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Details on Person UniProt:Q9UM47 NOTCH3

Class:IdReferenceGeneProduct:60524
_chainChangeLogsignal peptide:1-39 added on Fri February 6 2015;chain:40-2321 added on Fri February 6 2015;chain:1629-2321 added on Fri February 6 2015;chain:1662-2321 added on Fri February 6 2015
_displayNameUniProt:Q9UM47 NOTCH3
_timestamp2026-02-20 23:08:26
chainsignal peptide:1-39
chain:40-2321
chain:1629-2321
chain:1662-2321
checksum3E70EC12A59CD638
commentFUNCTION Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543, PubMed:14714274). 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 (By similarity).SUBUNIT Heterodimer of a C-terminal fragment N(TM) and a N-terminal fragment N(EC) which are probably linked by disulfide bonds (PubMed:19417009). Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH3. Interacts with PSMA1. Interacts with HIF1AN.INTERACTION Following proteolytical processing NICD is translocated to the nucleus.TISSUE SPECIFICITY Ubiquitously expressed in fetal and adult tissues.DOMAIN The EGF-like domains 10 and 11 are required for binding the ligands JAG1 and DLL1.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. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by TNF converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane.PTM Phosphorylated.PTM Hydroxylated by HIF1AN.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The gene represented in this entry may be involved in disease pathogenesis.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease may be caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the NOTCH family.
descriptionrecommendedName: Neurogenic locus notch homolog protein 3 shortName: Notch 3 component recommendedName: Notch 3 extracellular truncation /component component recommendedName: Notch 3 intracellular domain /component
geneNameNOTCH3
identifierQ9UM47
isSequenceChangedFALSE
keyword3D-structure
Activator
ANK repeat
Cell membrane
Developmental protein
Differentiation
Disease variant
Disulfide bond
EGF-like domain
Glycoprotein
Membrane
Methylation
Notch signaling pathway
Nucleus
Phosphoprotein
Proteomics identification
Receptor
Reference proteome
Repeat
Signal
Transcription
Transcription regulation
Transmembrane
Transmembrane helix
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
nameNOTCH3
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:1606769] ENSEMBL:ENSG00000074181 NOTCH3 [Homo sapiens]
secondaryIdentifierNOTC3_HUMAN
Q9UEB3
Q9UPL3
Q9Y6L8
sequenceLength2321
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:156995] NOTCH3(1572-2321) [Golgi membrane] [Homo sapiens]
[EntityWithAccessionedSequence:157070] NOTCH3(40-2321) [Golgi lumen] [Homo sapiens]
[EntityWithAccessionedSequence:157102] Pre-NOTCH3 [endoplasmic reticulum membrane] [Homo sapiens]
[EntityWithAccessionedSequence:157116] NOTCH3(40-1571) [Golgi lumen] [Homo sapiens]
[EntityWithAccessionedSequence:157203] NEXT3 [plasma membrane] [Homo sapiens]
[EntityWithAccessionedSequence:157220] NOTCH3(40-1571) [plasma membrane] [Homo sapiens]
[EntityWithAccessionedSequence:157231] NOTCH3(1572-2321) [plasma membrane] [Homo sapiens]
[EntityWithAccessionedSequence:157639] NOTCH3(40-1628) [extracellular region] [Homo sapiens]
[EntityWithAccessionedSequence:157647] NICD3 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:157657] NOTCH3(1629-1661) [plasma membrane] [Homo sapiens]
List all 25 refering instances
(referenceSequence)[ModifiedResidue:1467297] O-fucosyl-L-threonine at 748
[ModifiedResidue:1467298] O-fucosyl-L-threonine at 445
[ModifiedResidue:1467305] O-glucosyl-L-serine at 513
[ModifiedResidue:1467316] O-glucosyl-L-serine at 1252
[ModifiedResidue:1467317] O-fucosyl-L-threonine at 211
[ModifiedResidue:1467326] O-glucosyl-L-serine at 663
[ModifiedResidue:1467335] O-fucosyl-L-serine at 671
[ModifiedResidue:1467342] O-glucosyl-L-serine at 125
[ModifiedResidue:1467345] O-glucosyl-L-serine at 437
[ModifiedResidue:1467347] O-glucosyl-L-serine at 588
List all 33 refering instances
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No pathways have been reviewed or authored by UniProt:Q9UM47 NOTCH3 (60524)