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Aliases for NOTCH2 Gene

Aliases for NOTCH2 Gene

  • Notch 2 2 3 4
  • HN2 3 4
  • Notch (Drosophila) Homolog 2 2
  • Notch Homolog 2 (Drosophila) 2
  • Notch Homolog 2 3
  • HJCYS 3
  • AGS2 3

External Ids for NOTCH2 Gene

Previous GeneCards Identifiers for NOTCH2 Gene

  • GC01M120900
  • GC01M119292
  • GC01M119601
  • GC01M119800
  • GC01M120100
  • GC01M120256
  • GC01M120454
  • GC01M118312

Summaries for NOTCH2 Gene

Entrez Gene Summary for NOTCH2 Gene

  • 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. [provided by RefSeq, Jan 2011]

GeneCards Summary for NOTCH2 Gene

NOTCH2 (Notch 2) is a Protein Coding gene. Diseases associated with NOTCH2 include notch2-related alagille syndrome and alagille syndrome 2. Among its related pathways are Signaling by GPCR and PAK Pathway. GO annotations related to this gene include calcium ion binding and transcription factor activity, ligand-activated RNA polymerase II transcription factor binding. An important paralog of this gene is JAG2.

UniProtKB/Swiss-Prot for NOTCH2 Gene

  • 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. Positively regulates self-renewal of liver cancer cells (PubMed:25985737).

Gene Wiki entry for NOTCH2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NOTCH2 Gene

Genomics for NOTCH2 Gene

Regulatory Elements for NOTCH2 Gene

Genomic Location for NOTCH2 Gene

Chromosome:
1
Start:
119,911,553 bp from pter
End:
120,069,703 bp from pter
Size:
158,151 bases
Orientation:
Minus strand

Genomic View for NOTCH2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for NOTCH2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NOTCH2 Gene

Proteins for NOTCH2 Gene

  • Protein details for NOTCH2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q04721-NOTC2_HUMAN
    Recommended name:
    Neurogenic locus notch homolog protein 2
    Protein Accession:
    Q04721
    Secondary Accessions:
    • Q5T3X7
    • Q99734
    • Q9H240

    Protein attributes for NOTCH2 Gene

    Size:
    2471 amino acids
    Molecular mass:
    265405 Da
    Quaternary structure:
    • Heterodimer of a C-terminal fragment N(TM) and an N-terminal fragment N(EC) which are probably linked by disulfide bonds (By similarity). Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH2. Interacts with RELA/p65 (By similarity). Interacts with HIF1AN. Interacts (via ANK repeats) with C8orf4, the interaction inhibits the nuclear translocation of NOTCH2 N2ICD (PubMed:25985737).

    Three dimensional structures from OCA and Proteopedia for NOTCH2 Gene

neXtProt entry for NOTCH2 Gene

Proteomics data for NOTCH2 Gene at MOPED

Post-translational modifications for NOTCH2 Gene

  • Can be either O-glucosylated or O-xylosylated at Ser-613 by POGLUT1.
  • Hydroxylated by HIF1AN.
  • 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).
  • Ubiquitination at Lys 1705
  • Glycosylation at Asn 46, Asn 155, Ser 613, Asn 733, Asn 1102, and Asn 1465
  • Modification sites at PhosphoSitePlus

Other Protein References for NOTCH2 Gene

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for NOTCH2 (Notch 2)

No data available for DME Specific Peptides for NOTCH2 Gene

Domains & Families for NOTCH2 Gene

Gene Families for NOTCH2 Gene

Suggested Antigen Peptide Sequences for NOTCH2 Gene

Graphical View of Domain Structure for InterPro Entry

Q04721

UniProtKB/Swiss-Prot:

NOTC2_HUMAN :
  • Contains 35 EGF-like domains.
  • Belongs to the NOTCH family.
  • Contains 6 ANK repeats.
Domain:
  • Contains 35 EGF-like domains.
Family:
  • Belongs to the NOTCH family.
Similarity:
  • Contains 6 ANK repeats.
  • Contains 3 LNR (Lin/Notch) repeats.
genes like me logo Genes that share domains with NOTCH2: view

Function for NOTCH2 Gene

Molecular function for NOTCH2 Gene

GENATLAS Biochemistry:
Drosophila Notch homolog 2,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 neoplasia associated translocations
UniProtKB/Swiss-Prot 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. Positively regulates self-renewal of liver cancer cells (PubMed:25985737).

LifeMap Function Summary for NOTCH2 Gene

During embryonic development, NOTCH2 as signaling molecule is secreted from the following cells

Gene Ontology (GO) - Molecular Function for NOTCH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004872 receptor activity NAS 9244302
GO:0005509 calcium ion binding IEA --
GO:0005515 protein binding IPI 10079256
GO:0038049 transcription factor activity, ligand-activated RNA polymerase II transcription factor binding TAS 9244302
genes like me logo Genes that share ontologies with NOTCH2: view
genes like me logo Genes that share phenotypes with NOTCH2: view

Animal Models for NOTCH2 Gene

MGI Knock Outs for NOTCH2:

Animal Model Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for NOTCH2

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for NOTCH2 Gene

Localization for NOTCH2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NOTCH2 Gene

Cell membrane; Single-pass type I membrane protein.
Notch 2 intracellular domain: Nucleus. Cytoplasm. Note=Following proteolytical processing NICD is translocated to the nucleus. Retained at the cytoplasm by C8orf4 (PubMed:25985737). {ECO:0000269 PubMed:25985737}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NOTCH2 Gene COMPARTMENTS Subcellular localization image for NOTCH2 gene
Compartment Confidence
nucleus 2
plasma membrane 2
cytoskeleton 1
extracellular 1

Gene Ontology (GO) - Cellular Components for NOTCH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane TAS --
GO:0005576 extracellular region TAS --
GO:0005634 nucleus IDA 1303260
GO:0005654 nucleoplasm TAS --
GO:0005789 endoplasmic reticulum membrane TAS --
genes like me logo Genes that share ontologies with NOTCH2: view

Pathways & Interactions for NOTCH2 Gene

genes like me logo Genes that share pathways with NOTCH2: view

PCR Array Products

SIGNOR curated interactions for NOTCH2 Gene

Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for NOTCH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001709 cell fate determination TAS 9244302
GO:0002315 marginal zone B cell differentiation ISS --
GO:0003184 pulmonary valve morphogenesis IMP 16773578
GO:0006355 regulation of transcription, DNA-templated TAS 9244302
GO:0006367 transcription initiation from RNA polymerase II promoter TAS --
genes like me logo Genes that share ontologies with NOTCH2: view

Drugs & Compounds for NOTCH2 Gene

(6) Drugs for NOTCH2 Gene - From: DGIdb and ApexBio

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
FLI-06 Pharma 0
MK0752 Pharma inhibitor, other Notch signaling pathway inhibitor, Other 0
OMP-59R5 Pharma 0
PF-03084014 Pharma other Other 0
REGN421 Pharma other, Inhibitor Other, Notch pathway inhibitors 0
genes like me logo Genes that share compounds with NOTCH2: view

Transcripts for NOTCH2 Gene

Unigene Clusters for NOTCH2 Gene

Notch 2:
Representative Sequences:

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for NOTCH2

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for NOTCH2 Gene

No ASD Table

Relevant External Links for NOTCH2 Gene

GeneLoc Exon Structure for
NOTCH2
ECgene alternative splicing isoforms for
NOTCH2

Expression for NOTCH2 Gene

mRNA expression in normal human tissues for NOTCH2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for NOTCH2 Gene

This gene is overexpressed in Adrenal (32.5) and Bone (8.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for NOTCH2 Gene



SOURCE GeneReport for Unigene cluster for NOTCH2 Gene Hs.487360

mRNA Expression by UniProt/SwissProt for NOTCH2 Gene

Q04721-NOTC2_HUMAN
Tissue specificity: Expressed in the brain, heart, kidney, lung, skeletal muscle and liver. Ubiquitously expressed in the embryo.
genes like me logo Genes that share expression patterns with NOTCH2: view

Protein tissue co-expression partners for NOTCH2 Gene

Primer Products

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for NOTCH2 Gene

Orthologs for NOTCH2 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for NOTCH2 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia NOTCH2 35
  • 91 (n)
  • 94.98 (a)
NOTCH2 36
  • 95 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NOTCH2 35
  • 91.83 (n)
  • 95.31 (a)
NOTCH2 36
  • 95 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Notch2 35
  • 87.14 (n)
  • 92.59 (a)
Notch2 16
Notch2 36
  • 92 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia NOTCH2 35
  • 99.76 (n)
  • 99.82 (a)
rat
(Rattus norvegicus)
Mammalia Notch2 35
  • 86.84 (n)
  • 92.23 (a)
oppossum
(Monodelphis domestica)
Mammalia NOTCH2 36
  • 87 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NOTCH2 36
  • 80 (a)
OneToOne
chicken
(Gallus gallus)
Aves NOTCH2 35
  • 74.1 (n)
  • 77.2 (a)
NOTCH2 36
  • 76 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100486344 35
  • 68.89 (n)
  • 70.41 (a)
zebrafish
(Danio rerio)
Actinopterygii notch2 35
  • 61.03 (n)
  • 58.99 (a)
notch2 36
  • 55 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG15388 37
  • 39 (a)
N 37
  • 49 (a)
SP1070 37
  • 38 (a)
N 36
  • 42 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea F55G1.13 37
  • 29 (a)
F55H12.3 37
  • 27 (a)
lin-12 37
  • 25 (a)
mup-4 37
  • 25 (a)
R05G6.9 37
  • 26 (a)
W02C12.1 37
  • 38 (a)
Y69H2.11 37
  • 28 (a)
Y69H2.12 37
  • 30 (a)
Y69H2.2 37
  • 28 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SWI6 38
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 41 (a)
OneToOne
Species with no ortholog for NOTCH2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for NOTCH2 Gene

ENSEMBL:
Gene Tree for NOTCH2 (if available)
TreeFam:
Gene Tree for NOTCH2 (if available)

Paralogs for NOTCH2 Gene

Paralogs for NOTCH2 Gene

(15) SIMAP similar genes for NOTCH2 Gene using alignment to 4 proteins:

Pseudogenes.org Pseudogenes for NOTCH2 Gene

genes like me logo Genes that share paralogs with NOTCH2: view

Variants for NOTCH2 Gene

Sequence variations from dbSNP and Humsavar for NOTCH2 Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type MAF
rs191275 -- 120,020,786(-) TTAGA(A/C/G)TATTA intron-variant
rs327187 -- 120,000,490(-) AGGGC(A/G)CAATC intron-variant
rs327189 -- 120,000,161(-) ATAGC(A/G)CTATA intron-variant
rs327190 -- 119,999,873(-) TGTCT(G/T)TCTTT intron-variant
rs327192 -- 119,991,942(-) GGAAG(G/T)TGTGT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for NOTCH2 Gene

Variant ID Type Subtype PubMed ID
nsv524681 CNV Gain 19592680
dgv93e1 CNV Complex 17122850
nsv428201 CNV Gain 18775914
dgv94e1 CNV Complex 17122850
nsv831226 CNV Gain+Loss 17160897
nsv436325 CNV Deletion 17901297
nsv2610 CNV Loss 18451855
dgv95e1 CNV Complex 17122850
dgv96e1 CNV Complex 17122850
dgv97e1 CNV Complex 17122850
nsv820378 CNV Duplication 20802225
esv22009 CNV Gain+Loss 19812545
nsv824331 CNV Gain 20364138
nsv10683 CNV Gain 18304495
dgv98e1 CNV Complex 17122850
nsv514912 CNV Complex 21397061
nsv872181 CNV Gain 21882294

Variation tolerance for NOTCH2 Gene

Residual Variation Intolerance Score: 1.87% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.41; 63.75% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for NOTCH2 Gene

HapMap Linkage Disequilibrium report
NOTCH2
Human Gene Mutation Database (HGMD)
NOTCH2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NOTCH2 Gene

Disorders for NOTCH2 Gene

MalaCards: The human disease database

(10) MalaCards diseases for NOTCH2 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, NovoSeek, and GeneCards

Disorder Aliases PubMed IDs
notch2-related alagille syndrome
  • alagille syndrome 2
alagille syndrome 2
  • alagille-watson syndrome
hajdu-cheney syndrome
  • acroosteolysis dominant type
alagille syndrome due to a notch2 point mutation
  • alagille-watson syndrome due to a notch2 point mutation
alagille syndrome
  • alagille-watson syndrome
- elite association

UniProtKB/Swiss-Prot

NOTC2_HUMAN
  • 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:0000269 PubMed: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:0000269 PubMed:21378985, ECO:0000269 PubMed: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.

Relevant External Links for NOTCH2

Genetic Association Database (GAD)
NOTCH2
Human Genome Epidemiology (HuGE) Navigator
NOTCH2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
NOTCH2
genes like me logo Genes that share disorders with NOTCH2: view

No data available for Genatlas for NOTCH2 Gene

Publications for NOTCH2 Gene

  1. Expression profile of Notch-related genes in multidrug resistant K562/A02 cells compared with parental K562 cells. (PMID: 19302234) Yan S. … Ji C. (Int J Lab Hematol 2010) 23 67
  2. Therapeutic antibody targeting of individual Notch receptors. (PMID: 20393564) Wu Y. … Siebel C.W. (Nature 2010) 23 67
  3. Jagged-Notch signaling ensures dorsal skeletal identity in the vertebrate face. (PMID: 20431122) Zuniga E. … Crump J.G. (Development 2010) 23 67
  4. NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. (PMID: 19904829) Fan X. … Eberhart C.G. (Stem Cells 2010) 23 67
  5. The contribution of Notch1 to nephron segmentation in the developing kidney is revealed in a sensitized Notch2 background and can be augmented by reducing Mint dosage. (PMID: 19914235) Surendran K. … Kopan R. (Dev. Biol. 2010) 23 67

Products for NOTCH2 Gene

Sources for NOTCH2 Gene

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