P46531 (NOTC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neurogenic locus notch homolog protein 1
Short name=Notch 1
Short name=hN1

Alternative name(s):
Translocation-associated notch protein TAN-1

Cleaved into the following 2 chains:

1. Notch 1 extracellular truncation
2. Notch 1 intracellular domain
   Short name=NICD

Gene names

Name:	NOTCH1
Synonyms:	TAN1

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	2555 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. May be important for normal lymphocyte function. In altered form, may contribute to transformation or progression in some T-cell neoplasms. Involved in the maturation of both CD4+ and CD8+ cells in the thymus. May be important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, may function as a receptor for neuronal DNER and may be involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May enhance HIF1A function by sequestering HIF1AN away from HIF1A By similarity.
Subunit structure	Heterodimer of a C-terminal fragment N(TM) and an N-terminal fragment N(EC) which are probably linked by disulfide bonds. Interacts with DNER, DTX1, DTX2 and RBPJ/RBPSUH. Also interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH1. Notch 1 intracellular domain interacts with SNW1; the interaction involves multimerized NOTCH1 NICD and is implicated in a formation of an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ. The activated membrane-bound form interacts with AAK1 which promotes NOTCH1 stabilization. Forms a trimeric complex with FBXW7 and SGK1. Interacts with HIF1AN. HIF1AN negatively regulates the function of notch intracellular domain (NICD), accelerating myogenic differentiation By similarity. Interacts (via NICD) with SNAI1 (via zinc fingers); the interaction induces SNAI1 degradation via MDM2-mediated ubiquitination and inhibits SNAI1-induced cell invasion. Interacts (via NICD) with MDM2A. Ref.5 Ref.7 Ref.8 Ref.9 Ref.11 Ref.14 Ref.15 Ref.16 Ref.17
Subcellular location	Cell membrane; Single-pass type I membrane protein By similarity. Notch 1 intracellular domain: Nucleus By similarity. Note: Following proteolytical processing NICD is translocated to the nucleus By similarity.
Tissue specificity	In fetal tissues most abundant in spleen, brain stem and lung. Also present in most adult tissues where it is found mainly in lymphoid 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). Following endocytosis, 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. O-glycosylated on the EGF-like domains. Contains both O-linked fucose and O-linked glucose. Ref.10 Ubiquitinated; undergoes 'Lys-29'-linked polyubiquitination catalyzed by ITCH. Monoubiquitination at Lys-1759 is required for activation by gamma-secretase cleavage, it promotes interaction with AAK1, which stabilizes it. Deubiquitination by EIF3F is necessary for nuclear import of activated Notch. Ref.12 Hydroxylated at Asn-1955 by HIF1AN. Hydroxylated at Asn-2022 by HIF1AN By similarity. Hydroxylation reduces affinity for HI1AN and may thus indirectly modulate negative regulation of NICD By similarity.
Involvement in disease	Aortic valve disease 1 (AOVD1) [MIM:109730]: A common defect in the aortic valve in which two rather than three leaflets are present. It is often associated with aortic valve calcification, stenosis and insufficiency. In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.22
Sequence similarities	Belongs to the NOTCH family. Contains 5 ANK repeats. Contains 36 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
Domain	ANK repeat EGF-like domain Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium Metal-binding
Molecular function	Activator Developmental protein Receptor
PTM	Disulfide bond Glycoprotein Hydroxylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	Notch receptor processing Traceable author statement. Source: Reactome Notch signaling involved in heart development Inferred from mutant phenotype Ref.22PubMed 17662764. Source: BHF-UCL Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation Inferred from electronic annotation. Source: Compara anagen Inferred from electronic annotation. Source: Compara aortic valve morphogenesis Inferred from mutant phenotype Ref.22PubMed 17662764. Source: BHF-UCL arterial endothelial cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL atrioventricular node development Inferred from electronic annotation. Source: Compara atrioventricular valve morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL auditory receptor cell fate commitment Inferred from electronic annotation. Source: Compara axonogenesis Inferred from electronic annotation. Source: Compara branching morphogenesis of an epithelial tube Inferred from electronic annotation. Source: Compara cardiac chamber formation Inferred from sequence or structural similarity. Source: BHF-UCL cardiac left ventricle morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL cardiac muscle cell proliferation Inferred from electronic annotation. Source: Compara cardiac right atrium morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL cardiac right ventricle formation Inferred from electronic annotation. Source: Compara cardiac vascular smooth muscle cell development Inferred from sequence or structural similarity. Source: BHF-UCL cell fate specification Inferred from electronic annotation. Source: Compara cell migration involved in endocardial cushion formation Inferred from sequence or structural similarity. Source: BHF-UCL cellular response to follicle-stimulating hormone stimulus Inferred from direct assay PubMed 20613903. Source: BHF-UCL collecting duct development Inferred from electronic annotation. Source: Compara compartment pattern specification Inferred from electronic annotation. Source: Compara coronary artery morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL coronary vein morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL distal tubule development Inferred from electronic annotation. Source: Compara embryonic hindlimb morphogenesis Inferred from electronic annotation. Source: Compara endocardial cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL endocardium morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL endoderm development Inferred from electronic annotation. Source: Compara epithelial to mesenchymal transition involved in endocardial cushion formation Inferred from sequence or structural similarity. Source: BHF-UCL forebrain development Inferred from electronic annotation. Source: Compara foregut morphogenesis Inferred from electronic annotation. Source: Compara glial cell differentiation Inferred from electronic annotation. Source: Compara glomerular mesangial cell development Inferred from electronic annotation. Source: Compara growth involved in heart morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL hair follicle morphogenesis Inferred from electronic annotation. Source: Compara heart looping Inferred from sequence or structural similarity. Source: BHF-UCL humoral immune response Inferred from electronic annotation. Source: Compara immune response Non-traceable author statement Ref.3. Source: UniProtKB in utero embryonic development Inferred from electronic annotation. Source: Compara inflammatory response to antigenic stimulus Inferred from electronic annotation. Source: Compara interleukin-4 secretion Inferred from electronic annotation. Source: Compara keratinocyte differentiation Inferred from electronic annotation. Source: Compara left/right axis specification Inferred from electronic annotation. Source: Compara liver development Inferred from electronic annotation. Source: Compara lung development Inferred from electronic annotation. Source: Compara mitral valve formation Inferred from mutant phenotype Ref.22. Source: BHF-UCL negative regulation of BMP signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of anoikis Inferred from mutant phenotype PubMed 17984306. Source: BHF-UCL negative regulation of calcium ion-dependent exocytosis Inferred from electronic annotation. Source: Compara negative regulation of canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of cell-substrate adhesion Inferred from direct assay PubMed 16501043. Source: BHF-UCL negative regulation of glial cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of myoblast differentiation Inferred from mutant phenotype Ref.8. Source: UniProtKB negative regulation of myotube differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of oligodendrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of ossification Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of osteoblast differentiation Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of photoreceptor cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of pro-B cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of stem cell differentiation Inferred from mutant phenotype PubMed 19682396. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB neural tube development Inferred from electronic annotation. Source: Compara neuronal stem cell maintenance Inferred from expression pattern PubMed 19682396. Source: UniProtKB pericardium morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of BMP signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of JAK-STAT cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of astrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cardiac muscle cell proliferation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of cell migration Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of epithelial cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of epithelial to mesenchymal transition Inferred from mutant phenotype PubMed 17984306. Source: BHF-UCL positive regulation of keratinocyte differentiation Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter in response to hypoxia Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription of Notch receptor target Inferred from sequence or structural similarity. Source: BHF-UCL prostate gland epithelium morphogenesis Inferred from electronic annotation. Source: Compara pulmonary valve morphogenesis Inferred from mutant phenotype Ref.22. Source: BHF-UCL regulation of epithelial cell proliferation involved in prostate gland development Inferred from electronic annotation. Source: Compara regulation of extracellular matrix assembly Inferred from sequence or structural similarity. Source: BHF-UCL regulation of somitogenesis Inferred from electronic annotation. Source: Compara regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL response to muramyl dipeptide Inferred from electronic annotation. Source: Compara secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development Inferred from electronic annotation. Source: Compara somatic stem cell division Inferred from electronic annotation. Source: Compara sprouting angiogenesis Inferred from electronic annotation. Source: Compara transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome vasculogenesis involved in coronary vascular morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL venous endothelial cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL ventricular septum morphogenesis Inferred from mutant phenotype Ref.22. Source: BHF-UCL ventricular trabecula myocardium morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	Golgi membrane Traceable author statement. Source: Reactome MAML1-RBP-Jkappa- ICN1 complex Inferred from direct assay PubMed 16510869. Source: UniProtKB cell surface Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome endoplasmic reticulum membrane Traceable author statement. Source: Reactome extracellular region Traceable author statement. Source: Reactome integral to membrane Non-traceable author statement. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome plasma membrane Traceable author statement. Source: Reactome
Molecular_function	RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription Inferred from sequence or structural similarity. Source: BHF-UCL calcium ion binding Inferred from electronic annotation. Source: InterPro chromatin DNA binding Inferred from electronic annotation. Source: Compara core promoter binding Inferred from sequence or structural similarity. Source: UniProtKB enzyme binding Inferred from sequence or structural similarity. Source: UniProtKB enzyme inhibitor activity Inferred from sequence or structural similarity. Source: UniProtKB receptor activity Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PIN1	Q13526	9	EBI-636374,EBI-714158
RBPJ	Q06330	2	EBI-636374,EBI-632552
SNW1	Q13573	3	EBI-636374,EBI-632715

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Chain

19 – 2555

2537

Neurogenic locus notch homolog protein 1

PRO_0000007674

Chain

1721 – 2555

835

Notch 1 extracellular truncation By similarity

PRO_0000007675

Chain

1754 – 2555

802

Notch 1 intracellular domain By similarity

PRO_0000007676

Regions

Topological domain

19 – 1735

1717

Extracellular Potential

Transmembrane

1736 – 1756

21

Helical; Potential

Topological domain

1757 – 2555

799

Cytoplasmic Potential

Domain

20 – 58

39

EGF-like 1

Domain

59 – 99

41

EGF-like 2

Domain

102 – 139

38

EGF-like 3

Domain

140 – 176

37

EGF-like 4

Domain

178 – 216

39

EGF-like 5; calcium-binding Potential

Domain

218 – 255

38

EGF-like 6

Domain

257 – 293

37

EGF-like 7; calcium-binding Potential

Domain

295 – 333

39

EGF-like 8; calcium-binding Potential

Domain

335 – 371

37

EGF-like 9; calcium-binding Potential

Domain

372 – 410

39

EGF-like 10

Domain

412 – 450

39

EGF-like 11; calcium-binding Potential

Domain

452 – 488

37

EGF-like 12; calcium-binding Potential

Domain

490 – 526

37

EGF-like 13; calcium-binding Potential

Domain

528 – 564

37

EGF-like 14; calcium-binding Potential

Domain

566 – 601

36

EGF-like 15; calcium-binding Potential

Domain

603 – 639

37

EGF-like 16; calcium-binding Potential

Domain

641 – 676

36

EGF-like 17; calcium-binding Potential

Domain

678 – 714

37

EGF-like 18; calcium-binding Potential

Domain

716 – 751

36

EGF-like 19; calcium-binding Potential

Domain

753 – 789

37

EGF-like 20

Domain

791 – 827

37

EGF-like 21; calcium-binding Potential

Domain

829 – 867

39

EGF-like 22

Domain

869 – 905

37

EGF-like 23; calcium-binding Potential

Domain

907 – 943

37

EGF-like 24

Domain

945 – 981

37

EGF-like 25; calcium-binding Potential

Domain

983 – 1019

37

EGF-like 26

Domain

1021 – 1057

37

EGF-like 27

Domain

1059 – 1095

37

EGF-like 28

Domain

1097 – 1143

47

EGF-like 29

Domain

1145 – 1181

37

EGF-like 30

Domain

1183 – 1219

37

EGF-like 31; calcium-binding Potential

Domain

1221 – 1265

45

EGF-like 32; calcium-binding Potential

Domain

1267 – 1305

39

EGF-like 33

Domain

1307 – 1346

40

EGF-like 34

Domain

1348 – 1384

37

EGF-like 35

Domain

1387 – 1426

40

EGF-like 36

Repeat

1449 – 1489

41

LNR 1

Repeat

1490 – 1531

42

LNR 2

Repeat

1532 – 1571

40

LNR 3

Repeat

1927 – 1956

30

ANK 1

Repeat

1960 – 1990

31

ANK 2

Repeat

1994 – 2023

30

ANK 3

Repeat

2027 – 2056

30

ANK 4

Repeat

2060 – 2089

30

ANK 5

Region

1947 – 1955

9

HIF1AN-binding By similarity

Region

2014 – 2022

9

HIF1AN-binding By similarity

Compositional bias

1575 – 1578

4

Poly-Val

Compositional bias

1661 – 1664

4

Poly-Arg

Compositional bias

1728 – 1731

4

Poly-Pro

Compositional bias

1740 – 1743

4

Poly-Ala

Compositional bias

1901 – 1904

4

Poly-Glu

Compositional bias

2259 – 2262

4

Poly-Gly

Compositional bias

2403 – 2406

4

Poly-Gln

Compositional bias

2410 – 2417

8

Poly-Pro

Compositional bias

2521 – 2524

4

Poly-Ser

Sites

Metal binding

1457

1

Calcium; via carbonyl oxygen

Metal binding

1460

1

Calcium

Metal binding

1475

1

Calcium

Metal binding

1478

1

Calcium

Site

1664 – 1665

2

Cleavage; by furin-like protease By similarity

Amino acid modifications

Modified residue

1955

1

(3S)-3-hydroxyasparagine; by HIF1AN; partial Ref.5

Modified residue

2022

1

(3S)-3-hydroxyasparagine; by HIF1AN By similarity

Glycosylation

41

1

N-linked (GlcNAc...) Potential

Glycosylation

959

1

N-linked (GlcNAc...) Potential

Glycosylation

1179

1

N-linked (GlcNAc...) Potential

Glycosylation

1241

1

N-linked (GlcNAc...) Potential

Glycosylation

1489

1

N-linked (GlcNAc...) Potential

Glycosylation

1587

1

N-linked (GlcNAc...) Potential

Disulfide bond

24 ↔ 37

By similarity

Disulfide bond

31 ↔ 46

By similarity

Disulfide bond

48 ↔ 57

By similarity

Disulfide bond

63 ↔ 74

By similarity

Disulfide bond

68 ↔ 87

By similarity

Disulfide bond

89 ↔ 98

By similarity

Disulfide bond

106 ↔ 117

By similarity

Disulfide bond

111 ↔ 127

By similarity

Disulfide bond

129 ↔ 138

By similarity

Disulfide bond

144 ↔ 155

By similarity

Disulfide bond

149 ↔ 164

By similarity

Disulfide bond

166 ↔ 175

By similarity

Disulfide bond

182 ↔ 195

By similarity

Disulfide bond

189 ↔ 204

By similarity

Disulfide bond

206 ↔ 215

By similarity

Disulfide bond

222 ↔ 233

By similarity

Disulfide bond

227 ↔ 243

By similarity

Disulfide bond

245 ↔ 254

By similarity

Disulfide bond

261 ↔ 272

By similarity

Disulfide bond

266 ↔ 281

By similarity

Disulfide bond

283 ↔ 292

By similarity

Disulfide bond

299 ↔ 312

By similarity

Disulfide bond

306 ↔ 321

By similarity

Disulfide bond

323 ↔ 332

By similarity

Disulfide bond

339 ↔ 350

By similarity

Disulfide bond

344 ↔ 359

By similarity

Disulfide bond

361 ↔ 370

By similarity

Disulfide bond

376 ↔ 387

By similarity

Disulfide bond

381 ↔ 398

By similarity

Disulfide bond

400 ↔ 409

By similarity

Disulfide bond

416 ↔ 429

By similarity

Disulfide bond

423 ↔ 438

By similarity

Disulfide bond

440 ↔ 449

By similarity

Disulfide bond

456 ↔ 467

By similarity

Disulfide bond

461 ↔ 476

By similarity

Disulfide bond

478 ↔ 487

By similarity

Disulfide bond

494 ↔ 505

By similarity

Disulfide bond

499 ↔ 514

By similarity

Disulfide bond

516 ↔ 525

By similarity

Disulfide bond

532 ↔ 543

By similarity

Disulfide bond

537 ↔ 552

By similarity

Disulfide bond

554 ↔ 563

By similarity

Disulfide bond

570 ↔ 580

By similarity

Disulfide bond

575 ↔ 589

By similarity

Disulfide bond

591 ↔ 600

By similarity

Disulfide bond

607 ↔ 618

By similarity

Disulfide bond

612 ↔ 627

By similarity

Disulfide bond

629 ↔ 638

By similarity

Disulfide bond

645 ↔ 655

By similarity

Disulfide bond

650 ↔ 664

By similarity

Disulfide bond

666 ↔ 675

By similarity

Disulfide bond

682 ↔ 693

By similarity

Disulfide bond

687 ↔ 702

By similarity

Disulfide bond

704 ↔ 713

By similarity

Disulfide bond

720 ↔ 730

By similarity

Disulfide bond

725 ↔ 739

By similarity

Disulfide bond

741 ↔ 750

By similarity

Disulfide bond

757 ↔ 768

By similarity

Disulfide bond

762 ↔ 777

By similarity

Disulfide bond

779 ↔ 788

By similarity

Disulfide bond

795 ↔ 806

By similarity

Disulfide bond

800 ↔ 815

By similarity

Disulfide bond

817 ↔ 826

By similarity

Disulfide bond

833 ↔ 844

By similarity

Disulfide bond

838 ↔ 855

By similarity

Disulfide bond

857 ↔ 866

By similarity

Disulfide bond

873 ↔ 884

By similarity

Disulfide bond

878 ↔ 893

By similarity

Disulfide bond

895 ↔ 904

By similarity

Disulfide bond

911 ↔ 922

By similarity

Disulfide bond

916 ↔ 931

By similarity

Disulfide bond

933 ↔ 942

By similarity

Disulfide bond

949 ↔ 960

By similarity

Disulfide bond

954 ↔ 969

By similarity

Disulfide bond

971 ↔ 980

By similarity

Disulfide bond

987 ↔ 998

By similarity

Disulfide bond

992 ↔ 1007

By similarity

Disulfide bond

1009 ↔ 1018

By similarity

Disulfide bond

1025 ↔ 1036

By similarity

Disulfide bond

1030 ↔ 1045

By similarity

Disulfide bond

1047 ↔ 1056

By similarity

Disulfide bond

1063 ↔ 1074

By similarity

Disulfide bond

1068 ↔ 1083

By similarity

Disulfide bond

1085 ↔ 1094

By similarity

Disulfide bond

1101 ↔ 1122

By similarity

Disulfide bond

1116 ↔ 1131

By similarity

Disulfide bond

1133 ↔ 1142

By similarity

Disulfide bond

1149 ↔ 1160

By similarity

Disulfide bond

1154 ↔ 1169

By similarity

Disulfide bond

1171 ↔ 1180

By similarity

Disulfide bond

1187 ↔ 1198

By similarity

Disulfide bond

1192 ↔ 1207

By similarity

Disulfide bond

1209 ↔ 1218

By similarity

Disulfide bond

1225 ↔ 1244

By similarity

Disulfide bond

1238 ↔ 1253

By similarity

Disulfide bond

1255 ↔ 1264

By similarity

Disulfide bond

1271 ↔ 1284

By similarity

Disulfide bond

1276 ↔ 1293

By similarity

Disulfide bond

1295 ↔ 1304

By similarity

Disulfide bond

1311 ↔ 1322

By similarity

Disulfide bond

1316 ↔ 1334

By similarity

Disulfide bond

1336 ↔ 1345

By similarity

Disulfide bond

1352 ↔ 1363

By similarity

Disulfide bond

1357 ↔ 1372

By similarity

Disulfide bond

1374 ↔ 1383

By similarity

Disulfide bond

1391 ↔ 1403

By similarity

Disulfide bond

1397 ↔ 1414

By similarity

Disulfide bond

1416 ↔ 1425

By similarity

Disulfide bond

1449 ↔ 1472

Ref.18

Disulfide bond

1454 ↔ 1467

Ref.18

Disulfide bond

1463 ↔ 1479

Ref.18

Disulfide bond

1490 ↔ 1514

By similarity

Disulfide bond

1496 ↔ 1509

By similarity

Disulfide bond

1505 ↔ 1521

By similarity

Disulfide bond

1536 ↔ 1549

By similarity

Disulfide bond

1545 ↔ 1561

By similarity

Cross-link

1759

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Natural variant

300

1

Q → R.
Corresponds to variant rs11574885 [ dbSNP | Ensembl ].

VAR_034898

Natural variant

879

1

R → W.
Corresponds to variant rs11574895 [ dbSNP | Ensembl ].

VAR_048990

Natural variant

1671

1

V → I.
Corresponds to variant rs2229968 [ dbSNP | Ensembl ].

VAR_046618

Experimental info

Sequence conflict

187

1

G → R in AAG33848. Ref.1

Sequence conflict

187

1

G → R in AAA60614. Ref.3

Sequence conflict

282

1

R → P in AAG33848. Ref.1

Sequence conflict

282

1

R → P in AAA60614. Ref.3

Sequence conflict

477

1

I → M in AAG33848. Ref.1

Sequence conflict

477

1

I → M in AAA60614. Ref.3

Sequence conflict

614 – 615

2

HG → LR in AAG33848. Ref.1

Sequence conflict

614 – 615

2

HG → LR in AAA60614. Ref.3

Sequence conflict

621

1

R → P in AAG33848. Ref.1

Sequence conflict

621

1

R → P in AAA60614. Ref.3

Sequence conflict

677

1

I → S in AAG33848. Ref.1

Sequence conflict

677

1

I → S in AAA60614. Ref.3

Sequence conflict

775

1

Y → I in AAG33848. Ref.1

Sequence conflict

775

1

Y → I in AAA60614. Ref.3

Sequence conflict

803

1

Q → K in AAG33848. Ref.1

Sequence conflict

803

1

Q → K in AAA60614. Ref.3

Sequence conflict

860 – 862

3

GWQ → AGAK in AAG33848. Ref.1

Sequence conflict

860 – 862

3

GWQ → AGAK in AAA60614. Ref.3

Sequence conflict

1021

1

D → V in AAG33848. Ref.1

Sequence conflict

1021

1

D → V in AAA60614. Ref.3

Sequence conflict

1028

1

Q → R in AAG33848. Ref.1

Sequence conflict

1028

1

Q → R in AAA60614. Ref.3

Sequence conflict

1032

1

H → L in AAG33848. Ref.1

Sequence conflict

1032

1

H → L in AAA60614. Ref.3

Sequence conflict

1040 – 1043

4

CGSY → RGLH in AAG33848. Ref.1

Sequence conflict

1040 – 1043

4

CGSY → RGLH in AAA60614. Ref.3

Secondary structure

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2555

Helix Strand Turn

Details...

Turn

415 – 417

3

Beta strand

418 – 420

3

Beta strand

422 – 424

3

Beta strand

428 – 431

4

Beta strand

433 – 439

7

Beta strand

444 – 446

3

Turn

455 – 458

4

Beta strand

466 – 469

4

Beta strand

474 – 477

4

Beta strand

482 – 487

6

Turn

493 – 496

4

Turn

500 – 502

3

Beta strand

504 – 507

4

Beta strand

512 – 515

4

Beta strand

520 – 525

6

Helix

1448 – 1450

3

Helix

1452 – 1457

6

Beta strand

1460 – 1462

3

Helix

1465 – 1467

3

Helix

1470 – 1472

3

Helix

1473 – 1476

4

Turn

1477 – 1482

6

Turn

1486 – 1489

4

Helix

1492 – 1494

3

Helix

1496 – 1498

3

Turn

1499 – 1501

3

Beta strand

1502 – 1504

3

Helix

1507 – 1509

3

Helix

1512 – 1519

8

Turn

1530 – 1532

3

Helix

1533 – 1539

7

Beta strand

1542 – 1544

3

Helix

1547 – 1549

3

Helix

1552 – 1559

8

Beta strand

1563 – 1565

3

Beta strand

1571 – 1580

10

Helix

1582 – 1587

6

Helix

1589 – 1600

12

Beta strand

1602 – 1606

5

Beta strand

1616 – 1620

5

Beta strand

1672 – 1681

10

Helix

1685 – 1688

4

Helix

1696 – 1708

13

Beta strand

1714 – 1716

3

Beta strand

1718 – 1724

7

Helix

1884 – 1890

7

Helix

1909 – 1914

6

Turn

1925 – 1927

3

Helix

1931 – 1937

7

Helix

1941 – 1949

9

Helix

1964 – 1970

7

Helix

1974 – 1982

9

Beta strand

1983 – 1985

3

Helix

1998 – 2005

8

Helix

2008 – 2016

9

Helix

2031 – 2037

7

Helix

2041 – 2049

9

Helix

2064 – 2071

8

Helix

2074 – 2082

9

Helix

2097 – 2103

7

Helix

2107 – 2115

9

Sequences

	Sequence		Length	Mass (Da)
	P46531 [UniParc]. Last modified September 23, 2008. Version 4. Checksum: E173C872D195F028	FASTA	2,555	272,505
	10 20 30 40 50 60 MPPLLAPLLC LALLPALAAR GPRCSQPGET CLNGGKCEAA NGTEACVCGG AFVGPRCQDP 70 80 90 100 110 120 NPCLSTPCKN AGTCHVVDRR GVADYACSCA LGFSGPLCLT PLDNACLTNP CRNGGTCDLL 130 140 150 160 170 180 TLTEYKCRCP PGWSGKSCQQ ADPCASNPCA NGGQCLPFEA SYICHCPPSF HGPTCRQDVN 190 200 210 220 230 240 ECGQKPGLCR HGGTCHNEVG SYRCVCRATH TGPNCERPYV PCSPSPCQNG GTCRPTGDVT 250 260 270 280 290 300 HECACLPGFT GQNCEENIDD CPGNNCKNGG ACVDGVNTYN CRCPPEWTGQ YCTEDVDECQ 310 320 330 340 350 360 LMPNACQNGG TCHNTHGGYN CVCVNGWTGE DCSENIDDCA SAACFHGATC HDRVASFYCE 370 380 390 400 410 420 CPHGRTGLLC HLNDACISNP CNEGSNCDTN PVNGKAICTC PSGYTGPACS QDVDECSLGA 430 440 450 460 470 480 NPCEHAGKCI NTLGSFECQC LQGYTGPRCE IDVNECVSNP CQNDATCLDQ IGEFQCICMP 490 500 510 520 530 540 GYEGVHCEVN TDECASSPCL HNGRCLDKIN EFQCECPTGF TGHLCQYDVD ECASTPCKNG 550 560 570 580 590 600 AKCLDGPNTY TCVCTEGYTG THCEVDIDEC DPDPCHYGSC KDGVATFTCL CRPGYTGHHC 610 620 630 640 650 660 ETNINECSSQ PCRHGGTCQD RDNAYLCFCL KGTTGPNCEI NLDDCASSPC DSGTCLDKID 670 680 690 700 710 720 GYECACEPGY TGSMCNINID ECAGNPCHNG GTCEDGINGF TCRCPEGYHD PTCLSEVNEC 730 740 750 760 770 780 NSNPCVHGAC RDSLNGYKCD CDPGWSGTNC DINNNECESN PCVNGGTCKD MTSGYVCTCR 790 800 810 820 830 840 EGFSGPNCQT NINECASNPC LNQGTCIDDV AGYKCNCLLP YTGATCEVVL APCAPSPCRN 850 860 870 880 890 900 GGECRQSEDY ESFSCVCPTG WQGQTCEVDI NECVLSPCRH GASCQNTHGG YRCHCQAGYS 910 920 930 940 950 960 GRNCETDIDD CRPNPCHNGG SCTDGINTAF CDCLPGFRGT FCEEDINECA SDPCRNGANC 970 980 990 1000 1010 1020 TDCVDSYTCT CPAGFSGIHC ENNTPDCTES SCFNGGTCVD GINSFTCLCP PGFTGSYCQH 1030 1040 1050 1060 1070 1080 DVNECDSQPC LHGGTCQDGC GSYRCTCPQG YTGPNCQNLV HWCDSSPCKN GGKCWQTHTQ 1090 1100 1110 1120 1130 1140 YRCECPSGWT GLYCDVPSVS CEVAAQRQGV DVARLCQHGG LCVDAGNTHH CRCQAGYTGS 1150 1160 1170 1180 1190 1200 YCEDLVDECS PSPCQNGATC TDYLGGYSCK CVAGYHGVNC SEEIDECLSH PCQNGGTCLD 1210 1220 1230 1240 1250 1260 LPNTYKCSCP RGTQGVHCEI NVDDCNPPVD PVSRSPKCFN NGTCVDQVGG YSCTCPPGFV 1270 1280 1290 1300 1310 1320 GERCEGDVNE CLSNPCDARG TQNCVQRVND FHCECRAGHT GRRCESVING CKGKPCKNGG 1330 1340 1350 1360 1370 1380 TCAVASNTAR GFICKCPAGF EGATCENDAR TCGSLRCLNG GTCISGPRSP TCLCLGPFTG 1390 1400 1410 1420 1430 1440 PECQFPASSP CLGGNPCYNQ GTCEPTSESP FYRCLCPAKF NGLLCHILDY SFGGGAGRDI 1450 1460 1470 1480 1490 1500 PPPLIEEACE LPECQEDAGN KVCSLQCNNH ACGWDGGDCS LNFNDPWKNC TQSLQCWKYF 1510 1520 1530 1540 1550 1560 SDGHCDSQCN SAGCLFDGFD CQRAEGQCNP LYDQYCKDHF SDGHCDQGCN SAECEWDGLD 1570 1580 1590 1600 1610 1620 CAEHVPERLA AGTLVVVVLM PPEQLRNSSF HFLRELSRVL HTNVVFKRDA HGQQMIFPYY 1630 1640 1650 1660 1670 1680 GREEELRKHP IKRAAEGWAA PDALLGQVKA SLLPGGSEGG RRRRELDPMD VRGSIVYLEI 1690 1700 1710 1720 1730 1740 DNRQCVQASS QCFQSATDVA AFLGALASLG SLNIPYKIEA VQSETVEPPP PAQLHFMYVA 1750 1760 1770 1780 1790 1800 AAAFVLLFFV GCGVLLSRKR RRQHGQLWFP EGFKVSEASK KKRREPLGED SVGLKPLKNA 1810 1820 1830 1840 1850 1860 SDGALMDDNQ NEWGDEDLET KKFRFEEPVV LPDLDDQTDH RQWTQQHLDA ADLRMSAMAP 1870 1880 1890 1900 1910 1920 TPPQGEVDAD CMDVNVRGPD GFTPLMIASC SGGGLETGNS EEEEDAPAVI SDFIYQGASL 1930 1940 1950 1960 1970 1980 HNQTDRTGET ALHLAARYSR SDAAKRLLEA SADANIQDNM GRTPLHAAVS ADAQGVFQIL 1990 2000 2010 2020 2030 2040 IRNRATDLDA RMHDGTTPLI LAARLAVEGM LEDLINSHAD VNAVDDLGKS ALHWAAAVNN 2050 2060 2070 2080 2090 2100 VDAAVVLLKN GANKDMQNNR EETPLFLAAR EGSYETAKVL LDHFANRDIT DHMDRLPRDI 2110 2120 2130 2140 2150 2160 AQERMHHDIV RLLDEYNLVR SPQLHGAPLG GTPTLSPPLC SPNGYLGSLK PGVQGKKVRK 2170 2180 2190 2200 2210 2220 PSSKGLACGS KEAKDLKARR KKSQDGKGCL LDSSGMLSPV DSLESPHGYL SDVASPPLLP 2230 2240 2250 2260 2270 2280 SPFQQSPSVP LNHLPGMPDT HLGIGHLNVA AKPEMAALGG GGRLAFETGP PRLSHLPVAS 2290 2300 2310 2320 2330 2340 GTSTVLGSSS GGALNFTVGG STSLNGQCEW LSRLQSGMVP NQYNPLRGSV APGPLSTQAP 2350 2360 2370 2380 2390 2400 SLQHGMVGPL HSSLAASALS QMMSYQGLPS TRLATQPHLV QTQQVQPQNL QMQQQNLQPA 2410 2420 2430 2440 2450 2460 NIQQQQSLQP PPPPPQPHLG VSSAASGHLG RSFLSGEPSQ ADVQPLGPSS LAVHTILPQE 2470 2480 2490 2500 2510 2520 SPALPTSLPS SLVPPVTAAQ FLTPPSQHSY SSPVDNTPSH QLQVPEHPFL TPSPESPDQW 2530 2540 2550 SSSSPHSNVS DWSEGVSSPP TSMQSQIARI PEAFK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete human notch 1 (hN1) cDNA sequence." Mann R.S., Blaumueller C.M., Zagouras P. Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms." Ellisen L.W., Bird J., West D.C., Soreng A.L., Reynolds T.C., Smith S.D., Sklar J. Cell 66:649-661(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-2443.
[4]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 489-2555. Tissue: Aortic endothelium.
[5]	"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: PROTEIN SEQUENCE OF 1947-1962, INTERACTION WITH HIF1AN, HYDROXYLATION AT ASN-1955, MASS SPECTROMETRY.
[6]	"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.
[7]	"Human deltex is a conserved regulator of Notch signalling." Matsuno K., Eastman D., Mitsiades T., Quinn A.M., Carcanciu M.L., Ordentlich P., Kadesch T., Artavanis-Tsakonas S. Nat. Genet. 19:74-78(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DTX1.
[8]	"SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function." Zhou S., Fujimuro M., Hsieh J.J., Chen L., Miyamoto A., Weinmaster G., Hayward S.D. Mol. Cell. Biol. 20:2400-2410(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SNW1.
[9]	"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.
[10]	"Mammalian Notch1 is modified with two unusual forms of O-linked glycosylation found on epidermal growth factor-like modules." Moloney D.J., Shair L.H., Lu F.M., Xia J., Locke R., Matta K.L., Haltiwanger R.S. J. Biol. Chem. 275:9604-9611(2000) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION.
[11]	"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.
[12]	"AIP4/Itch regulates Notch receptor degradation in the absence of ligand." Chastagner P., Israel A., Brou C. PLoS ONE 3:E2735-E2735(2008) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION BY ITCH.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[14]	"Notch1 binds and induces degradation of Snail in hepatocellular carcinoma." Lim S.O., Kim H.S., Quan X., Ahn S.M., Kim H., Hsieh D., Seong J.K., Jung G. BMC Biol. 9:83-83(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SNAI1 AND MDM2A.
[15]	"The adaptor-associated kinase 1, AAK1, is a positive regulator of the Notch pathway." Gupta-Rossi N., Ortica S., Meas-Yedid V., Heuss S., Moretti J., Olivo-Marin J.C., Israel A. J. Biol. Chem. 286:18720-18730(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AAK1.
[16]	"Serum- and glucocorticoid-inducible kinase 1 (SGK1) controls Notch1 signaling by downregulation of protein stability through Fbw7 ubiquitin ligase." Mo J.S., Ann E.J., Yoon J.H., Jung J., Choi Y.H., Kim H.Y., Ahn J.S., Kim S.M., Kim M.Y., Hong J.A., Seo M.S., Lang F., Choi E.J., Park H.S. J. Cell Sci. 124:100-112(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SGK1 AND FBXW7.
[17]	"Assembly of a Notch transcriptional activation complex requires multimerization." Vasquez-Del Carpio R., Kaplan F.M., Weaver K.L., VanWye J.D., Alves-Guerra M.C., Robbins D.J., Capobianco A.J. Mol. Cell. Biol. 31:1396-1408(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SNW1.
[18]	"Nuclear magnetic resonance structure of a prototype Lin12-Notch repeat module from human Notch1." Vardar D., North C.L., Sanchez-Irizarry C., Aster J.C., Blacklow S.C. Biochemistry 42:7061-7067(2003) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1446-1480 IN COMPLEX WITH CALCIUM IONS, DISULFIDE BONDS.
[19]	"Structural and functional properties of the human notch-1 ligand binding region." Hambleton S., Valeyev N.V., Muranyi A., Knott V., Werner J.M., McMichael A.J., Handford P.A., Downing A.K. Structure 12:2173-2183(2004) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 411-526.
[20]	"High-resolution crystal structure of the human Notch 1 ankyrin domain." Ehebauer M.T., Chirgadze D.Y., Hayward P., Martinez Arias A., Blundell T.L. Biochem. J. 392:13-20(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1872-2114.
[21]	"Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes." Nam Y., Sliz P., Song L., Aster J.C., Blacklow S.C. Cell 124:973-983(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 1872-2126 IN COMPLEX WITH RBPSUH AND MAML1.
[22]	"Mutations in NOTCH1 cause aortic valve disease." Garg V., Muth A.N., Ransom J.F., Schluterman M.K., Barnes R., King I.N., Grossfeld P.D., Srivastava D. Nature 437:270-274(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN AOVD1.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF308602 mRNA. Translation: AAG33848.1.
AL592301, AL354671 Genomic DNA. Translation: CAI13934.1.
AL354671, AL592301 Genomic DNA. Translation: CAI16149.1.
M73980 mRNA. Translation: AAA60614.1.
AB209873 mRNA. Translation: BAD93110.1.

IPI

IPI00412982.

PIR

A40043.

RefSeq

NP_060087.3. NM_017617.3.

UniGene

Hs.495473.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PB5	NMR	-	A	1446-1480	[»]
1TOZ	NMR	-	A	411-526	[»]
1YYH	X-ray	1.90	A/B	1872-2114	[»]
2F8X	X-ray	3.25	K	1872-2126	[»]
2F8Y	X-ray	1.55	A/B	1905-2126	[»]
2HE0	X-ray	1.90	A/B	1873-2114	[»]
2VJ3	X-ray	2.60	A	411-526	[»]
3ETO	X-ray	2.00	A/B	1447-1733	[»]
3I08	X-ray	3.20	A/C	1446-1664	[»]
			B/D	1665-1733	[»]
3L95	X-ray	2.19	X/Y	1448-1728	[»]
3NBN	X-ray	3.45	B/E	1872-2126	[»]
3V79	X-ray	3.85	K	1872-2126	[»]
			R	1759-1777	[»]

ProteinModelPortal

P46531.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29919N.

IntAct

P46531. 15 interactions.

MINT

MINT-1417018.

STRING

9606.ENSP00000277541.

PTM databases

PhosphoSite

P46531.

Polymorphism databases

DMDM

206729936.

Proteomic databases

PaxDb

P46531.

PRIDE

P46531.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000277541; ENSP00000277541; ENSG00000148400.

GeneID

4851.

KEGG

hsa:4851.

UCSC

uc004chz.3. human.

Organism-specific databases

CTD

4851.

GeneCards

GC09M139388.

H-InvDB

HIX0008549.

HGNC

HGNC:7881. NOTCH1.

HPA

CAB008112.
CAB022466.

MIM

109730. phenotype.
190198. gene.

neXtProt

NX_P46531.

Orphanet

1244. Bicuspid aortic valve.

PharmGKB

PA31683.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0666.

HOGENOM

HOG000234369.

HOVERGEN

HBG052650.

KO

K02599.

OMA

HGGYNCV.

OrthoDB

EOG4HX504.

Enzyme and pathway databases

Pathway_Interaction_DB

ps1pathway. Presenilin action in Notch and Wnt signaling.

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.

SignaLink

P46531.

Gene expression databases

ArrayExpress

P46531.

Bgee

P46531.

CleanEx

HS_NOTCH1.

Genevestigator

P46531.

GermOnline

ENSG00000148400. 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.
IPR022362. Notch_1.
IPR000800. Notch_dom.
IPR010660. Notch_NOD_dom.
IPR011656. Notch_NODP_dom.
[Graphical view]

Pfam

PF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
PF11936. DUF3454. 1 hit.
PF00008. EGF. 23 hits.
PF07645. EGF_CA. 5 hits.
PF12661. hEGF. 1 hit.
PF06816. NOD. 1 hit.
PF07684. NODP. 1 hit.
PF00066. Notch. 3 hits.
[Graphical view]

PIRSF

PIRSF002279. Notch. 1 hit.

PRINTS

PR01452. LNOTCHREPEAT.
PR01984. NOTCH1.

SMART

SM00248. ANK. 6 hits.
SM00181. EGF. 12 hits.
SM00179. EGF_CA. 24 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. 22 hits.
PS00022. EGF_1. 35 hits.
PS01186. EGF_2. 27 hits.
PS50026. EGF_3. 36 hits.
PS01187. EGF_CA. 20 hits.
PS50258. LNR. 3 hits.
[Graphical view]

ProtoNet

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Other

EvolutionaryTrace

P46531.

GenomeRNAi

4851.

NextBio

18684.

SOURCE

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Entry information

Entry name

NOTC1_HUMAN

Accession

Primary (citable) accession number: P46531
Secondary accession number(s): Q59ED8, Q5SXM3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	September 23, 2008
Last modified:	May 29, 2013
This is version 165 of the entry and version 4 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.