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

    Gene ID: 2321, updated on 28-Oct-2024

    Summary

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    Official Symbol
    FLT1provided by HGNC
    Official Full Name
    fms related receptor tyrosine kinase 1provided by HGNC
    Primary source
    HGNC:HGNC:3763
    See related
    Ensembl:ENSG00000102755 MIM:165070; AllianceGenome:HGNC:3763
    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]
    Expression
    Biased expression in placenta (RPKM 90.6), thyroid (RPKM 20.1) and 8 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See FLT1 in Genome Data Viewer
    Location:
    13q12.3
    Exon count:
    32
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (28300346..28495128, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (27522576..27717351, complement)
    RS_2024_09 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 poly(A) specific ribonuclease subunit PAN3 Neighboring gene NANOG hESC enhancer GRCh37_chr13:28812056-28812711 Neighboring gene RNA, U6 small nuclear 82, pseudogene Neighboring gene uncharacterized LOC124903140 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:28863191-28863692 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:28863693-28864192 Neighboring gene ReSE screen-validated silencer GRCh37_chr13:28870451-28870609 Neighboring gene uncharacterized LOC124903141 Neighboring gene Sharpr-MPRA regulatory region 10890 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr13:28896366-28897565 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:28902230-28902730 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5211 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7511 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7512 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7513 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7514 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:29004443-29005102 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:29010702-29011644 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:29012644-29013428 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:29014214-29014998 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_32819 Neighboring gene ReSE screen-validated silencer GRCh37_chr13:29041404-29041635 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5212 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5213 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5214 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:29078159-29078659 Neighboring gene Sharpr-MPRA regulatory region 5274 Neighboring gene Sharpr-MPRA regulatory region 7947 Neighboring gene uncharacterized LOC124903142 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5215 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5216 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7515 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7516 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr13:29148510-29149709 Neighboring gene uncharacterized LOC105370135 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:29157670-29158170

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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 Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Placental soluble fms-like tyrosine kinase expression in small for gestational age infants and risk for adverse outcomes. Spiel M, et al. Placenta, 2017 Apr. PMID 28454690
    2. Soluble Flt-1 gene therapy ameliorates albuminuria but accelerates tubulointerstitial injury in diabetic mice. Kosugi T, et al. Am J Physiol Renal Physiol, 2010 Mar. PMID 20015944
    3. Expression of soluble vascular endothelial growth factor receptor-1 in human monocyte-derived mature dendritic cells contributes to their antiangiogenic property. Kishuku M, et al. J Immunol, 2009 Dec 15. PMID 20007583
    4. Soluble fms-Like Tyrosine Kinase 1 as a Link Between Angiogenesis and Endothelial Dysfunction in Pediatric Patients With β-Thalassemia Intermedia. Tantawy AAG, et al. Clin Appl Thromb Hemost, 2017 Nov. PMID 28301910
    5. Soluble Flt-1 Has Cytotoxic Effects on BeWo Choriocarcinoma Cells. Yamashita M, et al. Reprod Sci, 2018 Jun. PMID 28322131

    See all (829) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Interaction of Purine and its Derivatives with A1, A2-Adenosine Receptors and Vascular Endothelial Growth Factor Receptor-1 (Vegf-R1) as a Therapeutic Alternative to Treat Cancer.
      Title: Interaction of Purine and its Derivatives with A1, A2-Adenosine Receptors and Vascular Endothelial Growth Factor Receptor-1 (Vegf-R1) as a Therapeutic Alternative to Treat Cancer.
    2. FLT1 activation in cancer cells promotes PARP-inhibitor resistance in breast cancer.
      Title: FLT1 activation in cancer cells promotes PARP-inhibitor resistance in breast cancer.
    3. Selective inhibition of HDAC6 regulates expression of the oncogenic driver EWSR1-FLI1 through the EWSR1 promoter in Ewing sarcoma.
      Title: Selective inhibition of HDAC6 regulates expression of the oncogenic driver EWSR1-FLI1 through the EWSR1 promoter in Ewing sarcoma.
    4. Gasdermin D regulates soluble fms-like tyrosine kinase 1 release in macrophages.
      Title: Gasdermin D regulates soluble fms-like tyrosine kinase 1 release in macrophages.
    5. Overexpression of Human sFLT1 in the Spongiotrophoblast Is Sufficient to Induce Placental Dysfunction and Fetal Growth Restriction in Transgenic Mice.
      Title: Overexpression of Human sFLT1 in the Spongiotrophoblast Is Sufficient to Induce Placental Dysfunction and Fetal Growth Restriction in Transgenic Mice.
    6. A defined clathrin-mediated trafficking pathway regulates sFLT1/VEGFR1 secretion from endothelial cells.
      Title: A defined clathrin-mediated trafficking pathway regulates sFLT1/VEGFR1 secretion from endothelial cells.
    7. Trafficking dynamics of VEGFR1, VEGFR2, and NRP1 in human endothelial cells.
      Title: Trafficking dynamics of VEGFR1, VEGFR2, and NRP1 in human endothelial cells.
    8. Persistently elevated sFlt-1 and recovery of reduced ADAMTS13 activity in malignant hypertension.
      Title: Persistently elevated sFlt-1 and recovery of reduced ADAMTS13 activity in malignant hypertension.
    9. Preeclamptic serum and soluble fms-like tyrosine kinase-1 suppress endothelial inward rectifier potassium currents.
      Title: Preeclamptic serum and soluble fms-like tyrosine kinase-1 suppress endothelial inward rectifier potassium currents.
    10. SOD3 regulates FLT1 to affect bone metabolism by promoting osteogenesis and inhibiting adipogenesis through PI3K/AKT and MAPK pathways.
      Title: SOD3 regulates FLT1 to affect bone metabolism by promoting osteogenesis and inhibiting adipogenesis through PI3K/AKT and MAPK pathways.
    Submit: New GeneRIF Correction See all GeneRIFs (726)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    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

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables growth factor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables placental growth factor receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transmembrane receptor protein tyrosine kinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables vascular endothelial growth factor receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables vascular endothelial growth factor receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables vascular endothelial growth factor receptor activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in angiogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in blood vessel morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell migration IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cell surface receptor protein tyrosine kinase signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in cellular response to vascular endothelial growth factor stimulus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in embryonic morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in hyaloid vascular plexus regression ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in monocyte chemotaxis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in multicellular organism development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of vascular endothelial cell proliferation IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in peptidyl-tyrosine phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of MAP kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of MAPK cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of MAPK cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of angiogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of cell migration IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of cell migration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of cell population proliferation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in sprouting angiogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in vascular endothelial growth factor receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in vascular endothelial growth factor receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in vascular endothelial growth factor receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in vascular endothelial growth factor receptor-1 signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in vascular endothelial growth factor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in actin cytoskeleton IDA
    Inferred from Direct Assay
    more info
    		  
    located_in endosome IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular space TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in focal adhesion HDA PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    part_of receptor complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of receptor complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    vascular endothelial growth factor receptor 1
    Names
    fms related tyrosine kinase 1
    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

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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), LRG_425

    mRNA and Protein(s)

    1. NM_001159920.2 → NP_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/TrEMBL
      A0A1W2PNW4
      Related
      ENSP00000484039.1, ENST00000615840.5
      Conserved Domains (5) summary
      cd07702
      Location:353 → 424
      Ig_VEGFR-1; Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1)
      smart00409
      Location:143 → 219
      IG; Immunoglobulin
      smart00410
      Location:568 → 640
      IG_like; Immunoglobulin like
      pfam13927
      Location:427 → 539
      Ig_3; Immunoglobulin domain
      cl11960
      Location:245 → 327
      Ig; Immunoglobulin domain

    2. NM_001160030.2 → NP_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, AL138712, EU360600, EU368830
      Consensus CDS
      CCDS53860.1
      UniProtKB/TrEMBL
      A0A1W2PNW4
      Related
      ENSP00000437631.1, ENST00000541932.5
      Conserved Domains (5) summary
      smart00410
      Location:568 → 640
      IG_like; Immunoglobulin like
      cd00096
      Location:248 → 252
      Ig; Ig strand B [structural motif]
      cd07702
      Location:333 → 424
      IgI_VEGFR-1; Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1); member of the I-set of Ig superfamily (IgSF) domains
      pfam13927
      Location:427 → 539
      Ig_3; Immunoglobulin domain
      cl11960
      Location:230 → 330
      Ig; Immunoglobulin domain

    3. NM_001160031.1 → NP_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
      ENSP00000442630.1, ENST00000539099.2
      Conserved Domains (4) summary
      cd05742
      Location:245 → 327
      Ig1_VEGFR_like; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins
      cd07702
      Location:353 → 424
      Ig2_VEGFR-1; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1)
      smart00410
      Location:237 → 328
      IG_like; Immunoglobulin like
      cl11960
      Location:439 → 466
      Ig; Immunoglobulin domain

    4. NM_002019.4 → NP_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
      A3E342, A3E344, A8KA71, B0LPF1, B2BF46, B2BF47, B2BF48, B3FR89, B5A923, F5H5L6, O60722, P16057, P17948, Q12954
      UniProtKB/TrEMBL
      L7RSL3
      Related
      ENSP00000282397.4, ENST00000282397.9
      Conserved Domains (8) summary
      cd05742
      Location:245 → 327
      Ig1_VEGFR_like; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins
      cd07702
      Location:353 → 424
      Ig2_VEGFR-1; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1)
      smart00408
      Location:676 → 738
      IGc2; Immunoglobulin C-2 Type
      smart00409
      Location:568 → 640
      IG; Immunoglobulin
      smart00410
      Location:237 → 328
      IG_like; Immunoglobulin like
      pfam07679
      Location:661 → 748
      I-set; Immunoglobulin I-set domain
      cd14207
      Location:819 → 1157
      PTKc_VEGFR1; Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors
      pfam07714
      Location:827 → 1154
      Pkinase_Tyr; Protein tyrosine kinase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

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

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060937.1 Alternate T2T-CHM13v2.0

      Range
      27522576..27717351 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P17948.2 GenPept UniProtKB/Swiss-Prot:P17948

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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