NOTCH4 notch 4 [Homo sapiens] - Gene

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Summary

Official Symbol: NOTCH4provided by HGNC
Official Full Name: notch 4provided by HGNC
Primary source: HGNC:7884
Locus tag: DAQB-143M3.4
See related: Ensembl:ENSG00000204301; HPRD:01290; MIM:164951; Vega:OTTHUMG00000031044
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: INT3; NOTCH3; FLJ16302; MGC74442
Summary: 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]

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Genomic context

Location :: 6p21.3

Sequence :: Chromosome: 6; NC_000006.11 (32162620..32191844, complement)

See NOTCH4 in Epigenomics, MapViewer

Chromosome 6 - NC_000006.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Detection of Notch1, Notch4, and DLL4 in thyroid glands and their regulation in various pathologies suggest that this pathway may play a role in thyroid carcinogenesis and angiogenesis.
Title: Delta-like 4/Notch pathway is differentially regulated in benign and malignant thyroid tissues.
Notch-1, Notch-4, and Jagged-1 are highly expressed in different subcellular locations in the breast cancer cell
Title: Notch-1 and notch-4 receptors as prognostic markers in breast cancer.
arachidonic acid significantly decreased methylation of the promoters of both KDR and Notch4 genes in Human umbilical vein endothelial cells.
Title: The CpG island methylation regulated expression of endothelial proangiogenic genes in response to β-carotene and arachidonic acid.
The receptors Notch2, -3, -4 and their ligands Jagged1, -2 and Delta1, -4 were detected at both the mRNA and protein level in early and late placenta
Title: Expression patterns of Notch receptors and their ligands Jagged and Delta in human placenta.
The stromal cell-mediated antiapoptotic effect on B- ALL cells is mediated by Notch-3 and -4 or Jagged-1/-2 and DLL-1 in a synergistic manner.
Title: Notch-3 and Notch-4 signaling rescue from apoptosis human B-ALL cells in contact with human bone marrow-derived mesenchymal stromal cells.
Only rs17604492 single nucleotide polymorphism of NOTCH4 gene was found to be weakly associated with susceptibility to Kawasaki Disease (KD) in a Korean population. Results indicate NOTCH4 doesn't contribute to susceptibility to KD.
Title: Notch homolog 4 polymorphism and Kawasaki disease.
This research examined the methylation status of a region surrounding the NOTCH4 -25 C/T site in leukocyte genomic DNA and human brain regions.
Title: Methylation analysis of the NOTCH4 -25 C/T polymorphism in schizophrenia.
Data show no detectable difference in the DNA binding site preferences of CSL before and after loading of four different Notch receptors and MAML1 proteins.
Title: Notch and MAML-1 complexation do not detectably alter the DNA binding specificity of the transcription factor CSL.
Studies indicate that different receptors and ligands expression in breast cancer and various ways in which the pathway can be inhibited.
Title: Breast cancer stem cells: something out of notching?
Study identifies an important role for cross talk between Notch4 and Nodal in metastatic melanoma, placing Notch4 upstream of Nodal.
Title: Regulation of the embryonic morphogen Nodal by Notch4 facilitates manifestation of the aggressive melanoma phenotype.

Submit: New GeneRIF Correction See all (55)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Common genetic variation and the control of HIV-1 in humans.

Common variants conferring risk of schizophrenia.

Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production.

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Products	Interactant	Other Gene	Source	Pubs	Description
Q99466	Q9NR61	DLL4	HPRD	PubMed
Q99466	Q969H0	FBXW7	HPRD	PubMed
Q99466	Q92585	MAML1	HPRD	PubMed
Q99466	Q8IZL2	MAML2	HPRD	PubMed
Q99466	Mastermind like 3	MAML3	HPRD	PubMed
Q99466	Q99466	NOTCH4	HPRD	PubMed
Q99466	P49768	PSEN1	HPRD	PubMed
Q99466	P49810	PSEN2	HPRD	PubMed
Q99466	Q06330	RBPJ	HPRD	PubMed
Q99466	Q15796	SMAD2	HPRD	PubMed
Q99466	P84022	SMAD3	HPRD	PubMed
Q99466	Q13485	SMAD4	HPRD	PubMed
BioGRID:110917	BioGRID:115138	MAML1	BioGRID	PubMed	Reconstituted Complex
BioGRID:110917	BioGRID:110358	MDM2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110917	BioGRID:113010	TP53	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110917	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-Western

Function	Evidence Code	Pubs
calcium ion binding	IEA Inferred from Electronic Annotation more info
calcium ion binding	TAS Traceable Author Statement more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein heterodimerization activity	TAS Traceable Author Statement more info	PubMed
receptor activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
Notch receptor processing	TAS Traceable Author Statement more info
Notch signaling pathway	IEA Inferred from Electronic Annotation more info
Notch signaling pathway	TAS Traceable Author Statement more info
cell differentiation	IEA Inferred from Electronic Annotation more info
cell differentiation	NAS Non-traceable Author Statement more info	PubMed
cell fate determination	TAS Traceable Author Statement more info	PubMed
embryo development	ISS Inferred from Sequence or Structural Similarity more info
endothelial cell morphogenesis	IEA Inferred from Electronic Annotation more info
gene expression	TAS Traceable Author Statement more info
hemopoiesis	TAS Traceable Author Statement more info	PubMed
mammary gland development	IDA Inferred from Direct Assay more info	PubMed
morphogenesis of a branching structure	ISS Inferred from Sequence or Structural Similarity more info
multicellular organismal development	IEA Inferred from Electronic Annotation more info
negative regulation of cell differentiation	NAS Non-traceable Author Statement more info	PubMed
negative regulation of endothelial cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
patterning of blood vessels	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transcription, DNA-dependent	TAS Traceable Author Statement more info	PubMed
regulation of developmental process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
Golgi lumen	TAS Traceable Author Statement more info
cell surface	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info
endoplasmic reticulum lumen	TAS Traceable Author Statement more info
extracellular region	TAS Traceable Author Statement more info
integral to membrane	IEA Inferred from Electronic Annotation more info
integral to plasma membrane	TAS Traceable Author Statement more info	PubMed
membrane	IEA Inferred from Electronic Annotation more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	TAS Traceable Author Statement more info	PubMed
plasma membrane	TAS Traceable Author Statement more info

General protein information

Preferred Names: neurogenic locus notch homolog protein 4

Names: neurogenic locus notch homolog protein 4; Notch homolog 4

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NCBI Reference Sequences (RefSeq)

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.

Genomic

NG_028190.1 RefSeqGene

Range

5001..34225

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_004557.3 → NP_004548.3 neurogenic locus notch homolog protein 4 preproprotein

Status: REVIEWED

Source sequence(s)

AL705928, BQ023880, D63395, U95299

Consensus CDS

CCDS34420.1

UniProtKB/Swiss-Prot

Q99466

Related

ENSP00000364163, OTTHUMP00000029050, ENST00000375023, OTTHUMT00000076045

Conserved Domains (6) summary

cd00054
Location:432 – 473
Blast Score: 109

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 ...

cd00204
Location:1661 – 1778
Blast Score: 251

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

pfam07684
Location:1378 – 1415
Blast Score: 102

NODP; NOTCH protein

pfam12796
Location:1638 – 1731
Blast Score: 199

Ank_2; Ankyrin repeats (3 copies)

cl02419
Location:1209 – 1246
Blast Score: 119

Notch; LNR domain

cl09941
Location:194 – 232
Blast Score: 103

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 ...

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000006.11 Reference GRCh37.p5 Primary Assembly

Range

32162620..32191844, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p5 ALT_REF_LOCI_1

Genomic

NT_167244.1 Reference GRCh37.p5 ALT_REF_LOCI_1

Range

3477358..3486924, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p5 ALT_REF_LOCI_2

Genomic

NT_113891.2 Reference GRCh37.p5 ALT_REF_LOCI_2

Range

3633298..3662520, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p5 ALT_REF_LOCI_4

Genomic

NT_167246.1 Reference GRCh37.p5 ALT_REF_LOCI_4

Range

3505441..3534689, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p5 ALT_REF_LOCI_5

Genomic

NT_167247.1 Reference GRCh37.p5 ALT_REF_LOCI_5

Range

3542444..3571691, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p5 ALT_REF_LOCI_6

Genomic

NT_167248.1 Reference GRCh37.p5 ALT_REF_LOCI_6

Range

3423638..3452865, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p5 ALT_REF_LOCI_7

Genomic

NT_167249.1 Reference GRCh37.p5 ALT_REF_LOCI_7

Range

3510346..3539573, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000138.1 Alternate HuRef

Range

31916815..31946041, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AB023961.1	BAB20317.1
genomic	AB024520.1	BAA88951.1
genomic	AB024578.1	BAA88952.1
genomic	AL662830.14 (18479..47701)	None
genomic	AL662884.11 (107668..136892)	None
genomic	AL845464.5	CAI41803.1
genomic	AL845509.6	CAI18564.1
genomic	BX284686.9	CAM26209.1
genomic	BX284927.5	CAM25850.1
genomic	BX927239.5 (54573..83821)	None
genomic	CR812478.6 (61911..71477)	None
genomic	CR933878.7 (64738..93985)	None
genomic	D86566.1	BAA13116.1
genomic	U89335.1	AAC63097.1
mRNA	AK131314.1	None
mRNA	AK290785.1	BAF83474.1
mRNA	AK293692.1	BAG57129.1
mRNA	AK294161.1	BAG57484.1
mRNA	AL705928.1	None
mRNA	BC033869.1	None
mRNA	BC063815.1	AAH63815.1
mRNA	BC140782.1	AAI40783.1
mRNA	BC144540.1	None
mRNA	BC144541.1	None
mRNA	BQ023880.1	None
mRNA	D63395.1	BAA09708.1
mRNA	U95299.1	AAC32288.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
Q5SPL1	GenPept	UniProtKB/TrEMBL:Q5SPL1
Q5STG5	GenPept	UniProtKB/TrEMBL:Q5STG5
Q6P3V5	GenPept	UniProtKB/TrEMBL:Q6P3V5
Q99466.2	GenPept	UniProtKB/Swiss-Prot:Q99466