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Aliases for NOTCH4 Gene

Aliases for NOTCH4 Gene

  • Notch 4 2 3 4
  • INT3 3 4 6
  • Neurogenic Locus Notch Homolog Protein 4 3
  • Notch (Drosophila) Homolog 4 2
  • Notch Homolog 4 (Drosophila) 2
  • Notch Homolog 4 3
  • HNotch4 4

External Ids for NOTCH4 Gene

Previous HGNC Symbols for NOTCH4 Gene

  • INT3

Previous GeneCards Identifiers for NOTCH4 Gene

  • GC06M032185
  • GC06M031933
  • GC06M032234
  • GC06M032231
  • GC06M032270
  • GC06M032166

Summaries for NOTCH4 Gene

Entrez Gene Summary for NOTCH4 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. This gene may be associated with susceptibility to schizophrenia in a small portion of cases. An alternative splice variant has been described but its biological nature has not been determined. [provided by RefSeq, Jul 2008]

GeneCards Summary for NOTCH4 Gene

NOTCH4 (Notch 4) is a Protein Coding gene. Diseases associated with NOTCH4 include pseudobulbar palsy and schizophrenia. 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 NOTCH2.

UniProtKB/Swiss-Prot for NOTCH4 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. May regulate branching morphogenesis in the developing vascular system (By similarity).

Gene Wiki entry for NOTCH4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NOTCH4 Gene

Genomics for NOTCH4 Gene

Regulatory Elements for NOTCH4 Gene

Genomic Location for NOTCH4 Gene

Start:
32,194,843 bp from pter
End:
32,224,067 bp from pter
Size:
29,225 bases
Orientation:
Minus strand

Genomic View for NOTCH4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for NOTCH4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

Proteins for NOTCH4 Gene

  • Protein details for NOTCH4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99466-NOTC4_HUMAN
    Recommended name:
    Neurogenic locus notch homolog protein 4
    Protein Accession:
    Q99466
    Secondary Accessions:
    • B0V183
    • B0V1X5
    • O00306
    • Q5SSY7
    • Q99458
    • Q99940
    • Q9H3S8
    • Q9UII9
    • Q9UIJ0

    Protein attributes for NOTCH4 Gene

    Size:
    2003 amino acids
    Molecular mass:
    209622 Da
    Quaternary structure:
    • Heterodimer of a C-terminal fragment N(TM) and a 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 NOTCH4.
    SequenceCaution:
    • Sequence=BAA09708.1; Type=Frameshift; Positions=1438, 1463; Evidence={ECO:0000305};

    Alternative splice isoforms for NOTCH4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NOTCH4 Gene

Proteomics data for NOTCH4 Gene at MOPED

Post-translational modifications for NOTCH4 Gene

  • Phosphorylated.
  • 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).
  • Glycosylation at Asn664, Asn714, Asn964, and Asn1143
  • Modification sites at PhosphoSitePlus

Other Protein References for NOTCH4 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for NOTCH4 Gene

Domains for NOTCH4 Gene

Gene Families for NOTCH4 Gene

HGNC:
  • ANKRD :Ankyrin repeat domain containing

Graphical View of Domain Structure for InterPro Entry

Q99466

UniProtKB/Swiss-Prot:

NOTC4_HUMAN :
  • Q99466
Domain:
  • Contains 29 EGF-like domains.
Family:
  • Belongs to the NOTCH family.
Similarity:
  • Contains 5 ANK repeats.
  • Contains 3 LNR (Lin/Notch) repeats.
genes like me logo Genes that share domains with NOTCH4: view

Function for NOTCH4 Gene

Molecular function for NOTCH4 Gene

GENATLAS Biochemistry: Drosophila Notch homolog 4,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,homologous to MMTV integration site int-3,containing a (CTG)n repeats polymorphism,with 2 isoforms L and S
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. May regulate branching morphogenesis in the developing vascular system (By similarity).

Gene Ontology (GO) - Molecular Function for NOTCH4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004872 receptor activity TAS 11823422
GO:0005509 calcium ion binding TAS 11823422
GO:0005515 protein binding IPI 11101851
GO:0046982 protein heterodimerization activity TAS 8681805
genes like me logo Genes that share ontologies with NOTCH4: view
genes like me logo Genes that share phenotypes with NOTCH4: view

Animal Models for NOTCH4 Gene

MGI Knock Outs for NOTCH4:

miRNA for NOTCH4 Gene

miRTarBase miRNAs that target NOTCH4

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for NOTCH4 Gene

Localization for NOTCH4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NOTCH4 Gene

Cell membrane; Single-pass type I membrane protein.
Notch 4 intracellular domain: Nucleus. Note=Following proteolytical processing NICD is translocated to the nucleus.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NOTCH4 Gene COMPARTMENTS Subcellular localization image for NOTCH4 gene
Compartment Confidence
nucleus 5
plasma membrane 5
cytosol 4
endoplasmic reticulum 4
extracellular 4
golgi apparatus 4
cytoskeleton 1
lysosome 1
mitochondrion 1

Gene Ontology (GO) - Cellular Components for NOTCH4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane TAS --
GO:0005576 extracellular region TAS --
GO:0005634 nucleus TAS 8681805
GO:0005654 nucleoplasm TAS --
GO:0005789 endoplasmic reticulum membrane TAS --
genes like me logo Genes that share ontologies with NOTCH4: view

Pathways for NOTCH4 Gene

genes like me logo Genes that share pathways with NOTCH4: view

Gene Ontology (GO) - Biological Process for NOTCH4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001569 patterning of blood vessels ISS --
GO:0001709 cell fate determination TAS 11823422
GO:0001763 morphogenesis of a branching structure ISS --
GO:0001886 endothelial cell morphogenesis IEA --
GO:0006367 transcription initiation from RNA polymerase II promoter TAS --
genes like me logo Genes that share ontologies with NOTCH4: view

Compounds for NOTCH4 Gene

(2) Novoseek inferred chemical compound relationships for NOTCH4 Gene

Compound -log(P) Hits PubMed IDs
snp 2 74.2 3
vegf 29.9 5
genes like me logo Genes that share compounds with NOTCH4: view

Transcripts for NOTCH4 Gene

Unigene Clusters for NOTCH4 Gene

Notch 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for NOTCH4 Gene

No ASD Table

Relevant External Links for NOTCH4 Gene

GeneLoc Exon Structure for
NOTCH4
ECgene alternative splicing isoforms for
NOTCH4

Expression for NOTCH4 Gene

mRNA expression in normal human tissues for NOTCH4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NOTCH4 Gene

This gene is overexpressed in Adipose - Visceral (Omentum) (4.6).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for NOTCH4 Gene

SOURCE GeneReport for Unigene cluster for NOTCH4 Gene Hs.436100

mRNA Expression by UniProt/SwissProt for NOTCH4 Gene

Q99466-NOTC4_HUMAN
Tissue specificity: Highly expressed in the heart, moderately in the lung and placenta and at low levels in the liver, skeletal muscle, kidney, pancreas, spleen, lymph node, thymus, bone marrow and fetal liver. No expression was seen in adult brain or peripheral blood leukocytes
genes like me logo Genes that share expressions with NOTCH4: view

Orthologs for NOTCH4 Gene

This gene was present in the common ancestor of animals.

Orthologs for NOTCH4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NOTCH4 35
  • 99.42 (n)
  • 99.4 (a)
NOTCH4 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia NOTCH4 35
  • 86.89 (n)
  • 86.38 (a)
NOTCH4 36
  • 86 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NOTCH4 35
  • 87.09 (n)
  • 86.42 (a)
NOTCH4 36
  • 86 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Notch4 35
  • 83.21 (n)
  • 82.4 (a)
Notch4 16
Notch4 36
  • 82 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NOTCH4 36
  • 71 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 27 (a)
ManyToMany
rat
(Rattus norvegicus)
Mammalia Notch4 35
  • 82.37 (n)
  • 80.98 (a)
lizard
(Anolis carolinensis)
Reptilia NOTCH4 36
  • 38 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta N 36
  • 28 (a)
OneToMany
SP1070 37
  • 37 (a)
CG15388 37
  • 39 (a)
worm
(Caenorhabditis elegans)
Secernentea F55G1.13 37
  • 27 (a)
R05G6.9 37
  • 28 (a)
Y69H2.11 37
  • 26 (a)
W02C12.1 37
  • 33 (a)
Y69H2.12 37
  • 29 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 30 (a)
ManyToMany
-- 36
  • 33 (a)
ManyToMany
-- 36
  • 30 (a)
ManyToMany
CSA.131 36
  • 26 (a)
ManyToMany
CSA.3605 36
  • 27 (a)
ManyToMany
Species with no ortholog for NOTCH4:
  • 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)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • 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)
  • 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)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • zebrafish (Danio rerio)

Evolution for NOTCH4 Gene

ENSEMBL:
Gene Tree for NOTCH4 (if available)
TreeFam:
Gene Tree for NOTCH4 (if available)

Paralogs for NOTCH4 Gene

Paralogs for NOTCH4 Gene

Selected SIMAP similar genes for NOTCH4 Gene using alignment to 4 proteins:

genes like me logo Genes that share paralogs with NOTCH4: view

Variants for NOTCH4 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for NOTCH4 Gene

Q99466-NOTC4_HUMAN
The poly-Leu region of NOTCH4 (in the signal peptide) is polymorphic and the number of Leu varies in the population (from 6 to 12)

Sequence variations from dbSNP and Humsavar for NOTCH4 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type MAF
rs45855 -- 32,221,704(-) TGAGG(A/T)TCAGA intron-variant
rs204987 -- 32,201,155(-) CAAAC(A/G)CAGCC synonymous-codon, reference
rs204988 -- 32,199,476(-) ccacc(C/T)gcctc intron-variant
rs206014 -- 32,215,924(-) tgagc(C/T)gagat intron-variant
rs206015 -- 32,214,982(-) GAGCA(C/T)TAAAT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for NOTCH4 Gene

Variant ID Type Subtype PubMed ID
dgv1929e1 CNV Complex 17122850
nsv830629 CNV Loss 17160897
nsv462877 CNV Loss 19166990
dgv6643n71 CNV Loss 21882294
dgv6644n71 CNV Loss 21882294
dgv6645n71 CNV Loss 21882294
nsv884712 CNV Loss 21882294
nsv884715 CNV Loss 21882294
nsv10826 CNV Loss 18304495
esv2677748 CNV Deletion 23128226

Relevant External Links for NOTCH4 Gene

HapMap Linkage Disequilibrium report
NOTCH4
Human Gene Mutation Database (HGMD)
NOTCH4

Disorders for NOTCH4 Gene

MalaCards: The human disease database

MalaCards: The human disease database. (2) Diseases for NOTCH4 Gene including...

Search for NOTCH4 Gene in MalaCards »

(5) University of Copenhagen DISEASES for NOTCH4 Gene

(14) Novoseek inferred disease relationships for NOTCH4 Gene

Disease -log(P) Hits PubMed IDs
schizophrenia 54.1 80
mammary tumor 39.3 2
schizoaffective disorder 24.8 4
tumors 18.5 28
hepatocellular carcinoma 16.5 5

Relevant External Links for NOTCH4

Genetic Association Database (GAD)
NOTCH4
Human Genome Epidemiology (HuGE) Navigator
NOTCH4
Tumor Gene Database (TGDB):
NOTCH4
genes like me logo Genes that share disorders with NOTCH4: view

No data available for UniProtKB/Swiss-Prot for NOTCH4 Gene

Publications for NOTCH4 Gene

  1. Gene organization of human NOTCH4 and (CTG)n polymorphism in this human counterpart gene of mouse proto-oncogene Int3. (PMID: 9168133) Sugaya K. … Mita K. (Gene 1997) 3 4 23
  2. Cloning, characterization, and the complete 56.8-kilobase DNA sequence of the human NOTCH4 gene. (PMID: 9693032) Li L. … Hood L. (Genomics 1998) 3 4 23
  3. NOTCH4 gene polymorphism and susceptibility to schizophrenia and schizoaffective disorder. (PMID: 11239712) Ujike H. … Kuroda S. (Neurosci. Lett. 2001) 3 23 48
  4. Association analysis of NOTCH4 loci in schizophrenia using family and population-based controls. (PMID: 11381257) Sklar P. … Wildenauer D.B. (Nat. Genet. 2001) 3 23 48
  5. Failure to confirm NOTCH4 association with schizophrenia in a large population-based sample from Scotland. (PMID: 11381258) McGinnis R.E. … St Clair D. (Nat. Genet. 2001) 3 23 48

Products for NOTCH4 Gene

Sources for NOTCH4 Gene

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