InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Notch1

Summary

InnateDB Protein

IDBP-149575.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Notch1

Protein Name

Notch gene homolog 1 (Drosophila)

Synonyms

9930111A19Rik; lin-12; Mis6; N1; Tan1;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000028288

InnateDB Gene

IDBG-149571 (Notch1)

Protein Structure

UniProt Annotation

Function

Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4+ and CD8+ cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, functions as a receptor for neuronal DNER and is involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation. May be involved in mesoderm development, somite formation and neurogenesis. May enhance HIF1A function by sequestering HIF1AN away from HIF1A. Required for the THBS4 function in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury. Involved in determination of left/right symmetry by modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO). {ECO:0000269PubMed:15965470, ECO:0000269PubMed:18299578, ECO:0000269PubMed:23160044, ECO:0000269PubMed:23615612}.

Subcellular Localization

Cell membrane; Single-pass type I membrane protein.Notch 1 intracellular domain: Nucleus. Note=Following proteolytical processing NICD is translocated to the nucleus.

Disease Associations

Tissue Specificity

Highly expressed in the brain, lung and thymus. Expressed at lower levels in the spleen, bone-marrow, spinal cord, eyes, mammary gland, liver, intestine, skeletal muscle, kidney and heart. In the hair follicle, highly expressed exclusively in the epithelial compartment. {ECO:0000269PubMed:15965470}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 44 experimentally validated interaction(s) in this database.
They are also associated with 181 interaction(s) predicted by orthology.

Experimentally validated
Total	44 [view]
Protein-Protein	39 [view]
Protein-DNA	5 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	181 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001047	core promoter binding
GO:0001190	RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription
GO:0003682	chromatin binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0004857	enzyme inhibitor activity
GO:0004872	receptor activity
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0019899	enzyme binding
GO:0031490	chromatin DNA binding
GO:0043565	sequence-specific DNA binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0001701	in utero embryonic development
GO:0001708	cell fate specification
GO:0001837	epithelial to mesenchymal transition
GO:0001889	liver development
GO:0001947	heart looping
GO:0002040	sprouting angiogenesis
GO:0002051	osteoblast fate commitment
GO:0002052	positive regulation of neuroblast proliferation
GO:0002437	inflammatory response to antigenic stimulus
GO:0003157	endocardium development
GO:0003160	endocardium morphogenesis
GO:0003162	atrioventricular node development
GO:0003169	coronary vein morphogenesis
GO:0003180	aortic valve morphogenesis
GO:0003181	atrioventricular valve morphogenesis
GO:0003184	pulmonary valve morphogenesis
GO:0003192	mitral valve formation
GO:0003198	epithelial to mesenchymal transition involved in endocardial cushion formation
GO:0003203	endocardial cushion morphogenesis
GO:0003207	cardiac chamber formation
GO:0003208	cardiac ventricle morphogenesis
GO:0003209	cardiac atrium morphogenesis
GO:0003213	cardiac right atrium morphogenesis
GO:0003214	cardiac left ventricle morphogenesis
GO:0003219	cardiac right ventricle formation
GO:0003222	ventricular trabecula myocardium morphogenesis
GO:0003241	growth involved in heart morphogenesis
GO:0003256	regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation
GO:0003264	regulation of cardioblast proliferation
GO:0003270	Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation
GO:0003273	cell migration involved in endocardial cushion formation
GO:0003344	pericardium morphogenesis
GO:0006351	transcription, DNA-templated
GO:0006357	regulation of transcription from RNA polymerase II promoter
GO:0006959	humoral immune response
GO:0007219	Notch signaling pathway
GO:0007221	positive regulation of transcription of Notch receptor target
GO:0007275	multicellular organismal development
GO:0007283	spermatogenesis
GO:0007368	determination of left/right symmetry
GO:0007386	compartment pattern specification
GO:0007409	axonogenesis
GO:0007420	brain development
GO:0007440	foregut morphogenesis
GO:0007492	endoderm development
GO:0007507	heart development
GO:0008284	positive regulation of cell proliferation
GO:0008285	negative regulation of cell proliferation
GO:0008544	epidermis development
GO:0009912	auditory receptor cell fate commitment
GO:0010001	glial cell differentiation
GO:0010468	regulation of gene expression
GO:0010718	positive regulation of epithelial to mesenchymal transition
GO:0010812	negative regulation of cell-substrate adhesion
GO:0010832	negative regulation of myotube differentiation
GO:0014031	mesenchymal cell development
GO:0014807	regulation of somitogenesis
GO:0021515	cell differentiation in spinal cord
GO:0021915	neural tube development
GO:0030154	cell differentiation
GO:0030182	neuron differentiation
GO:0030216	keratinocyte differentiation
GO:0030279	negative regulation of ossification
GO:0030324	lung development
GO:0030326	embryonic limb morphogenesis
GO:0030334	regulation of cell migration
GO:0030335	positive regulation of cell migration
GO:0030513	positive regulation of BMP signaling pathway
GO:0030514	negative regulation of BMP signaling pathway
GO:0030900	forebrain development
GO:0031069	hair follicle morphogenesis
GO:0031100	organ regeneration
GO:0031960	response to corticosteroid
GO:0032495	response to muramyl dipeptide
GO:0032496	response to lipopolysaccharide
GO:0035116	embryonic hindlimb morphogenesis
GO:0035148	tube formation
GO:0035914	skeletal muscle cell differentiation
GO:0035924	cellular response to vascular endothelial growth factor stimulus
GO:0042127	regulation of cell proliferation
GO:0042246	tissue regeneration
GO:0042640	anagen
GO:0043065	positive regulation of apoptotic process
GO:0043086	negative regulation of catalytic activity
GO:0045087	innate immune response (InnateDB)
GO:0045165	cell fate commitment
GO:0045596	negative regulation of cell differentiation
GO:0045603	positive regulation of endothelial cell differentiation
GO:0045618	positive regulation of keratinocyte differentiation
GO:0045662	negative regulation of myoblast differentiation
GO:0045665	negative regulation of neuron differentiation
GO:0045668	negative regulation of osteoblast differentiation
GO:0045687	positive regulation of glial cell differentiation
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0045955	negative regulation of calcium ion-dependent exocytosis
GO:0046427	positive regulation of JAK-STAT cascade
GO:0046533	negative regulation of photoreceptor cell differentiation
GO:0048103	somatic stem cell division
GO:0048663	neuron fate commitment
GO:0048708	astrocyte differentiation
GO:0048709	oligodendrocyte differentiation
GO:0048711	positive regulation of astrocyte differentiation
GO:0048715	negative regulation of oligodendrocyte differentiation
GO:0048754	branching morphogenesis of an epithelial tube
GO:0050678	regulation of epithelial cell proliferation
GO:0050679	positive regulation of epithelial cell proliferation
GO:0050767	regulation of neurogenesis
GO:0050768	negative regulation of neurogenesis
GO:0050793	regulation of developmental process
GO:0055008	cardiac muscle tissue morphogenesis
GO:0060038	cardiac muscle cell proliferation
GO:0060045	positive regulation of cardiac muscle cell proliferation
GO:0060253	negative regulation of glial cell proliferation
GO:0060271	cilium morphogenesis
GO:0060317	cardiac epithelial to mesenchymal transition
GO:0060411	cardiac septum morphogenesis
GO:0060412	ventricular septum morphogenesis
GO:0060528	secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development
GO:0060548	negative regulation of cell death
GO:0060740	prostate gland epithelium morphogenesis
GO:0060768	regulation of epithelial cell proliferation involved in prostate gland development
GO:0060842	arterial endothelial cell differentiation
GO:0060843	venous endothelial cell differentiation
GO:0060948	cardiac vascular smooth muscle cell development
GO:0060956	endocardial cell differentiation
GO:0060979	vasculogenesis involved in coronary vascular morphogenesis
GO:0060982	coronary artery morphogenesis
GO:0061314	Notch signaling involved in heart development
GO:0061344	regulation of cell adhesion involved in heart morphogenesis
GO:0061384	heart trabecula morphogenesis
GO:0061419	positive regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0070986	left/right axis specification
GO:0071372	cellular response to follicle-stimulating hormone stimulus
GO:0072017	distal tubule development
GO:0072044	collecting duct development
GO:0072144	glomerular mesangial cell development
GO:0072602	interleukin-4 secretion
GO:0090051	negative regulation of cell migration involved in sprouting angiogenesis
GO:0090090	negative regulation of canonical Wnt signaling pathway
GO:0097150	neuronal stem cell maintenance
GO:1901189	positive regulation of ephrin receptor signaling pathway
GO:1901201	regulation of extracellular matrix assembly
GO:1902263	apoptotic process involved in embryonic digit morphogenesis
GO:2000737	negative regulation of stem cell differentiation
GO:2000811	negative regulation of anoikis
GO:2000974	negative regulation of pro-B cell differentiation
GO:2001027	negative regulation of endothelial cell chemotaxis

Cellular Component

GO:0000139	Golgi membrane
GO:0001669	acrosomal vesicle
GO:0001726	ruffle
GO:0002193	MAML1-RBP-Jkappa- ICN1 complex
GO:0005576	extracellular region
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005789	endoplasmic reticulum membrane
GO:0005794	Golgi apparatus
GO:0005829	cytosol
GO:0005856	cytoskeleton
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0009986	cell surface
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0030027	lamellipodium
GO:0043235	receptor complex
GO:0071944	cell periphery

Protein Structure and Domains

PDB ID

MGI:97363

InterPro

IPR000742 Epidermal growth factor-like domain
IPR000800 Notch domain
IPR001881 EGF-like calcium-binding domain
IPR002110 Ankyrin repeat
IPR008297 Notch
IPR010660 Notch, NOD domain
IPR011656 Notch, NODP domain
IPR013111 EGF-like domain, extracellular
IPR020683 Ankyrin repeat-containing domain
IPR022355 Neurogenic locus Notch 4
IPR022362 Neurogenic locus Notch 1
IPR024600 Domain of unknown function DUF3454, notch

PFAM