3L95

Crystal structure of the human Notch1 Negative Regulatory Region (NRR) bound to the fab fragment of an antagonist antibody

External Resource: Annotation

Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
IMGT Antibody Annotation
SAbDab Antibody Annotation
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
C [auth X]	SCOP2B Superfamily	Notch domain	8034664	3001708	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)
A	C1-set_4	e3l95A2	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	V-set	e3l95A1	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)
D [auth L]	C1-set_4	e3l95L2	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)
D [auth L]	V-set	e3l95L1	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	V-set_8	e3l95B1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_8	ECOD (1.6)
B	C1-set_1	e3l95B2	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)
E [auth H]	V-set_8	e3l95H1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_8	ECOD (1.6)
E [auth H]	C1-set_1	e3l95H2	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)
C [auth X]	NOD	e3l95X4	A: a+b two layers	X: Alpha-beta plaits	H: Notch heterodimerization domain (From Topology)	T: Notch heterodimerization domain	F: NOD	ECOD (1.6)
C [auth X]	Notch	e3l95X1	A: few secondary structure elements	X: Lin12/Notch repeat (From Topology)	H: Lin12/Notch repeat (From Topology)	T: Lin12/Notch repeat	F: Notch	ECOD (1.6)
F [auth Y]	NOD	e3l95Y4	A: a+b two layers	X: Alpha-beta plaits	H: Notch heterodimerization domain (From Topology)	T: Notch heterodimerization domain	F: NOD	ECOD (1.6)
F [auth Y]	Notch	e3l95Y3	A: few secondary structure elements	X: Lin12/Notch repeat (From Topology)	H: Lin12/Notch repeat (From Topology)	T: Lin12/Notch repeat	F: Notch	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
D [auth L]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
B	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
E [auth H]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
C [auth X]	3.30.300.320	Alpha Beta	2-Layer Sandwich	GMP Synthetase	Chain A, domain 3	CATH (4.3.0)
C [auth X]	3.30.70.3310	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits		CATH (4.3.0)
F [auth Y]	3.30.300.320	Alpha Beta	2-Layer Sandwich	GMP Synthetase	Chain A, domain 3	CATH (4.3.0)
F [auth Y]	3.30.70.3310	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits		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, D [auth L]	Anti-NRR1 Fab	L-KAPPA	Homo sapiens (human)	IGKV1-3901, IGKV1D-3901, IGKJ101, IGKC01	V-DOMAIN V-KAPPA, C-DOMAIN C-KAPPA	IG	FAB-GAMMA-1_KAPPA	IMGT (202415-0)
B, E [auth H]	Anti-NRR1 Fab	VH-CH1	Homo sapiens (human)	IGHV3-7401, IGHV3-7402, IGHV3-7403, IGHJ401, IGHJ402, IGHJ403, IGHG101, IGHG102, IGHG1*04	V-DOMAIN VH, C-DOMAIN CH1	IG	FAB-GAMMA-1_KAPPA	IMGT (202415-0)

SAbDab Antibody Annotation SAbDab Database Homepage

Chain	Chain Class	Chain Subclass	Chain Type	Antigen Name(s)	Provenance Source
A, D [auth L]	Light Chain	IGKV1	Kappa	neurogenic locus notch homolog protein 1	SAbDab (2024-04-19)
B, E [auth H]	Heavy Chain	IGHV3	-	neurogenic locus notch homolog protein 1	SAbDab (2024-04-19)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
C [auth X], F [auth Y]	PF06816	NOTCH protein (NOD)	NOTCH protein	-	Family
C [auth X], F [auth Y]	PF07684	NOTCH protein (NODP)	NOTCH protein	-	Family
C [auth X], F [auth Y]	PF00066	LNR domain (Notch)	LNR domain	The LNR (Lin-12/Notch repeat) domain is found in three tandem copies in Notch related proteins. The structure of the domain has been determined by NMR [1] and was shown to contain three disulphide bonds and coordinate a calcium ion. Three repeats ar ...	The LNR (Lin-12/Notch repeat) domain is found in three tandem copies in Notch related proteins. The structure of the domain has been determined by NMR [1] and was shown to contain three disulphide bonds and coordinate a calcium ion. Three repeats are also found in the PAPP-A peptidase [2].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, D [auth L]	anti-NRR1 fab fragment light chain	-	-	-
B, E [auth H]	anti-NRR1 fab fragment heavy chain	-	-	-
C [auth X], F [auth Y]	Neurogenic locus notch homolog protein 1	DNA-binding transcription factor activity, RNA polymerase II-specific transcription regulator activity DNA-binding transcription factor activity DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription activator activity molecular transducer activity transmembrane signaling receptor activity signaling receptor activity DNA binding protein-containing complex binding binding chromatin binding organic cyclic compound binding nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription regulator activity DNA-binding transcription factor activity DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription activator activity molecular transducer activity transmembrane signaling receptor activity signaling receptor activity DNA binding protein-containing complex binding binding chromatin binding organic cyclic compound binding nucleic acid binding chromatin DNA binding protein binding signaling receptor binding Notch binding identical protein binding molecular function activator activity molecular function regulator activity transcription regulator activator activity enzyme regulator activity molecular function inhibitor activity enzyme inhibitor activity transcription coactivator activity transcription coregulator activity protein-macromolecule adaptor activity molecular adaptor activity cation binding ion binding calcium ion binding metal ion binding small molecule binding sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding double-stranded DNA binding cis-regulatory region sequence-specific DNA binding transcription regulatory region nucleic acid binding enzyme binding	developmental process heart development multicellular organismal process cardiac chamber morphogenesis animal organ development heart morphogenesis ventricular septum development circulatory system development multicellular organism development anatomical structure morphogenesis cardiac septum development cardiac septum morphogenesis ventricular septum morphogenesis cardiac chamber development anatomical structure development developmental process heart development multicellular organismal process cardiac chamber morphogenesis animal organ development heart morphogenesis ventricular septum development circulatory system development multicellular organism development anatomical structure morphogenesis cardiac septum development cardiac septum morphogenesis ventricular septum morphogenesis cardiac chamber development anatomical structure development animal organ morphogenesis cardiac ventricle development system development regulation of biological process regulation of cellular process regulation of cell adhesion biological regulation negative regulation of biological process negative regulation of cell adhesion cell adhesion cell-cell adhesion negative regulation of cell-cell adhesion mediated by cadherin cell-cell adhesion mediated by cadherin negative regulation of cell-cell adhesion negative regulation of cellular process regulation of cell-cell adhesion cellular process regulation of cell-cell adhesion mediated by cadherin cellular developmental process regulation of developmental process cell development regulation of neurogenesis regulation of cell differentiation regulation of gliogenesis negative regulation of glial cell proliferation regulation of cell development regulation of nervous system development neurogenesis negative regulation of neurogenesis regulation of glial cell proliferation gliogenesis cell differentiation regulation of multicellular organismal process negative regulation of nervous system development negative regulation of cell differentiation regulation of multicellular organismal development negative regulation of cell population proliferation cell population proliferation negative regulation of developmental process nervous system development negative regulation of gliogenesis negative regulation of cell development regulation of cell population proliferation glial cell proliferation negative regulation of multicellular organismal process negative regulation of stem cell differentiation stem cell differentiation regulation of stem cell differentiation epithelium development neuroendocrine cell differentiation tissue development epithelial cell differentiation generation of neurons neuron differentiation neuroepithelial cell differentiation columnar/cuboidal epithelial cell differentiation digestive system development foregut morphogenesis tube development digestive tract development tube morphogenesis digestive tract morphogenesis mesenchyme development mesenchymal cell development mesenchymal cell differentiation regulation of localization regulated exocytosis transport regulation of calcium ion-dependent exocytosis negative regulation of transport negative regulation of regulated secretory pathway vesicle-mediated transport regulation of regulated secretory pathway localization secretion by cell regulation of secretion by cell negative regulation of secretion negative regulation of exocytosis negative regulation of secretion by cell calcium-ion regulated exocytosis secretion regulation of transport negative regulation of calcium ion-dependent exocytosis export from cell regulation of vesicle-mediated transport establishment of localization regulation of secretion exocytosis regulation of exocytosis cell adhesion involved in heart morphogenesis regulation of cell adhesion involved in heart morphogenesis cellular biosynthetic process RNA metabolic process regulation of primary metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process organic substance metabolic process organic substance biosynthetic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of biosynthetic process cellular metabolic process primary metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process organic cyclic compound metabolic process regulation of gene expression biosynthetic process organic cyclic compound biosynthetic process metabolic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription macromolecule metabolic process regulation of metabolic process cellular response to stimulus response to organic substance response to stimulus cellular response to gonadotropin stimulus response to endogenous stimulus response to gonadotropin cellular response to endogenous stimulus cellular response to chemical stimulus response to hormone cellular response to follicle-stimulating hormone stimulus response to chemical cellular response to organic substance response to follicle-stimulating hormone cellular response to hormone stimulus heart growth developmental growth growth organ growth developmental growth involved in morphogenesis growth involved in heart morphogenesis smooth muscle cell differentiation positive regulation of smooth muscle cell differentiation regulation of smooth muscle cell differentiation positive regulation of biological process muscle cell differentiation positive regulation of muscle cell differentiation muscle structure development positive regulation of developmental process regulation of muscle cell differentiation positive regulation of cell differentiation positive regulation of cellular process cell surface receptor signaling pathway signaling cell communication Notch signaling pathway signal transduction endothelial cell differentiation endothelium development vasculature development blood vessel endothelial cell differentiation arterial endothelial cell differentiation blood vessel development endocardial cushion morphogenesis endocardial cushion development cardiac epithelial to mesenchymal transition epithelial to mesenchymal transition involved in endocardial cushion formation mesenchyme morphogenesis epithelial to mesenchymal transition endocardial cushion formation tissue morphogenesis anatomical structure formation involved in morphogenesis embryo development regulation of epithelial cell differentiation regulation of anatomical structure morphogenesis regulation of embryonic development regulation of development, heterochronic negative regulation of epithelial cell differentiation inhibition of neuroepithelial cell differentiation regulation of timing of cell differentiation neuronal stem cell population maintenance maintenance of cell number stem cell population maintenance negative regulation of cellular metabolic process negative regulation of RNA biosynthetic process negative regulation of nucleobase-containing compound metabolic process negative regulation of DNA-templated transcription negative regulation of metabolic process negative regulation of cellular biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of RNA metabolic process negative regulation of macromolecule metabolic process negative regulation of biosynthetic process regulation of glial cell differentiation negative regulation of oligodendrocyte differentiation negative regulation of glial cell differentiation central nervous system development oligodendrocyte differentiation glial cell differentiation regulation of oligodendrocyte differentiation apoptotic process involved in morphogenesis limb development appendage development embryonic limb morphogenesis embryonic morphogenesis cell death embryonic appendage morphogenesis apoptotic process involved in development apoptotic process involved in embryonic digit morphogenesis appendage morphogenesis apoptotic process embryonic digit morphogenesis programmed cell death limb morphogenesis cardiac muscle tissue development muscle tissue morphogenesis striated muscle tissue development cardiac muscle tissue morphogenesis muscle organ development muscle tissue development muscle organ morphogenesis immune response immune system process heart trabecula morphogenesis trabecula morphogenesis blood vessel morphogenesis vasculogenesis coronary vasculature development vasculogenesis involved in coronary vascular morphogenesis coronary vasculature morphogenesis sensory organ development photoreceptor cell differentiation visual system development retina development in camera-type eye neural retina development eye morphogenesis retinal cone cell differentiation eye photoreceptor cell differentiation sensory system development camera-type eye morphogenesis eye development camera-type eye photoreceptor cell differentiation retina morphogenesis in camera-type eye sensory organ morphogenesis camera-type eye development coronary sinus valve morphogenesis heart valve development heart valve morphogenesis coronary sinus valve development epidermal cell differentiation epidermis development cell fate specification cell fate commitment epidermal cell fate specification left/right axis specification pattern specification process left/right pattern formation axis specification regionalization regulation of cellular component organization extracellular matrix organization regulation of cellular component biogenesis cellular component organization cellular component biogenesis cellular component assembly regulation of extracellular matrix assembly cellular component organization or biogenesis regulation of extracellular matrix organization extracellular matrix assembly extracellular structure organization external encapsulating structure organization regulation of cell adhesion molecule production negative regulation of cell adhesion molecule production cell adhesion molecule production negative regulation of muscle cell differentiation regulation of striated muscle cell differentiation myotube differentiation negative regulation of myotube differentiation regulation of myotube differentiation negative regulation of striated muscle cell differentiation striated muscle cell differentiation positive regulation of cell population proliferation aortic valve development semi-lunar valve development aortic valve morphogenesis head development forebrain development brain development positive regulation of locomotion regulation of cell motility positive regulation of cell migration regulation of locomotion positive regulation of cell motility regulation of cell migration cell migration cell motility locomotion compartment pattern specification anterior/posterior pattern specification rhythmic process ovulation cycle process gonad development reproductive system development reproductive process female gonad development sex differentiation multicellular organismal reproductive process female sex differentiation development of primary female sexual characteristics developmental process involved in reproduction ovulation cycle development of primary sexual characteristics reproductive structure development luteolysis regulation of cell-substrate adhesion cell-substrate adhesion negative regulation of cell-substrate adhesion cell migration involved in heart development cell migration involved in endocardial cushion formation cardiac chamber formation positive regulation of keratinocyte differentiation regulation of epidermal cell differentiation positive regulation of epidermis development positive regulation of epithelial cell differentiation skin development keratinocyte differentiation positive regulation of multicellular organismal process regulation of epidermis development regulation of keratinocyte differentiation positive regulation of epidermal cell differentiation cardiac endothelial cell differentiation endocardium development cardiocyte differentiation endocardial cell differentiation outflow tract morphogenesis negative regulation of collagen metabolic process collagen biosynthetic process regulation of collagen biosynthetic process regulation of collagen metabolic process negative regulation of collagen biosynthetic process collagen metabolic process somitogenesis chordate embryonic development segmentation embryo development ending in birth or egg hatching somite development regulation of somitogenesis positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process positive regulation of gene expression positive regulation of cellular biosynthetic process cardiac ventricle morphogenesis in utero embryonic development regulation of molecular function regulation of catalytic activity negative regulation of molecular function negative regulation of catalytic activity defense response response to stress inflammatory response inflammatory response to antigenic stimulus prostate gland development gland development morphogenesis of an epithelium urogenital system development prostate gland epithelium morphogenesis prostate gland morphogenesis gland morphogenesis muscle hypertrophy regulation of muscle adaptation system process negative regulation of muscle hypertrophy regulation of system process striated muscle hypertrophy regulation of muscle system process muscle system process regulation of muscle hypertrophy regulation of cardiac muscle hypertrophy muscle adaptation regulation of response to stimulus cardiac muscle hypertrophy negative regulation of cardiac muscle hypertrophy cellular response to biotic stimulus response to tumor cell response to biotic stimulus cellular response to tumor cell pericardium morphogenesis morphogenesis of an epithelial sheet pericardium development cellular response to growth factor stimulus cellular response to vascular endothelial growth factor stimulus response to growth factor negative regulation of locomotion regulation of response to external stimulus endothelial cell migration negative regulation of chemotaxis negative regulation of endothelial cell migration tissue migration taxis negative regulation of epithelial cell migration ameboidal-type cell migration regulation of endothelial cell migration epithelial cell migration endothelial cell chemotaxis regulation of epithelial cell migration negative regulation of cell migration cell chemotaxis chemotaxis regulation of endothelial cell chemotaxis negative regulation of response to stimulus response to external stimulus regulation of chemotaxis epithelium migration negative regulation of response to external stimulus negative regulation of cell motility negative regulation of endothelial cell chemotaxis adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains adaptive immune response T-helper 17 type immune response transcription by RNA polymerase II negative regulation of myoblast differentiation regulation of myoblast differentiation myoblast differentiation respiratory tube development lung development respiratory system development positive regulation of epithelial cell proliferation regulation of epithelial cell proliferation epithelial cell proliferation cardiac ventricle formation cardiac right ventricle morphogenesis cardiac right ventricle formation organelle assembly plasma membrane bounded cell projection organization cell projection organization plasma membrane bounded cell projection assembly organelle organization cilium assembly cilium organization cell projection assembly artery development coronary artery morphogenesis artery morphogenesis determination of bilateral symmetry determination of left/right symmetry specification of symmetry regulation of stem cell proliferation stem cell proliferation astrocyte differentiation pulmonary valve morphogenesis pulmonary valve development positive regulation of cell communication cell surface receptor signaling pathway via STAT positive regulation of signal transduction positive regulation of receptor signaling pathway via STAT regulation of signal transduction positive regulation of receptor signaling pathway via JAK-STAT positive regulation of response to stimulus regulation of receptor signaling pathway via JAK-STAT regulation of signaling regulation of cell communication regulation of receptor signaling pathway via STAT cell surface receptor signaling pathway via JAK-STAT positive regulation of signaling regulation of epithelial cell proliferation involved in prostate gland development epithelial cell proliferation involved in prostate gland development positive regulation of nucleobase-containing compound metabolic process positive regulation of RNA metabolic process positive regulation of DNA-templated transcription positive regulation of RNA biosynthetic process negative regulation of biomineral tissue development regulation of biomineral tissue development biomineral tissue development regulation of programmed cell death positive regulation of apoptotic process involved in morphogenesis positive regulation of programmed cell death positive regulation of apoptotic process involved in development regulation of apoptotic process regulation of apoptotic process involved in development positive regulation of apoptotic process regulation of apoptotic process involved in morphogenesis venous blood vessel development venous blood vessel morphogenesis coronary vein morphogenesis neural tube development animal organ regeneration regeneration small GTPase-mediated signal transduction regulation of small GTPase mediated signal transduction intracellular signal transduction regulation of intracellular signal transduction regulation of Ras protein signal transduction intracellular signaling cassette positive regulation of Ras protein signal transduction Ras protein signal transduction positive regulation of intracellular signal transduction positive regulation of small GTPase mediated signal transduction secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development prostate glandular acinus development epithelial cell differentiation involved in prostate gland development glandular epithelial cell differentiation tube formation atrioventricular valve development atrioventricular valve morphogenesis branching morphogenesis of an epithelial tube morphogenesis of a branching structure epithelial tube morphogenesis morphogenesis of a branching epithelium tissue regeneration negative regulation of programmed cell death regulation of anoikis negative regulation of anoikis negative regulation of apoptotic process anoikis organonitrogen compound catabolic process organonitrogen compound metabolic process catabolic process protein catabolic process macromolecule catabolic process protein metabolic process organic substance catabolic process cardiac atrium morphogenesis cardiac right atrium morphogenesis cardiac atrium development molting cycle process hair cycle epidermis morphogenesis skin epidermis development hair follicle development molting cycle hair cycle process hair follicle morphogenesis embryonic hindlimb morphogenesis hindlimb morphogenesis cellular response to interleukin-17 response to interleukin-17 response to cytokine cytokine-mediated signaling pathway interleukin-17-mediated signaling pathway cellular response to cytokine stimulus positive regulation of endothelial cell differentiation regulation of endothelial cell differentiation cell migration involved in sprouting angiogenesis regulation of blood vessel endothelial cell migration negative regulation of blood vessel endothelial cell migration blood vessel endothelial cell migration regulation of cell migration involved in sprouting angiogenesis negative regulation of cell migration involved in sprouting angiogenesis angiogenesis sprouting angiogenesis cardiac vascular smooth muscle cell development vascular associated smooth muscle cell differentiation muscle cell development vascular associated smooth muscle cell development cardiac cell development cardiac vascular smooth muscle cell differentiation regulation of transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II ventricular cardiac muscle tissue morphogenesis ventricular cardiac muscle tissue development ventricular trabecula myocardium morphogenesis regulation of photoreceptor cell differentiation negative regulation of photoreceptor cell differentiation negative regulation of neuron differentiation regulation of neuron differentiation positive regulation of ERK1 and ERK2 cascade positive regulation of MAPK cascade regulation of MAPK cascade MAPK cascade ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade mitral valve morphogenesis atrioventricular valve formation mitral valve development mitral valve formation heart valve formation hair cell differentiation negative regulation of mechanoreceptor differentiation inner ear development regulation of mechanoreceptor differentiation regulation of inner ear auditory receptor cell differentiation negative regulation of epidermis development mechanoreceptor differentiation negative regulation of epidermal cell differentiation ear development inner ear receptor cell differentiation negative regulation of inner ear auditory receptor cell differentiation negative regulation of inner ear receptor cell differentiation inner ear auditory receptor cell differentiation regulation of inner ear receptor cell differentiation endocardium morphogenesis regulation of epithelial to mesenchymal transition positive regulation of cardiac epithelial to mesenchymal transition positive regulation of epithelial to mesenchymal transition regulation of cardiac epithelial to mesenchymal transition 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 enzyme-linked receptor protein 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 venous endothelial cell differentiation axonogenesis plasma membrane bounded cell projection morphogenesis neuron projection development cell morphogenesis cell projection morphogenesis neuron projection morphogenesis axon guidance axon development cell morphogenesis involved in neuron differentiation neuron projection guidance neuron development regulation of aorta morphogenesis regulation of artery morphogenesis aorta morphogenesis positive regulation of artery morphogenesis positive regulation of aorta morphogenesis aorta development cardiac muscle cell myoblast differentiation cardioblast differentiation somatic stem cell division stem cell division cell division cardiac conduction system development atrioventricular node development negative regulation of gene expression negative regulation of cold-induced thermogenesis homeostatic process adaptive thermogenesis multicellular organismal-level homeostasis regulation of cold-induced thermogenesis cold-induced thermogenesis temperature homeostasis ossification regulation of ossification negative regulation of ossification biological process involved in interspecies interaction between organisms response to lipid response to other organism response to oxygen-containing compound response to lipopolysaccharide response to bacterium response to external biotic stimulus response to molecule of bacterial origin kidney epithelium development nephron tubule development renal system development distal tubule development renal tubule development nephron development kidney development nephron epithelium development positive regulation of nervous system development regulation of astrocyte differentiation positive regulation of gliogenesis positive regulation of neurogenesis positive regulation of astrocyte differentiation positive regulation of cell development positive regulation of glial cell differentiation spermatogenesis sexual reproduction male gamete generation gamete generation negative regulation of cell proliferation involved in heart valve morphogenesis negative regulation of cell proliferation involved in heart morphogenesis cell proliferation involved in heart valve development regulation of cell proliferation involved in heart valve morphogenesis cell proliferation involved in heart valve morphogenesis cell proliferation involved in heart morphogenesis regulation of cell proliferation involved in heart morphogenesis homeostasis of number of cells within a tissue anatomical structure homeostasis tissue homeostasis homeostasis of number of cells cardiac muscle cell proliferation muscle cell proliferation cardiac muscle tissue growth striated muscle cell proliferation response to decreased oxygen levels cellular response to oxygen levels cellular response to hypoxia cellular response to decreased oxygen levels cellular response to stress response to hypoxia response to oxygen levels response to abiotic stimulus regulation of growth regulation of cardiac muscle tissue growth positive regulation of cardiac muscle cell proliferation regulation of organ growth regulation of heart growth regulation of cardiac muscle cell proliferation positive regulation of developmental growth positive regulation of heart growth regulation of developmental growth positive regulation of organ growth positive regulation of growth positive regulation of cardiac muscle tissue growth negative regulation of signaling regulation of canonical Wnt signaling pathway canonical Wnt signaling pathway negative regulation of cell communication negative regulation of Wnt signaling pathway Wnt signaling pathway regulation of Wnt signaling pathway negative regulation of signal transduction negative regulation of canonical Wnt signaling pathway negative regulation of hematopoietic progenitor cell differentiation regulation of pro-B cell differentiation negative regulation of pro-B cell differentiation regulation of lymphoid progenitor cell differentiation regulation of hematopoietic progenitor cell differentiation hemopoiesis negative regulation of lymphoid progenitor cell differentiation pro-B cell differentiation lymphoid progenitor cell differentiation hematopoietic progenitor cell differentiation positive regulation of transcription by RNA polymerase II positive regulation of transcription of Notch receptor target protein localization establishment of protein localization cellular localization nitrogen compound transport nucleocytoplasmic transport nuclear transport organic substance transport intracellular transport protein localization to nucleus import into nucleus establishment of protein localization to organelle protein transport cellular macromolecule localization macromolecule localization protein localization to organelle establishment of localization in cell protein import into nucleus intracellular protein transport negative regulation of cellular response to growth factor stimulus negative regulation of BMP signaling pathway negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway skeletal muscle cell differentiation skeletal muscle tissue development skeletal muscle organ development epithelial cell fate commitment positive regulation of viral genome replication positive regulation of viral process viral life cycle regulation of viral process regulation of viral life cycle viral genome replication viral process regulation of viral genome replication negative regulation of epithelial cell proliferation embryonic heart tube development embryonic heart tube morphogenesis heart looping embryonic organ development embryonic organ morphogenesis determination of heart left/right asymmetry hepaticobiliary system development liver development humoral immune response regulation of osteoblast differentiation negative regulation of osteoblast differentiation osteoblast differentiation negative regulation of extracellular matrix organization regulation of extracellular matrix constituent secretion negative regulation of cellular component organization negative regulation of extracellular matrix constituent secretion extracellular matrix constituent secretion endoderm development collecting duct development cell differentiation in spinal cord spinal cord development cardiac left ventricle morphogenesis response to organonitrogen compound response to muramyl dipeptide response to nitrogen compound connective tissue development mesangial cell development kidney vasculature development pericyte cell differentiation renal system vasculature development mesangial cell differentiation epithelial cell differentiation involved in kidney development glomerular mesangium development glomerular mesangial cell development glomerular mesangial cell differentiation glomerulus development epithelial cell development cell differentiation involved in kidney development glomerulus vasculature development regulation of Notch signaling pathway positive regulation of Notch signaling pathway neuroblast proliferation regulation of neuroblast proliferation regulation of neural precursor cell proliferation positive regulation of neural precursor cell proliferation positive regulation of neuroblast proliferation neural precursor cell proliferation cell surface receptor signaling pathway involved in heart development cardioblast proliferation regulation of cardioblast proliferation animal organ formation regulation of secondary heart field cardioblast proliferation Notch signaling involved in heart development Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation heart formation auditory receptor cell fate commitment inner ear receptor cell fate commitment neuron fate commitment	protein-containing complex receptor complex endosome membrane membrane-bounded organelle intracellular anatomical structure membrane endosome intracellular vesicle cellular anatomical entity intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle membrane bounding membrane of organelle protein-containing complex receptor complex endosome membrane membrane-bounded organelle intracellular anatomical structure membrane endosome intracellular vesicle cellular anatomical entity intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle membrane bounding membrane of organelle vesicle membrane cytoplasmic vesicle organelle cytoplasm vesicle organelle membrane cell periphery plasma membrane organelle subcompartment endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum endoplasmic reticulum membrane cell-cell junction adherens junction anchoring junction cell junction MAML1-RBP-Jkappa- ICN1 complex nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen cytosol Golgi membrane Golgi apparatus acrosomal vesicle secretory granule secretory vesicle apical part of cell plasma membrane region apical plasma membrane cell surface extracellular region

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
C [auth X], F [auth Y]	IPR013032	EGF-like, conserved site	Conserved Site
C [auth X], F [auth Y]	IPR022362	Neurogenic locus notch homolog protein 1	Family
C [auth X], F [auth Y]	IPR036770	Ankyrin repeat-containing domain superfamily	Homologous Superfamily
C [auth X], F [auth Y]	IPR000742	EGF-like domain	Domain
C [auth X], F [auth Y]	IPR035993	Notch-like domain superfamily	Homologous Superfamily
C [auth X], F [auth Y]	IPR011656	Notch, NODP domain	Domain
C [auth X], F [auth Y]	IPR010660	Notch, NOD domain	Domain
C [auth X], F [auth Y]	IPR008297	Notch	Family
C [auth X], F [auth Y]	IPR000800	Notch domain	Domain
C [auth X], F [auth Y]	IPR000152	EGF-type aspartate/asparagine hydroxylation site	PTM
C [auth X], F [auth Y]	IPR001881	EGF-like calcium-binding domain	Domain
C [auth X], F [auth Y]	IPR009030	Growth factor receptor cysteine-rich domain superfamily	Homologous Superfamily
C [auth X], F [auth Y]	IPR018097	EGF-like calcium-binding, conserved site	Conserved Site
C [auth X], F [auth Y]	IPR002110	Ankyrin repeat	Repeat
C [auth X], F [auth Y]	IPR024600	Notch, C-terminal	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
C [auth X], F [auth Y]	Pharos: P46531	aortic valve disease 1 Adams-Oliver syndrome glioblastoma squamous cell carcinoma T-cell leukemia Adams-Oliver syndrome 5 esophageal squamous cell carcinoma pilocytic astrocytoma head and neck squamous cell carcinoma astrocytic tumor breast carcinoma juvenile pilocytic astrocytoma skin cancer cancer cervical cancer aortic valve disease 1 Adams-Oliver syndrome glioblastoma squamous cell carcinoma T-cell leukemia Adams-Oliver syndrome 5 esophageal squamous cell carcinoma pilocytic astrocytoma head and neck squamous cell carcinoma astrocytic tumor breast carcinoma juvenile pilocytic astrocytoma skin cancer cancer cervical cancer malignant colon neoplasm congenital abnormality anaplastic astrocytoma gemistocytic astrocytoma protoplasmic astrocytoma skin neoplasm childhood cerebral astrocytoma Craniofacial Abnormalities adenoid cystic carcinoma fibrillary astrocytoma giant cell glioblastoma pancreatic ductal adenocarcinoma calcinosis lymphoma subependymal giant cell astrocytoma nervous system disorder heart valve disease salivary gland adenoid cystic carcinoma lung disease urinary bladder carcinoma acute T cell leukemia oligodendroglioma astrocytoma (excluding glioblastoma) heart, malformation of bladder benign neoplasm intestinal disease scoliosis breast adenocarcinoma breast disease liver disease lymphatic system disease squamous cell lung carcinoma malignant ependymoma tetralogy of fallot congenital anemia ulcerative colitis urinary bladder neoplasm Marfan syndrome diffuse astrocytoma aortic valve calcification benign colon neoplasm hematologic disease rheumatoid arthritis bladder carcinoma in situ breast cancer lung carcinoma cerebral astrocytoma colonic neoplasm malignant glioma thoracic aortic aneurysm urinary bladder cancer Crohn disease medulloblastoma Adams-Oliver syndrome 1 Ehlers-Danlos syndrome adult T-cell leukemia/lymphoma gastric carcinoma aortic valve disease pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia primitive neuroectodermal tumor inflammatory bowel disease bone disease

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), 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 R01GM133198.