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    FLT1 fms related tyrosine kinase 1 [ Homo sapiens (human) ]

    Gene ID: 2321, updated on 12-Mar-2017
    Official Symbol
    FLT1provided by HGNC
    Official Full Name
    fms related tyrosine kinase 1provided by HGNC
    Primary source
    HGNC:HGNC:3763
    See related
    Ensembl:ENSG00000102755 MIM:165070; Vega:OTTHUMG00000016648
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    FLT; FLT-1; VEGFR1; VEGFR-1
    Summary
    This gene encodes a member of the vascular endothelial growth factor receptor (VEGFR) family. VEGFR family members are receptor tyrosine kinases (RTKs) which contain an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and a tyrosine kinase (TK) domain within the cytoplasmic domain. This protein binds to VEGFR-A, VEGFR-B and placental growth factor and plays an important role in angiogenesis and vasculogenesis. Expression of this receptor is found in vascular endothelial cells, placental trophoblast cells and peripheral blood monocytes. Multiple transcript variants encoding different isoforms have been found for this gene. Isoforms include a full-length transmembrane receptor isoform and shortened, soluble isoforms. The soluble isoforms are associated with the onset of pre-eclampsia.[provided by RefSeq, May 2009]
    Orthologs
    Location:
    13q12.3
    Exon count:
    33
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 13 NC_000013.11 (28300346..28495128, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (28874483..29069265, complement)

    Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene PAN3 poly(A) specific ribonuclease subunit Neighboring gene eukaryotic translation elongation factor 1 alpha 1 pseudogene 3 Neighboring gene RNA, U6 small nuclear 82, pseudogene Neighboring gene uncharacterized LOC105370135 Neighboring gene eukaryotic translation initiation factor 4A1 pseudogene 7

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    NHGRI GWAS Catalog

    Description
    A genome-wide association study of a coronary artery disease risk variant.
    NHGRI GWA Catalog
    A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB.
    NHGRI GWA Catalog

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 downregulates Flt-1 expression in human mesenchymal stem cells PubMed
    Nef nef HIV-1 Nef upregulates FLT1 in podocytes PubMed
    Tat tat HIV-1 Tat inhibits the differentiation of mesenchymal stem cells (MSCs) to endothelial cells by downregulating the expression of VEGF-induced endothelial markers such as Flt-1, KDR and vWF PubMed
    tat HIV-1 Tat-mediated inhibition of autophagy in bystander macrophages/monocytic cells requires CXCR4, VEGFR1, and beta-integrins PubMed
    tat The mechanism of monocyte activation by HIV-1 Tat involves the binding of Tat to VEGFR-1/Flt-1 and activating signals through this receptor PubMed
    tat The soluble form of VEGFR-1 inhibits monocyte polarization and migration induced by HIV-1 Tat PubMed
    tat The biologic activities of HIV-1 Tat in human monocytes are, at least in part, elicited by Tat activation of VEGFR-1/Flt-1 PubMed

    Go to the HIV-1, Human Interaction Database

    • Angiogenesis, organism-specific biosystem (from WikiPathways)
      Angiogenesis, organism-specific biosystemThis pathway is a concise and simplified version of the basic proteins involved in angiogenesis. The proces is regulated by hyopoxia, which results in the transcription of eg. VEGF1, FGF2, PDGFbeta, ...
    • Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
      Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
    • Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
      Cytokine-cytokine receptor interaction, conserved biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
    • Endocytosis, organism-specific biosystem (from KEGG)
      Endocytosis, organism-specific biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
    • Endocytosis, conserved biosystem (from KEGG)
      Endocytosis, conserved biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
    • Focal Adhesion, organism-specific biosystem (from WikiPathways)
      Focal Adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
    • Focal adhesion, organism-specific biosystem (from KEGG)
      Focal adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
    • Focal adhesion, conserved biosystem (from KEGG)
      Focal adhesion, conserved biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
    • Glypican 1 network, organism-specific biosystem (from Pathway Interaction Database)
      Glypican 1 network, organism-specific biosystem
      Glypican 1 network
    • HIF-1 signaling pathway, organism-specific biosystem (from KEGG)
      HIF-1 signaling pathway, organism-specific biosystemHypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. It consists of two subunits: an inducibly-expressed HIF-1alpha subunit and a c...
    • HIF-2-alpha transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
      HIF-2-alpha transcription factor network, organism-specific biosystem
      HIF-2-alpha transcription factor network
    • Neurophilin interactions with VEGF and VEGFR, organism-specific biosystem (from REACTOME)
      Neurophilin interactions with VEGF and VEGFR, organism-specific biosystemThe plasma membrane-associated Neuropilin receptors NRP-1 and -2 bind some of the VEGF proteins and associate with VEGF receptor proteins. NRP-1 binds VEGF-A165, -B, and PLGF-2; NRP-2 also binds VEGF...
    • PI3K-Akt signaling pathway, organism-specific biosystem (from KEGG)
      PI3K-Akt signaling pathway, organism-specific biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
    • PI3K-Akt signaling pathway, conserved biosystem (from KEGG)
      PI3K-Akt signaling pathway, conserved biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
    • Rap1 signaling pathway, organism-specific biosystem (from KEGG)
      Rap1 signaling pathway, organism-specific biosystemRap1 is a small GTPase that controls diverse processes, such as cell adhesion, cell-cell junction formation and cell polarity. Like all G proteins, Rap1 cycles between an inactive GDP-bound and an ac...
    • Rap1 signaling pathway, conserved biosystem (from KEGG)
      Rap1 signaling pathway, conserved biosystemRap1 is a small GTPase that controls diverse processes, such as cell adhesion, cell-cell junction formation and cell polarity. Like all G proteins, Rap1 cycles between an inactive GDP-bound and an ac...
    • Ras signaling pathway, organism-specific biosystem (from KEGG)
      Ras signaling pathway, organism-specific biosystemThe Ras proteins are GTPases that function as molecular switches for signaling pathways regulating cell proliferation, survival, growth, migration, differentiation or cytoskeletal dynamism. Ras prote...
    • Rheumatoid arthritis, organism-specific biosystem (from KEGG)
      Rheumatoid arthritis, organism-specific biosystemRheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune...
    • Rheumatoid arthritis, conserved biosystem (from KEGG)
      Rheumatoid arthritis, conserved biosystemRheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune...
    • S1P3 pathway, organism-specific biosystem (from Pathway Interaction Database)
      S1P3 pathway, organism-specific biosystem
      S1P3 pathway
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by VEGF, organism-specific biosystem (from REACTOME)
      Signaling by VEGF, organism-specific biosystemIn normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angioge...
    • Signaling events mediated by VEGFR1 and VEGFR2, organism-specific biosystem (from Pathway Interaction Database)
      Signaling events mediated by VEGFR1 and VEGFR2, organism-specific biosystem
      Signaling events mediated by VEGFR1 and VEGFR2
    • Transcriptional misregulation in cancer, organism-specific biosystem (from KEGG)
      Transcriptional misregulation in cancer, organism-specific biosystem
      Transcriptional misregulation in cancer
    • Transcriptional misregulation in cancer, conserved biosystem (from KEGG)
      Transcriptional misregulation in cancer, conserved biosystem
      Transcriptional misregulation in cancer
    • VEGF binds to VEGFR leading to receptor dimerization, organism-specific biosystem (from REACTOME)
      VEGF binds to VEGFR leading to receptor dimerization, organism-specific biosystemThe binding of VEGF ligands to VEGFR receptors in the cell membrane induces dimerization and activation of the latter, initiating intracellular signaling cascades that result in proliferation, surviv...
    • VEGF ligand-receptor interactions, organism-specific biosystem (from REACTOME)
      VEGF ligand-receptor interactions, organism-specific biosystemThe VEGF family is encoded by seven genes (VEGF-A, B, C, D, E: PLGF (Placenta Growth Factor)-1, 2). Six isoforms of VEGF-A protein, containing 121, 145, 165, 183, 189, and 206 amino acid residues, an...
    • VEGFR1 specific signals, organism-specific biosystem (from Pathway Interaction Database)
      VEGFR1 specific signals, organism-specific biosystem
      VEGFR1 specific signals
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    angiogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    blood vessel morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    cell migration IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    cellular response to vascular endothelial growth factor stimulus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    embryonic morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    monocyte chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    peptidyl-tyrosine phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of MAP kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of MAPK cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of angiogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of cell migration IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of cell proliferation TAS
    Traceable Author Statement
    more info
    PubMed 
    positive regulation of phosphatidylinositol 3-kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of phosphatidylinositol 3-kinase signaling IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of phospholipase C activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of vascular endothelial growth factor receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    transmembrane receptor protein tyrosine kinase signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    vascular endothelial growth factor receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    vascular endothelial growth factor receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    vascular endothelial growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    vascular endothelial growth factor receptor-1 signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    vascular endothelial growth factor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    actin cytoskeleton IDA
    Inferred from Direct Assay
    more info
     
    endosome IEA
    Inferred from Electronic Annotation
    more info
     
    extracellular space TAS
    Traceable Author Statement
    more info
    PubMed 
    focal adhesion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    integral component of plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    plasma membrane IDA
    Inferred from Direct Assay
    more info
     
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    receptor complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Preferred Names
    vascular endothelial growth factor receptor 1
    Names
    fms-like tyrosine kinase 1
    fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)
    tyrosine-protein kinase FRT
    tyrosine-protein kinase receptor FLT
    vascular permeability factor receptor
    NP_001153392.1
    NP_001153502.1
    NP_001153503.1
    NP_002010.2

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_012003.1 RefSeqGene

      Range
      5001..199783
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001159920.1NP_001153392.1  vascular endothelial growth factor receptor 1 isoform 2 precursor

      See identical proteins and their annotated locations for NP_001153392.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2), also known as sFlt1 or sVEGFR-1, differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded soluble protein (isoform 2) has a shorter, distinct C-terminus and lacks the transmembrane and cytoplasmic regions of isoform 1.
      Source sequence(s)
      AL138712, AL139005
      Consensus CDS
      CCDS73556.1
      UniProtKB/Swiss-Prot
      P17948
      Related
      ENSP00000484039, OTTHUMP00000275032, ENST00000615840, OTTHUMT00000474549
      Conserved Domains (5) summary
      cd05742
      Location:245327
      Ig1_VEGFR_like; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins
      cd07702
      Location:353424
      Ig2_VEGFR-1; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1)
      smart00408
      Location:569640
      IGc2; Immunoglobulin C-2 Type
      smart00410
      Location:237328
      IG_like; Immunoglobulin like
      cl11960
      Location:447544
      Ig; Immunoglobulin domain
    2. NM_001160030.1NP_001153502.1  vascular endothelial growth factor receptor 1 isoform 3 precursor

      See identical proteins and their annotated locations for NP_001153502.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded soluble protein (isoform 3) has a shorter, distinct C-terminus and lacks the transmembrane and cytoplasmic regions of isoform 1.
      Source sequence(s)
      AK300392, EU360600, EU368830
      Consensus CDS
      CCDS53860.1
      UniProtKB/Swiss-Prot
      P17948
      Related
      ENSP00000437631, OTTHUMP00000275035, ENST00000541932, OTTHUMT00000474577
      Conserved Domains (5) summary
      cd05742
      Location:245327
      Ig1_VEGFR_like; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins
      cd07702
      Location:353424
      Ig2_VEGFR-1; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1)
      smart00408
      Location:569640
      IGc2; Immunoglobulin C-2 Type
      smart00410
      Location:237328
      IG_like; Immunoglobulin like
      cl11960
      Location:671708
      Ig; Immunoglobulin domain
    3. NM_001160031.1NP_001153503.1  vascular endothelial growth factor receptor 1 isoform 4 precursor

      See identical proteins and their annotated locations for NP_001153503.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded soluble protein (isoform 4) has a shorter, distinct C-terminus and lacks the transmembrane and cytoplasmic regions of isoform 1.
      Source sequence(s)
      DA844548, EU826561
      Consensus CDS
      CCDS53861.1
      UniProtKB/Swiss-Prot
      P17948
      Related
      ENSP00000442630, ENST00000539099
      Conserved Domains (4) summary
      cd05742
      Location:245327
      Ig1_VEGFR_like; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins
      cd07702
      Location:353424
      Ig2_VEGFR-1; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1)
      smart00410
      Location:237328
      IG_like; Immunoglobulin like
      cl11960
      Location:439466
      Ig; Immunoglobulin domain
    4. NM_002019.4NP_002010.2  vascular endothelial growth factor receptor 1 isoform 1 precursor

      See identical proteins and their annotated locations for NP_002010.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) the longest isoform (1). Isoform 1 is a transmembrane protein.
      Source sequence(s)
      AF063657, AL138712, BU151621, BX504049, DA851664
      Consensus CDS
      CCDS9330.1
      UniProtKB/Swiss-Prot
      P17948
      UniProtKB/TrEMBL
      L7RSL3
      Related
      ENSP00000282397, OTTHUMP00000018183, ENST00000282397, OTTHUMT00000044322
      Conserved Domains (8) summary
      cd05742
      Location:245327
      Ig1_VEGFR_like; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins
      cd07702
      Location:353424
      Ig2_VEGFR-1; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1)
      smart00408
      Location:676738
      IGc2; Immunoglobulin C-2 Type
      smart00409
      Location:568640
      IG; Immunoglobulin
      smart00410
      Location:237328
      IG_like; Immunoglobulin like
      pfam07679
      Location:661748
      I-set; Immunoglobulin I-set domain
      cd14207
      Location:8191157
      PTKc_VEGFR1; Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors
      pfam07714
      Location:8271154
      Pkinase_Tyr; Protein tyrosine kinase

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000013.11 Reference GRCh38.p7 Primary Assembly

      Range
      28300346..28495128 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017020485.1XP_016875974.1  vascular endothelial growth factor receptor 1 isoform X1

    2. XM_011535014.1XP_011533316.1  vascular endothelial growth factor receptor 1 isoform X2

      Conserved Domains (5) summary
      cd05742
      Location:245327
      Ig1_VEGFR_like; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins
      cd07702
      Location:353424
      Ig2_VEGFR-1; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1)
      smart00408
      Location:569640
      IGc2; Immunoglobulin C-2 Type
      smart00410
      Location:237328
      IG_like; Immunoglobulin like
      cl11960
      Location:660720
      Ig; Immunoglobulin domain

    Alternate CHM1_1.1

    Genomic

    1. NC_018924.2 Alternate CHM1_1.1

      Range
      28842736..29037594 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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