Notch4 notch 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Notch4provided by MGI
Official Full Name: notch 4provided by MGI
Primary source: MGI:MGI:107471
See related: Ensembl:ENSMUSG00000015468 AllianceGenome:MGI:107471
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: N4; Int3; Int-3
Summary: Enables Notch binding activity. Involved in branching involved in blood vessel morphogenesis and negative regulation of endothelial cell differentiation. Acts upstream of or within several processes, including negative regulation of Notch signaling pathway; positive regulation of angiogenesis; and positive regulation of aorta morphogenesis. Located in cytoplasmic vesicle and endoplasmic reticulum. Is expressed in several structures, including brain; cardiovascular system; genitourinary system; gut; and sensory organ. Used to study arteriovenous malformations of the brain. Human ortholog(s) of this gene implicated in autoimmune disease (multiple); dementia; ductal carcinoma in situ; schizophrenia; and systemic scleroderma. Orthologous to human NOTCH4 (notch receptor 4). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in lung adult (RPKM 37.2), adrenal adult (RPKM 14.3) and 14 other tissues See more
Orthologs: human all
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Genomic context

Location:: 17 B1; 17 18.15 cM

Exon count:: 30

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	17	NC_000083.7 (34783257..34807517)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	17	NC_000083.6 (34564286..34588543)

Chromosome 17 - NC_000083.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Inactivation of Notch4 Attenuated Pancreatic Tumorigenesis in Mice.
Title: Inactivation of Notch4 Attenuated Pancreatic Tumorigenesis in Mice.
Notch1 and Notch4 core binding domain peptibodies exhibit distinct ligand-binding and anti-angiogenic properties.
Title: Notch1 and Notch4 core binding domain peptibodies exhibit distinct ligand-binding and anti-angiogenic properties.
JAG1-NOTCH4 mechanosensing drives atherosclerosis.
Title: JAG1-NOTCH4 mechanosensing drives atherosclerosis.
Convergent lines of evidence support NOTCH4 as a schizophrenia risk gene.
Title: Convergent lines of evidence support NOTCH4 as a schizophrenia risk gene.
NOTCH4 Exhibits Anti-Inflammatory Activity in Activated Macrophages by Interfering With Interferon-gamma and TLR4 Signaling.
Title: NOTCH4 Exhibits Anti-Inflammatory Activity in Activated Macrophages by Interfering With Interferon-γ and TLR4 Signaling.
Notch4 signaling limits regulatory T-cell-mediated tissue repair and promotes severe lung inflammation in viral infections.
Title: Notch4 signaling limits regulatory T-cell-mediated tissue repair and promotes severe lung inflammation in viral infections.
Notch4 activation aggravates NF-kappaB-mediated inflammation in a mouse model of HIV-1-associated nephropathy
Title: Notch4 activation aggravates NF-κB-mediated inflammation in HIV-1-associated nephropathy.
Jag1 on alveolar macrophages interacts with Notch 4 on naive allergen-specific T cells to promote TH2 and TH17 cell differentiation
Title: A Jagged 1-Notch 4 molecular switch mediates airway inflammation induced by ultrafine particles.
Notch4 inhibited Mycobacterium tuberculosis-induced production of proinflammatory cytokines by interaction with TAK1 and inhibition of its activation.
Title: Notch4 Negatively Regulates the Inflammatory Response to Mycobacterium tuberculosis Infection by Inhibiting TAK1 Activation.
Int3 activates NF-kappaB in HC11 cells in absence of Rbpj through an association with the IKK signalosome. Int3 induced the canonical NF-kappaB activity and P50 phosphorylation in HC11 cells without altering the NF-kappaB2 pathway. The minimal domain within the Int3 protein required to activate NF-kappaB consists of the CDC10/Ankyrin (ANK) repeats domain.
Title: The ANK repeats of Notch-4/Int3 activate NF-κB canonical pathway in the absence of Rbpj and causes mammary tumorigenesis.

Submit: New GeneRIF Correction See all GeneRIFs (37)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (4)
Targeted (6) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Notch4 (e-PCR), detects polymorphism
- UniSTS:265732

M80456 (e-PCR)
- UniSTS:124982

Notch4 (e-PCR), detects polymorphism
- UniSTS:465466

UniSTS:465467 (e-PCR)
- UniSTS:465467

Notch4 (e-PCR), detects polymorphism
- UniSTS:465467

Notch4 (e-PCR), detects polymorphism
- UniSTS:144048

Notch4 (e-PCR), detects polymorphism
- UniSTS:496833

AA799611 (e-PCR)
- UniSTS:260590

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA-binding transcription activator activity, RNA polymerase II-specific	ISO Inferred from Sequence Orthology more info
enables Notch binding	IBA Inferred from Biological aspect of Ancestor more info
enables Notch binding	IPI Inferred from Physical Interaction more info	PubMed
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables cis-regulatory region sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in Notch signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in branching involved in blood vessel morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in endothelial cell differentiation	ISO Inferred from Sequence Orthology more info
involved_in endothelial cell morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in epithelial to mesenchymal transition	ISO Inferred from Sequence Orthology more info
involved_in mammary gland development	ISO Inferred from Sequence Orthology more info
involved_in morphogenesis of a branching structure	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of Notch signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell adhesion molecule production	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell-cell adhesion mediated by cadherin	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of endothelial cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of aorta morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of smooth muscle cell differentiation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of Notch signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of protein localization	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within regulation of protein processing	IDA Inferred from Direct Assay more info	PubMed
involved_in vasculature development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within venous blood vessel morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cell surface	ISO Inferred from Sequence Orthology more info
located_in cell surface	ISS Inferred from Sequence or Structural Similarity more info
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: neurogenic locus notch homolog protein 4

Names: Notch gene homolog 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_010929.2 → NP_035059.2 neurogenic locus notch homolog protein 4 precursor

See identical proteins and their annotated locations for NP_035059.2

Status: VALIDATED

Source sequence(s)

CT009767

Consensus CDS

CCDS28647.1

UniProtKB/Swiss-Prot

A2CG28, O35442, O88314, O88316, P31695, Q62389, Q62390, Q9R1W9, Q9R1X0

UniProtKB/TrEMBL

B2RQR1

Related

ENSMUSP00000015612.8, ENSMUST00000015612.14

Conserved Domains (9) summary

PTZ00322
Location:1748 → 1828

PTZ00322; 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional

smart00004
Location:1203 → 1241

NL; Domain found in Notch and Lin-12

smart00179
Location:191 → 229

EGF_CA; Calcium-binding EGF-like domain

cd00054
Location:429 → 470

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

sd00045
Location:1629 → 1659

ANK; ANK repeat [structural motif]

pfam06816
Location:1291 → 1337

NOD; NOTCH protein

pfam07684
Location:1376 → 1415

NODP; NOTCH protein

pfam00066
Location:1253 → 1281

Notch; LNR domain

pfam12796
Location:1633 → 1726

Ank_2; Ankyrin repeats (3 copies)

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000083.7 Reference GRCm39 C57BL/6J

Range

34783257..34807517

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036160366.1 → XP_036016259.1 neurogenic locus notch homolog protein 4 isoform X2

Conserved Domains (6) summary

smart00004
Location:1207 → 1245

NL; Domain found in Notch and Lin-12

smart00179
Location:195 → 233

EGF_CA; Calcium-binding EGF-like domain

cd00054
Location:433 → 474

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

pfam00066
Location:1255 → 1284

Notch; LNR domain

pfam06816
Location:1295 → 1344

NOD; NOTCH protein

pfam07684
Location:1379 → 1419

NODP; NOTCH protein
XM_006523798.4 → XP_006523861.1 neurogenic locus notch homolog protein 4 isoform X1

See identical proteins and their annotated locations for XP_006523861.1

UniProtKB/TrEMBL

B2RQR1

Conserved Domains (7) summary

smart00004
Location:1207 → 1245

NL; Domain found in Notch and Lin-12

smart00179
Location:195 → 233

EGF_CA; Calcium-binding EGF-like domain

COG0666
Location:1644 → 1819

ANKYR; Ankyrin repeat [Signal transduction mechanisms]

cd00054
Location:433 → 474

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

sd00045
Location:1633 → 1663

ANK; ANK repeat [structural motif]

pfam00066
Location:1257 → 1285

Notch; LNR domain

pfam12796
Location:1637 → 1730

Ank_2; Ankyrin repeats (3 copies)