IL7R encodes the interleukin-7 receptor subunit alpha (IL-7Ralpha, CD127), a type I cytokine receptor that serves as the ligand-binding alpha chain of two distinct receptor complexes. It heterodimerizes with the common gamma chain (IL2RG) to form the functional IL-7 receptor, and with CRLF2 to form the TSLP receptor. IL-7 binding triggers JAK1/JAK3-STAT5 signaling and engages PI3K-AKT and MAPK cascades. IL7R is essential for T cell development in the thymus and for survival and homeostatic proliferation of naive and memory T cells. It also regulates B cell progenitor differentiation. The protein has an extracellular domain with Ig-like and fibronectin type III folds, a single transmembrane helix, and a cytoplasmic domain containing box 1 motif for JAK association. An alternatively spliced soluble isoform modulates IL-7 bioavailability. Loss-of-function mutations cause T-B+NK+ severe combined immunodeficiency (SCID). Gain-of-function mutations occur in T-ALL and AML. Common variants (rs6897932) are associated with susceptibility to multiple sclerosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0030097 hemopoiesis | IBA GO_REF:0000033 | ACCEPT | Summary: IL7R is annotated to hemopoiesis by phylogenetic inference. IL-7/IL7R signaling is essential for lymphopoiesis, specifically T and B cell development from hematopoietic progenitors. Loss of IL7R causes SCID with absent T cells (PMID:9843216). Hemopoiesis is a reasonable broad-level annotation for a gene whose primary role is in lymphoid-lineage development. Reason: IL7R is a key regulator of lymphoid development. Hemopoiesis is a valid parent term that captures the role of IL7R in T and B cell development from hematopoietic stem cells. The IBA annotation is phylogenetically supported and consistent with the known biology. Supporting Evidence: PMID:9843216 Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency PMID:8128231 the gamma chain participates in the functional high-affinity receptor complexes for IL-7 that are involved in the differentiation of T and B cells |
| GO:0004917 interleukin-7 receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: IL7R is annotated to interleukin-7 receptor activity by phylogenetic inference. This is the most specific and accurate MF term for IL7R. The protein is the ligand-binding alpha chain of the IL-7 receptor complex. Crystal structure of IL-7/IL-7Ralpha confirms direct binding (PMID:19141282). Kondo et al. (PMID:8128231) showed that IL7R forms functional IL-7 receptor complexes with the gamma chain. Reason: This is the core molecular function of IL7R. IL7R is the defining ligand-binding subunit of the IL-7 receptor. Well-supported by phylogenetic inference and extensive experimental data. Supporting Evidence: PMID:8128231 the gamma chain participates in the functional high-affinity receptor complexes for IL-7 that are involved in the differentiation of T and B cells PMID:19141282 Structural and biophysical studies of the human IL-7/IL-7Ralpha complex |
| GO:0038111 interleukin-7-mediated signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: IL7R is annotated to IL-7-mediated signaling pathway by phylogenetic inference. IL7R is an essential component of IL-7 signaling. Upon IL-7 binding, IL7R heterodimerizes with IL2RG and activates JAK1/JAK3-STAT5 signaling (PMID:8128231, PMID:20974963). Reason: This is a core biological process for IL7R. As the ligand-binding subunit of the IL-7 receptor, IL7R is directly involved in IL-7-mediated signaling. Well-supported by phylogenetic and experimental evidence. Supporting Evidence: PMID:8128231 the gamma chain participates in the functional high-affinity receptor complexes for IL-7 PMID:20974963 the known activation of JAK1 and JAK3 by the related cytokine, IL-7 |
| GO:0009897 external side of plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IL7R is annotated as active at the external side of the plasma membrane by phylogenetic inference. IL7R is a type I transmembrane protein with its ligand-binding extracellular domain exposed on the cell surface. UniProt topology annotation confirms a large extracellular domain (residues 21-239) and subcellular location at the cell membrane (PMID:31748347). Reason: IL7R is a single-pass type I membrane protein whose receptor activity occurs at the external face of the plasma membrane. This is well-established for cytokine receptors of this family. Supporting Evidence: PMID:19141282 Structural and biophysical studies of the human IL-7/IL-7Ralpha complex |
| GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT | IBA GO_REF:0000033 | ACCEPT | Summary: IL7R is annotated as positively regulating JAK-STAT signaling by phylogenetic inference. IL-7 binding to IL7R triggers JAK1/JAK3 activation and STAT5 phosphorylation (PMID:8128231, PMID:20974963). The box 1 motif in the IL7R cytoplasmic domain is required for JAK interaction and activation (UniProt). Reason: Positive regulation of JAK-STAT signaling is a direct consequence of IL7R activation. The cytoplasmic domain of IL7R associates with JAK1 via its box 1 motif, and upon ligand-induced dimerization, JAK1 and JAK3 are activated, leading to STAT5 phosphorylation. This is core to IL7R function. Supporting Evidence: PMID:20974963 the known activation of JAK1 and JAK3 by the related cytokine, IL-7 PMID:8128231 the gamma chain participates in the functional high-affinity receptor complexes for IL-7 |
| GO:0004896 cytokine receptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: IL7R is annotated to cytokine receptor activity by InterPro domain mapping. IL7R is a member of the type I cytokine receptor family with the hematopoietin receptor superfamily signature. This is a valid parent term of the more specific interleukin-7 receptor activity. Reason: Cytokine receptor activity is a correct parent-level annotation. IL7R belongs to the type I cytokine receptor family and functions as a receptor for both IL-7 and TSLP cytokines. The IEA annotation is appropriately general given the domain-based evidence. Supporting Evidence: PMID:8128231 the gamma chain participates in the functional high-affinity receptor complexes for IL-7 |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: IL7R is annotated to extracellular region based on UniProt subcellular location mapping. This annotation reflects the secreted/soluble isoforms of IL7R (isoforms 2 and 4) that are produced by alternative splicing and lack the transmembrane domain. Reason: Soluble IL-7Ralpha isoforms are secreted and found in the extracellular region. UniProt confirms isoform 4 is secreted. The soluble receptor modulates IL-7 bioavailability. This annotation correctly captures the localization of soluble isoforms. Supporting Evidence: PMID:2317865 Cloning of the human and murine interleukin-7 receptors: demonstration of a soluble form |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IL7R is annotated to plasma membrane based on UniProt subcellular location vocabulary mapping. IL7R isoform 1 is a single-pass type I membrane protein localized to the plasma membrane. Reason: Plasma membrane localization is well-established for the major membrane-bound isoform of IL7R. Supported by UniProt subcellular location annotation and multiple experimental studies. Supporting Evidence: PMID:8128231 the gamma chain participates in the functional high-affinity receptor complexes for IL-7 |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: IL7R is annotated to membrane based on InterPro domain mapping. This is a very general CC term that is redundant with the more specific plasma membrane annotation. However, it is not incorrect. Reason: While very general and redundant with plasma membrane, this IEA annotation from InterPro is technically correct. IL7R is an integral membrane protein. |
| GO:0019221 cytokine-mediated signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: IL7R is annotated to cytokine-mediated signaling pathway by ARBA machine learning. This is a parent term of the more specific interleukin-7-mediated signaling pathway already annotated. It is correct but general. Reason: Cytokine-mediated signaling pathway is a valid broader annotation. IL7R participates in both IL-7 and TSLP cytokine signaling pathways. The IEA annotation is appropriately general. Supporting Evidence: PMID:20974963 TSLP signals via IL-7Ralpha and a specific TSLPR subunit |
| GO:0005515 protein binding | IPI PMID:19141282 Structural and biophysical studies of the human IL-7/IL-7Ral... | MODIFY | Summary: IL7R annotated as protein binding based on physical interaction with IL-7 (UniProtKB:P13232) from crystal structure determination. McElroy et al. solved the IL-7/IL-7Ralpha complex structure at 2.7 angstroms. This interaction is better captured by the more specific term interleukin-7 receptor activity (GO:0004917). Reason: Protein binding is uninformative for a receptor whose primary function is to bind its ligand. The IL-7/IL-7Ralpha interaction is the core receptor-ligand binding event and is better captured by interleukin-7 receptor activity. Additionally, a more specific binding term such as interleukin-7 binding (GO:0019982) would be appropriate. Proposed replacements: interleukin-7 binding Supporting Evidence: PMID:19141282 Structural and biophysical studies of the human IL-7/IL-7Ralpha complex |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Multiple protein binding annotations from the HuRI systematic Y2H interactome screen (Luck et al. 2020). Partners include TMEM120B, VAMP5, APOL3, MS4A1, ATP6V0C, SDC4, MALL, AGTRAP, CD302, FAM3C, TMEM60. These are high-throughput binary interaction data. Most of these interactions lack functional validation specific to IL7R biology. Reason: These protein binding annotations derive from systematic Y2H screening (HuRI). While technically valid as physical interactions, protein binding is uninformative. Many of these interactors (e.g., TMEM120B, VAMP5, ATP6V0C) have no established functional relationship with IL7R signaling. This is typical of high-throughput interaction data that generates many true-positive interactions of uncertain biological significance. Supporting Evidence: PMID:32296183 The dataset, versioned HI-III-20 (Human Interactome obtained from screening Space III, published in 2020), contains 52,569 verified PPIs involving 8,275 proteins (Supplementary Table 9) |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | MARK AS OVER ANNOTATED | Summary: Protein binding annotation based on interaction with SPOP (UniProtKB:O43791) from the Mo et al. (2022) neo-PPI cancer mutation screening study using BRET biosensors. SPOP is an E3 ubiquitin ligase adaptor that targets multiple substrates for degradation. Reason: This interaction with SPOP was identified in a systematic cancer mutation-focused differential interaction screen. The biological relevance of SPOP-IL7R interaction is not established in the context of normal IL7R biology. Protein binding is uninformative regardless. Supporting Evidence: PMID:35512704 the coupling of highly sensitive BRET biosensors with miniaturized coexpression in an ultra-HTS format allows large-scale monitoring of the interactions |
| GO:0005515 protein binding | IPI PMID:8266077 Interleukin-2 receptor gamma chain: a functional component o... | MODIFY | Summary: Protein binding annotation based on interaction with IL-7 (UniProtKB:P13232). This is a duplicate of the functionally relevant IL-7/IL-7Ralpha interaction already captured by the PMID:19141282 protein binding annotation and by the interleukin-7 receptor activity term. The PMID:8266077 reference corresponds to early studies on IL-7 receptor characterization. Reason: The IL7R-IL7 interaction is the core receptor-ligand event. Protein binding is uninformative; this should be annotated to the more specific interleukin-7 binding term. Proposed replacements: interleukin-7 binding Supporting Evidence: PMID:8128231 the gamma chain participates in the functional high-affinity receptor complexes for IL-7 |
| GO:0009897 external side of plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: IL7R annotated to external side of plasma membrane by Ensembl Compara ortholog transfer from mouse Il7r. This is consistent with the IBA annotation for the same term and the known biology of IL7R as a cell surface receptor. Reason: Correct and consistent with the IBA annotation and known cell surface localization. Redundant but valid independent evidence. |
| GO:0050830 defense response to Gram-positive bacterium | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IL7R annotated to defense response to Gram-positive bacterium by Ensembl ortholog transfer from mouse Il7r. IL-7/IL7R signaling is important for innate immune cell function and host defense, including responses to bacterial infection. Mouse studies have shown that IL-7 enhances innate immune responses. Reason: While IL7R does contribute to immune defense through its essential role in lymphocyte development and homeostasis, defense response to Gram-positive bacterium is not a core function. It is a downstream consequence of the broader immune system role. The annotation is transferred from mouse data and represents a pleiotropic effect rather than a direct molecular function of IL7R. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: IL7R localized to plasma membrane by HPA immunofluorescence data curation. IL7R is a single-pass type I transmembrane protein that localizes to the plasma membrane. Reason: Plasma membrane localization is well-established for IL7R isoform 1. The HPA immunofluorescence data provides direct experimental confirmation of membrane localization. |
| GO:0019725 cellular homeostasis | IDA PMID:35021100 In vivo availability of the cytokine IL-7 constrains the sur... | MODIFY | Summary: IL7R annotated to cellular homeostasis based on Park et al. (2022, PMID:35021100), which demonstrated that IL-7 availability constrains the survival and homeostasis of peripheral iNKT cells. The study showed that IL-7, not IL-15, is the homeostatic cytokine for iNKT cells, and that competition for IL-7 between iNKT and conventional T cells limits peripheral iNKT cell pool size. This directly supports IL7R involvement in cellular homeostasis. Reason: The annotation is well-supported by Park et al. (PMID:35021100) who demonstrated IL-7 as the key homeostatic cytokine for iNKT cells via IL-7R. However, "cellular homeostasis" (GO:0019725) is overly broad. The study specifically addresses T cell homeostasis, and IL7R's role in homeostatic regulation of T cell populations is its core contribution. A more specific term would better capture this function. Proposed replacements: T cell homeostasis Supporting Evidence: PMID:35021100 we came to the surprising conclusion that IL-7, not IL-15, is the homeostatic cytokine for iNKT cells PMID:35021100 the abundance of IL-7, and not IL-15, limits the size of the peripheral iNKT cell pool |
| GO:0004896 cytokine receptor activity | IDA PMID:20974963 Thymic stromal lymphopoietin-mediated STAT5 phosphorylation ... | ACCEPT | Summary: IL7R annotated to cytokine receptor activity based on Rochman et al. (2010) which demonstrated that IL7R functions as a shared receptor subunit for both IL-7 and TSLP cytokines. The study showed TSLP signals via IL-7Ralpha and a specific TSLPR (CRLF2) subunit, with JAK1 associated with IL-7Ralpha. This confirms IL7R has broad cytokine receptor activity beyond IL-7 alone. Reason: The cytokine receptor activity annotation is justified by the dual receptor role of IL7R, serving as a subunit for both IL-7R (with IL2RG) and TSLPR (with CRLF2). Rochman et al. experimentally demonstrated TSLP signaling through IL7R in primary human T cells. Supporting Evidence: PMID:20974963 TSLP signals via IL-7Ralpha and a specific TSLPR subunit that is highly related to the common cytokine receptor gamma chain |
| GO:0004917 interleukin-7 receptor activity | IDA PMID:8128231 Functional participation of the IL-2 receptor gamma chain in... | ACCEPT | Summary: IL7R annotated to interleukin-7 receptor activity based on Kondo et al. (1994) which demonstrated that the IL-2 receptor gamma chain participates in functional IL-7 receptor complexes. Using antibodies against the gamma chain, they showed it is required for high-affinity IL-7 binding and signal transduction, confirming IL7R as the ligand-binding alpha subunit of the functional IL-7 receptor. Reason: This is the core molecular function of IL7R. The Kondo et al. study provided key evidence that IL7R and IL2RG together form the functional IL-7 receptor, with IL7R as the alpha/ligand-binding subunit. Supporting Evidence: PMID:8128231 the gamma chain participates in the functional high-affinity receptor complexes for IL-7 that are involved in the differentiation of T and B cells |
| GO:0005886 plasma membrane | IC PMID:20974963 Thymic stromal lymphopoietin-mediated STAT5 phosphorylation ... | ACCEPT | Summary: IL7R localized to plasma membrane by curator inference (IC) based on the Rochman et al. study showing TSLP-mediated signaling through IL7R at the cell surface in primary CD4+ T cells. Reason: Plasma membrane localization is consistent with the function of IL7R as a cell surface cytokine receptor. The IC evidence is reasonable given that TSLP signaling occurs at the cell surface. Supporting Evidence: PMID:20974963 We now demonstrate the role of JAK1 and JAK2 in TSLP-mediated STAT5 phosphorylation in mouse and human primary CD4(+) T cells |
| GO:0005886 plasma membrane | IDA PMID:8128231 Functional participation of the IL-2 receptor gamma chain in... | ACCEPT | Summary: IL7R localized to plasma membrane by direct assay from Kondo et al. (1994), who used monoclonal antibodies to detect IL7R and gamma chain at the cell surface as part of the functional IL-7 receptor complex. Reason: Plasma membrane localization demonstrated by cell surface antibody binding studies. Supporting Evidence: PMID:8128231 Studies with monoclonal antibodies specific for the IL-2 receptor gamma chain showed that the gamma chain participates in the functional high-affinity receptor complexes for IL-7 |
| GO:0038111 interleukin-7-mediated signaling pathway | IDA PMID:8128231 Functional participation of the IL-2 receptor gamma chain in... | ACCEPT | Summary: IL7R annotated to IL-7-mediated signaling pathway by direct assay from Kondo et al. (1994). The study demonstrated that IL7R and the gamma chain form functional receptor complexes that transduce IL-7 signals involved in T and B cell differentiation. Reason: IL7R is a core component of the IL-7 signaling pathway. Kondo et al. demonstrated the functional IL-7 receptor requires both IL7R and gamma chain for signal transduction. Supporting Evidence: PMID:8128231 the gamma chain participates in the functional high-affinity receptor complexes for IL-7 that are involved in the differentiation of T and B cells |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868658 | KEEP AS NON CORE | Summary: IL7R annotated to clathrin-coated endocytic vesicle membrane from Reactome clathrin-mediated endocytosis pathway. Cytokine receptors including IL7R undergo clathrin-mediated endocytosis as part of receptor internalization and signal attenuation. IL7R is ubiquitinated by MARCHF8, leading to lysosomal degradation (PMID:39311660), which is consistent with endocytic trafficking. Reason: Clathrin-mediated endocytosis is a general mechanism for receptor internalization. While IL7R does undergo endocytosis as part of receptor turnover and signal regulation, this is not a core localization for IL7R function. Its primary functional site is the plasma membrane. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868659 | KEEP AS NON CORE | Summary: Duplicate Reactome annotation for clathrin-coated endocytic vesicle membrane from a different reaction in the endocytosis pathway. Reason: Same assessment as the other clathrin-coated endocytic vesicle annotations. Receptor endocytosis is not a core function. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868660 | KEEP AS NON CORE | Summary: Duplicate Reactome annotation for clathrin-coated endocytic vesicle membrane from endocytosis pathway. Reason: Same assessment as above. Receptor endocytosis is not a core function. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868661 | KEEP AS NON CORE | Summary: Duplicate Reactome annotation for clathrin-coated endocytic vesicle membrane from dynamin-mediated vesicle scission step. Reason: Same assessment as above. Receptor endocytosis is not a core function. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8869438 | KEEP AS NON CORE | Summary: Duplicate Reactome annotation for clathrin-coated endocytic vesicle membrane from clathrin-associated protein dissociation step. Reason: Same assessment as above. Receptor endocytosis is not a core function. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8871193 | KEEP AS NON CORE | Summary: Duplicate Reactome annotation for clathrin-coated endocytic vesicle membrane from AAK1 dissociation step. Reason: Same assessment as above. Receptor endocytosis is not a core function. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8871194 | KEEP AS NON CORE | Summary: Duplicate Reactome annotation for clathrin-coated endocytic vesicle membrane from RAB5 binding step. Reason: Same assessment as above. Receptor endocytosis is not a core function. |
| GO:0004896 cytokine receptor activity | IDA PMID:11418668 Human thymic stromal lymphopoietin preferentially stimulates... | ACCEPT | Summary: IL7R annotated to cytokine receptor activity based on Reche et al. (2001, PMID:11418668), which identified human TSLP and demonstrated that it signals through a heterodimeric receptor complex consisting of the TSLP receptor (TSLPR) and IL-7Ralpha. Cells transfected with both receptor subunits proliferated in response to TSLP, with induced phosphorylation of STAT3 and STAT5. This confirms IL7R functions as a cytokine receptor subunit for TSLP in addition to IL-7, supporting the broader cytokine receptor activity annotation. Reason: Reche et al. (PMID:11418668) directly demonstrated that IL7R (IL-7Ralpha) is a functional component of the TSLP receptor complex. Cells co-expressing TSLPR and IL-7Ralpha proliferated in response to TSLP with STAT3/STAT5 activation. This, together with the IL-7 receptor function, confirms IL7R has broad cytokine receptor activity serving as a shared subunit for both IL-7 and TSLP signaling. Consistent with the other GO:0004896 annotations (IEA, IDA from PMID:20974963). Supporting Evidence: PMID:11418668 Human TSLP is proposed to signal through a heterodimeric receptor complex that consists of a new member of the hemopoietin family termed human TSLP receptor and the IL-7R alpha-chain. Cells transfected with both receptor subunits proliferated in response to purified, recombinant human TSLP, with induced phosphorylation of Stat3 and Stat5. |
| GO:0008284 positive regulation of cell population proliferation | IDA PMID:11418668 Human thymic stromal lymphopoietin preferentially stimulates... | ACCEPT | Summary: IL7R annotated to positive regulation of cell population proliferation based on Reche et al. (2001, PMID:11418668). The study showed that cells transfected with TSLPR and IL-7Ralpha proliferated in response to TSLP. Additionally, TSLP enhanced dendritic cell maturation and the capacity to elicit proliferation of naive T cells. TSLP/IL7R signaling also promotes CD4+ T cell proliferation (PMID:20974963). Reason: Reche et al. (PMID:11418668) demonstrated that cells co-expressing TSLPR and IL-7Ralpha proliferated in response to TSLP, and that TSLP enhanced the capacity of dendritic cells to elicit naive T cell proliferation. This is further supported by Rochman et al. (PMID:20974963) showing TSLP-mediated proliferation of CD4+ T cells. While not a core molecular function, positive regulation of cell proliferation is a well-supported downstream biological process of IL7R signaling. Supporting Evidence: PMID:11418668 Cells transfected with both receptor subunits proliferated in response to purified, recombinant human TSLP, with induced phosphorylation of Stat3 and Stat5. PMID:20974963 we demonstrate the importance of STAT5 activation for TSLP-mediated survival and proliferation of CD4(+) T cells |
| GO:1904894 positive regulation of receptor signaling pathway via STAT | IDA PMID:11418668 Human thymic stromal lymphopoietin preferentially stimulates... | ACCEPT | Summary: IL7R annotated to positive regulation of receptor signaling pathway via STAT based on Reche et al. (2001, PMID:11418668). The study showed that cells co-expressing TSLPR and IL-7Ralpha exhibited induced phosphorylation of STAT3 and STAT5 in response to TSLP. This is further confirmed by Rochman et al. (PMID:20974963) who demonstrated JAK1/JAK2-mediated STAT5 phosphorylation in TSLP signaling through IL7R. Reason: Reche et al. (PMID:11418668) directly showed STAT3 and STAT5 phosphorylation upon TSLP signaling through IL7R/TSLPR. Rochman et al. (PMID:20974963) further elucidated the JAK1/JAK2 mechanism. IL7R positively regulates STAT signaling in both IL-7 (STAT5 via JAK1/JAK3) and TSLP (STAT3/STAT5 via JAK1/JAK2) contexts. Supporting Evidence: PMID:11418668 Cells transfected with both receptor subunits proliferated in response to purified, recombinant human TSLP, with induced phosphorylation of Stat3 and Stat5. PMID:20974963 We now demonstrate the role of JAK1 and JAK2 in TSLP-mediated STAT5 phosphorylation in mouse and human primary CD4(+) T cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-449958 | ACCEPT | Summary: IL7R at plasma membrane from Reactome IL-7 signaling pathway step where IL7:IL7R:JAK1 binds IL2RG:JAK3 to form the signaling complex. Reason: Plasma membrane localization is where IL7R functions as part of the IL-7 signaling complex. Reactome pathway annotation is consistent with known biology. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-449978 | ACCEPT | Summary: IL7R at plasma membrane from Reactome where IL7 binds IL7R:JAK1. Reason: Correct. IL-7 binding to IL7R occurs at the plasma membrane. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8866277 | ACCEPT | Summary: IL7R at plasma membrane from Reactome endocytosis pathway step where AP-2 binds endocytic cargo at the plasma membrane. Reason: Correct. IL7R is at the plasma membrane prior to endocytosis. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867754 | ACCEPT | Summary: IL7R at plasma membrane from Reactome endocytosis pathway. Reason: Correct. Plasma membrane localization during clathrin-coated pit formation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867756 | ACCEPT | Summary: IL7R at plasma membrane from Reactome endocytosis pathway (CLASP recruitment step). Reason: Correct. Redundant but valid Reactome evidence. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868071 | ACCEPT | Summary: IL7R at plasma membrane from Reactome endocytosis pathway (clathrin recruits PIK3C2A step). Reason: Correct. Redundant but valid. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868072 | ACCEPT | Summary: IL7R at plasma membrane from Reactome endocytosis pathway (PIK3C2A phosphorylation step). Reason: Correct. Redundant but valid. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868230 | ACCEPT | Summary: IL7R at plasma membrane from Reactome endocytosis pathway (SNX9 recruitment step). Reason: Correct. Redundant but valid. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868236 | ACCEPT | Summary: IL7R at plasma membrane from Reactome endocytosis pathway (dynamin recruitment step). Reason: Correct. Redundant but valid. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868648 | ACCEPT | Summary: IL7R at plasma membrane from Reactome endocytosis pathway (synaptojanin step). Reason: Correct. Redundant but valid. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868651 | ACCEPT | Summary: IL7R at plasma membrane from Reactome endocytosis pathway (endophilin step). Reason: Correct. Redundant but valid. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: IL7R at plasma membrane from Reactome endocytosis pathway (dynamin GTP hydrolysis step). Reason: Correct. Redundant but valid. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8983059 | ACCEPT | Summary: IL7R at plasma membrane from Reactome TSLP signaling pathway where STAT3 is phosphorylated by TSLP:IL7R:CRLF2:STAT3 complex. Reason: Correct. IL7R functions at the plasma membrane as part of the TSLP receptor signaling complex. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8983061 | ACCEPT | Summary: IL7R at plasma membrane from Reactome where TSLP binds CRLF2:IL7R. Reason: Correct. TSLP binding to the CRLF2/IL7R complex occurs at the plasma membrane. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8983063 | ACCEPT | Summary: IL7R at plasma membrane from Reactome IL-7 signaling where JAK3 is phosphorylated in the IL7:IL7R:JAK1:IL2RG:JAK3 complex. Reason: Correct. JAK3 phosphorylation in the IL-7 signaling complex occurs at the plasma membrane. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8983078 | ACCEPT | Summary: IL7R at plasma membrane from Reactome where p-STAT3 dissociates from TSLP:IL7R:CRLF2 complex. Reason: Correct. STAT3 dissociation from the TSLP receptor occurs at the plasma membrane. |
| GO:0005886 plasma membrane | TAS Reactome:R-NUL-8982998 | ACCEPT | Summary: IL7R at plasma membrane from Reactome where Stat3 binds IL7R:TSLP:CRLF2 complex. Reason: Correct. STAT3 recruitment to the TSLP receptor occurs at the plasma membrane. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1295540 | ACCEPT | Summary: IL7R at plasma membrane from Reactome where the IL7:IL7R:JAK1:IL2RG: JAK3 complex phosphorylates STAT5. Reason: Correct. STAT5 phosphorylation by the IL-7R signaling complex occurs at the plasma membrane. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6785165 | ACCEPT | Summary: IL7R at plasma membrane from Reactome where p-STAT5A/B dissociates from the IL-7 signaling complex. Reason: Correct. Phospho-STAT5 dissociation occurs at the plasma membrane before STAT5 translocation to the nucleus. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8983003 | ACCEPT | Summary: IL7R at plasma membrane from Reactome where the IL-7 receptor complex binds PI3K regulatory subunits and IRS1/IRS2. Reason: Correct. PI3K engagement by the IL-7R signaling complex occurs at the plasma membrane. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9025969 | ACCEPT | Summary: IL7R at plasma membrane from Reactome where STAT5 binds the activated IL-7 receptor complex. Reason: Correct. STAT5 recruitment to the activated receptor occurs at the plasma membrane. |
| GO:0000018 regulation of DNA recombination | TAS PMID:9495344 Impaired immunoglobulin gene rearrangement in mice lacking t... | KEEP AS NON CORE | Summary: IL7R annotated to regulation of DNA recombination from PMID:9495344. This publication is not available for direct review. IL-7/IL7R signaling is known to promote V(D)J recombination during lymphocyte development by inducing accessibility of immunoglobulin and TCR gene loci. However, IL7R does not directly regulate recombination; it signals to promote the conditions under which RAG-mediated recombination can occur. Reason: IL-7 signaling promotes V(D)J recombination indirectly by inducing chromatin accessibility and survival of recombining lymphocyte progenitors. This is a downstream consequence of IL7R signaling rather than a direct molecular function. The annotation is not wrong but represents a secondary effect of IL7R signaling in the context of lymphocyte development. |
| GO:0003823 antigen binding | TAS PMID:9495344 Impaired immunoglobulin gene rearrangement in mice lacking t... | REMOVE | Summary: IL7R annotated to antigen binding from PMID:9495344. This is a legacy annotation from PINC (2003). IL7R does not bind antigens; it binds its cytokine ligand IL-7. This appears to be an erroneous annotation, possibly from confusion about the protein's function or misinterpretation of the source publication. Reason: IL7R is a cytokine receptor, not an antigen-binding molecule. It binds IL-7 and TSLP cytokines, not antigens. This annotation appears to be an error from a legacy curation effort (PINC, 2003). The protein has no immunoglobulin variable domains or other antigen-binding structures. Its Ig-like fold is a structural domain of the cytokine receptor superfamily, not an antigen-recognition domain. |
| GO:0004917 interleukin-7 receptor activity | TAS PMID:8266077 Interleukin-2 receptor gamma chain: a functional component o... | ACCEPT | Summary: IL7R annotated to interleukin-7 receptor activity from PMID:8266077, a legacy annotation from PINC. This is the core molecular function of IL7R and is well-supported regardless of the specific reference. Reason: Interleukin-7 receptor activity is the primary molecular function of IL7R. This is supported by multiple lines of evidence including structural, biochemical, and genetic studies. Supporting Evidence: PMID:8128231 the gamma chain participates in the functional high-affinity receptor complexes for IL-7 |
| GO:0006955 immune response | TAS PMID:9843216 Defective IL7R expression in T(-)B(+)NK(+) severe combined i... | ACCEPT | Summary: IL7R annotated to immune response from PMID:9843216 (Puel et al. 1998), which reported that defective IL7R expression causes T-B+NK+ SCID. Loss of IL7R results in absent T cells, demonstrating its essential role in immune system development. Reason: IL7R is essential for T cell development and thus for adaptive immune responses. The SCID phenotype caused by IL7R deficiency directly demonstrates this. Immune response is a broad but valid annotation. Supporting Evidence: PMID:9843216 Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency |
| GO:0007165 signal transduction | TAS PMID:2317865 Cloning of the human and murine interleukin-7 receptors - de... | ACCEPT | Summary: IL7R annotated to signal transduction from the original cloning paper by Goodwin et al. (1990) which cloned the human IL-7 receptor and demonstrated it as a signaling receptor. Signal transduction is a broad parent term of the more specific IL-7-mediated signaling pathway annotation. Reason: Signal transduction is a correct broad annotation for IL7R. As a cytokine receptor, IL7R transduces signals from the extracellular ligand (IL-7 or TSLP) to intracellular effectors (JAK-STAT, PI3K-AKT, MAPK). This was established in the original cloning paper. Supporting Evidence: PMID:2317865 Cloning of the human and murine interleukin-7 receptors: demonstration of a soluble form and homology to a new receptor superfamily |
| GO:0007166 cell surface receptor signaling pathway | TAS PMID:9843216 Defective IL7R expression in T(-)B(+)NK(+) severe combined i... | ACCEPT | Summary: IL7R annotated to cell surface receptor signaling pathway from Puel et al. (1998). This is a correct broader annotation capturing the fact that IL7R signals from the cell surface. The study demonstrated that loss of IL7R causes SCID, establishing its role as an essential cell surface signaling receptor. Reason: Cell surface receptor signaling pathway accurately describes the mode of IL7R signaling. The annotation is correct, though broader than the more specific IL-7-mediated signaling pathway term. Supporting Evidence: PMID:9843216 Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency |
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