NOTCH3
entrez
4854
canonical
uniprot
Q9UM47
canonical
ensembl
ENSG00000074181
resolver
ensp
ENSP00000263388
resolver
ensp
ENSP00000601591
resolver
enst
ENST00000263388
resolver
genesymbol
NOTCH3
resolver
hgnc
HGNC:7883
resolver
uniprot
Q9UEB3
resolver
uniprot
Q9UPL3
resolver
uniprot
Q9Y6L8
resolver
uniprot_entry
NOTC3_HUMAN
resolver
uniprot_sec
Q9UEB3
resolver
uniprot_sec
Q9UPL3
resolver
uniprot_sec
Q9Y6L8
resolver
amino_acid_sequence
MGPGARGRRRRRRPMSPPPPPPPVRALPLLLLLAGPGAAAPPCLDGSPCANGGRCTQLPSREAACLCPPGWVGERCQLEDPCHSGPCAGRGVCQSSVVAGTARFSCRCPRGFRGPDCSLPDPCLSSPCAHGARCSVGPDGRFLCSCPPGYQGRSCRSDVDECRVGEPCRHGGTCLNTPGSFRCQCPAGYTGPLCENPAVPCAPSPCRNGGTCRQSGDLTYDCACLPGFEGQNCEVNVDDCPGHRCLNGGTCVDGVNTYNCQCPPEWTGQFCTEDVDECQLQPNACHNGGTCFNTLGGHSCVCVNGWTGESCSQNIDDCATAVCFHGATCHDRVASFYCACPMGKTGLLCHLDDACVSNPCHEDAICDTNPVNGRAICTCPPGFTGGACDQDVDECSIGANPCEHLGRCVNTQGSFLCQCGRGYTGPRCETDVNECLSGPCRNQATCLDRIGQFTCICMAGFTGTYCEVDIDECQSSPCVNGGVCKDRVNGFSCTCPSGFSGSTCQLDVDECASTPCRNGAKCVDQPDGYECRCAEGFEGTLCDRNVDDCSPDPCHHGRCVDGIASFSCACAPGYTGTRCESQVDECRSQPCRHGGKCLDLVDKYLCRCPSGTTGVNCEVNIDDCASNPCTFGVCRDGINRYDCVCQPGFTGPLCNVEINECASSPCGEGGSCVDGENGFRCLCPPGSLPPLCLPPSHPCAHEPCSHGICYDAPGGFRCVCEPGWSGPRCSQSLARDACESQPCRAGGTCSSDGMGFHCTCPPGVQGRQCELLSPCTPNPCEHGGRCESAPGQLPVCSCPQGWQGPRCQQDVDECAGPAPCGPHGICTNLAGSFSCTCHGGYTGPSCDQDINDCDPNPCLNGGSCQDGVGSFSCSCLPGFAGPRCARDVDECLSNPCGPGTCTDHVASFTCTCPPGYGGFHCEQDLPDCSPSSCFNGGTCVDGVNSFSCLCRPGYTGAHCQHEADPCLSRPCLHGGVCSAAHPGFRCTCLESFTGPQCQTLVDWCSRQPCQNGGRCVQTGAYCLCPPGWSGRLCDIRSLPCREAAAQIGVRLEQLCQAGGQCVDEDSSHYCVCPEGRTGSHCEQEVDPCLAQPCQHGGTCRGYMGGYMCECLPGYNGDNCEDDVDECASQPCQHGGSCIDLVARYLCSCPPGTLGVLCEINEDDCGPGPPLDSGPRCLHNGTCVDLVGGFRCTCPPGYTGLRCEADINECRSGACHAAHTRDCLQDPGGGFRCLCHAGFSGPRCQTVLSPCESQPCQHGGQCRPSPGPGGGLTFTCHCAQPFWGPRCERVARSCRELQCPVGVPCQQTPRGPRCACPPGLSGPSCRSFPGSPPGASNASCAAAPCLHGGSCRPAPLAPFFRCACAQGWTGPRCEAPAAAPEVSEEPRCPRAACQAKRGDQRCDRECNSPGCGWDGGDCSLSVGDPWRQCEALQCWRLFNNSRCDPACSSPACLYDNFDCHAGGRERTCNPVYEKYCADHFADGRCDQGCNTEECGWDGLDCASEVPALLARGVLVLTVLLPPEELLRSSADFLQRLSAILRTSLRFRLDAHGQAMVFPYHRPSPGSEPRARRELAPEVIGSVVMLEIDNRLCLQSPENDHCFPDAQSAADYLGALSAVERLDFPYPLRDVRGEPLEPPEPSVPLLPLLVAGAVLLLVILVLGVMVARRKREHSTLWFPEGFSLHKDVASGHKGRREPVGQDALGMKNMAKGESLMGEVATDWMDTECPEAKRLKVEEPGMGAEEAVDCRQWTQHHLVAADIRVAPAMALTPPQGDADADGMDVNVRGPDGFTPLMLASFCGGALEPMPTEEDEADDTSASIISDLICQGAQLGARTDRTGETALHLAARYARADAAKRLLDAGADTNAQDHSGRTPLHTAVTADAQGVFQILIRNRSTDLDARMADGSTALILAARLAVEGMVEELIASHADVNAVDELGKSALHWAAAVNNVEATLALLKNGANKDMQDSKEETPLFLAAREGSYEAAKLLLDHFANREITDHLDRLPRDVAQERLHQDIVRLLDQPSGPRSPPGPHGLGPLLCPPGAFLPGLKAAQSGSKKSRRPPGKAGLGPQGPRGRGKKLTLACPGPLADSSVTLSPVDSLDSPRPFGGPPASPGGFPLEGPYAAATATAVSLAQLGGPGRAGLGRQPPGGCVLSLGLLNPVAVPLDWARLPPPAPPGPSFLLPLAPGPQLLNPGTPVSPQERPPPYLAVPGHGEEYPAAGAHSSPPKARFLRVPSEHPYLTPSPESPEHWASPSPPSLSDWSESTPSPATATGAMATTTGALPAQPLPLSVPSSLAQAQTQLGPQPEVTPKRQVLA
uniprot
proteins
disease_involvement
DISEASE: Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, 1 (CADASIL1) [MIM:125310]: A cerebrovascular disease characterized by multiple subcortical infarcts, pseudobulbar palsy, dementia, and the presence of granular deposits in small cerebral arteries producing ischemic stroke. {ECO:0000269|PubMed:10227618, ECO:0000269|PubMed:10371548, ECO:0000269|PubMed:10802807, ECO:0000269|PubMed:10854111, ECO:0000269|PubMed:11058919, ECO:0000269|PubMed:11102981, ECO:0000269|PubMed:11559313, ECO:0000269|PubMed:11755616, ECO:0000269|PubMed:11810186, ECO:0000269|PubMed:12136071, ECO:0000269|PubMed:12146805, ECO:0000269|PubMed:12589106, ECO:0000269|PubMed:12810003, ECO:0000269|PubMed:14714274, ECO:0000269|PubMed:15229130, ECO:0000269|PubMed:15300988, ECO:0000269|PubMed:15350543, ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:15378071, ECO:0000269|PubMed:15818833, ECO:0000269|PubMed:16009764, ECO:0000269|PubMed:17235124, ECO:0000269|PubMed:18765654, ECO:0000269|PubMed:19153638, ECO:0000269|PubMed:19417009, ECO:0000269|PubMed:19528524, ECO:0000269|PubMed:23572112, ECO:0000269|PubMed:23602593, ECO:0000269|PubMed:24000151, ECO:0000269|PubMed:27423596, ECO:0000269|PubMed:30199759, ECO:0000269|PubMed:31960911, ECO:0000269|PubMed:32980981, ECO:0000269|PubMed:9388399}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1 (CARASIL1) [MIM:621295]: A cerebrovascular disease characterized by arteriopathy of cerebral small vessels and onset of neurologic symptoms in infancy or early childhood. Affected individuals present with periventricular or periatrial leukoencephalopathy, white matter lesions in the basal ganglia, microbleeds, enlarged ventricles, and white matter volume loss. Additional features include hypotonia, developmental delay, variably impaired intellectual development, spasticity, hyperreflexia, stoke, hemiparesis, seizures, coarse facial features, and strabismus. {ECO:0000269|PubMed:25870235, ECO:0000269|PubMed:32980981, ECO:0000269|PubMed:35026854}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Myofibromatosis, infantile 2 (IMF2) [MIM:615293]: A rare mesenchymal disorder characterized by the development of benign tumors in the skin, striated muscles, bones, and, more rarely, visceral organs. Subcutaneous or soft tissue nodules commonly involve the skin of the head, neck, and trunk. Skeletal and muscular lesions occur in about half of the patients. Lesions may be solitary or multicentric, and they may be present at birth or become apparent in early infancy or occasionally in adult life. Visceral lesions are associated with high morbidity and mortality. {ECO:0000269|PubMed:23731542}. Note=The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Lateral meningocele syndrome (LMNS) [MIM:130720]: A very rare skeletal disorder with facial anomalies, hypotonia and neurologic dysfunction due to meningocele, a protrusion of the meninges, unaccompanied by neural tissue, through a bony defect in the skull or vertebral column. LMNS facial features include hypertelorism and telecanthus, high arched eyebrows, ptosis, mid-facial hypoplasia, micrognathia, high and narrow palate, low-set ears and a hypotonic appearance. Additional variable features are connective tissue abnormalities, aortic dilation, a high-pitched nasal voice, wormian bones and osteolysis. {ECO:0000269|PubMed:25394726}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Lipodystrophy, familial partial, 1 (FPLD1) [MIM:608600]: A form of partial lipodystrophy, a disorder characterized by abnormal subcutaneous fat distribution. FPLD1 affected individuals have loss of subcutaneous adipose tissue from the upper and lower extremities, increased muscularity, and normal or increased distribution of fat in the trunk or abdomen. Patients develop metabolic complications including hypertriglyceridemia, hepatic steatosis, and insulin-dependent diabetes. FPLD1 is an autosomal dominant disorder with age-dependent penetrance. {ECO:0000269|PubMed:39652711}. Note=The disease may be caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: 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). {ECO:0000250|UniProtKB:Q9R172, ECO:0000269|PubMed:14714274, ECO:0000269|PubMed:15350543}.
uniprot
proteins
mass_dalton
243631
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. 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. {ECO:0000269|PubMed:15350543}.; PTM: Phosphorylated. {ECO:0000250}.; PTM: Hydroxylated by HIF1AN. {ECO:0000269|PubMed:18299578}.
uniprot
proteins
protein_family
NOTCH family
uniprot
proteins
pubmed
10079256
uniprot
proteins
pubmed
10227618
uniprot
proteins
pubmed
10371548
uniprot
proteins
pubmed
10802807
uniprot
proteins
pubmed
10854111
uniprot
proteins
pubmed
11058919
uniprot
proteins
pubmed
11101851
uniprot
proteins
pubmed
11102981
uniprot
proteins
pubmed
11559313
uniprot
proteins
pubmed
11755616
uniprot
proteins
pubmed
11810186
uniprot
proteins
pubmed
12136071
uniprot
proteins
pubmed
12146805
uniprot
proteins
pubmed
12370315
uniprot
proteins
pubmed
12589106
uniprot
proteins
pubmed
12810003
uniprot
proteins
pubmed
14714274
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
15229130
uniprot
proteins
pubmed
15300988
uniprot
proteins
pubmed
15350543
uniprot
proteins
pubmed
15364702
uniprot
proteins
pubmed
15378071
uniprot
proteins
pubmed
15818833
uniprot
proteins
pubmed
16009764
uniprot
proteins
pubmed
17235124
uniprot
proteins
pubmed
17292860
uniprot
proteins
pubmed
17573339
uniprot
proteins
pubmed
18273901
uniprot
proteins
pubmed
18299578
uniprot
proteins
pubmed
18765654
uniprot
proteins
pubmed
19153638
uniprot
proteins
pubmed
19417009
uniprot
proteins
pubmed
19528524
uniprot
proteins
pubmed
23572112
uniprot
proteins
pubmed
23602593
uniprot
proteins
pubmed
23731542
uniprot
proteins
pubmed
24000151
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
25394726
uniprot
proteins
pubmed
25870235
uniprot
proteins
pubmed
27423596
uniprot
proteins
pubmed
30199759
uniprot
proteins
pubmed
31960911
uniprot
proteins
pubmed
32980981
uniprot
proteins
pubmed
35026854
uniprot
proteins
pubmed
39652711
uniprot
proteins
pubmed
8878478
uniprot
proteins
pubmed
9388399
uniprot
proteins
sequence_length
2321
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15350543}; Single-pass type I membrane protein.; SUBCELLULAR LOCATION: [Notch 3 intracellular domain]: Nucleus. Note=Following proteolytical processing NICD is translocated to the nucleus.
uniprot
proteins
transmembrane_region
TRANSMEM 1644..1664; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins