JAG1 jagged 1 [Homo sapiens] - Gene

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Summary

Official Symbol: JAG1provided by HGNC
Official Full Name: jagged 1provided by HGNC
Primary source: HGNC:6188
See related: Ensembl:ENSG00000101384; HPRD:03562; MIM:601920; Vega:OTTHUMG00000031872
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: AGS; AHD; AWS; HJ1; CD339; JAGL1; MGC104644
Summary: The jagged 1 protein encoded by JAG1 is the human homolog of the Drosophilia jagged protein. Human jagged 1 is the ligand for the receptor notch 1, the latter a human homolog of the Drosophilia jagged receptor notch. Mutations that alter the jagged 1 protein cause Alagille syndrome. Jagged 1 signalling through notch 1 has also been shown to play a role in hematopoiesis. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 20p12.1-p11.23

Sequence :: Chromosome: 20; NC_000020.10 (10618332..10654694, complement)

See JAG1 in Epigenomics, MapViewer

Chromosome 20 - NC_000020.10 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?

miR-143/145 as activated independently by Jag-1/Notch and SRF in parallel pathways.
Title: The miR-143/145 cluster is a novel transcriptional target of Jagged-1/Notch signaling in vascular smooth muscle cells.
Both Notch3 and vascular smooth muscle cells differentiation marker proteins were upregulated, which were abrogated by Jagged1-specific siRNA.
Title: The role of endothelial cell-bound Jagged1 in Notch3-induced human coronary artery smooth muscle cell differentiation.
Notch1 and Jagged1 are up-regulated in human colon adenocarcinoma and suggests that Notch1/Jagged1 signaling might play a role in the development of colon adenocarcinoma.
Title: Up-regulated expression of Notch1 and Jagged1 in human colon adenocarcinoma.
as compared to MSC, OP9 cells were more efficient at inducing self-renewal and/or de novo generation of primitive (CD34(+) CD38(-) Lin(-)) cells, and suggest that such effects were due, at least in part, to the presence of Jagged-1 and DL1.
Title: In vitro effects of stromal cells expressing different levels of Jagged-1 and Delta-1 on the growth of primitive and intermediate CD34(+) cell subsets from human cord blood.
Jagged1 plays dual roles in cancer progression through an angiogenic function in tumor endothelial cells and through proliferation and chemoresistance in tumor cells.
Title: Targeting the notch ligand JAGGED1 in both tumor cells and stroma in ovarian cancer.
NOTCH2 expression and activation, independent of JAGGED1 expression, may contribute to the pathogenesis of hepatoblastoma.
Title: Activated NOTCH2 is overexpressed in hepatoblastomas: an immunohistochemical study.
Several JAG1 mutations were found in patients with tetralogy of Fallot.
Title: Novel and recurrent JAG1 mutations in patients with tetralogy of Fallot.
Disease-associating novel JAG1 gene variations were found in TOF patients, and seem to play an important role in the causation of the disease
Title: Mutational analysis of JAG1 gene in non-syndromic tetralogy of Fallot children.
The Jagged-1 intracellular domain (JICD) inhibits Notch1 signaling via a reduction in the protein stability of the Notch1 intracellular domain (Notch1-IC).
Title: The intracellular domain of Jagged-1 interacts with Notch1 intracellular domain and promotes its degradation through Fbw7 E3 ligase.
Endothelial JAGGED1 controls hemangioma stem cell-to-pericyte differentiation in a murine model of infantile hemangioma. Pericytes have a fundamental role in formation of blood vessels in IH.
Title: JAGGED1 signaling regulates hemangioma stem cell-to-pericyte/vascular smooth muscle cell differentiation.

Submit: New GeneRIF Correction See all (99)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Alagille syndrome (AGS) is a complex multisystem disorder involving primarily the liver, heart, eyes, face, and skeleton. The clinical features are highly variable, even within families. The major clinical manifestations of AGS are cholestasis, characterized by bile duct paucity on liver biopsy; congenital cardiac defects, primarily involving the pulmonary arteries; posterior embryotoxon in the eye; typical facial features; and butterfly vertebrae. Renal and central nervous abnormalities also occur. Mortality is approximately 10%, with vascular accidents, cardiac disease, and liver disease accounting for most of the deaths.

Diagnosis Testing

The diagnosis of AGS is primarily based on clinical findings. The two genes associated with AGS are JAG1 and NOTCH2. Sequence analysis of JAG1 detects mutations in more than 89% of individuals who meet clinical diagnostic criteria; fluorescence in situ hybridization (FISH) detects a microdeletion of 20p12, including the entire JAG1 gene, in approximately 7% of affected individuals. Mutations in NOTCH2 are observed in fewer than 1% of individuals with AGS.

Genetic Counseling

AGS is inherited in an autosomal dominant manner. Approximately 30%-50% of individuals have an inherited mutation and about 50%-70% have a de novo mutation. The parents of a child with a de novo mutation have a low but increased risk for recurrence because of the possibility of germline mosaicism. The offspring of an individual with Alagille syndrome have a 50% chance of having Alagille syndrome. Prenatal testing for pregnancies at increased risk is possible if the JAG1 or NOTCH2 disease-causing mutation in an affected family member is known. Prenatal testing cannot predict the occurrence or severity of clinical manifestations.

References

PMID: 20301450

Association of JAG1 with bone mineral density and osteoporotic fractures: a genome-wide association study and follow-up replication studies.

Deafness, congenital heart defects, and posterior embryotoxon

MIM: 601920

Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality.

Tetralogy of Fallot

MIM: 187500

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Interactions

Products	Interactant	Other Gene	Source	Pubs	Description
AL035456.26	NP_005243.1	FOS	BIND	PubMed	c-Fos interacts with Jagged1 promoter.
AL035456.26	NP_002219.1	JUN	BIND	PubMed	c-Jun interacts with Jagged1 promoter.
P78504	O00587	MFNG	HPRD	PubMed
P78504	P55196	MLLT4	HPRD	PubMed
P78504	P46531	NOTCH1	HPRD	PubMed
P78504	Q04721	NOTCH2	HPRD	PubMed
P78504	Q9UM47	NOTCH3	HPRD	PubMed
P78504	Q9H488	POFUT1	HPRD	PubMed
P78504	P07996	THBS1	HPRD	PubMed
BioGRID:106689	BioGRID:114593	HGS	BioGRID	PubMed	Affinity Capture-Western
BioGRID:106689	BioGRID:121593	MIB1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:106689	BioGRID:110447	MLLT4	BioGRID	PubMed	Two-hybrid
BioGRID:106689	BioGRID:114595	NEURL	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:106689	BioGRID:110913	NOTCH1	BioGRID	PubMed	Co-localization; Reconstituted Complex
BioGRID:106689	BioGRID:110915	NOTCH2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:106689	BioGRID:110916	NOTCH3	BioGRID	PubMed	Reconstituted Complex
BioGRID:106689	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western

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General gene information

Markers

Z94359 (e-PCR)
- UniSTS:42767

Jag1 (e-PCR), detects polymorphism
- UniSTS:143636

SHGC-33818 (e-PCR)
- UniSTS:35895

RH123107 (e-PCR)
- UniSTS:135487

PMC111189P2 (e-PCR)
- UniSTS:270221

STS-T96855 (e-PCR)
- UniSTS:31379

JAG1_1238 (e-PCR)
- UniSTS:277396

JAG1_v358 (e-PCR)
- UniSTS:277396

WI-8071 (e-PCR)
- UniSTS:64191

Z94625 (e-PCR)
- UniSTS:32962

WI-12707 (e-PCR)
- UniSTS:44738

WI-17032 (e-PCR)
- UniSTS:13027

D20S1091 (e-PCR)
- UniSTS:473578

Genotypes

See JAG1 SNP Geneview Report
See JAG1 SNP Genotype Report
See JAG1 SNP Variation Viewer Report

Homology

Map Viewer (Mouse, Rat)

Pathways from BioSystems

Activated NOTCH1 Transmits Signal to the Nucleus, organism-specific biosystem (from REACTOME)
Activated NOTCH1 Transmits Signal to the Nucleus, organism-specific biosystemMature NOTCH1 heterodimer on the cell surface is activated by one of its ligands: DLL1 (Cordle et al. 2008, Jarriault et al. 1998), DLL4 (Benedito et al. 2009), JAG1 (Li et al. 1998, Benedito et al. ...
Delta-Notch Signaling Pathway, organism-specific biosystem (from WikiPathways)
Delta-Notch Signaling Pathway, organism-specific biosystemThere are 4 Notch receptors in humans (Notch 1-4) that bind to a family of 5 ligands (Jagged 1 and 2 and Delta-like 1-3). The Notch receptors are expressed on the cell surface as heterodimeric protei...
Notch signaling pathway, organism-specific biosystem (from KEGG)
Notch signaling pathway, organism-specific biosystemThe Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch pro...
Notch signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
Notch signaling pathway, organism-specific biosystem
Notch signaling pathway
Notch signaling pathway, conserved biosystem (from KEGG)
Notch signaling pathway, conserved biosystemThe Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch pro...
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by NOTCH, organism-specific biosystem (from REACTOME)
Signaling by NOTCH, organism-specific biosystemThe Notch Signaling Pathway (NSP) is a highly conserved pathway for cell-cell communication. NSP is involved in the regulation of cellular differentiation, proliferation, and specification. For exam...
Signaling by NOTCH1, organism-specific biosystem (from REACTOME)
Signaling by NOTCH1, organism-specific biosystemNOTCH1 functions as both a transmembrane receptor presented on the cell surface and as a transcriptional regulator in the nucleus.NOTCH1 receptor presented on the plasma membrane is activated by a me...
Signaling by NOTCH2, organism-specific biosystem (from REACTOME)
Signaling by NOTCH2, organism-specific biosystemSimilar to NOTCH1, NOTCH2 is activated by delta-like and jagged ligands (DLL/JAG) expressed in trans on a neighboring cell. The activation triggers cleavage of NOTCH2, first by ADAM10 at the S2 cleav...
Signaling by NOTCH3, organism-specific biosystem (from REACTOME)
Signaling by NOTCH3, organism-specific biosystemSimilar to NOTCH1, NOTCH3 is activated by delta-like and jagged ligands (DLL/JAG) expressed in trans on a neighboring cell. The activation triggers cleavage of NOTCH3, first by ADAM10 at the S2 cleav...
Signaling by NOTCH4, organism-specific biosystem (from REACTOME)
Signaling by NOTCH4, organism-specific biosystemSimilar to NOTCH1, NOTCH4 is activated by delta-like and jagged ligands (DLL/JAG) expressed in trans on a neighboring cell. The activation triggers cleavage of NOTCH4, first by ADAM10 at the S2 cleav...

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
Notch binding	NAS Non-traceable Author Statement more info	PubMed
calcium ion binding	NAS Non-traceable Author Statement more info
growth factor activity	NAS Non-traceable Author Statement more info	PubMed
structural molecule activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
Notch receptor processing	TAS Traceable Author Statement more info
Notch signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
Notch signaling pathway	NAS Non-traceable Author Statement more info	PubMed
Notch signaling pathway	TAS Traceable Author Statement more info
angiogenesis	NAS Non-traceable Author Statement more info	PubMed
auditory receptor cell differentiation	IEA Inferred from Electronic Annotation more info
cell communication	IEA Inferred from Electronic Annotation more info
cell fate determination	NAS Non-traceable Author Statement more info	PubMed
distal tubule development	IEA Inferred from Electronic Annotation more info
endothelial cell differentiation	NAS Non-traceable Author Statement more info	PubMed
hemopoiesis	NAS Non-traceable Author Statement more info	PubMed
inner ear development	IEA Inferred from Electronic Annotation more info
keratinocyte differentiation	NAS Non-traceable Author Statement more info	PubMed
loop of Henle development	IEA Inferred from Electronic Annotation more info
morphogenesis of an epithelial sheet	IEA Inferred from Electronic Annotation more info
multicellular organismal development	NAS Non-traceable Author Statement more info
myoblast differentiation	NAS Non-traceable Author Statement more info	PubMed
negative regulation of fat cell differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of neuron differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of stem cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
nervous system development	NAS Non-traceable Author Statement more info	PubMed
neuronal stem cell maintenance	IEP Inferred from Expression Pattern more info	PubMed
organ morphogenesis	IEA Inferred from Electronic Annotation more info
positive regulation of Notch signaling pathway	IEA Inferred from Electronic Annotation more info
positive regulation of myeloid cell differentiation	IEA Inferred from Electronic Annotation more info
regulation of cell migration	NAS Non-traceable Author Statement more info	PubMed
regulation of cell proliferation	NAS Non-traceable Author Statement more info	PubMed
response to muramyl dipeptide	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
apical part of cell	IEA Inferred from Electronic Annotation more info
extracellular region	NAS Non-traceable Author Statement more info	PubMed
integral to plasma membrane	NAS Non-traceable Author Statement more info	PubMed
membrane	TAS Traceable Author Statement more info	PubMed
plasma membrane	TAS Traceable Author Statement more info

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General protein information

Preferred Names: protein jagged-1

Names: protein jagged-1

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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_007496.1 RefSeqGene

Range

5001..41363

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000214.2 → NP_000205.1 protein jagged-1 precursor

Status: REVIEWED

Source sequence(s)

AF028593, AI268246, BF056748, U73936, U77914

Consensus CDS

CCDS13112.1

UniProtKB/Swiss-Prot

P78504

UniProtKB/TrEMBL

Q99740

Related

ENSP00000254958, OTTHUMP00000030278, ENST00000254958, OTTHUMT00000077997

Conserved Domains (5) summary

cd00054
Location:629 – 665
Blast Score: 105

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 ...

pfam07657
Location:31 – 110
Blast Score: 298

MNNL; N terminus of Notch ligand

pfam01414
Location:167 – 229
Blast Score: 266

DSL; Delta serrate ligand

cl02515
Location:863 – 930
Blast Score: 214

VWC; von Willebrand factor type C domain

cl09941
Location:820 – 856
Blast Score: 102

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_000020.10 Reference GRCh37.p5 Primary Assembly

Range

10618332..10654694, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000152.1 Alternate HuRef

Range

10569771..10606135, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AL035456.26	CAC07198.1
genomic	CH471133.3	EAX10341.1
mRNA	AF003837.1	AAC51731.1
mRNA	AF028593.1	AAB84053.1
mRNA	AI268246.1	None
mRNA	AK302554.1	BAG63823.1
mRNA	AK312722.1	BAG35596.1
mRNA	BC028007.1	None
mRNA	BC098393.1	AAH98393.1
mRNA	BC126205.1	AAI26206.1
mRNA	BC126207.1	AAI26208.1
mRNA	BF056748.1	None
mRNA	U61276.1	AAB39007.1
mRNA	U73936.1	AAC52020.1
mRNA	U77720.1	AAC51323.1
mRNA	U77914.1	AAC50909.1
other-genetic	HQ258535.1	ADR83289.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P78504.3	GenPept	UniProtKB/Swiss-Prot:P78504
Q4KMR2	GenPept	UniProtKB/TrEMBL:Q4KMR2
Q99740	GenPept	UniProtKB/TrEMBL:Q99740