Notch 2

NOTCH2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2OO4
Identifiers
Aliases	NOTCH2, AGS2, HJCYS, hN2, Notch-2, notch 2, notch receptor 2
External IDs	OMIM: 600275; MGI: 97364; HomoloGene: 7865; GeneCards: NOTCH2; OMA:NOTCH2 - orthologs
Gene location (Human)
Chr.	Chromosome 1 (human)
End	120,100,779 bp
Gene location (Mouse)
Chr.	Chromosome 3 (mouse)
End	98,057,677 bp
RNA expression pattern
	Top expressed in
	retinal pigment epithelium; ; skin of hip; ; skin of thigh; ; ventricular zone; ; synovial joint; ; caput epididymis; ; vulva; ; lactiferous duct; ; tail of epididymis; ; skin of arm;
	Top expressed in
	ciliary body; ; retinal pigment epithelium; ; aortic valve; ; ascending aorta; ; vas deferens; ; vestibular sensory epithelium; ; cumulus cell; ; conjunctival fornix; ; epithelium of lens; ; molar;
	More reference expression data
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	calcium ion binding; protein binding; signaling receptor activity;
Cellular component	cytoplasm; integral component of membrane; endoplasmic reticulum membrane; membrane; Golgi membrane; receptor complex; plasma membrane; integral component of plasma membrane; nucleoplasm; extracellular region; cell surface; nucleus;
Biological process	Notch signaling pathway; cell differentiation; hemopoiesis; pulmonary valve morphogenesis; regulation of transcription, DNA-templated; positive regulation of Ras protein signal transduction; negative regulation of apoptotic process; marginal zone B cell differentiation; transcription, DNA-templated; nervous system development; stem cell population maintenance; multicellular organism development; atrial septum morphogenesis; regulation of developmental process; bone remodeling; animal organ morphogenesis; transcription initiation from RNA polymerase II promoter; Notch signaling involved in heart development; apoptotic process; cell fate determination; intracellular receptor signaling pathway; negative regulation of gene expression; negative regulation of growth rate; positive regulation of ERK1 and ERK2 cascade; regulation of osteoclast development; positive regulation of keratinocyte proliferation; regulation of actin cytoskeleton reorganization;
	Sources:Amigo / QuickGO
Orthologs
	4853
	18129
	ENSG00000134250
	ENSMUSG00000027878
	Q04721
	O35516
	NM_001200001; NM_024408
	NM_010928
	NP_001186930; NP_077719
	NP_035058
	Wikidata
View/Edit Human	View/Edit Mouse

Neurogenic locus notch homolog protein 2 (Notch 2) is a protein that in humans is encoded by the NOTCH2 gene.^[5]

NOTCH2 is associated with Alagille syndrome^[6] and Hajdu–Cheney syndrome.^[7]

Function

Notch 2 is a member of the notch family. Members of this type 1 transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple, different domain types. Notch family members play a role in a variety of developmental processes by controlling cell fate decisions. The Notch signaling network is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells. In Drosophila, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signaling pathway that plays a key role in development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remain to be determined. This protein is cleaved in the trans-Golgi network, and presented on the cell surface as a heterodimer. This protein functions as a receptor for membrane bound ligands, and may play a role in vascular, renal and hepatic development.^[8]

Mutations within the last coding exon of Notch2 that remove the PEST domain and escape the nonsense-mediated mRNA decay have been shown to be the main cause of the Hajdu–Cheney syndrome.^[9]^[10]^[11]

Interactions

NOTCH2 has been shown to interact with:

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000134250 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000027878 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Larsson C, Lardelli M, White I, Lendahl U (May 1995). "The human NOTCH1, 2, and 3 genes are located at chromosome positions 9q34, 1p13-p11, and 19p13.2-p13.1 in regions of neoplasia-associated translocation". Genomics. 24 (2): 253–8. doi:10.1006/geno.1994.1613. PMID 7698746.
^ Samejima H, Torii C, Kosaki R, Kurosawa K, Yoshihashi H, Muroya K, Okamoto N, Watanabe Y, Kosho T, Kubota M, Matsuda O, Goto M, Izumi K, Takahashi T, Kosaki K (2007). "Screening for Alagille syndrome mutations in the JAG1 and NOTCH2 genes using denaturing high-performance liquid chromatography". Genet. Test. 11 (3): 216–27. doi:10.1089/gte.2006.0519. PMID 17949281.
^ Simpson MA, Irving MD, Asilmaz E, Gray MJ, Dafou D, Elmslie FV, Mansour S, Holder SE, Brain CE, Burton BK, Kim KH, Pauli RM, Aftimos S, Stewart H, Kim CA, Holder-Espinasse M, Robertson SP, Drake WM, Trembath RC (2011-03-06). "Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss". Nature Genetics. 43 (4): 303–5. doi:10.1038/ng.779. PMID 21378985. S2CID 205357391.
^ "Entrez Gene: NOTCH2 Notch homolog 2 (Drosophila)".
^ Simpson MA, Irving MD, Asilmaz E, Gray MJ, Dafou D, Elmslie FV, Mansour S, Holder SE, et al. (2011). "Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss". Nature Genetics. 43 (4): 303–305. doi:10.1038/ng.779. PMID 21378985. S2CID 205357391.
^ Isidor B, Lindenbaum P, Pichon O, Bézieau S, Dina C, Jacquemont S, Martin-Coignard D, Thauvin-Robinet C, Le Merrer M, Mandel JL, David A, Faivre L, Cormier-Daire V, Redon R, Le Caignec C (2011). "Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis". Nature Genetics. 43 (4): 306–8. doi:10.1038/ng.778. PMID 21378989. S2CID 205357384.
^ Majewski J, Schwartzentruber JA, Caqueret A, Patry L, Marcadier J, Fryns JP, Boycott KM, Ste-Marie LG, McKiernan FE, Marik I, Van Esch H, Michaud JL, Samuels ME (2011). "Mutations in NOTCH2 in families with Hajdu-Cheney syndrome". Hum Mutat. 32 (10): 1114–7. doi:10.1002/humu.21546. PMID 21681853. S2CID 39342783.
^ ^a ^b Shimizu K, Chiba S, Saito T, Kumano K, Takahashi T, Hirai H (July 2001). "Manic fringe and lunatic fringe modify different sites of the Notch2 extracellular region, resulting in different signaling modulation". J. Biol. Chem. 276 (28): 25753–8. doi:10.1074/jbc.M103473200. PMID 11346656.
^ ^a ^b ^c Shimizu K, Chiba S, Hosoya N, Kumano K, Saito T, Kurokawa M, Kanda Y, Hamada Y, Hirai H (September 2000). "Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of Notch2". Mol. Cell. Biol. 20 (18): 6913–22. doi:10.1128/mcb.20.18.6913-6922.2000. PMC 88767. PMID 10958687.
^ Blaumueller CM, Qi H, Zagouras P, Artavanis-Tsakonas S (July 1997). "Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane". Cell. 90 (2): 281–91. doi:10.1016/s0092-8674(00)80336-0. PMID 9244302. S2CID 16544864.
^ Espinosa L, Inglés-Esteve J, Aguilera C, Bigas A (August 2003). "Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways". J. Biol. Chem. 278 (34): 32227–35. doi:10.1074/jbc.M304001200. PMID 12794074.
^ Shimizu K, Chiba S, Kumano K, Hosoya N, Takahashi T, Kanda Y, Hamada Y, Yazaki Y, Hirai H (November 1999). "Mouse jagged1 physically interacts with notch2 and other notch receptors. Assessment by quantitative methods". J. Biol. Chem. 274 (46): 32961–9. doi:10.1074/jbc.274.46.32961. PMID 10551863.

External links

GeneReviews/NCBI/UW/NIH entry on Alagille syndrome
OMIM entries on Alagille syndrome
Overview of all the structural information available in the PDB for UniProt: Q04721 (Neurogenic locus notch homolog protein 2) at the PDBe-KB.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000134250 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000027878 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid7698746-5] Larsson C, Lardelli M, White I, Lendahl U (May 1995). "The human NOTCH1, 2, and 3 genes are located at chromosome positions 9q34, 1p13-p11, and 19p13.2-p13.1 in regions of neoplasia-associated translocation". Genomics. 24 (2): 253–8. doi:10.1006/geno.1994.1613. PMID 7698746.

[pmid17949281-6] Samejima H, Torii C, Kosaki R, Kurosawa K, Yoshihashi H, Muroya K, Okamoto N, Watanabe Y, Kosho T, Kubota M, Matsuda O, Goto M, Izumi K, Takahashi T, Kosaki K (2007). "Screening for Alagille syndrome mutations in the JAG1 and NOTCH2 genes using denaturing high-performance liquid chromatography". Genet. Test. 11 (3): 216–27. doi:10.1089/gte.2006.0519. PMID 17949281.

[pmid21378985-7] Simpson MA, Irving MD, Asilmaz E, Gray MJ, Dafou D, Elmslie FV, Mansour S, Holder SE, Brain CE, Burton BK, Kim KH, Pauli RM, Aftimos S, Stewart H, Kim CA, Holder-Espinasse M, Robertson SP, Drake WM, Trembath RC (2011-03-06). "Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss". Nature Genetics. 43 (4): 303–5. doi:10.1038/ng.779. PMID 21378985. S2CID 205357391.

[entrez-8] "Entrez Gene: NOTCH2 Notch homolog 2 (Drosophila)".

[9] Simpson MA, Irving MD, Asilmaz E, Gray MJ, Dafou D, Elmslie FV, Mansour S, Holder SE, et al. (2011). "Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss". Nature Genetics. 43 (4): 303–305. doi:10.1038/ng.779. PMID 21378985. S2CID 205357391.

[10] Isidor B, Lindenbaum P, Pichon O, Bézieau S, Dina C, Jacquemont S, Martin-Coignard D, Thauvin-Robinet C, Le Merrer M, Mandel JL, David A, Faivre L, Cormier-Daire V, Redon R, Le Caignec C (2011). "Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis". Nature Genetics. 43 (4): 306–8. doi:10.1038/ng.778. PMID 21378989. S2CID 205357384.

[pmid21681853-11] Majewski J, Schwartzentruber JA, Caqueret A, Patry L, Marcadier J, Fryns JP, Boycott KM, Ste-Marie LG, McKiernan FE, Marik I, Van Esch H, Michaud JL, Samuels ME (2011). "Mutations in NOTCH2 in families with Hajdu-Cheney syndrome". Hum Mutat. 32 (10): 1114–7. doi:10.1002/humu.21546. PMID 21681853. S2CID 39342783.

[pmid11346656-12] Shimizu K, Chiba S, Saito T, Kumano K, Takahashi T, Hirai H (July 2001). "Manic fringe and lunatic fringe modify different sites of the Notch2 extracellular region, resulting in different signaling modulation". J. Biol. Chem. 276 (28): 25753–8. doi:10.1074/jbc.M103473200. PMID 11346656.

[pmid10958687-13] Shimizu K, Chiba S, Hosoya N, Kumano K, Saito T, Kurokawa M, Kanda Y, Hamada Y, Hirai H (September 2000). "Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of Notch2". Mol. Cell. Biol. 20 (18): 6913–22. doi:10.1128/mcb.20.18.6913-6922.2000. PMC 88767. PMID 10958687.

[pmid9244302-14] Blaumueller CM, Qi H, Zagouras P, Artavanis-Tsakonas S (July 1997). "Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane". Cell. 90 (2): 281–91. doi:10.1016/s0092-8674(00)80336-0. PMID 9244302. S2CID 16544864.

[pmid12794074-15] Espinosa L, Inglés-Esteve J, Aguilera C, Bigas A (August 2003). "Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways". J. Biol. Chem. 278 (34): 32227–35. doi:10.1074/jbc.M304001200. PMID 12794074.

[pmid10551863-16] Shimizu K, Chiba S, Kumano K, Hosoya N, Takahashi T, Kanda Y, Hamada Y, Yazaki Y, Hirai H (November 1999). "Mouse jagged1 physically interacts with notch2 and other notch receptors. Assessment by quantitative methods". J. Biol. Chem. 274 (46): 32961–9. doi:10.1074/jbc.274.46.32961. PMID 10551863.

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Notch 2

Contents

Function

Interactions

References

Further reading

External links