induced by inflammatory cytokines and subsequent loss of barrier function (PMID:19079332)
• The authors demonstrate for the first time that both the alpha-helix of the intermediate region and the (103)DXEKGD(108) motif play critical roles for the hydrolysis to GMP. (PMID:19150356)
• The results indicate that the GBP1, STAT1 and CXCL10 may be novel risk genes for the differentiation of PBM at the monocyte stage. (PMID:19223260)
• Positions of cysteine residues buried between the C-terminal domain of GBP1 and the rest of the protein are identified which report a large change of accessibility by the compound after addition of GTP. (PMID:19463820)
• Results identify intramolecular contacts of guanylate binding protein 1, which relay nucleotide-dependent structural changes from the N-terminus to the C-terminus and thereby mediate tetramer formation of the protein. (PMID:20450919)
• Animals carrying murine mammary carcinoma cells that had been given doxycycline for induction of human GBP-1 expression revealed a significantly reduced tumor growth compared with mock-treated mice. (PMID:20454519)
• These findings identify a role for IFN-alphaA-mediated GBP-1 expression in the prevention of intestinal epithelial apoptosis by commensal bacteria. (PMID:20483731)
• Data indicate that GBP-1 contributes to vascular dysfunction in chronic inflammatory diseases by inhibiting endothelial progenitor cell (EPC) angiogenic activity via the induction of premature EPC differentiation. (PMID:20716116)
• hGBP-1, hGBP-2 showed dimerization-related GTPase activity for GMP formation. (PMID:20923658)
• GBP-1 cellular 1ocalization depends on prenylation and dimerization. (PMID:21151871)
• higher GBP1 level in oral cavity squamous cell carcinoma tissue was associated with higher overall pathological stage, positive perineural invasion, and poorer prognosis (PMID:21714544)
• Data indicate that GBP1 guanine cap (i.e., C-terminal guanine-binding amino acid motif, particularly Arg240/Arg244) is key structural element responsible for dimerization and is essential for self-activation of GTPase activity. (PMID:22059445)
• establish GBP1 as a previously unknown link between EGFR activity and MMP1 expression and nominate it as a novel potential therapeutic target for inhibiting GBM invasion. (PMID:22162832)
• Data indicate that alpha12/13 represents a stable subdomain of guanylate-binding protein 1 (hGBP1). (PMID:22607347)
• Cytokine-induced GBP-1 retards cell proliferation by forming a negative feedback loop that suppresses beta-catenin / TCF signaling. (PMID:22692453)
• Thermodynamic insight as to how the stability of an intermediate catalytic complex regulates the product formation in hGBP1. (PMID:22859948)
• GBP1 inhibits proliferation, migration, invasion and tumor formation of colon tumor cells. (PMID:23042300)
• results suggested that GBP-1 acts directly as a tumor suppressor in CRC and the loss of GBP-1 expression might indicate tumor evasion from the IFN-gamma-dominated Th1 immune response. (PMID:23042300)
• GBP1/2 are critical effectors of antichlamydial interferon (IFN)gamma-mediated pathogen clearance via rerouting of bacterial inclusions in macrophages for lysosomal degradation. (PMID:23086406)
• Data indicate that among three deductive p53 response element (p53RE) present in the hGBP1 promoter region, two p53REs were found to be transactivated by p53. (PMID:23727578)
• GBP-1 is a novel member within the family of actin-remodeling proteins specifically mediating IFN-gamma-dependent defense strategies. (PMID:24190970)
• IFN-gamma-induced Guanylate Binding Protein-1 is a novel Actin Cytoskeleton Remodeling Factor. GBP-1 may induce actin remodeling via globular actin sequestering and/or filament capping. GBP-1 is a novel member within the family of actin remodeling proteins, specifically mediating IFN-gamma-dependent defense strategies. (PMID:24190970)
• GBP-1 is a downstream processor of IFN-gamma. (PMID:24337748)
• data show that dimer formation of hGBP1 involves multiple spatially distant regions of the protein, namely, the N-terminal LG domain and the C-terminal helices alpha13. (PMID:24991938)
• Molecular dynamics studies showed that only GTP decreases the formation of the GBP1:PIM1 complex through an allosteric mechanism, outlining the rational for the identification of new compounds potentially able to revert resistance to paclitaxel. (PMID:25081641)
• GBP1 overexpression is necessary for the radioresistant phenotype in clinically relevant radioresistant cells (PMID:25098609)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
rattus_norvegicus	Gbp1	ENSRNOG00000023943
rattus_norvegicus	Gbp3	ENSRNOG00000036885
rattus_norvegicus	Gbp1	ENSRNOG00000068984
drosophila_melanogaster	atl	FBGN0039213

Paralogs (10): GBP3 (ENSG00000117226), ATL2 (ENSG00000119787), RNF112 (ENSG00000128482), GBP5 (ENSG00000154451), GBP2 (ENSG00000162645), GBP4 (ENSG00000162654), GBP6 (ENSG00000183347), ATL3 (ENSG00000184743), ATL1 (ENSG00000198513), GBP7 (ENSG00000213512)

Protein

Protein identifiers

Guanylate-binding protein 1 — P32455 (reviewed: P32455)

Alternative names: GTP-binding protein 1, Guanine nucleotide-binding protein 1, Interferon-induced guanylate-binding protein 1

All UniProt accessions (2): A0A7P0TAZ1, P32455

UniProt curated annotations — full annotation on UniProt →

Function. Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens. Hydrolyzes GTP to GMP in two consecutive cleavage reactions: GTP is first hydrolyzed to GDP and then to GMP in a processive manner. Following infection, recruited to the pathogen-containing vacuoles or vacuole-escaped bacteria and promotes both inflammasome assembly and autophagy. Acts as a positive regulator of inflammasome assembly by facilitating the detection of inflammasome ligands from pathogens. Involved in the lysis of pathogen-containing vacuoles, releasing pathogens into the cytosol. Following pathogen release in the cytosol, forms a protein coat in a GTPase-dependent manner that encapsulates pathogens and promotes the detection of ligands by pattern recognition receptors. Plays a key role in inflammasome assembly in response to infection by Gram-negative bacteria: following pathogen release in the cytosol, forms a protein coat that encapsulates Gram-negative bacteria and directly binds to lipopolysaccharide (LPS), disrupting the O-antigen barrier and unmasking lipid A that is that detected by the non-canonical inflammasome effector CASP4/CASP11. Also promotes recruitment of proteins that mediate bacterial cytolysis, leading to release double-stranded DNA (dsDNA) that activates the AIM2 inflammasome. Involved in autophagy by regulating bacteriolytic peptide generation via its interaction with ubiquitin-binding protein SQSTM1, which delivers monoubiquitinated proteins to autolysosomes for the generation of bacteriolytic peptides. Confers protection to several pathogens, including the bacterial pathogens L.monocytogenes and M.bovis BCG as well as the protozoan pathogen T.gondii. Exhibits antiviral activity against influenza virus.

Subunit / interactions. Homodimer; homodimerization occurs upon GTP-binding and is required for the second hydrolysis step from GDP to GMP. Undergoes conformational changes and oligomerization upon GTP-binding and hydrolysis. Heterodimer with other family members, including GBP2, GBP3, GBP4 and GBP5. Dimerization regulates subcellular location to membranous structures and GTP hydrolysis promotes membrane fragmentation. Interacts with SQSTM1. Interacts (when phosphorylated) with 14-3-3 protein sigma (SFN); leading to GBP1 retention in the cytosol and inactivation.

Subcellular location. Cytoplasmic vesicle membrane. Golgi apparatus membrane. Cell membrane. Cytoplasm. Cytosol. Secreted.

Post-translational modifications. Isoprenylation is required for proper subcellular location. Phosphorylated at Ser-156 by PIM1 in absence of infection, inhibits GBP1: phosphorylation promotes interaction with 14-3-3 protein sigma (SFN), leading to GBP1 retention in the cytosol. Dephosphorylated in response to infection, liberating GBP1. (Microbial infection) Ubiquitinated by S.flexneri IpaH9.8, leading to its degradation by the proteasome, thereby preventing its ability to promote host defense against bacterial infection.

Induction. By IFNG during macrophage activation, and by TNF and IL1B.

Similarity. Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.

RefSeq proteins (1): NP_002044* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003191	Guanylate-bd/ATL_C	Domain
IPR015894	Guanylate-bd_N	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030386	G_GB1_RHD3_dom	Domain
IPR036543	Guanylate-bd_C_sf	Homologous_superfamily
IPR037684	GBP_C	Domain

Pfam: PF02263, PF02841

Catalyzed reactions (Rhea), 2 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)
• GDP + H2O = GMP + phosphate + H(+) (RHEA:22156)

UniProt features (112 total): mutagenesis site 33, helix 25, binding site 17, strand 14, cross-link 8, sequence variant 4, turn 3, modified residue 3, chain 1, propeptide 1, domain 1, lipid moiety-binding region 1, region of interest 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
1F5N	X-RAY DIFFRACTION	1.7
1DG3	X-RAY DIFFRACTION	1.8
2B8W	X-RAY DIFFRACTION	2.22
6K1Z	X-RAY DIFFRACTION	2.31
2BC9	X-RAY DIFFRACTION	2.8
2D4H	X-RAY DIFFRACTION	2.9
2B92	X-RAY DIFFRACTION	3.2
6K2D	X-RAY DIFFRACTION	3.6
8CQB	ELECTRON MICROSCOPY	3.7
6LOJ	X-RAY DIFFRACTION	3.72
8Q4L	ELECTRON MICROSCOPY	5.12
8R1A	ELECTRON MICROSCOPY	26.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32455-F1	91.48	0.77

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (17): 53; 67; 68; 69; 75; 97; 183; 184; 241; 247; 250; 48 …

Post-translational modifications (12): 156, 589, 590, 589, 207, 209, 210, 382, 562, 567, 573, 587

Mutagenesis-validated functional residues (33):

Position	Phenotype
48	abolished gtpase activity.
51	loss of gtpase activity. constitutively monomeric. expressed throughout the cytoplasm, loss of vesicular accumulation. i
61–63	impaired homooligomarization and localization to bacterial surface.
74	abolished gdp hydrolysis.
76	abolished gdpase activity.
87–88	does not affect localization to bacterial surface.
151	reduced phosphorylation by pim1.
153–158	abolished phosphorylation by pim1 and interaction with 14-3-3 protein sigma (sfn).
153	abolished phosphorylation by pim1.
155	abolished phosphorylation by pim1.
156	reduced phosphorylation by pim1, leading to hyperactivation and golgi fragmentation.
157	no effect.
184	strongly decreased nucleotide-binding.
207–210	does not affect localization to bacterial surface.
207	in 8kr mutant; abolished ubiquitination by s. flexneri ipah9.8 when associated with r-209, r-210, r-382, r-562, r-567, r
209	in 8kr mutant; abolished ubiquitination by s. flexneri ipah9.8 when associated with r-207, r-210, r-382, r-562, r-567, r
210	in 8kr mutant; abolished ubiquitination by s. flexneri ipah9.8 when associated with r-207, r-209, r-382, r-562, r-567, r
227–228	constitutively dimeric. localizes at vesicle-like structures at the plasma membrane.
244–246	does not affect localization to bacterial surface.
308	impairs membrane association; alone and when associated with a-309 and a-310.
309	impairs membrane association; when associated with a-308 and a-310.
310	impairs membrane association; when associated with a-308 and a-309.
382	in 8kr mutant; abolished ubiquitination by s. flexneri ipah9.8 when associated with r-207, r-209, r-210, r-562, r-567, r
427	no effect.
562	in 8kr mutant; abolished ubiquitination by s. flexneri ipah9.8 when associated with r-207, r-209, r-210, r-382, r-567, r

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-168276	NS1 Mediated Effects on Host Pathways
R-HSA-877300	Interferon gamma signaling
R-HSA-9948001	CASP4 inflammasome assembly
R-HSA-9953170	GBP-mediated host defense
R-HSA-9956593	Enterobacterial factors antagonize host defense
R-HSA-9968551	Regulation of GBP-mediated host defense

MSigDB gene sets: 435 (showing top): GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, WALLACE_PROSTATE_CANCER_RACE_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, MODULE_45, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, MODULE_128, KYNG_DNA_DAMAGE_DN

GO Biological Process (20): negative regulation of interleukin-2 production (GO:0032703), defense response to bacterium (GO:0042742), defense response to protozoan (GO:0042832), innate immune response (GO:0045087), regulation of calcium-mediated signaling (GO:0050848), negative regulation of T cell receptor signaling pathway (GO:0050860), defense response to virus (GO:0051607), cytolysis in another organism (GO:0051715), negative regulation of ERK1 and ERK2 cascade (GO:0070373), cellular response to type II interferon (GO:0071346), cellular response to interleukin-1 (GO:0071347), cellular response to tumor necrosis factor (GO:0071356), protein localization to vacuole (GO:0072665), positive regulation of pyroptotic inflammatory response (GO:0140639), non-canonical inflammasome complex assembly (GO:0160075), negative regulation of substrate adhesion-dependent cell spreading (GO:1900025), regulation of protein localization to plasma membrane (GO:1903076), negative regulation of protein localization to plasma membrane (GO:1903077), immune system process (GO:0002376), protein maturation (GO:0051604)

GO Molecular Function (16): lipopolysaccharide binding (GO:0001530), actin binding (GO:0003779), GTPase activity (GO:0003924), G protein activity (GO:0003925), GDP phosphatase activity (GO:0004382), GTP binding (GO:0005525), GDP binding (GO:0019003), enzyme binding (GO:0019899), cytokine binding (GO:0019955), spectrin binding (GO:0030507), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), Hsp90 protein binding (GO:0051879), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (12): Golgi membrane (GO:0000139), extracellular region (GO:0005576), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), vesicle membrane (GO:0012506), actin cytoskeleton (GO:0015629), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), symbiont cell surface (GO:0106139), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Influenza Infection	1
Interferon Signaling	1
Non-canonical inflammasome activation	1
Antimicrobial mechanism of IFN-stimulated genes	1
Infection with Enterobacteria	1
GBP-mediated host defense	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cellular response to cytokine stimulus	3
protein binding	3
cytoplasm	3
defense response	2
protein localization to plasma membrane	2
cytoskeletal protein binding	2
guanyl ribonucleotide binding	2
negative regulation of cytokine production	1
interleukin-2 production	1
regulation of interleukin-2 production	1
response to bacterium	1
response to protozoan	1
defense response to other organism	1
immune response	1
defense response to symbiont	1
calcium-mediated signaling	1
regulation of intracellular signal transduction	1
T cell receptor signaling pathway	1
regulation of T cell receptor signaling pathway	1
negative regulation of antigen receptor-mediated signaling pathway	1
response to virus	1
cytolysis	1
killing of cells of another organism	1
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
response to type II interferon	1
response to interleukin-1	1
response to tumor necrosis factor	1
protein localization to organelle	1
positive regulation of inflammatory response	1
pyroptotic inflammatory response	1
protein-containing complex assembly	1
negative regulation of cell-substrate adhesion	1
substrate adhesion-dependent cell spreading	1
regulation of substrate adhesion-dependent cell spreading	1
regulation of protein localization to cell periphery	1
regulation of protein localization to membrane	1
regulation of protein localization to plasma membrane	1

Protein interactions and networks

STRING

1476 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GBP1	MX1	P20591	791
GBP1	IFNG	P01579	746
GBP1	ISG20	Q96AZ6	739
GBP1	STAT1	P42224	735
GBP1	IFIT1	P09914	735
GBP1	IFI44	Q8TCB0	729
GBP1	IFIT2	P09913	728
GBP1	IFIT3	O14879	721
GBP1	SQSTM1	Q13501	721
GBP1	OAS2	P29728	698
GBP1	IRF7	Q92985	691
GBP1	RTP4	Q96DX8	644
GBP1	ISG15	P05161	643
GBP1	HLA-B	P01889	641
GBP1	ATL1	Q8WXF7	638

IntAct

67 interactions, top by confidence:

A	B	Type	Score
GBP1	GBP1	psi-mi:“MI:0407”(direct interaction)	0.860
GBP1	GBP1	psi-mi:“MI:0915”(physical association)	0.860
GBP1	GBP3	psi-mi:“MI:0915”(physical association)	0.790
GBP5	GBP1	psi-mi:“MI:0914”(association)	0.720
GBP1	GBP2	psi-mi:“MI:0914”(association)	0.720
GBP1	GBP2	psi-mi:“MI:0915”(physical association)	0.720
GBP1	GBP5	psi-mi:“MI:0915”(physical association)	0.720
GBP2	GBP1	psi-mi:“MI:0915”(physical association)	0.720
GBP5	GBP1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (57): GBP1 (Affinity Capture-MS), GBP3 (Affinity Capture-MS), GBP1 (Affinity Capture-MS), GBP2 (Affinity Capture-MS), GBP1 (Affinity Capture-MS), GBP1 (Affinity Capture-MS), GBP1 (Affinity Capture-MS), GBP1 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), GBP1 (Affinity Capture-MS), GBP1 (Affinity Capture-MS), GBP1 (Affinity Capture-MS), GBP1 (Proximity Label-MS), GBP3 (Affinity Capture-MS), GBP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JDV3, A0MWD1, A1E2I4, A4UUI3, A6QQL3, A7VK00, B0BNF1, B0KWP7, B1H120, B1MTN8, B2KIE9, B3GNI6, B5FW69, P20591, P20592, P32455, P32456, Q01514, Q0VCP4, Q14141, Q1MT80, Q28379, Q2KTC2, Q3SZN0, Q4R555, Q5D1D6, Q5I2P5, Q5R5G3, Q5R9T9, Q5RBE1, Q61107, Q63663, Q642H3, Q6AXA6, Q6IRQ5, Q6ZN66, Q6ZU15, Q8C1B7, Q8C650, Q8CFB4

Diamond homologs: A0A0G2JDV3, A4UUI3, P32455, P32456, Q01514, Q1MT80, Q5D1D6, Q5R9T9, Q5RBE1, Q61107, Q63663, Q6ZN66, Q8CFB4, Q8N8V2, Q91Z40, Q96PP8, Q96PP9, Q9H0R5, Q9Z0E6, A0E2L1, B6K0N7, P0CQ46, P0CQ47, A5DB26, Q4PEQ0, Q525S7, Q9UTE0, A0A386CAB9, Q9P5X6, C4JQN4, Q6BK59

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

111 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	82
Likely benign	15
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1320035	NM_002053.3(GBP1):c.1665+30_1665+35del	Likely pathogenic

SpliceAI

1410 predictions. Top by Δscore:

Variant	Effect	Δscore
1:89053465:GTTC:G	acceptor_gain	1.0000
1:89053467:TC:T	acceptor_gain	1.0000
1:89053468:CC:C	acceptor_gain	1.0000
1:89053469:C:CC	acceptor_gain	1.0000
1:89053469:CTAA:C	acceptor_loss	1.0000
1:89054677:GATA:G	donor_loss	1.0000
1:89054678:ATAC:A	donor_loss	1.0000
1:89054679:TAC:T	donor_loss	1.0000
1:89054680:ACCT:A	donor_loss	1.0000
1:89054871:TTCCA:T	acceptor_gain	1.0000
1:89054874:CA:C	acceptor_gain	1.0000
1:89054876:C:CC	acceptor_gain	1.0000
1:89056859:ACT:A	donor_gain	1.0000
1:89056860:CTC:C	donor_gain	1.0000
1:89056861:T:TA	donor_gain	1.0000
1:89056862:C:CA	donor_gain	1.0000
1:89057135:C:CC	acceptor_gain	1.0000
1:89057141:A:AC	acceptor_gain	1.0000
1:89057985:GACTT:G	donor_loss	1.0000
1:89057986:ACTT:A	donor_loss	1.0000
1:89057987:CTTAC:C	donor_loss	1.0000
1:89057988:TTA:T	donor_loss	1.0000
1:89057989:TAC:T	donor_loss	1.0000
1:89057990:A:AC	donor_gain	1.0000
1:89057990:A:AG	donor_loss	1.0000
1:89057991:C:CC	donor_gain	1.0000
1:89057991:C:CT	donor_loss	1.0000
1:89057991:CGAGG:C	donor_gain	1.0000
1:89058014:T:TA	donor_gain	1.0000
1:89058041:A:AC	donor_gain	1.0000

AlphaMissense

3918 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:89063083:T:A	K51I	0.982
1:89058934:A:G	W180R	0.981
1:89058934:A:T	W180R	0.981
1:89060320:G:C	F65L	0.979
1:89060320:G:T	F65L	0.979
1:89060322:A:G	F65L	0.979
1:89058080:A:C	F262L	0.978
1:89058080:A:T	F262L	0.978
1:89058082:A:G	F262L	0.978
1:89059376:G:C	S123R	0.970
1:89059376:G:T	S123R	0.970
1:89059378:T:G	S123R	0.970
1:89056905:G:C	F368L	0.969
1:89056905:G:T	F368L	0.969
1:89056907:A:G	F368L	0.969
1:89058176:G:C	F230L	0.969
1:89058176:G:T	F230L	0.969
1:89058178:A:G	F230L	0.969
1:89056890:G:C	F373L	0.959
1:89056890:G:T	F373L	0.959
1:89056892:A:G	F373L	0.959
1:89058158:A:C	F236L	0.957
1:89058158:A:T	F236L	0.957
1:89058160:A:G	F236L	0.957
1:89058917:G:C	F185L	0.957
1:89058917:G:T	F185L	0.957
1:89058919:A:G	F185L	0.957
1:89059373:G:C	S124R	0.953
1:89059373:G:T	S124R	0.953
1:89059375:T:G	S124R	0.953

dbSNP variants (sampled 300 via entrez): RS1000343842 (1:89058469 T>C), RS1000678072 (1:89057253 C>A,T), RS1000909571 (1:89051855 G>A), RS1001785870 (1:89057627 G>A), RS1001797443 (1:89057881 A>G,T), RS1002004366 (1:89062740 G>A), RS1002119203 (1:89064319 A>G), RS1002267677 (1:89062458 TAG>T), RS1002515709 (1:89067103 G>C), RS1003631692 (1:89064234 T>A), RS1003681792 (1:89061437 A>G), RS1004210768 (1:89055392 A>G), RS1004963066 (1:89054730 C>A,T), RS1005134972 (1:89060286 C>A,T), RS1005305000 (1:89054115 T>A)

Disease associations

OMIM: gene MIM:600411 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005833_1	Remission after SSRI treatment in MDD or openness	8.000000e-07
GCST012020_233	Serum metabolite levels	6.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0007914	openness measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3430900 (PROTEIN-PROTEIN INTERACTION)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

93 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression, increases expression	3
bisphenol A	affects cotreatment, increases methylation, affects expression	2
sodium arsenite	decreases expression	2
Arsenic	affects expression, decreases expression, increases abundance	2
Estradiol	decreases expression, increases expression	2
Formaldehyde	increases expression	2
Lipopolysaccharides	increases expression, decreases reaction	2
Tretinoin	increases expression	2
Cyclosporine	decreases expression	2
Genistein	decreases expression	2
Particulate Matter	increases abundance, affects cotreatment, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
TL8-506	affects cotreatment, increases expression	1
quinone	increases expression, increases reaction	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
apocarotenal	increases expression	1
propionaldehyde	increases expression	1
lead acetate	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
nickel chloride	increases expression	1
chloroquine diphosphate	decreases expression	1
tobacco tar	decreases expression, decreases reaction	1
ochratoxin A	decreases acetylation, decreases expression	1
potassium chromate(VI)	decreases expression	1
diallyl disulfide	decreases reaction, decreases expression	1
triadimefon	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3374667	Binding	Inhibition of GBP1 (unknown origin)-PIM1 (unknown origin) interaction at 100 nM by SPR analysis	Identification of the first inhibitor of the GBP1:PIM1 interaction. Implications for the development of a new class of anticancer agents against paclitaxel resistant cancer cells. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1FB	Abcam A-549 GBP1 KO	Cancer cell line	Male
CVCL_SP71	HAP1 GBP1 (-) 1	Cancer cell line	Male
CVCL_SP72	HAP1 GBP1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.