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NOTCH2

This gene encodes a member of the Notch family. Members of this Type 1 transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple, different domain types. Notch family members play a role in a variety of developmental processes by controlling cell fate decisions. The Notch signaling network is an evolutionarily conserved intercellular signaling pathway which regulates interactions between physically adjacent cells. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signaling pathway that plays a key role in development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remain to be determined. This protein is cleaved in the trans-Golgi network, and presented on the cell surface as a heterodimer. This protein functions as a receptor for membrane bound ligands, and may play a role in vascular, renal and hepatic development. Two transcript variants encoding different isoforms have been found for this gene.
Full Name
NOTCH2
Function
Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) 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 (PubMed:21378985, PubMed:21378989).
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 (PubMed:29149593).
Positively regulates self-renewal of liver cancer cells (PubMed:25985737).
Biological Process
Animal organ morphogenesisManual Assertion Based On ExperimentIEP:UniProtKB
Apoptotic processManual Assertion Based On ExperimentTAS:UniProtKB
Atrial septum morphogenesisManual Assertion Based On ExperimentIMP:BHF-UCL
Atrioventricular node development1 PublicationNAS:BHF-UCL
Axon guidanceManual Assertion Based On ExperimentIBA:GO_Central
Bone remodelingManual Assertion Based On ExperimentIMP:UniProtKB
Cell fate determinationManual Assertion Based On ExperimentTAS:UniProtKB
Cellular response to tumor cellManual Assertion Based On ExperimentIDA:UniProtKB
Cholangiocyte proliferationIEA:Ensembl
Ciliary body morphogenesisIEA:Ensembl
Defense response to bacteriumIEA:Ensembl
Embryonic limb morphogenesisIEA:Ensembl
Glomerular capillary formationIEA:Ensembl
Glomerular visceral epithelial cell developmentIEA:Ensembl
Heart loopingIEA:Ensembl
HemopoiesisManual Assertion Based On ExperimentTAS:UniProtKB
Hepatocyte proliferationIEA:Ensembl
Humoral immune responseIEA:Ensembl
In utero embryonic developmentIEA:Ensembl
Inflammatory response to antigenic stimulusIEA:Ensembl
Intrahepatic bile duct developmentIEA:Ensembl
Left/right axis specificationIEA:Ensembl
Marginal zone B cell differentiationISS:UniProtKB
Morphogenesis of an epithelial sheetIEA:Ensembl
Multicellular organism growthIEA:Ensembl
Myeloid dendritic cell differentiationIEA:Ensembl
Negative regulation of apoptotic processManual Assertion Based On ExperimentTAS:UniProtKB
Negative regulation of gene expressionManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of transcription by RNA polymerase IIIEA:Ensembl
Nervous system development1 PublicationNAS:UniProtKB
Notch signaling involved in heart development1 PublicationIC:BHF-UCL
Notch signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Placenta blood vessel developmentIEA:Ensembl
Positive regulation of apoptotic processIEA:Ensembl
Positive regulation of BMP signaling pathwayIEA:Ensembl
Positive regulation of ERK1 and ERK2 cascadeManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of keratinocyte proliferationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of osteoclast differentiationIEA:Ensembl
Positive regulation of Ras protein signal transductionManual Assertion Based On ExperimentIDA:UniProtKB
Proximal tubule developmentIEA:Ensembl
Pulmonary valve morphogenesisManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of actin cytoskeleton reorganizationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of osteoclast developmentManual Assertion Based On ExperimentIMP:UniProtKB
Wound healingIEA:Ensembl
Cellular Location
Notch 2 extracellular truncation
Cell membrane
Notch 2 intracellular domain
Nucleus
Cytoplasm
Following proteolytical processing NICD is translocated to the nucleus. Retained at the cytoplasm by TCIM (PubMed:25985737).
Involvement in disease
Alagille syndrome 2 (ALGS2):
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.
Hajdu-Cheney syndrome (HJCYS):
A rare, autosomal dominant 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.
Topology
Extracellular: 26-1677
Helical: 1678-1698
Cytoplasmic: 1699-2471
PTM
Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form (By similarity).
Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC) (By similarity).
Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT) (By similarity).
This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane (By similarity).
Hydroxylated by HIF1AN.
Can be either O-glucosylated or O-xylosylated at Ser-613 by POGLUT1.
Phosphorylated by GSK3. GSK3-mediated phosphorylation is necessary for NOTCH2 recognition by FBXW7, ubiquitination and degradation via the ubiquitin proteasome pathway.

Anti-NOTCH2 antibodies

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Target: NOTCH2
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human
Clone: NOD-15
Application*: IF, IP, WB
Target: NOTCH2
Host: Rat
Antibody Isotype: IgG2
Specificity: Human
Clone: CBWJN-0691
Application*: WB
Target: NOTCH2
Host: Rabbit
Specificity: Human, Mouse, Rat
Clone: D76A6
Application*: WB, IP, IF, F
Target: NOTCH2
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Rat
Clone: D67C8
Application*: WB, IP, IF
Target: NOTCH2
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human
Clone: 8A1
Application*: IP, WB
Target: NOTCH2
Host: Rat
Antibody Isotype: IgG2a
Specificity: Human
Clone: 7H239
Application*: E, WB
Target: NOTCH2
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human
Clone: 18H4L20
Application*: F, IC, IF, WB
Target: NOTCH2
Host: Hamster
Antibody Isotype: IgG
Specificity: Mouse, Rat
Clone: CBWJN-0100
Application*: F
Target: NOTCH2
Host: Rat
Antibody Isotype: IgG1
Specificity: Mouse
Clone: CBWJN-0084
Application*: F
Target: NOTCH2
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Rat
Clone: CBWJN-0064
Application*: IF, IP, WB
Target: NOTCH2
Host: Rat
Antibody Isotype: IgG2a
Specificity: Human
Clone: CBWJN-1481
Application*: WB
Target: NOTCH2
Host: Mouse
Antibody Isotype: IgG1
Specificity: Rat
Clone: CBWJN-1480
Application*: WB
Target: NOTCH2
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: CBWJN-0657
Application*: F
Target: NOTCH2
Host: Rat
Antibody Isotype: IgG1
Specificity: Mouse
Clone: CBWJN-1009
Application*: F, MC
Target: NOTCH2
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: CBWJN-1008
Application*: F, MC
Target: NOTCH2
Host: Rat
Antibody Isotype: IgG1, κ
Specificity: Human, Dog, Mouse
Clone: C651.6DbHN
Application*: F, IF, IH, IP, WB
Target: NOTCH2
Host: Mouse
Antibody Isotype: IgG2
Specificity: Human
Clone: MM084439M21
Application*: F
Target: NOTCH2
Host: Rat
Antibody Isotype: IgG2
Specificity: Human
Clone: MM0845-48N11
Application*: WB
For Research Use Only. Not For Clinical Use.
(P): Predicted
* Abbreviations
IFImmunofluorescence
IHImmunohistochemistry
IPImmunoprecipitation
WBWestern Blot
EELISA
MMicroarray
CIChromatin Immunoprecipitation
FFlow Cytometry
FNFunction Assay
IDImmunodiffusion
RRadioimmunoassay
TCTissue Culture
GSGel Supershift
NNeutralization
BBlocking
AActivation
IInhibition
DDepletion
ESELISpot
DBDot Blot
MCMass Cytometry/CyTOF
CTCytotoxicity
SStimulation
AGAgonist
APApoptosis
IMImmunomicroscopy
BABioassay
CSCostimulation
EMElectron Microscopy
IEImmunoelectrophoresis
PAPeptide Array
ICImmunocytochemistry
PEPeptide ELISA
MDMeDIP
SHIn situ hybridization
IAEnzyme Immunoassay
SEsandwich ELISA
PLProximity Ligation Assay
ECELISA(Cap)
EDELISA(Det)
BIBioimaging
IOImmunoassay
LFLateral Flow Immunoassay
LALuminex Assay
CImmunohistochemistry-Frozen Sections
PImmunohistologyp-Paraffin Sections
ISIntracellular Staining for Flow Cytometry
MSElectrophoretic Mobility Shift Assay
RIRNA Binding Protein Immunoprecipitation (RIP)
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