Q9UM47 (NOTC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neurogenic locus notch homolog protein 3
Short name=Notch 3

Cleaved into the following 2 chains:

1. Notch 3 extracellular truncation
2. Notch 3 intracellular domain

Gene names

Name:

NOTCH3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	2321 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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
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 process	Differentiation Notch signaling pathway Transcription Transcription regulation
Cellular component	Cell membrane Membrane Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	ANK repeat EGF-like domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Activator Developmental protein Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch receptor processing Traceable author statement. Source: Reactome Notch signaling pathway Traceable author statement. Source: Reactome forebrain development Inferred from electronic annotation. Source: Compara glomerular capillary formation Inferred from electronic annotation. Source: Compara negative regulation of neuron differentiation Inferred from electronic annotation. Source: Compara neuron fate commitment Inferred from electronic annotation. Source: Compara positive regulation of smooth muscle cell proliferation Inferred from electronic annotation. Source: Compara regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome
Cellular_component	Golgi membrane Traceable author statement. Source: Reactome cytosol Traceable author statement. Source: Reactome endoplasmic reticulum membrane Traceable author statement. Source: Reactome extracellular region Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleoplasm Traceable author statement. Source: Reactome plasma membrane Traceable author statement. Source: Reactome
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Psma1	Q9R1P4	2	EBI-1236377,EBI-991653	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 39	39	Potential
	Chain	40 – 2321	2282	Neurogenic locus notch homolog protein 3		PRO_0000007692
	Chain	1629 – 2321	693	Notch 3 extracellular truncation By similarity		PRO_0000007693
	Chain	1662 – 2321	660	Notch 3 intracellular domain By similarity		PRO_0000007694
Regions
	Topological domain	40 – 1643	1604	Extracellular Potential
	Transmembrane	1644 – 1664	21	Helical; Potential
	Topological domain	1665 – 2321	657	Cytoplasmic Potential
	Domain	40 – 77	38	EGF-like 1
	Domain	78 – 118	41	EGF-like 2
	Domain	119 – 156	38	EGF-like 3
	Domain	158 – 195	38	EGF-like 4; calcium-binding Potential
	Domain	197 – 234	38	EGF-like 5
	Domain	236 – 272	37	EGF-like 6; calcium-binding Potential
	Domain	274 – 312	39	EGF-like 7
	Domain	314 – 350	37	EGF-like 8; calcium-binding Potential
	Domain	351 – 389	39	EGF-like 9
	Domain	391 – 429	39	EGF-like 10; calcium-binding Potential
	Domain	431 – 467	37	EGF-like 11; calcium-binding Potential
	Domain	469 – 505	37	EGF-like 12; calcium-binding Potential
	Domain	507 – 543	37	EGF-like 13; calcium-binding Potential
	Domain	545 – 580	36	EGF-like 14; calcium-binding Potential
	Domain	582 – 618	37	EGF-like 15; calcium-binding Potential
	Domain	620 – 655	36	EGF-like 16; calcium-binding Potential
	Domain	657 – 693	37	EGF-like 17; calcium-binding Potential
	Domain	695 – 730	36	EGF-like 18
	Domain	734 – 770	37	EGF-like 19
	Domain	771 – 808	38	EGF-like 20
	Domain	810 – 847	38	EGF-like 21; calcium-binding Potential
	Domain	849 – 885	37	EGF-like 22; calcium-binding Potential
	Domain	887 – 922	36	EGF-like 23; calcium-binding Potential
	Domain	924 – 960	37	EGF-like 24
	Domain	962 – 998	37	EGF-like 25
	Domain	1000 – 1034	35	EGF-like 26
	Domain	1047 – 1082	36	EGF-like 27
	Domain	1084 – 1120	37	EGF-like 28
	Domain	1122 – 1158	37	EGF-like 29; calcium-binding Potential
	Domain	1160 – 1203	44	EGF-like 30; calcium-binding Potential
	Domain	1205 – 1244	40	EGF-like 31
	Domain	1246 – 1287	42	EGF-like 32
	Domain	1289 – 1325	37	EGF-like 33
	Domain	1335 – 1373	39	EGF-like 34
	Repeat	1387 – 1427	41	LNR 1
	Repeat	1428 – 1458	31	LNR 2
	Repeat	1467 – 1505	39	LNR 3
	Repeat	1838 – 1867	30	ANK 1
	Repeat	1871 – 1901	31	ANK 2
	Repeat	1905 – 1934	30	ANK 3
	Repeat	1938 – 1967	30	ANK 4
	Repeat	1971 – 2000	30	ANK 5
Sites
	Site	1571 – 1572	2	Cleavage; by furin-like protease By similarity
Amino acid modifications
	Glycosylation	1179	1	N-linked (GlcNAc...) Potential
	Glycosylation	1336	1	N-linked (GlcNAc...) Potential
	Glycosylation	1438	1	N-linked (GlcNAc...) Potential
	Disulfide bond	43 ↔ 55		By similarity
	Disulfide bond	49 ↔ 65		By similarity
	Disulfide bond	67 ↔ 76		By similarity
	Disulfide bond	82 ↔ 93		By similarity
	Disulfide bond	87 ↔ 106		By similarity
	Disulfide bond	108 ↔ 117		By similarity
	Disulfide bond	123 ↔ 134		By similarity
	Disulfide bond	128 ↔ 144		By similarity
	Disulfide bond	146 ↔ 155		By similarity
	Disulfide bond	162 ↔ 174		By similarity
	Disulfide bond	168 ↔ 183		By similarity
	Disulfide bond	185 ↔ 194		By similarity
	Disulfide bond	201 ↔ 212		By similarity
	Disulfide bond	206 ↔ 222		By similarity
	Disulfide bond	224 ↔ 233		By similarity
	Disulfide bond	240 ↔ 251		By similarity
	Disulfide bond	245 ↔ 260		By similarity
	Disulfide bond	262 ↔ 271		By similarity
	Disulfide bond	278 ↔ 291		By similarity
	Disulfide bond	285 ↔ 300		By similarity
	Disulfide bond	302 ↔ 311		By similarity
	Disulfide bond	318 ↔ 329		By similarity
	Disulfide bond	323 ↔ 338		By similarity
	Disulfide bond	340 ↔ 349		By similarity
	Disulfide bond	355 ↔ 366		By similarity
	Disulfide bond	360 ↔ 377		By similarity
	Disulfide bond	379 ↔ 388		By similarity
	Disulfide bond	395 ↔ 408		By similarity
	Disulfide bond	402 ↔ 417		By similarity
	Disulfide bond	419 ↔ 428		By similarity
	Disulfide bond	435 ↔ 446		By similarity
	Disulfide bond	440 ↔ 455		By similarity
	Disulfide bond	457 ↔ 466		By similarity
	Disulfide bond	473 ↔ 484		By similarity
	Disulfide bond	478 ↔ 493		By similarity
	Disulfide bond	495 ↔ 504		By similarity
	Disulfide bond	511 ↔ 522		By similarity
	Disulfide bond	516 ↔ 531		By similarity
	Disulfide bond	533 ↔ 542		By similarity
	Disulfide bond	549 ↔ 559		By similarity
	Disulfide bond	554 ↔ 568		By similarity
	Disulfide bond	570 ↔ 579		By similarity
	Disulfide bond	586 ↔ 597		By similarity
	Disulfide bond	591 ↔ 606		By similarity
	Disulfide bond	608 ↔ 617		By similarity
	Disulfide bond	624 ↔ 634		By similarity
	Disulfide bond	629 ↔ 643		By similarity
	Disulfide bond	645 ↔ 654		By similarity
	Disulfide bond	661 ↔ 672		By similarity
	Disulfide bond	666 ↔ 681		By similarity
	Disulfide bond	683 ↔ 692		By similarity
	Disulfide bond	699 ↔ 709		By similarity
	Disulfide bond	704 ↔ 718		By similarity
	Disulfide bond	720 ↔ 729		By similarity
	Disulfide bond	738 ↔ 749		By similarity
	Disulfide bond	743 ↔ 758		By similarity
	Disulfide bond	760 ↔ 769		By similarity
	Disulfide bond	775 ↔ 786		By similarity
	Disulfide bond	780 ↔ 796		By similarity
	Disulfide bond	798 ↔ 807		By similarity
	Disulfide bond	814 ↔ 826		By similarity
	Disulfide bond	820 ↔ 835		By similarity
	Disulfide bond	837 ↔ 846		By similarity
	Disulfide bond	853 ↔ 864		By similarity
	Disulfide bond	858 ↔ 873		By similarity
	Disulfide bond	875 ↔ 884		By similarity
	Disulfide bond	891 ↔ 901		By similarity
	Disulfide bond	896 ↔ 910		By similarity
	Disulfide bond	912 ↔ 921		By similarity
	Disulfide bond	928 ↔ 939		By similarity
	Disulfide bond	933 ↔ 948		By similarity
	Disulfide bond	950 ↔ 959		By similarity
	Disulfide bond	966 ↔ 977		By similarity
	Disulfide bond	971 ↔ 986		By similarity
	Disulfide bond	988 ↔ 997		By similarity
	Disulfide bond	1004 ↔ 1015		By similarity
	Disulfide bond	1009 ↔ 1022		By similarity
	Disulfide bond	1024 ↔ 1033		By similarity
	Disulfide bond	1040 ↔ 1061		By similarity
	Disulfide bond	1055 ↔ 1070		By similarity
	Disulfide bond	1072 ↔ 1081		By similarity
	Disulfide bond	1088 ↔ 1099		By similarity
	Disulfide bond	1093 ↔ 1108		By similarity
	Disulfide bond	1110 ↔ 1119		By similarity
	Disulfide bond	1126 ↔ 1137		By similarity
	Disulfide bond	1131 ↔ 1146		By similarity
	Disulfide bond	1148 ↔ 1157		By similarity
	Disulfide bond	1164 ↔ 1182		By similarity
	Disulfide bond	1176 ↔ 1191		By similarity
	Disulfide bond	1193 ↔ 1202		By similarity
	Disulfide bond	1209 ↔ 1222		By similarity
	Disulfide bond	1214 ↔ 1232		By similarity
	Disulfide bond	1234 ↔ 1243		By similarity
	Disulfide bond	1250 ↔ 1261		By similarity
	Disulfide bond	1255 ↔ 1275		By similarity
	Disulfide bond	1277 ↔ 1286		By similarity
	Disulfide bond	1293 ↔ 1304		By similarity
	Disulfide bond	1298 ↔ 1313		By similarity
	Disulfide bond	1315 ↔ 1324		By similarity
	Disulfide bond	1339 ↔ 1350		By similarity
	Disulfide bond	1344 ↔ 1361		By similarity
	Disulfide bond	1363 ↔ 1372		By similarity
	Disulfide bond	1387 ↔ 1410		By similarity
	Disulfide bond	1392 ↔ 1405		By similarity
	Disulfide bond	1401 ↔ 1417		By similarity
	Disulfide bond	1428 ↔ 1451		By similarity
	Disulfide bond	1433 ↔ 1446		By similarity
	Disulfide bond	1442 ↔ 1458		By similarity
	Disulfide bond	1467 ↔ 1493		By similarity
	Disulfide bond	1475 ↔ 1488		By similarity
	Disulfide bond	1484 ↔ 1500		By similarity
Natural variations
	Natural variant	43	1	C → G in CADASIL. Ref.25 Ref.28		VAR_044230
	Natural variant	49	1	C → F in CADASIL. Ref.25 Ref.28		VAR_044231
	Natural variant	49	1	C → Y in CADASIL. Ref.10 Ref.15 Ref.25 Ref.28		VAR_012871
	Natural variant	54	1	R → C in CADASIL. Ref.15		VAR_044232
	Natural variant	60	1	S → C in CADASIL. Ref.25 Ref.28		VAR_044233
	Natural variant	65	1	C → S in CADASIL. Ref.25 Ref.28		VAR_044234
	Natural variant	67	1	C → Y in CADASIL. Ref.22		VAR_044235
	Natural variant	71	1	W → C in CADASIL. Ref.10 Corresponds to variant rs28937321 [ dbSNP | Ensembl ].		VAR_012872
	Natural variant	76	1	C → R in CADASIL. Ref.20 Ref.24		VAR_044236
	Natural variant	76	1	C → W in CADASIL. Ref.25 Ref.28		VAR_044237
	Natural variant	77 – 82	6	Missing in CADASIL.		VAR_044238
	Natural variant	80 – 84	5	Missing in CADASIL.		VAR_044239
	Natural variant	87	1	C → R in CADASIL. Ref.25 Ref.28		VAR_044240
	Natural variant	87	1	C → Y in CADASIL. Ref.25		VAR_044241
	Natural variant	90	1	R → C in CADASIL. Ref.10 Ref.11 Ref.13 Ref.15 Ref.23 Ref.24 Ref.25 Ref.28		VAR_012873
	Natural variant	93	1	C → F in CADASIL. Ref.13 Ref.25 Ref.28		VAR_044242
	Natural variant	93	1	C → Y in CADASIL. Ref.20		VAR_044243
	Natural variant	106	1	C → W in CADASIL. Ref.25		VAR_044244
	Natural variant	108	1	C → W in CADASIL. Ref.27		VAR_044245
	Natural variant	108	1	C → Y in CADASIL. Ref.25 Ref.28		VAR_044246
	Natural variant	110	1	R → C in CADASIL. Ref.10 Ref.13 Ref.15 Ref.18 Ref.24 Ref.25 Ref.28		VAR_012874
	Natural variant	114 – 120	7	Missing in CADASIL.		VAR_012875
	Natural variant	117	1	C → F in CADASIL. Ref.11 Ref.13 Ref.25 Ref.28		VAR_044247
	Natural variant	118	1	S → C in CADASIL. Ref.29		VAR_044248
	Natural variant	123	1	C → F in CADASIL. Ref.13 Ref.25 Ref.28		VAR_044249
	Natural variant	123	1	C → Y in CADASIL. Ref.15		VAR_044250
	Natural variant	128	1	C → Y in CADASIL. Ref.20		VAR_044251
	Natural variant	133	1	R → 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 variant	134	1	C → W in CADASIL. Ref.18 Ref.19 Ref.25 Ref.28		VAR_044252
	Natural variant	141	1	R → C in CADASIL. Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.18 Ref.24 Ref.25 Ref.28		VAR_012877
	Natural variant	142	1	F → C in CADASIL. Ref.20		VAR_044253
	Natural variant	144	1	C → F in CADASIL. Ref.14		VAR_044254
	Natural variant	144	1	C → S in CADASIL. Ref.13 Ref.25 Ref.28		VAR_044255
	Natural variant	144	1	C → Y in CADASIL. Ref.13 Ref.25 Ref.28		VAR_044256
	Natural variant	145	1	S → C in CADASIL. Ref.25		VAR_044257
	Natural variant	146	1	C → R in CADASIL. Ref.10 Ref.15		VAR_012878
	Natural variant	149	1	G → C in CADASIL. Ref.25 Ref.28		VAR_044258
	Natural variant	150	1	Y → C in CADASIL. Ref.13 Ref.25 Ref.28		VAR_044259
	Natural variant	153 – 155	3	Missing in CADASIL.		VAR_044260
	Natural variant	153	1	R → C in CADASIL. Ref.10 Ref.12 Ref.13 Ref.15 Ref.18 Ref.24 Ref.25 Ref.28		VAR_012879
	Natural variant	155	1	C → S in CADASIL. Ref.25		VAR_044261
	Natural variant	162	1	C → S in CADASIL. Ref.15		VAR_044262
	Natural variant	169	1	R → 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 variant	170	1	H → R. Ref.10		VAR_012881
	Natural variant	171	1	G → C in CADASIL. Ref.10		VAR_012882
	Natural variant	174	1	C → F in CADASIL. Ref.23		VAR_044263
	Natural variant	174	1	C → R in CADASIL. Ref.23 Ref.25 Ref.28		VAR_044264
	Natural variant	174	1	C → Y in CADASIL. Ref.11 Ref.13 Ref.15 Ref.25 Ref.28		VAR_044265
	Natural variant	180	1	S → C in CADASIL. Ref.15		VAR_044266
	Natural variant	182	1	R → 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 variant	183	1	C → F in CADASIL. Ref.25 Ref.28		VAR_044267
	Natural variant	183	1	C → R in CADASIL. Ref.11 Ref.13 Ref.24 Ref.25		VAR_044268
	Natural variant	183	1	C → S in CADASIL. Ref.13 Ref.25 Ref.28		VAR_044269
	Natural variant	185	1	C → G in CADASIL. Ref.18		VAR_044270
	Natural variant	185	1	C → R in CADASIL. Ref.10 Ref.13 Ref.15 Ref.25 Ref.28		VAR_012884
	Natural variant	189	1	Y → C in CADASIL. Ref.24		VAR_044271
	Natural variant	194	1	C → F in CADASIL. Ref.13 Ref.25 Ref.28		VAR_044272
	Natural variant	194	1	C → R in CADASIL. Ref.20		VAR_044273
	Natural variant	194	1	C → S in CADASIL. Ref.24		VAR_044274
	Natural variant	194	1	C → Y in CADASIL. Ref.15		VAR_044275
	Natural variant	201	1	C → Y in CADASIL. Ref.25		VAR_044276
	Natural variant	206	1	C → Y in CADASIL. Ref.15		VAR_044277
	Natural variant	207	1	R → C in CADASIL. Ref.12 Ref.15 Ref.18 Ref.24 Ref.25 Ref.28		VAR_044278
	Natural variant	212	1	C → S in CADASIL. Ref.10 Ref.15 Ref.18		VAR_012885
	Natural variant	213	1	R → K in CADASIL. Ref.23		VAR_044279
	Natural variant	222	1	C → G in CADASIL. Ref.10 Ref.15 Ref.18		VAR_012886
	Natural variant	222	1	C → Y in CADASIL. Ref.20		VAR_044280
	Natural variant	224	1	C → Y in CADASIL. Ref.10 Ref.15		VAR_012887
	Natural variant	233	1	C → S in CADASIL. Ref.20		VAR_044281
	Natural variant	233	1	C → Y in CADASIL. Ref.25 Ref.28		VAR_044282
	Natural variant	239 – 253	15	Missing in CADASIL.		VAR_044283
	Natural variant	240	1	C → S in CADASIL. Ref.25 Ref.28		VAR_044284
	Natural variant	245	1	C → R in CADASIL. Ref.25 Ref.28		VAR_044285
	Natural variant	251	1	C → R in CADASIL. Ref.20 Ref.24		VAR_044286
	Natural variant	258	1	Y → C in CADASIL. Ref.10 Ref.15		VAR_012888
	Natural variant	260	1	C → Y in CADASIL. Ref.25 Ref.28		VAR_044287
	Natural variant	319	1	A → C in CADASIL; requires 2 nucleotide substitutions. Ref.28		VAR_044288
	Natural variant	332	1	R → C in CADASIL. Ref.17 Ref.24 Ref.25 Ref.28		VAR_044289
	Natural variant	335	1	S → C in CADASIL. Ref.25 Ref.28		VAR_044290
	Natural variant	337	1	Y → C in CADASIL. Ref.25 Ref.28		VAR_044291
	Natural variant	379	1	C → S in CADASIL. Ref.25 Ref.28		VAR_044292
	Natural variant	395	1	C → R in CADASIL. Ref.25 Ref.28		VAR_044293
	Natural variant	420	1	G → C in CADASIL. Ref.20		VAR_044294
	Natural variant	421	1	R → C in CADASIL. Ref.25 Ref.28		VAR_044295
	Natural variant	428	1	C → S in CADASIL. Ref.18		VAR_044296
	Natural variant	428	1	C → Y in CADASIL. Ref.25 Ref.28		VAR_044297
	Natural variant	440	1	C → G in CADASIL. Ref.20 Ref.24		VAR_044298
	Natural variant	440	1	C → R in CADASIL. Ref.25 Ref.28		VAR_044299
	Natural variant	446	1	C → S in CADASIL. Ref.25		VAR_044300
	Natural variant	449	1	R → C in CADASIL. Ref.20		VAR_044301
	Natural variant	455	1	C → R in CADASIL. Ref.21 Corresponds to variant rs28933698 [ dbSNP | Ensembl ].		VAR_044302
	Natural variant	484	1	C → F in CADASIL. Ref.28		VAR_044303
	Natural variant	484	1	C → Y in CADASIL. Ref.25		VAR_044304
	Natural variant	495	1	C → Y in CADASIL. Ref.25 Ref.28		VAR_044305
	Natural variant	496	1	P → L. Ref.10 Corresponds to variant rs11670799 [ dbSNP | Ensembl ].		VAR_012889
	Natural variant	511	1	C → R in CADASIL. Ref.25 Ref.28		VAR_044306
	Natural variant	542	1	C → Y in CADASIL. Ref.10 Ref.15		VAR_012890
	Natural variant	544	1	R → C in CADASIL. Ref.12		VAR_044307
	Natural variant	549	1	C → Y in CADASIL. Ref.25 Ref.28		VAR_044308
	Natural variant	558	1	R → C in CADASIL. Ref.10 Ref.15 Ref.18 Ref.25 Ref.28		VAR_012891
	Natural variant	578	1	R → C in CADASIL. Ref.10 Ref.15		VAR_012892
	Natural variant	607	1	R → C in CADASIL. Ref.15 Ref.24		VAR_044309
	Natural variant	728	1	R → C in CADASIL. Ref.10 Ref.15 Ref.28		VAR_012893
	Natural variant	775	1	C → S in CADASIL. Ref.28		VAR_044310
	Natural variant	953	1	G → C in CADASIL. Ref.20 Ref.24		VAR_044311
	Natural variant	984	1	F → C in CADASIL. Ref.15		VAR_044312
	Natural variant	985	1	R → C in CADASIL. Ref.10 Ref.15 Ref.18 Ref.25 Ref.28		VAR_012894
	Natural variant	1006	1	R → C in CADASIL. Ref.10 Ref.15		VAR_012895
	Natural variant	1015	1	C → R in CADASIL. Ref.12		VAR_044313
	Natural variant	1020	1	A → P. Corresponds to variant rs35769976 [ dbSNP | Ensembl ].		VAR_044314
	Natural variant	1021	1	Y → C in CADASIL. Ref.20		VAR_044315
	Natural variant	1031	1	R → C in CADASIL. Ref.10 Ref.15		VAR_012896
	Natural variant	1063	1	D → C in CADASIL; requires 2 nucleotide substitutions. Ref.18		VAR_044316
	Natural variant	1133	1	H → Q. Ref.10		VAR_012897
	Natural variant	1183	1	V → M. Ref.10 Corresponds to variant rs10408676 [ dbSNP | Ensembl ].		VAR_012898
	Natural variant	1231	1	R → C in CADASIL. Ref.10 Ref.15 Ref.24		VAR_012899
	Natural variant	1261	1	C → R in CADASIL. Ref.10 Ref.15		VAR_012900
	Natural variant	1261	1	C → Y in CADASIL. Ref.25 Ref.28		VAR_044317
	Natural variant	1515	1	L → P in brain small-vessel-disease; exhibits increased NOTCH3 signaling in a ligand-independent fashion. Ref.30		VAR_044318
	Natural variant	2223	1	A → V. Ref.1 Ref.10 Corresponds to variant rs1044009 [ dbSNP | Ensembl ].		VAR_012901

Sequences

	Sequence		Length	Mass (Da)
	Q9UM47 [UniParc]. Last modified February 8, 2011. Version 2. Checksum: 3E70EC12A59CD638	FASTA	2,321	243,631
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	U97669 mRNA. Translation: AAB91371.1. AF058900 , 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.
IPI	IPI00029819.
PIR	S78549.
RefSeq	NP_000426.2. NM_000435.2.
UniGene	Hs.8546.
3D structure databases
ProteinModelPortal	Q9UM47.
SMR	Q9UM47. Positions 390-505, 1791-2026.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UM47. 10 interactions.
MINT	MINT-2822317.
STRING	9606.ENSP00000263388.
PTM databases
PhosphoSite	Q9UM47.
Polymorphism databases
DMDM	20139284.
Proteomic databases
PaxDb	Q9UM47.
PRIDE	Q9UM47.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000263388; ENSP00000263388; ENSG00000074181.
GeneID	4854.
KEGG	hsa:4854.
UCSC	uc002nan.3. human.
Organism-specific databases
CTD	4854.
GeneCards	GC19M015270.
H-InvDB	HIX0040142. HIX0174419.
HGNC	HGNC:7883. NOTCH3.
HPA	CAB005393.
MIM	125310. phenotype. 600276. gene.
neXtProt	NX_Q9UM47.
Orphanet	136. CADASIL syndrome.
PharmGKB	PA31685.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0666.
HOGENOM	HOG000234369.
HOVERGEN	HBG052650.
InParanoid	Q9UM47.
KO	K02599.
OMA	LTFTCHC.
OrthoDB	EOG4C2H8K.
PhylomeDB	Q9UM47.
Enzyme and pathway databases
Reactome	REACT_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.
Gene expression databases
Bgee	Q9UM47.
CleanEx	HS_NOTCH3.
Genevestigator	Q9UM47.
GermOnline	ENSG00000074181. Homo sapiens.
Family and domain databases
Gene3D	1.25.40.20. 1 hit.
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. IPR024600. DUF3454_notch. IPR000742. EG-like_dom. IPR001881. EGF-like_Ca-bd. IPR013032. EGF-like_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_site. IPR018097. EGF_Ca-bd_CS. IPR008297. Notch. IPR022331. Notch_3. IPR000800. Notch_dom. IPR010660. Notch_NOD_dom. IPR011656. Notch_NODP_dom. [Graphical view]
Pfam	PF12796. 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]
PIRSF	PIRSF002279. Notch. 1 hit.
PRINTS	PR01452. LNOTCHREPEAT. PR01986. NOTCH3.
SMART	SM00248. ANK. 6 hits. SM00181. EGF. 15 hits. SM00179. EGF_CA. 19 hits. SM00004. NL. 3 hits. [Graphical view]
SUPFAM	SSF48403. ANK. 1 hit. SSF90193. Notch_region. 3 hits.
PROSITE	PS50297. 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]
ProtoNet	Search...
Other
GenomeRNAi	4854.
NextBio	18698.
SOURCE	Search...

Entry information

Entry name

NOTC3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 138 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.