Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses.
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Original discovery and cloning of IL-13 as a cytokine produced by activated T cells. Demonstrated IL-13 regulates inflammatory and immune responses and synergizes with IL-2 in regulating IFN-gamma synthesis.
"Recombinant IL-13 protein inhibits inflammatory cytokine production induced by lipopolysaccharide in human peripheral blood monocytes. Moreover, it synergizes with IL-2 in regulating interferon-gamma synthesis in large granular lymphocytes."
Interleukin 13, a T-cell-derived cytokine that regulates human monocyte and B-cell function.
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Independent cloning and characterization of IL-13. Showed IL-13 regulates monocyte and B cell function, including effects on macrophage activation.
"We show that the human and mouse proteins cause extensive morphological changes to human monocytes with an associated up-regulation of major histocompatibility complex class II antigens and the low-affinity receptor for immunoglobulin E (Fc epsilon RII or CD23)."
Interleukin 13 is a B cell stimulating factor.
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Demonstrated IL-13 stimulates B cell proliferation and activation, and promotes immunoglobulin production.
"it stimulates B cell proliferation in combination with anti-Ig and anti-CD40 antibodies; and (c) it induces IgE synthesis"
Activation of human eosinophils by IL-13. Induction of CD69 surface antigen, its relationship to messenger RNA expression, and promotion of cellular viability.
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Demonstrated IL-13 activates eosinophils, induces CD69 expression, and promotes eosinophil viability.
"our results demonstrate that IL-13 specifically activates human eosinophils, as determined by the expression of CD69 cell surface protein and mRNA expression. Furthermore, IL-13 significantly prolongs eosinophil survival in vitro."
Cloning of the human IL-13R alpha1 chain and reconstitution with the IL4R alpha of a functional IL-4/IL-13 receptor complex.
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Identified IL-13Ralpha1 and showed it reconstitutes a functional IL-4/IL-13 receptor with IL-4Ralpha, activating JAK1/TYK2 and STAT6.
"IL-13 and IL-4 were able to activate Stat6 in cells expressing both IL-4R alpha and IL-13R alpha1, while no activation was observed in cells expressing either one or the other alone."
Interleukin-4 (IL-4) and IL-13 bind to a shared heterodimeric complex on endothelial cells mediating vascular cell adhesion molecule-1 induction in the absence of the common gamma chain.
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Showed IL-4 and IL-13 share a receptor complex on endothelial cells and both induce VCAM-1, important for eosinophil recruitment.
"Interleukin-4 (IL-4) and IL-13 exert similar, nonadditive effects on endothelial cells, inducing vascular cell adhesion molecule-1 (VCAM-1) expression and subsequent transmigration of eosinophils."
IL-13 antibodies influence IL-13 clearance in humans by modulating scavenger activity of IL-13Rα2.
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Demonstrated IL-13Ralpha2 acts as a high-affinity decoy/scavenger receptor that mediates internalization and depletion of extracellular IL-13.
"Cells with high IL-13Ralpha2 expression rapidly and efficiently depleted extracellular IL-13, and this activity persisted in the presence of IMA-638 but not IMA-026. The potency and efficiency of this clearance pathway suggest that cell surface IL-13Ralpha2 acts as a scavenger for IL-13."
Human activation-induced cytidine deaminase is induced by IL-4 and negatively regulated by CD45: implication of CD45 as a Janus kinase phosphatase in antibody diversification.
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Showed IL-4 induces AID expression in B cells via JAK/STAT6 signaling pathway, with CD40 signaling enhancing the effect. IL-13 shares this signaling mechanism.
"IL-4 was able to induce AID expression in human primary B cells and B cell lines, and IL-4-induced AID expression was further enhanced by CD40 signaling. IL-4-dependent AID induction was inhibited by a dominant-negative STAT6, indicating that IL-4 induced AID expression via the Janus kinase (JAK)/STAT6 signaling pathway."
Enhanced interleukin (IL)-13 responses in mice lacking IL-13 receptor alpha 2.
IL-4 and IL-13 induce protection of porcine endothelial cells from killing by human complement and from apoptosis through activation of a phosphatidylinositide 3-kinase/Akt pathway.
Allergic dysregulation and hyperimmunoglobulinemia E in Foxp3 mutant mice.
Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system.
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Characterization of IL-13 receptor complex including IL-13Ralpha1 interaction and JAK-STAT signaling pathway activation.
"Here we present the crystal structures of the complete set of type I (IL-4R alpha/gamma(c)/IL-4) and type II (IL-4R alpha/IL-13R alpha1/IL-4, IL-4R alpha/IL-13R alpha1/IL-13) ternary signaling complexes."
Missense mutations in the MEFV gene are associated with fibromyalgia syndrome and correlate with elevated IL-1beta plasma levels.
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Measured IL-13 and other cytokine plasma levels in fibromyalgia patients. IL-13 was detected in plasma, confirming its extracellular localization.
"FMS patients and family members without rare variants differed from control subjects with regard to both TH1 (IFNγ) and TH2 (IL-5 and IL-13) cytokine levels"
Molecular basis for shared cytokine recognition revealed in the structure of an unusually high affinity complex between IL-13 and IL-13Ralpha2.
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Solved crystal structure of IL-13 bound to IL-13Ralpha2 at 3.05 angstroms, revealing the molecular basis for the high-affinity interaction with the decoy receptor.
"IL-13Ralpha2 uses peripheral receptor residues unused in the IL-13/IL-13Ralpha1 complex to generate a larger and more complementary interface for IL-13. This results in a four orders of magnitude increase in affinity, to the femtomolar level, compared to IL-13Ralpha1."
Goblet cells are derived from a FOXJ1-expressing progenitor in a human airway epithelium.
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Demonstrated IL-13 suppresses ciliated cell differentiation while promoting goblet cell metaplasia in lung epithelium.
"Treatment of differentiated HBEC cultures with the cytokine IL-13, an important mediator in asthma, increased the numbers of goblet cells and decreased the numbers of ciliated cells."
Chitinase 3-like 1 regulates cellular and tissue responses via IL-13 receptor α2.
Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat.
IL-13Rα2 uses TMEM219 in chitinase 3-like-1-induced signalling and effector responses.
IL-16 regulates macrophage polarization as a target gene of mir-145-3p.
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Demonstrated IL-4 and IL-13 cooperate in macrophage activation, IL-10 production, and negative regulation of inflammatory response.
"THP-1 cells were induced by IL-4 and IL-13 following PMA incubation (M2 polarized macrophages) or induced by IFN-gamma and LPS (M1 classical macrophage activation)."
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
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BioPlex 3.0 high-throughput interactome study identifying IL-13 interaction with IL-13Ralpha1 among proteome-scale interaction networks.
"Thousands of interactions assemble proteins into modules that impart spatial and functional organization to the cellular proteome."
Recent Advances in IL-13Rα2-Directed Cancer Immunotherapy.
IL13Rα2 as a crucial receptor for Chi3l1 in osteoclast differentiation and bone resorption through the MAPK/AKT pathway.
Solution structure of human IL-13 and implication for receptor binding.
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Solved NMR structure of IL-13 (residues 35-146), confirming the four-helix bundle architecture and identifying receptor binding interfaces.
"The high-resolution solution structure of human IL-13 has been determined by multidimensional NMR. The resulting structure is consistent with previous short-chain left-handed four-helix bundles, where a significant similarity in the folding topology between IL-13 and IL-4 was observed."
IL4R, IL13RA, JAK2 and TYK2 are tyrosine phosphorylated
JAK1 binds IL4R in IL13-bound IL13R type II
IL13:IL13RA:TYK2 binds IL4R:JAK2
STAT1,STAT3,STAT6 bind IL13:IL13R type II
STAT1,STAT3,STAT6 phosphorylation