InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: FLT3

Summary

InnateDB Protein

IDBP-19897.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

FLT3

Protein Name

fms-related tyrosine kinase 3

Synonyms

CD135; FLK-2; FLK2; STK1;

Species

Homo sapiens

Ensembl Protein

ENSP00000241453

InnateDB Gene

IDBG-19891 (FLT3)

Protein Structure

UniProt Annotation

Function

Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways. {ECO:0000269PubMed:10080542, ECO:0000269PubMed:11090077, ECO:0000269PubMed:14504097, ECO:0000269PubMed:16266983, ECO:0000269PubMed:16627759, ECO:0000269PubMed:18490735, ECO:0000269PubMed:20111072, ECO:0000269PubMed:21067588, ECO:0000269PubMed:21262971, ECO:0000269PubMed:21516120, ECO:0000269PubMed:7507245}.

Subcellular Localization

Membrane; Single-pass type I membrane protein. Endoplasmic reticulum lumen. Note=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. The activated kinase is rapidly targeted for degradation.

Disease Associations

Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. {ECO:0000269PubMed:11090077, ECO:0000269PubMed:11290608, ECO:0000269PubMed:11442493, ECO:0000269PubMed:14504097, ECO:0000269PubMed:16266983, ECO:0000269PubMed:18305215, ECO:0000269PubMed:8946930, ECO:0000269PubMed:9737679}. Note=The gene represented in this entry may be involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of FLT3 are frequent in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the activation loop of the kinase domain can result in a constitutively activated kinase.

Tissue Specificity

Detected in bone marrow, in hematopoietic stem cells, in myeloid progenitor cells and in granulocyte/macrophage progenitor cells (at protein level). Detected in bone marrow, liver, thymus, spleen and lymph node, and at low levels in kidney and pancreas. Highly expressed in T-cell leukemia. {ECO:0000269PubMed:18490735, ECO:0000269PubMed:7507245, ECO:0000269PubMed:8394751, ECO:0000269PubMed:8637232}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 24 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	24 [view]
Protein-Protein	23 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004714	transmembrane receptor protein tyrosine kinase activity
GO:0004896	cytokine receptor activity
GO:0005021	vascular endothelial growth factor-activated receptor activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0032403	protein complex binding
GO:0035259	glucocorticoid receptor binding
GO:0042803	protein homodimerization activity
GO:0043548	phosphatidylinositol 3-kinase binding

Biological Process

GO:0001776	leukocyte homeostasis
GO:0001934	positive regulation of protein phosphorylation
GO:0002318	myeloid progenitor cell differentiation
GO:0002320	lymphoid progenitor cell differentiation
GO:0002328	pro-B cell differentiation
GO:0002572	pro-T cell differentiation
GO:0006468	protein phosphorylation
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway
GO:0008284	positive regulation of cell proliferation
GO:0008285	negative regulation of cell proliferation
GO:0010243	response to organonitrogen compound
GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0019221	cytokine-mediated signaling pathway
GO:0030097	hemopoiesis
GO:0030098	lymphocyte differentiation
GO:0030183	B cell differentiation
GO:0031100	organ regeneration
GO:0035726	common myeloid progenitor cell proliferation
GO:0038084	vascular endothelial growth factor signaling pathway
GO:0042531	positive regulation of tyrosine phosphorylation of STAT protein
GO:0042981	regulation of apoptotic process
GO:0043406	positive regulation of MAP kinase activity
GO:0043410	positive regulation of MAPK cascade
GO:0043552	positive regulation of phosphatidylinositol 3-kinase activity
GO:0045578	negative regulation of B cell differentiation
GO:0046651	lymphocyte proliferation
GO:0046777	protein autophosphorylation
GO:0071345	cellular response to cytokine stimulus
GO:0071385	cellular response to glucocorticoid stimulus
GO:0097028	dendritic cell differentiation

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005788	endoplasmic reticulum lumen
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0009897	external side of plasma membrane
GO:0009986	cell surface
GO:0016021	integral component of membrane
GO:0043234	protein complex

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR007110 Immunoglobulin-like domain
IPR011009 Protein kinase-like domain
IPR013151 Immunoglobulin
IPR016243 Tyrosine-protein kinase, CSF-1/PDGF receptor
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF00047

PRINTS

PR00109

PIRSF

PIRSF000615
PIRSF500947

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References