Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0008754
UniProt IDP17948
Primary gene name(s)FLT1
Synonym gene name(s)FLT, FRT, VEGFR1
Protein nameVascular endothelial growth factor receptor 1
Protein functionTyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts, in vitro. Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion. {ECO:0000269|PubMed:11141500, ECO:0000269|PubMed:11312102, ECO:0000269|PubMed:11811792, ECO:0000269|PubMed:12796773, ECO:0000269|PubMed:14633857, ECO:0000269|PubMed:15735759, ECO:0000269|PubMed:16685275, ECO:0000269|PubMed:18079407, ECO:0000269|PubMed:18515749, ECO:0000269|PubMed:18583712, ECO:0000269|PubMed:18593464, ECO:0000269|PubMed:20512933, ECO:0000269|PubMed:20551949, ECO:0000269|PubMed:21752276, ECO:0000269|PubMed:7824266, ECO:0000269|PubMed:8248162, ECO:0000269|PubMed:8605350, ECO:0000269|PubMed:9299537}.
Subcellular locationIsoform 1: Cell membrane;
Single-pass type I membrane protein. Endosome. Note=Autophosphorylation promotes ubiquitination and endocytosis.;
SUBCELLULAR LOCATION: Isoform 2: Secreted {ECO:0000269|PubMed:8248162}.;
SUBCELLULAR LOCATION: Isoform 3: Secreted.;
SUBCELLULAR LOCATION: Isoform 4: Secreted.;
SUBCELLULAR LOCATION: Isoform 5: Cytoplasm {ECO:0000305}.;
SUBCELLULAR LOCATION: Isoform 6: Cytoplasm {ECO:0000305}.;
SUBCELLULAR LOCATION: Isoform 7: Cytoplasm {ECO:0000305}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P17948
Gene Ontology
(Biological Process)
Complete annatation
angiogenesis [GO:0001525];
blood vessel morphogenesis [GO:0048514];
cell differentiation [GO:0030154];
cell migration [GO:0016477];
cellular response to vascular endothelial growth factor stimulus [GO:0035924];
embryonic morphogenesis [GO:0048598];
monocyte chemotaxis [GO:0002548];
peptidyl-tyrosine phosphorylation [GO:0018108];
positive regulation of angiogenesis [GO:0045766];
positive regulation of cell migration [GO:0030335];
positive regulation of cell proliferation [GO:0008284];
positive regulation of MAPK cascade [GO:0043410];
positive regulation of MAP kinase activity [GO:0043406];
positive regulation of phosphatidylinositol 3-kinase activity [GO:0043552];
positive regulation of phosphatidylinositol 3-kinase signaling [GO:0014068];
positive regulation of phospholipase C activity [GO:0010863];
positive regulation of vascular endothelial growth factor receptor signaling pathway [GO:0030949];
protein autophosphorylation [GO:0046777];
transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169];
vascular endothelial growth factor receptor-1 signaling pathway [GO:0036323];
vascular endothelial growth factor receptor signaling pathway [GO:0048010]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
growth factor binding [GO:0019838];
placental growth factor-activated receptor activity [GO:0036332];
transmembrane receptor protein tyrosine kinase activity [GO:0004714];
vascular endothelial growth factor-activated receptor activity [GO:0005021];
VEGF-A-activated receptor activity [GO:0036326];
VEGF-B-activated receptor activity [GO:0036327]
Gene Ontology
(Cellular Component)
Complete annatation
endosome [GO:0005768];
extracellular space [GO:0005615];
focal adhesion [GO:0005925];
integral component of plasma membrane [GO:0005887];
plasma membrane [GO:0005886];
receptor complex [GO:0043235]
Protein-protein interaction108609
Phylogenetic treeP17948
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3unknownunknownunknown
AZA vs. DISUunknownunknownunknown
AZA vs. IL7unknownunknownunknown
AZA vs. SAHAunknownunknownunknown
DISU vs. CD3unknownunknownunknown
DISU vs. IL7unknownunknownunknown
DISU vs. SAHAunknownunknownunknown
DMSO vs. AZAunknownunknownunknown
DMSO vs. CD3unknownunknownunknown
DMSO vs. DISUunknownunknownunknown
DMSO vs. IL7unknownunknownunknown
DMSO vs. SAHAunknownunknownunknown
HIV vs. Mock in Activation-0.1301545620424440.8443948708081210.999983755607037
HIV vs. Mock in Latencyunknownunknownunknown
IL7 vs. CD3unknownunknownunknown
SAHA vs. CD3unknownunknownunknown
SAHA vs. IL7unknownunknownunknown
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock 1.128 1.60E-12 7.94E-10
Infected vs. Bystander 1.059 6.05E-12 9.46E-10
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 1.4232 0.000305467
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB01268 Sunitinib approved, investigational yes inhibitor
DB04879 Vatalanib investigational unknown unknown
DB05075 TG100801 investigational unknown unknown
DB06080 ABT-869 investigational unknown unknown
DB05913 OSI-930 investigational unknown unknown
DB06101 IMC-1C11 investigational unknown unknown
DB06589 Pazopanib approved yes inhibitor
DB06626 Axitinib approved, investigational yes inhibitor
DB07288 N-(4-chlorophenyl)-2-[(pyridin-4-ylmethyl)amino]benzamide experimental unknown unknown
DB08896 Regorafenib approved yes inhibitor
DB00398 Sorafenib approved, investigational yes inhibitor
DB09078 Lenvatinib approved yes Inhibitor
DB09079 Nintedanib approved yes Inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1FLT X-ray 1.7Å X/Y=132-226.
1QSV NMR - A=129-229.
1QSZ NMR - A=129-229.
1QTY X-ray 2.7Å T/U/X/Y=129-229.
1RV6 X-ray 2.4Å X/Y=130-229.
2XAC X-ray 2.7Å C/X=129-226.
3HNG X-ray 2.7Å A=801-1158.
4CKV X-ray 2.0Å X=132-225.
4CL7 X-ray 2.0Å A/B/C/D=132-225.
5ABD X-ray 2.0Å E/I/X=132-226.
5EX3 X-ray 2.4Å D=827-835.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 downregulates 21612582
Tat inhibited by 9269752
Tat activates 9269752
Tat cooperates with 20661303
Tat binds 9269752
Tat downregulates 22095559
Nef upregulates 18443354

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04014 Ras signaling pathway - Homo sapiens (human)
hsa04015 Rap1 signaling pathway - Homo sapiens (human)
hsa04060 Cytokine-cytokine receptor interaction - Homo sapiens (human)
hsa04066 HIF-1 signaling pathway - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04510 Focal adhesion - Homo sapiens (human)
hsa05202 Transcriptional misregulation in cancer - Homo sapiens (human)
hsa05323 Rheumatoid arthritis - Homo sapiens (human)