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Aliases for NOTCH2 Gene

Aliases for NOTCH2 Gene

  • Notch 2 2 3 4
  • HJCYS 3 6
  • AGS2 3 6
  • HN2 3 4
  • Neurogenic Locus Notch Homolog Protein 2 3
  • Notch (Drosophila) Homolog 2 2
  • Notch Homolog 2 (Drosophila) 2
  • Notch Homolog 2 3

External Ids for NOTCH2 Gene

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 alagille syndrome 2 and hajdu-cheney syndrome. Among its related pathways are Signaling by GPCR and ERK Signaling. GO annotations related to this gene include calcium ion binding and receptor activity. 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.

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

Genomic Location for NOTCH2 Gene

Start:
119,911,553 bp from pter
End:
120,100,748 bp from pter
Size:
189,196 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

Regulatory Elements 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.

    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).
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys1705
  • Glycosylation at Asn46, Asn155, Asn733, Asn1102, and Asn1465

Other Protein References for NOTCH2 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for NOTCH2 Gene

Domains for NOTCH2 Gene

Gene Families for NOTCH2 Gene

HGNC:
  • ANKRD :Ankyrin repeat domain containing

UniProtKB/Swiss-Prot:

NOTC2_HUMAN
Domain:
  • Contains 35 EGF-like domains.:
    • Q04721
Family:
  • Belongs to the NOTCH family.:
    • Q04721
Similarity:
  • Contains 6 ANK repeats.:
    • Q04721
  • Contains 3 LNR (Lin/Notch) repeats.:
    • Q04721
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.

LifeMap Function Summary for NOTCH2 Gene

During embryonic development, NOTCH2 as signaling molecule is secreted from the following cells
It affects 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 ligand-activated RNA polymerase II transcription factor binding transcription factor activity 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:

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting 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. Note=Following proteolytical processing NICD is translocated to the nucleus.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NOTCH2 Gene COMPARTMENTS Subcellular localization image for NOTCH2 gene
Compartment Confidence
nucleus 5
plasma membrane 5
endoplasmic reticulum 4
extracellular 4
golgi apparatus 4
cytoskeleton 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 for NOTCH2 Gene

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

Gene Ontology (GO) - Biological Process for NOTCH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription from RNA polymerase II promoter IEA --
GO:0001701 in utero embryonic development IEA --
GO:0001709 cell fate determination TAS 9244302
GO:0001890 placenta development --
GO:0002011 morphogenesis of an epithelial sheet IEA --
genes like me logo Genes that share ontologies with NOTCH2: view

Transcripts for NOTCH2 Gene

Unigene Clusters for NOTCH2 Gene

Notch 2:
Representative Sequences:

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

Integrated Proteomics: protein expression 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 expressions with NOTCH2: view

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
chimpanzee
(Pan troglodytes)
Mammalia NOTCH2 36
  • 99.76 (n)
  • 99.82 (a)
cow
(Bos Taurus)
Mammalia NOTCH2 36
  • 91 (n)
  • 94.98 (a)
NOTCH2 37
  • 95 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NOTCH2 36
  • 91.83 (n)
  • 95.31 (a)
NOTCH2 37
  • 95 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Notch2 36
  • 87.14 (n)
  • 92.59 (a)
Notch2 16
Notch2 37
  • 92 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NOTCH2 37
  • 87 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NOTCH2 37
  • 80 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Notch2 36
  • 86.84 (n)
  • 92.23 (a)
chicken
(Gallus gallus)
Aves NOTCH2 36
  • 74.1 (n)
  • 77.2 (a)
NOTCH2 37
  • 76 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100486344 36
  • 68.89 (n)
  • 70.41 (a)
zebrafish
(Danio rerio)
Actinopterygii notch2 36
  • 61.03 (n)
  • 58.99 (a)
notch2 37
  • 55 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta N 37
  • 42 (a)
OneToMany
N 38
  • 49 (a)
SP1070 38
  • 38 (a)
CG15388 38
  • 39 (a)
worm
(Caenorhabditis elegans)
Secernentea Y69H2.2 38
  • 28 (a)
F55G1.13 38
  • 29 (a)
R05G6.9 38
  • 26 (a)
lin-12 38
  • 25 (a)
Y69H2.11 38
  • 28 (a)
W02C12.1 38
  • 38 (a)
F55H12.3 38
  • 27 (a)
mup-4 38
  • 25 (a)
Y69H2.12 38
  • 30 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SWI6 39
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 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

Selected 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
rs327191 -- 119,997,853(-) gggat(C/T)acagg 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

Relevant External Links for NOTCH2 Gene

HapMap Linkage Disequilibrium report
NOTCH2
Human Gene Mutation Database (HGMD)
NOTCH2
Locus Specific Mutation Databases (LSDB)
NOTCH2

Disorders for NOTCH2 Gene

(2) OMIM Diseases for NOTCH2 Gene (600275)

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.

(3) University of Copenhagen DISEASES for NOTCH2 Gene

(6) Novoseek inferred disease relationships for NOTCH2 Gene

Disease -log(P) Hits PubMed IDs
alagille syndrome 78.1 5
lymphocytic leukemia chronic b-cell 33.9 1
cholestasis 28.5 1
tumors 13.6 11
cancer 0.41 2

Relevant External Links for NOTCH2

GeneTests
NOTCH2
GeneReviews
NOTCH2
Genetic Association Database (GAD)
NOTCH2
Human Genome Epidemiology (HuGE) Navigator
NOTCH2
genes like me logo Genes that share disorders with NOTCH2: view

Publications for NOTCH2 Gene

  1. Analysis of coding-polymorphisms in NOTCH-related genes reveals NUMBL poly-glutamine repeat to be associated with schizophrenia in Brazilian and Danish subjects. (PMID: 16899352) Passos Gregorio S. … Dias-Neto E. (Schizophr. Res. 2006) 3 23 49
  2. Regulation of CD23 expression by Notch2 in B-cell chronic lymphocytic leukemia. (PMID: 15621797) Schwarzmeier J.D. … Shehata M. (Leuk. Lymphoma 2005) 3 23
  3. Hairy-related transcription factors inhibit Notch-induced smooth muscle alpha-actin expression by interfering with Notch intracellular domain/CBF-1 complex interaction with the CBF-1-binding site. (PMID: 18239137) Tang Y. … Liaw L. (Circ. Res. 2008) 3 23
  4. A role for notch signaling in human corneal epithelial cell differentiation and proliferation. (PMID: 17652726) Ma A. … Albon J. (Invest. Ophthalmol. Vis. Sci. 2007) 3 23
  5. Notch2 signaling induces apoptosis and inhibits human MDA-MB-231 xenograft growth. (PMID: 17675579) O'Neill C.F. … Liaw L. (Am. J. Pathol. 2007) 3 23

Products for NOTCH2 Gene

Sources for NOTCH2 Gene

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