From NCBI Gene: Hemangioma, capillary infantileFrom UniProt: Hemangioma, capillary infantile (HCI): A condition characterized by dull red, firm, dome-shaped hemangiomas, sharply demarcated from surrounding skin, usually presenting at birth or occurring within the first two or three months of life. They result from highly proliferative, localized growth of capillary endothelium and generally undergo regression and involution without scarring. [MIM:602089] Plays a major role in tumor angiogenesis. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.

     From NCBI Gene: Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. This gene encodes one of the two receptors of the VEGF . This receptor, known as kinase insert domain receptor, is a type III receptor tyrosine kinase. It functions as the main mediator of VEGF-induced endothelial proliferation, survival, migration, tubular morphogenesis and sprouting. The signalling and trafficking of this receptor are regulated by multiple factors, including Rab GTPase, P2Y purine nucleotide receptor, integrin alphaVbeta3, T-cell protein tyrosine phosphatase, etc.. Mutations of this gene are implicated in infantile capillary hemangiomas. [provided by RefSeq, May 2009] From UniProt: Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC.

The following transcription factors affect gene expression:

• p53
• STAT3
• Sp1
• GATA-1
• Tal-1beta
• AML1a
• GATA-2
• Tal-1

Tissue specificity:

Detected in cornea (at protein level). Widely expressed.

Enzyme Regulation:

Present in an inactive conformation in the absence of bound ligand. Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by the small molecule PTK inhibitor SU5614 ((3Z)-5-Chloro-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylene]-1,3-dihydro-2H-indol-2-one). May be regulated by hydrogen sulfide (H(2)S) levels via a H(2)S-sensitive intracellular disulfide bond.

Molecular Function:

• Protein Tyrosine Kinase Activity
• Transmembrane Receptor Protein Tyrosine Kinase Activity
• Signal Transducer, Downstream Of Receptor, With Protein Tyrosine Kinase Activity
• Vascular Endothelial Growth Factor-Activated Receptor Activity
• Integrin Binding
• Atp Binding
• Growth Factor Binding
• Vascular Endothelial Growth Factor Binding
• Hsp90 Protein Binding

Biological Processes:

• Angiogenesis
• Vasculogenesis
• Positive Regulation Of Protein Phosphorylation
• Positive Regulation Of Endothelial Cell Proliferation
• Cell Migration Involved In Sprouting Angiogenesis
• Endothelium Development
• Transmembrane Receptor Protein Tyrosine Kinase Signaling Pathway
• Positive Regulation Of Cell Proliferation
• Regulation Of Cell Shape
• Positive Regulation Of Endothelial Cell Migration
• Positive Regulation Of Phosphatidylinositol 3-Kinase Signaling
• Viral Process
• Positive Regulation Of Macroautophagy
• Peptidyl-Tyrosine Phosphorylation
• Extracellular Matrix Organization
• Positive Regulation Of Cell Migration
• Embryonic Hemopoiesis
• Calcium-Mediated Signaling Using Intracellular Calcium Source
• Cellular Response To Vascular Endothelial Growth Factor Stimulus
• Positive Regulation Of Endothelial Cell Chemotaxis By Vegf-Activated Vascular Endothelial Growth Factor Receptor Signaling Pathway
• Peptidyl-Tyrosine Autophosphorylation
• Negative Regulation Of Apoptotic Process
• Positive Regulation Of Mapk Cascade
• Positive Regulation Of Angiogenesis
• Protein Autophosphorylation
• Vascular Endothelial Growth Factor Receptor Signaling Pathway
• Positive Regulation Of Positive Chemotaxis
• Positive Regulation Of Nitric-Oxide Synthase Biosynthetic Process
• Positive Regulation Of Focal Adhesion Assembly
• Positive Regulation Of Mitochondrial Depolarization
• Positive Regulation Of Erk1 And Erk2 Cascade
• Positive Regulation Of Mitochondrial Fission
• Negative Regulation Of Endothelial Cell Apoptotic Process
• Positive Regulation Of Vasculogenesis

Drug Bank:

• Ramucirumab
• Cabozantinib
• Lenvatinib
• Nintedanib
• Pazopanib
• Ponatinib
• Sorafenib
• Sunitinib
• Axitinib
• Regorafenib