KDR kinase insert domain receptor [Homo sapiens (human)] - Gene

Summary

Official Symbol: KDRprovided by HGNC
Official Full Name: kinase insert domain receptorprovided by HGNC
Primary source: HGNC:HGNC:6307
See related: Ensembl:ENSG00000128052 MIM:191306; AllianceGenome:HGNC:6307
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: FLK1; CD309; VEGFR; VEGFR2
Summary: 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]
Expression: Broad expression in placenta (RPKM 44.3), thyroid (RPKM 24.9) and 19 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4q12

Exon count:: 30

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (55078481..55125595, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (58566962..58614067, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (55944648..55991762, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

High expression of DEC2 distinguishes chondroblastic osteosarcoma and promotes tumour growth by activating the VEGFC/VEGFR2 signalling pathway.
Title: High expression of DEC2 distinguishes chondroblastic osteosarcoma and promotes tumour growth by activating the VEGFC/VEGFR2 signalling pathway.
The KDR Gene rs2071559 and the VEGF Gene rs6921438 May Be Associated with Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus.
Title: The KDR Gene rs2071559 and the VEGF Gene rs6921438 May Be Associated with Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus.
Vasorin promotes endothelial differentiation of glioma stem cells via stimulating the transcription of VEGFR2.
Title: Vasorin promotes endothelial differentiation of glioma stem cells via stimulating the transcription of VEGFR2.
Mutation in the Kinase Domain Alters the VEGFR2 Membrane Dynamics.
Title: Mutation in the Kinase Domain Alters the VEGFR2 Membrane Dynamics.
Prognostic Significance of Plasma VEGFA and VEGFR2 in Acute Ischemic Stroke-a Prospective Cohort Study.
Title: Prognostic Significance of Plasma VEGFA and VEGFR2 in Acute Ischemic Stroke-a Prospective Cohort Study.
Lack of VEGFA/KDR Signaling in Conventional Renal Cell Carcinoma Explains the Low Efficacy of Target Therapy and Frequent Adverse Events.
Title: Lack of VEGFA/KDR Signaling in Conventional Renal Cell Carcinoma Explains the Low Efficacy of Target Therapy and Frequent Adverse Events.
Tumor Infiltrating Effector Regulatory T Cells Express VEGF Receptor 2 in Patients With Colorectal Cancer.
Title: Tumor Infiltrating Effector Regulatory T Cells Express VEGF Receptor 2 in Patients With Colorectal Cancer.
The tyrosine kinase KDR is essential for the survival of HTLV-1-infected T cells by stabilizing the Tax oncoprotein.
Title: The tyrosine kinase KDR is essential for the survival of HTLV-1-infected T cells by stabilizing the Tax oncoprotein.
VEGFR2 blockade inhibits glioblastoma cell proliferation by enhancing mitochondrial biogenesis.
Title: VEGFR2 blockade inhibits glioblastoma cell proliferation by enhancing mitochondrial biogenesis.
Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor.
Title: Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor.

Submit: New GeneRIF Correction See all GeneRIFs (932)

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

Associated conditions

Description	Tests
Capillary infantile hemangioma MedGen: C1865871 OMIM: 602089 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Identification of a variant in KDR associated with serum VEGFR2 and pharmacodynamics of pazopanib. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 downregulates KDR expression in human mesenchymal stem cells	PubMed
Nef	nef	HIV-1 Nef upregulates VEGFR2 and its co-receptor neuropilin-1 and downregulates the expression of semaphorin 3a in podocytes	PubMed
Tat	tat	Inhibition of sigma receptor or VEGFR causes a significant decrease in HIV-1 Tat- and cocaine-induced H2O2 generation in human pulmonary arterial smooth muscle cells	PubMed
	tat	Downregulation of ZO-1 by treatment with HIV-1 Tat and cocaine is inhibited by VEGFR-2 or sigma receptor antagonists, suggesting that VEGFR-2 and sigma receptor are involved in the downregulation of ZO-1 by Tat and cocaine in pulmonary cells	PubMed
	tat	Microarray analysis indicates HIV-1 Tat-induced downregulation of kinase insert domain receptor (KDR; VEGFR2) in primary human brain microvascular endothelial cells	PubMed
	tat	HIV-1 Tat-induced upregulation of IL17 expression is dependent upon the VEGFR2 signaling pathway in human primary T cells	PubMed
	tat	Endothelial cell adherent to HIV-1 Tat induces upregulation of VEGFR2, integrin beta(3) subunit, pp60src and recruits VEGFR2, integrin beta(3) subunit, paxillin, focal adhesion kinase, and pp60src to ventral plasma membranes	PubMed
	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	Adhesion of endothelial cells to HIV-1 Tat triggers a signal transduction pathway, which leads to phosphorylation of VEGFR2 and pp60src and activation of ERK1/2	PubMed
	tat	The phosphorylation of vascular endothelial growth factor receptor type 2 (Flk-1/KDR) induces the ability of Tat to stimulate focal adhesion assembly and the migration of human brain micro vascular endothelial cells (HBMECs)	PubMed
	tat	Sulfated polymannuroguluronate, a novel anti-AIDS drug candidate, greatly arrests Tat-driven KDR phosphorylation and blocks the interaction between Tat and integrin beta1, thus inhibiting the phosphorylation of the kinases FAK, paxillin and MAPKs	PubMed
	tat	Kinase insert domain receptor (a type III receptor tyrosine kinase) 1 is upregulated in HIV-1 Tat and NC cotransfection of HEK 293T cells	PubMed
	tat	VEGFR2 is upregulated by HIV-1 Tat treatment in human epithelial cells	PubMed
	tat	HIV-1 Tat, through its basic region (amino acids 49-57), binds and activates VEGFR-2, an effect associated with Tat-mediated pathogenesis and induction of angiogenesis in AIDS-associated Kaposi's sarcoma	PubMed
	tat	The interaction of HIV-1 Tat with KDR/VEGFR2 is implicated in the activation of ERK1 and ERK2 signaling pathways	PubMed
	tat	The activation of AKT and the protection of Kaposi's sarcoma cells from apoptosis mediated by HIV-1 Tat involves the interaction of Tat with VEGFR2	PubMed
nucleocapsid	gag	KDR is upregulated in HIV-1 Tat and NC cotransfection of HEK 293T cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH70435 (e-PCR)
- UniSTS:1288

G20520 (e-PCR)
- UniSTS:62237

A005U41 (e-PCR)
- UniSTS:62238

SHGC-59221 (e-PCR)
- UniSTS:47905

SHGC-59525 (e-PCR)
- UniSTS:47937

SHGC-50925 (e-PCR)
- UniSTS:31855

KDR (e-PCR)
- UniSTS:479862

GDB:626090 (e-PCR)
- UniSTS:158389

GDB:626093 (e-PCR)
- UniSTS:158390

KDR (e-PCR)
- UniSTS:503486

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables GPI-linked ephrin receptor activity	IEA Inferred from Electronic Annotation more info
enables Hsp90 protein binding	TAS Traceable Author Statement more info	PubMed
enables boss receptor activity	IEA Inferred from Electronic Annotation more info
enables brain-derived neurotrophic factor receptor activity	IEA Inferred from Electronic Annotation more info
enables cadherin binding	IPI Inferred from Physical Interaction more info	PubMed
enables coreceptor activity	IEA Inferred from Electronic Annotation more info
enables epidermal growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables fibroblast growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables growth factor binding	IBA Inferred from Biological aspect of Ancestor more info
enables growth factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables hepatocyte growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXY142 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3Y41 kinase activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables insulin receptor activity	IEA Inferred from Electronic Annotation more info
enables insulin-like growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables integrin binding	IPI Inferred from Physical Interaction more info	PubMed
enables macrophage colony-stimulating factor receptor activity	IEA Inferred from Electronic Annotation more info
enables placental growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables platelet-derived growth factor alpha-receptor activity	IEA Inferred from Electronic Annotation more info
enables platelet-derived growth factor beta-receptor activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine kinase activity	EXP Inferred from Experiment more info	PubMed
enables protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine kinase collagen receptor activity	IEA Inferred from Electronic Annotation more info
enables stem cell factor receptor activity	IEA Inferred from Electronic Annotation more info
enables transmembrane receptor protein tyrosine kinase activity	TAS Traceable Author Statement more info	PubMed
enables transmembrane-ephrin receptor activity	IEA Inferred from Electronic Annotation more info
enables vascular endothelial growth factor binding	IPI Inferred from Physical Interaction 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

Process	Evidence Code	Pubs
involved_in Kit signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in angiogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in angiogenesis	TAS Traceable Author Statement more info	PubMed
involved_in blood vessel endothelial cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in brain-derived neurotrophic factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within branching involved in blood vessel morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in calcium ion homeostasis	IEA Inferred from Electronic Annotation more info
involved_in cell fate commitment	IEA Inferred from Electronic Annotation more info
involved_in cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell migration involved in sprouting angiogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to hydrogen sulfide	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to vascular endothelial growth factor stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in collagen-activated tyrosine kinase receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in embryonic hemopoiesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in endocardium development	IEA Inferred from Electronic Annotation more info
involved_in endothelial cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in endothelium development	ISS Inferred from Sequence or Structural Similarity more info
involved_in ephrin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in epidermal growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in epithelial cell maturation	IEA Inferred from Electronic Annotation more info
involved_in epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in fibroblast growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in hepatocyte growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in insulin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in insulin-like growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in lung alveolus development	IEA Inferred from Electronic Annotation more info
involved_in lymph vessel development	IEA Inferred from Electronic Annotation more info
involved_in macrophage colony-stimulating factor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in mesenchymal cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of endothelial cell apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in ovarian follicle development	IEA Inferred from Electronic Annotation more info
involved_in peptidyl-tyrosine autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in platelet-derived growth factor receptor-alpha signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in platelet-derived growth factor receptor-beta signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of BMP signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of angiogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of angiogenesis	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 blood vessel endothelial cell migration	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 migration involved in sprouting angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of endothelial cell chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of endothelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of endothelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of focal adhesion assembly	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of macroautophagy	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of mesenchymal cell proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of mitochondrial depolarization	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of mitochondrial fission	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA Inferred from Direct Assay 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 positive regulation of positive chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of stem cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of vasculogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in post-embryonic camera-type eye morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of bone development	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell shape	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of hematopoietic progenitor cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in semaphorin-plexin signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in stem cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in surfactant homeostasis	IEA Inferred from Electronic Annotation 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 signaling pathway	TAS Traceable Author Statement more info
involved_in vascular endothelial growth factor receptor-1 signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in vascular endothelial growth factor receptor-2 signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vascular endothelial growth factor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in vascular endothelial growth factor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vascular wound healing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vasculogenesis	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in anchoring junction	IEA Inferred from Electronic Annotation more info
located_in cell junction	ISS Inferred from Sequence or Structural Similarity more info
located_in early endosome	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in external side of plasma membrane	IEA Inferred from Electronic Annotation more info
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in membrane raft	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
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	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info
located_in sorting endosome	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: vascular endothelial growth factor receptor 2

Names: fetal liver kinase-1; kinase insert domain receptor (a type III receptor tyrosine kinase); protein-tyrosine kinase receptor Flk-1; soluble VEGFR2; tyrosine kinase growth factor receptor

NP_002244.1

EC 2.7.10.1

NCBI Reference Sequences (RefSeq)

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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

NG_012004.1 RefSeqGene

Range

5001..52115

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1198

mRNA and Protein(s)

NM_002253.4 → NP_002244.1 vascular endothelial growth factor receptor 2 precursor

See identical proteins and their annotated locations for NP_002244.1

Status: REVIEWED

Source sequence(s)

AC021220, AC111194

Consensus CDS

CCDS3497.1

UniProtKB/Swiss-Prot

A2RRS0, B5A925, C5IFA0, O60723, P35968, Q14178

UniProtKB/TrEMBL

Q59EB0

Related

ENSP00000263923.4, ENST00000263923.5

Conserved Domains (10) summary

cd05862
Location:239 → 326

Ig1_VEGFR; First immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R)

cd05864
Location:348 → 417

Ig2_VEGFR-2; Second immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2)

smart00408
Location:680 → 744

IGc2; Immunoglobulin C-2 Type

smart00409
Location:565 → 661

IG; Immunoglobulin

smart00410
Location:231 → 324

IG_like; Immunoglobulin like

pfam07679
Location:667 → 754

I-set; Immunoglobulin I-set domain

cd05103
Location:826 → 1167

PTKc_VEGFR2; Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2

pfam07714
Location:834 → 1160

Pkinase_Tyr; Protein tyrosine kinase

pfam13895
Location:551 → 661

Ig_2; Immunoglobulin domain

cl11960
Location:41 → 109

Ig; Immunoglobulin domain