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NOTCH2 notch 2 [ Homo sapiens (human) ]

Gene ID: 4853, updated on 11-Aug-2014
Official Symbol
NOTCH2provided by HGNC
Official Full Name
notch 2provided by HGNC
Primary source
HGNC:7882
See related
Ensembl:ENSG00000134250; HPRD:02606; MIM:600275; Vega:OTTHUMG00000012177
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]
See NOTCH2 in Epigenomics, MapViewer
Location:
1p13-p11
Exon count:
38
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 1 NC_000001.11 (119911553..120100748, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (120454176..120639880, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene notch 2 pseudogene 1 Neighboring gene ADAM metallopeptidase domain 30 Neighboring gene uncharacterized LOC101929178 Neighboring gene SEC22 vesicle trafficking protein homolog B (S. cerevisiae) (gene/pseudogene) Neighboring gene myomegalin-like

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Alagille syndrome 2
MedGen: C1857761 OMIM: 610205 GeneReviews: Alagille Syndrome
Compare labs
Hajdu-Cheney syndrome
MedGen: C0917715 OMIM: 102500 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Haploinsufficency

No evidence available (Last evaluated (2014-07-17)

ISCA Genome Curation Page
Triplosensitivity

No evidence available (Last evaluated (2014-07-17)

ISCA Genome Curation Page

NHGRI GWAS Catalog

Description
Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.
NHGRI GWA Catalog

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 Protein Interaction Database

  • Delta-Notch Signaling Pathway, organism-specific biosystem (from WikiPathways)
    Delta-Notch Signaling Pathway, organism-specific biosystemThere are 4 Notch receptors in humans (Notch 1-4) that bind to a family of 5 ligands (Jagged 1 and 2 and Delta-like 1-3). The Notch receptors are expressed on the cell surface as heterodimeric protei...
  • Dorso-ventral axis formation, organism-specific biosystem (from KEGG)
    Dorso-ventral axis formation, organism-specific biosystem
    Dorso-ventral axis formation
  • Dorso-ventral axis formation, conserved biosystem (from KEGG)
    Dorso-ventral axis formation, conserved biosystem
    Dorso-ventral axis formation
  • Gene Expression, organism-specific biosystem (from REACTOME)
    Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
  • Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
    Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
  • MicroRNAs in cancer, organism-specific biosystem (from KEGG)
    MicroRNAs in cancer, organism-specific biosystemMicroRNA (miRNA) is a cluster of small non-encoding RNA molecules of 21 - 23 nucleotides in length, which controls gene expression post-transcriptionally either via the degradation of target mRNAs or...
  • MicroRNAs in cancer, conserved biosystem (from KEGG)
    MicroRNAs in cancer, conserved biosystemMicroRNA (miRNA) is a cluster of small non-encoding RNA molecules of 21 - 23 nucleotides in length, which controls gene expression post-transcriptionally either via the degradation of target mRNAs or...
  • NOTCH2 Activation and Transmission of Signal to the Nucleus, organism-specific biosystem (from REACTOME)
    NOTCH2 Activation and Transmission of Signal to the Nucleus, organism-specific biosystemSimilar to NOTCH1, NOTCH2 is activated by Delta-like and Jagged ligands (DLL/JAG) expressed in trans on a neighboring cell (Shimizu et al. 1999, Shimizu et al. 2000, Hicks et al. 2000, Ji et al. 2004...
  • NOTCH2 intracellular domain regulates transcription, organism-specific biosystem (from REACTOME)
    NOTCH2 intracellular domain regulates transcription, organism-specific biosystemIn the nucleus, NICD2 forms a complex with RBPJ (CBF1, CSL) and MAML (mastermind). NICD2:RBPJ:MAML complex activates transcription from RBPJ-binding promoter elements (RBEs) (Wu et al. 2000). Besides...
  • Neural Crest Differentiation, organism-specific biosystem (from WikiPathways)
    Neural Crest Differentiation, organism-specific biosystemGene regulatory network model of cranial neural crest cell (CNCC) development, adaped from PMID: 19575671. Most interactions in the model are proposed to regulate transcription of core factors involv...
  • Notch Signaling Pathway, organism-specific biosystem (from WikiPathways)
    Notch Signaling Pathway, organism-specific biosystemThe Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch pro...
  • Notch signaling pathway, organism-specific biosystem (from KEGG)
    Notch signaling pathway, organism-specific biosystemThe Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch pro...
  • Notch signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    Notch signaling pathway, organism-specific biosystem
    Notch signaling pathway
  • Notch signaling pathway, conserved biosystem (from KEGG)
    Notch signaling pathway, conserved biosystemThe Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch pro...
  • Notch-HLH transcription pathway, organism-specific biosystem (from REACTOME)
    Notch-HLH transcription pathway, organism-specific biosystemTHE NOTCH-HLH TRANSCRIPTION PATHWAY: Notch signaling was first identified in Drosophila, where it has been studied in detail at the genetic, molecular, biochemical and cellular levels (reviewed in ...
  • Pre-NOTCH Expression and Processing, organism-specific biosystem (from REACTOME)
    Pre-NOTCH Expression and Processing, organism-specific biosystemIn humans and other mammals the NOTCH gene family has four members, NOTCH1, NOTCH2, NOTCH3 and NOTCH4, encoded on four different chromosomes. Their transcription is developmentally regulated and tiss...
  • Pre-NOTCH Processing in Golgi, organism-specific biosystem (from REACTOME)
    Pre-NOTCH Processing in Golgi, organism-specific biosystemNOTCH undergoes final posttranslational processing in the Golgi apparatus (Lardelli et al. 1994, Blaumueller et al. 1997, Weinmaster et al. 1991, Weinmaster et al. 1992, Uyttendaele et al. 1996). Mov...
  • Pre-NOTCH Processing in the Endoplasmic Reticulum, organism-specific biosystem (from REACTOME)
    Pre-NOTCH Processing in the Endoplasmic Reticulum, organism-specific biosystemIn the endoplasmic reticulum, glycosyl transferases modify NOTCH precursors by glycosylating conserved serine and threonine residues in EGF repeats of NOTCH. O-fucosyl transferase POFUT1 fucosylates...
  • Pre-NOTCH Transcription and Translation, organism-specific biosystem (from REACTOME)
    Pre-NOTCH Transcription and Translation, organism-specific biosystemIn humans, the NOTCH protein family has four members: NOTCH1, NOTCH2, NOTCH3 and NOTCH4. NOTCH1 protein was identified first, as the product of a chromosome 9 gene translocated in T-cell acute lympho...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by NOTCH, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH, organism-specific biosystemThe Notch Signaling Pathway (NSP) is a highly conserved pathway for cell-cell communication. NSP is involved in the regulation of cellular differentiation, proliferation, and specification. For exam...
  • Signaling by NOTCH2, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH2, organism-specific biosystemNOTCH2 is activated by binding Delta-like and Jagged ligands (DLL/JAG) expressed in trans on neighboring cells (Shimizu et al. 1999, Shimizu et al. 2000, Hicks et al. 2000, Ji et al. 2004). In trans ...
  • Thyroid hormone signaling pathway, organism-specific biosystem (from KEGG)
    Thyroid hormone signaling pathway, organism-specific biosystemThe thyroid hormones (THs) are important regulators of growth, development and metabolism. The action of TH is mainly mediated by T3 (3,5,3'-triiodo-L-thyronine). Thyroid hormones, L-thyroxine (T4) a...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
calcium ion binding IEA
Inferred from Electronic Annotation
more info
 
ligand-activated RNA polymerase II transcription factor binding transcription factor activity TAS
Traceable Author Statement
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
receptor activity NAS
Non-traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
Notch receptor processing TAS
Traceable Author Statement
more info
 
Notch signaling involved in heart development IC
Inferred by Curator
more info
PubMed 
Notch signaling pathway TAS
Traceable Author Statement
more info
 
apoptotic process TAS
Traceable Author Statement
more info
PubMed 
atrial septum morphogenesis IMP
Inferred from Mutant Phenotype
more info
PubMed 
bone remodeling IMP
Inferred from Mutant Phenotype
more info
 
cell cycle arrest IDA
Inferred from Direct Assay
more info
PubMed 
cell fate determination TAS
Traceable Author Statement
more info
PubMed 
cell growth IDA
Inferred from Direct Assay
more info
PubMed 
determination of left/right symmetry IEA
Inferred from Electronic Annotation
more info
 
embryonic limb morphogenesis IEA
Inferred from Electronic Annotation
more info
 
gene expression TAS
Traceable Author Statement
more info
 
hemopoiesis TAS
Traceable Author Statement
more info
PubMed 
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
 
interleukin-4 secretion IEA
Inferred from Electronic Annotation
more info
 
intracellular receptor signaling pathway TAS
Traceable Author Statement
more info
PubMed 
morphogenesis of an epithelial sheet IEA
Inferred from Electronic Annotation
more info
 
multicellular organismal development NAS
Non-traceable Author Statement
more info
PubMed 
negative regulation of apoptotic process TAS
Traceable Author Statement
more info
PubMed 
negative regulation of cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
nervous system development NAS
Non-traceable Author Statement
more info
PubMed 
organ morphogenesis IEP
Inferred from Expression Pattern
more info
PubMed 
placenta blood vessel development IEA
Inferred from Electronic Annotation
more info
 
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
 
pulmonary valve morphogenesis IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of transcription, DNA-templated TAS
Traceable Author Statement
more info
PubMed 
stem cell maintenance TAS
Traceable Author Statement
more info
PubMed 
transcription initiation from RNA polymerase II promoter TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
Golgi membrane TAS
Traceable Author Statement
more info
 
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
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 IDA
Inferred from Direct Assay
more info
PubMed 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
receptor complex IDA
Inferred from Direct Assay
more info
 
Preferred Names
neurogenic locus notch homolog protein 2
Names
neurogenic locus notch homolog protein 2
Notch homolog 2

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

  1. NG_008163.1 

    Range
    4960..163101
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001200001.1NP_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:629681
    Blast Score: 84
    PHA02887; EGF-like protein; Provisional
    cd00054
    Location:182218
    Blast Score: 117
    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 ...
  2. NM_024408.3NP_077719.2  neurogenic locus notch homolog protein 2 isoform 1 preproprotein

    See proteins identical to 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
    UniProtKB/TrEMBL
    Q9UFD5
    Related
    ENSP00000256646, OTTHUMP00000014035, ENST00000256646, OTTHUMT00000033679
    Conserved Domains (10) summary
    pfam06816
    Location:15391595
    Blast Score: 260
    NOD; NOTCH protein
    cd00054
    Location:182218
    Blast Score: 134
    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:19382062
    Blast Score: 306
    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 ...
    pfam00066
    Location:14991534
    Blast Score: 134
    Notch; LNR domain
    pfam05387
    Location:22922421
    Blast Score: 97
    Chorion_3; Chorion family 3
    pfam07223
    Location:21302422
    Blast Score: 154
    DUF1421; Protein of unknown function (DUF1421)
    pfam07684
    Location:16171673
    Blast Score: 172
    NODP; NOTCH protein
    pfam11936
    Location:23802445
    Blast Score: 252
    DUF3454; Domain of unknown function (DUF3454)
    pfam12796
    Location:19482040
    Blast Score: 211
    Ank_2; Ankyrin repeats (3 copies)
    cl02419
    Location:14591496
    Blast Score: 90
    Notch; LNR domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000001.11 

    Range
    119911553..120100748
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005270902.2XP_005270959.1  

    See proteins identical to XP_005270959.1

    Conserved Domains (10) summary
    pfam06816
    Location:15001556
    Blast Score: 260
    NOD; NOTCH protein
    cd00054
    Location:143179
    Blast Score: 134
    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:18992023
    Blast Score: 306
    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 ...
    pfam00066
    Location:14601495
    Blast Score: 134
    Notch; LNR domain
    pfam05387
    Location:22532382
    Blast Score: 97
    Chorion_3; Chorion family 3
    pfam07223
    Location:20912383
    Blast Score: 156
    DUF1421; Protein of unknown function (DUF1421)
    pfam07684
    Location:15781634
    Blast Score: 172
    NODP; NOTCH protein
    pfam11936
    Location:23412406
    Blast Score: 252
    DUF3454; Domain of unknown function (DUF3454)
    pfam12796
    Location:19092001
    Blast Score: 211
    Ank_2; Ankyrin repeats (3 copies)
    cl02419
    Location:14201457
    Blast Score: 90
    Notch; LNR domain
  2. XM_006710667.1XP_006710730.1  

    See proteins identical to XP_006710730.1

    Conserved Domains (10) summary
    pfam06816
    Location:15001556
    Blast Score: 260
    NOD; NOTCH protein
    cd00054
    Location:143179
    Blast Score: 134
    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:18992023
    Blast Score: 306
    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 ...
    pfam00066
    Location:14601495
    Blast Score: 134
    Notch; LNR domain
    pfam05387
    Location:22532382
    Blast Score: 97
    Chorion_3; Chorion family 3
    pfam07223
    Location:20912383
    Blast Score: 156
    DUF1421; Protein of unknown function (DUF1421)
    pfam07684
    Location:15781634
    Blast Score: 172
    NODP; NOTCH protein
    pfam11936
    Location:23412406
    Blast Score: 252
    DUF3454; Domain of unknown function (DUF3454)
    pfam12796
    Location:19092001
    Blast Score: 211
    Ank_2; Ankyrin repeats (3 copies)
    cl02419
    Location:14201457
    Blast Score: 90
    Notch; LNR domain
  3. XM_005270901.1XP_005270958.1  

    See proteins identical to XP_005270958.1

    Conserved Domains (10) summary
    pfam06816
    Location:15001556
    Blast Score: 260
    NOD; NOTCH protein
    cd00054
    Location:143179
    Blast Score: 134
    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:18992023
    Blast Score: 306
    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 ...
    pfam00066
    Location:14601495
    Blast Score: 134
    Notch; LNR domain
    pfam05387
    Location:22532382
    Blast Score: 97
    Chorion_3; Chorion family 3
    pfam07223
    Location:20912383
    Blast Score: 156
    DUF1421; Protein of unknown function (DUF1421)
    pfam07684
    Location:15781634
    Blast Score: 172
    NODP; NOTCH protein
    pfam11936
    Location:23412406
    Blast Score: 252
    DUF3454; Domain of unknown function (DUF3454)
    pfam12796
    Location:19092001
    Blast Score: 211
    Ank_2; Ankyrin repeats (3 copies)
    cl02419
    Location:14201457
    Blast Score: 90
    Notch; LNR domain

Alternate HuRef

Genomic

  1. AC_000133.1 

    Range
    118312713..118398477
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018912.2 

    Range
    120569670..120727793
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)