Neurogenic locus notch homolog protein 1

UniProt P46531 Organism Homo sapiens Gene NOTCH1, TAN1

Also known as: NOTCH1, TAN1

Function

Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) 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. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4(+) and CD8(+) cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, functions as a receptor for neuronal DNER and is involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation. May be involved in mesoderm development, somite formation and neurogenesis. May enhance HIF1A function by sequestering HIF1AN away from HIF1A. Required for the THBS4 function in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury. Involved in determination of left/right symmetry by modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO).

Classification

Family (Pfam): PF00023 Ank, PF12796 Ank_2, PF00008 EGF, PF07645 EGF_CA, PF12661 hEGF, PF06816 NOD, PF07684 NODP, PF00066 Notch
InterPro: Ankyrin_rpt, Ankyrin_rpt-contain_sf, EGF, EGF-like_Ca-bd_dom, EGF-like_CS, EGF-type_Asp/Asn_hydroxyl_site, EGF_Ca-bd_CS, Growth_fac_rcpt_cys_sf, Notch, Notch-like_dom_sf, Notch/Slit_guidance, NOTCH1_EGF-like, Notch_1, Notch_C, Notch_dom, Notch_NOD_dom, Notch_NODP_dom
Functional cluster: Venom Serine Proteases & Phospholipase A2

Experimental structures · PDB · 29

1PB5 NMR
1TOZ NMR
1YYH X-ray 1.90A
2F8X X-ray 3.25A
2F8Y X-ray 1.55A
2HE0 X-ray 1.90A
2VJ3 X-ray 2.60A
3ETO X-ray 2.00A
3I08 X-ray 3.20A
3L95 X-ray 2.19A
3NBN X-ray 3.45A
3V79 X-ray 3.85A
… and 17 more

A predicted model is available from AlphaFold.

Gene Ontology · 149

Disease associations

aortic valve disease 1 MONDO:0024523
Adams-Oliver syndrome 5 MONDO:0014459

Neighborhood · nearest proteins

Nearest neighbours of Neurogenic locus notch homolog protein 1: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

TM2 domain-containing protein 3 1 shared papers
SNW domain-containing protein 1 2 shared papers
Neurogenic locus notch homolog protein 1 7 shared papers
E3 ubiquitin-protein ligase DTX1 1 shared papers
Neurogenic locus notch homolog protein 4 3 shared papers
Mastermind-like protein 1 2 shared papers
AP2-associated protein kinase 1 1 shared papers
Neurogenic locus notch homolog protein 3 4 shared papers
TM2 domain-containing protein 3 1 shared papers
Recombining binding protein suppressor of hairless 2 shared papers
Zinc finger MIZ domain-containing protein 1 1 shared papers
Endothelial cell-specific molecule 1 1 shared papers

Literature · 31 cited papers

TM2D3, a mammalian homologue of Drosophila neurogenic gene product Almondex, regulates surface presentation of Notch receptors. Sci. Rep. · 2023
Structural basis of Notch recognition by human gamma-secretase. Nature · 2019
Two novel protein O-glucosyltransferases that modify sites distinct from POGLUT1 and affect Notch trafficking and signaling. Proc. Natl. Acad. Sci. U.S.A. · 2018
Structural and biochemical differences between the Notch and the amyloid precursor protein transmembrane domains. Sci. Adv. · 2017
The PIAS-like coactivator Zmiz1 is a direct and selective cofactor of Notch1 in T cell development and leukemia. Immunity · 2015
Identifying tandem Ankyrin repeats in protein structures. BMC Bioinformatics · 2014
Mutations in NOTCH1 cause Adams-Oliver syndrome. Am. J. Hum. Genet. · 2014
The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality. Nature · 2013
Alpha-arrestin 1 (ARRDC1) and beta-arrestins cooperate to mediate Notch degradation in mammals. J. Cell Sci. · 2013
The ubiquitin-specific protease 12 (USP12) is a negative regulator of notch signaling acting on notch receptor trafficking toward degradation. J. Biol. Chem. · 2012
Notch1 binds and induces degradation of Snail in hepatocellular carcinoma. BMC Biol. · 2011
The adaptor-associated kinase 1, AAK1, is a positive regulator of the Notch pathway. J. Biol. Chem. · 2011
… and 19 more in the literature graph

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