Human Recombinant NOTCH2 protein, His Tag (V2LY-0526-LY5820)

NOTCH2

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).

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

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).

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.

Extracellular: 26-1677
Helical: 1678-1698
Cytoplasmic: 1699-2471

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.