NOTCH3 Gene
protein-coding GIFtS : 69 GCID: GC19 M015270
notch 3 Notch (Drosophila) homolog 3, Notch homolog 3 (Drosophila)... CADASIL )
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Aliasesfor NOTCH3 gene
(According to
1 HGNC ,
2 Entrez Gene ,
3 UniProtKB/Swiss-Prot ,
4 UniProtKB/TrEMBL , 5 OMIM , 6 GeneLoc ,
7 Ensembl ,
8 DME ,
9 miRBase ,
and/or 10 fRNAdb )About This Section Aliases Notch 3 1 2 3 Notch Homolog 3 (Drosophila)1 CADASIL1 2 5 Neurogenic Locus Notch Homolog Protein 32 CASIL1 2 5 Notch Homolog 32 Notch (Drosophila) Homolog 31
Export aliases for NOTCH3 gene to outside databases Previous GC identifers: GC19M015649 GC19M015115 GC19M015131 GC19M014839
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Summariesfor NOTCH3 gene (According to Entrez Gene ,
Tocris Bioscience ,
Wikipedia's
Gene Wiki ,
PharmGKB ,UniProtKB/Swiss-Prot ,
and/or
UniProtKB/TrEMBL )
About This Section Entrez Gene summary for NOTCH3 : This gene encodes the third discovered human homologue of the Drosophilia melanogaster type I membrane protein notch. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway that plays a key role in neural development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remains to be determined. Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). (provided by RefSeq, Jul 2008) UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47 Function : Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fatedetermination. 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) Gene Wiki entry for NOTCH3 (Notch 3)
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Genomic Viewsfor NOTCH3 gene
(According to
GeneLoc and/or
HGNC , and/or
Entrez Gene (NCBI build 37) ,miRBase ,UCSC (hg19) and
Ensembl (release 69) ,
Regulatory elements and Epigenetics data according to
QIAGEN ,
SABiosciences , and/or
SwitchGear Genomics )About This Section RefSeq DNA sequence: NC_000019.9 NC_018930.1 NT_011295.11 Regulatory elements: SABiosciences Regulatory transcription factor binding sites in the NOTCH3 gene promoter:AP-2gamma GATA-2 C/EBPalpha CHOP-10 Pax-3 COMP1 STAT3 AP-2beta AP-2alpha AP-2alphaA Other transcription factors Search SABiosciences Chromatin IP Primers for NOTCH3 Epigenetics: QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human mouse rat
Genomic Location: Genomic View : UCSC Golden Path with GeneCards custom track Entrez Gene cytogenetic band: 19p13.2-p13.1 Ensembl cytogenetic band: 19p13.12 HGNC cytogenetic band: 19p13.2-p13.1 NOTCH3 Gene in genomic location: bands according to Ensembl, locations according to
Entrez Gene Ensembl GeneLoc information about chromosome 19 GeneLoc Exon Structure
GeneLoc location for GC19M015270: view genomic region
(about GC identifiers )
Start: 15,270,444 bp from pter End:
15,311,792 bp from pter
Size: 41,349 bases Orientation:
minus strand
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Proteinsfor NOTCH3 gene
(According to
1 UniProtKB ,
HORDE ,
neXtProt ,
Ensembl ,
and/or Reactome ,
Modification sites according to 2 PhosphoSitePlus ,
Specific Peptides from DME ,
Protein expression images according to data from SPIRE MOPED and PaxDb ,
RefSeq according to NCBI ,
PDB rendering according to OCA and/or Proteopedia ,
Recombinant Proteins
from
EMD Millipore ,
R&D Systems ,
GenScript ,
Enzo Life Sciences ,
OriGene ,
Novus Biologicals ,
Sino Biological ,
ProSpec , and/or
Uscn ,
EMD Millipore ,
R&D Systems ,
OriGene ,
GenScript ,
Cell Signaling Technology ,
Enzo Life Sciences , and/or
Uscn ,
Ontologies according to Gene
Ontology Consortium 01 Mar 2013 and
Entrez Gene ,
Antibodies by
EMD Millipore ,
R&D Systems ,
GenScript ,
Cell Signaling Technology ,
OriGene ,
Novus Biologicals ,
Thermo Fisher Scientific ,
Abcam , and/or
Uscn )
About This Section UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47 See
protein sequence )Recommended Name: Size : 2321 amino acids; 243631 DaSubunit : Heterodimer of a C-terminal fragment N(TM) and a N-terminal fragment N(EC) which are probably linked bydisulfide bonds (By similarity). Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH3. Interacts with PSMA1. Interacts with HIF1AN
Subcellular location : Cell membrane; Single-pass type I membrane proteinSubcellular location : Notch 3 intracellular domain: Nucleus. Note=Following proteolytical processing NICD istranslocated to the nucleus
Secondary accessions : Q9UEB3 Q9UPL3 Q9Y6L8Explore the universe of human proteins at neXtProt for NOTCH3: NX_Q9UM47 Post-translational modifications:
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. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). 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)1
Phosphorylated (By similarity)1 Hydroxylated by HIF1AN1 View modification sites using PhosphoSitePlus 2 View neXtProt modification sites for NX_Q9UM47 NOTCH3 Protein expression data from MOPED and PaxDb : About this image REFSEQ proteins: NP_000426.2 ENSEMBL proteins: ENSP00000263388 Reactome Protein details: Q9UM47 Human Recombinant Protein Products: Gene Ontology (GO): 5/7 cellular component terms (GO ID links to tree view) (see all 7 ): About this table
About GeneDecksing NOTCH3 Antibody Products: Assay Products for NOTCH3:
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Protein
Domains /for NOTCH3 gene (According to InterPro , ProtoNet ,
UniProtKB , and/or BLOCKS ,
Sets of similar genes according to GeneDecks )
About This Section About GeneDecksing 5/13 InterPro domains/families (see all 13 ):
Graphical View of Domain Structure for InterPro Entry Q9UM47 ProtoNet protein and cluster: Q9UM47
5 Blocks protein families : IPB000152 IPB000800 IPB001881 IPB002049 IPB002110 UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47 Similarity : Belongs to the NOTCH familySimilarity : Contains 5 ANK repeatsSimilarity : Contains 34 EGF-like domainsSimilarity : Contains 3 LNR (Lin/Notch) repeats
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Functionfor NOTCH3 gene
(According to 1 UniProtKB ,
Genatlas ,
LifeMap Discovery™ ,
IUBMB , and/or
2 DME ,
Human phenotypes from GenomeRNAi ,
Animal models from MGI Mar 06 2013,
SABiosciences ,
miRNA Gene Targets from miRTarBase
shRNA from
OriGene ,
RNAi from
EMD Millipore ,
siRNAs from
OriGene ,
QIAGEN ,
microRNA from QIAGEN ,
Gene Editing from DNA2.0 ,
Clones from EMD Millipore ,
OriGene ,
SwitchGear Genomics ,
GenScript ,
Sino Biological ,
DNA2.0 ,
and Vector BioLabs ,
Cell Lines from GenScript ,
LifeMap BioReagents ,
In Situ Hybridization Assays from Advanced Cell Diagnostics ,
Ontologies according to Gene Ontology Consortium 01 Mar 2013 via
Entrez Gene .)
About This Section Function Summary: UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47 Function : Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fatedetermination. 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)
Genatlas biochemistry entry for NOTCH3 Drosophila Notch homolog 3,mediating cell-cell interactions that specify cell fate during development,undergoing a first proteolytic cleavage by furin (PACE1) in the Golgi during trafficking of Notch to the cell surface,undergoing further cleavage by gamma secretase (see PSEN1) releasing an intracellular domain (NICD) which translocates to the nucleus and modulates transcription of target genes,putatively involved in translocation with acute lymphoblastic/myeloblastic leukemia and in the decision between the endocrine and exocrine fates in the developing pancreas Clone Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human mouse rat see all 3 )human mouse rat OriGene custom cloning services – gene synthesis, subcloning, mutagenesis,
variant library, vector shuttling GenScript: all cDNA clones in your preferred vector: NOTCH3 (NM_000435 ) Browse Sino Biological Human cDNA Clones DNA2.0 Custom Codon Optimized Gene
Synthesis Service for NOTCH3 Search Vector BioLabs for ready-to-use adenovirus/AAV for human, mouse, rat NOTCH3
In Situ AssayAdvanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOTCH3
Gene Ontology (GO): 4 molecular function terms (GO ID links to tree view) : About this table
About GeneDecksing Animal Models: Notch3 tm1Khan Notch3 tm1Grid 15/20 MGI mutant phenotypes (inferred from 7 alleles(MGI details for Notch3) (see all 20 ):About GeneDecksing
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Pathways & Interactionsfor NOTCH3 gene
(Pathways according to
EMD Millipore ,
R&D Systems ,
Cell Signaling Technology ,
KEGG ,
PharmGKB ,
BioSystems ,
Reactome ,
Tocris Bioscience ,
GeneGo (Thomson Reuters) ,
QIAGEN ,
and/or UniProtKB ,
Sets of similar genes according to GeneDecks ,
Interaction Networks according to
SABiosciences ,
and/or STRING ,
Interactions according to 1 UniProtKB ,
2 MINT ,
3 I2D , and/or
4 STRING ,
with links to IntAct and
Ensembl ,
Ontologies according to Gene Ontology Consortium 01 Mar 2013 via
Entrez Gene) .
About This Section Unified GeneCards pathways - 5/19 super-pathways (see all 19 ) About this table See pathways by source Super-pathway contained gene-specific pathways 1 Mature NOTCH heterodimer traffics to the plasma membrane 2 Notch Signaling Pathway 3 Generic Transcription Pathway 4 Pre-NOTCH Processing in Golgi 5 Signaling by NOTCH1 t(7 9)(NOTCH1:M1580_K2555) Translocation Mutant
Pathway sources See GeneCards unified pathways Show all pathways 4 3 4 5/17 (see all 17 )2 (Kegg details for NOTCH3) :About GeneDecksing Interactions: SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for NOTCH3 STRING Interaction
Network Preview (showing 5 interactants - click image to see 25)5/55 Interacting proteins for NOTCH3 (Q9UM47 1 , 2 , 3 ENSP00000263388 4 via UniProtKB, MINT, STRING , and/or I2D (see all 55 )About this table Gene Ontology (GO): 5/12 biological process terms (GO ID links to tree view) (see all 12 ): About this table
GO ID Qualified GO term Evidence PubMed IDs GO:0006355 regulation of transcription, DNA-dependent
IEA -- GO:0006367 transcription initiation from RNA polymerase II promoter
TAS -- GO:0007219 Notch signaling pathway
TAS -- GO:0007220 Notch receptor processing
TAS -- GO:0010467 gene expression
TAS --
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Drugs & Compoundsfor NOTCH3 gene (Chemical Compounds according to UniProtKB , Enzo Life Sciences ,
EMD Millipore , Tocris Bioscience
HMDB ,
BitterDB , and/or
Novoseek , and Drugs according to
DrugBank ,
Enzo Life Sciences , and/or
PharmGKB , with drugs/clinical trials/news
search links to CenterWatch )
About This Section About GeneDecksing Browse Tocris compounds for NOTCH3 3 Novoseek chemical compound relationships for NOTCH3 gene About this table NOTCH3 / NOTC3
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Transcriptsfor NOTCH3 gene (Secondary structures according to
fRNAdb ,Unigene
(Build 235 Homo sapiens; Mar 10 2013) or GenBank , Entrez Gene ,
DOTS (version 10), and/or
AceView ,
transcript ids from Ensembl
with links to UCSC , GeneLoc ,
alternative splicing isoforms according to ASD and/or
ECgene ,EMD Millipore ,
OriGene ,
QIAGEN ,
shRNA from
OriGene ,
microRNA from QIAGEN ,
OriGene ,
SwitchGear Genomics ,
GenScript ,
DNA2.0 ,
Vector BioLabs ,
Primers from
OriGene ,
SABiosciences , and/or
QIAGEN
)About This Section REFSEQ mRNAs for NOTCH3 gene: NM_000435.2 Unigene Cluster for NOTCH3:
Notch 3 Hs.8546 [show with all ESTs ] Unigene Representative Sequence: U97669 1 Ensembl transcript including schematic representation, and UCSC links where relevant : ENST00000263388 (uc002nan.3 uc002nao.1 ) Clone OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human mouse rat see all 3 )human mouse rat OriGene custom cloning services – gene synthesis, subcloning, mutagenesis,
variant library, vector shuttling GenScript: all cDNA clones in your preferred vector: NOTCH3 (NM_000435 ) DNA2.0 Custom Codon Optimized Gene
Synthesis Service for NOTCH3 Search Vector BioLabs for ready-to-use adenovirus/AAV for human, mouse, rat NOTCH3
Additional cDNA sequence: AB209447.1 U97669.1
5 DOTS entries : DT.217396 DT.91963540
DT.100815125 DT.75121130 DT.91646701 24/277 AceView cDNA sequences (see all 277 ):
AI274902 BM021193 BM841037 CA446395 CN483616 BU956081 BU553672 AI473478 BU556839 BU846477 CB270591 AI559175 AI091531 BI523794 T63511 AA301460 BM021466 BU859204 BI052410 AW194070 BQ919557 CR611252 BF435534 AI969777 GeneLoc Exon Structure 3 Alternative Splicing Database (ASD) splice patterns (SP) for NOTCH3 About this scheme ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20a · 20b ^ 21 ^ 22 ^ 23a · 23b ^ 24 ^ SP1 : - SP2 : - - SP3 :
ExUns: 25 ^ 26 ^ 27 ^ 28 ^ 29 ^ 30 ^ 31 ^ 32 SP1 : SP2 : SP3 :
ECgene alternative splicing isoforms for NOTCH3
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Expression for NOTCH3 gene
(RNA expression data according to
H-InvDB ,
NONCODE ,
miRBase , and
RNAdb ,
Expression images according to data from
BioGPS ,
Illumina Human BodyMap , and
CGAP
SAGE ,
Sets of similar genes according to GeneDecks ,
in vivo and in vitro expression data from LifeMap Discovery™ ,
plus additional links to
Genevestigator , and/or
SOURCE , and/or
BioGPS , and/or
UniProtKB ,SABiosciences ,
Primers from
OriGene ,
SABiosciences , and/or
QIAGEN ,
In Situ Hybridization Assays from Advanced Cell Diagnostics )
About This Section NOTCH3 expression in normal human tissues (normalized intensities) See probesets specificity/sensitivity at GeneAnnot About this image BioGPS CGAP TAG: GCAGAATAGA
About this image NOTCH3 expression in embryonic tissues and stem cells About this table See NOTCH3 Protein Expression from SPIRE MOPED and PaxDB Genevestigator expression for NOTCH3 SOURCE GeneReport for Unigene cluster: Hs.8546 UniProtKB/Swiss-Prot: NOTC3_HUMAN, Q9UM47 Tissue specificity : Ubiquitously expressed in fetal and adult tissuesSABiosciences Expression via Pathway-Focused PCR Arrays including NOTCH3 : Primer OriGene genome-wide validated SYBR primer pairs in human mouse rat Browse OriGene validated miRNA SYBR primer pairs SABiosciences RT2 qPCR Primer Assay in human mouse rat QIAGEN QuantiTect SYBR Green Assays in human mouse rat QIAGEN QuantiFast Probe-based Assays in human mouse rat In Situ Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOTCH3
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Orthologsfor NOTCH3 gene
(Orthologs according to
1,2 HomoloGene (2 older version, for species not in 1 newer version),
3 euGenes ,
4 SGD
,
5 MGI Mar 06 2013,
with possible further links to
Flybase
and/or
WormBase ,
and/or
6 Ensembl pan taxonomic compara ,
Gene Trees according to Ensembl and
TreeFam )
About This Section Orthologs for NOTCH3 gene from 5/19 species (see all 19 ) About this table
Organism
Taxonomic
Gene
Description
Human
Orthology
Details
lizard Reptilia NOTCH36
--
61(a)
1 ↔ 1
2(103176143-103207872)
tropical clawed frog Amphibia 1420334872
--
76.95(n)
142033487
zebrafish Actinopterygii AF152001.12
--
75.66(n)
58066 AF152001.1
fruit fly Insecta SP10703
Notch binding
38(a)
27D2 --
worm Secernentea W02C12.13
EGF-like protein
37(a)
IV(4008218-4014159) --
ENSEMBL Gene Tree for NOTCH3 (if available)TreeFam Gene Tree for NOTCH3 (if available)
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Paralogsfor NOTCH3 gene (Paralogs according to
1 HomoloGene ,2 Ensembl , and 3 SIMAP , Pseudogenes according to 4 Pseudogene.org Build 68)About This Section Paralogs for NOTCH3 gene NOTCH4 2 SNED1 2 NOTCH1 2 DLL3 2 DLL4 2 JAG2 2 CRB2 2 NOTCH2 2 JAG1 2 DNER 2 CRB1 2 DLL1 2 18 SIMAP similar genes for NOTCH3 using alignment to 5 protein entries: NOTC3_HUMAN (see all proteins ):SLIT2 ACAN F9 p22 factor IX F9 NOTCH2 CRB1 SVEP1 SLIT3 F9 SNED1 FBLN7 DLK2 NOTCH1 VCAN JAG1 EYS CUBN NCAN About GeneDecksing
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Genomic Variantsfor NOTCH3 gene (SNPs/Variants according to the
1 NCBI SNP Database ,
2 Ensembl ,
3 PupaSUITE ,
UniProtKB , and
DNA2.0 ,
Linkage Disequilibrium by HapMap ,
Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants , Mutations from the Human Gene
Mutation Database (HGMD) and the Locus Specific Mutation
Databases (LSDB) , Blood group antigen gene mutations by BGMUT ,
Resequencing Primers from QIAGEN ,
Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences )
About This Section Genomic Data Transcription Related Data Allele Frequencies SNP ID Valid Clinical Chr 19 pos Sequence # AA Type More # Allele Pop Total More
Browse Tocris compounds for 
Expression by the Database of Embryonic development, Stem cell research, and
Regenerative medicine 
Anatomical Compartment 
Negative
Selective marker
Microarrays
In-situ hybridization