Gene/Proteome Database (LMPD)

LMPD ID
LMP012531
Gene ID
25589
Species
Rattus norvegicus (Rat)
Gene Name
kinase insert domain receptor
Gene Symbol
Kdr
Synonyms
Vegfr-2;
Alternate Names
vascular endothelial growth factor receptor 2; FLK-1; fetal liver kinase 1; kinase insert domain protein receptor; protein-tyrosine kinase receptor flk-1; FLK1 kinase insert domain receptor (VEGF receptor 2); FLK1 kinase insert domain receptor (a type III receptor tyrosine kinase) (VEGF receptor 2);
Chromosome
14
Map Location
chromosome:14
EC Number
2.7.10.1
Summary
receptor for vascular endothelial growth factor (VEGF) [RGD, Feb 2006]
Orthologs
View orthologs and multiple alignments for Kdr

Proteins

vascular endothelial growth factor receptor 2 precursor
Refseq ID NP_037194
Protein GI 6981128
UniProt ID O08775
mRNA ID NM_013062
Length 1343
MESRALLAVALWFCVETRAASVGLPGDSLHPPKLSTQKDILTILANTTLQITCRGQRDLDWLWPNTPRDSEERVLVTECGDSIFCKTLTVPRVVGNDTGAYKCFYRDTDVSSIVYVYVQDHRSPFIASVSDEHGIVYITENKNKTVVIPCRGSISNLNVSLCARYPEKRFVPDGNRISWDSEKGFTIPSYMISYAGMVFCEAKINDETYQSIMYIVLVVGYRIYDVVLSPPHEIELSAGEKLVLNCTARTELNVGLDFSWQFPSSKHQHKKIVNRDVKSLPGTVAKMFLSTLTIDSVTKSDQGEYTCTAYSGLMTKKNKTFVRVHTKPFIAFGSGMKSLVEATVGSQVRIPVKYLSYPAPDIKWYRNGRPIESNYTMIVGDELTIMEVSERDAGNYTVILTNPISMEKQSHMVSLVVNVPPQIGEKALISPMDSYQYGTMQTLTCTVYANPPLHHIQWYWQLEEACSYRPSQTNPYTCKEWRHVKDFQGGNKIEVTKNQYALIEGKNKTVSTLVIQAAYVSALYKCEAINKAGRGERVISFHVIRGPEITVQPATQPTERESMSLLCTADRNTFENLTWYKLGSQATSVHMGESLTPVCKNLDALWKLNGTVFSNSTNDILIVAFQNASLQDQGNYVCSAQDKKTKKRHCLVKQLVILERMAPMITGNLENQTTTIGETIEVVCPTSGNPTPLITWFKDNETLVEDSGIVLKDGNRNLTIRRVRKEDGGLYTCQACNVLGCARAETLFIIEGVQEKTNLEVIILVGTAVIAMFFWLLLVILVRTVKRANEGELKTGYLSIVMDPDELPLDERCERLPYDASKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGACTKPGGPLMVIVEFCKFGNLSTYLRGKRNEFVPYKSKGARFRSGKDYVGELSVDLKRRLDSITSSQSSASSGFVEEKSLSDVEEEEASEELYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDPRLPLKWMAPETIFDRIYTIQSGVWSFGVLLWEIFSLGASPYPGVKIDEKFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPAFSELVEHLGNLLQANAQQDGKDYIVLPMSETLSMEEDSGLSLPTSPVSCMEEEEVCDPKFHYDNTAGISHYLQNSKRKSRPVSVKTFEDIPLEEPEVKVIPDDSQTDSGMVLASEELKTLEDRNKLSPSFGGMMPSKSRESVASEGSNQTSGYQSGYHSDDTDTTVYSSDEAGLLKLVDVAGHVDSGTTLRSSPV
sig_peptide: 1..19 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2167 peptide sequence: MESRALLAVALWFCVETRA mat_peptide: 20..1343 product: Vascular endothelial growth factor receptor 2 experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (O08775.1) calculated_mol_wt: 148246 peptide sequence: ASVGLPGDSLHPPKLSTQKDILTILANTTLQITCRGQRDLDWLWPNTPRDSEERVLVTECGDSIFCKTLTVPRVVGNDTGAYKCFYRDTDVSSIVYVYVQDHRSPFIASVSDEHGIVYITENKNKTVVIPCRGSISNLNVSLCARYPEKRFVPDGNRISWDSEKGFTIPSYMISYAGMVFCEAKINDETYQSIMYIVLVVGYRIYDVVLSPPHEIELSAGEKLVLNCTARTELNVGLDFSWQFPSSKHQHKKIVNRDVKSLPGTVAKMFLSTLTIDSVTKSDQGEYTCTAYSGLMTKKNKTFVRVHTKPFIAFGSGMKSLVEATVGSQVRIPVKYLSYPAPDIKWYRNGRPIESNYTMIVGDELTIMEVSERDAGNYTVILTNPISMEKQSHMVSLVVNVPPQIGEKALISPMDSYQYGTMQTLTCTVYANPPLHHIQWYWQLEEACSYRPSQTNPYTCKEWRHVKDFQGGNKIEVTKNQYALIEGKNKTVSTLVIQAAYVSALYKCEAINKAGRGERVISFHVIRGPEITVQPATQPTERESMSLLCTADRNTFENLTWYKLGSQATSVHMGESLTPVCKNLDALWKLNGTVFSNSTNDILIVAFQNASLQDQGNYVCSAQDKKTKKRHCLVKQLVILERMAPMITGNLENQTTTIGETIEVVCPTSGNPTPLITWFKDNETLVEDSGIVLKDGNRNLTIRRVRKEDGGLYTCQACNVLGCARAETLFIIEGVQEKTNLEVIILVGTAVIAMFFWLLLVILVRTVKRANEGELKTGYLSIVMDPDELPLDERCERLPYDASKWEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKTATCKTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVNLLGACTKPGGPLMVIVEFCKFGNLSTYLRGKRNEFVPYKSKGARFRSGKDYVGELSVDLKRRLDSITSSQSSASSGFVEEKSLSDVEEEEASEELYKDFLTLEHLICYSFQVAKGMEFLASRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDPRLPLKWMAPETIFDRIYTIQSGVWSFGVLLWEIFSLGASPYPGVKIDEKFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHEDPNQRPAFSELVEHLGNLLQANAQQDGKDYIVLPMSETLSMEEDSGLSLPTSPVSCMEEEEVCDPKFHYDNTAGISHYLQNSKRKSRPVSVKTFEDIPLEEPEVKVIPDDSQTDSGMVLASEELKTLEDRNKLSPSFGGMMPSKSRESVASEGSNQTSGYQSGYHSDDTDTTVYSSDEAGLLKLVDVAGHVDSGTTLRSSPV

Gene Information

Entrez Gene ID
25589
Gene Name
kinase insert domain receptor
Gene Symbol
Kdr
Species
Rattus norvegicus

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0030054 ISS:UniProtKB C cell junction
GO:0005737 IDA:RGD C cytoplasm
GO:0031410 IEA:UniProtKB-KW C cytoplasmic vesicle
GO:0005768 IEA:UniProtKB-KW C endosome
GO:0005887 ISS:UniProtKB C integral component of plasma membrane
GO:0043005 IDA:RGD C neuron projection
GO:0043025 IDA:RGD C neuronal cell body
GO:0005634 IEA:UniProtKB-KW C nucleus
GO:0005886 IDA:RGD C plasma membrane
GO:0005524 IEA:UniProtKB-KW F ATP binding
GO:0019838 IMP:RGD F growth factor binding
GO:0005021 IMP:RGD F vascular endothelial growth factor-activated receptor activity
GO:0007568 IEP:RGD P aging
GO:0001525 IEA:UniProtKB-KW P angiogenesis
GO:0035584 ISS:UniProtKB P calcium-mediated signaling using intracellular calcium source
GO:0035924 ISS:UniProtKB P cellular response to vascular endothelial growth factor stimulus
GO:0035162 ISS:UniProtKB P embryonic hemopoiesis
GO:0003416 IMP:RGD P endochondral bone growth
GO:0003158 ISS:UniProtKB P endothelium development
GO:0030212 IEP:RGD P hyaluronan metabolic process
GO:0008584 IDA:RGD P male gonad development
GO:0043066 ISS:UniProtKB P negative regulation of apoptotic process
GO:2000352 ISS:UniProtKB P negative regulation of endothelial cell apoptotic process
GO:0043524 IMP:RGD P negative regulation of neuron apoptotic process
GO:0048812 IMP:RGD P neuron projection morphogenesis
GO:0018108 ISS:UniProtKB P peptidyl-tyrosine phosphorylation
GO:0070374 ISS:UniProtKB P positive regulation of ERK1 and ERK2 cascade
GO:0043410 ISS:UniProtKB P positive regulation of MAPK cascade
GO:0032008 IMP:RGD P positive regulation of TOR signaling
GO:0045766 IDA:RGD P positive regulation of angiogenesis
GO:0050850 IMP:RGD P positive regulation of calcium-mediated signaling
GO:0030335 IMP:RGD P positive regulation of cell migration
GO:0008284 IMP:RGD P positive regulation of cell proliferation
GO:0007204 IMP:RGD P positive regulation of cytosolic calcium ion concentration
GO:0001938 ISS:UniProtKB P positive regulation of endothelial cell proliferation
GO:0048170 IMP:RGD P positive regulation of long-term neuronal synaptic plasticity
GO:0050769 IEP:RGD P positive regulation of neurogenesis
GO:0051770 ISS:UniProtKB P positive regulation of nitric-oxide synthase biosynthetic process
GO:0014068 IMP:RGD P positive regulation of phosphatidylinositol 3-kinase signaling
GO:0001934 ISS:UniProtKB P positive regulation of protein phosphorylation
GO:2001214 ISS:UniProtKB P positive regulation of vasculogenesis
GO:0045909 IGI:RGD P positive regulation of vasodilation
GO:0046777 IDA:RGD P protein autophosphorylation
GO:0042493 IMP:RGD P response to drug
GO:0001666 IMP:RGD P response to hypoxia
GO:0070482 IEP:RGD P response to oxygen levels
GO:0048010 IMP:RGD P vascular endothelial growth factor receptor signaling pathway
GO:0038084 IMP:GOC P vascular endothelial growth factor signaling pathway
GO:0001570 ISS:UniProtKB P vasculogenesis

KEGG Pathway Links

KEGG Pathway ID Description
ko04060 Cytokine-cytokine receptor interaction
rno04060 Cytokine-cytokine receptor interaction
ko04144 Endocytosis
rno04144 Endocytosis
ko04510 Focal adhesion
rno04510 Focal adhesion
ko04151 PI3K-Akt signaling pathway
rno04151 PI3K-Akt signaling pathway
ko05205 Proteoglycans in cancer
rno05205 Proteoglycans in cancer
ko04015 Rap1 signaling pathway
rno04015 Rap1 signaling pathway
rno04014 Ras signaling pathway
ko04370 VEGF signaling pathway
rno04370 VEGF signaling pathway

Domain Information

InterPro Annotations

Accession Description
IPR013098 Immunoglobulin I-set
IPR003599 Immunoglobulin subtype
IPR003598 Immunoglobulin subtype 2
IPR007110 Immunoglobulin-like domain
IPR013783 Immunoglobulin-like fold
IPR000719 Protein kinase domain
IPR017441 Protein kinase, ATP binding site
IPR011009 Protein kinase-like domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR008266 Tyrosine-protein kinase, active site
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR001824 Tyrosine-protein kinase, receptor class III, conserved site
IPR009136 VEGFR2_rcpt

UniProt Annotations

Entry Information

Gene Name
kinase insert domain receptor
Protein Entry
VGFR2_RAT
UniProt ID
O08775
Species
Rat

Comments

Comment Type Description
Catalytic Activity ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE- ProRule:PRU10028}.
Developmental Stage Increases during pregnancy (1.6-fold at 4 days) and lactation (3.8-fold at 7 days). Decreases in the early phases of involution (45%, 50% and 34% on days 1, 2, and 3 respectively)
Domain The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding
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. May be regulated by hydrogen sulfide (H(2)S) levels via a sensitive intracellular disulfide bond (By similarity)
Function 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 may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. 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 (By similarity)
Ptm Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-947 is important for interaction with SH2D2A/TSAD and VEGFA-mediated reorganization of the actin cytoskeleton. Phosphorylation at Tyr-1171 is important for interaction with PLCG1 and SHB. Phosphorylation at Tyr-1210 is important for interaction with NCK1 and FYN. Dephosphorylated by PTPRB. Dephosphorylated by PTPRJ at Tyr-797, Tyr-947, Tyr-992, Tyr-1050, Tyr-1055, Tyr-1171 and Tyr-1210 (By similarity)
Ptm N-glycosylated
Ptm The inhibitory disulfide bond between Cys-1020 and Cys-1041 may serve as a specific molecular switch for H(2)S-induced modification that regulates VEGFR2 function
Ptm Ubiquitinated. Tyrosine phosphorylation of the receptor promotes its poly-ubiquitination, leading to its degradation via the proteasome or lysosomal proteases (By similarity)
Similarity Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily
Similarity Contains 1 protein kinase domain
Similarity Contains 7 Ig-like C2-type (immunoglobulin-like) domains
Subcellular Location Cell membrane ; Single-pass type I membrane protein {ECO:0000250}. Cytoplasm . Nucleus {ECO:0000250}. Cytoplasmic vesicle . Early endosome {ECO:0000250}. Cell junction . Note=Detected on caveolae-enriched lipid rafts at the cell surface. Is recycled from the plasma membrane to endosomes and back again. Phosphorylation triggered by VEGFA binding promotes internalization and subsequent degradation. VEGFA binding triggers internalization and translocation to the nucleus. Localized with RAP1A at cell-cell junctions (By similarity)
Subunit Homodimer in the presence of bound dimeric VEGFA, VEGFC or VEGFD ligands; monomeric in the absence of bound ligands. Can also form heterodimers with FLT1/VEGFR1 and FLT4/VEGFR2. Interacts (tyrosine phosphorylated) with LFYN, NCK1, PLCG1. Interacts (tyrosine-phosphorylated active form preferentially) with DAB2IP (via C2 domain and active form preferentially); the interaction occurs at the late phase of VEGFA response and inhibits KDR/VEGFR2 activity. Interacts with SHBSH2D2A/TSAD, GRB2, MYOF, CBL and PDCD6 (By similarity)
Tissue Specificity Expressed in the post-pubertal mammary glands

Identical and Related Proteins

Unique RefSeq proteins for LMP012531 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
6981128 RefSeq NP_037194 1343 vascular endothelial growth factor receptor 2 precursor

Identical Sequences to LMP012531 proteins

Reference Database Accession Length Protein Name
GI:6981128 GenBank AAB97508.1 1343 VEGF receptor-2/FLK-1 [Rattus norvegicus]
GI:6981128 GenBank ACK07627.1 1343 Sequence 64 from patent US 7432341
GI:6981128 SwissProt O08775.1 1343 RecName: Full=Vascular endothelial growth factor receptor 2; Short=VEGFR-2; AltName: Full=Fetal liver kinase 1; Short=FLK-1; AltName: Full=Protein-tyrosine kinase receptor flk-1; AltName: CD_antigen=CD309; Flags: Precursor [Rattus norvegicus]

Related Sequences to LMP012531 proteins

Reference Database Accession Length Protein Name
GI:6981128 GenBank AAB97508.1 1343 VEGF receptor-2/FLK-1 [Rattus norvegicus]
GI:6981128 GenBank ACK07627.1 1343 Sequence 64 from patent US 7432341
GI:6981128 SwissProt O08775.1 1343 RecName: Full=Vascular endothelial growth factor receptor 2; Short=VEGFR-2; AltName: Full=Fetal liver kinase 1; Short=FLK-1; AltName: Full=Protein-tyrosine kinase receptor flk-1; AltName: CD_antigen=CD309; Flags: Precursor [Rattus norvegicus]