Notch1
entrez
18128
canonical
uniprot
Q01705
canonical
ensembl
ENSMUSG00000026923
resolver
ensp
ENSMUSP00000028288
resolver
genesymbol
Notch1
resolver
genesymbol_syn
Motch
resolver
uniprot
Q06007
resolver
uniprot
Q3TZW2
resolver
uniprot
Q3U3Y2
resolver
uniprot
Q61905
resolver
uniprot
Q7TQ50
resolver
uniprot
Q7TQ51
resolver
uniprot
Q7TQ52
resolver
uniprot
Q8K428
resolver
uniprot
Q99JC2
resolver
uniprot
Q9QW58
resolver
uniprot
Q9R0X7
resolver
uniprot_entry
NOTC1_MOUSE
resolver
uniprot_sec
Q06007
resolver
uniprot_sec
Q3TZW2
resolver
uniprot_sec
Q3U3Y2
resolver
uniprot_sec
Q61905
resolver
uniprot_sec
Q7TQ50
resolver
uniprot_sec
Q7TQ51
resolver
uniprot_sec
Q7TQ52
resolver
uniprot_sec
Q8K428
resolver
uniprot_sec
Q99JC2
resolver
uniprot_sec
Q9QW58
resolver
uniprot_sec
Q9R0X7
resolver
amino_acid_sequence
MPRLLTPLLCLTLLPALAARGLRCSQPSGTCLNGGRCEVANGTEACVCSGAFVGQRCQDSNPCLSTPCKNAGTCHVVDHGGTVDYACSCPLGFSGPLCLTPLDNACLANPCRNGGTCDLLTLTEYKCRCPPGWSGKSCQQADPCASNPCANGGQCLPFESSYICRCPPGFHGPTCRQDVNECSQNPGLCRHGGTCHNEIGSYRCACRATHTGPHCELPYVPCSPSPCQNGGTCRPTGDTTHECACLPGFAGQNCEENVDDCPGNNCKNGGACVDGVNTYNCRCPPEWTGQYCTEDVDECQLMPNACQNGGTCHNTHGGYNCVCVNGWTGEDCSENIDDCASAACFQGATCHDRVASFYCECPHGRTGLLCHLNDACISNPCNEGSNCDTNPVNGKAICTCPSGYTGPACSQDVDECALGANPCEHAGKCLNTLGSFECQCLQGYTGPRCEIDVNECISNPCQNDATCLDQIGEFQCICMPGYEGVYCEINTDECASSPCLHNGHCMDKINEFQCQCPKGFNGHLCQYDVDECASTPCKNGAKCLDGPNTYTCVCTEGYTGTHCEVDIDECDPDPCHYGSCKDGVATFTCLCQPGYTGHHCETNINECHSQPCRHGGTCQDRDNSYLCLCLKGTTGPNCEINLDDCASNPCDSGTCLDKIDGYECACEPGYTGSMCNVNIDECAGSPCHNGGTCEDGIAGFTCRCPEGYHDPTCLSEVNECNSNPCIHGACRDGLNGYKCDCAPGWSGTNCDINNNECESNPCVNGGTCKDMTSGYVCTCREGFSGPNCQTNINECASNPCLNQGTCIDDVAGYKCNCPLPYTGATCEVVLAPCATSPCKNSGVCKESEDYESFSCVCPTGWQGQTCEVDINECVKSPCRHGASCQNTNGSYRCLCQAGYTGRNCESDIDDCRPNPCHNGGSCTDGINTAFCDCLPGFQGAFCEEDINECASNPCQNGANCTDCVDSYTCTCPVGFNGIHCENNTPDCTESSCFNGGTCVDGINSFTCLCPPGFTGSYCQYDVNECDSRPCLHGGTCQDSYGTYKCTCPQGYTGLNCQNLVRWCDSAPCKNGGRCWQTNTQYHCECRSGWTGVNCDVLSVSCEVAAQKRGIDVTLLCQHGGLCVDEGDKHYCHCQAGYTGSYCEDEVDECSPNPCQNGATCTDYLGGFSCKCVAGYHGSNCSEEINECLSQPCQNGGTCIDLTNSYKCSCPRGTQGVHCEINVDDCHPPLDPASRSPKCFNNGTCVDQVGGYTCTCPPGFVGERCEGDVNECLSNPCDPRGTQNCVQRVNDFHCECRAGHTGRRCESVINGCRGKPCKNGGVCAVASNTARGFICRCPAGFEGATCENDARTCGSLRCLNGGTCISGPRSPTCLCLGSFTGPECQFPASSPCVGSNPCYNQGTCEPTSENPFYRCLCPAKFNGLLCHILDYSFTGGAGRDIPPPQIEEACELPECQVDAGNKVCNLQCNNHACGWDGGDCSLNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQLTEGQCNPLYDQYCKDHFSDGHCDQGCNSAECEWDGLDCAEHVPERLAAGTLVLVVLLPPDQLRNNSFHFLRELSHVLHTNVVFKRDAQGQQMIFPYYGHEEELRKHPIKRSTVGWATSSLLPGTSGGRQRRELDPMDIRGSIVYLEIDNRQCVQSSSQCFQSATDVAAFLGALASLGSLNIPYKIEAVKSEPVEPPLPSQLHLMYVAAAAFVLLFFVGCGVLLSRKRRRQHGQLWFPEGFKVSEASKKKRREPLGEDSVGLKPLKNASDGALMDDNQNEWGDEDLETKKFRFEEPVVLPDLSDQTDHRQWTQQHLDAADLRMSAMAPTPPQGEVDADCMDVNVRGPDGFTPLMIASCSGGGLETGNSEEEEDAPAVISDFIYQGASLHNQTDRTGETALHLAARYSRSDAAKRLLEASADANIQDNMGRTPLHAAVSADAQGVFQILLRNRATDLDARMHDGTTPLILAARLAVEGMLEDLINSHADVNAVDDLGKSALHWAAAVNNVDAAVVLLKNGANKDMQNNKEETPLFLAAREGSYETAKVLLDHFANRDITDHMDRLPRDIAQERMHHDIVRLLDEYNLVRSPQLHGTALGGTPTLSPTLCSPNGYLGNLKSATQGKKARKPSTKGLACGSKEAKDLKARRKKSQDGKGCLLDSSSMLSPVDSLESPHGYLSDVASPPLLPSPFQQSPSMPLSHLPGMPDTHLGISHLNVAAKPEMAALAGGSRLAFEPPPPRLSHLPVASSASTVLSTNGTGAMNFTVGAPASLNGQCEWLPRLQNGMVPSQYNPLRPGVTPGTLSTQAAGLQHSMMGPLHSSLSTNTLSPIIYQGLPNTRLATQPHLVQTQQVQPQNLQLQPQNLQPPSQPHLSVSSAANGHLGRSFLSGEPSQADVQPLGPSSLPVHTILPQESQALPTSLPSSMVPPMTTTQFLTPPSQHSYSSSPVDNTPSHQLQVPEHPFLTPSPESPDQWSSSSPHSNISDWSEGISSPPTTMPSQITHIPEAFK
uniprot
proteins
function
FUNCTION: Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4(+) and CD8(+) cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, functions as a receptor for neuronal DNER and is involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation. May be involved in mesoderm development, somite formation and neurogenesis. May enhance HIF1A function by sequestering HIF1AN away from HIF1A. Required for the THBS4 function in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury. Involved in determination of left/right symmetry by modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO). {ECO:0000269|PubMed:15965470, ECO:0000269|PubMed:18299578, ECO:0000269|PubMed:23160044, ECO:0000269|PubMed:23615612}.
uniprot
proteins
mass_dalton
270835
uniprot
proteins
mutagenesis
MUTAGEN 65; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 146; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 232; /note="T->V: No significant effect on its binding and activation by DLL1 or JAG1. No significant effect on RFNG-, LFNG- and MFNG-mediated enhancement of its activation by DLL1. Decrease in LFNG- and MFNG-mediated inhibition of its activation by JAG1. Significant decrease in LFNG- and MFNG-mediated inhibition of its activation by JAG1; when associated with V-1402."; /evidence="ECO:0000269|PubMed:28089369"; MUTAGEN 311; /note="T->V: Significant loss of binding and activation by DLL1 or JAG1. Decrease in RFNG-, LFNG- and MFNG-mediated enhancement of its activation by DLL1. Decrease in LFNG-mediated inhibition of its activation by JAG1. Significant loss of binding and activation by DLL1 or JAG1 and complete loss of RFNG- and LFNG-mediated enhancement of its activation by DLL1; when associated with V-466. Decreased localization to the plasma membrane; when associated with A-435."; /evidence="ECO:0000269|PubMed:28089369, ECO:0000269|PubMed:30127001"; MUTAGEN 341; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 349; /note="T->V: Reduced binding and activation by JAG1 but not DLL1. Decrease in MFNG-mediated enhancement of its activation by DLL1."; /evidence="ECO:0000269|PubMed:28089369"; MUTAGEN 378; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 435; /note="S->A: No effect on localization to the plasma membrane. No effect on binding and activation by DLL1. Decreased localization to the plasma membrane; when associated with V-311."; /evidence="ECO:0000269|PubMed:30127001"; MUTAGEN 458; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 466; /note="T->V: Reduced binding and activation by DLL1 but not JAG1. Decrease in RFNG- and LFNG-mediated enhancement of its activation by DLL1. Loss of RFNG-mediated enhancement of its activation by JAG1. Significant loss of binding and activation by DLL1 or JAG1 and complete loss of RFNG- and LFNG-mediated enhancement of its activation by DLL1; when associated with V-311."; /evidence="ECO:0000269|PubMed:28089369"; MUTAGEN 496; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 534; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 609; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 647; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 722; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 759; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 797; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 951; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 997; /note="T->V: Reduced binding and activation by DLL1 but not JAG1. No effect on RFNG-, LFNG- and MFNG-mediated enhancement of its activation by DLL1. No effect on LFNG- and MFNG-mediated inhibition of its activation by JAG1."; /evidence="ECO:0000269|PubMed:28089369"; MUTAGEN 1027; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 1035; /note="T->V: Reduced binding and activation by JAG1 but not DLL1. No effect on RFNG-, LFNG- and MFNG-mediated enhancement of its activation by DLL1. No effect on LFNG- and MFNG-mediated inhibition of its activation by JAG1."; /evidence="ECO:0000269|PubMed:28089369"; MUTAGEN 1065; /note="S->A: Reduced activity."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 1159; /note="T->V: No significant effect on its binding and activation by DLL1 or JAG1. No effect on RFNG-, LFNG- and MFNG-mediated enhancement of its activation by DLL1. No effect on LFNG- and MFNG-mediated inhibition of its activation by JAG1."; /evidence="ECO:0000269|PubMed:28089369"; MUTAGEN 1189; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 1273; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21757702"; MUTAGEN 1362; /note="T->V: No significant effect on its binding and activation by DLL1 or JAG1. No effect on RFNG-, LFNG- and MFNG-mediated enhancement of its activation by DLL1. No effect on LFNG- and MFNG-mediated inhibition of its activation by JAG1."; /evidence="ECO:0000269|PubMed:28089369"; MUTAGEN 1402; /note="T->V: No significant effect on its binding and activation by DLL1 or JAG1. No effect on RFNG-, LFNG- and MFNG-mediated enhancement of its activation by DLL1. Decrease in LFNG- and MFNG-mediated inhibition of its activation by JAG1. Significant decrease in LFNG- and MFNG-mediated inhibition of its activation by JAG1; when associated with V-232."; /evidence="ECO:0000269|PubMed:28089369"; MUTAGEN 1651..1654; /note="RQRR->AAAA: Processing by furin-like convertase abolished."; /evidence="ECO:0000269|PubMed:9653148"; MUTAGEN 1675; /note="C->S: Produces an activated, ligand-independent molecule; when associated with S-1682."; /evidence="ECO:0000269|PubMed:10882062"; MUTAGEN 1682; /note="C->S: Produces an activated, ligand-independent molecule; when associated with S-1675."; /evidence="ECO:0000269|PubMed:10882062"; MUTAGEN 1744; /note="V->L: NICD processing severely reduced."; MUTAGEN 1945; /note="N->A: Reduced ability to promote HIF1AN-dependent 2-oxoglutarate decarboxylation and greatly reduced transactivation capacity. Abolished ability to promote HIF1AN-dependent 2-oxoglutarate decarboxylation; when associated with G-2012. Almost abolished transactivation capacity; when associated with A-2012."; /evidence="ECO:0000269|PubMed:17573339, ECO:0000269|PubMed:18299578"; MUTAGEN 2012; /note="N->A: Slightly reduced ability to promote HIF1AN-dependent 2-oxoglutarate decarboxylation. Abolished ability to promote HIF1AN-dependent 2-oxoglutarate decarboxylation and almost abolished transactivation capacity; when associated with A-1945."; /evidence="ECO:0000269|PubMed:17573339, ECO:0000269|PubMed:18299578"; MUTAGEN 2012; /note="N->G: Reduced ability to promote HIF1AN-dependent 2-oxoglutarate decarboxylation. Abolished ability to promote HIF1AN-dependent 2-oxoglutarate decarboxylation; when associated with A-1945."; /evidence="ECO:0000269|PubMed:17573339, ECO:0000269|PubMed:18299578
uniprot
proteins
post_translational_modification
PTM: Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form (PubMed:10882062, PubMed:10882063). Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by ADAM17 to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT) (PubMed:10882062, PubMed:10882063). Following endocytosis, this fragment is then cleaved by one of the catalytic subunits of gamma-secretase (PSEN1 or PSEN2) to release a Notch-derived peptide containing the intracellular domain (NICD) from the membrane (PubMed:10882062, PubMed:11459941, PubMed:11518718). {ECO:0000269|PubMed:10882062, ECO:0000269|PubMed:10882063, ECO:0000269|PubMed:11459941, ECO:0000269|PubMed:11518718}.; PTM: Phosphorylated.; PTM: O-linked glycosylation by GALNT11 is involved in determination of left/right symmetry: glycosylation promotes activation of NOTCH1, possibly by promoting cleavage by ADAM17, modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO) (By similarity). O-glycosylated on the EGF-like domains (PubMed:21757702). O-glucosylated at Ser-435 by KDELC1 and KDELC2 (PubMed:30127001). Contains both O-linked fucose and O-linked glucose in the EGF-like domains 11, 12 and 13, which are interacting with the residues on DLL4 (By similarity). O-glycosylation at Ser-1027 is only partial (PubMed:21757702). MFNG-, RFNG- and LFNG-mediated modification of O-fucose residues at specific EGF-like domains results in inhibition of its activation by JAG1 and enhancement of its activation by DLL1 via an increased binding to DLL1 (PubMed:28089369). {ECO:0000250|UniProtKB:P46531, ECO:0000250|UniProtKB:Q07008, ECO:0000269|PubMed:21757702, ECO:0000269|PubMed:28089369, ECO:0000269|PubMed:30127001}.; PTM: Ubiquitinated. Undergoes 'Lys-29'-linked polyubiquitination by ITCH; promotes the lysosomal degradation of non-activated internalized NOTCH1 (PubMed:18628966, PubMed:23886940). Deubiquitination by USP12 is required for transport of internalized non-activated receptor from late endosomes to lysosomes for degradation (PubMed:22778262). Monoubiquitination at Lys-1749 is required for activation by gamma-secretase cleavage, it promotes interaction with AAK1, which stabilizes it. Deubiquitination by EIF3F is necessary for nuclear import of activated Notch (PubMed:15240571). {ECO:0000269|PubMed:15240571, ECO:0000269|PubMed:18628966, ECO:0000269|PubMed:22778262, ECO:0000269|PubMed:23886940}.; PTM: Hydroxylated at Asn-1945 and Asn-2012 by HIF1AN. Hydroxylation reduces affinity for HI1AN and may thus indirectly modulate negative regulation of NICD. {ECO:0000269|PubMed:17573339, ECO:0000269|PubMed:18299578}.
uniprot
proteins
protein_family
NOTCH family
uniprot
proteins
pubmed
10437788
uniprot
proteins
pubmed
10882062
uniprot
proteins
pubmed
10882063
uniprot
proteins
pubmed
11226752
uniprot
proteins
pubmed
11459941
uniprot
proteins
pubmed
11518718
uniprot
proteins
pubmed
12050162
uniprot
proteins
pubmed
12123574
uniprot
proteins
pubmed
12807718
uniprot
proteins
pubmed
1425352
uniprot
proteins
pubmed
1426644
uniprot
proteins
pubmed
15019995
uniprot
proteins
pubmed
15240571
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15802643
uniprot
proteins
pubmed
15965470
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17573339
uniprot
proteins
pubmed
18299578
uniprot
proteins
pubmed
18430783
uniprot
proteins
pubmed
18628966
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21464124
uniprot
proteins
pubmed
21757702
uniprot
proteins
pubmed
22778262
uniprot
proteins
pubmed
23160044
uniprot
proteins
pubmed
23615612
uniprot
proteins
pubmed
23886940
uniprot
proteins
pubmed
25038227
uniprot
proteins
pubmed
28089369
uniprot
proteins
pubmed
28498977
uniprot
proteins
pubmed
30127001
uniprot
proteins
pubmed
7956822
uniprot
proteins
pubmed
8440332
uniprot
proteins
pubmed
8449489
uniprot
proteins
pubmed
8486742
uniprot
proteins
pubmed
9384671
uniprot
proteins
pubmed
9653148
uniprot
proteins
sequence_length
2531
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10882062, ECO:0000269|PubMed:22778262, ECO:0000269|PubMed:28498977}; Single-pass type I membrane protein {ECO:0000305}. Late endosome membrane {ECO:0000269|PubMed:22778262}; Single-pass type I membrane protein {ECO:0000305}. Note=Nonactivated receptor is targeted for lysosomal degradation via the endosomal pathway; transport from late endosomes to lysosomes requires deubiquitination by USP12. {ECO:0000269|PubMed:22778262}.; SUBCELLULAR LOCATION: [Notch 1 intracellular domain]: Nucleus {ECO:0000269|PubMed:28498977}. Note=Following proteolytical processing NICD is translocated to the nucleus. Nuclear location may require MEGF10. {ECO:0000269|PubMed:28498977}.
uniprot
proteins
transmembrane_region
TRANSMEM 1726..1746; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P46531
uniprot
proteins