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Q9UM47 (NOTC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Neurogenic locus notch homolog protein 3

Short name=Notch 3
Gene names
Name:NOTCH3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length2321 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 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 By similarity.

Subunit structure

Heterodimer of a C-terminal fragment N(TM) and a N-terminal fragment N(EC) which are probably linked by disulfide bonds By similarity. Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH3. Interacts with PSMA1. Interacts with HIF1AN. Ref.5 Ref.6 Ref.7 Ref.8

Subcellular location

Cell membrane; Single-pass type I membrane protein.

Notch 3 intracellular domain: Nucleus. Note: Following proteolytical processing NICD is translocated to the nucleus.

Tissue specificity

Ubiquitously expressed in fetal and adult tissues.

Post-translational modification

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-alpha 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 By similarity.

Phosphorylated By similarity.

Hydroxylated by HIF1AN.

Involvement in disease

Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant (CADASIL) [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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.30 Ref.31

Sequence similarities

Belongs to the NOTCH family.

Contains 5 ANK repeats.

Contains 34 EGF-like domains.

Contains 3 LNR (Lin/Notch) repeats.

Ontologies

Keywords
   Biological processDifferentiation
Notch signaling pathway
Transcription
Transcription regulation
   Cellular componentCell membrane
Membrane
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainANK repeat
EGF-like domain
Repeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionActivator
Developmental protein
Receptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNotch receptor processing

Traceable author statement. Source: Reactome

Notch signaling pathway

Traceable author statement. Source: Reactome

forebrain development

Inferred from electronic annotation. Source: Ensembl

gene expression

Traceable author statement. Source: Reactome

glomerular capillary formation

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

neuron fate commitment

Inferred from electronic annotation. Source: Ensembl

positive regulation of smooth muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

   Cellular_componentGolgi membrane

Traceable author statement. Source: Reactome

actin cytoskeleton

Inferred from direct assay. Source: HPA

cytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

extracellular region

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

plasma membrane

Traceable author statement. Source: Reactome

receptor complex

Inferred from direct assay PubMed 23382219. Source: MGI

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction Ref.5Ref.7. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Psma1Q9R1P42EBI-1236377,EBI-991653From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3939 Potential
Chain40 – 23212282Neurogenic locus notch homolog protein 3
PRO_0000007692
Chain1629 – 2321693Notch 3 extracellular truncation By similarity
PRO_0000007693
Chain1662 – 2321660Notch 3 intracellular domain By similarity
PRO_0000007694

Regions

Topological domain40 – 16431604Extracellular Potential
Transmembrane1644 – 166421Helical; Potential
Topological domain1665 – 2321657Cytoplasmic Potential
Domain40 – 7738EGF-like 1
Domain78 – 11841EGF-like 2
Domain119 – 15638EGF-like 3
Domain158 – 19538EGF-like 4; calcium-binding Potential
Domain197 – 23438EGF-like 5
Domain236 – 27237EGF-like 6; calcium-binding Potential
Domain274 – 31239EGF-like 7
Domain314 – 35037EGF-like 8; calcium-binding Potential
Domain351 – 38939EGF-like 9
Domain391 – 42939EGF-like 10; calcium-binding Potential
Domain431 – 46737EGF-like 11; calcium-binding Potential
Domain469 – 50537EGF-like 12; calcium-binding Potential
Domain507 – 54337EGF-like 13; calcium-binding Potential
Domain545 – 58036EGF-like 14; calcium-binding Potential
Domain582 – 61837EGF-like 15; calcium-binding Potential
Domain620 – 65536EGF-like 16; calcium-binding Potential
Domain657 – 69337EGF-like 17; calcium-binding Potential
Domain695 – 73036EGF-like 18
Domain734 – 77037EGF-like 19
Domain771 – 80838EGF-like 20
Domain810 – 84738EGF-like 21; calcium-binding Potential
Domain849 – 88537EGF-like 22; calcium-binding Potential
Domain887 – 92236EGF-like 23; calcium-binding Potential
Domain924 – 96037EGF-like 24
Domain962 – 99837EGF-like 25
Domain1000 – 103435EGF-like 26
Domain1047 – 108236EGF-like 27
Domain1084 – 112037EGF-like 28
Domain1122 – 115837EGF-like 29; calcium-binding Potential
Domain1160 – 120344EGF-like 30; calcium-binding Potential
Domain1205 – 124440EGF-like 31
Domain1246 – 128742EGF-like 32
Domain1289 – 132537EGF-like 33
Domain1335 – 137339EGF-like 34
Repeat1387 – 142741LNR 1
Repeat1428 – 145831LNR 2
Repeat1467 – 150539LNR 3
Repeat1838 – 186730ANK 1
Repeat1871 – 190131ANK 2
Repeat1905 – 193430ANK 3
Repeat1938 – 196730ANK 4
Repeat1971 – 200030ANK 5

Sites

Site1571 – 15722Cleavage; by furin-like protease By similarity

Amino acid modifications

Glycosylation11791N-linked (GlcNAc...) Potential
Glycosylation13361N-linked (GlcNAc...) Potential
Glycosylation14381N-linked (GlcNAc...) Potential
Disulfide bond43 ↔ 55 By similarity
Disulfide bond49 ↔ 65 By similarity
Disulfide bond67 ↔ 76 By similarity
Disulfide bond82 ↔ 93 By similarity
Disulfide bond87 ↔ 106 By similarity
Disulfide bond108 ↔ 117 By similarity
Disulfide bond123 ↔ 134 By similarity
Disulfide bond128 ↔ 144 By similarity
Disulfide bond146 ↔ 155 By similarity
Disulfide bond162 ↔ 174 By similarity
Disulfide bond168 ↔ 183 By similarity
Disulfide bond185 ↔ 194 By similarity
Disulfide bond201 ↔ 212 By similarity
Disulfide bond206 ↔ 222 By similarity
Disulfide bond224 ↔ 233 By similarity
Disulfide bond240 ↔ 251 By similarity
Disulfide bond245 ↔ 260 By similarity
Disulfide bond262 ↔ 271 By similarity
Disulfide bond278 ↔ 291 By similarity
Disulfide bond285 ↔ 300 By similarity
Disulfide bond302 ↔ 311 By similarity
Disulfide bond318 ↔ 329 By similarity
Disulfide bond323 ↔ 338 By similarity
Disulfide bond340 ↔ 349 By similarity
Disulfide bond355 ↔ 366 By similarity
Disulfide bond360 ↔ 377 By similarity
Disulfide bond379 ↔ 388 By similarity
Disulfide bond395 ↔ 408 By similarity
Disulfide bond402 ↔ 417 By similarity
Disulfide bond419 ↔ 428 By similarity
Disulfide bond435 ↔ 446 By similarity
Disulfide bond440 ↔ 455 By similarity
Disulfide bond457 ↔ 466 By similarity
Disulfide bond473 ↔ 484 By similarity
Disulfide bond478 ↔ 493 By similarity
Disulfide bond495 ↔ 504 By similarity
Disulfide bond511 ↔ 522 By similarity
Disulfide bond516 ↔ 531 By similarity
Disulfide bond533 ↔ 542 By similarity
Disulfide bond549 ↔ 559 By similarity
Disulfide bond554 ↔ 568 By similarity
Disulfide bond570 ↔ 579 By similarity
Disulfide bond586 ↔ 597 By similarity
Disulfide bond591 ↔ 606 By similarity
Disulfide bond608 ↔ 617 By similarity
Disulfide bond624 ↔ 634 By similarity
Disulfide bond629 ↔ 643 By similarity
Disulfide bond645 ↔ 654 By similarity
Disulfide bond661 ↔ 672 By similarity
Disulfide bond666 ↔ 681 By similarity
Disulfide bond683 ↔ 692 By similarity
Disulfide bond699 ↔ 709 By similarity
Disulfide bond704 ↔ 718 By similarity
Disulfide bond720 ↔ 729 By similarity
Disulfide bond738 ↔ 749 By similarity
Disulfide bond743 ↔ 758 By similarity
Disulfide bond760 ↔ 769 By similarity
Disulfide bond775 ↔ 786 By similarity
Disulfide bond780 ↔ 796 By similarity
Disulfide bond798 ↔ 807 By similarity
Disulfide bond814 ↔ 826 By similarity
Disulfide bond820 ↔ 835 By similarity
Disulfide bond837 ↔ 846 By similarity
Disulfide bond853 ↔ 864 By similarity
Disulfide bond858 ↔ 873 By similarity
Disulfide bond875 ↔ 884 By similarity
Disulfide bond891 ↔ 901 By similarity
Disulfide bond896 ↔ 910 By similarity
Disulfide bond912 ↔ 921 By similarity
Disulfide bond928 ↔ 939 By similarity
Disulfide bond933 ↔ 948 By similarity
Disulfide bond950 ↔ 959 By similarity
Disulfide bond966 ↔ 977 By similarity
Disulfide bond971 ↔ 986 By similarity
Disulfide bond988 ↔ 997 By similarity
Disulfide bond1004 ↔ 1015 By similarity
Disulfide bond1009 ↔ 1022 By similarity
Disulfide bond1024 ↔ 1033 By similarity
Disulfide bond1040 ↔ 1061 By similarity
Disulfide bond1055 ↔ 1070 By similarity
Disulfide bond1072 ↔ 1081 By similarity
Disulfide bond1088 ↔ 1099 By similarity
Disulfide bond1093 ↔ 1108 By similarity
Disulfide bond1110 ↔ 1119 By similarity
Disulfide bond1126 ↔ 1137 By similarity
Disulfide bond1131 ↔ 1146 By similarity
Disulfide bond1148 ↔ 1157 By similarity
Disulfide bond1164 ↔ 1182 By similarity
Disulfide bond1176 ↔ 1191 By similarity
Disulfide bond1193 ↔ 1202 By similarity
Disulfide bond1209 ↔ 1222 By similarity
Disulfide bond1214 ↔ 1232 By similarity
Disulfide bond1234 ↔ 1243 By similarity
Disulfide bond1250 ↔ 1261 By similarity
Disulfide bond1255 ↔ 1275 By similarity
Disulfide bond1277 ↔ 1286 By similarity
Disulfide bond1293 ↔ 1304 By similarity
Disulfide bond1298 ↔ 1313 By similarity
Disulfide bond1315 ↔ 1324 By similarity
Disulfide bond1339 ↔ 1350 By similarity
Disulfide bond1344 ↔ 1361 By similarity
Disulfide bond1363 ↔ 1372 By similarity
Disulfide bond1387 ↔ 1410 By similarity
Disulfide bond1392 ↔ 1405 By similarity
Disulfide bond1401 ↔ 1417 By similarity
Disulfide bond1428 ↔ 1451 By similarity
Disulfide bond1433 ↔ 1446 By similarity
Disulfide bond1442 ↔ 1458 By similarity
Disulfide bond1467 ↔ 1493 By similarity
Disulfide bond1475 ↔ 1488 By similarity
Disulfide bond1484 ↔ 1500 By similarity

Natural variations

Natural variant431C → G in CADASIL. Ref.25 Ref.28
VAR_044230
Natural variant491C → F in CADASIL. Ref.25 Ref.28
VAR_044231
Natural variant491C → Y in CADASIL. Ref.10 Ref.15 Ref.25 Ref.28
VAR_012871
Natural variant541R → C in CADASIL. Ref.15
VAR_044232
Natural variant601S → C in CADASIL. Ref.25 Ref.28
VAR_044233
Natural variant651C → S in CADASIL. Ref.25 Ref.28
VAR_044234
Natural variant671C → Y in CADASIL. Ref.22
VAR_044235
Natural variant711W → C in CADASIL. Ref.10
Corresponds to variant rs28937321 [ dbSNP | Ensembl ].
VAR_012872
Natural variant761C → R in CADASIL. Ref.20 Ref.24
VAR_044236
Natural variant761C → W in CADASIL. Ref.25 Ref.28
VAR_044237
Natural variant77 – 826Missing in CADASIL.
VAR_044238
Natural variant80 – 845Missing in CADASIL.
VAR_044239
Natural variant871C → R in CADASIL. Ref.25 Ref.28
VAR_044240
Natural variant871C → Y in CADASIL. Ref.25
VAR_044241
Natural variant901R → C in CADASIL. Ref.10 Ref.11 Ref.13 Ref.15 Ref.23 Ref.24 Ref.25 Ref.28
VAR_012873
Natural variant931C → F in CADASIL. Ref.13 Ref.25 Ref.28
VAR_044242
Natural variant931C → Y in CADASIL. Ref.20
VAR_044243
Natural variant1061C → W in CADASIL. Ref.25
VAR_044244
Natural variant1081C → W in CADASIL. Ref.27
VAR_044245
Natural variant1081C → Y in CADASIL. Ref.25 Ref.28
VAR_044246
Natural variant1101R → C in CADASIL. Ref.10 Ref.13 Ref.15 Ref.18 Ref.24 Ref.25 Ref.28
VAR_012874
Natural variant114 – 1207Missing in CADASIL.
VAR_012875
Natural variant1171C → F in CADASIL. Ref.11 Ref.13 Ref.25 Ref.28
VAR_044247
Natural variant1181S → C in CADASIL. Ref.29
VAR_044248
Natural variant1231C → F in CADASIL. Ref.13 Ref.25 Ref.28
VAR_044249
Natural variant1231C → Y in CADASIL. Ref.15
VAR_044250
Natural variant1281C → Y in CADASIL. Ref.20
VAR_044251
Natural variant1331R → C in CADASIL. Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.18 Ref.23 Ref.25 Ref.26 Ref.28
VAR_012876
Natural variant1341C → W in CADASIL. Ref.18 Ref.19 Ref.25 Ref.28
VAR_044252
Natural variant1411R → C in CADASIL. Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.18 Ref.24 Ref.25 Ref.28
VAR_012877
Natural variant1421F → C in CADASIL. Ref.20
VAR_044253
Natural variant1441C → F in CADASIL. Ref.14
VAR_044254
Natural variant1441C → S in CADASIL. Ref.13 Ref.25 Ref.28
VAR_044255
Natural variant1441C → Y in CADASIL. Ref.13 Ref.25 Ref.28
VAR_044256
Natural variant1451S → C in CADASIL. Ref.25
VAR_044257
Natural variant1461C → R in CADASIL. Ref.10 Ref.15
VAR_012878
Natural variant1491G → C in CADASIL. Ref.25 Ref.28
VAR_044258
Natural variant1501Y → C in CADASIL. Ref.13 Ref.25 Ref.28
VAR_044259
Natural variant153 – 1553Missing in CADASIL.
VAR_044260
Natural variant1531R → C in CADASIL. Ref.10 Ref.12 Ref.13 Ref.15 Ref.18 Ref.24 Ref.25 Ref.28
VAR_012879
Natural variant1551C → S in CADASIL. Ref.25
VAR_044261
Natural variant1621C → S in CADASIL. Ref.15
VAR_044262
Natural variant1691R → C in CADASIL. Ref.10 Ref.11 Ref.13 Ref.15 Ref.23 Ref.24 Ref.25 Ref.28
Corresponds to variant rs28933696 [ dbSNP | Ensembl ].
VAR_012880
Natural variant1701H → R. Ref.10
Corresponds to variant rs147373451 [ dbSNP | Ensembl ].
VAR_012881
Natural variant1711G → C in CADASIL. Ref.10
VAR_012882
Natural variant1741C → F in CADASIL. Ref.23
VAR_044263
Natural variant1741C → R in CADASIL. Ref.23 Ref.25 Ref.28
VAR_044264
Natural variant1741C → Y in CADASIL. Ref.11 Ref.13 Ref.15 Ref.25 Ref.28
VAR_044265
Natural variant1801S → C in CADASIL. Ref.15
VAR_044266
Natural variant1821R → C in CADASIL. Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.18 Ref.24 Ref.25 Ref.28
Corresponds to variant rs28933697 [ dbSNP | Ensembl ].
VAR_012883
Natural variant1831C → F in CADASIL. Ref.25 Ref.28
VAR_044267
Natural variant1831C → R in CADASIL. Ref.11 Ref.13 Ref.24 Ref.25
VAR_044268
Natural variant1831C → S in CADASIL. Ref.13 Ref.25 Ref.28
VAR_044269
Natural variant1851C → G in CADASIL. Ref.18
VAR_044270
Natural variant1851C → R in CADASIL. Ref.10 Ref.13 Ref.15 Ref.25 Ref.28
VAR_012884
Natural variant1891Y → C in CADASIL. Ref.24
VAR_044271
Natural variant1941C → F in CADASIL. Ref.13 Ref.25 Ref.28
VAR_044272
Natural variant1941C → R in CADASIL. Ref.20
VAR_044273
Natural variant1941C → S in CADASIL. Ref.24
VAR_044274
Natural variant1941C → Y in CADASIL. Ref.15
VAR_044275
Natural variant2011C → Y in CADASIL. Ref.25
VAR_044276
Natural variant2061C → Y in CADASIL. Ref.15
VAR_044277
Natural variant2071R → C in CADASIL. Ref.12 Ref.15 Ref.18 Ref.24 Ref.25 Ref.28
VAR_044278
Natural variant2121C → S in CADASIL. Ref.10 Ref.15 Ref.18
VAR_012885
Natural variant2131R → K in CADASIL. Ref.23
VAR_044279
Natural variant2221C → G in CADASIL. Ref.10 Ref.15 Ref.18
VAR_012886
Natural variant2221C → Y in CADASIL. Ref.20
VAR_044280
Natural variant2241C → Y in CADASIL. Ref.10 Ref.15
VAR_012887
Natural variant2331C → S in CADASIL. Ref.20
VAR_044281
Natural variant2331C → Y in CADASIL. Ref.25 Ref.28
VAR_044282
Natural variant239 – 25315Missing in CADASIL.
VAR_044283
Natural variant2401C → S in CADASIL. Ref.25 Ref.28
VAR_044284
Natural variant2451C → R in CADASIL. Ref.25 Ref.28
VAR_044285
Natural variant2511C → R in CADASIL. Ref.20 Ref.24
VAR_044286
Natural variant2581Y → C in CADASIL. Ref.10 Ref.15
VAR_012888
Natural variant2601C → Y in CADASIL. Ref.25 Ref.28
VAR_044287
Natural variant3191A → C in CADASIL; requires 2 nucleotide substitutions. Ref.28
VAR_044288
Natural variant3321R → C in CADASIL. Ref.17 Ref.24 Ref.25 Ref.28
VAR_044289
Natural variant3351S → C in CADASIL. Ref.25 Ref.28
VAR_044290
Natural variant3371Y → C in CADASIL. Ref.25 Ref.28
VAR_044291
Natural variant3791C → S in CADASIL. Ref.25 Ref.28
VAR_044292
Natural variant3951C → R in CADASIL. Ref.25 Ref.28
VAR_044293
Natural variant4201G → C in CADASIL. Ref.20
VAR_044294
Natural variant4211R → C in CADASIL. Ref.25 Ref.28
VAR_044295
Natural variant4281C → S in CADASIL. Ref.18
VAR_044296
Natural variant4281C → Y in CADASIL. Ref.25 Ref.28
VAR_044297
Natural variant4401C → G in CADASIL. Ref.20 Ref.24
VAR_044298
Natural variant4401C → R in CADASIL. Ref.25 Ref.28
VAR_044299
Natural variant4461C → S in CADASIL. Ref.25
VAR_044300
Natural variant4491R → C in CADASIL. Ref.20
VAR_044301
Natural variant4551C → R in CADASIL. Ref.21
Corresponds to variant rs28933698 [ dbSNP | Ensembl ].
VAR_044302
Natural variant4841C → F in CADASIL. Ref.28
VAR_044303
Natural variant4841C → Y in CADASIL. Ref.25
VAR_044304
Natural variant4951C → Y in CADASIL. Ref.25 Ref.28
VAR_044305
Natural variant4961P → L. Ref.10
Corresponds to variant rs11670799 [ dbSNP | Ensembl ].
VAR_012889
Natural variant5111C → R in CADASIL. Ref.25 Ref.28
VAR_044306
Natural variant5421C → Y in CADASIL. Ref.10 Ref.15
VAR_012890
Natural variant5441R → C in CADASIL. Ref.12
Corresponds to variant rs201118034 [ dbSNP | Ensembl ].
VAR_044307
Natural variant5491C → Y in CADASIL. Ref.25 Ref.28
VAR_044308
Natural variant5581R → C in CADASIL. Ref.10 Ref.15 Ref.18 Ref.25 Ref.28
VAR_012891
Natural variant5781R → C in CADASIL. Ref.10 Ref.15
VAR_012892
Natural variant6071R → C in CADASIL. Ref.15 Ref.24
VAR_044309
Natural variant7281R → C in CADASIL. Ref.10 Ref.15 Ref.28
VAR_012893
Natural variant7751C → S in CADASIL. Ref.28
VAR_044310
Natural variant9531G → C in CADASIL. Ref.20 Ref.24
VAR_044311
Natural variant9841F → C in CADASIL. Ref.15
VAR_044312
Natural variant9851R → C in CADASIL. Ref.10 Ref.15 Ref.18 Ref.25 Ref.28
VAR_012894
Natural variant10061R → C in CADASIL. Ref.10 Ref.15
VAR_012895
Natural variant10151C → R in CADASIL. Ref.12
VAR_044313
Natural variant10201A → P.
Corresponds to variant rs35769976 [ dbSNP | Ensembl ].
VAR_044314
Natural variant10211Y → C in CADASIL. Ref.20
VAR_044315
Natural variant10311R → C in CADASIL. Ref.10 Ref.15
VAR_012896
Natural variant10631D → C in CADASIL; requires 2 nucleotide substitutions. Ref.18
VAR_044316
Natural variant11331H → Q. Ref.10
Corresponds to variant rs112197217 [ dbSNP | Ensembl ].
VAR_012897
Natural variant11831V → M. Ref.10
Corresponds to variant rs10408676 [ dbSNP | Ensembl ].
VAR_012898
Natural variant12311R → C in CADASIL. Ref.10 Ref.15 Ref.24
VAR_012899
Natural variant12611C → R in CADASIL. Ref.10 Ref.15
VAR_012900
Natural variant12611C → Y in CADASIL. Ref.25 Ref.28
VAR_044317
Natural variant15151L → P in brain small-vessel-disease; exhibits increased NOTCH3 signaling in a ligand-independent fashion. Ref.30
VAR_044318
Natural variant15191L → P in IMF2. Ref.31
VAR_069927
Natural variant22231A → V. Ref.1 Ref.10
Corresponds to variant rs1044009 [ dbSNP | Ensembl ].
VAR_012901

Sequences

Sequence LengthMass (Da)Tools
Q9UM47 [UniParc].

Last modified February 8, 2011. Version 2.
Checksum: 3E70EC12A59CD638

FASTA2,321243,631
        10         20         30         40         50         60 
MGPGARGRRR RRRPMSPPPP PPPVRALPLL LLLAGPGAAA PPCLDGSPCA NGGRCTQLPS 

        70         80         90        100        110        120 
REAACLCPPG WVGERCQLED PCHSGPCAGR GVCQSSVVAG TARFSCRCPR GFRGPDCSLP 

       130        140        150        160        170        180 
DPCLSSPCAH GARCSVGPDG RFLCSCPPGY QGRSCRSDVD ECRVGEPCRH GGTCLNTPGS 

       190        200        210        220        230        240 
FRCQCPAGYT GPLCENPAVP CAPSPCRNGG TCRQSGDLTY DCACLPGFEG QNCEVNVDDC 

       250        260        270        280        290        300 
PGHRCLNGGT CVDGVNTYNC QCPPEWTGQF CTEDVDECQL QPNACHNGGT CFNTLGGHSC 

       310        320        330        340        350        360 
VCVNGWTGES CSQNIDDCAT AVCFHGATCH DRVASFYCAC PMGKTGLLCH LDDACVSNPC 

       370        380        390        400        410        420 
HEDAICDTNP VNGRAICTCP PGFTGGACDQ DVDECSIGAN PCEHLGRCVN TQGSFLCQCG 

       430        440        450        460        470        480 
RGYTGPRCET DVNECLSGPC RNQATCLDRI GQFTCICMAG FTGTYCEVDI DECQSSPCVN 

       490        500        510        520        530        540 
GGVCKDRVNG FSCTCPSGFS GSTCQLDVDE CASTPCRNGA KCVDQPDGYE CRCAEGFEGT 

       550        560        570        580        590        600 
LCDRNVDDCS PDPCHHGRCV DGIASFSCAC APGYTGTRCE SQVDECRSQP CRHGGKCLDL 

       610        620        630        640        650        660 
VDKYLCRCPS GTTGVNCEVN IDDCASNPCT FGVCRDGINR YDCVCQPGFT GPLCNVEINE 

       670        680        690        700        710        720 
CASSPCGEGG SCVDGENGFR CLCPPGSLPP LCLPPSHPCA HEPCSHGICY DAPGGFRCVC 

       730        740        750        760        770        780 
EPGWSGPRCS QSLARDACES QPCRAGGTCS SDGMGFHCTC PPGVQGRQCE LLSPCTPNPC 

       790        800        810        820        830        840 
EHGGRCESAP GQLPVCSCPQ GWQGPRCQQD VDECAGPAPC GPHGICTNLA GSFSCTCHGG 

       850        860        870        880        890        900 
YTGPSCDQDI NDCDPNPCLN GGSCQDGVGS FSCSCLPGFA GPRCARDVDE CLSNPCGPGT 

       910        920        930        940        950        960 
CTDHVASFTC TCPPGYGGFH CEQDLPDCSP SSCFNGGTCV DGVNSFSCLC RPGYTGAHCQ 

       970        980        990       1000       1010       1020 
HEADPCLSRP CLHGGVCSAA HPGFRCTCLE SFTGPQCQTL VDWCSRQPCQ NGGRCVQTGA 

      1030       1040       1050       1060       1070       1080 
YCLCPPGWSG RLCDIRSLPC REAAAQIGVR LEQLCQAGGQ CVDEDSSHYC VCPEGRTGSH 

      1090       1100       1110       1120       1130       1140 
CEQEVDPCLA QPCQHGGTCR GYMGGYMCEC LPGYNGDNCE DDVDECASQP CQHGGSCIDL 

      1150       1160       1170       1180       1190       1200 
VARYLCSCPP GTLGVLCEIN EDDCGPGPPL DSGPRCLHNG TCVDLVGGFR CTCPPGYTGL 

      1210       1220       1230       1240       1250       1260 
RCEADINECR SGACHAAHTR DCLQDPGGGF RCLCHAGFSG PRCQTVLSPC ESQPCQHGGQ 

      1270       1280       1290       1300       1310       1320 
CRPSPGPGGG LTFTCHCAQP FWGPRCERVA RSCRELQCPV GVPCQQTPRG PRCACPPGLS 

      1330       1340       1350       1360       1370       1380 
GPSCRSFPGS PPGASNASCA AAPCLHGGSC RPAPLAPFFR CACAQGWTGP RCEAPAAAPE 

      1390       1400       1410       1420       1430       1440 
VSEEPRCPRA ACQAKRGDQR CDRECNSPGC GWDGGDCSLS VGDPWRQCEA LQCWRLFNNS 

      1450       1460       1470       1480       1490       1500 
RCDPACSSPA CLYDNFDCHA GGRERTCNPV YEKYCADHFA DGRCDQGCNT EECGWDGLDC 

      1510       1520       1530       1540       1550       1560 
ASEVPALLAR GVLVLTVLLP PEELLRSSAD FLQRLSAILR TSLRFRLDAH GQAMVFPYHR 

      1570       1580       1590       1600       1610       1620 
PSPGSEPRAR RELAPEVIGS VVMLEIDNRL CLQSPENDHC FPDAQSAADY LGALSAVERL 

      1630       1640       1650       1660       1670       1680 
DFPYPLRDVR GEPLEPPEPS VPLLPLLVAG AVLLLVILVL GVMVARRKRE HSTLWFPEGF 

      1690       1700       1710       1720       1730       1740 
SLHKDVASGH KGRREPVGQD ALGMKNMAKG ESLMGEVATD WMDTECPEAK RLKVEEPGMG 

      1750       1760       1770       1780       1790       1800 
AEEAVDCRQW TQHHLVAADI RVAPAMALTP PQGDADADGM DVNVRGPDGF TPLMLASFCG 

      1810       1820       1830       1840       1850       1860 
GALEPMPTEE DEADDTSASI ISDLICQGAQ LGARTDRTGE TALHLAARYA RADAAKRLLD 

      1870       1880       1890       1900       1910       1920 
AGADTNAQDH SGRTPLHTAV TADAQGVFQI LIRNRSTDLD ARMADGSTAL ILAARLAVEG 

      1930       1940       1950       1960       1970       1980 
MVEELIASHA DVNAVDELGK SALHWAAAVN NVEATLALLK NGANKDMQDS KEETPLFLAA 

      1990       2000       2010       2020       2030       2040 
REGSYEAAKL LLDHFANREI TDHLDRLPRD VAQERLHQDI VRLLDQPSGP RSPPGPHGLG 

      2050       2060       2070       2080       2090       2100 
PLLCPPGAFL PGLKAAQSGS KKSRRPPGKA GLGPQGPRGR GKKLTLACPG PLADSSVTLS 

      2110       2120       2130       2140       2150       2160 
PVDSLDSPRP FGGPPASPGG FPLEGPYAAA TATAVSLAQL GGPGRAGLGR QPPGGCVLSL 

      2170       2180       2190       2200       2210       2220 
GLLNPVAVPL DWARLPPPAP PGPSFLLPLA PGPQLLNPGT PVSPQERPPP YLAVPGHGEE 

      2230       2240       2250       2260       2270       2280 
YPAAGAHSSP PKARFLRVPS EHPYLTPSPE SPEHWASPSP PSLSDWSEST PSPATATGAM 

      2290       2300       2310       2320 
ATTTGALPAQ PLPLSVPSSL AQAQTQLGPQ PEVTPKRQVL A 

« Hide

References

« Hide 'large scale' references
[1]"Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia."
Joutel A., Corpechot C., Ducros A., Vahedi K., Chabriat H., Mouton P., Alamowitch S., Domenga V., Cecillion M., Marechal E., Maciazek J., Vayssiere C., Cruaud C., Cabanis E.-A., Ruchoux M.M., Weissenbach J., Bach J.-F., Bousser M.-G., Tournier-Lasserve E.
Nature 383:707-710(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-2223.
[2]Gunel M., Artavanis-Tsakonas S.
Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Human ligands of the Notch receptor."
Gray G.E., Mann R.S., Mitsiadis E., Henrique D., Carcangiu M.-L., Banks A., Leiman J., Ward D., Ish-Horowitz D., Artavanis-Tsakonas S.
Am. J. Pathol. 154:785-794(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF LIGANDS.
[5]"MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors."
Wu L., Aster J.C., Blacklow S.C., Lake R., Artavanis-Tsakonas S., Griffin J.D.
Nat. Genet. 26:484-489(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAML1.
[6]"Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors."
Wu L., Sun T., Kobayashi K., Gao P., Griffin J.D.
Mol. Cell. Biol. 22:7688-7700(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAML2 AND MAML3.
[7]"Conserved signal peptide of Notch3 inhibits interaction with proteasome."
Zhang Y., Jia L., Lee S.J., Wang M.M.
Biochem. Biophys. Res. Commun. 355:245-251(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PSMA1.
[8]"Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor."
Coleman M.L., McDonough M.A., Hewitson K.S., Coles C., Mecinovic J., Edelmann M., Cook K.M., Cockman M.E., Lancaster D.E., Kessler B.M., Oldham N.J., Ratcliffe P.J., Schofield C.J.
J. Biol. Chem. 282:24027-24038(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIF1AN.
[9]"Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways."
Zheng X., Linke S., Dias J.M., Zheng X., Gradin K., Wallis T.P., Hamilton B.R., Gustafsson M., Ruas J.L., Wilkins S., Bilton R.L., Brismar K., Whitelaw M.L., Pereira T., Gorman J.J., Ericson J., Peet D.J., Lendahl U., Poellinger L.
Proc. Natl. Acad. Sci. U.S.A. 105:3368-3373(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: HYDROXYLATION BY HIF1AN.
[10]"Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients."
Joutel A., Vahedi K., Corpechot C., Troesch A., Chabriat H., Vayssiere C., Cruaud C., Maciazek J., Weissenbach J., Bousser M.-G., Bach J.-F., Tournier-Lasserve E.
Lancet 350:1511-1515(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CADASIL TYR-49; CYS-71; CYS-90; CYS-110; CYS-133; CYS-141; ARG-146; CYS-153; CYS-169; CYS-171; CYS-182; ARG-185; SER-212; GLY-222; TYR-224; CYS-258; TYR-542; CYS-558; CYS-578; CYS-728; CYS-985; CYS-1006; CYS-1031; CYS-1231 AND ARG-1261, VARIANTS ARG-170; LEU-496; GLN-1133; MET-1183 AND VAL-2223.
[11]"Quantitative MRI in CADASIL: correlation with disability and cognitive performance."
Dichgans M., Filippi M., Bruening R., Iannucci G., Berchtenbreiter C., Minicucci L., Uttner I., Crispin A., Ludwig H., Gasser T., Yousry T.A.
Neurology 52:1361-1367(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CADASIL CYS-90; PHE-117; CYS-133; CYS-141; CYS-169; TYR-174; CYS-182 AND ARG-183.
[12]"Diagnostic Notch3 sequence analysis in CADASIL: three new mutations in Dutch patients. Dutch CADASIL Research Group."
Dutch CADASIL research group
Lesnik Oberstein S.A.J., Ferrari M.D., Bakker E., van Gestel J., Kneppers A.L.J., Frants R.R., Breuning M.H., Haan J.
Neurology 52:1913-1915(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CADASIL CYS-133; CYS-141; CYS-153; CYS-182; CYS-207; CYS-544 AND ARG-1015.
[13]"Small in-frame deletions and missense mutations in CADASIL: 3D models predict misfolding of Notch3 EGF-like repeat domains."
Dichgans M., Ludwig H., Mueller-Hoecker J., Messerschmidt A., Gasser T.
Eur. J. Hum. Genet. 8:280-285(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CADASIL 80-ASP--SER-84 DEL; CYS-90; PHE-93; CYS-110; PHE-117; PHE-123; CYS-133; CYS-141; SER-144; TYR-144; CYS-150; 153-ARG--CYS-155 DEL; CYS-153; CYS-169; TYR-174; CYS-182; ARG-183; SER-183; ARG-185 AND PHE-194.
[14]"Identification of a novel mutation C144F in the Notch3 gene in an Australian CADASIL pedigree."
Grigg R., Lea R., Sullivan A.A., Curtain R., MacMillian J., Griffiths L.
Hum. Mutat. 16:449-450(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CADASIL PHE-144.
[15]"Evaluation of DHPLC analysis in mutational scanning of Notch3, a gene with a high G-C content."
Escary J.-L., Cecillon M., Maciazek J., Lathrop M., Tournier-Lasserve E., Joutel A.
Hum. Mutat. 16:518-526(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CADASIL TYR-49; CYS-54; CYS-90; CYS-110; 114-GLY--PRO-120 DEL; TYR-123; CYS-133; CYS-141; ARG-146; CYS-153; SER-162; CYS-169; TYR-174; CYS-180; CYS-182; ARG-185; TYR-194; TYR-206; CYS-207; SER-212; GLY-222; TYR-224; CYS-258; TYR-542; CYS-558; CYS-578; CYS-607; CYS-728; CYS-984; CYS-985; CYS-1006; CYS-1031; CYS-1231 AND ARG-1261.
[16]"Splice site mutation causing a seven amino acid Notch3 in-frame deletion in CADASIL."
Joutel A., Chabriat H., Vahedi K., Domenga V., Vayssiere C., Ruchoux M.M., Lucas C., Leys D., Bousser M.-G., Tournier-Lasserve E.
Neurology 54:1874-1875(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CADASIL 114-GLY--PRO-120 DEL.
[17]"A novel mutation in the Notch3 gene in an Italian family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: genetic and magnetic resonance spectroscopic findings."
Oliveri R.L., Muglia M., De Stefano N., Mazzei R., Labate A., Conforti F.L., Patitucci A., Gabriele A.L., Tagarelli G., Magariello A., Zappia M., Gambardella A., Federico A., Quattrone A.
Arch. Neurol. 58:1418-1422(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CADASIL CYS-332.
[18]"Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis."
Joutel A., Favrole P., Labauge P., Chabriat H., Lescoat C., Andreux F., Domenga V., Cecillon M., Vahedi K., Ducros A., Cave-Riant F., Bousser M.G., Tournier-Lasserve E.
Lancet 358:2049-2051(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CADASIL CYS-110; CYS-133; TRP-134; CYS-141; CYS-153; CYS-182; GLY-185; CYS-207; SER-212; GLY-222; SER-428; CYS-558; CYS-985 AND CYS-1063.
[19]"Reversible coma with raised intracranial pressure: an unusual clinical manifestation of CADASIL."
Feuerhake F., Volk B., Ostertag C.B., Jungling F.D., Kassubek J., Orszagh M., Dichgans M.
Acta Neuropathol. 103:188-192(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CADASIL TRP-134.
[20]"CADASIL: a common form of hereditary arteriopathy causing brain infarcts and dementia."
Kalimo H., Ruchoux M.-M., Viitanen M., Kalaria R.N.
Brain Pathol. 12:371-384(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CADASIL ARG-76; TYR-93; TYR-128; CYS-142; ARG-194; TYR-222; SER-233; ARG-251; CYS-420; GLY-440; CYS-449; CYS-953 AND CYS-1021.
[21]"C455R notch3 mutation in a Colombian CADASIL kindred with early onset of stroke."
Arboleda-Velasquez J.F., Lopera F., Lopez E., Frosch M.P., Sepulveda-Falla D., Gutierrez J.E., Vargas S., Medina M., Martinez De Arrieta C., Lebo R.V., Slaugenhaupt S.A., Betensky R.A., Villegas A., Arcos-Burgos M., Rivera D., Restrepo J.C., Kosik K.S.
Neurology 59:277-279(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CADASIL ARG-455.
[22]"A novel mutation (C67Y)in the NOTCH3 gene in a Korean CADASIL patient."
Moon S.-Y., Kim H.-Y., Seok J.-I., Kwon J.-C., Ki C.-S., Kim J.-W., Suh Y.-L., Na D.L.
J. Korean Med. Sci. 18:141-144(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CADASIL TYR-67.
[23]"Genetic, clinical and pathological studies of CADASIL in Japan: a partial contribution of Notch3 mutations and implications of smooth muscle cell degeneration for the pathogenesis."
Santa Y., Uyama E., Chui D.H., Arima M., Kotorii S., Takahashi K., Tabira T.
J. Neurol. Sci. 212:79-84(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CADASIL CYS-90; CYS-133; CYS-169; ARG-174; PHE-174 AND LYS-213.
[24]"The influence of genetic and cardiovascular risk factors on the CADASIL phenotype."
Singhal S., Bevan S., Barrick T., Rich P., Markus H.S.
Brain 127:2031-2038(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CADASIL ARG-76; CYS-90; CYS-110; CYS-141; CYS-153; CYS-169; CYS-182; ARG-183; CYS-189; SER-194; CYS-207; ARG-251; CYS-332; GLY-440; CYS-607; CYS-953 AND CYS-1231.
[25]"Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients."
Opherk C., Peters N., Herzog J., Luedtke R., Dichgans M.
Brain 127:2533-2539(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CADASIL GLY-43; PHE-49; CYS-60; SER-65; TRP-76; 77-GLN--CYS-82 DEL; 80-ASP--SER-84 DEL; ARG-87; TYR-87; CYS-90; PHE-93; TRP-106; TYR-108; CYS-110; PHE-117; PHE-123; CYS-133; TRP-134; CYS-141; SER-144; TYR-144; CYS-145; CYS-149; CYS-150; 153-ARG--155-CYS DEL; CYS-153; SER-155; CYS-169; ARG-174; TYR-174; CYS-182; ARG-183; SER-183; PHE-183; ARG-185; PHE-194; TYR-201; CYS-207; TYR-233; 239-ASP--ASP-253 DEL; SER-240; ARG-245; TYR-260; CYS-332; CYS-335; CYS-337; SER-379; ARG-395; CYS-421; TYR-428; ARG-440; SER-446; TYR-484; TYR-495; ARG-511; TYR-549; CYS-558; CYS-985 AND TYR-1261.
[26]"Detection of the founder effect in Finnish CADASIL families."
Mykkaenen K., Savontaus M.L., Juvonen V., Sistonen P., Tuisku S., Tuominen S., Penttinen M., Lundkvist J., Viitanen M., Kalimo H., Peoyhoenen M.
Eur. J. Hum. Genet. 12:813-819(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CADASIL CYS-133.
[27]"Gene symbol: NOTCH3. Disease: CADASIL."
Rojas-Marcos I., Encarnacion M., Martinez-Yelamos S., Ferrer I., Arbizu T., Gil-Peralta A., Garcia-Lozano J.R.
Hum. Genet. 115:175-175(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CADASIL TRP-108.
[28]"Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies."
Peters N., Opherk C., Bergmann T., Castro M., Herzog J., Dichgans M.
Arch. Neurol. 62:1091-1094(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CADASIL GLY-43; PHE-49; CYS-60; SER-65; TRP-76; 80-ASP--SER-84 DEL; ARG-87; CYS-90; PHE-93; TYR-108; CYS-110; PHE-117; PHE-123; CYS-133; TRP-134; CYS-141; SER-144; TYR-144; CYS-149; CYS-150; CYS-153; 153-ARG--CYS-155 DEL; CYS-169; ARG-174; TYR-174; CYS-182; SER-183; PHE-183; ARG-185; PHE-194; CYS-207; TYR-233; SER-240; ARG-245; TYR-260; 239-ASP--ASP-253 DEL; CYS-319; CYS-332; CYS-335; CYS-337; SER-379; ARG-395; CYS-421; TYR-428; ARG-440; PHE-484; TYR-495; ARG-511; TYR-549; CYS-558; CYS-728; SER-775; CYS-985 AND TYR-1261.
[29]"Gene symbol: NOTCH3. Disease: cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy."
Soong B.W., Lee Y.-C., Lu Y.-C.
Hum. Genet. 116:242-242(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CADASIL CYS-118.
[30]"Activating NOTCH3 mutation in a patient with small-vessel-disease of the brain."
Fouillade C., Chabriat H., Riant F., Mine M., Arnoud M., Magy L., Bousser M.G., Tournier-Lasserve E., Joutel A.
Hum. Mutat. 29:452-452(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BRAIN SMALL-VESSEL-DISEASE PRO-1515.
[31]"Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis."
Martignetti J.A., Tian L., Li D., Ramirez M.C., Camacho-Vanegas O., Camacho S.C., Guo Y., Zand D.J., Bernstein A.M., Masur S.K., Kim C.E., Otieno F.G., Hou C., Abdel-Magid N., Tweddale B., Metry D., Fournet J.C., Papp E. expand/collapse author list , McPherson E.W., Zabel C., Vaksmann G., Morisot C., Keating B., Sleiman P.M., Cleveland J.A., Everman D.B., Zackai E., Hakonarson H.
Am. J. Hum. Genet. 92:1001-1007(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT IMF2 PRO-1519.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U97669 mRNA. Translation: AAB91371.1.
AF058900 expand/collapse EMBL AC list , AF058881, AF058882, AF058883, AF058884, AF058885, AF058886, AF058887, AF058888, AF058889, AF058890, AF058891, AF058892, AF058893, AF058894, AF058895, AF058896, AF058897, AF058898, AF058899 Genomic DNA. Translation: AAC14346.1.
AC004257 Genomic DNA. Translation: AAC04897.1.
AC004663 Genomic DNA. Translation: AAC15789.1.
CCDSCCDS12326.1.
PIRS78549.
RefSeqNP_000426.2. NM_000435.2.
UniGeneHs.8546.

3D structure databases

ProteinModelPortalQ9UM47.
SMRQ9UM47. Positions 390-505, 1791-2026.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110916. 15 interactions.
IntActQ9UM47. 13 interactions.
MINTMINT-2822317.
STRING9606.ENSP00000263388.

PTM databases

PhosphoSiteQ9UM47.

Polymorphism databases

DMDM322510053.

Proteomic databases

MaxQBQ9UM47.
PaxDbQ9UM47.
PRIDEQ9UM47.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263388; ENSP00000263388; ENSG00000074181.
GeneID4854.
KEGGhsa:4854.
UCSCuc002nan.3. human.

Organism-specific databases

CTD4854.
GeneCardsGC19M015270.
GeneReviewsNOTCH3.
H-InvDBHIX0040142.
HIX0174419.
HGNCHGNC:7883. NOTCH3.
HPACAB005393.
HPA044392.
MIM125310. phenotype.
600276. gene.
615293. phenotype.
neXtProtNX_Q9UM47.
Orphanet136. CADASIL.
2591. Infantile myofibromatosis.
PharmGKBPA31685.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0666.
HOGENOMHOG000234369.
HOVERGENHBG052650.
InParanoidQ9UM47.
KOK02599.
OMAMLEIDNR.
OrthoDBEOG7992RD.
PhylomeDBQ9UM47.
TreeFamTF351641.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_2001. Receptor-ligand binding initiates the second proteolytic cleavage of Notch receptor.
REACT_2155. NICD traffics to nucleus.
REACT_691. A third proteolytic cleavage releases NICD.
REACT_71. Gene Expression.
SignaLinkQ9UM47.

Gene expression databases

ArrayExpressQ9UM47.
BgeeQ9UM47.
CleanExHS_NOTCH3.
GenevestigatorQ9UM47.

Family and domain databases

Gene3D1.25.40.20. 1 hit.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR024600. DUF3454_notch.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR009030. Growth_fac_rcpt_N_dom.
IPR008297. Notch.
IPR022331. Notch_3.
IPR000800. Notch_dom.
IPR010660. Notch_NOD_dom.
IPR011656. Notch_NODP_dom.
[Graphical view]
PfamPF12796. Ank_2. 2 hits.
PF11936. DUF3454. 1 hit.
PF00008. EGF. 17 hits.
PF07645. EGF_CA. 5 hits.
PF12661. hEGF. 2 hits.
PF06816. NOD. 1 hit.
PF07684. NODP. 1 hit.
PF00066. Notch. 3 hits.
[Graphical view]
PIRSFPIRSF002279. Notch. 1 hit.
PRINTSPR01452. LNOTCHREPEAT.
PR01986. NOTCH3.
SMARTSM00248. ANK. 6 hits.
SM00181. EGF. 15 hits.
SM00179. EGF_CA. 19 hits.
SM00004. NL. 3 hits.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
SSF57184. SSF57184. 4 hits.
SSF90193. SSF90193. 3 hits.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 4 hits.
PS00010. ASX_HYDROXYL. 18 hits.
PS00022. EGF_1. 33 hits.
PS01186. EGF_2. 25 hits.
PS50026. EGF_3. 34 hits.
PS01187. EGF_CA. 16 hits.
PS50258. LNR. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNotch_3.
GenomeRNAi4854.
NextBio18698.
PROQ9UM47.
SOURCESearch...

Entry information

Entry nameNOTC3_HUMAN
AccessionPrimary (citable) accession number: Q9UM47
Secondary accession number(s): Q9UEB3, Q9UPL3, Q9Y6L8
Entry history
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: February 8, 2011
Last modified: July 9, 2014
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM