3B8Q | pdb_00003b8q

Crystal structure of the VEGFR2 kinase domain in complex with a naphthamide inhibitor

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Protein Modification Annotation

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d3b8qb_	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	Protein kinases, catalytic subunit	Vascular endothelial growth factor receptor 2 (kdr)	human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d3b8qa1	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	Protein kinases, catalytic subunit	Vascular endothelial growth factor receptor 2 (kdr)	human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d3b8qa2	Artifacts	Tags	Tags	Tags	C-terminal Tags	human (Homo sapiens ) [TaxId: 9606 ], human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	Protein kinase-like (PK-like)	8034993	3000066	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
B	Pkinase_Tyr	e3b8qB1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: Protein kinase	F: Pkinase_Tyr	ECOD (1.6)
A	Pkinase_Tyr	e3b8qA2	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: Protein kinase	F: Pkinase_Tyr	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	3.30.200.20	Alpha Beta	2-Layer Sandwich	Phosphorylase Kinase	domain 1	CATH (4.3.0)
B	1.10.510.10	Mainly Alpha	Orthogonal Bundle	Transferase(Phosphotransferase)	domain 1	CATH (4.3.0)
A	3.30.200.20	Alpha Beta	2-Layer Sandwich	Phosphorylase Kinase	domain 1	CATH (4.3.0)
A	1.10.510.10	Mainly Alpha	Orthogonal Bundle	Transferase(Phosphotransferase)	domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF07714	Protein tyrosine and serine/threonine kinase (PK_Tyr_Ser-Thr)	Protein tyrosine and serine/threonine kinase	Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphospha ...	Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity [1]; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Vascular endothelial growth factor receptor 2	protein tyrosine kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding protein tyrosine kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding cell adhesion molecule binding cadherin binding protein binding growth factor binding molecular transducer activity signaling receptor activity vascular endothelial growth factor receptor activity transmembrane receptor protein tyrosine kinase activity transmembrane receptor protein kinase activity transmembrane signaling receptor activity coreceptor activity identical protein binding Hsp90 protein binding heat shock protein binding protein-containing complex binding integrin binding signaling receptor binding vascular endothelial growth factor binding	multicellular organismal process multicellular organismal-level homeostasis chemical homeostasis homeostatic process multicellular organismal-level chemical homeostasis surfactant homeostasis regulation of cellular process regulation of developmental process cellular developmental process positive regulation of biological process regulation of vasculogenesis regulation of cell differentiation vasculogenesis positive regulation of developmental process multicellular organismal process multicellular organismal-level homeostasis chemical homeostasis homeostatic process multicellular organismal-level chemical homeostasis surfactant homeostasis regulation of cellular process regulation of developmental process cellular developmental process positive regulation of biological process regulation of vasculogenesis regulation of cell differentiation vasculogenesis positive regulation of developmental process multicellular organism development tube morphogenesis positive regulation of cell differentiation cell differentiation anatomical structure development positive regulation of cellular process blood vessel development system development developmental process regulation of biological process blood vessel morphogenesis tube development biological regulation vasculature development circulatory system development anatomical structure morphogenesis cellular process positive regulation of vasculogenesis cellular response to stimulus cellular response to growth factor stimulus cell surface receptor signaling pathway response to stimulus signaling response to endogenous stimulus cell surface receptor protein tyrosine kinase signaling pathway cell communication vascular endothelial growth factor signaling pathway cellular response to endogenous stimulus cellular response to vascular endothelial growth factor stimulus signal transduction response to growth factor enzyme-linked receptor protein signaling pathway regulation of multicellular organismal development animal organ development regulation of bone development skeletal system development regulation of multicellular organismal process bone development regulation of cellular component organization positive regulation of cellular component organization cell-substrate junction assembly positive regulation of cell-substrate junction organization cellular component organization cellular component biogenesis cell adhesion cellular component assembly cell junction assembly positive regulation of cell-substrate adhesion regulation of cell-substrate junction organization cellular component organization or biogenesis focal adhesion assembly positive regulation of focal adhesion assembly positive regulation of cellular component biogenesis regulation of cell-substrate adhesion positive regulation of cell adhesion regulation of cell adhesion cell-substrate adhesion positive regulation of cell-matrix adhesion regulation of cellular component biogenesis regulation of cell junction assembly positive regulation of cell junction assembly cell junction organization cell-matrix adhesion regulation of cell-matrix adhesion cell-substrate junction organization regulation of focal adhesion assembly regulation of cell-substrate junction assembly hemopoiesis cell development embryo development embryonic hemopoiesis embryonic organ development branching morphogenesis of an epithelial tube angiogenesis epithelial tube morphogenesis epithelium development morphogenesis of an epithelium tissue development branching involved in blood vessel morphogenesis tissue morphogenesis morphogenesis of a branching structure anatomical structure formation involved in morphogenesis morphogenesis of a branching epithelium inorganic ion homeostasis monoatomic ion homeostasis calcium ion homeostasis monoatomic cation homeostasis cell fate commitment positive regulation of cell communication positive regulation of signal transduction regulation of signal transduction intracellular signal transduction positive regulation of response to stimulus positive regulation of ERK1 and ERK2 cascade regulation of intracellular signal transduction intracellular signaling cassette regulation of signaling positive regulation of MAPK cascade positive regulation of intracellular signal transduction regulation of MAPK cascade regulation of response to stimulus MAPK cascade regulation of cell communication ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade positive regulation of signaling positive regulation of mesenchymal cell proliferation cell population proliferation positive regulation of cell population proliferation regulation of mesenchymal cell proliferation regulation of cell population proliferation mesenchymal cell proliferation endothelial cell differentiation endothelium development epithelial cell differentiation cell surface receptor protein serine/threonine kinase signaling pathway regulation of transmembrane receptor protein serine/threonine kinase signaling pathway positive regulation of BMP signaling pathway BMP signaling pathway cellular response to BMP stimulus regulation of BMP signaling pathway regulation of cellular response to growth factor stimulus positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway response to BMP transforming growth factor beta receptor superfamily signaling pathway heart development endocardium development positive regulation of locomotion regulation of cell motility regulation of blood vessel endothelial cell migration endothelial cell migration positive regulation of cell migration positive regulation of blood vessel endothelial cell migration regulation of locomotion positive regulation of endothelial cell migration positive regulation of cell motility regulation of cell migration blood vessel endothelial cell migration regulation of endothelial cell migration cell migration cell motility locomotion epithelial cell proliferation positive regulation of autophagy catabolic process macroautophagy autophagy regulation of catabolic process regulation of autophagy positive regulation of catabolic process positive regulation of metabolic process regulation of macroautophagy metabolic process positive regulation of macroautophagy process utilizing autophagic mechanism regulation of metabolic process positive regulation of organelle organization regulation of anatomical structure morphogenesis mitochondrion organization organelle fission mitochondrial fission regulation of organelle organization organelle organization regulation of mitochondrial fission regulation of mitochondrion organization positive regulation of mitochondrial fission wound healing angiogenesis involved in wound healing vascular wound healing response to stress response to wounding negative regulation of endothelial cell apoptotic process negative regulation of programmed cell death regulation of apoptotic process negative regulation of biological process regulation of programmed cell death cell death negative regulation of apoptotic process negative regulation of cellular process endothelial cell apoptotic process apoptotic process programmed cell death regulation of endothelial cell apoptotic process regulation of biosynthetic process negative regulation of metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of gene expression negative regulation of gene expression biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process macromolecule metabolic process negative regulation of macromolecule metabolic process endothelial cell proliferation positive regulation of epithelial cell proliferation regulation of endothelial cell proliferation positive regulation of endothelial cell proliferation regulation of epithelial cell proliferation vascular endothelial growth factor receptor signaling pathway lymph vessel development respiratory tube development lung development respiratory system development lung alveolus development camera-type eye morphogenesis sensory organ development eye development post-embryonic camera-type eye development visual system development post-embryonic camera-type eye morphogenesis eye morphogenesis post-embryonic eye morphogenesis sensory organ morphogenesis camera-type eye development animal organ morphogenesis post-embryonic development sensory system development cellular response to chemical stimulus response to chemical cellular response to hydrogen sulfide response to hydrogen sulfide regulation of mitochondrial depolarization positive regulation of membrane depolarization positive regulation of mitochondrial depolarization mitochondrial depolarization regulation of membrane depolarization regulation of mitochondrial membrane potential membrane depolarization regulation of biological quality regulation of membrane potential cell migration involved in sprouting angiogenesis sprouting angiogenesis regulation of stem cell proliferation positive regulation of stem cell proliferation stem cell proliferation protein phosphorylation protein autophosphorylation phosphorylation primary metabolic process macromolecule modification phosphate-containing compound metabolic process protein metabolic process protein modification process phosphorus metabolic process gonad development reproductive system development reproductive process female gonad development sex differentiation female sex differentiation development of primary female sexual characteristics developmental process involved in reproduction development of primary sexual characteristics reproductive structure development ovarian follicle development vascular endothelial growth factor receptor-2 signaling pathway developmental maturation epithelial cell development anatomical structure maturation epithelial cell maturation cell maturation nitric oxide mediated signal transduction nitric oxide-cGMP-mediated signaling regulation of nitric oxide mediated signal transduction regulation of nitric oxide-cGMP mediated signal transduction positive regulation of nitric oxide mediated signal transduction positive regulation of nitric oxide-cGMP mediated signal transduction positive regulation of cell migration involved in sprouting angiogenesis regulation of cell migration involved in sprouting angiogenesis blood vessel endothelial cell differentiation regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction phosphatidylinositol 3-kinase/protein kinase B signal transduction neuron apoptotic process negative regulation of neuron apoptotic process regulation of neuron apoptotic process regulation of cell shape cell morphogenesis regulation of cell morphogenesis peptidyl-tyrosine modification peptidyl-amino acid modification peptidyl-tyrosine phosphorylation positive chemotaxis chemotaxis regulation of response to external stimulus positive regulation of positive chemotaxis response to external stimulus regulation of chemotaxis positive regulation of chemotaxis regulation of positive chemotaxis positive regulation of response to external stimulus taxis positive regulation of endothelial cell chemotaxis endothelial cell chemotaxis cell chemotaxis regulation of endothelial cell chemotaxis semaphorin-plexin signaling pathway regulation of vasculature development positive regulation of angiogenesis positive regulation of vasculature development regulation of angiogenesis positive regulation of multicellular organismal process positive regulation of phosphorylation regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of phosphate metabolic process regulation of primary metabolic process positive regulation of protein modification process positive regulation of macromolecule metabolic process positive regulation of protein phosphorylation positive regulation of phosphorus metabolic process regulation of protein metabolic process regulation of phosphorus metabolic process regulation of phosphorylation regulation of hematopoietic progenitor cell differentiation hematopoietic progenitor cell differentiation	protein-containing complex receptor complex membrane-bounded organelle intracellular anatomical structure sorting endosome endosome intracellular vesicle intracellular membrane-bounded organelle endomembrane system intracellular organelle cellular anatomical structure cytoplasmic vesicle organelle cytoplasm protein-containing complex receptor complex membrane-bounded organelle intracellular anatomical structure sorting endosome endosome intracellular vesicle intracellular membrane-bounded organelle endomembrane system intracellular organelle cellular anatomical structure cytoplasmic vesicle organelle cytoplasm vesicle cell periphery plasma membrane membrane membrane microdomain membrane raft extracellular region cell surface external side of plasma membrane side of membrane Golgi apparatus cell junction anchoring junction early endosome nucleus endoplasmic reticulum

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR001824	Tyrosine-protein kinase, receptor class III, conserved site	Conserved Site
A, B	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
A, B	IPR020635	Tyrosine-protein kinase, catalytic domain	Domain
A, B	IPR000719	Protein kinase domain	Domain
A, B	IPR003599	Immunoglobulin domain subtype	Domain
A, B	IPR013151	Immunoglobulin-like beta-sandwich domain	Domain
A, B	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
A, B	IPR007110	Immunoglobulin-like domain	Domain
A, B	IPR017441	Protein kinase, ATP binding site	Binding Site
A, B	IPR001245	Serine-threonine/tyrosine-protein kinase, catalytic domain	Domain
A, B	IPR041348	VEGFR-2, transmembrane domain	Domain
A, B	IPR008266	Tyrosine-protein kinase, active site	Active Site
A, B	IPR009136	Vascular endothelial growth factor receptor 2 (VEGFR2)	Family
A, B	IPR055229	VEGFR1-3, fifth immunoglobulin-like domain	Domain
A, B	IPR003598	Immunoglobulin subtype 2	Domain
A, B	IPR013098	Immunoglobulin I-set	Domain
A, B	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A, B	IPR050122	Receptor Tyrosine Kinase	Family
A, B	IPR055238	VEGFR1-3, N-terminal Ig-like domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P35968	angiosarcoma capillary infantile hemangioma non-small cell lung carcinoma tubular adenocarcinoma adenocarcinoma Venous Thrombosis schizophrenia temporal lobe epilepsy esophageal cancer uremia cancer granular cell carcinoma multiple epiphyseal dysplasia breast carcinoma osteochondrodysplasia angiosarcoma capillary infantile hemangioma non-small cell lung carcinoma tubular adenocarcinoma adenocarcinoma Venous Thrombosis schizophrenia temporal lobe epilepsy esophageal cancer uremia cancer granular cell carcinoma multiple epiphyseal dysplasia breast carcinoma osteochondrodysplasia colorectal cancer lung adenocarcinoma major depressive disorder diabetic kidney disease spondyloepiphyseal dysplasia tarda, X-linked endometrial carcinoma malignant pancreatic neoplasm thyroid gland follicular carcinoma facioscapulohumeral muscular dystrophy medullary thyroid gland carcinoma gastrointestinal stromal tumor hepatocellular carcinoma myocardial ischemia hypertensive disorder breast disease ovarian cancer intracerebral hemorrhage pancreatic neoplasm colorectal carcinoma kidney disease renal cell carcinoma coronary artery disease lung cancer cystic fibrosis malignant ependymoma sinusitis endometriosis thyroid gland papillary carcinoma gastric adenocarcinoma Melnick-Needles syndrome ulcerative colitis glioblastoma neoplasm of esophagus breast cancer idiopathic pulmonary fibrosis interstitial lung disease pancreatic intraductal papillary-mucinous carcinoma invasive ductal breast carcinoma cribriform carcinoma lung disease Schwartz-Jampel syndrome malignant mesothelioma spondyloepiphyseal dysplasia thymic carcinoma transitional cell carcinoma gastric cancer interstitial cystitis intestinal disease pancreatic intraductal papillary-mucinous neoplasm ischemia reperfusion injury cribriform carcinoma of breast

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
A, B	PTR	Parent Component: TYR RESID: AA0039 PSI-MOD : O4'-phospho-L-tyrosine MOD:00048

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.