InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NOTCH2

Summary

InnateDB Protein

IDBP-101548.5

Last Modified

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

Gene Symbol

NOTCH2

Protein Name

notch 2

Synonyms

AGS2; HJCYS; hN2;

Species

Homo sapiens

Ensembl Protein

ENSP00000256646

InnateDB Gene

IDBG-101546 (NOTCH2)

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 (By similarity). Involved in bone remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation. {ECO:0000250, ECO:0000269PubMed:21378985, ECO:0000269PubMed:21378989}.

Subcellular Localization

Cell membrane; Single-pass type I membrane protein.Notch 2 intracellular domain: Nucleus. Note=Following proteolytical processing NICD is translocated to the nucleus.

Disease Associations

Alagille syndrome 2 (ALGS2) [MIM:610205]: A form of Alagille syndrome, an autosomal dominant multisystem disorder. It is clinically defined by hepatic bile duct paucity and cholestasis in association with cardiac, skeletal, and ophthalmologic manifestations. There are characteristic facial features and less frequent clinical involvement of the renal and vascular systems. {ECO:0000269PubMed:16773578}. Note=The disease is caused by mutations affecting the gene represented in this entry.Hajdu-Cheney syndrome (HJCYS) [MIM:102500]: A rare skeletal disorder characterized by the association of facial anomalies, acro-osteolysis, general osteoporosis, insufficient ossification of the skull, and periodontal disease (premature loss of permanent teeth). Other features include cleft palate, congenital heart defects, polycystic kidneys, orthopedic problems and anomalies of the genitalia, intestines and eyes. {ECO:0000269PubMed:21378985, ECO:0000269PubMed:21378989}. Note=The disease is caused by mutations affecting the gene represented in this entry. NOTCH2 mutations associated with Hajdu- Cheney syndrome cluster to the last coding exon of the gene. This suggests that the mutant mRNA products may escape nonsense- mediated decay and the resulting truncated NOTCH2 proteins act in a gain-of-function manner.

Tissue Specificity

Expressed in the brain, heart, kidney, lung, skeletal muscle and liver. Ubiquitously expressed in the embryo. {ECO:0000269PubMed:21378985}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 36 experimentally validated interaction(s) in this database.
They are also associated with 7 interaction(s) predicted by orthology.

Experimentally validated
Total	36 [view]
Protein-Protein	35 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	7 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004872	receptor activity
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0038049	ligand-activated RNA polymerase II transcription factor binding transcription factor activity

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0001701	in utero embryonic development
GO:0001709	cell fate determination
GO:0001890	placenta development
GO:0002011	morphogenesis of an epithelial sheet
GO:0002437	inflammatory response to antigenic stimulus
GO:0003184	pulmonary valve morphogenesis
GO:0006355	regulation of transcription, DNA-templated
GO:0006367	transcription initiation from RNA polymerase II promoter
GO:0006915	apoptotic process
GO:0006959	humoral immune response
GO:0007050	cell cycle arrest
GO:0007219	Notch signaling pathway
GO:0007220	Notch receptor processing
GO:0007275	multicellular organismal development
GO:0007368	determination of left/right symmetry
GO:0007399	nervous system development
GO:0008284	positive regulation of cell proliferation
GO:0008285	negative regulation of cell proliferation
GO:0009887	organ morphogenesis
GO:0010467	gene expression
GO:0016049	cell growth
GO:0019827	stem cell maintenance
GO:0030097	hemopoiesis
GO:0030154	cell differentiation
GO:0030326	embryonic limb morphogenesis
GO:0030513	positive regulation of BMP signaling pathway
GO:0030522	intracellular receptor signaling pathway
GO:0043065	positive regulation of apoptotic process
GO:0043066	negative regulation of apoptotic process
GO:0046579	positive regulation of Ras protein signal transduction
GO:0046849	bone remodeling
GO:0050793	regulation of developmental process
GO:0060413	atrial septum morphogenesis
GO:0060674	placenta blood vessel development
GO:0061073	ciliary body morphogenesis
GO:0061314	Notch signaling involved in heart development
GO:0072602	interleukin-4 secretion

Cellular Component

GO:0000139	Golgi membrane
GO:0005576	extracellular region
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005789	endoplasmic reticulum membrane
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0005929	cilium
GO:0009986	cell surface
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0043235	receptor complex

Protein Structure and Domains

PDB ID

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
IPR022336 Neurogenic locus Notch 2
IPR024600 Domain of unknown function DUF3454, notch

PFAM