Human Notch 1 Protein 4650

$270.00 – $900.00

Summary

Expression: HEK293
Functional: Yes (ELISA)
Amino Acid Range: Ala19-Gln526

SKU: 4650parent Categories: proteins, Recombinant proteins Tag: active proteins

Weight	1 lbs
Dimensions	9 × 5 × 2 in
accession	P46531
express system	HEK293
product tag	C-His-Avi
purity	> 95% as determined by Tris-Bis PAGE;> 95% as determined by HPLC
background	Human Notch-1 is a 300 kDa type I transmembrane glycoprotein that is one of four human Notch homologues involved in developmental processes.Notch-1 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. Affects the implementation of differentiation, proliferation and apoptotic programs.
molecular weight	The protein has a predicted MW of 56.5 kDa. Due to glycosylation, the protein migrates to 70-80 kDa based on Tris-Bis PAGE result.
available size	100 µg, 500 µg
endotoxin	Less than 1EU per μg by the LAL method.

Human Notch 1 Protein 4650

protein

Size and concentration 100, 500µg and lyophilized
Form Lyophilized
Storage Instructions Valid for 12 months from date of receipt when stored at -80°C. Recommend to aliquot the protein into smaller quantities for optimal storage. Please minimize freeze-thaw cycles.
Storage buffer Shipped at ambient temperature.
Purity > 95% as determined by Tris-Bis PAGE

target relevance
Human Notch-1 is a 300 kDa type I transmembrane glycoprotein that is one of four human Notch homologues involved in developmental processes.Notch-1 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. Affects the implementation of differentiation, proliferation and apoptotic programs.
Protein names Neurogenic locus notch homolog protein 1 (Notch 1) (hN1) (Translocation-associated notch protein TAN-1) [Cleaved into: Notch 1 extracellular truncation (NEXT); Notch 1 intracellular domain (NICD)]
Gene names NOTCH1,NOTCH1 TAN1
Protein family NOTCH family
Mass 9606Da
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. 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).
Catalytic activity BINDING 432; /ligand="Ca(2+)"; /ligand_id="ChEBI:CHEBI:29108"; /ligand_label="1"; /evidence="ECO:0000250\|UniProtKB:Q07008"; BINDING 435; /ligand="Ca(2+)"; /ligand_id="ChEBI:CHEBI:29108"; /ligand_label="1"; /evidence="ECO:0000250\|UniProtKB:Q07008"; BINDING 452; /ligand="Ca(2+)"; /ligand_id="ChEBI:CHEBI:29108"; /ligand_label="2"; /evidence="ECO:0000250\|UniProtKB:Q07008"; BINDING 453; /ligand="Ca(2+)"; /ligand_id="ChEBI:CHEBI:29108"; /ligand_label="2"; /evidence="ECO:0000250\|UniProtKB:Q07008"; BINDING 455; /ligand="Ca(2+)"; /ligand_id="ChEBI:CHEBI:29108"; /ligand_label="2"; /evidence="ECO:0000250\|UniProtKB:Q07008"; BINDING 469; /ligand="Ca(2+)"; /ligand_id="ChEBI:CHEBI:29108"; /ligand_label="2"; /evidence="ECO:0000250\|UniProtKB:Q07008"; BINDING 470; /ligand="Ca(2+)"; /ligand_id="ChEBI:CHEBI:29108"; /ligand_label="2"; /evidence="ECO:0000250\|UniProtKB:Q07008"; BINDING 490; /ligand="Ca(2+)"; /ligand_id="ChEBI:CHEBI:29108"; /ligand_label="3"; /evidence="ECO:0000250\|UniProtKB:Q07008"; BINDING 491; /ligand="Ca(2+)"; /ligand_id="ChEBI:CHEBI:29108"; /ligand_label="3"; /evidence="ECO:0000250\|UniProtKB:Q07008"; BINDING 493; /ligand="Ca(2+)"; /ligand_id="ChEBI:CHEBI:29108"; /ligand_label="3"; /evidence="ECO:0000250\|UniProtKB:Q07008"; BINDING 507; /ligand="Ca(2+)"; /ligand_id="ChEBI:CHEBI:29108"; /ligand_label="3"; /evidence="ECO:0000250\|UniProtKB:Q07008"; BINDING 508; /ligand="Ca(2+)"; /ligand_id="ChEBI:CHEBI:29108"; /ligand_label="3"; /evidence="ECO:0000250\|UniProtKB:Q07008"; BINDING 1457; /ligand="Ca(2+)"; /ligand_id="ChEBI:CHEBI:29108"; /ligand_label="4"; BINDING 1460; /ligand="Ca(2+)"; /ligand_id="ChEBI:CHEBI:29108"; /ligand_label="4"; BINDING 1475; /ligand="Ca(2+)"; /ligand_id="ChEBI:CHEBI:29108"; /ligand_label="4"; BINDING 1478; /ligand="Ca(2+)"; /ligand_id="ChEBI:CHEBI:29108"; /ligand_label="4"
Subellular location Cell membrane ; Single-pass type I membrane protein .; [Notch 1 intracellular domain]: Nucleus. Note=Following proteolytical processing NICD is translocated to the nucleus. Nuclear location may require MEGF10.
Tissues In fetal tissues most abundant in spleen, brain stem and lung. Also present in most adult tissues where it is found mainly in lymphoid tissues.
Structure Heterodimer of a C-terminal fragment N(TM) and an N-terminal fragment N(EC) which are probably linked by disulfide bonds. Interacts with DNER, DTX1, DTX2 and RBPJ/RBPSUH. Also interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH1 (PubMed:11101851, PubMed:12370315). The NOTCH1 intracellular domain interacts with SNW1; the interaction involves multimerized NOTCH1 NICD and is implicated in a formation of an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ (PubMed:10713164). The activated membrane-bound form interacts with AAK1 which promotes NOTCH1 stabilization. Forms a trimeric complex with FBXW7 and SGK1. Interacts with HIF1AN. HIF1AN negatively regulates the function of notch intracellular domain (NICD), accelerating myogenic differentiation (PubMed:17573339). Interacts (via NICD) with SNAI1 (via zinc fingers); the interaction induces SNAI1 degradation via MDM2-mediated ubiquitination and inhibits SNAI1-induced cell invasion. Interacts (via NICD) with MDM2A. Interacts (via NICD) with BCL6; the interaction decreases MAML1 recruitment by NOTCH1 NICD on target genes DNA and inhibits NOTCH1 transcractivation activity. Interacts with THBS4 (By similarity). Interacts (via the EGF-like repeat region) with CCN3 (via CTCK domain) (PubMed:12050162). Interacts (via EGF-like domains) with DLL4 (via N-terminal DSL and MNNL domains) (By similarity). Interacts with ZMIZ1. Interacts (via NICD domain) with MEGF10 (via the cytoplasmic domain). Interacts with DLL1 and JAG1 (By similarity). Interacts (via NICD domain) with PRAG1 (By similarity). Forms a complex with PRAG1, N1ICD and MAML1, in a MAML1-dependent manner (By similarity). Interacts (via transmembrane region) with PSEN1; the interaction is direct (PubMed:30598546). Interacts with ZFP64 (By similarity).
Post-translational modification 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). Following ligand binding, it is cleaved by ADAM17 to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT) (PubMed:24226769). Following endocytosis, this fragment is then cleaved by one of the catalytic subunits of gamma-secretase (PSEN1 or PSEN2), to release a Notch-derived peptide containing the intracellular domain (NICD) from the membrane (PubMed:30598546).; Phosphorylated.; O-glycosylated on the EGF-like domains (PubMed:24226769). O-glucosylated at Ser-435 by KDELC1 and KDELC2 (PubMed:30127001). Contains both O-linked fucose and O-linked glucose in the EGF-like domains 11, 12 and 13, which are interacting with the residues on DLL4 (By similarity). O-linked glycosylation by GALNT11 is involved in determination of left/right symmetry: glycosylation promotes activation of NOTCH1, possibly by promoting cleavage by ADAM17, modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO) (PubMed:24226769). MFNG-, RFNG- and LFNG-mediated modification of O-fucose residues at specific EGF-like domains results in inhibition of its activation by JAG1 and enhancement of its activation by DLL1 via an increased binding to DLL1 (By similarity).; Ubiquitinated. Undergoes 'Lys-29'-linked polyubiquitination by ITCH; promotes the lysosomal degradation of non-activated internalized NOTCH1 (PubMed:18628966, PubMed:23886940). Monoubiquitination at Lys-1759 is required for activation by gamma-secretase cleavage, it promotes interaction with AAK1, which stabilizes it. Deubiquitination by EIF3F is necessary for nuclear import of activated Notch (PubMed:24226769).; Hydroxylated at Asn-1955 by HIF1AN. Hydroxylated at Asn-2022 by HIF1AN (By similarity). Hydroxylation reduces affinity for HI1AN and may thus indirectly modulate negative regulation of NICD (By similarity).
Domain In
Target Relevance information above includes information from UniProt accession: P46531
The UniProt Consortium

Data

Human DLL4, hFc Tag captured on CM5 Chip via Protein A can bind Human Notch 1, His Tag with an affinity constant of 0.48 µM as determined in SPR assay (Biacore T200).

Immobilized Human Notch 1, His Tag at 1µg/ml (100µl/Well) on the plate. Dose response curve for Human DLL4, hFc Tag with the EC50 of 10.3ng/ml determined by ELISA (QC Test).

The purity of Human Notch 1 is greater than 95% as determined by SEC-HPLC.

Human Notch 1 on Tris-Bis PAGE under reduced conditions. The purity is greater than 95%.

Publications

Published literature highly relevant to the biological target of this product and referencing this antibody or clone are retrieved from PubMed database provided by The United States National Library of Medicine at the National Institutes of Health.