FLT3 is a class III receptor tyrosine kinase of haematopoietic progenitor cells and dendritic-cell precursors, related to KIT and CSF1R. It is a single-pass type I membrane protein whose five extracellular immunoglobulin-like domains are exposed at the cell surface and bind the cytokine FLT3 ligand; binding drives receptor dimerisation, releases the autoinhibited conformation and triggers autophosphorylation of the split intracellular kinase domain. Activated FLT3 recruits PI3K and SRC-family and SYK kinases and drives AKT, MTOR and ERK signalling, supporting proliferation, survival and differentiation of early progenitors, B-cell precursors and dendritic cells. Internal tandem duplications and kinase-domain mutations make the receptor constitutively active and are among the most frequent lesions in acute myeloid leukaemia; such mutants are partly retained in the endoplasmic reticulum rather than reaching the surface.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001776 leukocyte homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transferred from the mouse ortholog, whose loss reduces several leukocyte populations. Reason: A whole-organism consequence of impaired progenitor and dendritic-cell development rather than a core activity of the receptor, and the evidence is not human. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells |
| GO:0002318 myeloid progenitor cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Inferred from the mouse ortholog; consistent with the curated role in progenitor differentiation. Reason: The human receptor is expressed on CD34-positive progenitors and supports their proliferation, so the claim is plausible, but the specific differentiation programme is inferred rather than demonstrated in human cells. Supporting Evidence: PMID:7507245 STK-1, the human homolog of Flk-2/Flt-3, is selectively expressed in CD34+ human bone marrow cells and is involved in the proliferation of early progenitor/stem cells. |
| GO:0002328 pro-B cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: A mouse-derived role in early B lymphopoiesis. Reason: Well established for mouse Flt3 but inferred for human, and downstream of the receptor's signalling function. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: A parent of the transmembrane receptor protein tyrosine kinase activity already asserted. Reason: The specific receptor-kinase term is supported by the curated catalytic activity and by direct studies, and it entails this one. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000120 | TOO GENERAL | Summary: A parent of the transmembrane receptor protein tyrosine kinase activity already asserted. Reason: True but entailed by the specific receptor term, which is directly supported. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-9604767 | TOO GENERAL | Summary: Reactome records the tyrosine kinase activity of FLT3 in a signalling reaction. Reason: Correct but entailed by the specific transmembrane receptor kinase term. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-9706344 | TOO GENERAL | Summary: Same assessment as the other Reactome kinase rows. Reason: Entailed by the specific receptor tyrosine kinase term. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] |
| GO:0004713 protein tyrosine kinase activity | TAS Reactome:R-HSA-9706350 | TOO GENERAL | Summary: Same assessment as the other Reactome kinase rows. Reason: Entailed by the specific receptor tyrosine kinase term. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] |
| GO:0004714 transmembrane receptor protein tyrosine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: FLT3 is an active class III receptor tyrosine kinase. Reason: The ancestral assertion for this receptor clade holds, and human FLT3 autophosphorylates on ligand binding with a curated catalytic reaction. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt FLT3LG binding leads to dimerization and activation by autophosphorylation. |
| GO:0004714 transmembrane receptor protein tyrosine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated inference agreeing with the curated activity. Reason: Consistent with the catalytic reaction and the receptor architecture. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] |
| GO:0004714 transmembrane receptor protein tyrosine kinase activity | TAS PMID:19549778 Structural and functional alterations of FLT3 in acute myelo... | ACCEPT | Summary: The review of FLT3 structure and function in AML describes the receptor kinase and its activating mutations. Reason: Consistent with the curated catalytic activity and with the mechanism of ligand-induced activation. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Present in an inactive conformation in the absence of bound ligand. |
| GO:0004888 transmembrane signaling receptor activity | IEA GO_REF:0000117 | TOO GENERAL | Summary: A parent of the transmembrane receptor protein tyrosine kinase activity already asserted. Reason: The specific term states both the receptor and the catalytic nature of FLT3 and entails this one. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG |
| GO:0004896 cytokine receptor activity | ISS GO_REF:0000024 | ACCEPT | Summary: FLT3 is the receptor for the cytokine FLT3 ligand. Reason: UniProt describes FLT3 as a cell-surface receptor for the cytokine FLT3LG, whose binding drives dimerisation and activation, so the inferred term matches human biology. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG |
| GO:0005021 vascular endothelial growth factor receptor activity | TAS PMID:8394751 Human FLT3/FLK2 gene: cDNA cloning and expression in hematop... | REMOVE | Summary: FLT3 is not a VEGF receptor; its ligand is FLT3LG and its closest relatives are KIT and CSF1R. Reason: The FLT name is shared with the VEGF receptors FLT1 and FLT4, but the cited cloning paper places FLT3 with CSF1R and KIT, the class III receptor kinases, not with the VEGF receptor class. UniProt records FLT3LG as the ligand and no VEGF binding, and no study shows VEGF activating FLT3. The annotation appears to follow the gene name rather than the biology. Supporting Evidence: PMID:8394751 The deduced amino acid sequence shows that FLT3 codes for a receptor-type tyrosine kinase of 993 residues, presenting a strong similarity with the corresponding mouse FLT3/FLK2 protein as well as with the receptors for colony-stimulating factor 1 (CSF1R/FMS) and steel locus factor (SLFR/KIT). |
| GO:0005515 protein binding | IPI PMID:16982329 Constitutive c-jun N-terminal kinase activity in acute myelo... | MODIFY | Summary: The interactor is the PI3K regulatory subunit p85 (PIK3R1). Reason: Activated FLT3 recruits PI3K, and the gene separately carries phosphatidylinositol 3-kinase activator activity on direct evidence, so the informative replacement for the generic term is phosphatidylinositol 3-kinase binding. Proposed replacements: phosphatidylinositol 3-kinase binding Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. |
| GO:0005515 protein binding | IPI PMID:20098747 Expanding the substantial interactome of NEMO using protein ... | REMOVE | Summary: A NEMO hit from a protein-microarray interactome screen. Reason: The generic term carries no functional information and a microarray binding event supports no specific molecular function for FLT3. Supporting Evidence: PMID:20098747 Expanding the substantial interactome of NEMO using protein microarrays. |
| GO:0005515 protein binding | IPI PMID:23246379 FLT3 signals via the adapter protein Grb10 and overexpressio... | REMOVE | Summary: Bare protein binding for the GRB10 adapter. Reason: The interaction is real and functionally interesting, but GO has no informative binding term for an SH2 adapter of this kind, and the downstream consequence is already covered by the signalling annotations. Supporting Evidence: PMID:23246379 FLT3 signals via the adapter protein Grb10 and overexpression of Grb10 leads to aberrant cell proliferation in acute myeloid leukemia. |
| GO:0005515 protein binding | IPI PMID:24525236 SYK is a critical regulator of FLT3 in acute myeloid leukemi... | MODIFY | Summary: The interactor is the tyrosine kinase SYK. Reason: SYK binds and regulates FLT3 in AML cells, so protein kinase binding is the informative replacement for the uninformative generic term. Proposed replacements: protein kinase binding Supporting Evidence: PMID:24525236 SYK is a critical regulator of FLT3 in acute myeloid leukemia. |
| GO:0005515 protein binding | IPI PMID:27458164 Src-like adaptor protein 2 (SLAP2) binds to and inhibits FLT... | REMOVE | Summary: Bare protein binding for the mouse SLAP2 adapter. Reason: The adapter binds and inhibits FLT3 signalling, which is a regulatory relationship rather than a molecular function of FLT3, and the generic term is uninformative. Supporting Evidence: PMID:27458164 Src-like adaptor protein 2 (SLAP2) binds to and inhibits FLT3 signaling. |
| GO:0005515 protein binding | IPI PMID:28086240 ABL2 suppresses FLT3-ITD-induced cell proliferation through ... | MODIFY | Summary: The interactor is the tyrosine kinase ABL1. Reason: A kinase partner recovered in the same study that defines ABL2 regulation of FLT3-ITD signalling, so protein kinase binding replaces the generic term. Proposed replacements: protein kinase binding Supporting Evidence: PMID:28086240 ABL2 suppresses FLT3-ITD-induced cell proliferation through negative regulation of AKT signaling. |
| GO:0005515 protein binding | IPI PMID:28086240 ABL2 suppresses FLT3-ITD-induced cell proliferation through ... | MODIFY | Summary: The interactor is the SRC-family kinase LCK. Reason: UniProt records interactions of FLT3 with SRC-family kinases, so protein kinase binding is the informative replacement. Proposed replacements: protein kinase binding Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Interacts with FES, FER, LYN, FGR, HCK, SRC and GRB2. |
| GO:0005515 protein binding | IPI PMID:28086240 ABL2 suppresses FLT3-ITD-induced cell proliferation through ... | MODIFY | Summary: The interactor is the SRC-family kinase FYN. Reason: Same assessment as the other SRC-family rows. Proposed replacements: protein kinase binding Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Interacts with FES, FER, LYN, FGR, HCK, SRC and GRB2. |
| GO:0005515 protein binding | IPI PMID:28086240 ABL2 suppresses FLT3-ITD-induced cell proliferation through ... | REMOVE | Summary: Bare protein binding for the RasGAP RASA1. Reason: No informative molecular-function term applies to binding a GTPase-activating protein, and the generic term carries no information. Supporting Evidence: PMID:28086240 ABL2 suppresses FLT3-ITD-induced cell proliferation through negative regulation of AKT signaling. |
| GO:0005515 protein binding | IPI PMID:28086240 ABL2 suppresses FLT3-ITD-induced cell proliferation through ... | MODIFY | Summary: The interactor is the tyrosine kinase ABL2. Reason: ABL2 binds FLT3-ITD and suppresses its proliferative signalling, so protein kinase binding is the informative replacement. Proposed replacements: protein kinase binding Supporting Evidence: PMID:28086240 ABL2 suppresses FLT3-ITD-induced cell proliferation through negative regulation of AKT signaling. |
| GO:0005515 protein binding | IPI PMID:28086240 ABL2 suppresses FLT3-ITD-induced cell proliferation through ... | MODIFY | Summary: A second record of the SYK interaction. Reason: Same partner and same informative replacement as the other SYK row. Proposed replacements: protein kinase binding Supporting Evidence: PMID:24525236 SYK is a critical regulator of FLT3 in acute myeloid leukemia. |
| GO:0005515 protein binding | IPI PMID:28086240 ABL2 suppresses FLT3-ITD-induced cell proliferation through ... | REMOVE | Summary: Bare protein binding for the CRK adapter. Reason: An SH2 and SH3 adapter recruited to the phosphorylated receptor; no informative molecular-function term applies, and the generic term is uninformative. Supporting Evidence: PMID:28086240 ABL2 suppresses FLT3-ITD-induced cell proliferation through negative regulation of AKT signaling. |
| GO:0005515 protein binding | IPI PMID:28086240 ABL2 suppresses FLT3-ITD-induced cell proliferation through ... | REMOVE | Summary: Bare protein binding for the CRKL adapter. Reason: Same assessment as the CRK row. Supporting Evidence: PMID:28086240 ABL2 suppresses FLT3-ITD-induced cell proliferation through negative regulation of AKT signaling. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: The kinase domain binds ATP. Reason: FLT3 has an intact split tyrosine-kinase domain and a curated ATP-consuming catalytic reaction. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] |
| GO:0005788 endoplasmic reticulum lumen | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: An immature pool is retained in the ER, prominently for constitutively active mutants. Reason: UniProt records the ER-lumen location with the note that internal tandem duplication mutants are inefficiently transported to the cell surface. This is a genuine but secondary location; the functional site is the plasma membrane. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Constitutively activated mutant forms with internal tandem duplications are less efficiently transported to the cell surface and a significant proportion is retained in an immature form in the endoplasmic reticulum lumen. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: FLT3 acts at the plasma membrane, with its immunoglobulin-like ligand-binding domains exposed at the cell surface. Reason: The ancestral assertion for class III receptor kinases matches human FLT3, which is a single-pass type I membrane protein detected at the surface of normal and malignant haematopoietic cells and activated there by its ligand. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG |
| GO:0005886 plasma membrane | TAS PMID:8394751 Human FLT3/FLK2 gene: cDNA cloning and expression in hematop... | ACCEPT | Summary: The cloning paper describes FLT3 as a receptor-type tyrosine kinase of haematopoietic cells. Reason: A receptor-type kinase with a transmembrane segment resides in the plasma membrane, which later work confirmed directly. Supporting Evidence: PMID:8394751 The deduced amino acid sequence shows that FLT3 codes for a receptor-type tyrosine kinase of 993 residues |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-109699 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2316434 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2400009 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5672965 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6786789 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8854736 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9604767 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9607301 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9607304 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9695828 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9695831 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9695834 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9695838 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9695841 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9695845 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9695853 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9698000 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9698003 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9698005 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9698007 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9698008 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9698013 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9698029 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9698170 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9698174 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9698408 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9699578 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9702508 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9702510 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9702570 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9702578 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9702583 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9702589 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9702593 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9702601 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9702607 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9702613 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9702618 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9702623 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9702629 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9702638 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9702997 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9703008 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706287 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706293 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706298 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706304 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706308 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706312 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706315 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706319 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706323 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706328 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706330 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706336 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706340 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706344 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706345 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706350 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706354 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706356 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9706364 | ACCEPT | Summary: Reactome places FLT3, wild type or mutant, at the plasma membrane in a signalling reaction. Reason: The compartment matches the curated single-pass type I membrane topology and the surface expression of the receptor on haematopoietic cells. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0007166 cell surface receptor signaling pathway | IEA GO_REF:0000117 | TOO GENERAL | Summary: A parent of the cell surface receptor protein tyrosine kinase signaling pathway already asserted. Reason: The specific term is accepted here on phylogenetic and author evidence and entails this one. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG |
| GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: FLT3 initiates receptor tyrosine kinase signalling on ligand binding. Reason: The inherited assertion matches the human biology, in which ligand-induced dimerisation and autophosphorylation launch AKT, MTOR and ERK signalling. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt FLT3LG binding leads to dimerization and activation by autophosphorylation. |
| GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway | IEA GO_REF:0000002 | ACCEPT | Summary: Domain-based inference agreeing with the direct evidence. Reason: Consistent with the receptor architecture and curated function. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG |
| GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway | TAS PMID:7507245 STK-1, the human homolog of Flk-2/Flt-3, is selectively expr... | ACCEPT | Summary: STK-1, the human FLT3 homologue, signals in CD34-positive progenitors. Reason: The cited study links receptor expression and signalling to progenitor proliferation. Supporting Evidence: PMID:7507245 STK-1, the human homolog of Flk-2/Flt-3, is selectively expressed in CD34+ human bone marrow cells and is involved in the proliferation of early progenitor/stem cells. |
| GO:0008284 positive regulation of cell population proliferation | IBA GO_REF:0000033 | ACCEPT | Summary: FLT3 signalling drives proliferation of haematopoietic progenitors. Reason: Direct human evidence supports the inherited assertion, and constitutively active mutants drive uncontrolled proliferation in AML. Supporting Evidence: PMID:7507245 is involved in the proliferation of early progenitor/stem cells |
| GO:0008284 positive regulation of cell population proliferation | TAS PMID:19549778 Structural and functional alterations of FLT3 in acute myelo... | ACCEPT | Summary: Activating FLT3 alterations promote proliferation in acute myeloid leukaemia. Reason: Consistent with the curated statement that constitutive kinase activity promotes proliferation and resistance to apoptosis. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways. |
| GO:0008284 positive regulation of cell population proliferation | TAS PMID:7507245 STK-1, the human homolog of Flk-2/Flt-3, is selectively expr... | ACCEPT | Summary: The receptor supports proliferation of early progenitor and stem cells. Reason: Stated directly in the cited study. Supporting Evidence: PMID:7507245 is involved in the proliferation of early progenitor/stem cells |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-9706364 | KEEP AS NON CORE | Summary: Activated receptor is internalised into endosomes before degradation. Reason: A trafficking compartment on the route to degradation rather than the site of ligand sensing. UniProt notes the activated kinase is rapidly targeted for degradation. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt The activated kinase is rapidly targeted for degradation. |
| GO:0016020 membrane | IEA GO_REF:0000120 | MODIFY | Summary: Correct but less specific than the evidence allows. Reason: FLT3 is a single-pass type I protein of the plasma membrane, a term it already carries extensively. Proposed replacements: plasma membrane Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0016477 cell migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Class III receptor kinases influence progenitor migration. Reason: The inherited assertion is reasonable for this receptor family, but human FLT3's documented roles are proliferation, survival and differentiation; migration is secondary. Retained as non-core. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells |
| GO:0018108 peptidyl-tyrosine phosphorylation | TAS PMID:19549778 Structural and functional alterations of FLT3 in acute myelo... | ACCEPT | Summary: FLT3 phosphorylates tyrosines on itself and on downstream substrates. Reason: This is the catalytic process the receptor performs, with a curated catalytic reaction and documented substrates. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. |
| GO:0019221 cytokine-mediated signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: FLT3 transduces the signal of the cytokine FLT3 ligand. Reason: The receptor is activated by a cytokine and carries the signal into the cell, so it performs the receptor step of this pathway. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG |
| GO:0019221 cytokine-mediated signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Curator-judged transfer agreeing with the human biology. Reason: Human FLT3 is itself the cytokine receptor, so the inference adds no error. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG |
| GO:0019221 cytokine-mediated signaling pathway | TAS Reactome:R-HSA-9607240 | ACCEPT | Summary: Reactome models FLT3 signalling within cytokine signalling in the immune system. Reason: Consistent with the receptor's role for FLT3LG. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG |
| GO:0019838 growth factor binding | IBA GO_REF:0000033 | ACCEPT | Summary: The extracellular immunoglobulin-like domains bind FLT3 ligand. Reason: Ligand binding is the defining extracellular function of the receptor and is what triggers dimerisation and activation. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt FLT3LG binding leads to dimerization and activation by autophosphorylation. |
| GO:0030097 hemopoiesis | IDA PMID:7507245 STK-1, the human homolog of Flk-2/Flt-3, is selectively expr... | ACCEPT | Summary: FLT3 is expressed on CD34-positive marrow cells and supports early progenitor proliferation. Reason: Direct human evidence for a role in blood cell production, which is the principal physiological setting of this receptor. Supporting Evidence: PMID:7507245 STK-1, the human homolog of Flk-2/Flt-3, is selectively expressed in CD34+ human bone marrow cells and is involved in the proliferation of early progenitor/stem cells. |
| GO:0030097 hemopoiesis | IEA GO_REF:0000117 | ACCEPT | Summary: Rule-based assignment agreeing with the direct evidence. Reason: Consistent with the curated function in haematopoietic progenitors. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells |
| GO:0030183 B cell differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: FLT3 supports early B lymphopoiesis. Reason: Well supported in mouse and consistent with the progenitor role, but a lineage-specific developmental outcome rather than the core receptor function. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells |
| GO:0030183 B cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator-judged transfer of the same lineage role. Reason: Same assessment as the phylogenetic row. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | TOO GENERAL | Summary: A parent of the signaling receptor complex term already asserted. Reason: FLT3 forms a ligand-bound homodimer, recorded as a signaling receptor complex, which entails this top-level term. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Homodimer in the presence of bound FLT3LG. |
| GO:0035259 obsolete nuclear glucocorticoid receptor binding | IEA GO_REF:0000107 | REMOVE | Summary: An obsolete term transferred from the mouse ortholog, asserting a nuclear receptor interaction for a cell-surface kinase. Reason: FLT3 is a single-pass membrane receptor whose cytoplasmic kinase domain faces the cytosol; a binding function for the nuclear glucocorticoid receptor is not supported by any human data, and the term itself has been obsoleted in GO. The related cellular response to glucocorticoid row is retained as non-core. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Membrane; Single-pass type I membrane protein. |
| GO:0035726 common myeloid progenitor cell proliferation | ISS GO_REF:0000024 | ACCEPT | Summary: FLT3 drives proliferation of early myeloid progenitors. Reason: The human receptor is expressed on CD34-positive progenitors and is involved in their proliferation, which is exactly this term. Supporting Evidence: PMID:7507245 is involved in the proliferation of early progenitor/stem cells |
| GO:0038084 vascular endothelial growth factor signaling pathway | IEA GO_REF:0000108 | REMOVE | Summary: Derived from the incorrect VEGF receptor activity annotation. Reason: This row is generated by mapping from the molecular function GO:0005021, which is itself a misassignment based on the shared FLT gene-name prefix. FLT3 binds FLT3LG, not VEGF, and has no role in VEGF signalling. Supporting Evidence: PMID:8394751 presenting a strong similarity with the corresponding mouse FLT3/FLK2 protein as well as with the receptors for colony-stimulating factor 1 (CSF1R/FMS) and steel locus factor (SLFR/KIT) |
| GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein | TAS PMID:19549778 Structural and functional alterations of FLT3 in acute myelo... | KEEP AS NON CORE | Summary: FLT3 promotes STAT5 phosphorylation, strongly for mutant and only marginally for wild-type receptor. Reason: UniProt notes that activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B, so this is mainly a property of the constitutively active mutants. Retained as non-core. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. |
| GO:0042981 regulation of apoptotic process | TAS PMID:19549778 Structural and functional alterations of FLT3 in acute myelo... | KEEP AS NON CORE | Summary: FLT3 signalling supports survival, and mutant receptors confer resistance to apoptosis. Reason: A downstream consequence of PI3K and ERK signalling rather than a direct activity, and the strongest evidence comes from oncogenic mutants. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways. |
| GO:0043235 signaling receptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: Ligand binding converts the monomeric receptor into a signalling homodimer. Reason: UniProt records the monomer-to-homodimer transition on FLT3LG binding, so the receptor is genuinely part of a signalling receptor complex. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Monomer in the absence of bound FLT3LG. Homodimer in the presence of bound FLT3LG. |
| GO:0043406 positive regulation of MAP kinase activity | TAS PMID:19549778 Structural and functional alterations of FLT3 in acute myelo... | ACCEPT | Summary: FLT3 signalling activates ERK1 and ERK2. Reason: UniProt records promotion of RAS signalling and phosphorylation of MAPK1 and MAPK3 downstream of the receptor. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. |
| GO:0043410 positive regulation of MAPK cascade | TAS PMID:19549778 Structural and functional alterations of FLT3 in acute myelo... | ACCEPT | Summary: The receptor turns on the RAS-ERK cascade. Reason: Same curated basis as the MAP kinase activity row; the cascade term describes the pathway-level effect, which is likewise supported. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: A generic binding term transferred from the ortholog. Reason: FLT3 does assemble with multimeric signalling complexes, so the claim is not wrong, but it adds little to the specific kinase- and PI3K-binding terms proposed here. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Interacts with FES, FER, LYN, FGR, HCK, SRC and GRB2. |
| GO:0046651 lymphocyte proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Inferred lymphoid proliferation role, consistent with the early B-cell function. Reason: Inferred from the ortholog and lineage-specific; the general proliferative role is accepted separately. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells |
| GO:0046777 protein autophosphorylation | TAS PMID:19549778 Structural and functional alterations of FLT3 in acute myelo... | ACCEPT | Summary: Ligand-induced dimerisation leads to FLT3 autophosphorylation. Reason: Directly curated as the activation mechanism of the receptor. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt FLT3LG binding leads to dimerization and activation by autophosphorylation. |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | TAS PMID:12951584 The role of FLT3 in haematopoietic malignancies. | ACCEPT | Summary: FLT3 activates the PI3K-AKT axis. Reason: UniProt records promotion of AKT1 phosphorylation and MTOR activation downstream of the receptor, and PI3K recruitment is a direct consequence of receptor autophosphorylation. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. |
| GO:0071345 cellular response to cytokine stimulus | ISS GO_REF:0000024 | TOO GENERAL | Summary: A parent of the cytokine-mediated signaling pathway term already asserted. Reason: The pathway term is accepted here and entails this broader response term. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG |
| GO:0071345 cellular response to cytokine stimulus | TAS PMID:19549778 Structural and functional alterations of FLT3 in acute myelo... | TOO GENERAL | Summary: Same assessment as the companion row. Reason: Entailed by the accepted cytokine-mediated signaling pathway annotation. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG |
| GO:0071385 cellular response to glucocorticoid stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from rodent data on glucocorticoid regulation of FLT3. Reason: Plausible as a transcriptional or signalling response in rodent cells, but there is no human evidence and it is remote from the receptor's core function. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells |
| GO:0097028 dendritic cell differentiation | ISS GO_REF:0000024 | ACCEPT | Summary: FLT3 controls dendritic-cell development. Reason: UniProt states directly that the receptor regulates differentiation, proliferation and survival of dendritic cells, which makes this one of its principal physiological roles rather than a peripheral inference. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells |
| GO:0097421 liver regeneration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: A rodent-derived association with regenerating liver. Reason: No human evidence and no mechanistic link to the receptor's haematopoietic function. Retained as non-core rather than removed. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells |
| GO:0141038 phosphatidylinositol 3-kinase activator activity | TAS PMID:12951584 The role of FLT3 in haematopoietic malignancies. | ACCEPT | Summary: Phosphorylated FLT3 recruits and activates PI3K. Reason: PI3K activation is a direct consequence of receptor autophosphorylation and p85 recruitment, and the downstream AKT and MTOR activation is curated. Supporting Evidence: file:human/FLT3/FLT3-uniprot.txt Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. |
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Download this section (compressed HTML)Q: How much of the surface pool of FLT3 is lost in ITD-mutant cells, and does the ER-retained mutant signal from the ER rather than from the plasma membrane?
Q: Which of the many kinases recovered as FLT3 partners, SYK, ABL2 and the SRC-family members, act on the receptor and which are substrates?
Q: Does wild-type FLT3 signalling to STAT5 occur at all in primary human progenitors, given that it is reported as marginal in cell lines?
Experiment: Compare surface and total FLT3 by flow cytometry on non-permeabilised and permeabilised cells expressing wild-type or ITD receptors, and localise active signalling with phospho-specific antibodies and compartment-restricted inhibitors.
Hypothesis: ITD mutants signal predominantly from an intracellular compartment rather than the cell surface.
Experiment: Reconstitute each kinase with purified FLT3 intracellular domain, map phosphosites by mass spectrometry, then test the same sites by mutation in cells for proliferation and AKT activation.
Hypothesis: SYK and ABL2 have opposite effects on FLT3 output because one phosphorylates the receptor and the other acts downstream.
Experiment: Use labelled FLT3 ligand and conformation-selective antibodies on primary AML blasts and normal progenitors to quantify surface receptor and ligand-binding competence side by side.
Hypothesis: The ligand-binding surface of FLT3 is accessible on primary CD34-positive cells in a way that distinguishes wild-type from mutant receptors.
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