The Function of F2RL1
Receptor for trypsin and trypsin-like enzymes coupled to G proteins. Its function is mediated through the activation of several signaling pathways including phospholipase C (PLC), intracellular calcium, mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-kappaB and Rho. Can also be transactivated by cleaved F2R/PAR1. Involved in modulation of inflammatory responses and regulation of innate and adaptive immunity, and acts as a sensor for proteolytic enzymes generated during infection. Generally is promoting inflammation. Can signal synergistically with TLR4 and probably TLR2 in inflammatory responses and modulates TLR3 signaling. Has a protective role in establishing the endothelial barrier; the activity involves coagulation factor X. Proposed to have a bronchoprotective role in airway epithelium, but also shown to compromise the airway epithelial barrier by interrupting E-cadherin adhesion. Involved in the regulation of vascular tone; activation results in hypotension presumably mediated by vasodilation. Associates with a subset of G proteins alpha subunits such as G alpha-q, G alpha-11, G alpha-14, G alpha-12 and G alpha-13, but probably not with G(o) alpha, G(i) subunit alpha-1 and G(i) subunit alpha-2. However, according to PubMed:21627585 can signal through G(i) subunit alpha. Believed to be a class B receptor which internalizes as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptor, for extended periods of time. Mediates inhibition of TNF-alpha stimulated JNK phosphorylation via coupling to G alpha-q/11; the function involves dissociation of RIPK1 and TRADD from TNFR1. Mediates phosphorylation of nuclear factor NF-kappa-B RELA subunit at 'Ser-536'; the function involves IKBKB and is predominantly independent of G proteins. Involved in cellular migration. Involved in cytoskeletal rearrangement and chemotaxis through beta-arrestin-promoted scaffolds; the function is independent of G alpha-q/11 and involves promotion of cofilin dephosphoryltaion and actin filament severing. Induces redistribution of COPS5 from the plasma membrane to the cytosol and activation of the JNK cascade is mediated by COPS5. Involved in the recruitment of leukocytes to the sites of inflammation and is the major PAR receptor capable of modulating eosinophil function such as proinflammatory cytokine secretion, superoxide production and degranulation. During inflammation promotes dendritic cell maturation, trafficking to the lymph nodes and subsequent T-cell activation. Involved in antimicrobial response of innate immnune cells; activation enhances phagocytosis of Gram-positive and killing of Gram-negative bacteria. Acts synergistically with interferon-gamma in enhancing antiviral responses. Implicated in a number of acute and chronic inflammatory diseases such as of the joints, lungs, brain, gastrointestinal tract, periodontium, skin, and vascular systems, and in autoimmune disorders.
Protein names
Recommended name:
Proteinase-activated receptor 2Short name:
PAR-2Alternative name(s):
Coagulation factor II receptor-like 1G-protein coupled receptor 11
Thrombin receptor-like 1
- RS17568628 (F2RL1) ??
- RS2047076 (F2RL1) ??
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Top Gene-Substance Interactions
F2RL1 Interacts with These Diseases
Disease | Score |
Substances That Increase F2RL1
Substances | Interaction | Organism | Category |
Substances That Decrease F2RL1
Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Tissue specificity:
Widely expressed in tissues with especially high levels in pancreas, liver, kidney, small intestine, and colon. Moderate expression is detected in many organs, but none in brain or skeletal muscle.
Molecular Function:
- G-Protein Alpha-Subunit Binding
- G-Protein Beta-Subunit Binding
- G-Protein Coupled Receptor Activity
- Receptor Activity
- Receptor Binding
- Thrombin-Activated Receptor Activity
Biological Processes:
- Blood Coagulation
- Chemokine (C-C Motif) Ligand 2 Secretion
- Chemokine Secretion
- Defense Response To Virus
- Establishment Of Endothelial Barrier
- G-Protein Coupled Receptor Signaling Pathway
- Inflammatory Response
- Innate Immune Response
- Interferon-Gamma Secretion
- Interleukin-10 Secretion
- Interleukin-1 Beta Secretion
- Leukocyte Migration
- Leukocyte Proliferation
- Mature Conventional Dendritic Cell Differentiation
- Negative Regulation Of Chemokine Secretion
- Negative Regulation Of Jnk Cascade
- Negative Regulation Of Toll-Like Receptor 3 Signaling Pathway
- Negative Regulation Of Tumor Necrosis Factor-Mediated Signaling Pathway
- Neutrophil Activation
- Positive Regulation Of Actin Filament Depolymerization
- Positive Regulation Of Cell Migration
- Positive Regulation Of Chemotaxis
- Positive Regulation Of Cytokine Secretion Involved In Immune Response
- Positive Regulation Of Cytosolic Calcium Ion Concentration
- Positive Regulation Of Cytosolic Calcium Ion Concentration Involved In Phospholipase C-Activating G-Protein Coupled Signaling Pathway
- Positive Regulation Of Eosinophil Degranulation
- Positive Regulation Of Erk1 And Erk2 Cascade
- Positive Regulation Of Glomerular Filtration
- Positive Regulation Of I-Kappab Kinase/Nf-Kappab Signaling
- Positive Regulation Of Interleukin-6 Secretion
- Positive Regulation Of Interleukin-8 Secretion
- Positive Regulation Of Jnk Cascade
- Positive Regulation Of Leukocyte Chemotaxis
- Positive Regulation Of Neutrophil Mediated Killing Of Gram-Negative Bacterium
- Positive Regulation Of Phagocytosis, Engulfment
- Positive Regulation Of Phosphatidylinositol 3-Kinase Signaling
- Positive Regulation Of Positive Chemotaxis
- Positive Regulation Of Pseudopodium Assembly
- Positive Regulation Of Renin Secretion Into Blood Stream
- Positive Regulation Of Rho Protein Signal Transduction
- Positive Regulation Of Superoxide Anion Generation
- Positive Regulation Of Toll-Like Receptor 2 Signaling Pathway
- Positive Regulation Of Toll-Like Receptor 3 Signaling Pathway
- Positive Regulation Of Toll-Like Receptor 4 Signaling Pathway
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
- Positive Regulation Of Vasodilation
- Regulation Of Blood Coagulation
- Regulation Of I-Kappab Kinase/Nf-Kappab Signaling
- Regulation Of Jnk Cascade
- T Cell Activation Involved In Immune Response