Details for: GBP5

Gene ID: 115362

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: GBP5

Ensembl ID: ENSG00000154451

Description: guanylate binding protein 5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • T follicular helper cell CL0002038
    CSI 12.52
    rCSI 9.37%
    PRS 55.12
  • elicited macrophage CL0000861
    CSI 12.01
    rCSI 11.03%
    PRS 47.98
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 9.91
    rCSI 16.96%
    PRS 61.8
  • double negative thymocyte CL0002489
    CSI 8.7
    rCSI 6.05%
    PRS 48.98
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 8.37
    rCSI 16.69%
    PRS 58.69
  • neutrophil CL0000775
    CSI 7.06
    rCSI 39.5%
    PRS 54.54
  • activated type II NK T cell CL0000931
    CSI 5.95
    rCSI 6.7%
    PRS 56.74
  • effector memory CD4-positive, alpha-beta T cell CL0000905
    CSI 5.82
    rCSI 7.93%
    PRS 68.59
  • CD14-positive monocyte CL0001054
    CSI 4.88
    rCSI 6.08%
    PRS 52
  • alpha-beta T cell CL0000789
    CSI 4.51
    rCSI 5.28%
    PRS 55.74
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 4.37
    rCSI 3.33%
    PRS 51.69
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 4.32
    rCSI 3.1%
    PRS 53.14
  • regulatory T cell CL0000815
    CSI 4.11
    rCSI 4.77%
    PRS 63.93
  • intermediate monocyte CL0002393
    CSI 3.85
    rCSI 5.8%
    PRS 42.73
  • CD4-positive, alpha-beta thymocyte CL0000810
    CSI 3.8
    rCSI 3.04%
    PRS 62.22
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 3.57
    rCSI 4.31%
    PRS 48.22
  • mucosal invariant T cell CL0000940
    CSI 3.5
    rCSI 2.83%
    PRS 51.78
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 3.49
    rCSI 2.35%
    PRS 50.54
  • memory T cell CL0000813
    CSI 2.96
    rCSI 5.69%
    PRS 70.6
  • activated CD8-positive, alpha-beta T cell CL0000906
    CSI 2.85
    rCSI 2.8%
    PRS 69.08
  • CD16-negative, CD56-bright natural killer cell, human CL0000938
    CSI 2.83
    rCSI 2.12%
    PRS 73.55
  • alveolar macrophage CL0000583
    CSI 2.45
    rCSI 4.04%
    PRS 46.28
  • lung resident memory CD8-positive, alpha-beta T cell CL4033039
    CSI 2.31
    rCSI 5.99%
    PRS 72.16
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 2.21
    rCSI 2.02%
    PRS 55.5
  • CD16-positive, CD56-dim natural killer cell, human CL0000939
    CSI 2.16
    rCSI 1.44%
    PRS 66.76
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.16
    rCSI 1.95%
    PRS 37.8
  • mature T cell CL0002419
    CSI 2.14
    rCSI 1.67%
    PRS 57.08
  • naive T cell CL0000898
    CSI 2.14
    rCSI 1.49%
    PRS 53.29
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 2.07
    rCSI 2.72%
    PRS 53.9
  • mononuclear phagocyte CL0000113
    CSI 2.03
    rCSI 4.47%
    PRS 44.82
  • activated CD4-positive, alpha-beta T cell CL0000896
    CSI 2
    rCSI 1.85%
    PRS 61.31
  • CD4-positive helper T cell CL0000492
    CSI 1.95
    rCSI 1.48%
    PRS 52.74
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 1.94
    rCSI 1.15%
    PRS 54.96
  • monocyte CL0000576
    CSI 1.89
    rCSI 3.42%
    PRS 64.05
  • CD8-positive, alpha-beta memory T cell CL0000909
    CSI 1.87
    rCSI 1.95%
    PRS 71.59
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 1.85
    rCSI 1.82%
    PRS 55.88
  • multi-ciliated epithelial cell CL0005012
    CSI 1.76
    rCSI 1.76%
    PRS 35.71
  • group 3 innate lymphoid cell CL0001071
    CSI 1.68
    rCSI 1.26%
    PRS 44
  • exhausted T cell CL0011025
    CSI 1.62
    rCSI 27.41%
    PRS 74.21
  • activated CD4-positive, alpha-beta T cell, human CL0001043
    CSI 1.56
    rCSI 3.75%
    PRS 84.23
  • erythrocyte CL0000232
    CSI 1.54
    rCSI 3.5%
    PRS 46.64
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 1.53
    rCSI 1.83%
    PRS 60.89
  • CD4-positive, alpha-beta cytotoxic T cell CL0000934
    CSI 1.46
    rCSI 2.01%
    PRS 61.38
  • CD34-positive, CD56-positive, CD117-positive common innate lymphoid precursor, human CL0001074
    CSI 1.44
    rCSI 16.73%
    PRS 77.48
  • lung macrophage CL1001603
    CSI 1.42
    rCSI 3.18%
    PRS 47.12
  • T-helper 17 cell CL0000899
    CSI 1.2
    rCSI 0.95%
    PRS 62.48
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 1.17
    rCSI 3.36%
    PRS 57.8
  • alternatively activated macrophage CL0000890
    CSI 1.13
    rCSI 1.42%
    PRS 54.18
  • mature alpha-beta T cell CL0000791
    CSI 1.02
    rCSI 3.68%
    PRS 59.88
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 0.82
    rCSI 0.99%
    PRS 38.07
  • T-helper 1 cell CL0000545
    CSI 0.78
    rCSI 1.42%
    PRS 67.97
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 0.63
    rCSI 0.49%
    PRS 39.57
  • cytotoxic T cell CL0000910
    CSI 0.53
    rCSI 3.05%
    PRS 53.06
  • lung resident memory CD4-positive, alpha-beta T cell CL4033038
    CSI 0.53
    rCSI 5.22%
    PRS 82.24
  • megakaryocyte CL0000556
    CSI 0.46
    rCSI 1.98%
    PRS 56.87
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 0.4
    rCSI 2.42%
    PRS 66.05
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 0.35
    rCSI 1.75%
    PRS 51.45

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [GBP5](/details-gene/115362) (Guanylate Binding Protein 5) is an interferon-inducible GTPase that plays a critical role in the innate immune system. As a member of the guanylate-binding protein family, it functions as a sensor and effector molecule in host defense against intracellular pathogens, including bacteria and viruses. Its primary mechanism involves promoting the assembly of inflammasome complexes, leading to pyroptotic cell death and the maturation of pro-inflammatory cytokines like IL-1β and IL-18. Expression data indicates that **Overall**, [GBP5](/details-gene/115362) is a significant gene within a wide range of activated immune cells, particularly subsets of T cells and myeloid cells, highlighting its central function in orchestrating inflammatory and anti-pathogen responses. ## Cellular Roles and Expression Landscape The expression profile of [GBP5](/details-gene/115362) firmly establishes it as a key component of the immune system, with high significance across both myeloid and lymphoid lineages. **Overall**, its most significant expression is observed in cell types central to adaptive and innate immunity. It shows particularly high cell significance scores in [T follicular helper cell](/details-cell/CL0002038) (CSI: 12.52) and [elicited macrophage](/details-cell/CL0000861) (CSI: 12.01), suggesting a critical role in both antibody response coordination and direct pathogen clearance. High significance is also noted in various activated and effector T cell populations, including [activated CD8-positive, alpha-beta T cell, human](/details-cell/CL0001049) (CSI: 9.91), [effector memory CD4-positive, alpha-beta T cell](/details-cell/CL0000905) (CSI: 5.82), and [regulatory T cell](/details-cell/CL0000815) (CSI: 4.11). This broad expression across functionally diverse T cell subsets indicates a fundamental role in T cell biology, potentially linking interferon signaling to T cell-mediated immunity. Furthermore, [GBP5](/details-gene/115362) is prominent in the myeloid compartment, with high significance in [neutrophil](/details-cell/CL0000775) (CSI: 7.06) and multiple monocyte subsets, including [CD14-positive monocyte](/details-cell/CL0001054) (CSI: 4.88) and [intermediate monocyte](/details-cell/CL0002393) (CSI: 3.85). This pattern is consistent with its established function as a frontline defender in the innate immune response to infection. The collective expression landscape paints a picture of [GBP5](/details-gene/115362) as a versatile immune effector whose activity is integral to the function of the very cells that orchestrate host defense. ## Pathways and Molecular Function The functional annotations for [GBP5](/details-gene/115362) align precisely with its role as an interferon-stimulated immune effector. It is a GTPase ([GO:0003924](https://www.ebi.ac.uk/QuickGO/term/GO:0003924)) that is heavily involved in pathways related to interferon signaling, particularly [Interferon gamma signaling](/details-pathway/R-HSA-877300). This upstream regulation is the basis for its role in downstream effector functions. A primary function of [GBP5](/details-gene/115362) is the [Activation of innate immune response](/details-go/GO:0002218). It achieves this by acting as a scaffold to promote the assembly of inflammasome complexes, specifically showing activity in the [Positive regulation of aim2 inflammasome complex assembly](/details-go/GO:0140973) and [Positive regulation of nlrp3 inflammasome complex assembly](/details-go/GO:1900227). This role was demonstrated to be crucial for immunity in mammals [Link](https://doi.org/10.1126/science.1217141). Inflammasome activation subsequently leads to the [Positive regulation of pyroptotic inflammatory response](/details-go/GO:0140639) and the production of key inflammatory cytokines, including [interleukin-1 beta](/details-go/GO:0032731) and [interleukin-18](/details-go/GO:0032741). In addition to its anti-bacterial functions, [GBP5](/details-gene/115362) is annotated for [Defense response to virus](/details-go/GO:0051607). Research has shown that it can act as an inhibitor of HIV-1 infectivity [Link](https://doi.org/10.1016/j.chom.2016.02.019) and can exert broad antiviral activity by inhibiting the furin-mediated processing of viral envelope proteins, a mechanism required by numerous viruses for maturation and infectivity [Link](https://doi.org/10.1016/j.celrep.2019.04.063). Its molecular functions, including [Gtp binding](/details-go/GO:0005525) and [Identical protein binding](/details-go/GO:0042802), are essential for its ability to oligomerize and execute these scaffolding and enzymatic roles. ## Research Directions The established roles of [GBP5](/details-gene/115362) in inflammasome assembly and viral restriction provide a solid foundation for further investigation into its cell-type-specific functions and therapeutic potential. **Proposed Hypotheses:** 1. Given its high significance in multiple T cell subsets, including [T follicular helper cell](/details-cell/CL0002038) and [activated CD8-positive, alpha-beta T cell, human](/details-cell/CL0001049), [GBP5](/details-gene/115362) may possess cell-intrinsic functions that directly modulate T cell differentiation or effector activity, independent of its canonical role in myeloid cell inflammasomes. It could, for instance, regulate metabolic reprogramming or cytotoxic granule release upon T cell activation. 2. Based on its broad antiviral activity through furin inhibition [Link](https://doi.org/10.1016/j.celrep.2019.04.063), variations in the basal and interferon-inducible expression of [GBP5](/details-gene/115362) in different tissues could be a key determinant of host susceptibility to emerging furin-dependent viruses, such as certain coronaviruses and influenza strains. **Experimental Approach:** To test the hypothesis that [GBP5](/details-gene/115362) directly regulates T cell effector functions, a compelling experiment would be to use CRISPR-Cas9 to generate a [GBP5](/details-gene/115362) knockout in primary human CD8+ T cells. These modified cells, along with wild-type controls, would then be activated *in vitro* using anti-CD3/CD28 antibodies. The impact on effector function could be assessed by quantifying the production of key cytokines (e.g., IFN-γ, TNF-α) and cytolytic proteins (e.g., Granzyme B, Perforin) using flow cytometry and ELISA. Furthermore, a co-culture cytotoxicity assay with target tumor cells would reveal whether [GBP5](/details-gene/115362) is required for efficient T cell-mediated killing. **Therapeutic Potential:** As an intracellular protein central to host defense, [GBP5](/details-gene/115362) represents a complex but potentially valuable therapeutic node. Direct targeting may be challenging, but modulating its expression or the pathways it regulates could be beneficial. In infectious diseases or cancer immunotherapy, strategies to augment [GBP5](/details-gene/115362) expression (e.g., through targeted interferon delivery or gene therapy) could enhance anti-pathogen and anti-tumor immunity. Conversely, in autoinflammatory conditions characterized by excessive inflammasome activation, targeted inhibition of [GBP5](/details-gene/115362) function or its interaction with inflammasome components could offer a novel strategy to dampen pathological inflammation. Its specific role in promoting pyroptosis makes it a candidate for modulation in diseases where this form of cell death is either beneficial (cancer) or detrimental (sepsis, inflammatory disorders).

Genular Protein ID: 410940338

Symbol: GBP5_HUMAN

Name: Guanylate-binding protein 5

UniProtKB Accession Codes:

Q96PP8 B2RCE1 Q86TM5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChEBI 9 DMDM 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 1 ExpressionAtlas 1 GO 32 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 2 Rhea 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 15175044

Title: GBP-5 splicing variants: New guanylate-binding proteins with tumor-associated expression and antigenicity.

PubMed ID: 15175044

DOI: 10.1111/j.0022-202x.2004.22613.x

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 17266443

Title: Unique features of different members of the human guanylate-binding protein family.

PubMed ID: 17266443

DOI: 10.1089/jir.2007.0086

PubMed ID: 20180847

Title: Biochemical properties of the human guanylate binding protein 5 and a tumor-specific truncated splice variant.

PubMed ID: 20180847

DOI: 10.1111/j.1742-4658.2010.07586.x

PubMed ID: 21151871

Title: Intracellular trafficking of guanylate-binding proteins is regulated by heterodimerization in a hierarchical manner.

PubMed ID: 21151871

DOI: 10.1371/journal.pone.0014246

PubMed ID: 22461501

Title: GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals.

PubMed ID: 22461501

DOI: 10.1126/science.1217141

PubMed ID: 26996307

Title: Guanylate binding protein (GBP) 5 is an interferon-inducible inhibitor of HIV-1 infectivity.

PubMed ID: 26996307

DOI: 10.1016/j.chom.2016.02.019

PubMed ID: 31091448

Title: Guanylate-binding proteins 2 and 5 exert broad antiviral activity by inhibiting furin-mediated processing of viral envelope proteins.

PubMed ID: 31091448

DOI: 10.1016/j.celrep.2019.04.063

PubMed ID: 31216343

Title: Structural mechanism for guanylate-binding proteins (GBPs) targeting by the Shigella E3 ligase IpaH9.8.

PubMed ID: 31216343

DOI: 10.1371/journal.ppat.1007876

PubMed ID: 33876762

Title: Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins.

PubMed ID: 33876762

DOI: 10.1073/pnas.2022269118

Sequence Information:

  • Length: 586
  • Mass: 66617
  • Checksum: 95DDC02F0FB705D0
  • Sequence:
    • MALEIHMSDP MCLIENFNEQ LKVNQEALEI LSAITQPVVV VAIVGLYRTG KSYLMNKLAG 
KNKGFSVAST VQSHTKGIWI WCVPHPNWPN HTLVLLDTEG LGDVEKADNK NDIQIFALAL 
LLSSTFVYNT VNKIDQGAID LLHNVTELTD LLKARNSPDL DRVEDPADSA SFFPDLVWTL 
RDFCLGLEID GQLVTPDEYL ENSLRPKQGS DQRVQNFNLP RLCIQKFFPK KKCFIFDLPA 
HQKKLAQLET LPDDELEPEF VQQVTEFCSY IFSHSMTKTL PGGIMVNGSR LKNLVLTYVN 
AISSGDLPCI ENAVLALAQR ENSAAVQKAI AHYDQQMGQK VQLPMETLQE LLDLHRTSER 
EAIEVFMKNS FKDVDQSFQK ELETLLDAKQ NDICKRNLEA SSDYCSALLK DIFGPLEEAV 
KQGIYSKPGG HNLFIQKTEE LKAKYYREPR KGIQAEEVLQ KYLKSKESVS HAILQTDQAL 
TETEKKKKEA QVKAEAEKAE AQRLAAIQRQ NEQMMQERER LHQEQVRQME IAKQNWLAEQ 
QKMQEQQMQE QAAQLSTTFQ AQNRSLLSEL QHAQRTVNND DPCVLL