Notch signaling pathway - Rat Genome Database

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Keyword

NOTCH SIGNALING PATHWAY (PW:0000204)

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Description

Notch signaling, a highly conserved cell-cell signaling pathway, exerts an essential regulatory role in gene expression and controls cell fate determination, differentiation, and proliferation. Notch receptors and ligands, four and five respectively in mammals, are single transmembrane proteins connecting the cell-receiving and the cell-sending signal. The DSL domain of Dll/Jag ligands and the EGF-like repeats of Notch receptors mediate the interaction. The journey of Notch from transmembrane re

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ceptor to transcriptional regulator in the nucleus involves several processing events and it is heavily regulated. In the ER Notch is O-fucosylated on EGF-like repeats contain consensus O-fucose sites for Pofut1. Members of Fng can elongate the fucose modified residues by addition of N-acetylglycosamine. Glycosylation is important for proper Notch signaling in several ways but the underlying mechanisms remain to be elucidated. Notch is subject to a number of cleavage events designated S1 through S4. In the trans-Golgi during the secretion process, S1 is carried out by a furin-like convertase. The resulting heterodimeric Notch interacts with its ligand with subsequent shedding of the ectodomain and exposure of S2 site, target of ADAM/TACE. The gamma-secretase mediated S3/S4 events lead to release of NICD and translocation to the nucleus. In the absence of Notch, RBPJ (known as CSL) transcription factor recruits co-repressors that associate with histone deacetylase complexes and keep the chromatin in a transcriptional silent mode (different color, human gene)�. NICD displaces the co-repressors to form a ternary complex, with RBPJ and members of Maml that recruits transcription factors to turn on the expression of Hes/Hey target and effector genes. It is important to note that members of Hes and Hey transcriptional regulators are the mediators of Notch downstream effects acting as transcriptional regulators, mostly repression. The mechanisms are not well understood; they are suspected to involve both DNA-dependent and independent events. Maml can also downregulate Notch by participating in the recruitment of kinases; phosphorylated NICD is target to ubiquitination and degradation. Ligands can also exert an inhibitory effect but the mechanisms are poorly understood. Proper Notch signaling is required for many aspects of development; alterations in Notch have been implicated in a number of conditions exemplified by congenital heart diseases, cerebral stroke and cancer.� To see the ontology report for annotations, GViewer and download, click here [click to see associated GO term - GO:0007219, KEGG map map04330 and entry at Reactome - REACT_299.2]...(less)

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Ontology path Diagram

Genes in Pathway:

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Notch signaling pathway
	Symbol	Object Name	GBrowse	Evidence	Chr	Start	Stop	Reference	Source
G	Adam10	ADAM metallopeptidase domain 10		ISS	8	75,200,657	75,289,572	RGD:2302204	RGD
G	Adam10	ADAM metallopeptidase domain 10		ISS	8	75,200,657	75,289,572	RGD:1300252	RGD
G	Adam10	ADAM metallopeptidase domain 10		ISO	8	75,200,657	75,289,572	RGD:6484113	PID
G	Adam12	ADAM metallopeptidase domain 12		ISO	1	193,384,457	193,650,892	RGD:6484113	PID
G	Adam17	ADAM metallopeptidase domain 17		ISS	6	41,882,432	41,930,755	RGD:2302204	RGD
G	Adam17	ADAM metallopeptidase domain 17		IEA	6	41,882,432	41,930,755	RGD:6907045	KEGG
G	Aph1a	anterior pharynx defective 1 homolog A (C. elegans)		ISS	2	190,679,692	190,683,202	RGD:2302204	RGD
G	Aph1a	anterior pharynx defective 1 homolog A (C. elegans)		IEA	2	190,679,692	190,683,202	RGD:6907045	KEGG
G	Aph1a	anterior pharynx defective 1 homolog A (C. elegans)		ISO	2	190,679,692	190,683,202	RGD:6484113	PID
G	Aph1b	anterior pharynx defective 1 homolog B (C. elegans)		ISS	8	71,122,681	71,143,726	RGD:2302204	RGD
G	Aph1b	anterior pharynx defective 1 homolog B (C. elegans)		IEA	8	71,122,681	71,143,726	RGD:6907045	KEGG
G	Aph1b	anterior pharynx defective 1 homolog B (C. elegans)		ISO	8	71,122,681	71,143,726	RGD:6484113	PID
G	Cbl	Cbl proto-oncogene, E3 ubiquitin protein ligase		ISO	8	47,135,357	47,211,889	RGD:6484113	PID
G	Ccnd1	cyclin D1		ISO	1	205,357,235	205,366,757	RGD:6484113	PID
G	Cdkn1a	cyclin-dependent kinase inhibitor 1A		ISO	20	7,376,325	7,386,778	RGD:6484113	PID
G	Cir1	corepressor interacting with RBPJ, 1		IEA	3	55,789,080	55,818,634	RGD:6907045	KEGG
G	Cntn1	contactin 1		ISO	7	130,658,836	130,845,071	RGD:6484113	PID
G	Cntn6	contactin 6		ISO	4	140,078,007	140,450,348	RGD:6484113	PID
G	Crebbp	CREB binding protein		IEA	10	11,598,680	11,724,122	RGD:6907045	KEGG
G	Ctbp1	C-terminal binding protein 1		IEA	14	83,022,824	83,050,335	RGD:6907045	KEGG
G	Ctbp1	C-terminal binding protein 1		ISO	14	83,022,824	83,050,335	RGD:6484113	PID
G	Ctbp2	C-terminal binding protein 2		IEA	1	192,463,615	192,492,935	RGD:6907045	KEGG
G	Cul1	cullin 1		ISO	4	75,636,914	75,705,724	RGD:6484113	PID
G	Dlk1	delta-like 1 homolog (Drosophila)		ISO	6	134,022,016	134,043,058	RGD:6484113	PID
G	Dll1	delta-like 1 (Drosophila)		ISS	1	54,240,395	54,248,183	RGD:2302204	RGD
G	Dll1	delta-like 1 (Drosophila)		TAS	1	54,240,395	54,248,183	RGD:1304491	RGD
G	Dll1	delta-like 1 (Drosophila)		ISO	1	54,240,395	54,248,183	RGD:6484113	PID
G	Dll1	delta-like 1 (Drosophila)		IEA	1	54,240,395	54,248,183	RGD:6907045	KEGG
G	Dll3	delta-like 3 (Drosophila)		TAS	1	83,373,482	83,381,219	RGD:1304491	RGD
G	Dll3	delta-like 3 (Drosophila)		ISS	1	83,373,482	83,381,219	RGD:2302204	RGD
G	Dll3	delta-like 3 (Drosophila)		ISO	1	83,373,482	83,381,219	RGD:6484113	PID
G	Dll3	delta-like 3 (Drosophila)		IEA	1	83,373,482	83,381,219	RGD:6907045	KEGG
G	Dll4	delta-like 4 (Drosophila)		ISS	3	105,844,671	105,854,738	RGD:2302204	RGD
G	Dll4	delta-like 4 (Drosophila)		ISO	3	105,844,671	105,854,738	RGD:6484113	PID
G	Dll4	delta-like 4 (Drosophila)		IEA	3	105,844,671	105,854,738	RGD:6907045	KEGG
G	Dner	delta/notch-like EGF repeat containing		ISO	9	83,716,070	83,821,294	RGD:6484113	PID
G	Dnm1	dynamin 1		ISO	3	11,434,778	11,478,452	RGD:6484113	PID
G	Dtx2	deltex homolog 2 (Drosophila)		IEA	12	21,758,490	21,798,085	RGD:6907045	KEGG
G	Dtx3	deltex homolog 3 (Drosophila)		IEA	7	67,145,276	67,149,937	RGD:6907045	KEGG
G	Dtx3l	deltex 3-like (Drosophila)		IEA	11	66,649,508	66,659,119	RGD:6907045	KEGG
G	Dtx4	deltex homolog 4 (Drosophila)		IEA	1	215,396,194	215,416,879	RGD:6907045	KEGG
G	Dvl1	dishevelled, dsh homolog 1 (Drosophila)		IEA	5	172,705,951	172,717,626	RGD:6907045	KEGG
G	Dvl3	dishevelled, dsh homolog 3 (Drosophila)		IEA	11	82,597,654	82,622,175	RGD:6907045	KEGG
G	Eno1	enolase 1, (alpha)		ISO	5	167,394,131	167,405,516	RGD:6484113	PID
G	Ep300	E1A binding protein p300		ISO	7	119,938,507	120,008,886	RGD:6484113	PID
G	Ep300	E1A binding protein p300		IEA	7	119,938,507	120,008,886	RGD:6907045	KEGG
G	Eps15	epidermal growth factor receptor pathway substrate 15		ISO	5	130,639,805	130,739,014	RGD:6484113	PID
G	Fbxw7	F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase		ISO	2	176,675,226	176,750,737	RGD:6484113	PID
G	Furin	furin (paired basic amino acid cleaving enzyme)		ISO	1	136,209,969	136,222,057	RGD:6484113	PID
G	Gata3	GATA binding protein 3		ISO	17	79,991,587	80,011,574	RGD:6484113	PID
G	Hdac1	histone deacetylase 1		IEA	5	148,672,515	148,699,810	RGD:6907045	KEGG
G	Hdac1	histone deacetylase 1		ISO	5	148,672,515	148,699,810	RGD:6484113	PID
G	Hdac1l	histone deacetylase 1-like		IEA	9	78,410,666	78,412,120	RGD:6907045	KEGG
G	Hdac2	histone deacetylase 2		IEA	20	41,162,093	41,186,492	RGD:6907045	KEGG
G	Hes1	hairy and enhancer of split 1 (Drosophila)		ISS	11	72,603,482	72,605,673	RGD:5135539	RGD
G	Hes1	hairy and enhancer of split 1 (Drosophila)		IEA	11	72,603,482	72,605,673	RGD:6907045	KEGG
G	Hes5	hairy and enhancer of split 5 (Drosophila)		ISS	5	171,763,869	171,764,636	RGD:5135539	RGD
G	Hes5	hairy and enhancer of split 5 (Drosophila)		IEA	5	171,763,869	171,764,636	RGD:6907045	KEGG
G	Hes7	hairy and enhancer of split 7 (Drosophila)		ISS	10	55,879,891	55,882,414	RGD:5135539	RGD
G	Hey1	hairy/enhancer-of-split related with YRPW motif 1		ISS	2	95,174,030	95,176,430	RGD:5135539	RGD
G	Hey1	hairy/enhancer-of-split related with YRPW motif 1		IDA	2	95,174,030	95,176,430	RGD:70528	RGD
G	Hey2	hairy/enhancer-of-split related with YRPW motif 2		ISS	1	27,505,117	27,515,204	RGD:5135539	RGD
G	Hey2	hairy/enhancer-of-split related with YRPW motif 2		IDA	1	27,505,117	27,515,204	RGD:70528	RGD
G	Heyl	hairy/enhancer-of-split related with YRPW motif-like		ISS	5	142,544,185	142,561,176	RGD:5135539	RGD
G	Il4	interleukin 4		ISO	10	39,074,582	39,080,134	RGD:6484113	PID
G	Itch	itchy E3 ubiquitin protein ligase		ISO	3	145,644,315	145,707,190	RGD:6484113	PID
G	Jag1	jagged 1		ISS	3	125,181,063	125,216,481	RGD:2302204	RGD
G	Jag1	jagged 1		IDA	3	125,181,063	125,216,481	RGD:69863	RGD
G	Jag1	jagged 1		IMP	3	125,181,063	125,216,481	RGD:1334443	RGD
G	Jag1	jagged 1		ISO	3	125,181,063	125,216,481	RGD:6484113	PID
G	Jag1	jagged 1		IEA	3	125,181,063	125,216,481	RGD:6907045	KEGG
G	Jag2	jagged 2		TAS	6	137,909,633	137,931,120	RGD:69864	RGD
G	Jag2	jagged 2		ISS	6	137,909,633	137,931,120	RGD:2302204	RGD
G	Jag2	jagged 2		ISO	6	137,909,633	137,931,120	RGD:6484113	PID
G	Jag2	jagged 2		IEA	6	137,909,633	137,931,120	RGD:6907045	KEGG
G	Kat2a	K(lysine) acetyltransferase 2A		IEA	10	89,642,002	89,649,953	RGD:6907045	KEGG
G	Kdm1a	lysine (K)-specific demethylase 1A		ISO	5	155,299,289	155,358,404	RGD:6484113	PID
G	Lfng	LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase		ISS	12	14,497,704	14,505,723	RGD:727405	RGD
G	Lfng	LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase		ISS	12	14,497,704	14,505,723	RGD:2302204	RGD
G	Lfng	LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase		IEA	12	14,497,704	14,505,723	RGD:6907045	KEGG
G	Lnx1	ligand of numb-protein X 1, E3 ubiquitin protein ligase		ISO	14	35,888,702	35,992,436	RGD:6484113	PID
G	Maml1	mastermind like 1 (Drosophila)		ISS	10	35,814,839	35,850,122	RGD:2302204	RGD
G	Maml1	mastermind like 1 (Drosophila)		ISO	10	35,814,839	35,850,122	RGD:6484113	PID
G	Maml1	mastermind like 1 (Drosophila)		IEA	10	35,814,839	35,850,122	RGD:6907045	KEGG
G	Maml2	mastermind like 2 (Drosophila)		ISS	8	10,161,588	10,523,668	RGD:2302204	RGD
G	Maml2	mastermind like 2 (Drosophila)		ISO	8	10,161,588	10,523,668	RGD:6484113	PID
G	Maml2	mastermind like 2 (Drosophila)		IEA	8	10,161,588	10,523,668	RGD:6907045	KEGG
G	Maml3	mastermind like 3 (Drosophila)		ISS	2	140,574,982	140,740,461	RGD:2302204	RGD
G	Mark2	MAP/microtubule affinity-regulating kinase 2		ISO	1	209,958,902	210,022,099	RGD:6484113	PID
G	Mfap2	microfibrillar-associated protein 2		ISO	5	159,868,933	159,874,481	RGD:6484113	PID
G	Mfap5	microfibrillar associated protein 5		ISO	4	158,959,286	158,981,967	RGD:6484113	PID
G	Mfng	MFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase		ISS	7	116,717,405	116,735,280	RGD:2302204	RGD
G	Mfng	MFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase		ISS	7	116,717,405	116,735,280	RGD:1302739	RGD
G	Mfng	MFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase		IEA	7	116,717,405	116,735,280	RGD:6907045	KEGG
G	Mib1	mindbomb E3 ubiquitin protein ligase 1		ISS	18	2,106,102	2,224,819	RGD:1334454	RGD
G	Mib1	mindbomb E3 ubiquitin protein ligase 1		ISO	18	2,106,102	2,224,819	RGD:6484113	PID
G	Myc	myelocytomatosis oncogene		ISO	7	98,953,142	98,958,060	RGD:6484113	PID
G	Mycbp	c-myc binding protein		ISO	5	143,196,136	143,203,083	RGD:6484113	PID
G	Ncor1	nuclear receptor co-repressor 1		ISO	10	48,481,110	48,628,538	RGD:6484113	PID
G	Ncor2	nuclear receptor co-repressor 2		ISO	12	32,617,643	32,725,753	RGD:6484113	PID
G	Ncor2	nuclear receptor co-repressor 2		IEA	12	32,617,643	32,725,753	RGD:6907045	KEGG
G	Ncstn	nicastrin		ISS	13	88,060,484	88,076,493	RGD:2302204	RGD
G	Ncstn	nicastrin		TAS	13	88,060,484	88,076,493	RGD:724403	RGD
G	Ncstn	nicastrin		IEA	13	88,060,484	88,076,493	RGD:6907045	KEGG
G	Ncstn	nicastrin		ISO	13	88,060,484	88,076,493	RGD:6484113	PID
G	Neurl1a	neuralized homolog 1A (Drosophila)		ISS	1	252,502,664	252,573,249	RGD:1334462	RGD
G	Neurl2	neuralized homolog 2 (Drosophila)		ISS	3	155,863,669	155,865,955	RGD:1334462	RGD
G	Notch1	notch 1		IED	3	4,631,797	4,677,640	RGD:1358543	RGD
G	Notch1	notch 1		IDA	3	4,631,797	4,677,640	RGD:2306423	RGD
G	Notch1	notch 1		IDA	3	4,631,797	4,677,640	RGD:724389	RGD
G	Notch1	notch 1		IMP	3	4,631,797	4,677,640	RGD:1334443	RGD
G	Notch1	notch 1		ISS	3	4,631,797	4,677,640	RGD:2302204	RGD
G	Notch1	notch 1		ISO	3	4,631,797	4,677,640	RGD:6484113	PID
G	Notch1	notch 1		IEA	3	4,631,797	4,677,640	RGD:6907045	KEGG
G	Notch2	notch 2		TAS	2	192,839,350	192,986,589	RGD:69906	RGD
G	Notch2	notch 2		ISS	2	192,839,350	192,986,589	RGD:2302204	RGD
G	Notch2	notch 2		ISO	2	192,839,350	192,986,589	RGD:6484113	PID
G	Notch2	notch 2		IEA	2	192,839,350	192,986,589	RGD:6907045	KEGG
G	Notch3	notch 3		ISS	7	12,688,267	12,740,015	RGD:2302204	RGD
G	Notch3	notch 3		IDA	7	12,688,267	12,740,015	RGD:2306423	RGD
G	Notch3	notch 3		IDA	7	12,688,267	12,740,015	RGD:625426	RGD
G	Notch3	notch 3		ISO	7	12,688,267	12,740,015	RGD:6484113	PID
G	Notch3	notch 3		IEA	7	12,688,267	12,740,015	RGD:6907045	KEGG
G	Notch4	notch 4		IDA	20	4,263,205	4,287,312	RGD:1304484	RGD
G	Notch4	notch 4		ISS	20	4,263,205	4,287,312	RGD:2302204	RGD
G	Notch4	notch 4		ISO	20	4,263,205	4,287,312	RGD:6484113	PID
G	Notch4	notch 4		IEA	20	4,263,205	4,287,312	RGD:6907045	KEGG
G	Numb	numb homolog (Drosophila)		TAS	6	107,838,216	107,882,302	RGD:724390	RGD
G	Numb	numb homolog (Drosophila)		ISO	6	107,838,216	107,882,302	RGD:6484113	PID
G	Numb	numb homolog (Drosophila)		IEA	6	107,838,216	107,882,302	RGD:6907045	KEGG
G	Numbl	numb homolog (Drosophila)-like		ISS	1	82,333,804	82,356,657	RGD:1334451	RGD
G	Numbl	numb homolog (Drosophila)-like		IEA	1	82,333,804	82,356,657	RGD:6907045	KEGG
G	Pcaf	p300/CBP-associated factor		IEA	9	882,928	889,661	RGD:6907045	KEGG
G	Pofut1	protein O-fucosyltransferase 1		ISS	3	143,592,269	143,614,466	RGD:2302204	RGD
G	Pofut1	protein O-fucosyltransferase 1		ISS	3	143,592,269	143,614,466	RGD:1334453	RGD
G	Psen1	presenilin 1		ISS	6	107,737,543	107,776,357	RGD:2302204	RGD
G	Psen1	presenilin 1		TAS	6	107,737,543	107,776,357	RGD:724403	RGD
G	Psen1	presenilin 1		IEA	6	107,737,543	107,776,357	RGD:6907045	KEGG
G	Psen1	presenilin 1		ISO	6	107,737,543	107,776,357	RGD:6484113	PID
G	Psen2	presenilin 2		ISS	13	95,934,674	95,951,836	RGD:2302204	RGD
G	Psen2	presenilin 2		IEA	13	95,934,674	95,951,836	RGD:6907045	KEGG
G	Psenen	presenilin enhancer 2 homolog (C. elegans)		ISS	1	85,607,051	85,608,248	RGD:2302204	RGD
G	Psenen	presenilin enhancer 2 homolog (C. elegans)		ISO	1	85,607,051	85,608,248	RGD:6484113	PID
G	Psenen	presenilin enhancer 2 homolog (C. elegans)		IEA	1	85,607,051	85,608,248	RGD:6907045	KEGG
G	Ptcra	pre T-cell antigen receptor alpha		IEA				RGD:6907045	KEGG
G	Rab11a	RAB11a, member RAS oncogene family		ISO	8	68,931,925	68,979,514	RGD:6484113	PID
G	Rbbp8	retinoblastoma binding protein 8		ISO	18	3,266,565	3,333,153	RGD:6484113	PID
G	Rbpj	recombination signal binding protein for immunoglobulin kappa J region		IDA				RGD:2306423	RGD
G	Rbpj	recombination signal binding protein for immunoglobulin kappa J region		ISO				RGD:6484113	PID
G	Rbpj	recombination signal binding protein for immunoglobulin kappa J region		IEA				RGD:6907045	KEGG
G	Rbpjl	recombination signal binding protein for immunoglobulin kappa J region-like		IEA	3	155,425,120	155,437,490	RGD:6907045	KEGG
G	Rbpjl2	recombination signal binding protein for immunoglobulin kappa J region-like 2		IEA	5	4,663,833	4,665,775	RGD:6907045	KEGG
G	Rfng	RFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase		ISS				RGD:2302204	RGD
G	Rfng	RFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase		IMP				RGD:633801	RGD
G	Rfng	RFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase		IEA				RGD:6907045	KEGG
G	Skp1	S-phase kinase-associated protein 1		ISO	10	37,665,417	37,680,338	RGD:6484113	PID
G	Skp2	S-phase kinase-associated protein 2, E3 ubiquitin protein ligase		ISO	2	58,769,164	58,797,229	RGD:6484113	PID
G	Snw1	SNW domain containing 1		IEA	6	111,688,742	111,712,826	RGD:6907045	KEGG
G	Spen	spen homolog, transcriptional regulator (Drosophila)		ISO	5	160,359,738	160,414,311	RGD:6484113	PID
G	Sspo	SCO-spondin		ISO	4	76,533,300	76,587,372	RGD:6484113	PID
G	Yy1	YY1 transcription factor		ISO	6	133,132,419	133,156,686	RGD:6484113	PID
altered Notch signaling pathway
	Symbol	Object Name	GBrowse	Evidence	Chr	Start	Stop	Reference	Source
G	Dll1	delta-like 1 (Drosophila)		ISS	1	54,240,395	54,248,183	RGD:1304492	RGD
G	Dll3	delta-like 3 (Drosophila)		ISS	1	83,373,482	83,381,219	RGD:1304493	RGD
G	Hey1	hairy/enhancer-of-split related with YRPW motif 1		ISS	2	95,174,030	95,176,430	RGD:1334460	RGD
G	Jag1	jagged 1		ISS	3	125,181,063	125,216,481	RGD:1304484	RGD
G	Jag2	jagged 2		ISS	6	137,909,633	137,931,120	RGD:1304492	RGD
G	Notch1	notch 1		ISS	3	4,631,797	4,677,640	RGD:724389	RGD
G	Notch2	notch 2		ISS	2	192,839,350	192,986,589	RGD:69906	RGD
G	Notch3	notch 3		TAS	7	12,688,267	12,740,015	RGD:625426	RGD
G	Notch4	notch 4		ISS	20	4,263,205	4,287,312	RGD:1304484	RGD
G	Numb	numb homolog (Drosophila)		ISS	6	107,838,216	107,882,302	RGD:1334451	RGD
G	Pofut1	protein O-fucosyltransferase 1		ISS	3	143,592,269	143,614,466	RGD:1334453	RGD
altered Notch signaling pathway involving promoters
	Symbol	Object Name	GBrowse	Evidence	Chr	Start	Stop	Reference	Source
G	Hey1	hairy/enhancer-of-split related with YRPW motif 1		ISS	2	95,174,030	95,176,430	RGD:1334460	RGD
altered Notch signaling pathway involving the macromolecules modifying the main players
	Symbol	Object Name	GBrowse	Evidence	Chr	Start	Stop	Reference	Source
G	Numb	numb homolog (Drosophila)		ISS	6	107,838,216	107,882,302	RGD:1334451	RGD
G	Pofut1	protein O-fucosyltransferase 1		ISS	3	143,592,269	143,614,466	RGD:1334453	RGD
G	Psen2	presenilin 2		ISS	13	95,934,674	95,951,836	RGD:2302525	RGD
altered Notch signaling pathway involving the main players
	Symbol	Object Name	GBrowse	Evidence	Chr	Start	Stop	Reference	Source
G	Dll3	delta-like 3 (Drosophila)		ISS	1	83,373,482	83,381,219	RGD:1304493	RGD
G	Jag1	jagged 1		ISS	3	125,181,063	125,216,481	RGD:1334443	RGD
G	Notch1	notch 1		ISS	3	4,631,797	4,677,640	RGD:1334450	RGD
G	Notch3	notch 3		ISS	7	12,688,267	12,740,015	RGD:1334442	RGD

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)

Object Type	Pathway Object	Pathway Object Description
Complex	gamma-convertase	a multiprotein protease complex containing Psen1 or 2, Aph1, Ncstn and Psenen
Functional Class	Dll_ligands	delta-like Notch ligands
Functional Class	Fng	fringe 3-beta-N-acetylglucosaminyltransferase members
Functional Class	Jag_ligands	Jagged Notch ligands
Functional Class	Maml	mastermind-like family members
Functional Class	Notch_receptors	Notch family members

Pathway Gene Annotations

Disease Annotations Associated with Genes in the Notch signaling pathway

Diseases/Genes

Genes/Diseases

Disease Terms	Gene Symbols
Alagille Syndrome	Jag1 , Notch2
Alopecia Areata	Notch4
CADASIL	Notch3
Gaucher Disease	Il4
Pancreatic Neoplasms	Il4 , Myc , Notch1
Pick Disease of the Brain	Psen1
Rubinstein-Taybi Syndrome	Crebbp , Ep300
Osteoporosis	Myc
Dementia	Notch4
Retinal Diseases	Ccnd1
Deafness	Jag1
Ataxia	Cntn1
Respiratory Tract Infections	Il4
Heart Defects, Congenital	Jag1
Cholestasis	Il4
Hearing Loss, Sensorineural	Gata3
Carcinoma, Renal Cell	Myc , Ccnd1 , Skp2
Obesity	Myc
Seizures	Ccnd1 , Neurl1a
Diabetes Mellitus, Type 2	Adam17
Cholangiocarcinoma	Notch1
Dysostoses	Dll3
Cardiomegaly	Myc , Ccnd1 , Yy1
Demyelinating Diseases	Myc
Cardiomyopathy, Dilated	Psen1 , Psen2 , Rbpj
Nephrosis	Gata3
Hypoparathyroidism	Gata3
Hypertension, Pulmonary	Il4 , Myc
Hypothyroidism	Ncor1
Cardiomyopathy, Hypertrophic	Yy1
Osteoarthritis	Jag1 , Ncor2 , Adam12
Polycystic Kidney Diseases	Myc
Ovarian Neoplasms	Ccnd1 , Cdkn1a , Hdac2 , Hdac1 , Skp2
Polycystic Kidney, Autosomal Dominant	Cdkn1a , Myc
Esophageal Neoplasms	Myc
Arteriosclerosis	Furin , Notch4
Acute Kidney Injury	Myc
Aortic Aneurysm, Thoracic	Adam10 , Adam17
Breast Neoplasms	Myc , Ccnd1 , Cdkn1a , Ep300 , Psen2 , Hdac1 , Ncor2 , Skp2
Rhinitis	Il4
Polycystic Kidney, Autosomal Recessive	Myc
Polycystic kidney disease, type 1	Myc
Wilms Tumor	Myc
Hyperparathyroidism	Myc
Uterine Cervical Neoplasms	Ccnd1 , Cdkn1a , Hdac2 , Hdac1 , Skp2
Urinary Bladder Neoplasms	Myc
Carcinoma, Squamous Cell	Ccnd1
Tetralogy of Fallot	Jag1
Intracranial Arteriovenous Malformations	Notch4
Alzheimer Disease	Psen1 , Psen2 , Ncstn
Alzheimer disease type 4	Psen2
Arthritis, Rheumatoid	Notch4
Huntington Disease	Ncor1
Nephritis	Il4
Diabetes Mellitus, Type 1	Notch4
Hypersensitivity, Delayed	Gata3
Colorectal Neoplasms	Ccnd1 , Ep300
Hypertension	Eno1 , Ep300
Prostatic Neoplasms	Myc , Ccnd1 , Cdkn1a , Hdac2 , Ep300 , Hdac1 , Skp2
Prostatic Hyperplasia	Myc
Carcinoma, Hepatocellular	Myc , Ep300 , Skp2
Pancreatitis, Chronic	Jag1 , Dll1
Respiratory Hypersensitivity	Il4
Polycystic Ovary Syndrome	Ncor1
Penile Neoplasms	Ccnd1
Seckel syndrome 2	Rbbp8
Scleroderma, Systemic	Notch4
Hypertension, Renal	Cdkn1a
Barakat syndrome	Gata3
Cerebral Hemorrhage	Psen1
Hidradenitis suppurativa, familial	Psen1 , Ncstn , Psenen
Adenocarcinoma of lung	Myc
Cerebral Amyloid Angiopathy	Psen1
Nasopharyngeal Neoplasms	Ccnd1
Biliary Atresia	Dlk1
Clear-cell metastatic renal cell carcinoma	Myc
Hemorrhage	Psen1 , Psen2
Burkitt Lymphoma	Myc
Giant Cell Arteritis	Jag1 , Dll1
Papillary renal cell carcinoma, sporadic	Myc
DiGeorge Syndrome	Dvl1
Phyllodes Tumor	Cdkn1a
Heart Valve Diseases	Notch1
Heart Diseases	Ep300
Arthritis, Experimental	Il4 , Jag1
Asthma	Il4 , Gata3
Glioma	Dlk1
Behcet Syndrome	Il4
Biliary Tract Neoplasms	Il4
Brain Injuries	Skp2
Bronchiolitis Obliterans	Il4
Burns	Ccnd1
Carcinoma, Intraductal, Noninfiltrating	Ccnd1 , Cdkn1a , Notch4
Carcinoma, Transitional Cell	Ccnd1 , Skp2
Hypoxia, Brain	Ep300
Peritoneal Diseases	Notch1
Colonic Neoplasms	Myc
Common Cold	Il4
Cystitis	Il4
Diabetes Mellitus, Experimental	Furin , Ep300 , Myc
Dermatitis, Irritant	Il4
Encephalomyelitis	Adam17
Encephalomyelitis, Autoimmune, Experimental	Jag1 , Dll1
Endometrial Hyperplasia	Skp2
Leukemia, Myeloid, Acute	Crebbp
Heart Arrest	Ep300
von Hippel-Lindau Disease	Ccnd1
Erectile Dysfunction	Ccnd1
Infarction	Notch3
Influenza, Human	Il4
Nematode Infections	Il4
Leiomyoma	Myc
Leukemia, Plasma Cell	Myc
Multiple Myeloma	Myc , Notch2 , Ccnd1
Liver Neoplasms, Experimental	Notch1 , Ccnd1
Lymphatic Metastasis	Skp2
Mammary Neoplasms, Experimental	Ccnd1 , Notch4
Mammary Neoplasms, Animal	Notch4
Multiple Sclerosis	Il4 , Jag1 , Notch4
Myocardial Infarction	Dvl1
Otitis Media with Effusion	Il4
Pulmonary Fibrosis	Il4 , Psen2
Rhinitis, Allergic, Perennial	Il4
Schizophrenia	Dvl1 , Notch4
Shock, Hemorrhagic	Myc
Tuberculosis, Pulmonary	Il4
Spinal Cord Injuries	Il4
Status Epilepticus	Adam10
Prolactinoma	Myc
Reperfusion Injury	Ccnd1
Leukemia, B-Cell	Myc
Leukemia-Lymphoma, Adult T-Cell	Notch1
Leukemia, Promyelocytic, Acute	Notch1
AIDS-Associated Nephropathy	Notch4
Bronchial Hyperreactivity	Gata3
Endometrial Neoplasms	Jag1 , Notch1 , Ccnd1 , Cdkn1a , Hdac2 , Notch4 , Hdac1 , Ncor2 , Skp2
Carcinoma, Lobular	Ccnd1
Cervical Intraepithelial Neoplasia	Ccnd1 , Hdac2 , Hdac1 , Skp2
Rhabdoid Tumor	Myc
Hyperoxia	Cdkn1a
Prostatic Intraepithelial Neoplasia	Ccnd1 , Hdac1
Anti-Glomerular Basement Membrane Disease	Il4
Carotid Artery Injuries	Jag1 , Myc , Notch3
Osteoarthritis, Knee	Il4
Carcinoma, Pancreatic Ductal	Il4 , Notch1
Frontotemporal Dementia	Psen1
AORTIC VALVE DISEASE 1	Notch1
SPONDYLOCOSTAL DYSOSTOSIS 1, AUTOSOMAL RECESSIVE	Dll3
SPONDYLOCOSTAL DYSOSTOSIS 3, AUTOSOMAL RECESSIVE	Lfng
AUTOIMMUNE DISEASE, SYNDROMIC MULTISYSTEM	Itch
NOONAN SYNDROME-LIKE DISORDER WITH OR WITHOUT JUVENILE MYELOMONOCYTIC LEUKEMIA	Cbl
SPONDYLOCOSTAL DYSOSTOSIS 4, AUTOSOMAL RECESSIVE	Hes7
Alzheimer Disease, Familial, 3, with Spastic Paraparesis and Apraxia	Psen1
Cardiomyopathy, Dilated, 1u	Psen1
Cardiomyopathy, Dilated, 1V	Psen2
Myopathy, Congenital, Compton-North	Cntn1
Lung Reperfusion Injury	Myc
Kidney Reperfusion Injury	Myc
Renal Fibrosis	Myc
Liver Injury	Myc
Transplant Rejection	Myc

Pathway Annotations Associated with Genes in the Notch signaling pathway

Pathways/Genes

Genes/Pathways

Pathway Terms	Gene Symbols
mitogen activated protein kinase signaling pathway	Myc
Wnt signaling pathway	Crebbp , Ctbp1 , Myc , Psen1 , Ctbp2 , Ccnd1 , Ep300 , Dvl1 , Cul1 , Dvl3 , Skp1
Alzheimer disease pathway	Adam10 , Psen1 , Adam17 , Psen2 , Ncstn , Aph1a , Psenen , Aph1b
Huntington disease pathway	Crebbp , Hdac1l , Ep300 , Hdac1 , Hdac2
prion diseases pathway	Notch1
glycolysis/gluconeogenesis pathway	Eno1
long term potentiation	Crebbp , Ep300
cell cycle pathway, mitotic	Crebbp , Myc , Ccnd1 , Cdkn1a , Hdac1l , Hdac2 , Ep300 , Cul1 , Hdac1 , Skp1 , Skp2
G1 phase pathway	Ccnd1
S phase pathway	Ccnd1
Hedgehog signaling pathway	Crebbp , Hdac2 , Hdac1 , Sspo
insulin signaling pathway	Cbl
ubiquitin/proteasome degradation pathway	Cul1 , Itch , Skp1 , Cbl , Skp2
Rab family mediated signaling pathway	Rab11a
epidermal growth factor/neuregulin signaling pathway	Adam10 , Cdkn1a , Adam17 , Cbl , Adam12 , Myc
mTOR signaling pathway	Sspo , Yy1
O-linked glycan biosynthetic pathway	Lfng , Rfng , Mfng , Pofut1
p38 MAPK signaling pathway	Dlk1
the planar cell polarity Wnt signaling pathway	Dvl1
canonical Wnt signaling pathway	Crebbp , Dvl1 , Dvl3
Notch signaling pathway	Adam10 , Crebbp , Ctbp1 , Eno1 , Il4 , Jag1 , Jag2 , Myc , Notch1 , Notch2 , Furin , Psen1 , Ncor1 , Cntn6 , Hes1 , Ctbp2 , Ccnd1 , Cdkn1a , Dll1 , Dll3 , Dnm1 , Rab11a , Dlk1 , Hdac1l , Hdac2 , Ep300 , Numb , Adam17 , Lfng , Dvl1 , Notch3 , Psen2 , Gata3 , Cntn1 , Rfng , Hes5 , Ptcra , Hey1 , Hey2 , Ncstn , Mark2 , Mfng , Pofut1 , Notch4 , Rbpjl , Heyl , Eps15 , Pcaf , Hes7 , Mfap2 , Neurl2 , Neurl1a , Mib1 , Kat2a , Numbl , Mfap5 , Cul1 , Lnx1 , Maml3 , Maml1 , Dvl3 , Rbbp8 , Cir1 , Dll4 , Hdac1 , Ncor2 , Rbpjl2 , Aph1a , Dtx4 , Psenen , Dner , Itch , Skp1 , Sspo , Cbl , Dtx2 , Snw1 , Skp2 , Aph1b , Kdm1a , Dtx3l , Dtx3 , Adam12 , Maml2 , Spen , Rbpj , Mycbp , Fbxw7 , Yy1
Jak-Stat signaling pathway	Crebbp , Il4 , Ccnd1 , Ep300 , Cbl , Myc
phosphatidylinositol 3-kinase-Akt signaling pathway	Cdkn1a
tumor necrosis factor mediated signaling pathway	Adam17
vascular endothelial growth factor signaling pathway	Cbl
autophagy pathway	Rab11a
endocytosis pathway	Dnm1 , Eps15 , Itch , Cbl , Rab11a
platelet-derived growth factor signaling pathway	Cbl , Myc
ephrin - ephrin receptor bidirectional signaling axis	Dnm1 , Cbl
altered Notch signaling pathway	Jag1 , Jag2 , Notch1 , Notch2 , Dll1 , Dll3 , Numb , Notch3 , Hey1 , Pofut1 , Notch4
fibroblast growth factor signaling pathway	Cbl
transforming growth factor-beta superfamily mediated signaling pathway	Crebbp , Myc , Ep300 , Cul1 , Skp1
altered Notch signaling pathway involving the main players	Jag1 , Notch1 , Dll3 , Notch3
altered Notch signaling pathway involving the macromolecules modifying the main players	Numb , Psen2 , Pofut1
altered Notch signaling pathway involving promoters	Hey1
CADASIL pathway	Notch3
Alagille syndrome pathway	Jag1
hypoxia inducible factor pathway	Crebbp , Eno1 , Ep300 , Furin
Reelin signaling pathway	Cbl
proteasome degradation pathway involving cullin-dependent ubiquitin ligases	Cul1
neddylation pathway	Cul1
transforming growth factor-beta Smad dependent signaling pathway	Crebbp , Itch
vasopressin signaling pathway	Rab11a
nuclear factor kappa B signaling pathway	Sspo
estrogen signaling pathway	Crebbp , Ncor1 , Ep300 , Ncor2
interleukin-6 signaling pathway	Adam10 , Adam17 , Myc
androgen signaling pathway	Crebbp , Ncor1 , Ep300 , Ncor2
eicosanoid signaling pathway	Dnm1 , Rab11a
cortisol signaling pathway	Crebbp , Ncor1 , Ep300 , Ncor2
neurotrophic factor signaling pathway	Psen1 , Psen2
scatter factor/hepatocyte growth factor signaling pathway	Cbl
non-canonical Wnt signaling pathway	Dvl1 , Dvl3
prostate cancer pathway	Crebbp , Ccnd1 , Cdkn1a , Ep300
bladder cancer pathway	Ccnd1 , Cdkn1a , Myc
endometrial cancer pathway	Ccnd1 , Myc
colorectal cancer pathway	Ccnd1 , Myc
pancreatic cancer pathway	Ccnd1
Endoplasmic Reticulum-associated degradation pathway	Cul1 , Skp1
insulin responsive facilitative sugar transporter mediated glucose transport pathway	Rab11a
glycolysis pathway	Eno1
gluconeogenesis pathway	Eno1
glypican signaling pathway	Furin
syndecan signaling pathway	Psen1 , Ncstn , Aph1a , Psenen , Aph1b , Adam12
thyroid cancer pathway	Ccnd1 , Myc
small cell lung cancer pathway	Myc , Ccnd1 , Skp2
non-small cell lung cancer pathway	Ccnd1
acute myeloid leukemia pathway	Ccnd1 , Myc
chronic myeloid leukemia pathway	Ctbp1 , Ctbp2 , Ccnd1 , Cdkn1a , Hdac1l , Hdac2 , Hdac1 , Cbl , Myc
glioma pathway	Ccnd1 , Cdkn1a
vasopressin signaling pathway via receptor type 2	Rab11a
p53 signaling pathway	Crebbp , Ccnd1 , Cdkn1a , Ep300 , Hdac1 , Skp2 , Yy1
T cell receptor signaling pathway	Cbl , Il4
cytokine mediated signaling pathway	Il4
tamoxifen pharmacodynamics pathway	Ncor1 , Ncor2
type II interferon signaling pathway	Crebbp , Ep300 , Cbl
interleukin-2 signaling pathway	Myc
interleukin-4 signaling pathway	Cbl , Il4
interleukin-12 signaling pathway	Il4
interleukin-27 signaling pathway	Gata3
forkhead class A signaling pathway	Crebbp , Dlk1 , Ep300
ceramide signaling pathway	Ccnd1 , Myc
interleukin-3 signaling pathway	Hdac1
erythropoietin signaling pathway	Cbl
E-cadherin signaling pathway	Ccnd1
retinoic acid signaling pathway	Ncor1 , Ncor2
renal cell cancer pathway	Crebbp , Ep300
basal cell carcinoma pathway	Dvl1 , Dvl3
melanoma pathway	Ccnd1 , Cdkn1a
asthma disease pathway	Il4
autoimmune thyroid disease pathway	Il4
allograft rejection pathway	Il4
myocarditis pathway	Ccnd1
maturity onset diabetes of the young pathway	Hes1
Mycobacterium tuberculosis infection pathway	Crebbp , Ep300
Leishmania infection pathway	Il4
influenza A virus infection pathway	Crebbp , Ep300 , Furin
hepatitis C virus infection pathway	Cdkn1a
measles infection pathway	Ccnd1 , Il4
spliceosome pathway	Snw1
Fc gamma receptor mediated signaling pathway	Dnm1
Fc epsilon receptor mediated signaling pathway	Il4
RNA degradation pathway	Eno1

Phenotype Annotations Associated with Genes in the Notch signaling pathway

Phenotype/Gene

Gene/Phenotype

References Associated with the Notch signaling pathway:

Ontology Path Diagram:

Import into Pathway Studio:

Notch signaling pathway.gpp