Pathway Human Homo sapiens

Signaling by NOTCH1

R-HSA-1980143 in Reactome release 97: under Signaling by NOTCH, with 74 genes placed in it by the mapping files and 2 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-1980143 (mouse), R-RNO-1980143 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-1980143.6
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2012-03-13
Last updated: 2020-03-16
Events inside: 2, counted from the record

NOTCH1 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 membrane bound ligand expressed in trans on the surface of a neighboring cell. In trans, ligand binding triggers proteolytic cleavage of NOTCH1 and results in release of the NOTCH1 intracellular domain, NICD1, into the cytosol.

NICD1 translocates to the nucleus where it associates with RBPJ (also known as CSL or CBF) and mastermind-like (MAML) proteins (MAML1, MAML2 or MAML3; possibly also MAMLD1) to form NOTCH1 coactivator complex. NOTCH1 coactivator complex activates transcription of genes that possess RBPJ binding sites in their promoters.

Literature Reactome attaches

Localization of the delta-like-1-binding site in human Notch-1 and its modulation by calcium affinityJ Biol Chem, 2008, vol. 283, p. 11785-93PubMed 18296446
Delta-1 activation of notch-1 signaling results in HES-1 transactivationMol Cell Biol, 1998, vol. 18, p. 7423-31PubMed 9819428
The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesisCell, 2009, vol. 137, p. 1124-35PubMed 19524514
The human homolog of rat Jagged1 expressed by marrow stroma inhibits differentiation of 32D cells through interaction with Notch1Immunity, 1998, vol. 8, p. 43-55PubMed 9462510
Isolation and functional analysis of a cDNA for human Jagged2, a gene encoding a ligand for the Notch1 receptorMol Cell Biol, 1997, vol. 17, p. 6057-67PubMed 9315665
Physical interaction of Delta1, Jagged1, and Jagged2 with Notch1 and Notch3 receptorsBiochem Biophys Res Commun, 2000, vol. 276, p. 385-9PubMed 11006133
Fringe glycosyltransferases differentially modulate Notch1 proteolysis induced by Delta1 and Jagged1Mol Biol Cell, 2005, vol. 16, p. 927-42PubMed 15574878
An obligatory role of mind bomb-1 in notch signaling of mammalian developmentPLoS One, 2007, vol. 2, p. e1221PubMed 18043734
Mind bomb-2 is an E3 ligase for Notch ligandJ Biol Chem, 2005, vol. 280, p. 22335-42PubMed 15824097
Neuralized-2 regulates a Notch ligand in cooperation with Mind bomb-1J Biol Chem, 2006, vol. 281, p. 36391-400PubMed 17003037
Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by DeltaDev Cell, 2003, vol. 4, p. 67-82PubMed 12530964
Drosophila neuralized is a ubiquitin ligase that promotes the internalization and degradation of deltaDev Cell, 2001, vol. 1, p. 783-94PubMed 11740940
Neuralized-like 1 (Neurl1) targeted to the plasma membrane by N-myristoylation regulates the Notch ligand Jagged1J Biol Chem, 2008, vol. 283, p. 3846-53PubMed 18077452
Metalloprotease ADAM10 is required for Notch1 site 2 cleavageJ Biol Chem, 2009, vol. 284, p. 31018-27PubMed 19726682
A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACEMol Cell, 2000, vol. 5, p. 207-16PubMed 10882063
The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblastsHum Mol Genet, 2002, vol. 11, p. 2615-24PubMed 12354787
Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesisCell, 1997, vol. 90, p. 271-80PubMed 9244301
A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domainNature, 1999, vol. 398, p. 518-22PubMed 10206645
Notch-1 signalling requires ligand-induced proteolytic release of intracellular domainNature, 1998, vol. 393, p. 382-6PubMed 9620803
Embryonic lethality in mice homozygous for a processing-deficient allele of Notch1Nature, 2000, vol. 405, p. 966-70PubMed 10879540
A histone deacetylase corepressor complex regulates the Notch signal transduction pathwayGenes Dev, 1998, vol. 12, p. 2269-77PubMed 9694793
SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC functionMol Cell Biol, 2000, vol. 20, p. 2400-10PubMed 10713164
A corepressor/coactivator exchange complex required for transcriptional activation by nuclear receptors and other regulated transcription factorsCell, 2004, vol. 116, p. 511-26PubMed 14980219
TBL1 and TBLR1 phosphorylation on regulated gene promoters overcomes dual CtBP and NCoR/SMRT transcriptional repression checkpointsMol Cell, 2008, vol. 29, p. 755-66PubMed 18374649
Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complexGenes Dev, 2002, vol. 16, p. 1397-411PubMed 12050117
p300 and PCAF act cooperatively to mediate transcriptional activation from chromatin templates by notch intracellular domains in vitroMol Cell Biol, 2002, vol. 22, p. 7812-9PubMed 12391150
Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexesCell, 2006, vol. 124, p. 973-83PubMed 16530044
Signalling downstream of activated mammalian NotchNature, 1995, vol. 377, p. 355-8PubMed 7566092
Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexesNat Struct Mol Biol, 2010, vol. 17, p. 1312-7PubMed 20972443
The Notch target genes Hey1 and Hey2 are required for embryonic vascular developmentGenes Dev, 2004, vol. 18, p. 901-11PubMed 15107403
Analysis of HeyL expression in wild-type and Notch pathway mutant mouse embryosMech Dev, 2000, vol. 98, p. 175-8PubMed 11044625
Comparative analysis of the human and mouse Hey1 promoter: Hey genes are new Notch target genesBiochem Biophys Res Commun, 2000, vol. 275, p. 652-60PubMed 10964718
NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growthProc Natl Acad Sci U S A, 2006, vol. 103, p. 18261-6PubMed 17114293
Molecular interaction between TLE1 and the carboxyl-terminal domain of HES-1 containing the WRPW motifBiochem Biophys Res Commun, 1996, vol. 223, p. 701-5PubMed 8687460
The WRPW motif of the hairy-related basic helix-loop-helix repressor proteins acts as a 4-amino-acid transcription repression and protein-protein interaction domainMol Cell Biol, 1996, vol. 16, p. 2670-7PubMed 8649374
Groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with hairy-related bHLH proteinsCell, 1994, vol. 79, p. 805-15PubMed 8001118
Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnoverMol Cell, 2004, vol. 16, p. 509-20PubMed 15546612
The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homologJ Biol Chem, 2001, vol. 276, p. 35847-53PubMed 11461910
SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradationMol Cell Biol, 2001, vol. 21, p. 7403-15PubMed 11585921
FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiationNat Rev Cancer, 2008, vol. 8, p. 83-93PubMed 18094723
Hypoxia requires notch signaling to maintain the undifferentiated cell stateDev Cell, 2005, vol. 9, p. 617-28PubMed 16256737
F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturationCell, 2003, vol. 115, p. 163-75PubMed 14567914
DNER acts as a neuron-specific Notch ligand during Bergmann glial developmentNat Neurosci, 2005, vol. 8, p. 873-80PubMed 15965470
Human deltex is a conserved regulator of Notch signallingNat Genet, 1998, vol. 19, p. 74-8PubMed 9590294
Murine homologs of deltex define a novel gene family involved in vertebrate Notch signaling and neurogenesisInt J Dev Neurosci, 2001, vol. 19, p. 21-35PubMed 11226752
Regulation of Notch signalling by non-visual beta-arrestinNat Cell Biol, 2005, vol. 7, p. 1191-201PubMed 16284625
Itch/AIP4 mediates Deltex degradation through the formation of K29-linked polyubiquitin chainsEMBO Rep, 2006, vol. 7, p. 1147-53PubMed 17028573
Cis-interactions between Notch and Delta generate mutually exclusive signalling statesNature, 2010, vol. 465, p. 86-90PubMed 20418862
dlk acts as a negative regulator of Notch1 activation through interactions with specific EGF-like repeatsExp Cell Res, 2005, vol. 303, p. 343-59PubMed 15652348
The atypical mammalian ligand Delta-like homologue 1 (Dlk1) can regulate Notch signalling in DrosophilaBMC Dev Biol, 2008, vol. 8, p. 11PubMed 18237417
Asymmetric distribution of numb protein during division of the sensory organ precursor cell confers distinct fates to daughter cellsCell, 1994, vol. 76, p. 477-91PubMed 8313469
Numb regulates post-endocytic trafficking and degradation of Notch1J Biol Chem, 2009, vol. 284, p. 26427-38PubMed 19567869
AIP4/Itch regulates Notch receptor degradation in the absence of ligandPLoS One, 2008, vol. 3, p. e2735PubMed 18628966

Reactome's record lists 9 orthologous events, R-MMU-1980143 (Mus musculus), R-RNO-1980143 (Rattus norvegicus) among the species this site serves, and 7 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"Signaling by NOTCH1". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-1980143 with StableID: R-HSA-1980143.6 (accessed 2026-09-30 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 74 genes in this human pathway; showing 1 to 74, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneADAM10	AuthorityHGNC:188	Mapping file id102 NCBI file	EvidenceIEA
GeneADAM17	AuthorityHGNC:195	Mapping file id6868 NCBI file	EvidenceIEA
GeneAPH1A	AuthorityHGNC:29509	Mapping file id51107 NCBI file	EvidenceIEA
GeneAPH1B	AuthorityHGNC:24080	Mapping file id83464 NCBI file	EvidenceIEA
GeneARRB1	AuthorityHGNC:711	Mapping file id408 NCBI file	EvidenceIEA
GeneARRB2	AuthorityHGNC:712	Mapping file id409 NCBI file	EvidenceIEA
GeneCCNC	AuthorityHGNC:1581	Mapping file id892 NCBI file	EvidenceIEA
GeneCDK8	AuthorityHGNC:1779	Mapping file id1024 NCBI file	EvidenceIEA
GeneCNTN1	AuthorityHGNC:2171	Mapping file id1272 NCBI file	EvidenceIEA
GeneCREBBP	AuthorityHGNC:2348	Mapping file id1387 NCBI file	EvidenceIEA, TAS
GeneCUL1	AuthorityHGNC:2551	Mapping file id8454 NCBI file	EvidenceIEA
GeneDLK1	AuthorityHGNC:2907	Mapping file id8788 NCBI file	EvidenceIEA
GeneDLL1	AuthorityHGNC:2908	Mapping file id28514 NCBI file	EvidenceIEA
GeneDLL4	AuthorityHGNC:2910	Mapping file id54567 NCBI file	EvidenceIEA
GeneDNER	AuthorityHGNC:24456	Mapping file id92737 NCBI file	EvidenceIEA
GeneDTX1	AuthorityHGNC:3060	Mapping file id1840 NCBI file	EvidenceIEA, TAS
GeneDTX2	AuthorityHGNC:15973	Mapping file id113878 NCBI file	EvidenceIEA, TAS
GeneDTX4	AuthorityHGNC:29151	Mapping file id23220 NCBI file	EvidenceIEA, TAS
GeneEP300	AuthorityHGNC:3373	Mapping file id2033 NCBI file	EvidenceIEA, TAS
GeneFBXW7	AuthorityHGNC:16712	Mapping file id55294 NCBI file	EvidenceIEA
GeneHDAC1	AuthorityHGNC:4852	Mapping file id3065 NCBI file	EvidenceIEA
GeneHDAC10	AuthorityHGNC:18128	Mapping file id83933 NCBI file	EvidenceIEA
GeneHDAC11	AuthorityHGNC:19086	Mapping file id79885 NCBI file	EvidenceIEA
GeneHDAC2	AuthorityHGNC:4853	Mapping file id3066 NCBI file	EvidenceIEA
GeneHDAC3	AuthorityHGNC:4854	Mapping file id8841 NCBI file	EvidenceIEA
GeneHDAC4	AuthorityHGNC:14063	Mapping file id9759 NCBI file	EvidenceIEA
GeneHDAC5	AuthorityHGNC:14068	Mapping file id10014 NCBI file	EvidenceIEA
GeneHDAC6	AuthorityHGNC:14064	Mapping file id10013 NCBI file	EvidenceIEA
GeneHDAC7	AuthorityHGNC:14067	Mapping file id51564 NCBI file	EvidenceIEA
GeneHDAC8	AuthorityHGNC:13315	Mapping file id55869 NCBI file	EvidenceIEA
GeneHDAC9	AuthorityHGNC:14065	Mapping file id9734 NCBI file	EvidenceIEA
GeneHES1	AuthorityHGNC:5192	Mapping file id3280 NCBI file	EvidenceIEA
GeneHES5	AuthorityHGNC:19764	Mapping file id388585 NCBI file	EvidenceTAS
GeneHEY1	AuthorityHGNC:4880	Mapping file id23462 NCBI file	EvidenceIEA
GeneHEY2	AuthorityHGNC:4881	Mapping file id23493 NCBI file	EvidenceIEA
GeneHEYL	AuthorityHGNC:4882	Mapping file id26508 NCBI file	EvidenceIEA
GeneHIF1A	AuthorityHGNC:4910	Mapping file id3091 NCBI file	EvidenceIEA
GeneITCH	AuthorityHGNC:13890	Mapping file id83737 NCBI file	EvidenceIEA, TAS
GeneJAG1	AuthorityHGNC:6188	Mapping file id182 NCBI file	EvidenceIEA
GeneJAG2	AuthorityHGNC:6189	Mapping file id3714 NCBI file	EvidenceIEA, TAS
GeneKAT2A	AuthorityHGNC:4201	Mapping file id2648 NCBI file	EvidenceIEA, TAS
GeneKAT2B	AuthorityHGNC:8638	Mapping file id8850 NCBI file	EvidenceIEA, TAS
GeneMAML1	AuthorityHGNC:13632	Mapping file id9794 NCBI file	EvidenceIEA, TAS
GeneMAML2	AuthorityHGNC:16259	Mapping file id84441 NCBI file	EvidenceIEA, TAS
GeneMAML3	AuthorityHGNC:16272	Mapping file id55534 NCBI file	EvidenceIEA, TAS
GeneMAMLD1	AuthorityHGNC:2568	Mapping file id10046 NCBI file	EvidenceIEA, TAS
GeneMIB1	AuthorityHGNC:21086	Mapping file id57534 NCBI file	EvidenceIEA
GeneMIB2	AuthorityHGNC:30577	Mapping file id142678 NCBI file	EvidenceIEA
GeneMYC	AuthorityHGNC:7553	Mapping file id4609 NCBI file	EvidenceTAS
GeneNBEA	AuthorityHGNC:7648	Mapping file id26960 NCBI file	EvidenceIEA
GeneNCOR1	AuthorityHGNC:7672	Mapping file id9611 NCBI file	EvidenceIEA
GeneNCOR2	AuthorityHGNC:7673	Mapping file id9612 NCBI file	EvidenceIEA
GeneNCSTN	AuthorityHGNC:17091	Mapping file id23385 NCBI file	EvidenceIEA
GeneNEURL1	AuthorityHGNC:7761	Mapping file id9148 NCBI file	EvidenceIEA
GeneNEURL1B	AuthorityHGNC:35422	Mapping file id54492 NCBI file	EvidenceIEA
GeneNOTCH1	AuthorityHGNC:7881	Mapping file id4851 NCBI file	EvidenceIEA, TAS
GeneNUMB	AuthorityHGNC:8060	Mapping file id8650 NCBI file	EvidenceIEA
GenePSEN1	AuthorityHGNC:9508	Mapping file id5663 NCBI file	EvidenceIEA
GenePSEN2	AuthorityHGNC:9509	Mapping file id5664 NCBI file	EvidenceIEA
GenePSENEN	AuthorityHGNC:30100	Mapping file id55851 NCBI file	EvidenceIEA
GeneRBPJ	AuthorityHGNC:5724	Mapping file id3516 NCBI file	EvidenceIEA, TAS
GeneRBX1	AuthorityHGNC:9928	Mapping file id9978 NCBI file	EvidenceIEA
GeneRPS27A	AuthorityHGNC:10417	Mapping file id6233 NCBI file	EvidenceIEA, TAS
GeneSKP1	AuthorityHGNC:10899	Mapping file id6500 NCBI file	EvidenceIEA
GeneSNW1	AuthorityHGNC:16696	Mapping file id22938 NCBI file	EvidenceIEA, TAS
GeneTBL1X	AuthorityHGNC:11585	Mapping file id6907 NCBI file	EvidenceIEA
GeneTBL1XR1	AuthorityHGNC:29529	Mapping file id79718 NCBI file	EvidenceIEA
GeneTLE1	AuthorityHGNC:11837	Mapping file id7088 NCBI file	EvidenceIEA
GeneTLE2	AuthorityHGNC:11838	Mapping file id7089 NCBI file	EvidenceIEA
GeneTLE3	AuthorityHGNC:11839	Mapping file id7090 NCBI file	EvidenceIEA
GeneTLE4	AuthorityHGNC:11840	Mapping file id7091 NCBI file	EvidenceIEA
GeneUBA52	AuthorityHGNC:12458	Mapping file id7311 NCBI file	EvidenceIEA, TAS
GeneUBB	AuthorityHGNC:12463	Mapping file id7314 NCBI file	EvidenceIEA, TAS
GeneUBC	AuthorityHGNC:12468	Mapping file id7316 NCBI file	EvidenceIEA, TAS

Evidence codes on this page: IEA, TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Signaling by NOTCHR-HSA-157118241 genes

Children

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.