Annotations: 4CBZ

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	MNNL	e4cbzA3	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: C2 domain (From Topology)	T: C2 domain	F: MNNL	ECOD (1.6)
A	DSL	e4cbzA1	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: DSL	ECOD (1.6)
A	hEGF_4	e4cbzA2	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: hEGF_4	ECOD (1.6)
A	EGF_2_like	e4cbzA5	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: EGF_2_like	ECOD (1.6)
A	hEGF_6	e4cbzA4	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: hEGF_6	ECOD (1.6)
B	MNNL	e4cbzB4	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: C2 domain (From Topology)	T: C2 domain	F: MNNL	ECOD (1.6)
B	DSL	e4cbzB2	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: DSL	ECOD (1.6)
B	EGF_2_like	e4cbzB3	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: EGF_2_like	ECOD (1.6)
B	hEGF_6	e4cbzB1	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: hEGF_6	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.60.40.3510	Mainly Beta	Sandwich	Immunoglobulin-like		CATH (4.3.0)
B	2.60.40.3510	Mainly Beta	Sandwich	Immunoglobulin-like		CATH (4.3.0)
B	2.10.25.140	Mainly Beta	Ribbon	Laminin		CATH (4.3.0)
B	2.10.25.10	Mainly Beta	Ribbon	Laminin	Laminin	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF01414	Delta serrate ligand (DSL)	Delta serrate ligand	This family has been redefined to correspond to the EGF-like domain defined by structure.	Domain
A, B	PF00008	EGF-like domain (EGF)	EGF-like domain	There is no clear separation between noise and signal. Pfam:PF00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is t ...	There is no clear separation between noise and signal. Pfam:PF00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.	Domain
A, B	PF07657	N terminus of Notch ligand C2-like domain (MNNL)	N terminus of Notch ligand C2-like domain	This entry represents a region of conserved sequence at the N terminus of several Notch ligand proteins. The entry has been extended to correspond to the C2-like domain defined by the protein structure.	Domain
A, B	PF21700	Delta-like/Jagged, EGF-like domain (DL-JAG_EGF-like)	Delta-like/Jagged, EGF-like domain	This entry represents a EGF-like domain found in delta-like, jagged and Wnt inhibitory factor 1, which are involved in different signalling pathways [1-5].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	PROTEIN JAGGED-1	protein binding binding signaling receptor binding Notch binding molecular function activator activity molecular function regulator activity signaling receptor regulator activity growth factor activity receptor ligand activity signaling receptor activator activity phospholipid binding lipid binding molecular adaptor activity cation binding protein binding binding signaling receptor binding Notch binding molecular function activator activity molecular function regulator activity signaling receptor regulator activity growth factor activity receptor ligand activity signaling receptor activator activity phospholipid binding lipid binding molecular adaptor activity cation binding ion binding calcium ion binding metal ion binding small molecule binding structural molecule activity	multicellular organismal process regulation of cellular process cellular developmental process regulation of developmental process negative regulation of biological process regulation of cell differentiation neurogenesis multicellular organism development neuron differentiation cell differentiation anatomical structure development negative regulation of cellular process negative regulation of cell differentiation system development multicellular organismal process regulation of cellular process cellular developmental process regulation of developmental process negative regulation of biological process regulation of cell differentiation neurogenesis multicellular organism development neuron differentiation cell differentiation anatomical structure development negative regulation of cellular process negative regulation of cell differentiation system development developmental process regulation of biological process negative regulation of developmental process biological regulation nervous system development generation of neurons cellular process negative regulation of neuron differentiation regulation of neuron differentiation heart development animal organ development cell development mesenchyme development endocardial cushion cell development tissue development cardiocyte differentiation circulatory system development endocardial cushion development endocardial cushion cell differentiation cardiac cell development tissue morphogenesis anatomical structure morphogenesis epithelium development morphogenesis of an epithelium morphogenesis of an epithelial sheet muscle structure development myoblast differentiation negative regulation of stem cell differentiation stem cell differentiation regulation of stem cell differentiation neuroendocrine cell differentiation epithelial cell differentiation neuroepithelial cell differentiation columnar/cuboidal epithelial cell differentiation camera-type eye morphogenesis sensory organ development ciliary body morphogenesis eye development visual system development eye morphogenesis sensory organ morphogenesis camera-type eye development animal organ morphogenesis sensory system development hemopoiesis regulation of cell adhesion negative regulation of cell adhesion cell adhesion cell-cell adhesion negative regulation of cell-cell adhesion regulation of cell-cell adhesion cardiac chamber morphogenesis heart morphogenesis cardiac septum development cardiac septum morphogenesis cardiac chamber development negative regulation of locomotion regulation of cell motility regulation of locomotion regulation of cell migration negative regulation of cell motility cell migration cell motility negative regulation of cell migration locomotion endothelium development regulation of epithelial cell differentiation regulation of multicellular organismal process regulation of multicellular organismal development negative regulation of epithelial cell differentiation endothelial cell differentiation regulation of endothelial cell differentiation negative regulation of endothelial cell differentiation epidermis development hair cell differentiation inner ear development mechanoreceptor differentiation epidermal cell differentiation ear development inner ear auditory receptor cell differentiation inner ear receptor cell differentiation blood vessel morphogenesis tube development artery development vasculature development pulmonary artery morphogenesis tube morphogenesis artery morphogenesis blood vessel development nephron development kidney development renal system development cellular response to stimulus cell surface receptor signaling pathway response to stimulus signaling cell communication Notch signaling pathway signal transduction cardiac right ventricle morphogenesis cardiac ventricle morphogenesis cardiac ventricle development positive regulation of macromolecule biosynthetic process regulation of primary metabolic process nucleobase-containing compound metabolic process positive regulation of metabolic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II organic substance biosynthetic process positive regulation of macromolecule metabolic process regulation of nucleobase-containing compound metabolic process regulation of transcription by RNA polymerase II positive regulation of nucleobase-containing compound metabolic process cellular metabolic process primary metabolic process regulation of cellular metabolic process positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process organic cyclic compound metabolic process regulation of gene expression biosynthetic process organic cyclic compound biosynthetic process metabolic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of DNA-templated transcription regulation of metabolic process positive regulation of DNA-templated transcription cellular biosynthetic process positive regulation of biological process RNA metabolic process positive regulation of cellular metabolic process RNA biosynthetic process nucleic acid biosynthetic process organic substance metabolic process positive regulation of biosynthetic process positive regulation of cellular process regulation of RNA biosynthetic process regulation of biosynthetic 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 positive regulation of RNA biosynthetic process positive regulation of cellular biosynthetic process embryo development regulation of anatomical structure morphogenesis regulation of embryonic development regulation of development, heterochronic inhibition of neuroepithelial cell differentiation regulation of timing of cell differentiation neuronal stem cell population maintenance maintenance of cell number stem cell population maintenance regulation of reproductive process reproductive process fat cell differentiation negative regulation of fat cell differentiation regulation of fat cell differentiation skin development keratinocyte differentiation adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains lymphocyte mediated immunity T cell mediated immunity immune response immune system process leukocyte mediated immunity adaptive immune response immune effector process cardiac neural crest cell development involved in heart development neural crest cell development cardiac neural crest cell development involved in outflow tract morphogenesis stem cell development neural crest cell differentiation cardiac neural crest cell differentiation involved in heart development outflow tract morphogenesis mesenchymal cell differentiation angiogenesis anatomical structure formation involved in morphogenesis aorta morphogenesis aorta development renal filtration cell differentiation kidney epithelium development glomerular epithelial cell differentiation nephron epithelium development epithelial cell differentiation involved in kidney development glomerular epithelium development glomerulus development podocyte development epithelial cell development cell differentiation involved in kidney development glomerular epithelial cell development podocyte differentiation regulation of cell development positive regulation of developmental process positive regulation of cell differentiation regulation of immune system process regulation of myeloid cell differentiation myeloid cell differentiation positive regulation of myeloid cell differentiation regulation of hemopoiesis regulation of epithelial to mesenchymal transition positive regulation of cardiac epithelial to mesenchymal transition positive regulation of epithelial to mesenchymal transition cardiac epithelial to mesenchymal transition regulation of cardiac epithelial to mesenchymal transition epithelial to mesenchymal transition positive regulation of multicellular organismal process nephron tubule development loop of Henle development renal tubule development heart valve development aortic valve development heart valve morphogenesis semi-lunar valve development aortic valve morphogenesis cell fate determination cell fate commitment blood vessel remodeling tissue remodeling pulmonary valve morphogenesis pulmonary valve development cell population proliferation regulation of cell population proliferation regulation of epithelial cell proliferation epithelial cell proliferation regulation of osteoblast differentiation osteoblast differentiation positive regulation of osteoblast differentiation ossification regulation of cell-substrate adhesion cell-substrate adhesion negative regulation of cell-matrix adhesion cell-matrix adhesion regulation of cell-matrix adhesion negative regulation of cell-substrate adhesion response to organic substance response to organonitrogen compound response to chemical response to oxygen-containing compound response to muramyl dipeptide response to nitrogen compound positive regulation of cell communication positive regulation of signal transduction regulation of signal transduction positive regulation of response to stimulus regulation of signaling regulation of response to stimulus regulation of Notch signaling pathway regulation of cell communication positive regulation of Notch signaling pathway positive regulation of signaling distal tubule development	membrane cellular anatomical entity cell-cell junction adherens junction anchoring junction cell junction cell periphery apical part of cell plasma membrane plasma membrane region apical plasma membrane extracellular region

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR018097	EGF-like calcium-binding, conserved site	Conserved Site
A, B	IPR026219	Jagged/Serrate protein	Family
A, B	IPR013032	EGF-like, conserved site	Conserved Site
A, B	IPR001881	EGF-like calcium-binding domain	Domain
A, B	IPR001007	VWFC domain	Domain
A, B	IPR001774	Delta/Serrate/lag-2 (DSL) protein	Domain
A, B	IPR000742	EGF-like domain	Domain
A, B	IPR011651	Notch ligand, N-terminal domain	Domain
A, B	IPR009030	Growth factor receptor cysteine-rich domain superfamily	Homologous Superfamily
A, B	IPR000152	EGF-type aspartate/asparagine hydroxylation site	PTM

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P78504	tetralogy of fallot Alagille syndrome glioblastoma Alagille syndrome due to a JAG1 point mutation pancreatic ductal adenocarcinoma Corneal Opacity salivary gland adenoid cystic carcinoma adenoid cystic carcinoma bone disease giant cell glioblastoma breast carcinoma medulloblastoma oligodendroglioma deafness, congenital heart defects, and posterior embryotoxon pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia tetralogy of fallot Alagille syndrome glioblastoma Alagille syndrome due to a JAG1 point mutation pancreatic ductal adenocarcinoma Corneal Opacity salivary gland adenoid cystic carcinoma adenoid cystic carcinoma bone disease giant cell glioblastoma breast carcinoma medulloblastoma oligodendroglioma deafness, congenital heart defects, and posterior embryotoxon pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia Emery-Dreifuss muscular dystrophy gastric carcinoma schizophrenia juvenile dermatomyositis thoracic aortic aneurysm astrocytic tumor lung cancer malignant ependymoma cancer cholestasis craniosynostosis neurodegenerative disease osteosarcoma dermatomyositis peripheral neuropathy primitive neuroectodermal tumor salivary gland cancer adenoma subependymal giant cell astrocytoma large cell medulloblastoma tuberculosis atypical teratoid rhabdoid tumor lung carcinoma breast cancer malignant glioma cerebrovascular disorder congenital heart disease cystic fibrosis non-small cell lung carcinoma Duchenne muscular dystrophy pilocytic astrocytoma psoriasis adrenal cortex carcinoma intellectual disability Alagille syndrome due to a NOTCH2 point mutation lung benign neoplasm Charcot-Marie-Tooth disease malignant pancreatic neoplasm

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.