Details for: FGR

Gene ID: 2268

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: FGR

Ensembl ID: ENSG00000000938

Description: FGR proto-oncogene, Src family tyrosine kinase

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • CD14-low, CD16-positive monocyte CL0002396
    CSI 90.69
    rCSI 69.88%
    PRS 84.71
  • elicited macrophage CL0000861
    CSI 32.42
    rCSI 29.77%
    PRS 88.84
  • non-classical monocyte CL0000875
    CSI 29.62
    rCSI 47.48%
    PRS 91.08
  • intermediate monocyte CL0002393
    CSI 26.36
    rCSI 39.78%
    PRS 86.69
  • classical monocyte CL0000860
    CSI 22.62
    rCSI 33.54%
    PRS 92.64
  • promonocyte CL0000559
    CSI 21.15
    rCSI 36.24%
    PRS 87.09
  • alternatively activated macrophage CL0000890
    CSI 19.01
    rCSI 23.91%
    PRS 90.08
  • cerebral cortex endothelial cell CL1001602
    CSI 18.55
    rCSI 32.08%
    PRS 73.78
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 17.93
    rCSI 13.64%
    PRS 92.94
  • CD14-positive monocyte CL0001054
    CSI 17.76
    rCSI 22.12%
    PRS 89.94
  • CD16-positive, CD56-dim natural killer cell, human CL0000939
    CSI 17.24
    rCSI 11.49%
    PRS 92.1
  • dendritic cell, human CL0001056
    CSI 13.71
    rCSI 21.06%
    PRS 89.36
  • mature B cell CL0000785
    CSI 12.44
    rCSI 10.81%
    PRS 90.19
  • B cell CL0000236
    CSI 12.32
    rCSI 16.48%
    PRS 88.07
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 11.46
    rCSI 15.02%
    PRS 91.32
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 11.09
    rCSI 67.12%
    PRS 91.57
  • monocyte CL0000576
    CSI 10.3
    rCSI 18.62%
    PRS 86.16
  • mature NK T cell CL0000814
    CSI 9.68
    rCSI 12.38%
    PRS 90.2
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 9.6
    rCSI 11.47%
    PRS 94.61
  • early lymphoid progenitor CL0000936
    CSI 9.15
    rCSI 8.03%
    PRS 86.5
  • CD16-negative, CD56-bright natural killer cell, human CL0000938
    CSI 8.78
    rCSI 6.58%
    PRS 95.35
  • mononuclear phagocyte CL0000113
    CSI 8.72
    rCSI 19.2%
    PRS 85.3
  • Langerhans cell CL0000453
    CSI 7.79
    rCSI 11.9%
    PRS 91.35
  • myeloid dendritic cell CL0000782
    CSI 7.63
    rCSI 11.05%
    PRS 92.87
  • dendritic cell CL0000451
    CSI 6.58
    rCSI 8.11%
    PRS 84.87
  • lung interstitial macrophage CL4033043
    CSI 6.52
    rCSI 14.64%
    PRS 92.24
  • lung macrophage CL1001603
    CSI 6.48
    rCSI 14.47%
    PRS 88.3
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 6.43
    rCSI 5.86%
    PRS 92.15
  • conventional dendritic cell CL0000990
    CSI 5.73
    rCSI 4.78%
    PRS 80.93
  • retinal blood vessel endothelial cell CL0002585
    CSI 5.5
    rCSI 8.78%
    PRS 85.23
  • granulocyte CL0000094
    CSI 5.36
    rCSI 8.19%
    PRS 88.28
  • group 3 innate lymphoid cell CL0001071
    CSI 5.31
    rCSI 3.99%
    PRS 87.18
  • unswitched memory B cell CL0000970
    CSI 5.08
    rCSI 4.27%
    PRS 93.05
  • alveolar macrophage CL0000583
    CSI 4.99
    rCSI 8.22%
    PRS 85.2
  • myeloid cell CL0000763
    CSI 4.76
    rCSI 19.6%
    PRS 88.4
  • pulmonary capillary endothelial cell CL4028001
    CSI 4.71
    rCSI 8.98%
    PRS 90.63
  • myelocyte CL0002193
    CSI 4.64
    rCSI 30.45%
    PRS 93.63
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 4.56
    rCSI 5.51%
    PRS 88.69
  • inflammatory macrophage CL0000863
    CSI 4.33
    rCSI 7.39%
    PRS 94.51
  • myeloid leukocyte CL0000766
    CSI 4.11
    rCSI 3.8%
    PRS 83.24
  • CD4-positive, alpha-beta cytotoxic T cell CL0000934
    CSI 3.91
    rCSI 5.38%
    PRS 94.83
  • Kupffer cell CL0000091
    CSI 3.76
    rCSI 8.6%
    PRS 82.56
  • transitional stage B cell CL0000818
    CSI 3.56
    rCSI 11.64%
    PRS 94.85
  • neutrophil CL0000775
    CSI 3.17
    rCSI 17.72%
    PRS 82.53
  • CD34-positive, CD56-positive, CD117-positive common innate lymphoid precursor, human CL0001074
    CSI 2.6
    rCSI 30.23%
    PRS 94.48
  • immature B cell CL0000816
    CSI 2.55
    rCSI 1.9%
    PRS 91.23
  • class switched memory B cell CL0000972
    CSI 2.51
    rCSI 1.87%
    PRS 92.32
  • cytotoxic T cell CL0000910
    CSI 2.09
    rCSI 12%
    PRS 84.58
  • blood vessel endothelial cell CL0000071
    CSI 2.08
    rCSI 4.31%
    PRS 78.66
  • alpha-beta T cell CL0000789
    CSI 1.86
    rCSI 2.18%
    PRS 93.48
  • CD8-positive, alpha-beta memory T cell CL0000909
    CSI 1.77
    rCSI 1.84%
    PRS 92.78
  • myeloid dendritic cell, human CL0001057
    CSI 1.56
    rCSI 8.78%
    PRS 93.18
  • activated type II NK T cell CL0000931
    CSI 1.39
    rCSI 1.57%
    PRS 92.91
  • promyelocyte CL0000836
    CSI 1.27
    rCSI 1.84%
    PRS 86.9
  • professional antigen presenting cell CL0000145
    CSI 1.26
    rCSI 4.34%
    PRS 91.63
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 0.91
    rCSI 4.55%
    PRS 92.16
  • immature innate lymphoid cell CL0001082
    CSI 0.83
    rCSI 25.81%
    PRS 97.7
  • colon macrophage CL0009038
    CSI 0.59
    rCSI 2.75%
    PRS 92.33
  • metallothionein-positive alveolar macrophage CL4033042
    CSI 0.55
    rCSI 6.02%
    PRS 91.06
  • decidual natural killer cell, human CL0002343
    CSI 0.52
    rCSI 5.25%
    PRS 92.13

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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Comma-separated if multiple.
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 [FGR](/details-gene/2268) (FGR proto-oncogene, Src family tyrosine kinase) is a protein-coding gene located on chromosome 1p35.3. It encodes a non-receptor tyrosine kinase belonging to the Src family, which are key regulators of intracellular signaling pathways. The primary function of [FGR](/details-gene/2268) is associated with immune system processes, particularly within the innate immune response. Expression data indicates that [FGR](/details-gene/2268) is a defining and highly active component of myeloid lineage cells, including various subsets of monocytes and macrophages. Its involvement in Fc-gamma receptor signaling and phagocytosis underscores its critical role in pathogen clearance and immune surveillance. ## Cellular Roles and Expression Landscape The expression profile of [FGR](/details-gene/2268) strongly suggests a specialized function within the myeloid compartment of the immune system. **Overall**, the gene shows its most significant expression and is a key marker for monocyte populations, especially the `[CD14-low, CD16-positive monocyte](/details-cell/CL0002396)` (CSI: 90.69), also known as the non-classical monocyte. High significance is also observed in `[elicited macrophage](/details-cell/CL0000861)`, `[intermediate monocyte](/details-cell/CL0002393)`, and `[classical monocyte](/details-cell/CL0000860)`, highlighting its pervasive role across the monocyte-to-macrophage differentiation and activation axis. Beyond monocytes, [FGR](/details-gene/2268) demonstrates significant expression in other key innate and adaptive immune cells, including `[CD16-positive, CD56-dim natural killer cell, human](/details-cell/CL0000939)` and `[B cell](/details-cell/CL0000236)`. This pattern of expression is consistent with early research identifying its specific expression in natural immunity effector cells ([Link](https://doi.org/10.1128/mcb.10.4.1789-1792.1990)). The data collectively portrays [FGR](/details-gene/2268) not just as a lineage marker, but as a crucial functional kinase in cells responsible for phagocytosis, antibody-dependent cellular responses, and general immune activation. ## Pathways and Molecular Function [FGR](/details-gene/2268) functions as a non-membrane spanning protein tyrosine kinase ([GO:0004715](https://www.ebi.ac.uk/QuickGO/term/GO:0004715)) that participates in a multitude of signaling cascades essential for immune defense. Its involvement is central to the `[Innate immune response](/details-ontology/GO0045087)` and more specifically, the `[Fc-gamma receptor signaling pathway involved in phagocytosis](/details-ontology/GO0038096)`. This is supported by its annotated molecular functions, including `[Immunoglobulin receptor binding](/details-ontology/GO0034987)`, and its role in the Reactome pathway for `[Fcgamma receptor (fcgr) dependent phagocytosis](/details-pathway/R-HSA-2029480)`. Studies have confirmed a physical association between Fgr and the Fc gamma receptor II in neutrophils, linking it directly to downstream signaling upon antibody binding ([Link](https://doi.org/10.1073/pnas.90.13.6305)). Furthermore, [FGR](/details-gene/2268) is implicated in signaling from `[Integrin-mediated signaling pathway](/details-ontology/GO0007229)` and plays a role in `[Neutrophil degranulation](/details-pathway/R-HSA-6798695)` and the `[Positive regulation of cytokine production](/details-ontology/GO0001819)`. This indicates its role extends beyond phagocytosis to include cell adhesion, migration, and the amplification of inflammatory responses. Notably, several annotated pathways relate to pathogen interaction, such as `[Defense response to gram-positive bacterium](/details-ontology/GO0050830)` and `[Leishmania infection](/details-pathway/R-HSA-9658195)`, suggesting that [FGR](/details-gene/2268) is a key molecular node during host-pathogen encounters. ## Research Directions The function of [FGR](/details-gene/2268) as a critical signaling kinase in myeloid cells presents several avenues for further investigation, particularly concerning its role in disease pathogenesis and as a potential therapeutic target. ### Proposed Hypotheses 1. **Hypothesis 1:** Given its exceptionally high significance in `[CD14-low, CD16-positive monocyte](/details-cell/CL0002396)` and its direct link to Fc-gamma receptor signaling, [FGR](/details-gene/2268) may be the dominant Src family kinase responsible for mediating antibody-dependent cellular cytotoxicity (ADCC) and inflammatory cytokine release specifically within this non-classical monocyte subset, which is known to be expanded in chronic inflammatory conditions. 2. **Hypothesis 2:** The prominent feature of [FGR](/details-gene/2268) in `[Leishmania infection](/details-pathway/R-HSA-9658195)` pathways suggests that Leishmania parasites may actively modulate [FGR](/details-gene/2268) kinase activity within macrophages to subvert the phagocytic machinery, thereby creating a permissible intracellular niche for their survival and replication. ### Key Experimental Approach To test Hypothesis 2, a targeted genetic approach could be employed. Differentiated macrophage-like cells (e.g., from primary human monocytes or the THP-1 cell line) could be subjected to CRISPR-Cas9-mediated knockout of the [FGR](/details-gene/2268) gene. These `FGR`-knockout cells, alongside wild-type controls, would then be infected with *Leishmania major* promastigotes. The functional consequences could be assessed by: * **Quantifying parasite load:** Using microscopy or qPCR to measure the number of intracellular amastigotes at various time points post-infection. A significant reduction in parasite survival in the knockout cells would support the hypothesis. * **Analyzing phagosome maturation:** Assessing the localization of phagolysosomal markers (e.g., LAMP1) to parasite-containing vacuoles. Failure of these markers to co-localize in wild-type cells, but not in knockout cells, would suggest [FGR](/details-gene/2268) is involved in arresting this process. ### Therapeutic Potential As a tyrosine kinase, [FGR](/details-gene/2268) represents a tractable drug target. Its high expression in myeloid cells, which are often key drivers of autoimmune and inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease), makes it a candidate for therapeutic **inhibition**. A specific FGR inhibitor could potentially dampen excessive myeloid cell activation and cytokine production in these contexts. Furthermore, as a proto-oncogene, its activity could be dysregulated in certain myeloid malignancies, offering another context for targeted inhibition. The primary challenge would be developing highly specific inhibitors that do not cross-react with other closely related Src family kinases to minimize off-target effects.

Genular Protein ID: 1297010885

Symbol: FGR_HUMAN

Name: Tyrosine-protein kinase Fgr

UniProtKB Accession Codes:

P09769 D3DPL7 Q9UIQ3

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CPTAC 2 CTD 1 ChEBI 7 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 4 DrugCentral 1 EC 2 ELM 1 EMBL 14 Ensembl 4 ExpressionAtlas 1 GO 42 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 12 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 PIR 1 PRINTS 3 PRO 1 PROSITE 5 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 5 RefSeq 5 Rhea 3 SIGNOR 1 SMART 3 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 3275868

Title: Primary structure of the human fgr proto-oncogene product p55c-fgr.

PubMed ID: 3275868

DOI: 10.1128/mcb.8.1.259-266.1988

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 2852026

Title: Structure and expression of c-fgr protooncogene mRNA in Epstein-Barr virus converted cell lines.

PubMed ID: 2852026

DOI: 10.1038/bjc.1988.294

PubMed ID: 3330776

Title: Isolation and sequencing of cDNA clones homologous to the v-fgr oncogene from a human B lymphocyte cell line, IM-9.

PubMed ID: 3330776

PubMed ID: 1690869

Title: Structure of the complete human c-fgr proto-oncogene and identification of multiple transcriptional start sites.

PubMed ID: 1690869

PubMed ID: 3023853

Title: Structure, expression, and chromosomal location of the human c-fgr gene.

PubMed ID: 3023853

DOI: 10.1128/mcb.6.2.511-517.1986

PubMed ID: 2181286

Title: Specific expression of human c-fgr in natural immunity effector cells.

PubMed ID: 2181286

DOI: 10.1128/mcb.10.4.1789-1792.1990

PubMed ID: 1737799

Title: Diverse biologic properties imparted by the c-fgr proto-oncogene.

PubMed ID: 1737799

DOI: 10.1016/s0021-9258(19)50753-0

PubMed ID: 8327512

Title: Association of immunoglobulin G Fc receptor II with Src-like protein-tyrosine kinase Fgr in neutrophils.

PubMed ID: 8327512

DOI: 10.1073/pnas.90.13.6305

PubMed ID: 7519620

Title: Beta 2 integrin-dependent protein tyrosine phosphorylation and activation of the FGR protein tyrosine kinase in human neutrophils.

PubMed ID: 7519620

DOI: 10.1083/jcb.126.4.1111

PubMed ID: 8603737

Title: Activation of SRC family kinases in human neutrophils. Evidence that p58C-FGR and p53/56LYN redistributed to a Triton X-100-insoluble cytoskeletal fraction, also enriched in the caveolar protein caveolin, display an enhanced kinase activity.

PubMed ID: 8603737

DOI: 10.1016/0014-5793(96)00029-4

PubMed ID: 10739672

Title: Clustering of beta(2)-integrins on human neutrophils activates dual signaling pathways to PtdIns 3-kinase.

PubMed ID: 10739672

DOI: 10.1006/excr.2000.4816

PubMed ID: 11078731

Title: Phosphatidic acid regulates tyrosine phosphorylating activity in human neutrophils: enhancement of Fgr activity.

PubMed ID: 11078731

DOI: 10.1074/jbc.m006571200

PubMed ID: 12435267

Title: Fgr but not Syk tyrosine kinase is a target for beta 2 integrin-induced c-Cbl-mediated ubiquitination in adherent human neutrophils.

PubMed ID: 12435267

DOI: 10.1042/bj20021201

PubMed ID: 17164290

Title: Sorting of Fas ligand to secretory lysosomes is regulated by mono-ubiquitylation and phosphorylation.

PubMed ID: 17164290

DOI: 10.1242/jcs.03315

PubMed ID: 19369195

Title: Large-scale proteomics analysis of the human kinome.

PubMed ID: 19369195

DOI: 10.1074/mcp.m800588-mcp200

PubMed ID: 17344846

Title: Patterns of somatic mutation in human cancer genomes.

PubMed ID: 17344846

DOI: 10.1038/nature05610

Sequence Information:

  • Length: 529
  • Mass: 59479
  • Checksum: 6B8C1E08414E0F9C
  • Sequence:
    • MGCVFCKKLE PVATAKEDAG LEGDFRSYGA ADHYGPDPTK ARPASSFAHI PNYSNFSSQA 
INPGFLDSGT IRGVSGIGVT LFIALYDYEA RTEDDLTFTK GEKFHILNNT EGDWWEARSL 
SSGKTGCIPS NYVAPVDSIQ AEEWYFGKIG RKDAERQLLS PGNPQGAFLI RESETTKGAY 
SLSIRDWDQT RGDHVKHYKI RKLDMGGYYI TTRVQFNSVQ ELVQHYMEVN DGLCNLLIAP 
CTIMKPQTLG LAKDAWEISR SSITLERRLG TGCFGDVWLG TWNGSTKVAV KTLKPGTMSP 
KAFLEEAQVM KLLRHDKLVQ LYAVVSEEPI YIVTEFMCHG SLLDFLKNPE GQDLRLPQLV 
DMAAQVAEGM AYMERMNYIH RDLRAANILV GERLACKIAD FGLARLIKDD EYNPCQGSKF 
PIKWTAPEAA LFGRFTIKSD VWSFGILLTE LITKGRIPYP GMNKREVLEQ VEQGYHMPCP 
PGCPASLYEA MEQTWRLDPE ERPTFEYLQS FLEDYFTSAE PQYQPGDQT

Genular Protein ID: 3208359896

Symbol: P78453_HUMAN

Name: N/A

UniProtKB Accession Codes:

P78453

Database IDs:

ARBA 1 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 9 Gene3D 2 InterPro 5 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 2 PROSITE 4 PROSITE-ProRule 2 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 1 SMART 1 SUPFAM 2

Citations:

PubMed ID: 2852026

Title: Structure and expression of c-fgr protooncogene mRNA in Epstein-Barr virus converted cell lines.

PubMed ID: 2852026

Sequence Information:

  • Length: 177
  • Mass: 19354
  • Checksum: 11ACD7F3BAF3D43E
  • Sequence:
    • MGCVFCKKLE PVATAKEDAG LEGDFRSYGA ADHYGPDPTK ARPASSFAHI PNYSNFSSQA 
INPGFLDSGT IRGVSGIGVT LFIALYDYEA RTEDDLTFTK GEKFHILNNT EGDWWEARSL 
SSGKTGCIPS NYVAPVDSIQ AEEWYFGKIG RKDAERQLLS PGNPQGAFLI RESETTK