Reviewed, UniProtKB/Swiss-Prot P35968 (VGFR2_HUMAN)

Names and origin

Protein names

Recommended name:
    Vascular endothelial growth factor receptor 2
      Short name=VEGFR-2
    EC=2.7.10.1
Alternative name(s):
    Kinase insert domain receptor
    Protein-tyrosine kinase receptor Flk-1
    CD_antigen=CD309

Gene names

Name:	KDR
Synonyms:	FLK1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1356 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Receptor for VEGF or VEGFC. Has a tyrosine-protein kinase activity. The VEGF-kinase ligand/receptor signaling system plays a key role in vascular development and regulation of vascular permeability. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with SHB upon VEGF activation. Interacts with HIV-1 Tat.
Subcellular location	Membrane; Single-pass type I membrane protein.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. Contains 7 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Angiogenesis Differentiation Host-virus interaction
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell migration Inferred from direct assay. Source: UniProtKB positive regulation of positive chemotaxis Inferred from direct assay. Source: UniProtKB protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro regulation of cell shape Inferred from direct assay. Source: UniProtKB
Cellular component	integral to plasma membrane Ref.3 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro growth factor binding Ref.5 Inferred from physical interaction. Source: UniProtKB vascular endothelial growth factor receptor activity Ref.5 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FLT4	P35916	1	EBI-1005487,EBI-1005467
NRP1	O14786	1	EBI-1005487,EBI-1187100

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Potential

Chain

20 – 1356

1337

Vascular endothelial growth factor receptor 2

PRO_0000016771

Regions

Topological domain

20 – 764

745

Extracellular Potential

Transmembrane

765 – 789

25

Potential

Topological domain

790 – 1356

567

Cytoplasmic Potential

Domain

46 – 110

65

Ig-like C2-type 1

Domain

141 – 207

67

Ig-like C2-type 2

Domain

224 – 320

97

Ig-like C2-type 3

Domain

328 – 414

87

Ig-like C2-type 4

Domain

421 – 548

128

Ig-like C2-type 5

Domain

551 – 660

110

Ig-like C2-type 6

Domain

667 – 753

87

Ig-like C2-type 7

Domain

834 – 1162

329

Protein kinase

Nucleotide binding

840 – 848

9

ATP By similarity

Sites

Active site

1028

1

Proton acceptor By similarity

Binding site

868

1

ATP By similarity

Site

1175

1

Interaction with SHB By similarity

Amino acid modifications

Modified residue

1054

1

Phosphotyrosine

Modified residue

1059

1

Phosphotyrosine; by autocatalysis

Glycosylation

46

1

N-linked (GlcNAc...) Potential

Glycosylation

66

1

N-linked (GlcNAc...) Potential

Glycosylation

96

1

N-linked (GlcNAc...) Potential

Glycosylation

143

1

N-linked (GlcNAc...) Potential

Glycosylation

158

1

N-linked (GlcNAc...) Potential

Glycosylation

245

1

N-linked (GlcNAc...) Potential

Glycosylation

318

1

N-linked (GlcNAc...) Potential

Glycosylation

374

1

N-linked (GlcNAc...) Potential

Glycosylation

395

1

N-linked (GlcNAc...) Potential

Glycosylation

511

1

N-linked (GlcNAc...) Potential

Glycosylation

523

1

N-linked (GlcNAc...) Potential

Glycosylation

580

1

N-linked (GlcNAc...) Potential

Glycosylation

613

1

N-linked (GlcNAc...) Potential

Glycosylation

619

1

N-linked (GlcNAc...) Potential

Glycosylation

631

1

N-linked (GlcNAc...) Potential

Glycosylation

675

1

N-linked (GlcNAc...) Potential

Glycosylation

704

1

N-linked (GlcNAc...) Potential

Glycosylation

721

1

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

2

1

Q → R in a lung adenocarcinoma sample; somatic mutation.

VAR_042053

Natural variant

136

1

V → M: dbSNP rs35636987.

VAR_042054

Natural variant

248

1

A → G in a renal clear cell carcinoma sample; somatic mutation.

VAR_042055

Natural variant

275

1

R → L in a colorectal cancer sample; somatic mutation.

VAR_036126

Natural variant

297

1

V → I: dbSNP rs2305948.

VAR_022071

Natural variant

462

1

L → V: dbSNP rs56286620.

VAR_042056

Natural variant

472

1

Q → H: dbSNP rs1870377.

VAR_020353

Natural variant

482

1

C → R: dbSNP rs34231037.

VAR_042057

Natural variant

539

1

G → R: dbSNP rs55716939.

VAR_042058

Natural variant

689

1

T → M: dbSNP rs34038364.

VAR_042059

Natural variant

814

1

D → N: dbSNP rs35603373.

VAR_042060

Natural variant

848

1

V → E: dbSNP rs1139776.

VAR_046679

Natural variant

873

1

G → R in a colorectal cancer sample; somatic mutation.

VAR_036127

Natural variant

952

1

V → I: dbSNP rs13129474.

VAR_046680

Natural variant

1065

1

A → T: dbSNP rs56302315.

VAR_042061

Experimental info

Sequence conflict

2

1

Q → E in AAC16450. Ref.2

Sequence conflict

772

1

A → T in AAA59459 and CAA43837. Ref.3

Sequence conflict

787

1

R → G in AAA59459 and CAA43837. Ref.3

Sequence conflict

835

1

K → N in AAA59459 and CAA43837. Ref.3

Sequence conflict

1347

1

S → T in AAA59459 and CAA43837. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1356

Helix Strand Turn

Details...

Helix

824 – 827

4

Helix

831 – 833

3

Beta strand

834 – 841

8

Beta strand

844 – 855

12

Beta strand

858 – 860

3

Beta strand

862 – 870

9

Helix

876 – 892

17

Beta strand

901 – 905

5

Beta strand

907 – 910

4

Beta strand

913 – 917

5

Helix

924 – 929

6

Turn

930 – 933

4

Helix

1002 – 1021

20

Helix

1031 – 1033

3

Beta strand

1034 – 1036

3

Beta strand

1042 – 1044

3

Helix

1068 – 1071

4

Helix

1074 – 1077

4

Helix

1084 – 1099

16

Helix

1115 – 1120

6

Helix

1133 – 1142

10

Helix

1147 – 1149

3

Helix

1153 – 1167

15

Sequences

	Sequence		Length	Mass (Da)
	P35968-1 [UniParc]. Last modified December 1, 2000. Version 2. Checksum: 59E7C44B05CFEBB3	FASTA	1,356	151,527
	10 20 30 40 50 60 MQSKVLLAVA LWLCVETRAA SVGLPSVSLD LPRLSIQKDI LTIKANTTLQ ITCRGQRDLD 70 80 90 100 110 120 WLWPNNQSGS EQRVEVTECS DGLFCKTLTI PKVIGNDTGA YKCFYRETDL ASVIYVYVQD 130 140 150 160 170 180 YRSPFIASVS DQHGVVYITE NKNKTVVIPC LGSISNLNVS LCARYPEKRF VPDGNRISWD 190 200 210 220 230 240 SKKGFTIPSY MISYAGMVFC EAKINDESYQ SIMYIVVVVG YRIYDVVLSP SHGIELSVGE 250 260 270 280 290 300 KLVLNCTART ELNVGIDFNW EYPSSKHQHK KLVNRDLKTQ SGSEMKKFLS TLTIDGVTRS 310 320 330 340 350 360 DQGLYTCAAS SGLMTKKNST FVRVHEKPFV AFGSGMESLV EATVGERVRI PAKYLGYPPP 370 380 390 400 410 420 EIKWYKNGIP LESNHTIKAG HVLTIMEVSE RDTGNYTVIL TNPISKEKQS HVVSLVVYVP 430 440 450 460 470 480 PQIGEKSLIS PVDSYQYGTT QTLTCTVYAI PPPHHIHWYW QLEEECANEP SQAVSVTNPY 490 500 510 520 530 54