Neurogenic locus notch homolog protein 2

UniProt Q04721 Organism Homo sapiens Gene NOTCH2

Also known as: NOTCH2

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 (By similarity). Involved in bone remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation. Positively regulates self-renewal of liver cancer cells.

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_2, Notch_C, Notch_dom, Notch_NOD_dom, Notch_NODP_dom
Functional cluster: Venom Serine Proteases & Phospholipase A2

Experimental structures · PDB · 2

2OO4 X-ray 2.00A
5MWB X-ray 1.86A

A predicted model is available from AlphaFold.

Gene Ontology · 46

Disease associations

acroosteolysis dominant type MONDO:0007057
Alagille syndrome due to a NOTCH2 point mutation MONDO:0012439

Neighborhood · nearest proteins

Nearest neighbours of Neurogenic locus notch homolog protein 2: 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

Major intrinsically disordered Notch2-binding receptor 1 1 shared papers
Neurogenic locus notch homolog protein 3 5 shared papers
Neurogenic locus notch homolog protein 4 3 shared papers
Major intrinsically disordered NOTCH2-binding receptor 1-like homolog 1 shared papers
Major intrinsically disordered NOTCH2-binding receptor 1-like 1 shared papers
Midkine 1 shared papers
Transcriptional and immune response regulator 1 shared papers
Transcriptional and immune response regulator 1 shared papers
Notch-regulated ankyrin repeat-containing protein 1 shared papers
Notch homolog 2 N-terminal-like protein R 1 shared papers
Neurogenic locus notch homolog protein 1 4 shared papers
Neurogenic locus notch homolog protein 3 2 shared papers

Literature · 27 cited papers

Loss of MINAR2 impairs motor function and causes Parkinson's disease-like symptoms in mice. Brain Commun. · 2020
Human-specific NOTCH2NL genes affect Notch signaling and cortical neurogenesis. Cell · 2018
MINAR1 is a Notch2-binding protein that inhibits angiogenesis and breast cancer growth. J. Mol. Cell Biol. · 2018
NOTCH2 Hajdu-Cheney mutations escape SCFFBW7-dependent proteolysis to promote osteoporosis. Mol. Cell · 2017
C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signalling. Nat. Commun. · 2015
Mutations in NOTCH2 in patients with Hajdu-Cheney syndrome. Osteoporos. Int. · 2013
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
Serpentine fibula-polycystic kidney syndrome caused by truncating mutations in NOTCH2. Hum. Mutat. · 2011
Serpentine fibula polycystic kidney syndrome is part of the phenotypic spectrum of Hajdu-Cheney syndrome. Eur. J. Hum. Genet. · 2012
Mutations in NOTCH2 in families with Hajdu-Cheney syndrome. Hum. Mutat. · 2011
Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis. Nat. Genet. · 2011
Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. Nat. Genet. · 2011
… and 15 more in the literature graph

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