Reviewed, UniProtKB/Swiss-Prot P46531 (NOTC1_HUMAN)

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- Recommended name:
            Notch 1 extracellular truncation
    2- Recommended name:
            Notch 1 intracellular domain

Gene names

Name:	NOTCH1
Synonyms:	TAN1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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 RBP-J kappa 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 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 RBPSUH. Also interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH1.
Subcellular location	Cell membrane; Single-pass type I membrane proteinBy similarity. Notch 1 intracellular domain: NucleusBy 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). 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.
Involvement in disease	NOTCH1 truncation is associated with T-cell acute lymphoblastic leukemia. Defects in NOTCH1 are a cause of aortic valve disease [MIM:109730]. The disorder consists of an early developmental defect in the aortic valve and a later de-repression of calcium deposition that causes progressive aortic valve disease. Calcification of the aortic valve is the third leading cause of heart disease in adults. The incidence increases with age, and it is often associated with a bicuspid aortic valve present in 1-2% of the population.
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
Ligand	Calcium Metal-binding
Molecular function	Activator Developmental protein Receptor
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	Notch signaling pathway Traceable author statement. Source: UniProtKB immune response Ref.3 Non-traceable author statement. Source: UniProtKB negative regulation of myoblast differentiation Inferred from mutant phenotype. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Non-traceable author statement. Source: UniProtKB nucleus Traceable author statement. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: UniProtKB receptor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RBPJ	Q06330	1	EBI-636374,EBI-632552
SNW1	Q13573	2	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	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
	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
	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