Reviewed,
UniProtKB/Swiss-Prot Q04721 (NOTC2_HUMAN)
Last modified
November 25, 2008.
Version 105.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
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Names and origin
| Protein names | Recommended name: Neurogenic locus notch homolog protein 2 Short name=Notch 2 Short name=hN2 Cleaved into the following 2 chains: 1- Recommended name: Notch 2 extracellular truncation 2- Recommended name: Notch 2 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 | 2471 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 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 By similarity. Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH2. |
| Subcellular location | Cell membrane; Single-pass type I membrane protein. Notch 2 intracellular domain: Nucleus. Note= Following proteolytical processing NICD is translocated to the nucleus. |
| Tissue specificity | Expressed in the brain, heart, kidney, lung, skeletal muscle and liver. |
| 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 | Defects in NOTCH2 are the cause of Alagille syndrome type 2 (ALGS2) [MIM:610205]. Alagille syndrome is an autosomal dominant multisystem disorder defined clinically by hepatic bile duct paucity and cholestasis in association with cardiac, skeletal, and ophthalmologic manifestations. There are characteristic facial features and less frequent clinical involvement of the renal and vascular systems. |
| Sequence similarities | Belongs to the NOTCH family. Contains 6 ANK repeats. Contains 35 EGF-like domains. Contains 3 LNR (Lin/Notch) repeats. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 25 | 25 | Potential | ||||||||
| Chain | 26 – 2471 | 2446 | Neurogenic locus notch homolog protein 2 | PRO_0000007683 | |||||||
| Chain | 1666 – 2471 | 806 | Notch 2 extracellular truncation By similarity | PRO_0000007684 | |||||||
| Chain | 1697 – 2471 | 775 | Notch 2 intracellular domain By similarity | PRO_0000007685 | |||||||
Regions | |||||||||||
| Topological domain | 26 – 1677 | 1652 | Extracellular Potential | ||||||||
| Transmembrane | 1678 – 1698 | 21 | Potential | ||||||||
| Topological domain | 1699 – 2471 | 773 | Cytoplasmic Potential | ||||||||
| Domain | 26 – 63 | 38 | EGF-like 1 | ||||||||
| Domain | 64 – 102 | 39 | EGF-like 2 | ||||||||
| Domain | 105 – 143 | 39 | EGF-like 3 | ||||||||
| Domain | 144 – 180 | 37 | EGF-like 4 | ||||||||
| Domain | 182 – 219 | 38 | EGF-like 5; calcium-binding Potential | ||||||||
| Domain | 221 – 258 | 38 | EGF-like 6 | ||||||||
| Domain | 260 – 296 | 37 | EGF-like 7; calcium-binding Potential | ||||||||
| Domain | 298 – 336 | 39 | EGF-like 8; calcium-binding Potential | ||||||||
| Domain | 338 – 374 | 37 | EGF-like 9; calcium-binding Potential | ||||||||
| Domain | 375 – 413 | 39 | EGF-like 10 | ||||||||
| Domain | 415 – 454 | 40 | EGF-like 11; calcium-binding Potential | ||||||||
| Domain | 456 – 492 | 37 | EGF-like 12; calcium-binding Potential | ||||||||
| Domain | 494 – 530 | 37 | EGF-like 13; calcium-binding Potential | ||||||||
| Domain | 532 – 568 | 37 | EGF-like 14; calcium-binding Potential | ||||||||
| Domain | 570 – 605 | 36 | EGF-like 15; calcium-binding Potential | ||||||||
| Domain | 607 – 643 | 37 | EGF-like 16; calcium-binding Potential | ||||||||
| Domain | 645 – 680 | 36 | EGF-like 17; calcium-binding Potential | ||||||||
| Domain | 682 – 718 | 37 | EGF-like 18; calcium-binding Potential | ||||||||
| Domain | 720 – 755 | 36 | EGF-like 19 | ||||||||
| Domain | 757 – 793 | 37 | EGF-like 20; calcium-binding Potential | ||||||||
| Domain | 795 – 831 | 37 | EGF-like 21; calcium-binding Potential | ||||||||
| Domain | 833 – 871 | 39 | EGF-like 22 | ||||||||
| Domain | 873 – 909 | 37 | EGF-like 23; calcium-binding Potential | ||||||||
| Domain | 911 – 947 | 37 | EGF-like 24; calcium-binding Potential | ||||||||
| Domain | 949 – 985 | 37 | EGF-like 25; calcium-binding Potential | ||||||||
| Domain | 987 – 1023 | 37 | EGF-like 26; calcium-binding Potential | ||||||||
| Domain | 1025 – 1061 | 37 | EGF-like 27; calcium-binding Potential | ||||||||
| Domain | 1063 – 1099 | 37 | EGF-like 28 | ||||||||
| Domain | 1101 – 1147 | 47 | EGF-like 29 | ||||||||
| Domain | 1149 – 1185 | 37 | EGF-like 30; calcium-binding Potential | ||||||||
| Domain | 1187 – 1223 | 37 | EGF-like 31; calcium-binding Potential | ||||||||
| Domain | 1225 – 1262 | 38 | EGF-like 32; calcium-binding Potential | ||||||||
| Domain | 1264 – 1302 | 39 | EGF-like 33 | ||||||||
| Domain | 1304 – 1343 | 40 | EGF-like 34 | ||||||||
| Domain | 1374 – 1412 | 39 | EGF-like 35 | ||||||||
| Repeat | 1425 – 1465 | 41 | LNR 1 | ||||||||
| Repeat | 1466 – 1502 | 37 | LNR 2 | ||||||||
| Repeat | 1503 – 1544 | 42 | LNR 3 | ||||||||
| Repeat | 1827 – 1871 | 45 | ANK 1 | ||||||||
| Repeat | 1876 – 1905 | 30 | ANK 2 | ||||||||
| Repeat | 1909 – 1939 | 31 | ANK 3 | ||||||||
| Repeat | 1943 – 1972 | 30 | ANK 4 | ||||||||
| Repeat | 1976 – 2005 | 30 | ANK 5 | ||||||||
| Repeat | 2009 – 2038 | 30 | ANK 6 | ||||||||
| Region | 1425 – 1677 | 253 | Negative regulatory region (NRR) | ||||||||
| Compositional bias | 1645 – 1648 | 4 | Poly-Ala | ||||||||
| Compositional bias | 1994 – 1997 | 4 | Poly-Leu | ||||||||
| Compositional bias | 2426 – 2429 | 4 | Poly-Ser | ||||||||
Amino acid modifications | |||||||||||
| Modified residue | 1716 | 1 | Phosphothreonine | ||||||||
| Modified residue | 1778 | 1 | Phosphoserine | ||||||||
| Modified residue | 1802 | 1 | Phosphothreonine | ||||||||
| Modified residue | 1804 | 1 | Phosphoserine | ||||||||
| Modified residue | 1808 | 1 | Phosphothreonine | ||||||||
| Modified residue | 1841 | 1 | Phosphoserine | ||||||||
| Modified residue | 1842 | 1 | Phosphoserine | ||||||||
| Modified residue | 1845 | 1 | Phosphoserine | ||||||||
| Modified residue | 2070 | 1 | Phosphoserine | ||||||||
| Modified residue | 2074 | 1 | Phosphothreonine | ||||||||
| Modified residue | 2078 | 1 | Phosphoserine By similarity | ||||||||
| Modified residue | 2081 | 1 | Phosphoserine | ||||||||
| Modified residue | 2097 | 1 | Phosphothreonine | ||||||||
| Glycosylation | 46 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 155 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 733 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 1102 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 1465 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Disulfide bond | 28 ↔ 41 | By similarity | |||||||||
| Disulfide bond | 35 ↔ 51 | By similarity | |||||||||
| Disulfide bond | 53 ↔ 62 | By similarity | |||||||||
| Disulfide bond | 68 ↔ 79 | By similarity | |||||||||
| Disulfide bond | 73 ↔ 90 | By similarity | |||||||||
| Disulfide bond | 92 ↔ 101 | By similarity | |||||||||
| Disulfide bond | 109 ↔ 121 | By similarity | |||||||||
| Disulfide bond | 115 ↔ 131 | By similarity | |||||||||
| Disulfide bond | 133 ↔ 142 | By similarity | |||||||||
| Disulfide bond | 148 ↔ 159 | By similarity | |||||||||
| Disulfide bond | 153 ↔ 168 | By similarity | |||||||||
| Disulfide bond | 170 ↔ 179 | ||||||||||

Clusters with