Notch1

UniProt ID: Q01705
Organism: Mus musculus
Review Status: IN PROGRESS
📝 Provide Detailed Feedback

Gene Description

Notch1 is the canonical mouse Notch receptor, a single-pass transmembrane protein that mediates juxtacrine cell-cell signaling. Ligand binding by DLL/JAG family proteins triggers ADAM and gamma-secretase cleavage, releasing the Notch intracellular domain (NICD), which enters the nucleus and forms an RBPJ/MAML transcriptional coactivator complex to activate target genes. In mouse, Notch1 has central roles in cell-fate decisions during embryogenesis and tissue homeostasis, with especially strong evidence for cardiovascular development, neurogenesis/gliogenesis, hematopoietic stem cell regulation, angiogenesis, and inhibition of myogenic differentiation.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0007219 Notch signaling pathway
IBA
GO_REF:0000033
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
IBA
GO_REF:0000033
PENDING
Summary: TODO: Review this GOA annotation
GO:0007411 axon guidance
IBA
GO_REF:0000033
PENDING
Summary: TODO: Review this GOA annotation
GO:0009986 cell surface
IBA
GO_REF:0000033
PENDING
Summary: TODO: Review this GOA annotation
GO:0043235 receptor complex
IBA
GO_REF:0000033
PENDING
Summary: TODO: Review this GOA annotation
GO:0001525 angiogenesis
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0001701 in utero embryonic development
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0001947 heart looping
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0002011 morphogenesis of an epithelial sheet
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0002064 epithelial cell development
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0002437 inflammatory response to antigenic stimulus
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0005509 calcium ion binding
IEA
GO_REF:0000002
PENDING
Summary: TODO: Review this GOA annotation
GO:0005634 nucleus
IEA
GO_REF:0000120
PENDING
Summary: TODO: Review this GOA annotation
GO:0005829 cytosol
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
IEA
GO_REF:0000120
PENDING
Summary: TODO: Review this GOA annotation
GO:0006355 regulation of DNA-templated transcription
IEA
GO_REF:0000002
PENDING
Summary: TODO: Review this GOA annotation
GO:0006959 humoral immune response
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0007219 Notch signaling pathway
IEA
GO_REF:0000120
PENDING
Summary: TODO: Review this GOA annotation
GO:0010001 glial cell differentiation
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0010718 positive regulation of epithelial to mesenchymal transition
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0010720 positive regulation of cell development
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0012505 endomembrane system
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0016020 membrane
IEA
GO_REF:0000120
PENDING
Summary: TODO: Review this GOA annotation
GO:0030154 cell differentiation
IEA
GO_REF:0000002
PENDING
Summary: TODO: Review this GOA annotation
GO:0030326 embryonic limb morphogenesis
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0030513 positive regulation of BMP signaling pathway
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0030858 positive regulation of epithelial cell differentiation
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0031902 late endosome membrane
IEA
GO_REF:0000044
PENDING
Summary: TODO: Review this GOA annotation
GO:0035850 epithelial cell differentiation involved in kidney development
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0038023 signaling receptor activity
IEA
GO_REF:0000002
PENDING
Summary: TODO: Review this GOA annotation
GO:0042981 regulation of apoptotic process
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0045165 cell fate commitment
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0048589 developmental growth
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0048608 reproductive structure development
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0048844 artery morphogenesis
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0050793 regulation of developmental process
IEA
GO_REF:0000002
PENDING
Summary: TODO: Review this GOA annotation
GO:0070986 left/right axis specification
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0072012 glomerulus vasculature development
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0072080 nephron tubule development
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:2000136 regulation of cell proliferation involved in heart morphogenesis
IEA
GO_REF:0000117
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:17210915
Baf60c is a nuclear Notch signaling component required for t...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:21102556
RITA, a novel modulator of Notch signalling, acts via nuclea...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:22258620
Pten coordinates retinal neurogenesis by regulating Notch si...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:38891776
Pin1 Downregulation Is Involved in Excess Retinoic Acid-Indu...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:8749394
Physical interaction between a novel domain of the receptor ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0000122 negative regulation of transcription by RNA polymerase II
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0001554 luteolysis
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0001669 acrosomal vesicle
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0001837 epithelial to mesenchymal transition
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0002052 positive regulation of neuroblast proliferation
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0002193 MAML1-RBP-Jkappa- ICN1 complex
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0003151 outflow tract morphogenesis
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0003180 aortic valve morphogenesis
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0003184 pulmonary valve morphogenesis
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0003192 mitral valve formation
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0003264 regulation of cardioblast proliferation
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0003713 transcription coactivator activity
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0004888 transmembrane signaling receptor activity
IEA
GO_REF:0000120
PENDING
Summary: TODO: Review this GOA annotation
GO:0007221 positive regulation of transcription of Notch receptor target
IEA
GO_REF:0000120
PENDING
Summary: TODO: Review this GOA annotation
GO:0007283 spermatogenesis
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0007507 heart development
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0008284 positive regulation of cell population proliferation
IEA
GO_REF:0000120
PENDING
Summary: TODO: Review this GOA annotation
GO:0008285 negative regulation of cell population proliferation
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0010628 positive regulation of gene expression
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0010629 negative regulation of gene expression
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0010667 negative regulation of cardiac muscle cell apoptotic process
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0010812 negative regulation of cell-substrate adhesion
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0021515 cell differentiation in spinal cord
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0031100 animal organ regeneration
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0032496 response to lipopolysaccharide
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0032966 negative regulation of collagen biosynthetic process
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0035148 tube formation
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0035924 cellular response to vascular endothelial growth factor stimulus
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0042127 regulation of cell population proliferation
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0042246 tissue regeneration
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0042802 identical protein binding
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0043235 receptor complex
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0045603 positive regulation of endothelial cell differentiation
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0045662 negative regulation of myoblast differentiation
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0045665 negative regulation of neuron differentiation
IEA
GO_REF:0000120
PENDING
Summary: TODO: Review this GOA annotation
GO:0045687 positive regulation of glial cell differentiation
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0045893 positive regulation of DNA-templated transcription
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IEA
GO_REF:0000120
PENDING
Summary: TODO: Review this GOA annotation
GO:0046579 positive regulation of Ras protein signal transduction
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0048708 astrocyte differentiation
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0048709 oligodendrocyte differentiation
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0051152 positive regulation of smooth muscle cell differentiation
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0060354 negative regulation of cell adhesion molecule production
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0060412 ventricular septum morphogenesis
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0062043 positive regulation of cardiac epithelial to mesenchymal transition
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0070374 positive regulation of ERK1 and ERK2 cascade
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0071228 cellular response to tumor cell
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0071372 cellular response to follicle-stimulating hormone stimulus
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0090051 negative regulation of cell migration involved in sprouting angiogenesis
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0097150 neuronal stem cell population maintenance
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:2000048 negative regulation of cell-cell adhesion mediated by cadherin
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:2000737 negative regulation of stem cell differentiation
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:2000811 negative regulation of anoikis
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:2001027 negative regulation of endothelial cell chemotaxis
IEA
GO_REF:0000107
PENDING
Summary: TODO: Review this GOA annotation
GO:0000122 negative regulation of transcription by RNA polymerase II
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0001837 epithelial to mesenchymal transition
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0002193 MAML1-RBP-Jkappa- ICN1 complex
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0003151 outflow tract morphogenesis
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0003180 aortic valve morphogenesis
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0003184 pulmonary valve morphogenesis
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0003192 mitral valve formation
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0003713 transcription coactivator activity
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0004888 transmembrane signaling receptor activity
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0005634 nucleus
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0007219 Notch signaling pathway
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0007507 heart development
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0008284 positive regulation of cell population proliferation
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0008285 negative regulation of cell population proliferation
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0010629 negative regulation of gene expression
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0010812 negative regulation of cell-substrate adhesion
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0035148 tube formation
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0035924 cellular response to vascular endothelial growth factor stimulus
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0042802 identical protein binding
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0045662 negative regulation of myoblast differentiation
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0045893 positive regulation of DNA-templated transcription
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0046579 positive regulation of Ras protein signal transduction
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0051152 positive regulation of smooth muscle cell differentiation
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0060354 negative regulation of cell adhesion molecule production
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0060412 ventricular septum morphogenesis
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0070374 positive regulation of ERK1 and ERK2 cascade
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0071228 cellular response to tumor cell
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0071372 cellular response to follicle-stimulating hormone stimulus
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0090051 negative regulation of cell migration involved in sprouting angiogenesis
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:2000048 negative regulation of cell-cell adhesion mediated by cadherin
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:2000737 negative regulation of stem cell differentiation
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:2000811 negative regulation of anoikis
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:2001027 negative regulation of endothelial cell chemotaxis
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0008285 negative regulation of cell population proliferation
IDA
PMID:26491108
Notch-Tnf signalling is required for development and homeost...
PENDING
Summary: TODO: Review this GOA annotation
GO:0008285 negative regulation of cell population proliferation
IMP
PMID:26491108
Notch-Tnf signalling is required for development and homeost...
PENDING
Summary: TODO: Review this GOA annotation
GO:2000137 negative regulation of cell proliferation involved in heart morphogenesis
IDA
PMID:26491108
Notch-Tnf signalling is required for development and homeost...
PENDING
Summary: TODO: Review this GOA annotation
GO:2000137 negative regulation of cell proliferation involved in heart morphogenesis
IMP
PMID:26491108
Notch-Tnf signalling is required for development and homeost...
PENDING
Summary: TODO: Review this GOA annotation
GO:1990433 CSL-Notch-Mastermind transcription factor complex
ISO
GO_REF:0000119
PENDING
Summary: TODO: Review this GOA annotation
GO:0001669 acrosomal vesicle
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0002052 positive regulation of neuroblast proliferation
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0003264 regulation of cardioblast proliferation
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0004888 transmembrane signaling receptor activity
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0005634 nucleus
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0007219 Notch signaling pathway
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0007221 positive regulation of transcription of Notch receptor target
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0007283 spermatogenesis
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0010628 positive regulation of gene expression
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0010667 negative regulation of cardiac muscle cell apoptotic process
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0032966 negative regulation of collagen biosynthetic process
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0042127 regulation of cell population proliferation
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0045603 positive regulation of endothelial cell differentiation
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0045665 negative regulation of neuron differentiation
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0045687 positive regulation of glial cell differentiation
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0048708 astrocyte differentiation
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0062043 positive regulation of cardiac epithelial to mesenchymal transition
ISO
GO_REF:0000096
PENDING
Summary: TODO: Review this GOA annotation
GO:0098685 Schaffer collateral - CA1 synapse
IMP
PMID:21315255
Activity-induced Notch signaling in neurons requires Arc/Arg...
PENDING
Summary: TODO: Review this GOA annotation
GO:0098685 Schaffer collateral - CA1 synapse
IDA
PMID:21315255
Activity-induced Notch signaling in neurons requires Arc/Arg...
PENDING
Summary: TODO: Review this GOA annotation
GO:0098685 Schaffer collateral - CA1 synapse
IMP
PMID:26635527
Notch1 Regulates Hippocampal Plasticity Through Interaction ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0098685 Schaffer collateral - CA1 synapse
IDA
PMID:26635527
Notch1 Regulates Hippocampal Plasticity Through Interaction ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0098839 postsynaptic density membrane
IEP
PMID:21315255
Activity-induced Notch signaling in neurons requires Arc/Arg...
PENDING
Summary: TODO: Review this GOA annotation
GO:0098839 postsynaptic density membrane
IDA
PMID:21315255
Activity-induced Notch signaling in neurons requires Arc/Arg...
PENDING
Summary: TODO: Review this GOA annotation
GO:0098839 postsynaptic density membrane
IDA
PMID:26635527
Notch1 Regulates Hippocampal Plasticity Through Interaction ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0098978 glutamatergic synapse
IMP
PMID:26635527
Notch1 Regulates Hippocampal Plasticity Through Interaction ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0098978 glutamatergic synapse
IDA
PMID:26635527
Notch1 Regulates Hippocampal Plasticity Through Interaction ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0099565 chemical synaptic transmission, postsynaptic
IMP
PMID:21315255
Activity-induced Notch signaling in neurons requires Arc/Arg...
PENDING
Summary: TODO: Review this GOA annotation
GO:0099565 chemical synaptic transmission, postsynaptic
IDA
PMID:21315255
Activity-induced Notch signaling in neurons requires Arc/Arg...
PENDING
Summary: TODO: Review this GOA annotation
GO:0007219 Notch signaling pathway
ISS
GO_REF:0000024
PENDING
Summary: TODO: Review this GOA annotation
GO:0007219 Notch signaling pathway
IMP
PMID:14701881
Notch promotes epithelial-mesenchymal transition during card...
PENDING
Summary: TODO: Review this GOA annotation
GO:0007219 Notch signaling pathway
IMP
PMID:20007915
Distinct roles for cell-autonomous Notch signaling in cardio...
PENDING
Summary: TODO: Review this GOA annotation
GO:0007219 Notch signaling pathway
IGI
PMID:20890042
Integration of a Notch-dependent mesenchymal gene program an...
PENDING
Summary: TODO: Review this GOA annotation
GO:0061344 regulation of cell adhesion involved in heart morphogenesis
IMP
PMID:14701881
Notch promotes epithelial-mesenchymal transition during card...
PENDING
Summary: TODO: Review this GOA annotation
GO:0070168 negative regulation of biomineral tissue development
IMP
PMID:26491108
Notch-Tnf signalling is required for development and homeost...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:22110751
Inhibitory role of Notch1 in calcific aortic valve disease.
PENDING
Summary: TODO: Review this GOA annotation
GO:0010008 endosome membrane
TAS
Reactome:R-MMU-9793875
PENDING
Summary: TODO: Review this GOA annotation
GO:0010832 negative regulation of myotube differentiation
IMP
PMID:18299578
Interaction with factor inhibiting HIF-1 defines an addition...
PENDING
Summary: TODO: Review this GOA annotation
GO:0050768 negative regulation of neurogenesis
IMP
PMID:18299578
Interaction with factor inhibiting HIF-1 defines an addition...
PENDING
Summary: TODO: Review this GOA annotation
GO:0071456 cellular response to hypoxia
IDA
PMID:18299578
Interaction with factor inhibiting HIF-1 defines an addition...
PENDING
Summary: TODO: Review this GOA annotation
GO:0140537 transcription regulator activator activity
IDA
PMID:18299578
Interaction with factor inhibiting HIF-1 defines an addition...
PENDING
Summary: TODO: Review this GOA annotation
GO:0006357 regulation of transcription by RNA polymerase II
IMP
PMID:20007915
Distinct roles for cell-autonomous Notch signaling in cardio...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060379 cardiac muscle cell myoblast differentiation
IMP
PMID:20007915
Distinct roles for cell-autonomous Notch signaling in cardio...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:27719760
BLOS2 negatively regulates Notch signaling during neural and...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:18430783
Zfp64 participates in Notch signaling and regulates differen...
PENDING
Summary: TODO: Review this GOA annotation
GO:0030163 protein catabolic process
IDA
PMID:28561022
IL-17 induced NOTCH1 activation in oligodendrocyte progenito...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:28561022
IL-17 induced NOTCH1 activation in oligodendrocyte progenito...
PENDING
Summary: TODO: Review this GOA annotation
GO:0006606 protein import into nucleus
IDA
PMID:28561022
IL-17 induced NOTCH1 activation in oligodendrocyte progenito...
PENDING
Summary: TODO: Review this GOA annotation
GO:0010467 gene expression
IDA
PMID:28561022
IL-17 induced NOTCH1 activation in oligodendrocyte progenito...
PENDING
Summary: TODO: Review this GOA annotation
GO:0072538 T-helper 17 type immune response
IDA
PMID:28561022
IL-17 induced NOTCH1 activation in oligodendrocyte progenito...
PENDING
Summary: TODO: Review this GOA annotation
GO:0097400 interleukin-17-mediated signaling pathway
IDA
PMID:28561022
IL-17 induced NOTCH1 activation in oligodendrocyte progenito...
PENDING
Summary: TODO: Review this GOA annotation
GO:0007221 positive regulation of transcription of Notch receptor target
IGI
PMID:12794108
Notch-regulated ankyrin-repeat protein inhibits Notch1 signa...
PENDING
Summary: TODO: Review this GOA annotation
GO:0007221 positive regulation of transcription of Notch receptor target
IGI
PMID:23160044
BCL6 controls neurogenesis through Sirt1-dependent epigeneti...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003713 transcription coactivator activity
IDA
PMID:17658278
Notch directly regulates Gata3 expression during T helper 2 ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003713 transcription coactivator activity
IDA
PMID:9111338
RBP-L, a transcription factor related to RBP-Jkappa.
PENDING
Summary: TODO: Review this GOA annotation
GO:0003713 transcription coactivator activity
IDA
PMID:17336907
Notch signaling is essential for ventricular chamber develop...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:24667410
Notch4 reveals a novel mechanism regulating Notch signal tra...
PENDING
Summary: TODO: Review this GOA annotation
GO:0070168 negative regulation of biomineral tissue development
IDA
PMID:23583836
Endothelial nitric oxide signaling regulates Notch1 in aorti...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:17336907
Notch signaling is essential for ventricular chamber develop...
PENDING
Summary: TODO: Review this GOA annotation
GO:0120163 negative regulation of cold-induced thermogenesis
IMP
PMID:25038826
Inhibition of Notch signaling promotes browning of white adi...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003180 aortic valve morphogenesis
IMP
PMID:26491108
Notch-Tnf signalling is required for development and homeost...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003182 coronary sinus valve morphogenesis
IMP
PMID:26491108
Notch-Tnf signalling is required for development and homeost...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003184 pulmonary valve morphogenesis
IMP
PMID:26491108
Notch-Tnf signalling is required for development and homeost...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003332 negative regulation of extracellular matrix constituent secretion
IMP
PMID:26491108
Notch-Tnf signalling is required for development and homeost...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
IDA
PMID:26491108
Notch-Tnf signalling is required for development and homeost...
PENDING
Summary: TODO: Review this GOA annotation
GO:0010614 negative regulation of cardiac muscle hypertrophy
IMP
PMID:26491108
Notch-Tnf signalling is required for development and homeost...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060412 ventricular septum morphogenesis
IMP
PMID:26491108
Notch-Tnf signalling is required for development and homeost...
PENDING
Summary: TODO: Review this GOA annotation
GO:1902339 positive regulation of apoptotic process involved in morphogenesis
IDA
PMID:26491108
Notch-Tnf signalling is required for development and homeost...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003180 aortic valve morphogenesis
IGI
PMID:27107132
Endothelial Notch1 Is Required for Proper Development of the...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003184 pulmonary valve morphogenesis
IGI
PMID:27107132
Endothelial Notch1 Is Required for Proper Development of the...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003203 endocardial cushion morphogenesis
IGI
PMID:27107132
Endothelial Notch1 Is Required for Proper Development of the...
PENDING
Summary: TODO: Review this GOA annotation
GO:0048873 homeostasis of number of cells within a tissue
IGI
PMID:27107132
Endothelial Notch1 Is Required for Proper Development of the...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060412 ventricular septum morphogenesis
IGI
PMID:27107132
Endothelial Notch1 Is Required for Proper Development of the...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003180 aortic valve morphogenesis
IGI
PMID:23583836
Endothelial nitric oxide signaling regulates Notch1 in aorti...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005634 nucleus
IDA
PMID:23583836
Endothelial nitric oxide signaling regulates Notch1 in aorti...
PENDING
Summary: TODO: Review this GOA annotation
GO:0010628 positive regulation of gene expression
IGI
PMID:23583836
Endothelial nitric oxide signaling regulates Notch1 in aorti...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:28089369
Deciphering the Fringe-Mediated Notch Code: Identification o...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:28498977
Consequences of MEGF10 deficiency on myoblast function and N...
PENDING
Summary: TODO: Review this GOA annotation
GO:0048845 venous blood vessel morphogenesis
IMP
PMID:18952909
Artery and vein size is balanced by Notch and ephrin B2/EphB...
PENDING
Summary: TODO: Review this GOA annotation
GO:1903849 positive regulation of aorta morphogenesis
IMP
PMID:18952909
Artery and vein size is balanced by Notch and ephrin B2/EphB...
PENDING
Summary: TODO: Review this GOA annotation
GO:0010468 regulation of gene expression
IMP
PMID:11076679
Oscillating expression of c-Hey2 in the presomitic mesoderm ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:21191019
A protein (ORF2) encoded by the latency-related gene of bovi...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045070 positive regulation of viral genome replication
IMP
PMID:21191019
A protein (ORF2) encoded by the latency-related gene of bovi...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003197 endocardial cushion development
IMP
PMID:14701881
Notch promotes epithelial-mesenchymal transition during card...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:21985982
Delta-like 1-Lysine613 regulates notch signaling.
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:18676613
The intracellular region of Notch ligands Dll1 and Dll3 regu...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:24715457
Cadherin-based adhesions in the apical endfoot are required ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005912 adherens junction
IDA
PMID:24715457
Cadherin-based adhesions in the apical endfoot are required ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0016324 apical plasma membrane
IDA
PMID:24715457
Cadherin-based adhesions in the apical endfoot are required ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:12050162
The nephroblastoma overexpressed gene (NOV/ccn3) protein ass...
PENDING
Summary: TODO: Review this GOA annotation
GO:0006357 regulation of transcription by RNA polymerase II
IMP
PMID:25535395
Notch inhibition induces mitotically generated hair cells in...
PENDING
Summary: TODO: Review this GOA annotation
GO:0008285 negative regulation of cell population proliferation
IMP
PMID:25535395
Notch inhibition induces mitotically generated hair cells in...
PENDING
Summary: TODO: Review this GOA annotation
GO:0042127 regulation of cell population proliferation
IGI
PMID:25535395
Notch inhibition induces mitotically generated hair cells in...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045607 regulation of inner ear auditory receptor cell differentiation
IMP
PMID:25535395
Notch inhibition induces mitotically generated hair cells in...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045608 negative regulation of inner ear auditory receptor cell differentiation
IMP
PMID:25535395
Notch inhibition induces mitotically generated hair cells in...
PENDING
Summary: TODO: Review this GOA annotation
GO:0090090 negative regulation of canonical Wnt signaling pathway
IMP
PMID:25535395
Notch inhibition induces mitotically generated hair cells in...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005112 Notch binding
IPI
PMID:24667410
Notch4 reveals a novel mechanism regulating Notch signal tra...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005783 endoplasmic reticulum
IDA
PMID:24667410
Notch4 reveals a novel mechanism regulating Notch signal tra...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
IDA
PMID:24667410
Notch4 reveals a novel mechanism regulating Notch signal tra...
PENDING
Summary: TODO: Review this GOA annotation
GO:0008593 regulation of Notch signaling pathway
IGI
PMID:24667410
Notch4 reveals a novel mechanism regulating Notch signal tra...
PENDING
Summary: TODO: Review this GOA annotation
GO:0031410 cytoplasmic vesicle
IDA
PMID:24667410
Notch4 reveals a novel mechanism regulating Notch signal tra...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045747 positive regulation of Notch signaling pathway
IDA
PMID:24667410
Notch4 reveals a novel mechanism regulating Notch signal tra...
PENDING
Summary: TODO: Review this GOA annotation
GO:0071944 cell periphery
IDA
PMID:23284756
Ascl1 (Mash1) knockout perturbs differentiation of nonneuron...
PENDING
Summary: TODO: Review this GOA annotation
GO:0043235 receptor complex
ISO
PMID:23382219
Structural basis for endosomal trafficking of diverse transm...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060271 cilium assembly
ISS
GO_REF:0000024
PENDING
Summary: TODO: Review this GOA annotation
GO:1902263 apoptotic process involved in embryonic digit morphogenesis
IMP
PMID:16245338
Notch1 signals through Jagged2 to regulate apoptosis in the ...
PENDING
Summary: TODO: Review this GOA annotation
ISS
GO_REF:0000024
PENDING
Summary: TODO: Review this GOA annotation
GO:0005856 cytoskeleton
ISS
GO_REF:0000024
PENDING
Summary: TODO: Review this GOA annotation
GO:0030027 lamellipodium
ISS
GO_REF:0000024
PENDING
Summary: TODO: Review this GOA annotation
GO:0008285 negative regulation of cell population proliferation
ISS
GO_REF:0000024
PENDING
Summary: TODO: Review this GOA annotation
GO:0035148 tube formation
ISS
GO_REF:0000024
PENDING
Summary: TODO: Review this GOA annotation
GO:0035924 cellular response to vascular endothelial growth factor stimulus
ISS
GO_REF:0000024
PENDING
Summary: TODO: Review this GOA annotation
GO:0090051 negative regulation of cell migration involved in sprouting angiogenesis
ISS
GO_REF:0000024
PENDING
Summary: TODO: Review this GOA annotation
GO:2001027 negative regulation of endothelial cell chemotaxis
ISS
GO_REF:0000024
PENDING
Summary: TODO: Review this GOA annotation
GO:0035914 skeletal muscle cell differentiation
IMP
PMID:22147266
Analysis of early C2C12 myogenesis identifies stably and dif...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005634 nucleus
IDA
PMID:17685488
Monitoring Notch1 activity in development: evidence for a fe...
PENDING
Summary: TODO: Review this GOA annotation
GO:0000122 negative regulation of transcription by RNA polymerase II
IMP
PMID:14701881
Notch promotes epithelial-mesenchymal transition during card...
PENDING
Summary: TODO: Review this GOA annotation
GO:0000122 negative regulation of transcription by RNA polymerase II
IMP
PMID:16025100
Mutations in NOTCH1 cause aortic valve disease.
PENDING
Summary: TODO: Review this GOA annotation
GO:0005634 nucleus
IMP
PMID:20007915
Distinct roles for cell-autonomous Notch signaling in cardio...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:14701881
Notch promotes epithelial-mesenchymal transition during card...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:16025100
Mutations in NOTCH1 cause aortic valve disease.
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:17303760
Combined loss of Hey1 and HeyL causes congenital heart defec...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:20007915
Distinct roles for cell-autonomous Notch signaling in cardio...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003180 aortic valve morphogenesis
ISS
GO_REF:0000024
PENDING
Summary: TODO: Review this GOA annotation
GO:0003213 cardiac right atrium morphogenesis
IMP
PMID:20007915
Distinct roles for cell-autonomous Notch signaling in cardio...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003241 growth involved in heart morphogenesis
IMP
PMID:20007915
Distinct roles for cell-autonomous Notch signaling in cardio...
PENDING
Summary: TODO: Review this GOA annotation
GO:0014031 mesenchymal cell development
IMP
PMID:17303760
Combined loss of Hey1 and HeyL causes congenital heart defec...
PENDING
Summary: TODO: Review this GOA annotation
GO:0030279 negative regulation of ossification
IMP
PMID:21493891
Diet-induced aortic valve disease in mice haploinsufficient ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045892 negative regulation of DNA-templated transcription
IMP
PMID:19695258
Notch1 represses osteogenic pathways in aortic valve cells.
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:15107403
The Notch target genes Hey1 and Hey2 are required for embryo...
PENDING
Summary: TODO: Review this GOA annotation
GO:0055008 cardiac muscle tissue morphogenesis
IMP
PMID:20007915
Distinct roles for cell-autonomous Notch signaling in cardio...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060045 positive regulation of cardiac muscle cell proliferation
IMP
PMID:20007915
Distinct roles for cell-autonomous Notch signaling in cardio...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060317 cardiac epithelial to mesenchymal transition
IMP
PMID:17303760
Combined loss of Hey1 and HeyL causes congenital heart defec...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060411 cardiac septum morphogenesis
IMP
PMID:20007915
Distinct roles for cell-autonomous Notch signaling in cardio...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060842 arterial endothelial cell differentiation
IMP
PMID:15107403
The Notch target genes Hey1 and Hey2 are required for embryo...
PENDING
Summary: TODO: Review this GOA annotation
GO:0000122 negative regulation of transcription by RNA polymerase II
IMP
PMID:20890042
Integration of a Notch-dependent mesenchymal gene program an...
PENDING
Summary: TODO: Review this GOA annotation
GO:0001947 heart looping
IGI
PMID:12730124
Notch signaling regulates left-right asymmetry determination...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003160 endocardium morphogenesis
IMP
PMID:20890042
Integration of a Notch-dependent mesenchymal gene program an...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003162 atrioventricular node development
IMP
PMID:21266778
Notch signaling regulates murine atrioventricular conduction...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003169 coronary vein morphogenesis
IMP
PMID:21311046
Differential Notch signaling in the epicardium is required f...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003181 atrioventricular valve morphogenesis
IMP
PMID:14701881
Notch promotes epithelial-mesenchymal transition during card...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003181 atrioventricular valve morphogenesis
IMP
PMID:21266778
Notch signaling regulates murine atrioventricular conduction...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003198 epithelial to mesenchymal transition involved in endocardial cushion formation
IMP
PMID:14701881
Notch promotes epithelial-mesenchymal transition during card...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003203 endocardial cushion morphogenesis
IMP
PMID:14701881
Notch promotes epithelial-mesenchymal transition during card...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003207 cardiac chamber formation
IMP
PMID:20890042
Integration of a Notch-dependent mesenchymal gene program an...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003208 cardiac ventricle morphogenesis
IMP
PMID:21311046
Differential Notch signaling in the epicardium is required f...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003209 cardiac atrium morphogenesis
IMP
PMID:20890042
Integration of a Notch-dependent mesenchymal gene program an...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003214 cardiac left ventricle morphogenesis
IMP
PMID:20890042
Integration of a Notch-dependent mesenchymal gene program an...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003273 cell migration involved in endocardial cushion formation
IMP
PMID:20890042
Integration of a Notch-dependent mesenchymal gene program an...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003344 pericardium morphogenesis
IMP
PMID:14701881
Notch promotes epithelial-mesenchymal transition during card...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003344 pericardium morphogenesis
IMP
PMID:20890042
Integration of a Notch-dependent mesenchymal gene program an...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003344 pericardium morphogenesis
IMP
PMID:21311046
Differential Notch signaling in the epicardium is required f...
PENDING
Summary: TODO: Review this GOA annotation
GO:0010718 positive regulation of epithelial to mesenchymal transition
IMP
PMID:20890042
Integration of a Notch-dependent mesenchymal gene program an...
PENDING
Summary: TODO: Review this GOA annotation
GO:0030334 regulation of cell migration
IMP
PMID:20890042
Integration of a Notch-dependent mesenchymal gene program an...
PENDING
Summary: TODO: Review this GOA annotation
GO:0030335 positive regulation of cell migration
IMP
PMID:20890042
Integration of a Notch-dependent mesenchymal gene program an...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IMP
PMID:21311046
Differential Notch signaling in the epicardium is required f...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060038 cardiac muscle cell proliferation
IMP
PMID:21311046
Differential Notch signaling in the epicardium is required f...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060843 venous endothelial cell differentiation
IMP
PMID:20890042
Integration of a Notch-dependent mesenchymal gene program an...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060948 cardiac vascular smooth muscle cell development
IMP
PMID:21311046
Differential Notch signaling in the epicardium is required f...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060956 endocardial cell differentiation
IMP
PMID:20890042
Integration of a Notch-dependent mesenchymal gene program an...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060979 vasculogenesis involved in coronary vascular morphogenesis
IMP
PMID:21311046
Differential Notch signaling in the epicardium is required f...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060982 coronary artery morphogenesis
IMP
PMID:21311046
Differential Notch signaling in the epicardium is required f...
PENDING
Summary: TODO: Review this GOA annotation
GO:0061384 heart trabecula morphogenesis
IMP
PMID:20890042
Integration of a Notch-dependent mesenchymal gene program an...
PENDING
Summary: TODO: Review this GOA annotation
GO:0070986 left/right axis specification
IGI
PMID:12730124
Notch signaling regulates left-right asymmetry determination...
PENDING
Summary: TODO: Review this GOA annotation
GO:1901201 regulation of extracellular matrix assembly
IMP
PMID:21311046
Differential Notch signaling in the epicardium is required f...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005634 nucleus
IDA
PMID:17336907
Notch signaling is essential for ventricular chamber develop...
PENDING
Summary: TODO: Review this GOA annotation
GO:1901189 positive regulation of ephrin receptor signaling pathway
IC
PMID:17336907
Notch signaling is essential for ventricular chamber develop...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003157 endocardium development
IMP
PMID:17336907
Notch signaling is essential for ventricular chamber develop...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003222 ventricular trabecula myocardium morphogenesis
IMP
PMID:17336907
Notch signaling is essential for ventricular chamber develop...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005654 nucleoplasm
TAS
Reactome:R-MMU-4396387
PENDING
Summary: TODO: Review this GOA annotation
GO:0005654 nucleoplasm
TAS
Reactome:R-MMU-9667655
PENDING
Summary: TODO: Review this GOA annotation
GO:0005654 nucleoplasm
TAS
Reactome:R-MMU-9824206
PENDING
Summary: TODO: Review this GOA annotation
GO:0005654 nucleoplasm
TAS
Reactome:R-MMU-9824230
PENDING
Summary: TODO: Review this GOA annotation
GO:0005654 nucleoplasm
TAS
Reactome:R-MMU-9824231
PENDING
Summary: TODO: Review this GOA annotation
GO:0005654 nucleoplasm
TAS
Reactome:R-MMU-9824278
PENDING
Summary: TODO: Review this GOA annotation
GO:0005654 nucleoplasm
TAS
Reactome:R-NUL-2064853
PENDING
Summary: TODO: Review this GOA annotation
GO:0005654 nucleoplasm
TAS
Reactome:R-NUL-2064883
PENDING
Summary: TODO: Review this GOA annotation
GO:0005654 nucleoplasm
TAS
Reactome:R-NUL-2065560
PENDING
Summary: TODO: Review this GOA annotation
GO:0005654 nucleoplasm
TAS
Reactome:R-NUL-4396363
PENDING
Summary: TODO: Review this GOA annotation
GO:0005829 cytosol
TAS
Reactome:R-MMU-2067638
PENDING
Summary: TODO: Review this GOA annotation
GO:0005829 cytosol
TAS
Reactome:R-MMU-209285
PENDING
Summary: TODO: Review this GOA annotation
GO:0005829 cytosol
TAS
Reactome:R-NUL-2065902
PENDING
Summary: TODO: Review this GOA annotation
GO:0019899 enzyme binding
IPI
PMID:17573339
Asparaginyl hydroxylation of the Notch ankyrin repeat domain...
PENDING
Summary: TODO: Review this GOA annotation
GO:0019899 enzyme binding
IPI
PMID:18299578
Interaction with factor inhibiting HIF-1 defines an addition...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:19245366
MYPT1, the targeting subunit of smooth-muscle myosin phospha...
PENDING
Summary: TODO: Review this GOA annotation
GO:0004857 enzyme inhibitor activity
IDA
PMID:17573339
Asparaginyl hydroxylation of the Notch ankyrin repeat domain...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005634 nucleus
IDA
PMID:18299578
Interaction with factor inhibiting HIF-1 defines an addition...
PENDING
Summary: TODO: Review this GOA annotation
GO:0007219 Notch signaling pathway
IDA
PMID:21419176
The EGF-like proteins DLK1 and DLK2 function as inhibitory n...
PENDING
Summary: TODO: Review this GOA annotation
GO:0043086 negative regulation of catalytic activity
IDA
PMID:17573339
Asparaginyl hydroxylation of the Notch ankyrin repeat domain...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005576 extracellular region
TAS
Reactome:R-MMU-2053938
PENDING
Summary: TODO: Review this GOA annotation
GO:0005576 extracellular region
TAS
Reactome:R-MMU-2053963
PENDING
Summary: TODO: Review this GOA annotation
GO:0005576 extracellular region
TAS
Reactome:R-MMU-2066712
PENDING
Summary: TODO: Review this GOA annotation
GO:0005576 extracellular region
TAS
Reactome:R-MMU-2067638
PENDING
Summary: TODO: Review this GOA annotation
GO:0005576 extracellular region
TAS
Reactome:R-MMU-2071906
PENDING
Summary: TODO: Review this GOA annotation
GO:0005576 extracellular region
TAS
Reactome:R-MMU-2077477
PENDING
Summary: TODO: Review this GOA annotation
GO:0005576 extracellular region
TAS
Reactome:R-MMU-2077479
PENDING
Summary: TODO: Review this GOA annotation
GO:0005576 extracellular region
TAS
Reactome:R-NUL-2065902
PENDING
Summary: TODO: Review this GOA annotation
GO:0005576 extracellular region
TAS
Reactome:R-NUL-209162
PENDING
Summary: TODO: Review this GOA annotation
GO:0000139 Golgi membrane
TAS
Reactome:R-MMU-2023158
PENDING
Summary: TODO: Review this GOA annotation
GO:0000139 Golgi membrane
TAS
Reactome:R-MMU-2032750
PENDING
Summary: TODO: Review this GOA annotation
GO:0005789 endoplasmic reticulum membrane
TAS
Reactome:R-MMU-2023179
PENDING
Summary: TODO: Review this GOA annotation
GO:0005789 endoplasmic reticulum membrane
TAS
Reactome:R-MMU-2032750
PENDING
Summary: TODO: Review this GOA annotation
GO:0005789 endoplasmic reticulum membrane
TAS
Reactome:R-MMU-9824249
PENDING
Summary: TODO: Review this GOA annotation
GO:0005789 endoplasmic reticulum membrane
TAS
Reactome:R-NUL-1986584
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
TAS
Reactome:R-MMU-209285
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
TAS
Reactome:R-NUL-2063915
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
TAS
Reactome:R-NUL-209162
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
TAS
Reactome:R-MMU-2053938
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:15574878
Fringe glycosyltransferases differentially modulate Notch1 p...
PENDING
Summary: TODO: Review this GOA annotation
GO:0009986 cell surface
IDA
PMID:15574878
Fringe glycosyltransferases differentially modulate Notch1 p...
PENDING
Summary: TODO: Review this GOA annotation
GO:0002437 inflammatory response to antigenic stimulus
IGI
PMID:17658279
Direct regulation of Gata3 expression determines the T helpe...
PENDING
Summary: TODO: Review this GOA annotation
GO:0006959 humoral immune response
IGI
PMID:17658279
Direct regulation of Gata3 expression determines the T helpe...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003219 cardiac right ventricle formation
IMP
PMID:19620969
A regulatory pathway involving Notch1/beta-catenin/Isl1 dete...
PENDING
Summary: TODO: Review this GOA annotation
GO:0007219 Notch signaling pathway
IMP
PMID:19620969
A regulatory pathway involving Notch1/beta-catenin/Isl1 dete...
PENDING
Summary: TODO: Review this GOA annotation
GO:0090090 negative regulation of canonical Wnt signaling pathway
IMP
PMID:19620969
A regulatory pathway involving Notch1/beta-catenin/Isl1 dete...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:20547764
ZFP423 coordinates Notch and bone morphogenetic protein sign...
PENDING
Summary: TODO: Review this GOA annotation
GO:0030513 positive regulation of BMP signaling pathway
IDA
PMID:20547764
ZFP423 coordinates Notch and bone morphogenetic protein sign...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045893 positive regulation of DNA-templated transcription
IDA
PMID:20547764
ZFP423 coordinates Notch and bone morphogenetic protein sign...
PENDING
Summary: TODO: Review this GOA annotation
GO:2000974 negative regulation of pro-B cell differentiation
IMP
PMID:12032823
Overexpression of the Notch target genes Hes in vivo induces...
PENDING
Summary: TODO: Review this GOA annotation
GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT
IDA
PMID:15156153
Hes binding to STAT3 mediates crosstalk between Notch and JA...
PENDING
Summary: TODO: Review this GOA annotation
GO:0000122 negative regulation of transcription by RNA polymerase II
IDA
PMID:12032823
Overexpression of the Notch target genes Hes in vivo induces...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045893 positive regulation of DNA-templated transcription
IDA
PMID:12666205
Hes1 but not Hes5 regulates an astrocyte versus oligodendroc...
PENDING
Summary: TODO: Review this GOA annotation
GO:0048711 positive regulation of astrocyte differentiation
IDA
PMID:12666205
Hes1 but not Hes5 regulates an astrocyte versus oligodendroc...
PENDING
Summary: TODO: Review this GOA annotation
GO:0048715 negative regulation of oligodendrocyte differentiation
IDA
PMID:12666205
Hes1 but not Hes5 regulates an astrocyte versus oligodendroc...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060253 negative regulation of glial cell proliferation
IDA
PMID:12666205
Hes1 but not Hes5 regulates an astrocyte versus oligodendroc...
PENDING
Summary: TODO: Review this GOA annotation
GO:0072017 distal tubule development
IEP
PMID:15821257
Segmental expression of Notch and Hairy genes in nephrogenes...
PENDING
Summary: TODO: Review this GOA annotation
GO:0072044 collecting duct development
IEP
PMID:15821257
Segmental expression of Notch and Hairy genes in nephrogenes...
PENDING
Summary: TODO: Review this GOA annotation
GO:0072144 glomerular mesangial cell development
IEP
PMID:15821257
Segmental expression of Notch and Hairy genes in nephrogenes...
PENDING
Summary: TODO: Review this GOA annotation
GO:0007219 Notch signaling pathway
IMP
PMID:19154718
Hey2 regulation by FGF provides a Notch-independent mechanis...
PENDING
Summary: TODO: Review this GOA annotation
GO:0009912 auditory receptor cell fate commitment
IMP
PMID:19154718
Hey2 regulation by FGF provides a Notch-independent mechanis...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045665 negative regulation of neuron differentiation
IGI
PMID:10205173
Hes1 and Hes5 as notch effectors in mammalian neuronal diffe...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045955 negative regulation of calcium ion-dependent exocytosis
IMP
PMID:19251639
Notch and Wnt signals cooperatively control cell proliferati...
PENDING
Summary: TODO: Review this GOA annotation
GO:0050679 positive regulation of epithelial cell proliferation
IGI
PMID:19251639
Notch and Wnt signals cooperatively control cell proliferati...
PENDING
Summary: TODO: Review this GOA annotation
GO:0032495 response to muramyl dipeptide
IDA
PMID:21156799
Intracellular pathogen sensor NOD2 programs macrophages to t...
PENDING
Summary: TODO: Review this GOA annotation
GO:0030514 negative regulation of BMP signaling pathway
IMP
PMID:19695258
Notch1 represses osteogenic pathways in aortic valve cells.
PENDING
Summary: TODO: Review this GOA annotation
GO:0045668 negative regulation of osteoblast differentiation
IMP
PMID:19695258
Notch1 represses osteogenic pathways in aortic valve cells.
PENDING
Summary: TODO: Review this GOA annotation
GO:0002051 osteoblast fate commitment
NAS
PMID:16025100
Mutations in NOTCH1 cause aortic valve disease.
PENDING
Summary: TODO: Review this GOA annotation
GO:0003160 endocardium morphogenesis
IEP
PMID:16025100
Mutations in NOTCH1 cause aortic valve disease.
PENDING
Summary: TODO: Review this GOA annotation
GO:0045892 negative regulation of DNA-templated transcription
IDA
PMID:16025100
Mutations in NOTCH1 cause aortic valve disease.
PENDING
Summary: TODO: Review this GOA annotation
GO:0060528 secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development
IMP
PMID:16360140
Notch signaling is required for normal prostatic epithelial ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060740 prostate gland epithelium morphogenesis
IMP
PMID:16360140
Notch signaling is required for normal prostatic epithelial ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0060768 regulation of epithelial cell proliferation involved in prostate gland development
IMP
PMID:16360140
Notch signaling is required for normal prostatic epithelial ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0001701 in utero embryonic development
IMP
PMID:7789282
Notch1 is required for the coordinate segmentation of somite...
PENDING
Summary: TODO: Review this GOA annotation
GO:0007368 determination of left/right symmetry
IMP
PMID:7789282
Notch1 is required for the coordinate segmentation of somite...
PENDING
Summary: TODO: Review this GOA annotation
GO:0014807 regulation of somitogenesis
IMP
PMID:7789282
Notch1 is required for the coordinate segmentation of somite...
PENDING
Summary: TODO: Review this GOA annotation
GO:0021915 neural tube development
IMP
PMID:7789282
Notch1 is required for the coordinate segmentation of somite...
PENDING
Summary: TODO: Review this GOA annotation
GO:0043069 negative regulation of programmed cell death
IMP
PMID:7789282
Notch1 is required for the coordinate segmentation of somite...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005634 nucleus
IDA
PMID:16324690
BMP7 inhibits branching morphogenesis in the prostate gland ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045893 positive regulation of DNA-templated transcription
IDA
PMID:9111338
RBP-L, a transcription factor related to RBP-Jkappa.
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:10958687
Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly in...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:9315665
Isolation and functional analysis of a cDNA for human Jagged...
PENDING
Summary: TODO: Review this GOA annotation
GO:0001889 liver development
IMP
PMID:15226394
Notch signaling controls hepatoblast differentiation by alte...
PENDING
Summary: TODO: Review this GOA annotation
GO:0010468 regulation of gene expression
IMP
PMID:9102301
Conservation of the Notch signalling pathway in mammalian ne...
PENDING
Summary: TODO: Review this GOA annotation
GO:0030182 neuron differentiation
IMP
PMID:9102301
Conservation of the Notch signalling pathway in mammalian ne...
PENDING
Summary: TODO: Review this GOA annotation
GO:0050767 regulation of neurogenesis
IMP
PMID:9102301
Conservation of the Notch signalling pathway in mammalian ne...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
TAS
Reactome:R-MMU-2053963
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
TAS
Reactome:R-MMU-2066712
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
TAS
Reactome:R-MMU-2067638
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
TAS
Reactome:R-MMU-2071906
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
TAS
Reactome:R-MMU-2077477
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
TAS
Reactome:R-MMU-2077479
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
TAS
Reactome:R-NUL-2065902
PENDING
Summary: TODO: Review this GOA annotation
GO:0005634 nucleus
IDA
PMID:17079689
Canonical notch signaling functions as a commitment switch i...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
IDA
PMID:17079689
Canonical notch signaling functions as a commitment switch i...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045618 positive regulation of keratinocyte differentiation
IGI
PMID:16618808
Cross-regulation between Notch and p63 in keratinocyte commi...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045618 positive regulation of keratinocyte differentiation
IDA
PMID:17079689
Canonical notch signaling functions as a commitment switch i...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:16618808
Cross-regulation between Notch and p63 in keratinocyte commi...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IGI
PMID:16618808
Cross-regulation between Notch and p63 in keratinocyte commi...
PENDING
Summary: TODO: Review this GOA annotation
GO:0031490 chromatin DNA binding
IDA
PMID:17658278
Notch directly regulates Gata3 expression during T helper 2 ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:17658278
Notch directly regulates Gata3 expression during T helper 2 ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0046533 negative regulation of photoreceptor cell differentiation
IMP
PMID:16452096
Notch 1 inhibits photoreceptor production in the developing ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005737 cytoplasm
IDA
PMID:15965470
DNER acts as a neuron-specific Notch ligand during Bergmann ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0010001 glial cell differentiation
IMP
PMID:15965470
DNER acts as a neuron-specific Notch ligand during Bergmann ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005634 nucleus
IDA
PMID:16607638
Jag2-Notch1 signaling regulates oral epithelial differentiat...
PENDING
Summary: TODO: Review this GOA annotation
GO:0007440 foregut morphogenesis
IMP
PMID:16107537
Direct regulation of intestinal fate by Notch.
PENDING
Summary: TODO: Review this GOA annotation
GO:0045165 cell fate commitment
IMP
PMID:16107537
Direct regulation of intestinal fate by Notch.
PENDING
Summary: TODO: Review this GOA annotation
GO:0050678 regulation of epithelial cell proliferation
IMP
PMID:16107537
Direct regulation of intestinal fate by Notch.
PENDING
Summary: TODO: Review this GOA annotation
GO:0002040 sprouting angiogenesis
IMP
PMID:15809373
Essential role of endothelial Notch1 in angiogenesis.
PENDING
Summary: TODO: Review this GOA annotation
GO:0031069 hair follicle morphogenesis
IMP
PMID:15978571
Notch1 is essential for postnatal hair follicle development ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0030326 embryonic limb morphogenesis
IGI
PMID:16169548
Notch1 and 2 cooperate in limb ectoderm to receive an early ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0043065 positive regulation of apoptotic process
IGI
PMID:16169548
Notch1 and 2 cooperate in limb ectoderm to receive an early ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0035116 embryonic hindlimb morphogenesis
IMP
PMID:16245338
Notch1 signals through Jagged2 to regulate apoptosis in the ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:16145673
Fjx1: a notch-inducible secreted ligand with specific bindin...
PENDING
Summary: TODO: Review this GOA annotation
GO:0048754 branching morphogenesis of an epithelial tube
IMP
PMID:15064243
Functional diversity of notch family genes in fetal lung dev...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005634 nucleus
IDA
PMID:10206645
A presenilin-1-dependent gamma-secretase-like protease media...
PENDING
Summary: TODO: Review this GOA annotation
GO:0007409 axonogenesis
IMP
PMID:16120638
Notch signaling coordinates the patterning of striatal compa...
PENDING
Summary: TODO: Review this GOA annotation
GO:0030900 forebrain development
IMP
PMID:16120638
Notch signaling coordinates the patterning of striatal compa...
PENDING
Summary: TODO: Review this GOA annotation
GO:0030900 forebrain development
IGI
PMID:16120638
Notch signaling coordinates the patterning of striatal compa...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045665 negative regulation of neuron differentiation
IMP
PMID:16120638
Notch signaling coordinates the patterning of striatal compa...
PENDING
Summary: TODO: Review this GOA annotation
GO:0048663 neuron fate commitment
IGI
PMID:16120638
Notch signaling coordinates the patterning of striatal compa...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:15902259
The Mesp2 transcription factor establishes segmental borders...
PENDING
Summary: TODO: Review this GOA annotation
GO:0001708 cell fate specification
IMP
PMID:15068794
High commitment of embryonic keratinocytes to terminal diffe...
PENDING
Summary: TODO: Review this GOA annotation
GO:0007409 axonogenesis
IDA
PMID:15598981
Targeted deletion of numb and numblike in sensory neurons re...
PENDING
Summary: TODO: Review this GOA annotation
GO:0030154 cell differentiation
IMP
PMID:12186854
Notch1 control of oligodendrocyte differentiation in the spi...
PENDING
Summary: TODO: Review this GOA annotation
GO:0030216 keratinocyte differentiation
IMP
PMID:15068794
High commitment of embryonic keratinocytes to terminal diffe...
PENDING
Summary: TODO: Review this GOA annotation
GO:0003682 chromatin binding
IDA
PMID:15689374
RBPjkappa-dependent Notch function regulates Gata2 and is es...
PENDING
Summary: TODO: Review this GOA annotation
GO:0006357 regulation of transcription by RNA polymerase II
IGI
PMID:15689374
RBPjkappa-dependent Notch function regulates Gata2 and is es...
PENDING
Summary: TODO: Review this GOA annotation
GO:0030324 lung development
IMP
PMID:15064243
Functional diversity of notch family genes in fetal lung dev...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045596 negative regulation of cell differentiation
IMP
PMID:15064243
Functional diversity of notch family genes in fetal lung dev...
PENDING
Summary: TODO: Review this GOA annotation
GO:0008284 positive regulation of cell population proliferation
IGI
PMID:15509736
Fibroblast growth factor receptor signaling promotes radial ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II
IDA
PMID:12783854
Periodic repression by the bHLH factor Hes7 is an essential ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0048103 somatic stem cell division
IGI
PMID:15509736
Fibroblast growth factor receptor signaling promotes radial ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0008544 epidermis development
IGI
PMID:15525534
gamma-secretase functions through Notch signaling to maintai...
PENDING
Summary: TODO: Review this GOA annotation
GO:0031069 hair follicle morphogenesis
IMP
PMID:15525534
gamma-secretase functions through Notch signaling to maintai...
PENDING
Summary: TODO: Review this GOA annotation
GO:0043065 positive regulation of apoptotic process
IDA
PMID:15081359
Notch activation induces apoptosis in neural progenitor cell...
PENDING
Summary: TODO: Review this GOA annotation
GO:0001837 epithelial to mesenchymal transition
IMP
PMID:14701881
Notch promotes epithelial-mesenchymal transition during card...
PENDING
Summary: TODO: Review this GOA annotation
GO:0007492 endoderm development
IMP
PMID:14657333
Notch signaling controls multiple steps of pancreatic differ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0030154 cell differentiation
IMP
PMID:14657333
Notch signaling controls multiple steps of pancreatic differ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane
IC
PMID:10551863
Mouse jagged1 physically interacts with notch2 and other not...
PENDING
Summary: TODO: Review this GOA annotation
GO:0007219 Notch signaling pathway
IC
PMID:10551863
Mouse jagged1 physically interacts with notch2 and other not...
PENDING
Summary: TODO: Review this GOA annotation
GO:0048103 somatic stem cell division
IDA
PMID:12717450
A role for Wnt signalling in self-renewal of haematopoietic ...
PENDING
Summary: TODO: Review this GOA annotation
GO:0007368 determination of left/right symmetry
IMP
PMID:12730124
Notch signaling regulates left-right asymmetry determination...
PENDING
Summary: TODO: Review this GOA annotation
GO:0005515 protein binding
IPI
PMID:10551863
Mouse jagged1 physically interacts with notch2 and other not...
PENDING
Summary: TODO: Review this GOA annotation
GO:0007386 compartment pattern specification
IMP
PMID:12001066
Segmentation defects of Notch pathway mutants and absence of...
PENDING
Summary: TODO: Review this GOA annotation

References

Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs
Combined Automated Annotation using Multiple IEA Methods
Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation.
A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain.
Mouse jagged1 physically interacts with notch2 and other notch receptors. Assessment by quantitative methods.
Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of Notch2.
Oscillating expression of c-Hey2 in the presomitic mesoderm suggests that the segmentation clock may use combinatorial signaling through multiple interacting bHLH factors.
Segmentation defects of Notch pathway mutants and absence of a synergistic phenotype in lunatic fringe/radical fringe double mutant mice.
Overexpression of the Notch target genes Hes in vivo induces lymphoid and myeloid alterations.
The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway.
Notch1 control of oligodendrocyte differentiation in the spinal cord.
Hes1 but not Hes5 regulates an astrocyte versus oligodendrocyte fate choice in glial restricted precursors.
A role for Wnt signalling in self-renewal of haematopoietic stem cells.
Notch signaling regulates left-right asymmetry determination by inducing Nodal expression.
Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock.
Notch-regulated ankyrin-repeat protein inhibits Notch1 signaling: multiple Notch1 signaling pathways involved in T cell development.
Notch signaling controls multiple steps of pancreatic differentiation.
Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation.
Functional diversity of notch family genes in fetal lung development.
High commitment of embryonic keratinocytes to terminal differentiation through a Notch1-caspase 3 regulatory mechanism.
Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathway.
The Notch target genes Hey1 and Hey2 are required for embryonic vascular development.
Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling.
Notch signaling controls hepatoblast differentiation by altering the expression of liver-enriched transcription factors.
Fibroblast growth factor receptor signaling promotes radial glial identity and interacts with Notch1 signaling in telencephalic progenitors.
gamma-secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesis.
Fringe glycosyltransferases differentially modulate Notch1 proteolysis induced by Delta1 and Jagged1.
Targeted deletion of numb and numblike in sensory neurons reveals their essential functions in axon arborization.
RBPjkappa-dependent Notch function regulates Gata2 and is essential for the formation of intra-embryonic hematopoietic cells.
Essential role of endothelial Notch1 in angiogenesis.
Segmental expression of Notch and Hairy genes in nephrogenesis.
The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity.
DNER acts as a neuron-specific Notch ligand during Bergmann glial development.
Notch1 is essential for postnatal hair follicle development and homeostasis.
Mutations in NOTCH1 cause aortic valve disease.
Direct regulation of intestinal fate by Notch.
Notch signaling coordinates the patterning of striatal compartments.
Fjx1: a notch-inducible secreted ligand with specific binding sites in developing mouse embryos and adult brain.
Notch1 and 2 cooperate in limb ectoderm to receive an early Jagged2 signal regulating interdigital apoptosis.
Notch1 signals through Jagged2 to regulate apoptosis in the apical ectodermal ridge of the developing limb bud.
BMP7 inhibits branching morphogenesis in the prostate gland and interferes with Notch signaling.
Notch signaling is required for normal prostatic epithelial cell proliferation and differentiation.
Notch 1 inhibits photoreceptor production in the developing mammalian retina.
Jag2-Notch1 signaling regulates oral epithelial differentiation and palate development.
Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation.
Canonical notch signaling functions as a commitment switch in the epidermal lineage.
Baf60c is a nuclear Notch signaling component required for the establishment of left-right asymmetry.
Combined loss of Hey1 and HeyL causes congenital heart defects because of impaired epithelial to mesenchymal transition.
Notch signaling is essential for ventricular chamber development.
Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor.
Notch directly regulates Gata3 expression during T helper 2 cell differentiation.
Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch.
Monitoring Notch1 activity in development: evidence for a feedback regulatory loop.
Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways.
Zfp64 participates in Notch signaling and regulates differentiation in mesenchymal cells.
The intracellular region of Notch ligands Dll1 and Dll3 regulates their trafficking and signaling activity.
Artery and vein size is balanced by Notch and ephrin B2/EphB4 during angiogenesis.
Hey2 regulation by FGF provides a Notch-independent mechanism for maintaining pillar cell fate in the organ of Corti.
MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH).
Notch and Wnt signals cooperatively control cell proliferation and tumorigenesis in the intestine.
A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate.
Notch1 represses osteogenic pathways in aortic valve cells.
Distinct roles for cell-autonomous Notch signaling in cardiomyocytes of the embryonic and adult heart.
ZFP423 coordinates Notch and bone morphogenetic protein signaling, selectively up-regulating Hes5 gene expression.
Integration of a Notch-dependent mesenchymal gene program and Bmp2-driven cell invasiveness regulates murine cardiac valve formation.
RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J.
Intracellular pathogen sensor NOD2 programs macrophages to trigger Notch1 activation.
A protein (ORF2) encoded by the latency-related gene of bovine herpesvirus 1 interacts with Notch1 and Notch3.
Notch signaling regulates murine atrioventricular conduction and the formation of accessory pathways.
Differential Notch signaling in the epicardium is required for cardiac inflow development and coronary vessel morphogenesis.
Activity-induced Notch signaling in neurons requires Arc/Arg3.1 and is essential for synaptic plasticity in hippocampal networks.
The EGF-like proteins DLK1 and DLK2 function as inhibitory non-canonical ligands of NOTCH1 receptor that modulate each other's activities.
Diet-induced aortic valve disease in mice haploinsufficient for the Notch pathway effector RBPJK/CSL.
Delta-like 1-Lysine613 regulates notch signaling.
Inhibitory role of Notch1 in calcific aortic valve disease.
Analysis of early C2C12 myogenesis identifies stably and differentially expressed transcriptional regulators whose knock-down inhibits myoblast differentiation.
Pten coordinates retinal neurogenesis by regulating Notch signalling.
BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets.
Ascl1 (Mash1) knockout perturbs differentiation of nonneuronal cells in olfactory epithelium.
Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins.
Endothelial nitric oxide signaling regulates Notch1 in aortic valve disease.
Notch4 reveals a novel mechanism regulating Notch signal transduction.
Cadherin-based adhesions in the apical endfoot are required for active Notch signaling to control neurogenesis in vertebrates.
Inhibition of Notch signaling promotes browning of white adipose tissue and ameliorates obesity.
Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway.
Notch-Tnf signalling is required for development and homeostasis of arterial valves.
Notch1 Regulates Hippocampal Plasticity Through Interaction with the Reelin Pathway, Glutamatergic Transmission and CREB Signaling.
Endothelial Notch1 Is Required for Proper Development of the Semilunar Valves and Cardiac Outflow Tract.
BLOS2 negatively regulates Notch signaling during neural and hematopoietic stem and progenitor cell development.
Deciphering the Fringe-Mediated Notch Code: Identification of Activating and Inhibiting Sites Allowing Discrimination between Ligands.
Consequences of MEGF10 deficiency on myoblast function and Notch1 interactions.
IL-17 induced NOTCH1 activation in oligodendrocyte progenitor cells enhances proliferation and inflammatory gene expression.
Pin1 Downregulation Is Involved in Excess Retinoic Acid-Induced Failure of Neural Tube Closure.
Notch1 is required for the coordinate segmentation of somites.
Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J kappa/Su(H).
Conservation of the Notch signalling pathway in mammalian neurogenesis.
RBP-L, a transcription factor related to RBP-Jkappa.
Isolation and functional analysis of a cDNA for human Jagged2, a gene encoding a ligand for the Notch1 receptor.
Reactome:R-MMU-2023158
Glycosylation of Pre-Notch by Fringe
Reactome:R-MMU-2023179
Glucosylation of Pre-Notch by Poglut1
Reactome:R-MMU-2032750
Sel1l negatively regulates Pre-Notch exit from endoplasmic reticulum
Reactome:R-MMU-2053938
Dll4 binds Notch1
Reactome:R-MMU-2053963
Notch1 binds Jag1
Reactome:R-MMU-2066712
Dner binds Notch1
Reactome:R-MMU-2067638
Gamma secretase cleaves Dner:Notch1 complex
Reactome:R-MMU-2071906
Notch1 binds Dlk1
Reactome:R-MMU-2077477
Numb recruits Itch to Notch1
Reactome:R-MMU-2077479
Itch ubiquitinates Notch
Reactome:R-MMU-209285
The transmembrane complex Murine gamma-secretase cleaves Murine NEXT at the S3 site leaving NTM and releasing NICD into the cytoplasm
Reactome:R-MMU-4396387
mNOTCH1 coactivator complex bind promoters of Hey genes
Reactome:R-MMU-9667655
Nbea binds nicd1
Reactome:R-MMU-9793875
Dll3 binds Notch1
Reactome:R-MMU-9824206
Lef1:Ctnnb1, Nicd (Notch), and Tbx6 bind the Hes7 gene in presomitic mesoderm
Reactome:R-MMU-9824230
Hes7 binds the Lfng gene
Reactome:R-MMU-9824231
Rbpj:Nicd and Msgn1 bind the Lfng gene
Reactome:R-MMU-9824249
Expression of Notch1 in presomitic mesoderm
Reactome:R-MMU-9824278
Hes7 binds the Hes7 gene
Reactome:R-NUL-1986584
Fucosylation of Pre-Notch by POFUT1
Reactome:R-NUL-2063915
ADAM17 cleaves Notch1 at S2
Reactome:R-NUL-2064853
FBXW7 binds phosphorylated NICD1
Reactome:R-NUL-2064883
FBXW7 mediates ubiquitination of phosphorylated NICD1
Reactome:R-NUL-2065560
mNICD1 binds HIF1A
Reactome:R-NUL-2065902
Gamma secretase complex cleaves Cntn1-actived Notch1
Reactome:R-NUL-209162
Murine ADAM10 cleaves Notch at the S2 site producing transmembrane spanning NEXT and ligand-bound NECD
Reactome:R-NUL-4396363
mNICD1 Chimeric Enhancer Complex binds Hes1 promoter

📚 Additional Documentation

Deep Research Bioreason

(Notch1-deep-research-bioreason.md)

BioReason Chat Export

Exported on March 22, 2026 at 01:24 AM


Organism: Mus musculus

Sequence:

MPRLLTPLLCLTLLPALAARGLRCSQPSGTCLNGGRCEVANGTEACVCSGAFVGQRCQDSNPCLSTPCKNAGTCHVVDHGGTVDYACSCPLGFSGPLCLTPLDNACLANPCRNGGTCDLLTLTEYKCRCPPGWSGKSCQQADPCASNPCANGGQCLPFESSYICRCPPGFHGPTCRQDVNECSQNPGLCRHGGTCHNEIGSYRCACRATHTGPHCELPYVPCSPSPCQNGGTCRPTGDTTHECACLPGFAGQNCEENVDDCPGNNCKNGGACVDGVNTYNCRCPPEWTGQYCTEDVDECQLMPNACQNGGTCHNTHGGYNCVCVNGWTGEDCSENIDDCASAACFQGATCHDRVASFYCECPHGRTGLLCHLNDACISNPCNEGSNCDTNPVNGKAICTCPSGYTGPACSQDVDECALGANPCEHAGKCLNTLGSFECQCLQGYTGPRCEIDVNECISNPCQNDATCLDQIGEFQCICMPGYEGVYCEINTDECASSPCLHNGHCMDKINEFQCQCPKGFNGHLCQYDVDECASTPCKNGAKCLDGPNTYTCVCTEGYTGTHCEVDIDECDPDPCHYGSCKDGVATFTCLCQPGYTGHHCETNINECHSQPCRHGGTCQDRDNSYLCLCLKGTTGPNCEINLDDCASNPCDSGTCLDKIDGYECACEPGYTGSMCNVNIDECAGSPCHNGGTCEDGIAGFTCRCPEGYHDPTCLSEVNECNSNPCIHGACRDGLNGYKCDCAPGWSGTNCDINNNECESNPCVNGGTCKDMTSGYVCTCREGFSGPNCQTNINECASNPCLNQGTCIDDVAGYKCNCPLPYTGATCEVVLAPCATSPCKNSGVCKESEDYESFSCVCPTGWQGQTCEVDINECVKSPCRHGASCQNTNGSYRCLCQAGYTGRNCESDIDDCRPNPCHNGGSCTDGINTAFCDCLPGFQGAFCEEDINECASNPCQNGANCTDCVDSYTCTCPVGFNGIHCENNTPDCTESSCFNGGTCVDGINSFTCLCPPGFTGSYCQYDVNECDSRPCLHGGTCQDSYGTYKCTCPQGYTGLNCQNLVRWCDSAPCKNGGRCWQTNTQYHCECRSGWTGVNCDVLSVSCEVAAQKRGIDVTLLCQHGGLCVDEGDKHYCHCQAGYTGSYCEDEVDECSPNPCQNGATCTDYLGGFSCKCVAGYHGSNCSEEINECLSQPCQNGGTCIDLTNSYKCSCPRGTQGVHCEINVDDCHPPLDPASRSPKCFNNGTCVDQVGGYTCTCPPGFVGERCEGDVNECLSNPCDPRGTQNCVQRVNDFHCECRAGHTGRRCESVINGCRGKPCKNGGVCAVASNTARGFICRCPAGFEGATCENDARTCGSLRCLNGGTCISGPRSPTCLCLGSFTGPECQFPASSPCVGSNPCYNQGTCEPTSENPFYRCLCPAKFNGLLCHILDYSFTGGAGRDIPPPQIEEACELPECQVDAGNKVCNLQCNNHACGWDGGDCSLNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQLTEGQCNPLYDQYCKDHFSDGHCDQGCNSAECEWDGLDCAEHVPERLAAGTLVLVVLLPPDQLRNNSFHFLRELSHVLHTNVVFKRDAQGQQMIFPYYGHEEELRKHPIKRSTVGWATSSLLPGTSGGRQRRELDPMDIRGSIVYLEIDNRQCVQSSSQCFQSATDVAAFLGALASLGSLNIPYKIEAVKSEPVEPPLPSQLHLMYVAAAAFVLLFFVGCGVLLSRKRRRQHGQLWFPEGFKVSEASKKKRREPLGEDSVGLKPLKNASDGALMDDNQNEWGDEDLETKKFRFEEPVVLPDLSDQTDHRQWTQQHLDAADLRMSAMAPTPPQGEVDADCMDVNVRGPDGFTPLMIASCSGGGLETGNSEEEEDAPAVISDFIYQGASLHNQTDRTGETALHLAARYSRSDAAKRLLEASADANIQDNMGRTPLHAAVSADAQGVFQILLRNRATDLDARMHDGTTPLILAARLAVEGM

Thinking Trace

I begin with the InterPro architecture. A broad family signature, IPR008297 (Notch family, residues 5–2000), blankets essentially the entire polypeptide, immediately placing the protein within the Notch receptor lineage. The N-terminal half is densely packed with extracellular EGF modules: IPR000742 (EGF-like domain, residues 20–1426), IPR001881 (EGF-like calcium-binding domain, residues 59–1384), IPR018097 (EGF-like calcium-binding conserved site, residues 178–1253), and IPR049883 (NOTCH1, EGF-like calcium-binding domain, residues 178–900). These repeated EGF repeats and their Ca2+-binding motifs generate a rigid, cysteine-rich scaffold that enforces precise intermolecular contacts and mechanosensing at the cell surface. This extracellular region is further supported by IPR009030 (Growth factor receptor cysteine-rich domain superfamily, residues 288–1311), emphasizing a disulfide-stabilized receptor fold, and by IPR000152 (EGF-type aspartate/asparagine hydroxylation site, residues 195–1255) and IPR013032 (EGF-like conserved site, residues 344–1374), which together indicate extensive post-translational hydroxylation and glycosylation typical of secreted or surface-exposed EGF arrays. This extracellular EGF architecture causes high-affinity, Ca2+-tunable binding and force-dependent activation characteristic of Notch receptors.

Proceeding into the intracellular signaling core, a series of Notch-specific modules appears: IPR022362 (Neurogenic locus notch homolog protein 1 family, residues 1426–1714) leads into IPR000800 (Notch domain, residues 1442–1571), IPR035993 (Notch-like domain superfamily, residues 1448–1561), IPR010660 (Notch, NOD domain, residues 1566–1622), and IPR011656 (Notch, NODP domain, residues 1660–1722). This ordered block encodes the canonical heterodimerization and negative regulatory apparatus of Notch receptors: the NOD/NODP cassette forms the negative regulatory region that clamps the receptor’s intracellular tail until activating endocytosis and mechanical tension unlock it. Downstream, IPR036770 (Ankyrin repeat-containing domain superfamily, residues 1858–2000) and IPR002110 (Ankyrin repeat, residues 1870–1980) specify a C-terminal ankyrin-repeat platform that binds transcriptional co-regulators. The combined evidence—extracellular EGF arrays, followed by the NOD/NODP switch and a C-terminal ankyrin scaffold—defines a single-pass type I receptor that signals by proteolytic activation and intracellular complex assembly.

From this architecture, the molecular function resolves as follows. The extracellular EGF array and calcium-binding sites enforce ligand-gated activation and support protein-protein interactions at the surface; the intracellular ankyrin repeats and the activated signaling core drive assembly of transcriptional effector complexes. This causally establishes protein binding (GO:0005515) as the operative activity: the receptor binds extracellular ligands and intracellular partners to translate a surface cue into transcriptional control.

The biological process follows from this signaling logic. Notch receptors govern binary fate decisions by inducing gene expression programs that restrain or promote differentiation. The EGF-driven activation and ankyrin-mediated transcriptional assembly together enforce control of lineage bifurcation and timing, aligning with cell fate determination (GO:0001708). This process-level inference arises directly from the coupling of an extracellular ligand-gated module to an intracellular transcriptional hub.

Cellular location is dictated by the single-pass type I topology and the extracellular EGF region. Such receptors are synthesized into the secretory pathway and displayed at the cell surface, where they function as membrane-bound signal transducers. This places the protein at the plasma membrane/cell surface and classifies it as an integral component of membrane, matching a single-pass type I membrane protein.

Mechanistically, the extracellular EGF platform binds Delta/Serrate/Jagged-type ligands on neighboring cells; endocytosis and Ca2+-stabilized EGF architecture transmit mechanical force that unlocks the NOD/NODP switch, triggering intramembrane proteolysis and liberation of the intracellular domain. The released intracellular fragment then engages the ankyrin-repeat platform to recruit CSL/RBPJ transcription complexes and coactivators, thereby rewiring gene expression to bias cell fate. Likely interaction partners include membrane ligands and extracellular modulators that deliver activation cues, as well as intracellular DNA-binding and co-regulatory assemblies that implement the transcriptional output.

Functional Summary

A single-pass cell-surface receptor that uses a long calcium-stabilized EGF repeat array to sense extracellular cues and trigger intramembrane signaling. Upon ligand engagement and endocytic activation, a built-in regulatory switch releases the intracellular tail, which then assembles transcriptional effector complexes via ankyrin repeats to reprogram gene expression. This signaling cascade governs binary fate decisions and timing of differentiation by coupling extracellular recognition to intracellular transcriptional control at the plasma membrane.

UniProt Summary

Functions as a receptor for several membrane-bound ligands that are presented on the surface of adjacent cells. Activates transcription factors that are involved in lineage specification. May play a role in cell-fate determination (By similarity).

InterPro Domains

  • Notch (IPR008297, family) — residues 5-2000
  • EGF-like domain (IPR000742, domain) — residues 20-1426
  • EGF-like calcium-binding domain (IPR001881, domain) — residues 59-1384
  • EGF-like calcium-binding, conserved site (IPR018097, conserved_site) — residues 178-1253
  • NOTCH1, EGF-like calcium-binding domain (IPR049883, domain) — residues 178-900
  • EGF-type aspartate/asparagine hydroxylation site (IPR000152, ptm) — residues 195-1255
  • Growth factor receptor cysteine-rich domain superfamily (IPR009030, homologous_superfamily) — residues 288-1311
  • EGF-like, conserved site (IPR013032, conserved_site) — residues 344-1374
  • Neurogenic locus notch homolog protein 1 (IPR022362, family) — residues 1426-1714
  • Notch domain (IPR000800, domain) — residues 1442-1571
  • Notch-like domain superfamily (IPR035993, homologous_superfamily) — residues 1448-1561
  • Notch, NOD domain (IPR010660, domain) — residues 1566-1622
  • Notch, NODP domain (IPR011656, domain) — residues 1660-1722
  • Ankyrin repeat-containing domain superfamily (IPR036770, homologous_superfamily) — residues 1858-2000
  • Ankyrin repeat (IPR002110, repeat) — residues 1870-1980

GO Terms

Molecular Function: molecular_function (GO:0003674), molecular function regulator activity (GO:0098772), binding (GO:0005488), transcription regulator activity (GO:0140110), enzyme regulator activity (GO:0030234), molecular function activator activity (GO:0140677), heterocyclic compound binding (GO:1901363), chromatin binding (GO:0003682), organic cyclic compound binding (GO:0097159), transcription coregulator activity (GO:0003712), protein binding (GO:0005515), molecular function inhibitor activity (GO:0140678), nucleic acid binding (GO:0003676), signaling receptor binding (GO:0005102), chromatin DNA binding (GO:0031490), enzyme binding (GO:0019899), enzyme inhibitor activity (GO:0004857), transcription coactivator activity (GO:0003713), Notch binding (GO:0005112), DNA binding (GO:0003677)

Biological Process: biological_process (GO:0008150), biological regulation (GO:0065007), response to stimulus (GO:0050896), reproductive process (GO:0022414), regulation of biological process (GO:0050789), reproduction (GO:0000003), multicellular organismal process (GO:0032501), metabolic process (GO:0008152), homeostatic process (GO:0042592), immune system process (GO:0002376), localization (GO:0051179), signaling (GO:0023052), growth (GO:0040007), negative regulation of biological process (GO:0048519), positive regulation of biological process (GO:0048518), developmental process (GO:0032502), cellular process (GO:0009987), anatomical structure development (GO:0048856), negative regulation of signaling (GO:0023057), cell division (GO:0051301), developmental process involved in reproduction (GO:0003006), anatomical structure formation involved in morphogenesis (GO:0048646), multicellular organismal-level homeostasis (GO:0048871), regulation of response to stimulus (GO:0048583), negative regulation of cellular process (GO:0048523), biosynthetic process (GO:0009058), positive regulation of viral process (GO:0048524), establishment of localization (GO:0051234), catabolic process (GO:0009056), macromolecule localization (GO:0033036), developmental growth (GO:0048589), cell population proliferation (GO:0008283), nitrogen compound metabolic process (GO:0006807), negative regulation of multicellular organismal process (GO:0051241), cell death (GO:0008219), positive regulation of locomotion (GO:0040017), regulation of signaling (GO:0023051), negative regulation of developmental process (GO:0051093), signal transduction (GO:0007165), negative regulation of transport (GO:0051051), regulation of viral process (GO:0050792), primary metabolic process (GO:0044238), morphogenesis of a branching structure (GO:0001763), positive regulation of developmental process (GO:0051094), negative regulation of response to stimulus (GO:0048585), regulation of growth (GO:0040008), cellular localization (GO:0051641), immune response (GO:0006955), positive regulation of multicellular organismal process (GO:0051240), molting cycle (GO:0042303), pattern specification process (GO:0007389), cellular component organization or biogenesis (GO:0071840), regulation of multicellular organismal process (GO:0051239), negative regulation of metabolic process (GO:0009892), regulation of cellular process (GO:0050794), cellular response to stimulus (GO:0051716), regulation of locomotion (GO:0040012), cellular developmental process (GO:0048869), response to abiotic stimulus (GO:0009628), organ growth (GO:0035265), positive regulation of response to stimulus (GO:0048584), regulation of metabolic process (GO:0019222), molting cycle process (GO:0022404), regulation of molecular function (GO:0065009), export from cell (GO:0140352), cell communication (GO:0007154), positive regulation of cellular process (GO:0048522), anatomical structure morphogenesis (GO:0009653), cell motility (GO:0048870), response to chemical (GO:0042221), regulation of reproductive process (GO:2000241), positive regulation of growth (GO:0045927), regulation of developmental process (GO:0050793), positive regulation of signaling (GO:0023056), multicellular organism development (GO:0007275), regulation of localization (GO:0032879), organic substance metabolic process (GO:0071704), cellular metabolic process (GO:0044237), positive regulation of metabolic process (GO:0009893), response to stress (GO:0006950), cellular component morphogenesis (GO:0032989), negative regulation of cellular component organization (GO:0051129), regulation of cell motility (GO:2000145), regulation of system process (GO:0044057), animal organ development (GO:0048513), neural retina development (GO:0003407), regulation of vesicle-mediated transport (GO:0060627), positive regulation of apoptotic process involved in development (GO:1904747), negative regulation of cellular response to growth factor stimulus (GO:0090288), retina development in camera-type eye (GO:0060041), negative regulation of secretion (GO:0051048), regulation of development, heterochronic (GO:0040034), cardiac septum morphogenesis (GO:0060411), regulation of anatomical structure morphogenesis (GO:0022603), secretion by cell (GO:0032940), nephron development (GO:0072006), trabecula morphogenesis (GO:0061383), negative regulation of muscle hypertrophy (GO:0014741), positive regulation of epidermis development (GO:0045684), positive regulation of nitrogen compound metabolic process (GO:0051173), positive regulation of cell differentiation (GO:0045597), appendage development (GO:0048736), organic substance biosynthetic process (GO:1901576), negative regulation of cell population proliferation (GO:0008285), protein metabolic process (GO:0019538), specification of symmetry (GO:0009799), cellular biosynthetic process (GO:0044249), response to oxygen-containing compound (GO:1901700), prostate gland epithelium morphogenesis (GO:0060740), macromolecule metabolic process (GO:0043170), positive regulation of cell motility (GO:2000147), positive regulation of biosynthetic process (GO:0009891), homeostasis of number of cells (GO:0048872), endocardial cushion formation (GO:0003272), muscle structure development (GO:0061061), regulation of cell population proliferation (GO:0042127), regulation of cell death (GO:0010941), regionalization (GO:0003002), response to nitrogen compound (GO:1901698), negative regulation of cell differentiation (GO:0045596), transport (GO:0006810), humoral immune response (GO:0006959), positive regulation of cell communication (GO:0010647), regulation of cellular metabolic process (GO:0031323), hair cycle process (GO:0022405), regulation of primary metabolic process (GO:0080090), negative regulation of signal transduction (GO:0009968), response to hypoxia (GO:0001666), regulation of viral genome replication (GO:0045069), negative regulation of cell death (GO:0060548), cell differentiation (GO:0030154), negative regulation of nervous system development (GO:0051961), system development (GO:0048731), response to oxygen levels (GO:0070482), cardiac septum development (GO:0003279), regulation of cell adhesion (GO:0030155), regulation of organ growth (GO:0046620), heart growth (GO:0060419), tube development (GO:0035295), cell morphogenesis (GO:0000902), animal organ morphogenesis (GO:0009887), cell surface receptor signaling pathway (GO:0007166), regulation of cellular component organization (GO:0051128), negative regulation of biomineral tissue development (GO:0070168), regulation of ossification (GO:0030278), positive regulation of cell population proliferation (GO:0008284), tube morphogenesis (GO:0035239), positive regulation of developmental growth (GO:0048639), negative regulation of cell communication (GO:0010648), apoptotic process involved in development (GO:1902742), axis specification (GO:0009798), retina morphogenesis in camera-type eye (GO:0060042), hair follicle morphogenesis (GO:0031069), morphogenesis of a branching epithelium (GO:0061138), positive regulation of organ growth (GO:0046622), cardiac chamber development (GO:0003205), negative regulation of cellular metabolic process (GO:0031324), cell fate commitment (GO:0045165), embryonic morphogenesis (GO:0048598), cellular response to chemical stimulus (GO:0070887), glomerulus development (GO:0032835), tissue homeostasis (GO:0001894), stem cell division (GO:0017145), hair cycle (GO:0042633), regulation of cold-induced thermogenesis (GO:0120161), developmental growth involved in morphogenesis (GO:0060560), negative regulation of photoreceptor cell differentiation (GO:0046533), regulation of signal transduction (GO:0009966), foregut morphogenesis (GO:0007440), regulation of macromolecule metabolic process (GO:0060255), reproductive structure development (GO:0048608), cellular aromatic compound metabolic process (GO:0006725), regulation of muscle adaptation (GO:0043502), positive regulation of epithelial to mesenchymal transition (GO:0010718), establishment of protein localization (GO:0045184), regulation of cellular component biogenesis (GO:0044087), regulation of apoptotic process involved in development (GO:1904748), intracellular transport (GO:0046907), negative regulation of macromolecule metabolic process (GO:0010605), muscle cell proliferation (GO:0033002), embryo development (GO:0009790), regulation of catalytic activity (GO:0050790), negative regulation of nitrogen compound metabolic process (GO:0051172), regulation of epidermis development (GO:0045682), positive regulation of macromolecule metabolic process (GO:0010604), blood vessel development (GO:0001568), heterocycle metabolic process (GO:0046483), negative regulation of molecular function (GO:0044092), establishment of localization in cell (GO:0051649), appendage morphogenesis (GO:0035107), cellular nitrogen compound metabolic process (GO:0034641), apoptotic process involved in morphogenesis (GO:0060561), angiogenesis (GO:0001525), regulation of multicellular organismal development (GO:2000026), regulation of viral transcription (GO:0046782), positive regulation of cellular metabolic process (GO:0031325), cellular response to stress (GO:0033554), epithelial cell proliferation (GO:0050673), cellular macromolecule localization (GO:0070727), negative regulation of biosynthetic process (GO:0009890), regulation of cellular response to growth factor stimulus (GO:0090287), positive regulation of cell death (GO:0010942), tissue morphogenesis (GO:0048729), programmed cell death (GO:0012501), adaptive immune response (GO:0002250), cell development (GO:0048468), prostate gland morphogenesis (GO:0060512), cardiac muscle tissue growth (GO:0055017), cell fate determination (GO:0001708), heart valve development (GO:0003170), negative regulation of ossification (GO:0030279), inflammatory response to antigenic stimulus (GO:0002437), organic cyclic compound metabolic process (GO:1901360), forebrain development (GO:0030900), hair follicle development (GO:0001942), regulation of nitrogen compound metabolic process (GO:0051171), regulation of cell differentiation (GO:0045595), cellular component organization (GO:0016043), inner ear development (GO:0048839), organic substance catabolic process (GO:1901575), positive regulation of nervous system development (GO:0051962), negative regulation of secretion by cell (GO:1903531), regulation of developmental growth (GO:0048638), endocardium development (GO:0003157), cell migration (GO:0016477), positive regulation of signal transduction (GO:0009967), regulation of secretion by cell (GO:1903530), positive regulation of viral genome replication (GO:0045070), regulation of transport (GO:0051049), organonitrogen compound metabolic process (GO:1901564), defense response (GO:0006952), response to organic substance (GO:0010033), anatomical structure homeostasis (GO:0060249), regulation of viral life cycle (GO:1903900), tissue development (GO:0009888), nucleobase-containing compound metabolic process (GO:0006139), head development (GO:0060322), regulation of cell communication (GO:0010646), regulation of biosynthetic process (GO:0009889), cardiac chamber morphogenesis (GO:0003206), heart valve morphogenesis (GO:0003179), negative regulation of cold-induced thermogenesis (GO:0120163), endoderm development (GO:0007492), regulation of hematopoietic progenitor cell differentiation (GO:1901532), nephron epithelium development (GO:0072009), cell projection organization (GO:0030030), regulation of Notch signaling pathway (GO:0008593), somatic stem cell division (GO:0048103), regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090092), positive regulation of cardiac muscle cell proliferation (GO:0060045), regulation of receptor signaling pathway via STAT (GO:1904892), regulation of epithelial cell proliferation (GO:0050678), semi-lunar valve development (GO:1905314), muscle cell differentiation (GO:0042692), embryonic heart tube development (GO:0035050), cell surface receptor signaling pathway involved in heart development (GO:0061311), circulatory system development (GO:0072359), response to decreased oxygen levels (GO:0036293), positive regulation of cell migration (GO:0030335), regulation of osteoblast differentiation (GO:0045667), cell projection morphogenesis (GO:0048858), pulmonary valve morphogenesis (GO:0003184), cytokine-mediated signaling pathway (GO:0019221), negative regulation of exocytosis (GO:0045920), ventricular septum development (GO:0003281), positive regulation of Notch signaling pathway (GO:0045747), regulation of cell proliferation involved in heart morphogenesis (GO:2000136), cellular response to organic substance (GO:0071310), establishment of protein localization to organelle (GO:0072594), cell migration involved in heart development (GO:0060973), positive regulation of epithelial cell differentiation (GO:0030858), limb morphogenesis (GO:0035108), regulation of muscle cell differentiation (GO:0051147), hepaticobiliary system development (GO:0061008), skeletal muscle cell differentiation (GO:0035914), Notch signaling pathway (GO:0007219), cardiac atrium morphogenesis (GO:0003209), positive regulation of macromolecule biosynthetic process (GO:0010557), apoptotic process (GO:0006915), adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains (GO:0002460), regulation of nucleobase-containing compound metabolic process (GO:0019219), epithelium development (GO:0060429), gland morphogenesis (GO:0022612), positive regulation of cellular biosynthetic process (GO:0031328), atrioventricular valve morphogenesis (GO:0003181), regulation of epithelial cell differentiation (GO:0030856), respiratory system development (GO:0060541), response to peptide (GO:1901652), regulation of programmed cell death (GO:0043067), protein catabolic process (GO:0030163), gland development (GO:0048732), cell differentiation involved in kidney development (GO:0061005), cardiac ventricle development (GO:0003231), morphogenesis of an epithelium (GO:0002009), positive regulation of neurogenesis (GO:0050769), skin development (GO:0043588), regulation of cell migration (GO:0030334), neuron development (GO:0048666), coronary vasculature development (GO:0060976), branching morphogenesis of an epithelial tube (GO:0048754), cardiac ventricle morphogenesis (GO:0003208), macromolecule catabolic process (GO:0009057), embryonic organ development (GO:0048568), cell morphogenesis involved in differentiation (GO:0000904), exocytosis (GO:0006887), renal tubule development (GO:0061326), nucleic acid metabolic process (GO:0090304), camera-type eye photoreceptor cell differentiation (GO:0060219), regulation of extracellular matrix organization (GO:1903053), negative regulation of cellular biosynthetic process (GO:0031327), negative regulation of Wnt signaling pathway (GO:0030178), mesenchymal cell differentiation (GO:0048762), negative regulation of cardiac muscle hypertrophy (GO:0010614), gene expression (GO:0010467), negative regulation of nucleobase-containing compound metabolic process (GO:0045934), regulation of cardiac muscle cell proliferation (GO:0060043), renal system development (GO:0072001), cardiac muscle cell proliferation (GO:0060038), reproductive system development (GO:0061458), negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090101), embryonic organ morphogenesis (GO:0048562), negative regulation of hematopoietic progenitor cell differentiation (GO:1901533), positive regulation of cell development (GO:0010720), urogenital system development (GO:0001655), positive regulation of gene expression (GO:0010628), muscle organ morphogenesis (GO:0048644), positive regulation of receptor signaling pathway via STAT (GO:1904894), positive regulation of nucleobase-containing compound metabolic process (GO:0045935), regulation of extracellular matrix assembly (GO:1901201), respiratory tube development (GO:0030323), response to organonitrogen compound (GO:0010243), positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090100), prostate gland development (GO:0030850), venous blood vessel development (GO:0060841), negative regulation of macromolecule biosynthetic process (GO:0010558), cardiac atrium development (GO:0003230), cardiocyte differentiation (GO:0035051), blood vessel endothelial cell differentiation (GO:0060837), regulation of epithelial to mesenchymal transition (GO:0010717), glomerulus vasculature development (GO:0072012), digestive tract development (GO:0048565), neuron differentiation (GO:0030182), cardiac cell development (GO:0055006), epithelial tube morphogenesis (GO:0060562), nitrogen compound transport (GO:0071705), embryonic digit morphogenesis (GO:0042733), regulation of macromolecule biosynthetic process (GO:0010556), cellular response to oxygen levels (GO:0071453), sensory system development (GO:0048880), vasculature development (GO:0001944), connective tissue development (GO:0061448), regulation of glial cell proliferation (GO:0060251), glial cell differentiation (GO:0010001), organic substance transport (GO:0071702), embryonic heart tube morphogenesis (GO:0003143), negative regulation of muscle cell differentiation (GO:0051148), regulation of gene expression (GO:0010468), regulation of cardiac muscle tissue growth (GO:0055021), striated muscle cell proliferation (GO:0014855), intracellular protein transport (GO:0006886), negative regulation of osteoblast differentiation (GO:0045668), epithelial cell development (GO:0002064), regulation of embryonic development (GO:0045995), heart trabecula morphogenesis (GO:0061384), epidermal cell fate specification (GO:0009957), sprouting angiogenesis (GO:0002040), heart development (GO:0007507), artery development (GO:0060840), cellular response to hypoxia (GO:0071456), positive regulation of heart growth (GO:0060421), atrioventricular valve development (GO:0003171), organonitrogen compound catabolic process (GO:1901565), epithelial cell fate commitment (GO:0072148), neuron fate commitment (GO:0048663), muscle cell development (GO:0055001), aromatic compound biosynthetic process (GO:0019438), regulation of cell development (GO:0060284), sensory organ development (GO:0007423), regulation of exocytosis (GO:0017157), secretion (GO:0046903), regulation of Wnt signaling pathway (GO:0030111), regulation of glial cell differentiation (GO:0045685), positive regulation of epithelial cell proliferation (GO:0050679), neurogenesis (GO:0022008), positive regulation of RNA metabolic process (GO:0051254), ventricular septum morphogenesis (GO:0060412), inflammatory response (GO:0006954), negative regulation of epithelial cell proliferation (GO:0050680), left/right pattern formation (GO:0060972), muscle tissue development (GO:0060537), regulation of stem cell proliferation (GO:0072091), regulation of cellular biosynthetic process (GO:0031326), regulation of cardiac muscle hypertrophy (GO:0010611), cellular nitrogen compound biosynthetic process (GO:0044271), embryonic appendage morphogenesis (GO:0035113), protein localization (GO:0008104), muscle organ development (GO:0007517), negative regulation of cell development (GO:0010721), embryo development ending in birth or egg hatching (GO:0009792), regulation of neuron differentiation (GO:0045664), macromolecule biosynthetic process (GO:0009059), organic cyclic compound biosynthetic process (GO:1901362), negative regulation of BMP signaling pathway (GO:0030514), digestive system development (GO:0055123), cell part morphogenesis (GO:0032990), sensory organ morphogenesis (GO:0090596), nuclear transport (GO:0051169), aortic valve morphogenesis (GO:0003180), regulation of BMP signaling pathway (GO:0030510), regulation of muscle system process (GO:0090257), regulation of epidermal cell differentiation (GO:0045604), brain development (GO:0007420), negative regulation of neurogenesis (GO:0050768), regulation of heart growth (GO:0060420), heart morphogenesis (GO:0003007), nervous system development (GO:0007399), epidermis development (GO:0008544), protein transport (GO:0015031), positive regulation of cardiac muscle tissue growth (GO:0055023), heterocycle biosynthetic process (GO:0018130), vasculogenesis (GO:0001570), central nervous system development (GO:0007417), negative regulation of glial cell proliferation (GO:0060253), inner ear receptor cell differentiation (GO:0060113), regulation of RNA metabolic process (GO:0051252), response to cytokine (GO:0034097), negative regulation of catalytic activity (GO:0043086), muscle tissue morphogenesis (GO:0060415), neural tube development (GO:0021915), positive regulation of programmed cell death (GO:0043068), positive regulation of epidermal cell differentiation (GO:0045606), regulation of nervous system development (GO:0051960), mesenchyme development (GO:0060485), negative regulation of neuron differentiation (GO:0045665), left/right axis specification (GO:0070986), digestive tract morphogenesis (GO:0048546), epithelial cell differentiation (GO:0030855), nucleobase-containing compound biosynthetic process (GO:0034654), regulation of biomineral tissue development (GO:0070167), determination of bilateral symmetry (GO:0009855), lung development (GO:0030324), stem cell differentiation (GO:0048863), mesenchyme morphogenesis (GO:0072132), myoblast differentiation (GO:0045445), blood vessel morphogenesis (GO:0048514), negative regulation of epithelial cell differentiation (GO:0030857), limb development (GO:0060173), regulation of secretion (GO:0051046), vesicle-mediated transport (GO:0016192), homeostasis of number of cells within a tissue (GO:0048873), negative regulation of RNA metabolic process (GO:0051253), kidney development (GO:0001822), anterior/posterior pattern specification (GO:0009952), regulation of apoptotic process (GO:0042981), negative regulation of gliogenesis (GO:0014014), striated muscle tissue development (GO:0014706), ear development (GO:0043583), cardiac left ventricle morphogenesis (GO:0003214), skeletal muscle tissue development (GO:0007519), ventricular trabecula myocardium morphogenesis (GO:0003222), regulation of oligodendrocyte differentiation (GO:0048713), liver development (GO:0001889), positive regulation of RNA biosynthetic process (GO:1902680), artery morphogenesis (GO:0048844), cardiac epithelial to mesenchymal transition (GO:0060317), nucleocytoplasmic transport (GO:0006913), regulation of astrocyte differentiation (GO:0048710), response to interleukin-17 (GO:0097396), positive regulation of BMP signaling pathway (GO:0030513), cardiac muscle tissue development (GO:0048738), photoreceptor cell differentiation (GO:0046530), kidney epithelium development (GO:0072073), endocardial cushion morphogenesis (GO:0003203), columnar/cuboidal epithelial cell differentiation (GO:0002065), gliogenesis (GO:0042063), neuron projection development (GO:0031175), endothelium development (GO:0003158), epidermal cell differentiation (GO:0009913), regulation of keratinocyte differentiation (GO:0045616), nucleic acid-templated transcription (GO:0097659), pericardium development (GO:0060039), mechanoreceptor differentiation (GO:0042490), determination of left/right symmetry (GO:0007368), pulmonary valve development (GO:0003177), eye morphogenesis (GO:0048592), hindlimb morphogenesis (GO:0035137), smooth muscle cell differentiation (GO:0051145), oligodendrocyte differentiation (GO:0048709), endocardial cushion development (GO:0003197), epidermis morphogenesis (GO:0048730), negative regulation of regulated secretory pathway (GO:1903306), regulation of neurogenesis (GO:0050767), negative regulation of canonical Wnt signaling pathway (GO:0090090), regulation of canonical Wnt signaling pathway (GO:0060828), inner ear auditory receptor cell differentiation (GO:0042491), cell morphogenesis involved in neuron differentiation (GO:0048667), skeletal muscle organ development (GO:0060538), regulation of striated muscle cell differentiation (GO:0051153), positive regulation of gliogenesis (GO:0014015), positive regulation of glial cell differentiation (GO:0045687)

Cellular Component: cellular_component (GO:0005575), cellular anatomical entity (GO:0110165), intracellular anatomical structure (GO:0005622), organelle (GO:0043226), membrane (GO:0016020), membrane-enclosed lumen (GO:0031974), cytosol (GO:0005829), cell surface (GO:0009986), cell periphery (GO:0071944), cell junction (GO:0030054), organelle subcompartment (GO:0031984), apical part of cell (GO:0045177), cytoplasm (GO:0005737), endomembrane system (GO:0012505), nucleoplasm (GO:0005654), extracellular region (GO:0005576), organelle membrane (GO:0031090), cytoplasmic vesicle (GO:0031410), intracellular organelle (GO:0043229), apical plasma membrane (GO:0016324), endoplasmic reticulum subcompartment (GO:0098827), nuclear outer membrane-endoplasmic reticulum membrane network (GO:0042175), Golgi apparatus (GO:0005794), plasma membrane region (GO:0098590), organelle lumen (GO:0043233), endoplasmic reticulum (GO:0005783), anchoring junction (GO:0070161), membrane-bounded organelle (GO:0043227), plasma membrane (GO:0005886), intracellular membrane-bounded organelle (GO:0043231), bounding membrane of organelle (GO:0098588), endoplasmic reticulum membrane (GO:0005789), vesicle (GO:0031982), intracellular organelle lumen (GO:0070013), cell-cell junction (GO:0005911), Golgi membrane (GO:0000139), intracellular vesicle (GO:0097708), nucleus (GO:0005634), nuclear lumen (GO:0031981), adherens junction (GO:0005912)


Generated by BioReason

Deep Research Bioreason Rl

(Notch1-deep-research-bioreason-rl.md)

BioReason Chat Export

Exported on March 22, 2026 at 01:24 AM


Organism: Mus musculus

Sequence:

MPRLLTPLLCLTLLPALAARGLRCSQPSGTCLNGGRCEVANGTEACVCSGAFVGQRCQDSNPCLSTPCKNAGTCHVVDHGGTVDYACSCPLGFSGPLCLTPLDNACLANPCRNGGTCDLLTLTEYKCRCPPGWSGKSCQQADPCASNPCANGGQCLPFESSYICRCPPGFHGPTCRQDVNECSQNPGLCRHGGTCHNEIGSYRCACRATHTGPHCELPYVPCSPSPCQNGGTCRPTGDTTHECACLPGFAGQNCEENVDDCPGNNCKNGGACVDGVNTYNCRCPPEWTGQYCTEDVDECQLMPNACQNGGTCHNTHGGYNCVCVNGWTGEDCSENIDDCASAACFQGATCHDRVASFYCECPHGRTGLLCHLNDACISNPCNEGSNCDTNPVNGKAICTCPSGYTGPACSQDVDECALGANPCEHAGKCLNTLGSFECQCLQGYTGPRCEIDVNECISNPCQNDATCLDQIGEFQCICMPGYEGVYCEINTDECASSPCLHNGHCMDKINEFQCQCPKGFNGHLCQYDVDECASTPCKNGAKCLDGPNTYTCVCTEGYTGTHCEVDIDECDPDPCHYGSCKDGVATFTCLCQPGYTGHHCETNINECHSQPCRHGGTCQDRDNSYLCLCLKGTTGPNCEINLDDCASNPCDSGTCLDKIDGYECACEPGYTGSMCNVNIDECAGSPCHNGGTCEDGIAGFTCRCPEGYHDPTCLSEVNECNSNPCIHGACRDGLNGYKCDCAPGWSGTNCDINNNECESNPCVNGGTCKDMTSGYVCTCREGFSGPNCQTNINECASNPCLNQGTCIDDVAGYKCNCPLPYTGATCEVVLAPCATSPCKNSGVCKESEDYESFSCVCPTGWQGQTCEVDINECVKSPCRHGASCQNTNGSYRCLCQAGYTGRNCESDIDDCRPNPCHNGGSCTDGINTAFCDCLPGFQGAFCEEDINECASNPCQNGANCTDCVDSYTCTCPVGFNGIHCENNTPDCTESSCFNGGTCVDGINSFTCLCPPGFTGSYCQYDVNECDSRPCLHGGTCQDSYGTYKCTCPQGYTGLNCQNLVRWCDSAPCKNGGRCWQTNTQYHCECRSGWTGVNCDVLSVSCEVAAQKRGIDVTLLCQHGGLCVDEGDKHYCHCQAGYTGSYCEDEVDECSPNPCQNGATCTDYLGGFSCKCVAGYHGSNCSEEINECLSQPCQNGGTCIDLTNSYKCSCPRGTQGVHCEINVDDCHPPLDPASRSPKCFNNGTCVDQVGGYTCTCPPGFVGERCEGDVNECLSNPCDPRGTQNCVQRVNDFHCECRAGHTGRRCESVINGCRGKPCKNGGVCAVASNTARGFICRCPAGFEGATCENDARTCGSLRCLNGGTCISGPRSPTCLCLGSFTGPECQFPASSPCVGSNPCYNQGTCEPTSENPFYRCLCPAKFNGLLCHILDYSFTGGAGRDIPPPQIEEACELPECQVDAGNKVCNLQCNNHACGWDGGDCSLNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQLTEGQCNPLYDQYCKDHFSDGHCDQGCNSAECEWDGLDCAEHVPERLAAGTLVLVVLLPPDQLRNNSFHFLRELSHVLHTNVVFKRDAQGQQMIFPYYGHEEELRKHPIKRSTVGWATSSLLPGTSGGRQRRELDPMDIRGSIVYLEIDNRQCVQSSSQCFQSATDVAAFLGALASLGSLNIPYKIEAVKSEPVEPPLPSQLHLMYVAAAAFVLLFFVGCGVLLSRKRRRQHGQLWFPEGFKVSEASKKKRREPLGEDSVGLKPLKNASDGALMDDNQNEWGDEDLETKKFRFEEPVVLPDLSDQTDHRQWTQQHLDAADLRMSAMAPTPPQGEVDADCMDVNVRGPDGFTPLMIASCSGGGLETGNSEEEEDAPAVISDFIYQGASLHNQTDRTGETALHLAARYSRSDAAKRLLEASADANIQDNMGRTPLHAAVSADAQGVFQILLRNRATDLDARMHDGTTPLILAARLAVEGM

Thinking Trace

I begin with the InterPro architecture. A broad family signature, IPR008297 (Notch family, residues 5–2000), blankets essentially the entire polypeptide, immediately placing the protein within the Notch receptor lineage. The N-terminal half is densely packed with extracellular EGF modules: IPR000742 (EGF-like domain, residues 20–1426), IPR001881 (EGF-like calcium-binding domain, residues 59–1384), IPR018097 (EGF-like calcium-binding conserved site, residues 178–1253), and IPR049883 (NOTCH1, EGF-like calcium-binding domain, residues 178–900). These repeated EGF repeats and their Ca2+-binding motifs generate a rigid, cysteine-rich scaffold that enforces precise intermolecular contacts and mechanosensing at the cell surface. This extracellular region is further supported by IPR009030 (Growth factor receptor cysteine-rich domain superfamily, residues 288–1311), emphasizing a disulfide-stabilized receptor fold, and by IPR000152 (EGF-type aspartate/asparagine hydroxylation site, residues 195–1255) and IPR013032 (EGF-like conserved site, residues 344–1374), which together indicate extensive post-translational hydroxylation and glycosylation typical of secreted or surface-exposed EGF arrays. This extracellular EGF architecture causes high-affinity, Ca2+-tunable binding and force-dependent activation characteristic of Notch receptors.

Proceeding into the intracellular signaling core, a series of Notch-specific modules appears: IPR022362 (Neurogenic locus notch homolog protein 1 family, residues 1426–1714) leads into IPR000800 (Notch domain, residues 1442–1571), IPR035993 (Notch-like domain superfamily, residues 1448–1561), IPR010660 (Notch, NOD domain, residues 1566–1622), and IPR011656 (Notch, NODP domain, residues 1660–1722). This ordered block encodes the canonical heterodimerization and negative regulatory apparatus of Notch receptors: the NOD/NODP cassette forms the negative regulatory region that clamps the receptor’s intracellular tail until activating endocytosis and mechanical tension unlock it. Downstream, IPR036770 (Ankyrin repeat-containing domain superfamily, residues 1858–2000) and IPR002110 (Ankyrin repeat, residues 1870–1980) specify a C-terminal ankyrin-repeat platform that binds transcriptional co-regulators. The combined evidence—extracellular EGF arrays, followed by the NOD/NODP switch and a C-terminal ankyrin scaffold—defines a single-pass type I receptor that signals by proteolytic activation and intracellular complex assembly.

From this architecture, the molecular function resolves as follows. The extracellular EGF array and calcium-binding sites enforce ligand-gated activation and support protein-protein interactions at the surface; the intracellular ankyrin repeats and the activated signaling core drive assembly of transcriptional effector complexes. This causally establishes protein binding (GO:0005515) as the operative activity: the receptor binds extracellular ligands and intracellular partners to translate a surface cue into transcriptional control.

The biological process follows from this signaling logic. Notch receptors govern binary fate decisions by inducing gene expression programs that restrain or promote differentiation. The EGF-driven activation and ankyrin-mediated transcriptional assembly together enforce control of lineage bifurcation and timing, aligning with cell fate determination (GO:0001708). This process-level inference arises directly from the coupling of an extracellular ligand-gated module to an intracellular transcriptional hub.

Cellular location is dictated by the single-pass type I topology and the extracellular EGF region. Such receptors are synthesized into the secretory pathway and displayed at the cell surface, where they function as membrane-bound signal transducers. This places the protein at the plasma membrane/cell surface and classifies it as an integral component of membrane, matching a single-pass type I membrane protein.

Mechanistically, the extracellular EGF platform binds Delta/Serrate/Jagged-type ligands on neighboring cells; endocytosis and Ca2+-stabilized EGF architecture transmit mechanical force that unlocks the NOD/NODP switch, triggering intramembrane proteolysis and liberation of the intracellular domain. The released intracellular fragment then engages the ankyrin-repeat platform to recruit CSL/RBPJ transcription complexes and coactivators, thereby rewiring gene expression to bias cell fate. Likely interaction partners include membrane ligands and extracellular modulators that deliver activation cues, as well as intracellular DNA-binding and co-regulatory assemblies that implement the transcriptional output.

Functional Summary

A single-pass cell-surface receptor that uses a long calcium-stabilized EGF repeat array to sense extracellular cues and trigger intramembrane signaling. Upon ligand engagement and endocytic activation, a built-in regulatory switch releases the intracellular tail, which then assembles transcriptional effector complexes via ankyrin repeats to reprogram gene expression. This signaling cascade governs binary fate decisions and timing of differentiation by coupling extracellular recognition to intracellular transcriptional control at the plasma membrane.

UniProt Summary

Functions as a receptor for several membrane-bound ligands that are presented on the surface of adjacent cells. Activates transcription factors that are involved in lineage specification. May play a role in cell-fate determination (By similarity).

InterPro Domains

  • Notch (IPR008297, family) — residues 5-2000
  • EGF-like domain (IPR000742, domain) — residues 20-1426
  • EGF-like calcium-binding domain (IPR001881, domain) — residues 59-1384
  • EGF-like calcium-binding, conserved site (IPR018097, conserved_site) — residues 178-1253
  • NOTCH1, EGF-like calcium-binding domain (IPR049883, domain) — residues 178-900
  • EGF-type aspartate/asparagine hydroxylation site (IPR000152, ptm) — residues 195-1255
  • Growth factor receptor cysteine-rich domain superfamily (IPR009030, homologous_superfamily) — residues 288-1311
  • EGF-like, conserved site (IPR013032, conserved_site) — residues 344-1374
  • Neurogenic locus notch homolog protein 1 (IPR022362, family) — residues 1426-1714
  • Notch domain (IPR000800, domain) — residues 1442-1571
  • Notch-like domain superfamily (IPR035993, homologous_superfamily) — residues 1448-1561
  • Notch, NOD domain (IPR010660, domain) — residues 1566-1622
  • Notch, NODP domain (IPR011656, domain) — residues 1660-1722
  • Ankyrin repeat-containing domain superfamily (IPR036770, homologous_superfamily) — residues 1858-2000
  • Ankyrin repeat (IPR002110, repeat) — residues 1870-1980

GO Terms

Molecular Function: molecular_function (GO:0003674), molecular function regulator activity (GO:0098772), binding (GO:0005488), transcription regulator activity (GO:0140110), enzyme regulator activity (GO:0030234), molecular function activator activity (GO:0140677), heterocyclic compound binding (GO:1901363), chromatin binding (GO:0003682), organic cyclic compound binding (GO:0097159), transcription coregulator activity (GO:0003712), protein binding (GO:0005515), molecular function inhibitor activity (GO:0140678), nucleic acid binding (GO:0003676), signaling receptor binding (GO:0005102), chromatin DNA binding (GO:0031490), enzyme binding (GO:0019899), enzyme inhibitor activity (GO:0004857), transcription coactivator activity (GO:0003713), Notch binding (GO:0005112), DNA binding (GO:0003677)

Biological Process: biological_process (GO:0008150), biological regulation (GO:0065007), response to stimulus (GO:0050896), reproductive process (GO:0022414), regulation of biological process (GO:0050789), reproduction (GO:0000003), multicellular organismal process (GO:0032501), metabolic process (GO:0008152), homeostatic process (GO:0042592), immune system process (GO:0002376), localization (GO:0051179), signaling (GO:0023052), growth (GO:0040007), negative regulation of biological process (GO:0048519), positive regulation of biological process (GO:0048518), developmental process (GO:0032502), cellular process (GO:0009987), anatomical structure development (GO:0048856), negative regulation of signaling (GO:0023057), cell division (GO:0051301), developmental process involved in reproduction (GO:0003006), anatomical structure formation involved in morphogenesis (GO:0048646), multicellular organismal-level homeostasis (GO:0048871), regulation of response to stimulus (GO:0048583), negative regulation of cellular process (GO:0048523), biosynthetic process (GO:0009058), positive regulation of viral process (GO:0048524), establishment of localization (GO:0051234), catabolic process (GO:0009056), macromolecule localization (GO:0033036), developmental growth (GO:0048589), cell population proliferation (GO:0008283), nitrogen compound metabolic process (GO:0006807), negative regulation of multicellular organismal process (GO:0051241), cell death (GO:0008219), positive regulation of locomotion (GO:0040017), regulation of signaling (GO:0023051), negative regulation of developmental process (GO:0051093), signal transduction (GO:0007165), negative regulation of transport (GO:0051051), regulation of viral process (GO:0050792), primary metabolic process (GO:0044238), morphogenesis of a branching structure (GO:0001763), positive regulation of developmental process (GO:0051094), negative regulation of response to stimulus (GO:0048585), regulation of growth (GO:0040008), cellular localization (GO:0051641), immune response (GO:0006955), positive regulation of multicellular organismal process (GO:0051240), molting cycle (GO:0042303), pattern specification process (GO:0007389), cellular component organization or biogenesis (GO:0071840), regulation of multicellular organismal process (GO:0051239), negative regulation of metabolic process (GO:0009892), regulation of cellular process (GO:0050794), cellular response to stimulus (GO:0051716), regulation of locomotion (GO:0040012), cellular developmental process (GO:0048869), response to abiotic stimulus (GO:0009628), organ growth (GO:0035265), positive regulation of response to stimulus (GO:0048584), regulation of metabolic process (GO:0019222), molting cycle process (GO:0022404), regulation of molecular function (GO:0065009), export from cell (GO:0140352), cell communication (GO:0007154), positive regulation of cellular process (GO:0048522), anatomical structure morphogenesis (GO:0009653), cell motility (GO:0048870), response to chemical (GO:0042221), regulation of reproductive process (GO:2000241), positive regulation of growth (GO:0045927), regulation of developmental process (GO:0050793), positive regulation of signaling (GO:0023056), multicellular organism development (GO:0007275), regulation of localization (GO:0032879), organic substance metabolic process (GO:0071704), cellular metabolic process (GO:0044237), positive regulation of metabolic process (GO:0009893), response to stress (GO:0006950), cellular component morphogenesis (GO:0032989), negative regulation of cellular component organization (GO:0051129), regulation of cell motility (GO:2000145), regulation of system process (GO:0044057), animal organ development (GO:0048513), neural retina development (GO:0003407), regulation of vesicle-mediated transport (GO:0060627), positive regulation of apoptotic process involved in development (GO:1904747), negative regulation of cellular response to growth factor stimulus (GO:0090288), retina development in camera-type eye (GO:0060041), negative regulation of secretion (GO:0051048), regulation of development, heterochronic (GO:0040034), cardiac septum morphogenesis (GO:0060411), regulation of anatomical structure morphogenesis (GO:0022603), secretion by cell (GO:0032940), nephron development (GO:0072006), trabecula morphogenesis (GO:0061383), negative regulation of muscle hypertrophy (GO:0014741), positive regulation of epidermis development (GO:0045684), positive regulation of nitrogen compound metabolic process (GO:0051173), positive regulation of cell differentiation (GO:0045597), appendage development (GO:0048736), organic substance biosynthetic process (GO:1901576), negative regulation of cell population proliferation (GO:0008285), protein metabolic process (GO:0019538), specification of symmetry (GO:0009799), cellular biosynthetic process (GO:0044249), response to oxygen-containing compound (GO:1901700), prostate gland epithelium morphogenesis (GO:0060740), macromolecule metabolic process (GO:0043170), positive regulation of cell motility (GO:2000147), positive regulation of biosynthetic process (GO:0009891), homeostasis of number of cells (GO:0048872), endocardial cushion formation (GO:0003272), muscle structure development (GO:0061061), regulation of cell population proliferation (GO:0042127), regulation of cell death (GO:0010941), regionalization (GO:0003002), response to nitrogen compound (GO:1901698), negative regulation of cell differentiation (GO:0045596), transport (GO:0006810), humoral immune response (GO:0006959), positive regulation of cell communication (GO:0010647), regulation of cellular metabolic process (GO:0031323), hair cycle process (GO:0022405), regulation of primary metabolic process (GO:0080090), negative regulation of signal transduction (GO:0009968), response to hypoxia (GO:0001666), regulation of viral genome replication (GO:0045069), negative regulation of cell death (GO:0060548), cell differentiation (GO:0030154), negative regulation of nervous system development (GO:0051961), system development (GO:0048731), response to oxygen levels (GO:0070482), cardiac septum development (GO:0003279), regulation of cell adhesion (GO:0030155), regulation of organ growth (GO:0046620), heart growth (GO:0060419), tube development (GO:0035295), cell morphogenesis (GO:0000902), animal organ morphogenesis (GO:0009887), cell surface receptor signaling pathway (GO:0007166), regulation of cellular component organization (GO:0051128), negative regulation of biomineral tissue development (GO:0070168), regulation of ossification (GO:0030278), positive regulation of cell population proliferation (GO:0008284), tube morphogenesis (GO:0035239), positive regulation of developmental growth (GO:0048639), negative regulation of cell communication (GO:0010648), apoptotic process involved in development (GO:1902742), axis specification (GO:0009798), retina morphogenesis in camera-type eye (GO:0060042), hair follicle morphogenesis (GO:0031069), morphogenesis of a branching epithelium (GO:0061138), positive regulation of organ growth (GO:0046622), cardiac chamber development (GO:0003205), negative regulation of cellular metabolic process (GO:0031324), cell fate commitment (GO:0045165), embryonic morphogenesis (GO:0048598), cellular response to chemical stimulus (GO:0070887), glomerulus development (GO:0032835), tissue homeostasis (GO:0001894), stem cell division (GO:0017145), hair cycle (GO:0042633), regulation of cold-induced thermogenesis (GO:0120161), developmental growth involved in morphogenesis (GO:0060560), negative regulation of photoreceptor cell differentiation (GO:0046533), regulation of signal transduction (GO:0009966), foregut morphogenesis (GO:0007440), regulation of macromolecule metabolic process (GO:0060255), reproductive structure development (GO:0048608), cellular aromatic compound metabolic process (GO:0006725), regulation of muscle adaptation (GO:0043502), positive regulation of epithelial to mesenchymal transition (GO:0010718), establishment of protein localization (GO:0045184), regulation of cellular component biogenesis (GO:0044087), regulation of apoptotic process involved in development (GO:1904748), intracellular transport (GO:0046907), negative regulation of macromolecule metabolic process (GO:0010605), muscle cell proliferation (GO:0033002), embryo development (GO:0009790), regulation of catalytic activity (GO:0050790), negative regulation of nitrogen compound metabolic process (GO:0051172), regulation of epidermis development (GO:0045682), positive regulation of macromolecule metabolic process (GO:0010604), blood vessel development (GO:0001568), heterocycle metabolic process (GO:0046483), negative regulation of molecular function (GO:0044092), establishment of localization in cell (GO:0051649), appendage morphogenesis (GO:0035107), cellular nitrogen compound metabolic process (GO:0034641), apoptotic process involved in morphogenesis (GO:0060561), angiogenesis (GO:0001525), regulation of multicellular organismal development (GO:2000026), regulation of viral transcription (GO:0046782), positive regulation of cellular metabolic process (GO:0031325), cellular response to stress (GO:0033554), epithelial cell proliferation (GO:0050673), cellular macromolecule localization (GO:0070727), negative regulation of biosynthetic process (GO:0009890), regulation of cellular response to growth factor stimulus (GO:0090287), positive regulation of cell death (GO:0010942), tissue morphogenesis (GO:0048729), programmed cell death (GO:0012501), adaptive immune response (GO:0002250), cell development (GO:0048468), prostate gland morphogenesis (GO:0060512), cardiac muscle tissue growth (GO:0055017), cell fate determination (GO:0001708), heart valve development (GO:0003170), negative regulation of ossification (GO:0030279), inflammatory response to antigenic stimulus (GO:0002437), organic cyclic compound metabolic process (GO:1901360), forebrain development (GO:0030900), hair follicle development (GO:0001942), regulation of nitrogen compound metabolic process (GO:0051171), regulation of cell differentiation (GO:0045595), cellular component organization (GO:0016043), inner ear development (GO:0048839), organic substance catabolic process (GO:1901575), positive regulation of nervous system development (GO:0051962), negative regulation of secretion by cell (GO:1903531), regulation of developmental growth (GO:0048638), endocardium development (GO:0003157), cell migration (GO:0016477), positive regulation of signal transduction (GO:0009967), regulation of secretion by cell (GO:1903530), positive regulation of viral genome replication (GO:0045070), regulation of transport (GO:0051049), organonitrogen compound metabolic process (GO:1901564), defense response (GO:0006952), response to organic substance (GO:0010033), anatomical structure homeostasis (GO:0060249), regulation of viral life cycle (GO:1903900), tissue development (GO:0009888), nucleobase-containing compound metabolic process (GO:0006139), head development (GO:0060322), regulation of cell communication (GO:0010646), regulation of biosynthetic process (GO:0009889), cardiac chamber morphogenesis (GO:0003206), heart valve morphogenesis (GO:0003179), negative regulation of cold-induced thermogenesis (GO:0120163), endoderm development (GO:0007492), regulation of hematopoietic progenitor cell differentiation (GO:1901532), nephron epithelium development (GO:0072009), cell projection organization (GO:0030030), regulation of Notch signaling pathway (GO:0008593), somatic stem cell division (GO:0048103), regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090092), positive regulation of cardiac muscle cell proliferation (GO:0060045), regulation of receptor signaling pathway via STAT (GO:1904892), regulation of epithelial cell proliferation (GO:0050678), semi-lunar valve development (GO:1905314), muscle cell differentiation (GO:0042692), embryonic heart tube development (GO:0035050), cell surface receptor signaling pathway involved in heart development (GO:0061311), circulatory system development (GO:0072359), response to decreased oxygen levels (GO:0036293), positive regulation of cell migration (GO:0030335), regulation of osteoblast differentiation (GO:0045667), cell projection morphogenesis (GO:0048858), pulmonary valve morphogenesis (GO:0003184), cytokine-mediated signaling pathway (GO:0019221), negative regulation of exocytosis (GO:0045920), ventricular septum development (GO:0003281), positive regulation of Notch signaling pathway (GO:0045747), regulation of cell proliferation involved in heart morphogenesis (GO:2000136), cellular response to organic substance (GO:0071310), establishment of protein localization to organelle (GO:0072594), cell migration involved in heart development (GO:0060973), positive regulation of epithelial cell differentiation (GO:0030858), limb morphogenesis (GO:0035108), regulation of muscle cell differentiation (GO:0051147), hepaticobiliary system development (GO:0061008), skeletal muscle cell differentiation (GO:0035914), Notch signaling pathway (GO:0007219), cardiac atrium morphogenesis (GO:0003209), positive regulation of macromolecule biosynthetic process (GO:0010557), apoptotic process (GO:0006915), adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains (GO:0002460), regulation of nucleobase-containing compound metabolic process (GO:0019219), epithelium development (GO:0060429), gland morphogenesis (GO:0022612), positive regulation of cellular biosynthetic process (GO:0031328), atrioventricular valve morphogenesis (GO:0003181), regulation of epithelial cell differentiation (GO:0030856), respiratory system development (GO:0060541), response to peptide (GO:1901652), regulation of programmed cell death (GO:0043067), protein catabolic process (GO:0030163), gland development (GO:0048732), cell differentiation involved in kidney development (GO:0061005), cardiac ventricle development (GO:0003231), morphogenesis of an epithelium (GO:0002009), positive regulation of neurogenesis (GO:0050769), skin development (GO:0043588), regulation of cell migration (GO:0030334), neuron development (GO:0048666), coronary vasculature development (GO:0060976), branching morphogenesis of an epithelial tube (GO:0048754), cardiac ventricle morphogenesis (GO:0003208), macromolecule catabolic process (GO:0009057), embryonic organ development (GO:0048568), cell morphogenesis involved in differentiation (GO:0000904), exocytosis (GO:0006887), renal tubule development (GO:0061326), nucleic acid metabolic process (GO:0090304), camera-type eye photoreceptor cell differentiation (GO:0060219), regulation of extracellular matrix organization (GO:1903053), negative regulation of cellular biosynthetic process (GO:0031327), negative regulation of Wnt signaling pathway (GO:0030178), mesenchymal cell differentiation (GO:0048762), negative regulation of cardiac muscle hypertrophy (GO:0010614), gene expression (GO:0010467), negative regulation of nucleobase-containing compound metabolic process (GO:0045934), regulation of cardiac muscle cell proliferation (GO:0060043), renal system development (GO:0072001), cardiac muscle cell proliferation (GO:0060038), reproductive system development (GO:0061458), negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090101), embryonic organ morphogenesis (GO:0048562), negative regulation of hematopoietic progenitor cell differentiation (GO:1901533), positive regulation of cell development (GO:0010720), urogenital system development (GO:0001655), positive regulation of gene expression (GO:0010628), muscle organ morphogenesis (GO:0048644), positive regulation of receptor signaling pathway via STAT (GO:1904894), positive regulation of nucleobase-containing compound metabolic process (GO:0045935), regulation of extracellular matrix assembly (GO:1901201), respiratory tube development (GO:0030323), response to organonitrogen compound (GO:0010243), positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090100), prostate gland development (GO:0030850), venous blood vessel development (GO:0060841), negative regulation of macromolecule biosynthetic process (GO:0010558), cardiac atrium development (GO:0003230), cardiocyte differentiation (GO:0035051), blood vessel endothelial cell differentiation (GO:0060837), regulation of epithelial to mesenchymal transition (GO:0010717), glomerulus vasculature development (GO:0072012), digestive tract development (GO:0048565), neuron differentiation (GO:0030182), cardiac cell development (GO:0055006), epithelial tube morphogenesis (GO:0060562), nitrogen compound transport (GO:0071705), embryonic digit morphogenesis (GO:0042733), regulation of macromolecule biosynthetic process (GO:0010556), cellular response to oxygen levels (GO:0071453), sensory system development (GO:0048880), vasculature development (GO:0001944), connective tissue development (GO:0061448), regulation of glial cell proliferation (GO:0060251), glial cell differentiation (GO:0010001), organic substance transport (GO:0071702), embryonic heart tube morphogenesis (GO:0003143), negative regulation of muscle cell differentiation (GO:0051148), regulation of gene expression (GO:0010468), regulation of cardiac muscle tissue growth (GO:0055021), striated muscle cell proliferation (GO:0014855), intracellular protein transport (GO:0006886), negative regulation of osteoblast differentiation (GO:0045668), epithelial cell development (GO:0002064), regulation of embryonic development (GO:0045995), heart trabecula morphogenesis (GO:0061384), epidermal cell fate specification (GO:0009957), sprouting angiogenesis (GO:0002040), heart development (GO:0007507), artery development (GO:0060840), cellular response to hypoxia (GO:0071456), positive regulation of heart growth (GO:0060421), atrioventricular valve development (GO:0003171), organonitrogen compound catabolic process (GO:1901565), epithelial cell fate commitment (GO:0072148), neuron fate commitment (GO:0048663), muscle cell development (GO:0055001), aromatic compound biosynthetic process (GO:0019438), regulation of cell development (GO:0060284), sensory organ development (GO:0007423), regulation of exocytosis (GO:0017157), secretion (GO:0046903), regulation of Wnt signaling pathway (GO:0030111), regulation of glial cell differentiation (GO:0045685), positive regulation of epithelial cell proliferation (GO:0050679), neurogenesis (GO:0022008), positive regulation of RNA metabolic process (GO:0051254), ventricular septum morphogenesis (GO:0060412), inflammatory response (GO:0006954), negative regulation of epithelial cell proliferation (GO:0050680), left/right pattern formation (GO:0060972), muscle tissue development (GO:0060537), regulation of stem cell proliferation (GO:0072091), regulation of cellular biosynthetic process (GO:0031326), regulation of cardiac muscle hypertrophy (GO:0010611), cellular nitrogen compound biosynthetic process (GO:0044271), embryonic appendage morphogenesis (GO:0035113), protein localization (GO:0008104), muscle organ development (GO:0007517), negative regulation of cell development (GO:0010721), embryo development ending in birth or egg hatching (GO:0009792), regulation of neuron differentiation (GO:0045664), macromolecule biosynthetic process (GO:0009059), organic cyclic compound biosynthetic process (GO:1901362), negative regulation of BMP signaling pathway (GO:0030514), digestive system development (GO:0055123), cell part morphogenesis (GO:0032990), sensory organ morphogenesis (GO:0090596), nuclear transport (GO:0051169), aortic valve morphogenesis (GO:0003180), regulation of BMP signaling pathway (GO:0030510), regulation of muscle system process (GO:0090257), regulation of epidermal cell differentiation (GO:0045604), brain development (GO:0007420), negative regulation of neurogenesis (GO:0050768), regulation of heart growth (GO:0060420), heart morphogenesis (GO:0003007), nervous system development (GO:0007399), epidermis development (GO:0008544), protein transport (GO:0015031), positive regulation of cardiac muscle tissue growth (GO:0055023), heterocycle biosynthetic process (GO:0018130), vasculogenesis (GO:0001570), central nervous system development (GO:0007417), negative regulation of glial cell proliferation (GO:0060253), inner ear receptor cell differentiation (GO:0060113), regulation of RNA metabolic process (GO:0051252), response to cytokine (GO:0034097), negative regulation of catalytic activity (GO:0043086), muscle tissue morphogenesis (GO:0060415), neural tube development (GO:0021915), positive regulation of programmed cell death (GO:0043068), positive regulation of epidermal cell differentiation (GO:0045606), regulation of nervous system development (GO:0051960), mesenchyme development (GO:0060485), negative regulation of neuron differentiation (GO:0045665), left/right axis specification (GO:0070986), digestive tract morphogenesis (GO:0048546), epithelial cell differentiation (GO:0030855), nucleobase-containing compound biosynthetic process (GO:0034654), regulation of biomineral tissue development (GO:0070167), determination of bilateral symmetry (GO:0009855), lung development (GO:0030324), stem cell differentiation (GO:0048863), mesenchyme morphogenesis (GO:0072132), myoblast differentiation (GO:0045445), blood vessel morphogenesis (GO:0048514), negative regulation of epithelial cell differentiation (GO:0030857), limb development (GO:0060173), regulation of secretion (GO:0051046), vesicle-mediated transport (GO:0016192), homeostasis of number of cells within a tissue (GO:0048873), negative regulation of RNA metabolic process (GO:0051253), kidney development (GO:0001822), anterior/posterior pattern specification (GO:0009952), regulation of apoptotic process (GO:0042981), negative regulation of gliogenesis (GO:0014014), striated muscle tissue development (GO:0014706), ear development (GO:0043583), cardiac left ventricle morphogenesis (GO:0003214), skeletal muscle tissue development (GO:0007519), ventricular trabecula myocardium morphogenesis (GO:0003222), regulation of oligodendrocyte differentiation (GO:0048713), liver development (GO:0001889), positive regulation of RNA biosynthetic process (GO:1902680), artery morphogenesis (GO:0048844), cardiac epithelial to mesenchymal transition (GO:0060317), nucleocytoplasmic transport (GO:0006913), regulation of astrocyte differentiation (GO:0048710), response to interleukin-17 (GO:0097396), positive regulation of BMP signaling pathway (GO:0030513), cardiac muscle tissue development (GO:0048738), photoreceptor cell differentiation (GO:0046530), kidney epithelium development (GO:0072073), endocardial cushion morphogenesis (GO:0003203), columnar/cuboidal epithelial cell differentiation (GO:0002065), gliogenesis (GO:0042063), neuron projection development (GO:0031175), endothelium development (GO:0003158), epidermal cell differentiation (GO:0009913), regulation of keratinocyte differentiation (GO:0045616), nucleic acid-templated transcription (GO:0097659), pericardium development (GO:0060039), mechanoreceptor differentiation (GO:0042490), determination of left/right symmetry (GO:0007368), pulmonary valve development (GO:0003177), eye morphogenesis (GO:0048592), hindlimb morphogenesis (GO:0035137), smooth muscle cell differentiation (GO:0051145), oligodendrocyte differentiation (GO:0048709), endocardial cushion development (GO:0003197), epidermis morphogenesis (GO:0048730), negative regulation of regulated secretory pathway (GO:1903306), regulation of neurogenesis (GO:0050767), negative regulation of canonical Wnt signaling pathway (GO:0090090), regulation of canonical Wnt signaling pathway (GO:0060828), inner ear auditory receptor cell differentiation (GO:0042491), cell morphogenesis involved in neuron differentiation (GO:0048667), skeletal muscle organ development (GO:0060538), regulation of striated muscle cell differentiation (GO:0051153), positive regulation of gliogenesis (GO:0014015), positive regulation of glial cell differentiation (GO:0045687)

Cellular Component: cellular_component (GO:0005575), cellular anatomical entity (GO:0110165), intracellular anatomical structure (GO:0005622), organelle (GO:0043226), membrane (GO:0016020), membrane-enclosed lumen (GO:0031974), cytosol (GO:0005829), cell surface (GO:0009986), cell periphery (GO:0071944), cell junction (GO:0030054), organelle subcompartment (GO:0031984), apical part of cell (GO:0045177), cytoplasm (GO:0005737), endomembrane system (GO:0012505), nucleoplasm (GO:0005654), extracellular region (GO:0005576), organelle membrane (GO:0031090), cytoplasmic vesicle (GO:0031410), intracellular organelle (GO:0043229), apical plasma membrane (GO:0016324), endoplasmic reticulum subcompartment (GO:0098827), nuclear outer membrane-endoplasmic reticulum membrane network (GO:0042175), Golgi apparatus (GO:0005794), plasma membrane region (GO:0098590), organelle lumen (GO:0043233), endoplasmic reticulum (GO:0005783), anchoring junction (GO:0070161), membrane-bounded organelle (GO:0043227), plasma membrane (GO:0005886), intracellular membrane-bounded organelle (GO:0043231), bounding membrane of organelle (GO:0098588), endoplasmic reticulum membrane (GO:0005789), vesicle (GO:0031982), intracellular organelle lumen (GO:0070013), cell-cell junction (GO:0005911), Golgi membrane (GO:0000139), intracellular vesicle (GO:0097708), nucleus (GO:0005634), nuclear lumen (GO:0031981), adherens junction (GO:0005912)


Generated by BioReason

Deep Research Openai

(Notch1-deep-research-openai.md)

provider: openai
model: o3-deep-research-2025-06-26
cached: false
start_time: '2026-03-20T00:35:47.451004'
end_time: '2026-03-20T00:43:40.321730'
duration_seconds: 472.87
template_file: templates/gene_research_go_focused.md
template_variables:
organism: mouse
gene_id: Notch1
gene_symbol: Notch1
uniprot_accession: Q01705
protein_description: 'RecName: Full=Neurogenic locus notch homolog protein 1; Short=Notch
1; AltName: Full=Motch A {ECO:0000303|PubMed:8440332}; AltName: Full=mT14; AltName:
Full=p300; Contains: RecName: Full=Notch 1 extracellular truncation {ECO:0000303|PubMed:10882062};
Short=NEXT {ECO:0000303|PubMed:10882062}; Contains: RecName: Full=Notch 1 intracellular
domain; Short=NICD; Flags: Precursor;'
gene_info: Name=Notch1; Synonyms=Motch {ECO:0000303|PubMed:8440332};
organism_full: Mus musculus (Mouse).
protein_family: Belongs to the NOTCH family. .
protein_domains: Ankyrin_rpt. (IPR002110); Ankyrin_rpt-contain_sf. (IPR036770);
EGF. (IPR000742); EGF-like_Ca-bd_dom. (IPR001881); EGF-like_CS. (IPR013032)
provider_config:
timeout: 600
max_retries: 3
parameters:
allowed_domains: []
temperature: 0.1
top_p: 1.0
citation_count: 98


Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

  • UniProt Accession: Q01705
  • Protein Description: RecName: Full=Neurogenic locus notch homolog protein 1; Short=Notch 1; AltName: Full=Motch A {ECO:0000303|PubMed:8440332}; AltName: Full=mT14; AltName: Full=p300; Contains: RecName: Full=Notch 1 extracellular truncation {ECO:0000303|PubMed:10882062}; Short=NEXT {ECO:0000303|PubMed:10882062}; Contains: RecName: Full=Notch 1 intracellular domain; Short=NICD; Flags: Precursor;
  • Gene Information: Name=Notch1; Synonyms=Motch {ECO:0000303|PubMed:8440332};
  • Organism (full): Mus musculus (Mouse).
  • Protein Family: Belongs to the NOTCH family. .
  • Key Domains: Ankyrin_rpt. (IPR002110); Ankyrin_rpt-contain_sf. (IPR036770); EGF. (IPR000742); EGF-like_Ca-bd_dom. (IPR001881); EGF-like_CS. (IPR013032)

MANDATORY VERIFICATION STEPS:

  1. Check if the gene symbol "Notch1" matches the protein description above
  2. Verify the organism is correct: Mus musculus (Mouse).
  3. Check if protein family/domains align with what you find in literature
  4. If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'Notch1' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene Notch1 (gene ID: Notch1, UniProt: Q01705) in mouse.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Notch1 (Mus musculus) – Function and Biological Roles

Introduction and Key Concepts

Notch1 (Neurogenic locus notch homolog 1) is a single-pass transmembrane receptor in the mouse, encoded by the Notch1 gene (UniProt Q01705). It belongs to the highly conserved Notch family of receptors (Notch1–4 in mammals) that mediate cell–cell communication and cell fate decisions (www.nature.com) (www.nature.com). Notch1 was originally identified by homology to Drosophila Notch (a “neurogenic” gene controlling nervous system development) and shares the fundamental role of regulating how cells differentiate during development and homeostasis (www.nature.com). In essence, Notch1 functions as a ligand-activated signaling receptor: when activated by neighboring cells, it directly influences gene transcription in the nucleus, thereby altering cell behavior. This pathway is crucial for many developmental processes and continues to operate throughout the lifespan, with roles in maintaining adult tissue structure and responding to injury (www.nature.com). Consistent with its broad importance, Notch signaling (and Notch1 in particular) has been linked to numerous human diseases, including developmental disorders and cancers (www.nature.com).

Structure and Processing: The Notch1 protein is produced as a large precursor (~2530 amino acids) that undergoes proteolytic processing and contains several defined domains important for its function. The extracellular region of mouse Notch1 features 36 EGF-like repeats (epidermal growth factor–like domains) which facilitate ligand binding (pmc.ncbi.nlm.nih.gov). Within these repeats, a specific segment (around EGF repeats 11–12) is critical for recognizing Notch ligands (such as Delta-like and Jagged family proteins) (pmc.ncbi.nlm.nih.gov). Adjacent to the EGF repeats is the negative regulatory region (NRR), composed of three cysteine-rich LIN-12/Notch repeats (LNRs) and a heterodimerization (HD) domain (pmc.ncbi.nlm.nih.gov). In the Golgi apparatus, the nascent Notch1 precursor is cleaved at the HD domain by a furin-like convertase (this is called the S1 cleavage), separating the protein into an N-terminal extracellular subunit and a C-terminal transmembrane subunit that remain non-covalently associated (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This processing yields the mature heterodimeric Notch1 receptor that is transported to the cell surface (pmc.ncbi.nlm.nih.gov). The LNR–HD region keeps the receptor in an autoinhibited conformation, preventing signaling in the absence of ligand (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Notch1 is activated through direct cell–cell contact. When a Notch ligand (e.g. DLL1, DLL4, JAG1, or JAG2 on a neighboring cell) binds to the Notch1 extracellular domain, it induces a conformational change and “pulling” force that exposes the receptor’s cleavage site in the HD domain (pmc.ncbi.nlm.nih.gov). This leads to the second proteolytic cut (the S2 cleavage) by ADAM-family metalloproteases at the cell surface (pmc.ncbi.nlm.nih.gov). After this ligand-triggered S2 cleavage, the remaining membrane-tethered fragment of Notch1 – called NEXT (Notch extracellular truncation) – is rapidly cleaved within its transmembrane segment by the γ-secretase complex (S3 cleavage) (pmc.ncbi.nlm.nih.gov). The γ-secretase enzyme (a multi-subunit protease complex including Presenilin) releases the Notch1 intracellular domain (NICD) from the membrane (pmc.ncbi.nlm.nih.gov). This NICD is the key effector of Notch signaling: it translocates from the cytoplasm into the nucleus to regulate gene expression (pmc.ncbi.nlm.nih.gov). The NICD contains several functional domains: an RBPJ association module (RAM) near its N-terminus, seven ankyrin repeats (ANK) that serve as protein–protein interaction surfaces, two nuclear localization sequences (NLS) flanking the ANK region (ensuring NICD enters the nucleus), and a C-terminal PEST domain rich in proline, glutamic acid, serine, threonine (pmc.ncbi.nlm.nih.gov). The PEST motif carries degradation signals that target NICD for ubiquitin-mediated proteasomal turnover, thereby limiting the duration of Notch1 signaling (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Notch1’s overall architecture is shared by other Notch receptors, with Notch2–4 having similar domain organization and differing mostly in the number of EGF repeats and length of their PEST regions (pmc.ncbi.nlm.nih.gov).

Activation Mechanism and Signaling Pathway

Once liberated by γ-secretase, the Notch1 intracellular domain (NICD) acts as a transcriptional regulator. Canonical Notch signaling involves NICD partnering with a DNA-binding protein of the CSL family (also known as RBPJ in mammals, CBF1/Su(H)/Lag-1 in other species) (www.nature.com) (pmc.ncbi.nlm.nih.gov). In the absence of NICD, RBPJ/CSL is bound to target gene promoters along with corepressor proteins and histone deacetylases, keeping those target genes silenced (pmc.ncbi.nlm.nih.gov). When NICD enters the nucleus, it directly binds to RBPJ/CSL, via the RAM and ankyrin domains, and converts it into a transcriptional activator complex (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). NICD binding displaces the pre-bound corepressors and allows recruitment of coactivator proteins – most importantly, a Mastermind-like (MAML) protein, which bridges NICD and CSL and helps recruit the transcriptional machinery (pmc.ncbi.nlm.nih.gov). The assembled NICD–CSL–MAML complex drives expression of Notch target genes (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). A classic family of direct Notch targets are the Hairy/Enhancer of Split (HES) genes and their relatives the HEY genes, which encode transcriptional repressors that in turn modulate cell differentiation programs (pmc.ncbi.nlm.nih.gov). Thus, the primary outcome of Notch1 activation is changes in gene expression in the signal-receiving cell, typically leading to context-dependent effects like cell fate specification or inhibition of differentiation. Notch signaling is unusual in that the receptor itself (NICD fragment) becomes a part of the nuclear transcription factor complex, a mechanism often described as “signal transduction by proteolysis.” This directness bypasses second messengers and allows immediate transcriptional response to cell–cell interactions (www.nature.com). Importantly, Notch signaling is highly context-dependent – the same signal can have different outcomes depending on the cell type and the network of other signals and transcription factors present (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

The Notch pathway is conserved across metazoans and generally operates at short range, requiring cells to be in direct contact (pmc.ncbi.nlm.nih.gov). Mammals have five canonical Notch ligands (Delta-like 1, 3, 4 and Jagged-1, 2), which are themselves transmembrane proteins presented on adjacent cells (pmc.ncbi.nlm.nih.gov). Notch1–ligand binding is a unidirectional signaling event: the cell expressing the ligand acts as the “signaling” cell, and the cell expressing Notch1 receives the signal. Notch1 activation typically influences binary cell fate decisions – for example, helping one cell adopt a primary fate while its neighbors adopt an alternative fate, a process famously described as lateral inhibition in neurogenesis (pmc.ncbi.nlm.nih.gov). Notch1 can also mediate inductive signaling, where a steady Notch signal drives neighboring cells into a particular differentiated state. The specificity of action is partly achieved by the fact that Notch1’s influence is limited to the nucleus of the cell that produces NICD (there is no diffusion of NICD to other cells), and by the localized nature of ligand–receptor contact (often within epithelial cell junctions or niche microenvironments). After NICD initiates target gene transcription, its activity is attenuated by phosphorylation and ubiquitylation (primarily via the E3 ubiquitin ligase FBXW7 acting on the PEST domain), causing NICD degradation (pmc.ncbi.nlm.nih.gov). This built-in negative feedback ensures Notch1 signals are transient unless continually stimulated by ligand. Notch1 signaling can also be modulated by glycosylation of its EGF repeats (mediated by enzymes like Fringe), which alters ligand binding affinity and receptor activation (pmc.ncbi.nlm.nih.gov).

Recent insights: While the canonical CSL-dependent pathway is the best-understood mode of Notch1 action, studies show that Notch1 has additional non-canonical roles and regulatory modes. For instance, Notch1 and its ligands can interact within the same cell (“cis-interactions”) to inhibit signaling. In a 2024 study, Thambyrajah et al. demonstrated that in embryonic hematopoietic stem cells, Jagged1 ligands expressed on the same cell surface bind Notch1 in cis and prevent its activation, thereby preserving the stem cell fate (pmc.ncbi.nlm.nih.gov). If Notch1 in these cells is forcibly activated (bypassing cis-inhibition), the stem cells prematurely differentiate, indicating that Notch1 inactivity is required to maintain the stem cell state in that context (pmc.ncbi.nlm.nih.gov). This cis-inhibition mechanism highlights how cells can autonomously modulate Notch1 signaling strength by co-expressing ligands, adding a layer of control beyond external ligand availability. Another frontier in Notch1 biology is its transcription-independent functions. A 2023 study reported a form of “Notch1 cortical signaling” in which the Notch1 protein at the cell membrane (particularly the transmembrane domain and remaining juxtamembrane portions after NICD release) helps organize the cortical actin cytoskeleton and cell–cell junctions (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). White et al. (2023) found that Notch1 at epithelial adherens junctions interacts with an effector protein FAM83H and stabilizes E-cadherin-based cell adhesion, which in turn restrains EGFR signaling and excessive cell proliferation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Notably, this structural role required the presence of the Notch1 transmembrane segment (TMD) but not the NICD, suggesting it operates independently of gene transcription. Such non-canonical functions appear specialized (observed in mammary epithelial architectures and previously in endothelial cells (pmc.ncbi.nlm.nih.gov)) but reveal that Notch1 receptors can influence cell architecture and signaling at the cortex in addition to their classical nuclear role. These discoveries underscore that Notch1 is a versatile signaling module, with ongoing research uncovering new modes of action.

Biological Functions in Development and Homeostasis

Developmental roles: Notch1 is a master regulator of cell fate during embryonic development. Through iterative cell–cell signaling events, Notch1 helps pattern tissues and coordinate differentiation. In general, Notch1 activation tends to maintain an undifferentiated state or progenitor character in cells that receive the signal, thereby postponing or redirecting their differentiation. For example, in the nervous system, Notch1 signaling in neural progenitor cells inhibits neuronal differentiation, ensuring that not all cells convert into neurons at once. This mechanism – initially discovered from the neurogenic phenotype of Notch mutants in flies – is conserved in mammals and is critical for balancing neural stem cell maintenance with neuron production (www.nature.com). Loss of Notch activity in neural precursors leads to premature neuronal differentiation and depletion of the progenitor pool, whereas excessive Notch1 can block neurons from forming. Notch1 also plays repeated roles at later stages of neurodevelopment, influencing gliogenesis and synaptic patterning (often through induction of Hes/Hey genes that suppress proneural factors). Because of these roles, Notch1 is required for proper brain development and has been implicated in neurodevelopmental disorders when dysregulated (www.nature.com).

In the hematopoietic and immune system, Notch1 provides a famous example of a binary cell-fate switch. Notch1 signaling is essential for T-cell lineage commitment in the thymus. Experimental studies showed that if Notch1 is disabled in hematopoietic progenitor cells, those progenitors fail to become T cells and instead default to the B-cell lineage – even when they reside in the thymic environment (pmc.ncbi.nlm.nih.gov). In a landmark 2001 study, Radtke and colleagues demonstrated that Notch1–deficient common lymphoid precursors adopt a B cell fate in the thymus, whereas normally the thymus (via Notch-Delta signals) instructs them to become T cells (pmc.ncbi.nlm.nih.gov). Thus, Notch1 serves as a pivotal switch that directs lymphoid precursors towards the T cell program and away from the B cell program. Consistently, Delta-like ligands (especially DLL4) presented by thymic epithelial cells activate Notch1 on immigrant progenitors to trigger the T-cell developmental pathway. Beyond T cells, Notch1 (and related receptors) also influence other blood cell lineages and the formation of hematopoietic stem cells. During embryogenesis, Notch1 is required for the emergence of definitive hematopoietic stem cells from hemogenic endothelium in the aorta-gonad-mesonephros region (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). If Notch signaling is blocked at that stage, fewer HSCs are produced. In the adult bone marrow, Notch signals (from niche cells) continue to support HSC maintenance and may bias differentiation outcomes for lymphocytes and other lineages, although redundancy with other Notch receptors exists.

Notch1 is indispensable for proper organogenesis and tissue patterning. Mice lacking functional Notch1 die in mid-gestation, reflecting widespread developmental failures (www.nature.com). Notch1-null or Notch1 signal–deficient embryos display defects in somite segmentation (leading to irregular formation of the vertebral column segments) and in vascular development (www.nature.com). Notch1, together with DLL1 and DLL4, is crucial for the formation of the embryonic vasculature: it helps specify arterial endothelial cell identity and coordinate angiogenic sprouting. For instance, in developing blood vessels, cells with higher Notch1 activity adopt an arterial fate while suppressing venous differentiation, and Notch1-DLL4 interactions between endothelial tip and stalk cells refine the pattern of new vessel branching. Notch1 is also involved in the development of the heart (cardiac outflow tract and valves), pancreas, kidneys, and many other structures by modulating the differentiation of progenitors in those tissues. In each context, Notch1 often acts reiteratively: for example, controlling the proliferation of a progenitor pool, then later influencing the choice of specific cell subtypes that arise. Many of these roles have been defined by conditional knockout studies in mice. In the intestinal epithelium, Notch1 and Notch2 signals maintain the balance between absorptive enterocytes and secretory cells (goblet and others) – Notch activation promotes the absorptive cell fate and prevents secretory differentiation. Accordingly, inhibiting Notch (with γ-secretase inhibitors) in adult mice causes a rapid increase in goblet cells in the gut and loss of proliferative crypt progenitors, explaining why diarrhea is a side effect of systemic Notch blockade (pmc.ncbi.nlm.nih.gov). Notch1 signaling similarly maintains stem or progenitor states in the skin, inner ear, lung airways, and other renewing tissues, while coordinating proper differentiation timing. As Bray and Bigas (2025) note, Notch signaling often has “iterative roles” during development – first controlling the state of a progenitor, then later the fate of its progeny – and these roles can continue into adulthood in tissue maintenance and repair (www.nature.com). For example, Notch1 activity persists in adult neural stem cell niches (subventricular zone and hippocampus), where it restrains differentiation and promotes stem cell self-renewal, contributing to ongoing neurogenesis in a regulated manner (www.nature.com). In summary, Notch1’s primary biological function is to act as a context-dependent cell fate regulator: by transmitting local cell–cell signals into changes in gene expression, it shapes developmental patterning and ensures the proper balance between progenitors and differentiated cells in many tissues (pmc.ncbi.nlm.nih.gov) (www.nature.com).

Homeostasis and regeneration: Notch1’s influence extends beyond embryonic development into adult tissue homeostasis. Many adult stem cell systems exploit Notch signaling to control differentiation. We have mentioned the intestine and bone marrow as examples; similarly, in the epidermis, Notch1 promotes differentiation of keratinocytes. When Notch1 is active in a basal skin cell, it drives that cell to exit the stem cell compartment and differentiate into a spinous/intermediate cell, helping form the stratified layers. If Notch1 is lost in skin progenitors, those cells can expand excessively and fail to differentiate properly (www.nature.com). This role of Notch1 in inducing differentiation in skin (and thus restraining unchecked growth) is one reason that Notch1 is considered a tumor suppressor in the epidermis – Notch1-deficient skin can develop epidermal cancers (squamous cell carcinomas) due to accumulation of undifferentiated, proliferative cells (www.nature.com). In other contexts, Notch1 can act to support proliferation: for example, Notch signaling is involved in liver regeneration and cardiac injury responses, where it may help reactive progenitor cells expand or transform. The outcome depends on how the Notch1 targets interface with other pathways (e.g. Notch1 crosstalks with Wnt, TGF-β, and hypoxia pathways in various stem cell niches (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov)). Overall, Notch1 provides a means for cells in a community (tissue) to communicate and coordinate behavior, maintaining tissue architecture. This is vividly illustrated by the recent finding that Notch1 at cell junctions strengthens adhesion: in a confluent epithelial layer, Notch1’s presence at the cortex helps cells sense confluency and suppresses further growth (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In summary, from embryogenesis through adulthood, Notch1 plays a “gate-keeper” role in cell fate and differentiation, ensuring the right cells form at the right time and place, and that stem cell pools are neither prematurely exhausted nor overgrown. When this regulation goes awry, developmental defects or diseases can result.

Notch1 in Disease Contexts and Therapeutic Developments

Given its central role in regulating cell proliferation and differentiation, it is not surprising that NOTCH1 is involved in many diseases. Aberrant Notch1 signaling – either excessive or deficient – can contribute to oncogenesis, developmental syndromes, and other pathologies. Notch1 is somewhat unusual in that it can function as an oncogene in some tissues and a tumor suppressor in others (pmc.ncbi.nlm.nih.gov) (www.nature.com).

Oncogenic Notch1: The clearest example of Notch1 as an oncogenic driver is in T-cell acute lymphoblastic leukemia (T-ALL). NOTCH1 was first linked to human T-ALL in the early 1990s, and subsequent genomic studies revealed that more than 50% of T-ALL patients have somatic activating mutations in the NOTCH1 gene (pmc.ncbi.nlm.nih.gov). These mutations typically occur either in the HD domain (extracellular heterodimerization region) or in the C-terminal PEST domain of Notch1 (pmc.ncbi.nlm.nih.gov). HD domain mutations (e.g. small deletions or amino-acid substitutions) destabilize the autoinhibited conformation, essentially making the receptor prone to ligand-independent activation (pmc.ncbi.nlm.nih.gov). PEST domain mutations remove the degron signals, prolonging the NICD’s half-life in the nucleus (pmc.ncbi.nlm.nih.gov). Both types of mutations lead to excessive Notch1 signaling in T-cell progenitors. This drives leukemia by altering transcription of genes that control cell growth and metabolism – for example, Notch1 directly upregulates MYC and other oncogenic programs in T-ALL cells (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In mouse models, forced activation of Notch1 in hematopoietic stem cells or thymocytes is sufficient to induce T-cell leukemias (pmc.ncbi.nlm.nih.gov). The clinical relevance is significant: NOTCH1 status is being explored as a prognostic marker in T-ALL, and components of Notch signaling are targets for therapy (see below). Notch1 is also mutated or overactivated in certain solid tumors. For instance, about 10–15% of human non-small cell lung carcinomas (especially lung adenocarcinoma) have mutations in Notch pathway genes, sometimes including NOTCH1. Notch1 activation is linked to poor differentiation and stem-like tumor cell phenotype in some solid cancers such as triple-negative breast cancer and pancreatic ductal carcinoma (pmc.ncbi.nlm.nih.gov). On the other hand, in some tumors Notch1 acts as a tumor suppressor: frequent loss-of-function mutations in NOTCH1 are found in squamous cell carcinomas of the skin, esophagus, and head and neck (www.nature.com), suggesting that when Notch1’s prodifferentiation signal is removed, cells become prone to malignant transformation. Indeed, a study in mouse skin showed that Notch1 deletion led to spontaneous basal cell carcinomas, whereas activating Notch1 caused those cells to exit the cell cycle via differentiation (www.nature.com). This dichotomy exemplifies the context-dependent nature of Notch1 – promoting cancer in settings like T cells (where it sustains an undifferentiated, proliferative state) but suppressing cancer in settings like stratified epithelia (where it is needed to induce differentiation of potential cancer-initiating cells). Beyond cancer, germline mutations in Notch pathway components can cause developmental disorders. NOTCH1 germline mutations in humans have been associated with congenital heart defects, such as bicuspid aortic valve and left ventricular outflow tract malformations (pmc.ncbi.nlm.nih.gov). In these cases, heterozygous loss of Notch1 impairs valve formation and can lead to early-onset calcification of valves (pmc.ncbi.nlm.nih.gov). (Mutations in the ligand JAG1 or in NOTCH2 cause Alagille syndrome, a complex developmental disease affecting the liver, heart, and other organs (pmc.ncbi.nlm.nih.gov) – highlighting again that balanced Notch signaling is vital for normal organ development.)

Therapeutic targeting of Notch1: The prominent role of Notch1 in diseases like T-ALL has motivated efforts to develop Notch pathway inhibitors. The simplest way to block Notch signaling is to prevent NICD production via γ-secretase inhibitors (GSIs), since γ-secretase is required for S3 cleavage of all Notch receptors. In fact, one of the first clinical trials (launched in 2006) for Notch-related therapy used a GSI (MK-0752) in patients with refractory T-ALL (pmc.ncbi.nlm.nih.gov). The drug did achieve a reduction in leukemia burden in some cases (one T-ALL patient had ~45% tumor mass reduction in 4 weeks), but unfortunately the trial had to be halted due to dose-limiting toxicity – namely, severe gastrointestinal side effects (secretory diarrhea) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This toxicity was anticipated from animal studies: GSIs cause an overproduction of goblet cells in the intestines by blocking Notch1/2, disrupting gut homeostasis. The GSI trial outcome underscored a key challenge: Notch1 is so important in normal physiology that systemic inhibition leads to mechanism-related side effects (pmc.ncbi.nlm.nih.gov). Since then, researchers have pursued more selective strategies to inhibit Notch1 in cancer while sparing other tissues. One approach has been to develop monoclonal antibodies against specific Notch receptors or ligands. Brontictuzumab is a humanized antibody that binds the negative regulatory region of NOTCH1, stabilizing the autoinhibited conformation and preventing ligand activation. In a Phase I study (initiated 2013) of brontictuzumab in patients with advanced solid tumors, there were signs of anti-tumor activity: 2 out of 48 patients achieved partial tumor responses and 4 others had stable disease for ≥6 months, particularly in tumors like adenoid cystic carcinoma that are known to often have aberrant Notch activation (pmc.ncbi.nlm.nih.gov). Notably, adenoid cystic carcinomas with activating NOTCH1 mutations responded, suggesting target engagement (pmc.ncbi.nlm.nih.gov). However, even with this receptor-specific blockade, toxicities were observed – including grade 3 diarrhea and fatigue in some patients, which were dose-limiting (pmc.ncbi.nlm.nih.gov). These events reflect on-target effects of Notch1 inhibition in normal gut and perhaps other tissues. Other Notch-targeting agents have been tested, such as antibodies against Notch2/3 (e.g. tarextumab) and ligand blockers or decoys, with mixed results and sometimes unexpected pro-tumor effects in certain contexts (since Notch can also suppress tumors). There are also inhibitors of the Notch transcription complex under investigation (e.g. small molecules inhibiting RBPJ–NICD interaction or MAML function) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), which might offer another route to dial down Notch1-driven gene expression. None of these therapies have yet achieved regulatory approval, due in part to the narrow therapeutic window.

Interestingly, one area where Notch1 status is being leveraged is cancer immunotherapy. Emerging evidence suggests that tumors harboring Notch pathway mutations (often loss-of-function) may respond differently to immune checkpoint blockade. Notch-inactivating mutations can lead to a less differentiated, more antigenic tumor cell phenotype and a pro-inflammatory microenvironment – for example, via increased T cell infiltration or higher expression of immune genes (pmc.ncbi.nlm.nih.gov). A recent clinical study in 2023 found that NSCLC patients with NOTCH1 mutations had significantly better outcomes on PD-1/PD-L1 inhibitor therapy than those with wild-type Notch1 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Specifically, NOTCH1-mutant lung cancer patients showed higher tumor mutational burden and achieved superior overall survival under checkpoint blockade (median overall survival was longer, and on multivariate analysis Notch1 mutation was associated with a hazard ratio ~0.4 for death) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This suggests that loss of Notch1 signaling in a tumor might increase immune visibility (perhaps by upregulating neoantigen expression or interferon pathways), making them more susceptible to immunotherapy. While this finding needs further validation, it points to NOTCH1 mutation as a potential biomarker for immunotherapy response in certain cancers. More broadly, it exemplifies how deepening our understanding of Notch1’s role in tumor biology could inform personalized treatment strategies – either by directly targeting the pathway or by exploiting its downstream effects on tumor–immune interactions.

Conclusion: Notch1 is a fundamental signaling protein that ties together cell-to-cell communication with gene regulation. Through its ligand-induced proteolysis mechanism, Notch1 directly converts external signals at the cell membrane into changes in transcriptional programs in the nucleus. It controls critical decisions in cell fate, proliferation, and differentiation in a context-dependent manner. Modern research (2023–2024) continues to reveal new facets of Notch1 biology – from cis-inhibitory loops that fine-tune stem cell signals (pmc.ncbi.nlm.nih.gov), to non-traditional roles in strengthening cell junctions and controlling cell polarity (pmc.ncbi.nlm.nih.gov). These insights expand our view of how Notch1 functions beyond the classical paradigm. Clinically, Notch1 stands as a double-edged sword: its dysregulation can lead to severe diseases, yet it is a challenging therapeutic target due to its importance in normal physiology. Ongoing work in developmental biology, structural biochemistry, and clinical oncology is converging to unravel how to modulate Notch1 safely and effectively. By learning how Notch1’s “molecular decisions” are made and modulated, scientists hope to design interventions that can, for example, shut down a Notch1-driven leukemia or stimulate regenerative healing in tissues, without collateral damage. Notch1 thus remains a focus of intense research as both a paradigm of cell signaling and a key node in human health and disease (pmc.ncbi.nlm.nih.gov) (www.nature.com).

References: (Publication dates and URLs are provided in citations throughout the text)

Citations

  1. AnnotationURLCitation(end_index=519, start_index=379, title='Embryonic lethality in mice homozygous for a processing-deficient allele of Notch1 | Nature', type='url_citation', url='https://www.nature.com/articles/35016111#:~:text=The%20Notch%20genes%20encode%20single,11%7D.%20Not%20all%20observations')
  2. AnnotationURLCitation(end_index=679, start_index=520, title='Modes of Notch signalling in development and disease | Nature Reviews Molecular Cell Biology', type='url_citation', url='https://www.nature.com/articles/s41580-025-00835-2#:~:text=Many%20different%20animal%20developmental%20and,that%20it%20has%20many%20diverse')
  3. AnnotationURLCitation(end_index=1073, start_index=914, title='Modes of Notch signalling in development and disease | Nature Reviews Molecular Cell Biology', type='url_citation', url='https://www.nature.com/articles/s41580-025-00835-2#:~:text=Many%20different%20animal%20developmental%20and,that%20it%20has%20many%20diverse')
  4. AnnotationURLCitation(end_index=1613, start_index=1454, title='Modes of Notch signalling in development and disease | Nature Reviews Molecular Cell Biology', type='url_citation', url='https://www.nature.com/articles/s41580-025-00835-2#:~:text=Many%20different%20animal%20developmental%20and,that%20it%20has%20many%20diverse')
  5. AnnotationURLCitation(end_index=1941, start_index=1786, title='Modes of Notch signalling in development and disease | Nature Reviews Molecular Cell Biology', type='url_citation', url='https://www.nature.com/articles/s41580-025-00835-2#:~:text=state%20of%20progenitor%20cells%20but,was%20uncovered%2C%20and%20it%20became')
  6. AnnotationURLCitation(end_index=2457, start_index=2300, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=The%20extracellular%20domain%20%28N,domain%20are%20involved%20in%20ligand')
  7. AnnotationURLCitation(end_index=2774, start_index=2617, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=The%20extracellular%20domain%20%28N,domain%20are%20involved%20in%20ligand')
  8. AnnotationURLCitation(end_index=3070, start_index=2946, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=binding,for%20the%20stability%20of%20the')
  9. AnnotationURLCitation(end_index=3516, start_index=3359, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=apparatus%2C%20NOTCH%20receptors%20are%20cleaved,secretase.%20The%20NOTCH')
  10. AnnotationURLCitation(end_index=3650, start_index=3517, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=then%20experience%20S3%20cleavage%2C%20changing,2')
  11. AnnotationURLCitation(end_index=3913, start_index=3756, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=apparatus%2C%20NOTCH%20receptors%20are%20cleaved,secretase.%20The%20NOTCH')
  12. AnnotationURLCitation(end_index=4196, start_index=4036, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=NOTCH%20receptors%20are%20resistant%20to,NEXT%20can%20be%20further%20cleaved')
  13. AnnotationURLCitation(end_index=4334, start_index=4197, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=S2%20cleavage%20is%20the%20only,58%7D.%20Once%20bound')
  14. AnnotationURLCitation(end_index=4788, start_index=4628, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=NOTCH%20receptors%20are%20resistant%20to,NEXT%20can%20be%20further%20cleaved')
  15. AnnotationURLCitation(end_index=5061, start_index=4901, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=NOTCH%20receptors%20are%20resistant%20to,NEXT%20can%20be%20further%20cleaved')
  16. AnnotationURLCitation(end_index=5442, start_index=5309, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=then%20experience%20S3%20cleavage%2C%20changing,2')
  17. AnnotationURLCitation(end_index=5726, start_index=5593, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=then%20experience%20S3%20cleavage%2C%20changing,2')
  18. AnnotationURLCitation(end_index=5991, start_index=5858, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=then%20experience%20S3%20cleavage%2C%20changing,2')
  19. AnnotationURLCitation(end_index=6521, start_index=6365, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=Located%20after%20the%20membrane,like%20repeats%2C%20the%20glycosylation')
  20. AnnotationURLCitation(end_index=6852, start_index=6678, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=the%20nucleus%2C%20and%20seven%20ankyrin,is%20controlled%20by%20constitutive%20endocytosis')
  21. AnnotationURLCitation(end_index=6981, start_index=6853, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=domains,4%20have%20similar%20structures%20to')
  22. AnnotationURLCitation(end_index=7354, start_index=7181, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=contain%20degradation%20signals%20and%20are,appreciable%20amount%20of%20NOTCH%20receptors')
  23. AnnotationURLCitation(end_index=7827, start_index=7680, title='Embryonic lethality in mice homozygous for a processing-deficient allele of Notch1 | Nature', type='url_citation', url='https://www.nature.com/articles/35016111#:~:text=emerge%20for%20the%20Notch%20signalling,associated%20with%20a%20single%20point')
  24. AnnotationURLCitation(end_index=7992, start_index=7828, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=match%20at%20L1990%20which%20contains,inhibitor%20of%20MAML1%2C%20inhibits%20the')
  25. AnnotationURLCitation(end_index=8313, start_index=8155, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=In%20the%20traditional%20model%20of,targeting%20MAML%20are%20under%20study')
  26. AnnotationURLCitation(end_index=8628, start_index=8470, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=In%20the%20traditional%20model%20of,targeting%20MAML%20are%20under%20study')
  27. AnnotationURLCitation(end_index=8793, start_index=8629, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=match%20at%20L1990%20which%20contains,inhibitor%20of%20MAML1%2C%20inhibits%20the')
  28. AnnotationURLCitation(end_index=9179, start_index=9021, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=In%20the%20traditional%20model%20of,targeting%20MAML%20are%20under%20study')
  29. AnnotationURLCitation(end_index=9425, start_index=9261, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=match%20at%20L1990%20which%20contains,inhibitor%20of%20MAML1%2C%20inhibits%20the')
  30. AnnotationURLCitation(end_index=9584, start_index=9426, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=In%20the%20traditional%20model%20of,targeting%20MAML%20are%20under%20study')
  31. AnnotationURLCitation(end_index=9895, start_index=9806, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=co,23')
  32. AnnotationURLCitation(end_index=10573, start_index=10433, title='Embryonic lethality in mice homozygous for a processing-deficient allele of Notch1 | Nature', type='url_citation', url='https://www.nature.com/articles/35016111#:~:text=The%20Notch%20genes%20encode%20single,11%7D.%20Not%20all%20observations')
  33. AnnotationURLCitation(end_index=10926, start_index=10776, title='Notch signaling pathway: architecture, disease, and therapeutics - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/35332121/#:~:text=the%20transcription%20of%20target%20genes,Collectively%2C%20the%20NOTCH')
  34. AnnotationURLCitation(end_index=11099, start_index=10927, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=development%20and%20homeostasis%20of%20multiple,with%20new%20perspectives%20to%20inspire')
  35. AnnotationURLCitation(end_index=11338, start_index=11234, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=three%20cleavages,42')
  36. AnnotationURLCitation(end_index=11616, start_index=11496, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=Humans%20and%20mice%20have%20five,50')
  37. AnnotationURLCitation(end_index=12186, start_index=12031, title='Notch 1–Deficient Common Lymphoid Precursors Adopt a B Cell Fate in the Thymus - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2193487/#:~:text=Notch%20proteins%20have%20been%20shown,family%20members%20in%20T%20cell')
  38. AnnotationURLCitation(end_index=12984, start_index=12847, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=domains,appreciable%20amount%20of%20NOTCH%20receptors')
  39. AnnotationURLCitation(end_index=13431, start_index=13271, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=of%20NOTCH%20receptors%20is%20involved,loss%20of%20which%20decreases%20NOTCH')
  40. AnnotationURLCitation(end_index=14112, start_index=13975, title='Cis inhibition of NOTCH1 through JAGGED1 sustains embryonic hematopoietic stem cell fate - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10882055/#:~:text=inconsistent,clusters%20of%20the%20embryonic%20aorta')
  41. AnnotationURLCitation(end_index=14492, start_index=14329, title='Cis inhibition of NOTCH1 through JAGGED1 sustains embryonic hematopoietic stem cell fate - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10882055/#:~:text=uncover%20that%20the%20HSC%20phenotype,clusters%20of%20the%20embryonic%20aorta')
  42. AnnotationURLCitation(end_index=15227, start_index=15045, title='Notch1 cortical signaling regulates epithelial architecture and cell–cell adhesion - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10555887/#:~:text=Notch1%20cortical%20signaling%20mechanism%20that,control%20of%20epithelial%20adherens%20junctions')
  43. AnnotationURLCitation(end_index=15379, start_index=15228, title='Notch1 cortical signaling regulates epithelial architecture and cell–cell adhesion - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10555887/#:~:text=These%20findings%20are%20consistent%20with,ICD%20or%20a%20TMD%20in')
  44. AnnotationURLCitation(end_index=15769, start_index=15615, title='Notch1 cortical signaling regulates epithelial architecture and cell–cell adhesion - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10555887/#:~:text=transcriptional%20signaling,actin%20through%20the%20effector%20FAM83H')
  45. AnnotationURLCitation(end_index=15948, start_index=15770, title='Notch1 cortical signaling regulates epithelial architecture and cell–cell adhesion - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10555887/#:~:text=activity%20may%20be%20negatively%20regulated,EGFR%20phosphorylation%2C%20we%20next%20examined')
  46. AnnotationURLCitation(end_index=16431, start_index=16254, title='Notch1 cortical signaling regulates epithelial architecture and cell–cell adhesion - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10555887/#:~:text=as%20Notch1%20cortical%20signaling%2C%20where,case%2C%20and%20substantial%20structural%20and')
  47. AnnotationURLCitation(end_index=17696, start_index=17537, title='Modes of Notch signalling in development and disease | Nature Reviews Molecular Cell Biology', type='url_citation', url='https://www.nature.com/articles/s41580-025-00835-2#:~:text=Many%20different%20animal%20developmental%20and,that%20it%20has%20many%20diverse')
  48. AnnotationURLCitation(end_index=18376, start_index=18221, title='Modes of Notch signalling in development and disease | Nature Reviews Molecular Cell Biology', type='url_citation', url='https://www.nature.com/articles/s41580-025-00835-2#:~:text=state%20of%20progenitor%20cells%20but,was%20uncovered%2C%20and%20it%20became')
  49. AnnotationURLCitation(end_index=18954, start_index=18787, title='Notch 1–Deficient Common Lymphoid Precursors Adopt a B Cell Fate in the Thymus - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2193487/#:~:text=a%20bipotential%20T%2FB%20precursor%20toward,of%20lymphoid%20precursors%20to%20home')
  50. AnnotationURLCitation(end_index=19359, start_index=19192, title='Notch 1–Deficient Common Lymphoid Precursors Adopt a B Cell Fate in the Thymus - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2193487/#:~:text=a%20bipotential%20T%2FB%20precursor%20toward,of%20lymphoid%20precursors%20to%20home')
  51. AnnotationURLCitation(end_index=20122, start_index=19967, title='Cis inhibition of NOTCH1 through JAGGED1 sustains embryonic hematopoietic stem cell fate - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10882055/#:~:text=Hematopoietic%20stem%20cells%20,to%20increasing%20levels%20of%20NOTCH1')
  52. AnnotationURLCitation(end_index=20294, start_index=20123, title='Cis inhibition of NOTCH1 through JAGGED1 sustains embryonic hematopoietic stem cell fate - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10882055/#:~:text=signaling%20is%20essential%20for%20arterial,HSC%20phenotype%20in%20the%20hematopoietic')
  53. AnnotationURLCitation(end_index=20927, start_index=20766, title='Embryonic lethality in mice homozygous for a processing-deficient allele of Notch1 | Nature', type='url_citation', url='https://www.nature.com/articles/35016111#:~:text=clearly%20support%20this%20processing%20model%2C,early%20embryonic%20development%20in%20vivo')
  54. AnnotationURLCitation(end_index=21278, start_index=21117, title='Embryonic lethality in mice homozygous for a processing-deficient allele of Notch1 | Nature', type='url_citation', url='https://www.nature.com/articles/35016111#:~:text=clearly%20support%20this%20processing%20model%2C,early%20embryonic%20development%20in%20vivo')
  55. AnnotationURLCitation(end_index=22821, start_index=22673, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=patients%20with%20T,in%20preclinical%20and%20clinical%20settings')
  56. AnnotationURLCitation(end_index=23420, start_index=23261, title='Modes of Notch signalling in development and disease | Nature Reviews Molecular Cell Biology', type='url_citation', url='https://www.nature.com/articles/s41580-025-00835-2#:~:text=Many%20different%20animal%20developmental%20and,that%20it%20has%20many%20diverse')
  57. AnnotationURLCitation(end_index=23813, start_index=23663, title='Modes of Notch signalling in development and disease | Nature Reviews Molecular Cell Biology', type='url_citation', url='https://www.nature.com/articles/s41580-025-00835-2#:~:text=via%20the%20highly%20conserved%20Notch,that%20it%20has%20many%20diverse')
  58. AnnotationURLCitation(end_index=24270, start_index=24118, title='Notch 1–Deficient Common Lymphoid Precursors Adopt a B Cell Fate in the Thymus - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2193487/#:~:text=match%20at%20L84%20Notch%20proteins,family%20members%20in%20T%20cell')
  59. AnnotationURLCitation(end_index=24426, start_index=24271, title='Modes of Notch signalling in development and disease | Nature Reviews Molecular Cell Biology', type='url_citation', url='https://www.nature.com/articles/s41580-025-00835-2#:~:text=state%20of%20progenitor%20cells%20but,was%20uncovered%2C%20and%20it%20became')
  60. AnnotationURLCitation(end_index=25207, start_index=25071, title='Modes of Notch signalling in development and disease | Nature Reviews Molecular Cell Biology', type='url_citation', url='https://www.nature.com/articles/s41580-025-00835-2#:~:text=match%20at%20L586%20136,33%2C%20416%E2%80%93421%20%282003')
  61. AnnotationURLCitation(end_index=25663, start_index=25527, title='Modes of Notch signalling in development and disease | Nature Reviews Molecular Cell Biology', type='url_citation', url='https://www.nature.com/articles/s41580-025-00835-2#:~:text=match%20at%20L586%20136,33%2C%20416%E2%80%93421%20%282003')
  62. AnnotationURLCitation(end_index=26221, start_index=26057, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=cleavage%20and%20thus%20NOTCH%20signaling,to%20amplify%20the%20immune%20response')
  63. AnnotationURLCitation(end_index=26391, start_index=26222, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=Independent%20of%20CSL%2C%20NICD%20can,%CE%BAB%2C%20mTORC%2C%20PTEN%2C%20AKT%2C%20Wnt')
  64. AnnotationURLCitation(end_index=26938, start_index=26760, title='Notch1 cortical signaling regulates epithelial architecture and cell–cell adhesion - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10555887/#:~:text=activity%20may%20be%20negatively%20regulated,EGFR%20phosphorylation%2C%20we%20next%20examined')
  65. AnnotationURLCitation(end_index=27090, start_index=26939, title='Notch1 cortical signaling regulates epithelial architecture and cell–cell adhesion - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10555887/#:~:text=These%20findings%20are%20consistent%20with,ICD%20or%20a%20TMD%20in')
  66. AnnotationURLCitation(end_index=28029, start_index=27888, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=match%20at%20L1039%20T,NOTCH1%20has%20also%20been%20found')
  67. AnnotationURLCitation(end_index=28119, start_index=28030, title='Modes of Notch signalling in development and disease | Nature Reviews Molecular Cell Biology', type='url_citation', url='https://www.nature.com/articles/s41580-025-00835-2#:~:text=135,Cancer')
  68. AnnotationURLCitation(end_index=28588, start_index=28447, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=match%20at%20L1039%20T,NOTCH1%20has%20also%20been%20found')
  69. AnnotationURLCitation(end_index=28862, start_index=28731, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=T,Furthermore%2C%20mutations%20disrupting%20the')
  70. AnnotationURLCitation(end_index=29185, start_index=29054, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=T,Furthermore%2C%20mutations%20disrupting%20the')
  71. AnnotationURLCitation(end_index=29418, start_index=29287, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=T,Furthermore%2C%20mutations%20disrupting%20the')
  72. AnnotationURLCitation(end_index=29811, start_index=29691, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=T,NOTCH1%20has%20also%20been%20found')
  73. AnnotationURLCitation(end_index=29958, start_index=29812, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=match%20at%20L1131%20N,as%20LUNAR1%2C%20which%20is%20essential')
  74. AnnotationURLCitation(end_index=30208, start_index=30088, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=T,NOTCH1%20has%20also%20been%20found')
  75. AnnotationURLCitation(end_index=30964, start_index=30802, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=NOTCH%20was%20first%20identified%20as,cancer%20and%20colorectal%20cancer%20was')
  76. AnnotationURLCitation(end_index=31307, start_index=31171, title='Modes of Notch signalling in development and disease | Nature Reviews Molecular Cell Biology', type='url_citation', url='https://www.nature.com/articles/s41580-025-00835-2#:~:text=match%20at%20L586%20136,33%2C%20416%E2%80%93421%20%282003')
  77. AnnotationURLCitation(end_index=31749, start_index=31613, title='Modes of Notch signalling in development and disease | Nature Reviews Molecular Cell Biology', type='url_citation', url='https://www.nature.com/articles/s41580-025-00835-2#:~:text=match%20at%20L586%20136,33%2C%20416%E2%80%93421%20%282003')
  78. AnnotationURLCitation(end_index=32443, start_index=32338, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=Adams,645%E2%80%93647')
  79. AnnotationURLCitation(end_index=32670, start_index=32565, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=Adams,645%E2%80%93647')
  80. AnnotationURLCitation(end_index=32969, start_index=32821, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=leukemia%20%28T,these%20discoveries%2C%20the%20relationship%20of')
  81. AnnotationURLCitation(end_index=33678, start_index=33530, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=patients%20with%20T,in%20preclinical%20and%20clinical%20settings')
  82. AnnotationURLCitation(end_index=34103, start_index=33955, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=patients%20with%20T,in%20preclinical%20and%20clinical%20settings')
  83. AnnotationURLCitation(end_index=34237, start_index=34104, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=match%20at%20L1799%20treatment%20in,Other%20drugs')
  84. AnnotationURLCitation(end_index=34715, start_index=34567, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=patients%20with%20T,in%20preclinical%20and%20clinical%20settings')
  85. AnnotationURLCitation(end_index=35630, start_index=35462, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=NOTCH1%20%20%7C%20Brontictuzumab%20%28OMP,DLTs%20included%20diarrhea%20and%20fatigue')
  86. AnnotationURLCitation(end_index=35908, start_index=35740, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=NOTCH1%20%20%7C%20Brontictuzumab%20%28OMP,DLTs%20included%20diarrhea%20and%20fatigue')
  87. AnnotationURLCitation(end_index=36213, start_index=36075, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=NCT01778439,DLTs%20included%20diarrhea%20and%20fatigue')
  88. AnnotationURLCitation(end_index=36892, start_index=36728, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=match%20at%20L1990%20which%20contains,inhibitor%20of%20MAML1%2C%20inhibits%20the')
  89. AnnotationURLCitation(end_index=37051, start_index=36893, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=In%20the%20traditional%20model%20of,targeting%20MAML%20are%20under%20study')
  90. AnnotationURLCitation(end_index=37842, start_index=37711, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=T,response%2C%20PR%20partial%20response%2C%20SD')
  91. AnnotationURLCitation(end_index=38155, start_index=38027, title='NOTCH1 Mutations Predict Superior Outcomes of Immune Checkpoint Blockade in Non-Small Cell Lung Cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10710100/#:~:text=NOTCH1%20is%20frequently%20mutated%20in,ICB')
  92. AnnotationURLCitation(end_index=38285, start_index=38156, title='NOTCH1 Mutations Predict Superior Outcomes of Immune Checkpoint Blockade in Non-Small Cell Lung Cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10710100/#:~:text=significantly%20superior%20OS%20than%20WT,WT')
  93. AnnotationURLCitation(end_index=38700, start_index=38572, title='NOTCH1 Mutations Predict Superior Outcomes of Immune Checkpoint Blockade in Non-Small Cell Lung Cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10710100/#:~:text=NOTCH1%20is%20frequently%20mutated%20in,ICB')
  94. AnnotationURLCitation(end_index=38830, start_index=38701, title='NOTCH1 Mutations Predict Superior Outcomes of Immune Checkpoint Blockade in Non-Small Cell Lung Cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10710100/#:~:text=significantly%20superior%20OS%20than%20WT,WT')
  95. AnnotationURLCitation(end_index=40127, start_index=39990, title='Cis inhibition of NOTCH1 through JAGGED1 sustains embryonic hematopoietic stem cell fate - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10882055/#:~:text=inconsistent,clusters%20of%20the%20embryonic%20aorta')
  96. AnnotationURLCitation(end_index=40367, start_index=40216, title='Notch1 cortical signaling regulates epithelial architecture and cell–cell adhesion - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10555887/#:~:text=These%20findings%20are%20consistent%20with,ICD%20or%20a%20TMD%20in')
  97. AnnotationURLCitation(end_index=41334, start_index=41176, title='Notch signaling pathway: architecture, disease, and therapeutics - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8948217/#:~:text=In%20the%20traditional%20model%20of,targeting%20MAML%20are%20under%20study')
  98. AnnotationURLCitation(end_index=41490, start_index=41335, title='Modes of Notch signalling in development and disease | Nature Reviews Molecular Cell Biology', type='url_citation', url='https://www.nature.com/articles/s41580-025-00835-2#:~:text=state%20of%20progenitor%20cells%20but,was%20uncovered%2C%20and%20it%20became')

Bioreason Rl Review

(Notch1-bioreason-rl-review.md)

BioReason-Pro RL Review: Notch1 (mouse)

Source: Notch1-deep-research-bioreason-rl.md

  • Correctness: 4/5
  • Completeness: 4/5

Functional Summary Review

The BioReason functional summary is largely accurate:

A single-pass cell-surface receptor that uses a long calcium-stabilized EGF repeat array to sense extracellular cues and trigger intramembrane signaling. Upon ligand engagement and endocytic activation, a built-in regulatory switch releases the intracellular tail, which then assembles transcriptional effector complexes via ankyrin repeats to reprogram gene expression. This signaling cascade governs binary fate decisions and timing of differentiation by coupling extracellular recognition to intracellular transcriptional control at the plasma membrane.

This correctly describes: (1) the EGF repeat extracellular domain with calcium stabilization, (2) the proteolytic activation mechanism (intramembrane signaling), (3) the release of the intracellular domain (NICD), (4) the ankyrin repeat-mediated assembly of transcriptional complexes, and (5) the role in cell fate determination (GO:0001708). The curated review confirms Notch1 as "the canonical mouse Notch receptor" with roles in "cell-fate decisions during embryogenesis and tissue homeostasis."

The mention of "endocytic activation" is slightly misleading -- endocytosis by the ligand-presenting (signal-sending) cell provides the pulling force, but the Notch-bearing cell undergoes proteolytic cleavage at the membrane. The summary could be read as suggesting the Notch receptor itself is endocytosed for activation, which is not the primary mechanism.

A minor inaccuracy: the primary molecular function is described as "protein binding" (GO:0005515), which is too generic. The curated review identifies more specific functions including GO:0005112 (Notch binding), GO:0038023 (signaling receptor activity), and the transcriptional coactivator role. BioReason does not explicitly name the RBPJ/CSL transcription factor partnership in the summary, though the thinking trace does.

Comparison with interpro2go:

The curated review has six GO_REF:0000002 annotations: GO:0005509 (calcium ion binding), GO:0006355 (regulation of DNA-templated transcription), GO:0030154 (cell differentiation), GO:0038023 (signaling receptor activity), GO:0042981 (regulation of apoptotic process), and GO:0050793 (regulation of developmental process). BioReason's functional summary captures most of these conceptually (calcium stabilization, transcriptional regulation, cell fate/differentiation, receptor signaling) but misses the apoptotic connection. BioReason adds substantial value in explaining the proteolytic activation mechanism and the NOD/NODP regulatory switch, which interpro2go cannot convey.

Notes on thinking trace

The trace provides excellent analysis of the domain architecture, correctly interpreting the EGF repeat array, the NOD/NODP negative regulatory region, and the ankyrin repeat transcriptional scaffold. The mechanistic model of force-dependent activation and intramembrane proteolysis is accurate. The mention of Delta/Serrate/Jagged ligands and CSL/RBPJ complexes shows good biological context.

📄 View Raw YAML

id: Q01705
gene_symbol: Notch1
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: Notch1 is the canonical mouse Notch receptor, a single-pass transmembrane protein that mediates juxtacrine cell-cell
  signaling. Ligand binding by DLL/JAG family proteins triggers ADAM and gamma-secretase cleavage, releasing the Notch intracellular
  domain (NICD), which enters the nucleus and forms an RBPJ/MAML transcriptional coactivator complex to activate target genes.
  In mouse, Notch1 has central roles in cell-fate decisions during embryogenesis and tissue homeostasis, with especially strong
  evidence for cardiovascular development, neurogenesis/gliogenesis, hematopoietic stem cell regulation, angiogenesis, and
  inhibition of myogenic differentiation.
alternative_products:
- name: '1'
  id: Q01705-1
- name: '2'
  id: Q01705-2
  sequence_note: VSP_001402, VSP_001403, VSP_001404
- name: '3'
  id: Q01705-3
  sequence_note: VSP_043064
- name: '4'
  id: Q01705-4
  sequence_note: VSP_043065
existing_annotations:
- term:
    id: GO:0007219
    label: Notch signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007411
    label: axon guidance
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0043235
    label: receptor complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0001525
    label: angiogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0001701
    label: in utero embryonic development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0001947
    label: heart looping
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0002011
    label: morphogenesis of an epithelial sheet
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0002064
    label: epithelial cell development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0002437
    label: inflammatory response to antigenic stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0006959
    label: humoral immune response
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007219
    label: Notch signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010001
    label: glial cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010718
    label: positive regulation of epithelial to mesenchymal transition
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010720
    label: positive regulation of cell development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0012505
    label: endomembrane system
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030154
    label: cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030326
    label: embryonic limb morphogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030513
    label: positive regulation of BMP signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030858
    label: positive regulation of epithelial cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0035850
    label: epithelial cell differentiation involved in kidney development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0038023
    label: signaling receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0042981
    label: regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045165
    label: cell fate commitment
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0048589
    label: developmental growth
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0048608
    label: reproductive structure development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0048844
    label: artery morphogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0050793
    label: regulation of developmental process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0070986
    label: left/right axis specification
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0072012
    label: glomerulus vasculature development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0072080
    label: nephron tubule development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:2000136
    label: regulation of cell proliferation involved in heart morphogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17210915
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21102556
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22258620
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:38891776
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8749394
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0001554
    label: luteolysis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0001669
    label: acrosomal vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0001837
    label: epithelial to mesenchymal transition
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0002052
    label: positive regulation of neuroblast proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0002193
    label: MAML1-RBP-Jkappa- ICN1 complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003151
    label: outflow tract morphogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003180
    label: aortic valve morphogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003184
    label: pulmonary valve morphogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003192
    label: mitral valve formation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003264
    label: regulation of cardioblast proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0004888
    label: transmembrane signaling receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007221
    label: positive regulation of transcription of Notch receptor target
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007283
    label: spermatogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007507
    label: heart development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0008285
    label: negative regulation of cell population proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010667
    label: negative regulation of cardiac muscle cell apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010812
    label: negative regulation of cell-substrate adhesion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0021515
    label: cell differentiation in spinal cord
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0031100
    label: animal organ regeneration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0032496
    label: response to lipopolysaccharide
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0032966
    label: negative regulation of collagen biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0035148
    label: tube formation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0035924
    label: cellular response to vascular endothelial growth factor stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0042127
    label: regulation of cell population proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0042246
    label: tissue regeneration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0043235
    label: receptor complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045603
    label: positive regulation of endothelial cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045662
    label: negative regulation of myoblast differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045665
    label: negative regulation of neuron differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045687
    label: positive regulation of glial cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0046579
    label: positive regulation of Ras protein signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0048708
    label: astrocyte differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0048709
    label: oligodendrocyte differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0051152
    label: positive regulation of smooth muscle cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060354
    label: negative regulation of cell adhesion molecule production
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060412
    label: ventricular septum morphogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0062043
    label: positive regulation of cardiac epithelial to mesenchymal transition
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0070374
    label: positive regulation of ERK1 and ERK2 cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0071228
    label: cellular response to tumor cell
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0071372
    label: cellular response to follicle-stimulating hormone stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0090051
    label: negative regulation of cell migration involved in sprouting angiogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0097150
    label: neuronal stem cell population maintenance
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:2000048
    label: negative regulation of cell-cell adhesion mediated by cadherin
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:2000737
    label: negative regulation of stem cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:2000811
    label: negative regulation of anoikis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:2001027
    label: negative regulation of endothelial cell chemotaxis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0001837
    label: epithelial to mesenchymal transition
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0002193
    label: MAML1-RBP-Jkappa- ICN1 complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003151
    label: outflow tract morphogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003180
    label: aortic valve morphogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003184
    label: pulmonary valve morphogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003192
    label: mitral valve formation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0004888
    label: transmembrane signaling receptor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007219
    label: Notch signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007507
    label: heart development
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0008285
    label: negative regulation of cell population proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010812
    label: negative regulation of cell-substrate adhesion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0035148
    label: tube formation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0035924
    label: cellular response to vascular endothelial growth factor stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045662
    label: negative regulation of myoblast differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0046579
    label: positive regulation of Ras protein signal transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0051152
    label: positive regulation of smooth muscle cell differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060354
    label: negative regulation of cell adhesion molecule production
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060412
    label: ventricular septum morphogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0070374
    label: positive regulation of ERK1 and ERK2 cascade
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0071228
    label: cellular response to tumor cell
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0071372
    label: cellular response to follicle-stimulating hormone stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0090051
    label: negative regulation of cell migration involved in sprouting angiogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:2000048
    label: negative regulation of cell-cell adhesion mediated by cadherin
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:2000737
    label: negative regulation of stem cell differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:2000811
    label: negative regulation of anoikis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:2001027
    label: negative regulation of endothelial cell chemotaxis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0008285
    label: negative regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:26491108
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0008285
    label: negative regulation of cell population proliferation
  evidence_type: IMP
  original_reference_id: PMID:26491108
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:2000137
    label: negative regulation of cell proliferation involved in heart morphogenesis
  evidence_type: IDA
  original_reference_id: PMID:26491108
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:2000137
    label: negative regulation of cell proliferation involved in heart morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:26491108
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:1990433
    label: CSL-Notch-Mastermind transcription factor complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0001669
    label: acrosomal vesicle
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0002052
    label: positive regulation of neuroblast proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003264
    label: regulation of cardioblast proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0004888
    label: transmembrane signaling receptor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007219
    label: Notch signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007221
    label: positive regulation of transcription of Notch receptor target
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007283
    label: spermatogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010667
    label: negative regulation of cardiac muscle cell apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0032966
    label: negative regulation of collagen biosynthetic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0042127
    label: regulation of cell population proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045603
    label: positive regulation of endothelial cell differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045665
    label: negative regulation of neuron differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045687
    label: positive regulation of glial cell differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0048708
    label: astrocyte differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0062043
    label: positive regulation of cardiac epithelial to mesenchymal transition
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0098685
    label: Schaffer collateral - CA1 synapse
  evidence_type: IMP
  original_reference_id: PMID:21315255
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0098685
    label: Schaffer collateral - CA1 synapse
  evidence_type: IDA
  original_reference_id: PMID:21315255
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0098685
    label: Schaffer collateral - CA1 synapse
  evidence_type: IMP
  original_reference_id: PMID:26635527
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0098685
    label: Schaffer collateral - CA1 synapse
  evidence_type: IDA
  original_reference_id: PMID:26635527
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0098839
    label: postsynaptic density membrane
  evidence_type: IEP
  original_reference_id: PMID:21315255
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0098839
    label: postsynaptic density membrane
  evidence_type: IDA
  original_reference_id: PMID:21315255
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0098839
    label: postsynaptic density membrane
  evidence_type: IDA
  original_reference_id: PMID:26635527
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IMP
  original_reference_id: PMID:26635527
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IDA
  original_reference_id: PMID:26635527
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0099565
    label: chemical synaptic transmission, postsynaptic
  evidence_type: IMP
  original_reference_id: PMID:21315255
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0099565
    label: chemical synaptic transmission, postsynaptic
  evidence_type: IDA
  original_reference_id: PMID:21315255
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007219
    label: Notch signaling pathway
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007219
    label: Notch signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:14701881
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007219
    label: Notch signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:20007915
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007219
    label: Notch signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:20890042
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0061344
    label: regulation of cell adhesion involved in heart morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:14701881
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0070168
    label: negative regulation of biomineral tissue development
  evidence_type: IMP
  original_reference_id: PMID:26491108
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:22110751
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9793875
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010832
    label: negative regulation of myotube differentiation
  evidence_type: IMP
  original_reference_id: PMID:18299578
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0050768
    label: negative regulation of neurogenesis
  evidence_type: IMP
  original_reference_id: PMID:18299578
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0071456
    label: cellular response to hypoxia
  evidence_type: IDA
  original_reference_id: PMID:18299578
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0140537
    label: transcription regulator activator activity
  evidence_type: IDA
  original_reference_id: PMID:18299578
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:20007915
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060379
    label: cardiac muscle cell myoblast differentiation
  evidence_type: IMP
  original_reference_id: PMID:20007915
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27719760
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18430783
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030163
    label: protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:28561022
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28561022
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0006606
    label: protein import into nucleus
  evidence_type: IDA
  original_reference_id: PMID:28561022
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010467
    label: gene expression
  evidence_type: IDA
  original_reference_id: PMID:28561022
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0072538
    label: T-helper 17 type immune response
  evidence_type: IDA
  original_reference_id: PMID:28561022
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0097400
    label: interleukin-17-mediated signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:28561022
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007221
    label: positive regulation of transcription of Notch receptor target
  evidence_type: IGI
  original_reference_id: PMID:12794108
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007221
    label: positive regulation of transcription of Notch receptor target
  evidence_type: IGI
  original_reference_id: PMID:23160044
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IDA
  original_reference_id: PMID:17658278
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IDA
  original_reference_id: PMID:9111338
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IDA
  original_reference_id: PMID:17336907
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24667410
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0070168
    label: negative regulation of biomineral tissue development
  evidence_type: IDA
  original_reference_id: PMID:23583836
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:17336907
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0120163
    label: negative regulation of cold-induced thermogenesis
  evidence_type: IMP
  original_reference_id: PMID:25038826
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003180
    label: aortic valve morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:26491108
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003182
    label: coronary sinus valve morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:26491108
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003184
    label: pulmonary valve morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:26491108
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003332
    label: negative regulation of extracellular matrix constituent secretion
  evidence_type: IMP
  original_reference_id: PMID:26491108
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:26491108
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010614
    label: negative regulation of cardiac muscle hypertrophy
  evidence_type: IMP
  original_reference_id: PMID:26491108
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060412
    label: ventricular septum morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:26491108
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:1902339
    label: positive regulation of apoptotic process involved in morphogenesis
  evidence_type: IDA
  original_reference_id: PMID:26491108
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003180
    label: aortic valve morphogenesis
  evidence_type: IGI
  original_reference_id: PMID:27107132
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003184
    label: pulmonary valve morphogenesis
  evidence_type: IGI
  original_reference_id: PMID:27107132
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003203
    label: endocardial cushion morphogenesis
  evidence_type: IGI
  original_reference_id: PMID:27107132
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0048873
    label: homeostasis of number of cells within a tissue
  evidence_type: IGI
  original_reference_id: PMID:27107132
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060412
    label: ventricular septum morphogenesis
  evidence_type: IGI
  original_reference_id: PMID:27107132
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003180
    label: aortic valve morphogenesis
  evidence_type: IGI
  original_reference_id: PMID:23583836
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:23583836
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IGI
  original_reference_id: PMID:23583836
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28089369
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28498977
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0048845
    label: venous blood vessel morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:18952909
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:1903849
    label: positive regulation of aorta morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:18952909
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010468
    label: regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:11076679
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21191019
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045070
    label: positive regulation of viral genome replication
  evidence_type: IMP
  original_reference_id: PMID:21191019
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003197
    label: endocardial cushion development
  evidence_type: IMP
  original_reference_id: PMID:14701881
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21985982
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18676613
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24715457
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: IDA
  original_reference_id: PMID:24715457
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0016324
    label: apical plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:24715457
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12050162
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:25535395
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0008285
    label: negative regulation of cell population proliferation
  evidence_type: IMP
  original_reference_id: PMID:25535395
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0042127
    label: regulation of cell population proliferation
  evidence_type: IGI
  original_reference_id: PMID:25535395
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045607
    label: regulation of inner ear auditory receptor cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:25535395
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045608
    label: negative regulation of inner ear auditory receptor cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:25535395
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0090090
    label: negative regulation of canonical Wnt signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:25535395
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005112
    label: Notch binding
  evidence_type: IPI
  original_reference_id: PMID:24667410
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:24667410
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:24667410
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0008593
    label: regulation of Notch signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:24667410
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: IDA
  original_reference_id: PMID:24667410
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045747
    label: positive regulation of Notch signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:24667410
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0071944
    label: cell periphery
  evidence_type: IDA
  original_reference_id: PMID:23284756
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0043235
    label: receptor complex
  evidence_type: ISO
  original_reference_id: PMID:23382219
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:1902263
    label: apoptotic process involved in embryonic digit morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:16245338
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0001726
    label: ruffle
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005856
    label: cytoskeleton
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030027
    label: lamellipodium
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0008285
    label: negative regulation of cell population proliferation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0035148
    label: tube formation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0035924
    label: cellular response to vascular endothelial growth factor stimulus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0090051
    label: negative regulation of cell migration involved in sprouting angiogenesis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:2001027
    label: negative regulation of endothelial cell chemotaxis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0035914
    label: skeletal muscle cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:22147266
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17685488
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:14701881
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:16025100
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IMP
  original_reference_id: PMID:20007915
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:14701881
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:16025100
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:17303760
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:20007915
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003180
    label: aortic valve morphogenesis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003213
    label: cardiac right atrium morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:20007915
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003241
    label: growth involved in heart morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:20007915
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0014031
    label: mesenchymal cell development
  evidence_type: IMP
  original_reference_id: PMID:17303760
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030279
    label: negative regulation of ossification
  evidence_type: IMP
  original_reference_id: PMID:21493891
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:19695258
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:15107403
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0055008
    label: cardiac muscle tissue morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:20007915
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060045
    label: positive regulation of cardiac muscle cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:20007915
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060317
    label: cardiac epithelial to mesenchymal transition
  evidence_type: IMP
  original_reference_id: PMID:17303760
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060411
    label: cardiac septum morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:20007915
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060842
    label: arterial endothelial cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:15107403
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:20890042
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0001947
    label: heart looping
  evidence_type: IGI
  original_reference_id: PMID:12730124
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003160
    label: endocardium morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:20890042
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003162
    label: atrioventricular node development
  evidence_type: IMP
  original_reference_id: PMID:21266778
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003169
    label: coronary vein morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:21311046
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003181
    label: atrioventricular valve morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:14701881
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003181
    label: atrioventricular valve morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:21266778
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003198
    label: epithelial to mesenchymal transition involved in endocardial cushion formation
  evidence_type: IMP
  original_reference_id: PMID:14701881
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003203
    label: endocardial cushion morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:14701881
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003207
    label: cardiac chamber formation
  evidence_type: IMP
  original_reference_id: PMID:20890042
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003208
    label: cardiac ventricle morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:21311046
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003209
    label: cardiac atrium morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:20890042
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003214
    label: cardiac left ventricle morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:20890042
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003273
    label: cell migration involved in endocardial cushion formation
  evidence_type: IMP
  original_reference_id: PMID:20890042
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003344
    label: pericardium morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:14701881
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003344
    label: pericardium morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:20890042
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003344
    label: pericardium morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:21311046
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010718
    label: positive regulation of epithelial to mesenchymal transition
  evidence_type: IMP
  original_reference_id: PMID:20890042
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030334
    label: regulation of cell migration
  evidence_type: IMP
  original_reference_id: PMID:20890042
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: IMP
  original_reference_id: PMID:20890042
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:21311046
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060038
    label: cardiac muscle cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:21311046
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060843
    label: venous endothelial cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:20890042
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060948
    label: cardiac vascular smooth muscle cell development
  evidence_type: IMP
  original_reference_id: PMID:21311046
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060956
    label: endocardial cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:20890042
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060979
    label: vasculogenesis involved in coronary vascular morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:21311046
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060982
    label: coronary artery morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:21311046
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0061384
    label: heart trabecula morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:20890042
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0070986
    label: left/right axis specification
  evidence_type: IGI
  original_reference_id: PMID:12730124
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:1901201
    label: regulation of extracellular matrix assembly
  evidence_type: IMP
  original_reference_id: PMID:21311046
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17336907
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:1901189
    label: positive regulation of ephrin receptor signaling pathway
  evidence_type: IC
  original_reference_id: PMID:17336907
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003157
    label: endocardium development
  evidence_type: IMP
  original_reference_id: PMID:17336907
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003222
    label: ventricular trabecula myocardium morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:17336907
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-4396387
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9667655
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9824206
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9824230
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9824231
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9824278
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-2064853
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-2064883
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-2065560
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-4396363
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2067638
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-209285
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-2065902
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IPI
  original_reference_id: PMID:17573339
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IPI
  original_reference_id: PMID:18299578
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:19245366
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0004857
    label: enzyme inhibitor activity
  evidence_type: IDA
  original_reference_id: PMID:17573339
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:18299578
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007219
    label: Notch signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:21419176
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0043086
    label: negative regulation of catalytic activity
  evidence_type: IDA
  original_reference_id: PMID:17573339
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2053938
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2053963
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2066712
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2067638
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2071906
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2077477
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2077479
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-2065902
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-209162
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2023158
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2032750
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2023179
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2032750
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9824249
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-1986584
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-209285
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-2063915
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-209162
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2053938
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15574878
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IDA
  original_reference_id: PMID:15574878
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0002437
    label: inflammatory response to antigenic stimulus
  evidence_type: IGI
  original_reference_id: PMID:17658279
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0006959
    label: humoral immune response
  evidence_type: IGI
  original_reference_id: PMID:17658279
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003219
    label: cardiac right ventricle formation
  evidence_type: IMP
  original_reference_id: PMID:19620969
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007219
    label: Notch signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:19620969
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0090090
    label: negative regulation of canonical Wnt signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:19620969
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20547764
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030513
    label: positive regulation of BMP signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:20547764
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:20547764
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:2000974
    label: negative regulation of pro-B cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:12032823
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0046427
    label: positive regulation of receptor signaling pathway via JAK-STAT
  evidence_type: IDA
  original_reference_id: PMID:15156153
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:12032823
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:12666205
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0048711
    label: positive regulation of astrocyte differentiation
  evidence_type: IDA
  original_reference_id: PMID:12666205
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0048715
    label: negative regulation of oligodendrocyte differentiation
  evidence_type: IDA
  original_reference_id: PMID:12666205
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060253
    label: negative regulation of glial cell proliferation
  evidence_type: IDA
  original_reference_id: PMID:12666205
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0072017
    label: distal tubule development
  evidence_type: IEP
  original_reference_id: PMID:15821257
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0072044
    label: collecting duct development
  evidence_type: IEP
  original_reference_id: PMID:15821257
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0072144
    label: glomerular mesangial cell development
  evidence_type: IEP
  original_reference_id: PMID:15821257
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007219
    label: Notch signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:19154718
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0009912
    label: auditory receptor cell fate commitment
  evidence_type: IMP
  original_reference_id: PMID:19154718
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045665
    label: negative regulation of neuron differentiation
  evidence_type: IGI
  original_reference_id: PMID:10205173
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045955
    label: negative regulation of calcium ion-dependent exocytosis
  evidence_type: IMP
  original_reference_id: PMID:19251639
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0050679
    label: positive regulation of epithelial cell proliferation
  evidence_type: IGI
  original_reference_id: PMID:19251639
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0032495
    label: response to muramyl dipeptide
  evidence_type: IDA
  original_reference_id: PMID:21156799
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030514
    label: negative regulation of BMP signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:19695258
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045668
    label: negative regulation of osteoblast differentiation
  evidence_type: IMP
  original_reference_id: PMID:19695258
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0002051
    label: osteoblast fate commitment
  evidence_type: NAS
  original_reference_id: PMID:16025100
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003160
    label: endocardium morphogenesis
  evidence_type: IEP
  original_reference_id: PMID:16025100
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:16025100
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060528
    label: secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development
  evidence_type: IMP
  original_reference_id: PMID:16360140
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060740
    label: prostate gland epithelium morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:16360140
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0060768
    label: regulation of epithelial cell proliferation involved in prostate gland development
  evidence_type: IMP
  original_reference_id: PMID:16360140
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0001701
    label: in utero embryonic development
  evidence_type: IMP
  original_reference_id: PMID:7789282
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007368
    label: determination of left/right symmetry
  evidence_type: IMP
  original_reference_id: PMID:7789282
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0014807
    label: regulation of somitogenesis
  evidence_type: IMP
  original_reference_id: PMID:7789282
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0021915
    label: neural tube development
  evidence_type: IMP
  original_reference_id: PMID:7789282
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0043069
    label: negative regulation of programmed cell death
  evidence_type: IMP
  original_reference_id: PMID:7789282
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:16324690
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:9111338
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10958687
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9315665
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0001889
    label: liver development
  evidence_type: IMP
  original_reference_id: PMID:15226394
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010468
    label: regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:9102301
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030182
    label: neuron differentiation
  evidence_type: IMP
  original_reference_id: PMID:9102301
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0050767
    label: regulation of neurogenesis
  evidence_type: IMP
  original_reference_id: PMID:9102301
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2053963
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2066712
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2067638
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2071906
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2077477
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-2077479
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-2065902
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17079689
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:17079689
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045618
    label: positive regulation of keratinocyte differentiation
  evidence_type: IGI
  original_reference_id: PMID:16618808
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045618
    label: positive regulation of keratinocyte differentiation
  evidence_type: IDA
  original_reference_id: PMID:17079689
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:16618808
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IGI
  original_reference_id: PMID:16618808
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0031490
    label: chromatin DNA binding
  evidence_type: IDA
  original_reference_id: PMID:17658278
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:17658278
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0046533
    label: negative regulation of photoreceptor cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:16452096
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:15965470
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0010001
    label: glial cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:15965470
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:16607638
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007440
    label: foregut morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:16107537
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045165
    label: cell fate commitment
  evidence_type: IMP
  original_reference_id: PMID:16107537
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0050678
    label: regulation of epithelial cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:16107537
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0002040
    label: sprouting angiogenesis
  evidence_type: IMP
  original_reference_id: PMID:15809373
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0031069
    label: hair follicle morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:15978571
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030326
    label: embryonic limb morphogenesis
  evidence_type: IGI
  original_reference_id: PMID:16169548
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: IGI
  original_reference_id: PMID:16169548
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0035116
    label: embryonic hindlimb morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:16245338
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:16145673
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0048754
    label: branching morphogenesis of an epithelial tube
  evidence_type: IMP
  original_reference_id: PMID:15064243
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:10206645
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007409
    label: axonogenesis
  evidence_type: IMP
  original_reference_id: PMID:16120638
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030900
    label: forebrain development
  evidence_type: IMP
  original_reference_id: PMID:16120638
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030900
    label: forebrain development
  evidence_type: IGI
  original_reference_id: PMID:16120638
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045665
    label: negative regulation of neuron differentiation
  evidence_type: IMP
  original_reference_id: PMID:16120638
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0048663
    label: neuron fate commitment
  evidence_type: IGI
  original_reference_id: PMID:16120638
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:15902259
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0001708
    label: cell fate specification
  evidence_type: IMP
  original_reference_id: PMID:15068794
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007409
    label: axonogenesis
  evidence_type: IDA
  original_reference_id: PMID:15598981
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030154
    label: cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:12186854
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030216
    label: keratinocyte differentiation
  evidence_type: IMP
  original_reference_id: PMID:15068794
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:15689374
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IGI
  original_reference_id: PMID:15689374
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030324
    label: lung development
  evidence_type: IMP
  original_reference_id: PMID:15064243
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045596
    label: negative regulation of cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:15064243
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IGI
  original_reference_id: PMID:15509736
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:12783854
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0048103
    label: somatic stem cell division
  evidence_type: IGI
  original_reference_id: PMID:15509736
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0008544
    label: epidermis development
  evidence_type: IGI
  original_reference_id: PMID:15525534
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0031069
    label: hair follicle morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:15525534
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: IDA
  original_reference_id: PMID:15081359
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0001837
    label: epithelial to mesenchymal transition
  evidence_type: IMP
  original_reference_id: PMID:14701881
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007492
    label: endoderm development
  evidence_type: IMP
  original_reference_id: PMID:14657333
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0030154
    label: cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:14657333
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IC
  original_reference_id: PMID:10551863
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007219
    label: Notch signaling pathway
  evidence_type: IC
  original_reference_id: PMID:10551863
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0048103
    label: somatic stem cell division
  evidence_type: IDA
  original_reference_id: PMID:12717450
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007368
    label: determination of left/right symmetry
  evidence_type: IMP
  original_reference_id: PMID:12730124
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10551863
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
- term:
    id: GO:0007386
    label: compartment pattern specification
  evidence_type: IMP
  original_reference_id: PMID:12001066
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence
    similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative
    changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000096
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000119
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10205173
  title: Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation.
  findings: []
- id: PMID:10206645
  title: A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain.
  findings: []
- id: PMID:10551863
  title: Mouse jagged1 physically interacts with notch2 and other notch receptors. Assessment by quantitative methods.
  findings: []
- id: PMID:10958687
  title: Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation
    of Notch2.
  findings: []
- id: PMID:11076679
  title: Oscillating expression of c-Hey2 in the presomitic mesoderm suggests that the segmentation clock may use combinatorial
    signaling through multiple interacting bHLH factors.
  findings: []
- id: PMID:12001066
  title: Segmentation defects of Notch pathway mutants and absence of a synergistic phenotype in lunatic fringe/radical fringe
    double mutant mice.
  findings: []
- id: PMID:12032823
  title: Overexpression of the Notch target genes Hes in vivo induces lymphoid and myeloid alterations.
  findings: []
- id: PMID:12050162
  title: The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits
    myoblast differentiation via Notch signaling pathway.
  findings: []
- id: PMID:12186854
  title: Notch1 control of oligodendrocyte differentiation in the spinal cord.
  findings: []
- id: PMID:12666205
  title: Hes1 but not Hes5 regulates an astrocyte versus oligodendrocyte fate choice in glial restricted precursors.
  findings: []
- id: PMID:12717450
  title: A role for Wnt signalling in self-renewal of haematopoietic stem cells.
  findings: []
- id: PMID:12730124
  title: Notch signaling regulates left-right asymmetry determination by inducing Nodal expression.
  findings: []
- id: PMID:12783854
  title: Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock.
  findings: []
- id: PMID:12794108
  title: 'Notch-regulated ankyrin-repeat protein inhibits Notch1 signaling: multiple Notch1 signaling pathways involved in
    T cell development.'
  findings: []
- id: PMID:14657333
  title: Notch signaling controls multiple steps of pancreatic differentiation.
  findings: []
- id: PMID:14701881
  title: Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation.
  findings: []
- id: PMID:15064243
  title: Functional diversity of notch family genes in fetal lung development.
  findings: []
- id: PMID:15068794
  title: High commitment of embryonic keratinocytes to terminal differentiation through a Notch1-caspase 3 regulatory mechanism.
  findings: []
- id: PMID:15081359
  title: Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathway.
  findings: []
- id: PMID:15107403
  title: The Notch target genes Hey1 and Hey2 are required for embryonic vascular development.
  findings: []
- id: PMID:15156153
  title: Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling.
  findings: []
- id: PMID:15226394
  title: Notch signaling controls hepatoblast differentiation by altering the expression of liver-enriched transcription factors.
  findings: []
- id: PMID:15509736
  title: Fibroblast growth factor receptor signaling promotes radial glial identity and interacts with Notch1 signaling in
    telencephalic progenitors.
  findings: []
- id: PMID:15525534
  title: gamma-secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning
    or initial morphogenesis.
  findings: []
- id: PMID:15574878
  title: Fringe glycosyltransferases differentially modulate Notch1 proteolysis induced by Delta1 and Jagged1.
  findings: []
- id: PMID:15598981
  title: Targeted deletion of numb and numblike in sensory neurons reveals their essential functions in axon arborization.
  findings: []
- id: PMID:15689374
  title: RBPjkappa-dependent Notch function regulates Gata2 and is essential for the formation of intra-embryonic hematopoietic
    cells.
  findings: []
- id: PMID:15809373
  title: Essential role of endothelial Notch1 in angiogenesis.
  findings: []
- id: PMID:15821257
  title: Segmental expression of Notch and Hairy genes in nephrogenesis.
  findings: []
- id: PMID:15902259
  title: The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity.
  findings: []
- id: PMID:15965470
  title: DNER acts as a neuron-specific Notch ligand during Bergmann glial development.
  findings: []
- id: PMID:15978571
  title: Notch1 is essential for postnatal hair follicle development and homeostasis.
  findings: []
- id: PMID:16025100
  title: Mutations in NOTCH1 cause aortic valve disease.
  findings: []
- id: PMID:16107537
  title: Direct regulation of intestinal fate by Notch.
  findings: []
- id: PMID:16120638
  title: Notch signaling coordinates the patterning of striatal compartments.
  findings: []
- id: PMID:16145673
  title: 'Fjx1: a notch-inducible secreted ligand with specific binding sites in developing mouse embryos and adult brain.'
  findings: []
- id: PMID:16169548
  title: Notch1 and 2 cooperate in limb ectoderm to receive an early Jagged2 signal regulating interdigital apoptosis.
  findings: []
- id: PMID:16245338
  title: Notch1 signals through Jagged2 to regulate apoptosis in the apical ectodermal ridge of the developing limb bud.
  findings: []
- id: PMID:16324690
  title: BMP7 inhibits branching morphogenesis in the prostate gland and interferes with Notch signaling.
  findings: []
- id: PMID:16360140
  title: Notch signaling is required for normal prostatic epithelial cell proliferation and differentiation.
  findings: []
- id: PMID:16452096
  title: Notch 1 inhibits photoreceptor production in the developing mammalian retina.
  findings: []
- id: PMID:16607638
  title: Jag2-Notch1 signaling regulates oral epithelial differentiation and palate development.
  findings: []
- id: PMID:16618808
  title: Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation.
  findings: []
- id: PMID:17079689
  title: Canonical notch signaling functions as a commitment switch in the epidermal lineage.
  findings: []
- id: PMID:17210915
  title: Baf60c is a nuclear Notch signaling component required for the establishment of left-right asymmetry.
  findings: []
- id: PMID:17303760
  title: Combined loss of Hey1 and HeyL causes congenital heart defects because of impaired epithelial to mesenchymal transition.
  findings: []
- id: PMID:17336907
  title: Notch signaling is essential for ventricular chamber development.
  findings: []
- id: PMID:17573339
  title: Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor.
  findings: []
- id: PMID:17658278
  title: Notch directly regulates Gata3 expression during T helper 2 cell differentiation.
  findings: []
- id: PMID:17658279
  title: Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch.
  findings: []
- id: PMID:17685488
  title: 'Monitoring Notch1 activity in development: evidence for a feedback regulatory loop.'
  findings: []
- id: PMID:18299578
  title: Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia
    signaling pathways.
  findings: []
- id: PMID:18430783
  title: Zfp64 participates in Notch signaling and regulates differentiation in mesenchymal cells.
  findings: []
- id: PMID:18676613
  title: The intracellular region of Notch ligands Dll1 and Dll3 regulates their trafficking and signaling activity.
  findings: []
- id: PMID:18952909
  title: Artery and vein size is balanced by Notch and ephrin B2/EphB4 during angiogenesis.
  findings: []
- id: PMID:19154718
  title: Hey2 regulation by FGF provides a Notch-independent mechanism for maintaining pillar cell fate in the organ of Corti.
  findings: []
- id: PMID:19245366
  title: MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a substrate for the asparaginyl hydroxylase
    factor inhibiting hypoxia-inducible factor (FIH).
  findings: []
- id: PMID:19251639
  title: Notch and Wnt signals cooperatively control cell proliferation and tumorigenesis in the intestine.
  findings: []
- id: PMID:19620969
  title: A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate.
  findings: []
- id: PMID:19695258
  title: Notch1 represses osteogenic pathways in aortic valve cells.
  findings: []
- id: PMID:20007915
  title: Distinct roles for cell-autonomous Notch signaling in cardiomyocytes of the embryonic and adult heart.
  findings: []
- id: PMID:20547764
  title: ZFP423 coordinates Notch and bone morphogenetic protein signaling, selectively up-regulating Hes5 gene expression.
  findings: []
- id: PMID:20890042
  title: Integration of a Notch-dependent mesenchymal gene program and Bmp2-driven cell invasiveness regulates murine cardiac
    valve formation.
  findings: []
- id: PMID:21102556
  title: RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J.
  findings: []
- id: PMID:21156799
  title: Intracellular pathogen sensor NOD2 programs macrophages to trigger Notch1 activation.
  findings: []
- id: PMID:21191019
  title: A protein (ORF2) encoded by the latency-related gene of bovine herpesvirus 1 interacts with Notch1 and Notch3.
  findings: []
- id: PMID:21266778
  title: Notch signaling regulates murine atrioventricular conduction and the formation of accessory pathways.
  findings: []
- id: PMID:21311046
  title: Differential Notch signaling in the epicardium is required for cardiac inflow development and coronary vessel morphogenesis.
  findings: []
- id: PMID:21315255
  title: Activity-induced Notch signaling in neurons requires Arc/Arg3.1 and is essential for synaptic plasticity in hippocampal
    networks.
  findings: []
- id: PMID:21419176
  title: The EGF-like proteins DLK1 and DLK2 function as inhibitory non-canonical ligands of NOTCH1 receptor that modulate
    each other's activities.
  findings: []
- id: PMID:21493891
  title: Diet-induced aortic valve disease in mice haploinsufficient for the Notch pathway effector RBPJK/CSL.
  findings: []
- id: PMID:21985982
  title: Delta-like 1-Lysine613 regulates notch signaling.
  findings: []
- id: PMID:22110751
  title: Inhibitory role of Notch1 in calcific aortic valve disease.
  findings: []
- id: PMID:22147266
  title: Analysis of early C2C12 myogenesis identifies stably and differentially expressed transcriptional regulators whose
    knock-down inhibits myoblast differentiation.
  findings: []
- id: PMID:22258620
  title: Pten coordinates retinal neurogenesis by regulating Notch signalling.
  findings: []
- id: PMID:23160044
  title: BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets.
  findings: []
- id: PMID:23284756
  title: Ascl1 (Mash1) knockout perturbs differentiation of nonneuronal cells in olfactory epithelium.
  findings: []
- id: PMID:23382219
  title: Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins.
  findings: []
- id: PMID:23583836
  title: Endothelial nitric oxide signaling regulates Notch1 in aortic valve disease.
  findings: []
- id: PMID:24667410
  title: Notch4 reveals a novel mechanism regulating Notch signal transduction.
  findings: []
- id: PMID:24715457
  title: Cadherin-based adhesions in the apical endfoot are required for active Notch signaling to control neurogenesis in
    vertebrates.
  findings: []
- id: PMID:25038826
  title: Inhibition of Notch signaling promotes browning of white adipose tissue and ameliorates obesity.
  findings: []
- id: PMID:25535395
  title: Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway.
  findings: []
- id: PMID:26491108
  title: Notch-Tnf signalling is required for development and homeostasis of arterial valves.
  findings: []
- id: PMID:26635527
  title: Notch1 Regulates Hippocampal Plasticity Through Interaction with the Reelin Pathway, Glutamatergic Transmission and
    CREB Signaling.
  findings: []
- id: PMID:27107132
  title: Endothelial Notch1 Is Required for Proper Development of the Semilunar Valves and Cardiac Outflow Tract.
  findings: []
- id: PMID:27719760
  title: BLOS2 negatively regulates Notch signaling during neural and hematopoietic stem and progenitor cell development.
  findings: []
- id: PMID:28089369
  title: 'Deciphering the Fringe-Mediated Notch Code: Identification of Activating and Inhibiting Sites Allowing Discrimination
    between Ligands.'
  findings: []
- id: PMID:28498977
  title: Consequences of MEGF10 deficiency on myoblast function and Notch1 interactions.
  findings: []
- id: PMID:28561022
  title: IL-17 induced NOTCH1 activation in oligodendrocyte progenitor cells enhances proliferation and inflammatory gene
    expression.
  findings: []
- id: PMID:38891776
  title: Pin1 Downregulation Is Involved in Excess Retinoic Acid-Induced Failure of Neural Tube Closure.
  findings: []
- id: PMID:7789282
  title: Notch1 is required for the coordinate segmentation of somites.
  findings: []
- id: PMID:8749394
  title: Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J kappa/Su(H).
  findings: []
- id: PMID:9102301
  title: Conservation of the Notch signalling pathway in mammalian neurogenesis.
  findings: []
- id: PMID:9111338
  title: RBP-L, a transcription factor related to RBP-Jkappa.
  findings: []
- id: PMID:9315665
  title: Isolation and functional analysis of a cDNA for human Jagged2, a gene encoding a ligand for the Notch1 receptor.
  findings: []
- id: Reactome:R-MMU-2023158
  title: Glycosylation of Pre-Notch by Fringe
  findings: []
- id: Reactome:R-MMU-2023179
  title: Glucosylation of Pre-Notch by Poglut1
  findings: []
- id: Reactome:R-MMU-2032750
  title: Sel1l negatively regulates Pre-Notch exit from endoplasmic reticulum
  findings: []
- id: Reactome:R-MMU-2053938
  title: Dll4 binds Notch1
  findings: []
- id: Reactome:R-MMU-2053963
  title: Notch1 binds Jag1
  findings: []
- id: Reactome:R-MMU-2066712
  title: Dner binds Notch1
  findings: []
- id: Reactome:R-MMU-2067638
  title: Gamma secretase cleaves Dner:Notch1 complex
  findings: []
- id: Reactome:R-MMU-2071906
  title: Notch1 binds Dlk1
  findings: []
- id: Reactome:R-MMU-2077477
  title: Numb recruits Itch to Notch1
  findings: []
- id: Reactome:R-MMU-2077479
  title: Itch ubiquitinates Notch
  findings: []
- id: Reactome:R-MMU-209285
  title: The transmembrane complex Murine gamma-secretase cleaves Murine NEXT at the S3 site leaving NTM and releasing NICD
    into the cytoplasm
  findings: []
- id: Reactome:R-MMU-4396387
  title: mNOTCH1 coactivator complex bind promoters of Hey genes
  findings: []
- id: Reactome:R-MMU-9667655
  title: Nbea binds nicd1
  findings: []
- id: Reactome:R-MMU-9793875
  title: Dll3 binds Notch1
  findings: []
- id: Reactome:R-MMU-9824206
  title: Lef1:Ctnnb1, Nicd (Notch), and Tbx6 bind the Hes7 gene in presomitic mesoderm
  findings: []
- id: Reactome:R-MMU-9824230
  title: Hes7 binds the Lfng gene
  findings: []
- id: Reactome:R-MMU-9824231
  title: Rbpj:Nicd and Msgn1 bind the Lfng gene
  findings: []
- id: Reactome:R-MMU-9824249
  title: Expression of Notch1 in presomitic mesoderm
  findings: []
- id: Reactome:R-MMU-9824278
  title: Hes7 binds the Hes7 gene
  findings: []
- id: Reactome:R-NUL-1986584
  title: Fucosylation of Pre-Notch by POFUT1
  findings: []
- id: Reactome:R-NUL-2063915
  title: ADAM17 cleaves Notch1 at S2
  findings: []
- id: Reactome:R-NUL-2064853
  title: FBXW7 binds phosphorylated NICD1
  findings: []
- id: Reactome:R-NUL-2064883
  title: FBXW7 mediates ubiquitination of phosphorylated NICD1
  findings: []
- id: Reactome:R-NUL-2065560
  title: mNICD1 binds HIF1A
  findings: []
- id: Reactome:R-NUL-2065902
  title: Gamma secretase complex cleaves Cntn1-actived Notch1
  findings: []
- id: Reactome:R-NUL-209162
  title: Murine ADAM10 cleaves Notch at the S2 site producing transmembrane spanning NEXT and ligand-bound NECD
  findings: []
- id: Reactome:R-NUL-4396363
  title: mNICD1 Chimeric Enhancer Complex binds Hes1 promoter
  findings: []