3S37

Structural basis for the function of two anti-VEGF receptor antibodies

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
IMGT Antibody Annotation
SAbDab Antibody Annotation
Thera-SAbDab Antibody Annotation
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A [auth L]	d3s37l2	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	C1 set domains (antibody constant domain-like)	automated matches	mouse (Mus musculus ) [TaxId: 10090 ], human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A [auth L]	d3s37l1	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	mouse (Mus musculus ) [TaxId: 10090 ], human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B [auth H]	d3s37h_	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	V set domains (antibody variable domain-like)	automated matches	mouse (Mus musculus ) [TaxId: 10090 ], human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A [auth L]	C1-set_4	e3s37L2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_4	ECOD (1.6)
A [auth L]	V-set	e3s37L1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set	ECOD (1.6)
B [auth H]	C1-set_1	e3s37H2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_1	ECOD (1.6)
B [auth H]	V-set_12	e3s37H1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_12	ECOD (1.6)
C [auth X]	C1-set_3	e3s37X1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_3	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A [auth L]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
B [auth H]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
C [auth X]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)

IMGT Antibody Annotation IMGT Database Homepage

Chain	Protein Name	Description	Organism Name	Gene Allele Name(s)	Domain Name(s)	Receptor Type	Receptor Description	Provenance Source
A [auth L]	1121B, IMC_1121B Fab, ramucirumab, anti-KDR (VEGFR2, FLK1, CD309)	L-KAPPA	Homo sapiens (human)	IGKV1-1201, IGKV1D-1201, IGKV1-1202, IGKV1D-1202, IGKJ401, IGKJ402, IGKC*01	V-DOMAIN V-KAPPA, C-DOMAIN C-KAPPA	IG	FAB-GAMMA-1_KAPPA	IMGT (202444-0)
B [auth H]	1121B, IMC_1121B Fab, ramucirumab, anti-KDR (VEGFR2, FLK1, CD309)	VH-CH1	Homo sapiens (human)	IGHV3-2101, IGHV3-2102, IGHV3-2104, IGHV3-2103, IGHJ302, IGHG101, IGHG102, IGHG103	V-DOMAIN VH, C-DOMAIN CH1	IG	FAB-GAMMA-1_KAPPA	IMGT (202444-0)
C [auth X]	KDR, EGFR2, FLK1, CD309 domain 3	1C-LIKE	Homo sapiens (human)	KDR*01	C-LIKE-DOMAIN KDR(Pr225-325_d3,326-327)	RPI	KDR(Pr225-325_d3,326-327)	IMGT (202444-0)

SAbDab Antibody Annotation SAbDab Database Homepage

Chain	Chain Class	Chain Subclass	Chain Type	Antigen Name(s)	Provenance Source
A [auth L]	Light Chain	IGKV1	Kappa	vascular endothelial growth factor receptor 2	SAbDab (2024-11-08)
B [auth H]	Heavy Chain	IGHV3	-	vascular endothelial growth factor receptor 2	SAbDab (2024-11-08)

Thera-SAbDab Antibody Annotation Thera-SAbDab Database Homepage

Chain	Name	Target	Provenance Source
A [auth L]	Ramucirumab	KDR/CD309/VEGFR2	Therapeutic SAbDab (2024-11-08)
B [auth H]	Pulocimab	KDR/CD309/VEGFR2	Therapeutic SAbDab (2024-11-08)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
C [auth X]	PF00047	Immunoglobulin domain (ig)	Immunoglobulin domain	Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-prot ...	Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A [auth L]	1121B Fab light chain	-	-	-
B [auth H]	1121B Fab heavy chain	-	-	-
C [auth X]	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 organic cyclic compound 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 catabolic process macroautophagy autophagy positive regulation of cellular metabolic process regulation of autophagy cellular catabolic process positive regulation of metabolic process positive regulation of macroautophagy process utilizing autophagic mechanism positive regulation of autophagy cellular metabolic process regulation of cellular metabolic process regulation of catabolic process positive regulation of catabolic process regulation of macroautophagy regulation of cellular catabolic process positive regulation of cellular catabolic process metabolic process 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 cellular biosynthetic process negative regulation of cellular metabolic process negative regulation of macromolecule metabolic process regulation of biosynthetic process negative regulation of metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process negative regulation of cellular biosynthetic process regulation of cellular 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 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 protein phosphorylation protein autophosphorylation phosphorylation primary metabolic process peptidyl-tyrosine modification peptidyl-tyrosine autophosphorylation macromolecule modification peptidyl-amino acid modification phosphate-containing compound metabolic process protein metabolic process peptidyl-tyrosine phosphorylation protein modification process phosphorus metabolic process 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 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 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 positive regulation of macromolecule biosynthetic process regulation of nitric-oxide synthase biosynthetic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process nitric-oxide synthase biosynthetic process positive regulation of nitric-oxide synthase biosynthetic process positive regulation of cellular biosynthetic process regulation of cell shape cell morphogenesis regulation of cell morphogenesis 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 regulation of phosphate 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 cellular anatomical entity intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle organelle cytoplasm protein-containing complex receptor complex membrane-bounded organelle intracellular anatomical structure sorting endosome endosome intracellular vesicle cellular anatomical entity intracellular membrane-bounded organelle endomembrane system intracellular organelle 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
C [auth X]	IPR001824	Tyrosine-protein kinase, receptor class III, conserved site	Conserved Site
C [auth X]	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
C [auth X]	IPR020635	Tyrosine-protein kinase, catalytic domain	Domain
C [auth X]	IPR000719	Protein kinase domain	Domain
C [auth X]	IPR003599	Immunoglobulin domain subtype	Domain
C [auth X]	IPR013151	Immunoglobulin-like beta-sandwich domain	Domain
C [auth X]	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
C [auth X]	IPR007110	Immunoglobulin-like domain	Domain
C [auth X]	IPR017441	Protein kinase, ATP binding site	Binding Site
C [auth X]	IPR001245	Serine-threonine/tyrosine-protein kinase, catalytic domain	Domain
C [auth X]	IPR041348	VEGFR-2, transmembrane domain	Domain
C [auth X]	IPR008266	Tyrosine-protein kinase, active site	Active Site
C [auth X]	IPR009136	Vascular endothelial growth factor receptor 2 (VEGFR2)	Family
C [auth X]	IPR003598	Immunoglobulin subtype 2	Domain
C [auth X]	IPR013098	Immunoglobulin I-set	Domain
C [auth X]	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
C [auth X]	IPR050122	Receptor Tyrosine Kinase	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
C [auth X]	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 diabetic kidney disease major depressive disorder spondyloepiphyseal dysplasia tarda, X-linked endometrial carcinoma thyroid gland follicular carcinoma malignant pancreatic neoplasm facioscapulohumeral muscular dystrophy medullary thyroid gland carcinoma gastrointestinal stromal tumor hepatocellular carcinoma myocardial ischemia breast disease hypertensive disorder ovarian cancer colorectal carcinoma intracerebral hemorrhage pancreatic neoplasm renal cell carcinoma coronary artery disease kidney disease cystic fibrosis lung cancer sinusitis malignant ependymoma endometriosis thyroid gland papillary carcinoma ulcerative colitis gastric adenocarcinoma Melnick-Needles syndrome glioblastoma breast cancer neoplasm of esophagus idiopathic pulmonary fibrosis interstitial lung disease pancreatic intraductal papillary-mucinous carcinoma invasive ductal breast carcinoma cribriform carcinoma Schwartz-Jampel syndrome lung disease spondyloepiphyseal dysplasia malignant mesothelioma thymic carcinoma transitional cell carcinoma gastric cancer interstitial cystitis intestinal disease pancreatic intraductal papillary-mucinous neoplasm ischemia reperfusion injury cribriform carcinoma of breast

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.