NOTCH2 notch receptor 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NOTCH2provided by HGNC
Official Full Name: notch receptor 2provided by HGNC
Primary source: HGNC:HGNC:7882
See related: Ensembl:ENSG00000134250 MIM:600275
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: hN2; AGS2; HJCYS
Summary: This gene encodes 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 which regulates interactions between physically adjacent cells. In Drosophilia, 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. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]
Expression: Ubiquitous expression in testis (RPKM 12.9), ovary (RPKM 12.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p12

Exon count:: 34

Annotation release	Status	Assembly	Chr	Location
109.20210226	current	GRCh38.p13 (GCF_000001405.39)	1	NC_000001.11 (119911553..120069662, complement)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (120454176..120612276, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Evolution of Human Brain Size-Associated NOTCH2NL Genes Proceeds toward Reduced Protein Levels.
Title: Evolution of Human Brain Size-Associated NOTCH2NL Genes Proceeds toward Reduced Protein Levels.
Clinical Characteristics of Neuronal Intranuclear Inclusion Disease-Related Retinopathy With CGG Repeat Expansions in the NOTCH2NLC Gene.
Title: Clinical Characteristics of Neuronal Intranuclear Inclusion Disease-Related Retinopathy With CGG Repeat Expansions in the NOTCH2NLC Gene.
CAFs-derived MFAP5 promotes bladder cancer malignant behavior through NOTCH2/HEY1 signaling.
Title: CAFs-derived MFAP5 promotes bladder cancer malignant behavior through NOTCH2/HEY1 signaling.
GGC repeat expansion in NOTCH2NLC is rare in European patients with essential tremor.
Title: GGC repeat expansion in NOTCH2NLC is rare in European patients with essential tremor.
NOTCH2 participates in Jagged1-induced osteogenic differentiation in human periodontal ligament cells.
Title: NOTCH2 participates in Jagged1-induced osteogenic differentiation in human periodontal ligament cells.
ADAM10 mediates ectopic proximal tubule development and renal fibrosis through Notch signalling.
Title: ADAM10 mediates ectopic proximal tubule development and renal fibrosis through Notch signalling.
ZNF774 is a potent suppressor of hepatocarcinogenesis through dampening the NOTCH2 signaling.
Title: ZNF774 is a potent suppressor of hepatocarcinogenesis through dampening the NOTCH2 signaling.
Notch Inhibition Prevents Differentiation of Human Limbal Stem/Progenitor Cells in vitro.
Title: Notch Inhibition Prevents Differentiation of Human Limbal Stem/Progenitor Cells in vitro.
High NOTCH2 expression is associated with bladder cancer.
Title: Long non-coding RNA ARAP1-AS1 promotes the progression of bladder cancer by regulating miR-4735-3p/NOTCH2 axis.
The GGC repeated expansion in the 5'UTR of the NOTCH2NLC gene is associated with the pathogenesis of NIID.
Title: Long-read sequencing identified repeat expansions in the 5'UTR of the <i>NOTCH2NLC</i> gene from Chinese patients with neuronal intranuclear inclusion disease.

Submit: New GeneRIF Correction See all GeneRIFs (199)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Alagille syndrome 2 MedGen: C1857761 OMIM: 610205	Compare labs
Hajdu-Cheney syndrome MedGen: C0917715 OMIM: 102500 GeneReviews: Not available	Compare labs
Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. GeneReviews: Not available

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2014-07-17) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2014-07-17) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat interacts with the EGF-like repeats 1-6 (amino acids 26-256) of Human Notch2, suggesting Tat might modulate Notch2 function, thus affecting various AIDS-associated pathologies	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-75405 (e-PCR)
- UniSTS:10001

Cda0hb04 (e-PCR)
- UniSTS:35355

NOTCH2_1357 (e-PCR)
- UniSTS:277535

G63387 (e-PCR)
- UniSTS:140351

RH120586 (e-PCR)
- UniSTS:132419

G62977 (e-PCR)
- UniSTS:140102

G62978 (e-PCR)
- UniSTS:140103

SHGC-106854 (e-PCR)
- UniSTS:170056

SHGC-75400 (e-PCR)
- UniSTS:26191

SHGC-152728 (e-PCR)
- UniSTS:184937

RH123942 (e-PCR)
- UniSTS:136317

AL034022 (e-PCR)
- UniSTS:93569

SHGC-54558 (e-PCR)
- UniSTS:8614

RH69557 (e-PCR)
- UniSTS:87239

RH123510 (e-PCR)
- UniSTS:135886

AL033980 (e-PCR)
- UniSTS:93392

D1S2696 (e-PCR)
- UniSTS:211

G19892 (e-PCR)
- UniSTS:76761

A002B26 (e-PCR)
- UniSTS:76762

AL033805 (e-PCR)
- UniSTS:93663

Homology

Homologs of the NOTCH2 gene: The NOTCH2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 244 organisms have orthologs with human gene NOTCH2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
NF-kappaB binding	IEA Inferred from Electronic Annotation more info
calcium ion binding	IEA Inferred from Electronic Annotation more info
enzyme binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
signaling receptor activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
Notch signaling involved in heart development	IC Inferred by Curator more info	PubMed
Notch signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Notch signaling pathway	IDA Inferred from Direct Assay more info	PubMed
Notch signaling pathway	TAS Traceable Author Statement more info
animal organ morphogenesis	IEP Inferred from Expression Pattern more info	PubMed
apoptotic process	TAS Traceable Author Statement more info	PubMed
atrial septum morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
axon guidance	IBA Inferred from Biological aspect of Ancestor more info	PubMed
bone remodeling	IMP Inferred from Mutant Phenotype more info	PubMed
cell cycle arrest	IDA Inferred from Direct Assay more info	PubMed
cell fate determination	TAS Traceable Author Statement more info	PubMed
cholangiocyte proliferation	IEA Inferred from Electronic Annotation more info
ciliary body morphogenesis	IEA Inferred from Electronic Annotation more info
defense response to bacterium	IEA Inferred from Electronic Annotation more info
embryonic limb morphogenesis	IEA Inferred from Electronic Annotation more info
glomerular capillary formation	IEA Inferred from Electronic Annotation more info
glomerular visceral epithelial cell development	IEA Inferred from Electronic Annotation more info
heart looping	IEA Inferred from Electronic Annotation more info
hemopoiesis	TAS Traceable Author Statement more info	PubMed
hepatocyte proliferation	IEA Inferred from Electronic Annotation more info
humoral immune response	IEA Inferred from Electronic Annotation more info
in utero embryonic development	IEA Inferred from Electronic Annotation more info
inflammatory response to antigenic stimulus	IEA Inferred from Electronic Annotation more info
intrahepatic bile duct development	IEA Inferred from Electronic Annotation more info
left/right axis specification	IEA Inferred from Electronic Annotation more info
marginal zone B cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
morphogenesis of an epithelial sheet	IEA Inferred from Electronic Annotation more info
multicellular organism development	NAS Non-traceable Author Statement more info	PubMed
multicellular organism growth	IEA Inferred from Electronic Annotation more info
myeloid dendritic cell differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of apoptotic process	TAS Traceable Author Statement more info	PubMed
negative regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
negative regulation of growth rate	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
nervous system development	NAS Non-traceable Author Statement more info	PubMed
placenta blood vessel development	IEA Inferred from Electronic Annotation more info
positive regulation of BMP signaling pathway	IEA Inferred from Electronic Annotation more info
positive regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
positive regulation of Ras protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
positive regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
positive regulation of keratinocyte proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of osteoclast differentiation	IEA Inferred from Electronic Annotation more info
proximal tubule development	IEA Inferred from Electronic Annotation more info
pulmonary valve morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of actin cytoskeleton reorganization	IDA Inferred from Direct Assay more info	PubMed
regulation of osteoclast development	IMP Inferred from Mutant Phenotype more info	PubMed
stem cell population maintenance	TAS Traceable Author Statement more info	PubMed
transcription initiation from RNA polymerase II promoter	TAS Traceable Author Statement more info
wound healing	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
Golgi membrane	TAS Traceable Author Statement more info
cell surface	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cell surface	IDA Inferred from Direct Assay more info	PubMed
cilium	IEA Inferred from Electronic Annotation more info
endoplasmic reticulum membrane	TAS Traceable Author Statement more info
extracellular region	TAS Traceable Author Statement more info
integral component of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
membrane	HDA more info	PubMed
nucleoplasm	IDA Inferred from Direct Assay more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
receptor complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
receptor complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: neurogenic locus notch homolog protein 2

Names: Notch homolog 2; notch 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008163.1 RefSeqGene

Range

5001..163101

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001200001.2 → NP_001186930.1 neurogenic locus notch homolog protein 2 isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 3' UTR and coding sequence compared to variant 1. The resulting isoform (2) has a shorter and distinct C-terminus compared to isoform 1.

Source sequence(s)

AF315356, BC071562, DB290699

UniProtKB/Swiss-Prot

Q04721

UniProtKB/TrEMBL

Q6IQ50

Conserved Domains (2) summary

PHA02887
Location:629 → 681

PHA02887; EGF-like protein; Provisional

cd00054
Location:182 → 218

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
NM_024408.4 → NP_077719.2 neurogenic locus notch homolog protein 2 isoform 1 preproprotein

See identical proteins and their annotated locations for NP_077719.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AF315356, AL133036, BC071562, DB290699

Consensus CDS

CCDS908.1

UniProtKB/Swiss-Prot

Q04721

UniProtKB/TrEMBL

Q6IQ50, Q9UFD5

Related

ENSP00000256646.2, ENST00000256646.7

Conserved Domains (9) summary

cd00054
Location:182 → 218

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00204
Location:1938 → 2062

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

pfam05387
Location:2292 → 2421

Chorion_3; Chorion family 3

pfam00066
Location:1423 → 1456

Notch; LNR domain

pfam06816
Location:1540 → 1591

NOD; NOTCH protein

pfam07684
Location:1620 → 1673

NODP; NOTCH protein

pfam11936
Location:2381 → 2444

DUF3454; Domain of unknown function (DUF3454)

pfam12796
Location:1948 → 2040

Ank_2; Ankyrin repeats (3 copies)

sd00045
Location:1943 → 1974

ANK; ANK repeat [structural motif]