Reviewed,
UniProtKB/Swiss-Prot P46531 (NOTC1_HUMAN)
Last modified
November 25, 2008.
Version 109.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
Third-party data |
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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 |
| ||||
| 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
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 | |||||||||

Clusters with