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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

NOTCH1 Gene

protein-coding GIFtS: 70
GCID: GC09M139388

notch 1

(Previous names: Notch (Drosophila) homolog 1 (translocation-associated),...)
(Previous symbol: TAN1)

Explore 139 diseases affiliated with
NOTCH1 via

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Notch 1¹ ² ³		Notch Homolog 1, Translocation-Associated (Drosophila)¹
TAN1¹ ² ³ ⁵		Neurogenic Locus Notch Homolog Protein 1²
Translocation-Associated Notch Protein TAN-1² ³		Notch Homolog 1, Translocation-Associated²
HN1¹		EC 2.1.2.11⁸
Notch (Drosophila) Homolog 1 (Translocation-Associated)¹		EC 3.4.21.68⁸

External Ids:	HGNC: 7881¹	Entrez Gene: 4851²	Ensembl: ENSG00000148400⁷	OMIM: 190198⁵	UniProtKB: P46531³

Export aliases for NOTCH1 gene to outside databases

Previous GC identifers: GC09M130458 GC09M131078 GC09M132829 GC09M134746 GC09M136664 GC09M138508 GC09M108848

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for NOTCH1:

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 multiple roles during development. (provided by

RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: NOTC1_HUMAN, P46531

Function: Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 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. May be important for normal lymphocyte

function. In altered form, may contribute to transformation or progression in some T-cell neoplasms. Involved in the

maturation of both CD4+ and CD8+ cells in the thymus. May be important for follicular differentiation and possibly

cell fate selection within the follicle. During cerebellar development, may function as a receptor for neuronal DNER

and may be involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May

enhance HIF1A function by sequestering HIF1AN away from HIF1A (By similarity)

Gene Wiki entry for NOTCH1 (Notch-1)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000009.11 NC_018920.1 NT_024000.16

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the NOTCH1 gene promoter:
c-Fos AP-1 ATF-2 c-Jun NF-kappaB NF-kappaB1
Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids

Search SABiosciences Chromatin IP Primers for NOTCH1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat NOTCH1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 9q34.3 Ensembl cytogenetic band: 9q34.3 HGNC cytogenetic band: 9q34.3

NOTCH1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NOTCH1 gene location

GeneLoc information about chromosome 9 GeneLoc Exon Structure

GeneLoc location for GC09M139388: view genomic region (about GC identifiers)

Start:	139,388,896 bp from pter	End:	139,440,314 bp from pter
Size:	51,419 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: NOTC1_HUMAN, P46531 (See protein sequence)

Recommended Name: Neurogenic locus notch homolog protein 1 precursor

Size: 2555 amino acids; 272505 Da

Subunit: Heterodimer of a C-terminal fragment N(TM) and an N-terminal fragment N(EC) which are probably linked by

disulfide bonds. Interacts with DNER, DTX1, DTX2 and RBPJ/RBPSUH. Also interacts with MAML1, MAML2 and MAML3 which act

as transcriptional coactivators for NOTCH1. Notch 1 intracellular domain interacts with SNW1; the interaction involves

multimerized NOTCH1 NICD and is implicated in a formation of an intermediate preactivation complex which associates

with DNA-bound CBF-1/RBPJ. The activated membrane-bound form interacts with AAK1 which promotes NOTCH1 stabilization.

Forms a trimeric complex with FBXW7 and SGK1. Interacts with HIF1AN. HIF1AN negatively regulates the function of notch

intracellular domain (NICD), accelerating myogenic differentiation (By similarity). Interacts (via NICD) with SNAI1

(via zinc fingers); the interaction induces SNAI1 degradation via MDM2-mediated ubiquitination and inhibits

SNAI1-induced cell invasion. Interacts (via NICD) with MDM2A

Subcellular location: Cell membrane; Single-pass type I membrane protein (By similarity)

Subcellular location: Notch 1 intracellular domain: Nucleus (By similarity). Note=Following proteolytical processing

NICD is translocated to the nucleus (By similarity)

6/12 PDB 3D structures from and Proteopedia for NOTCH1 (see all 12):

1PB5 (3D)

1TOZ (3D)

1YYH (3D)

2F8X (3D)

2F8Y (3D)

2HE0 (3D)

Secondary accessions: Q59ED8 Q5SXM3

Explore the universe of human proteins at neXtProt for NOTCH1: NX_P46531

Post-translational modifications:

Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like

convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible

form. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is

cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch

extracellular truncation (NEXT). Following endocytosis, this fragment is then cleaved by presenilin dependent

gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane (By

similarity)¹

Phosphorylated (By similarity)¹

O-glycosylated on the EGF-like domains. Contains both O-linked fucose and O-linked glucose¹

Ubiquitinated; undergoes 'Lys-29'-linked polyubiquitination catalyzed by ITCH. Monoubiquitination at Lys-1759 is

required for activation by gamma-secretase cleavage, it promotes interaction with AAK1, which stabilizes it.

Deubiquitination by EIF3F is necessary for nuclear import of activated Notch¹

Hydroxylated at Asn-1955 by HIF1AN. Hydroxylated at Asn-2022 by HIF1AN (By similarity). Hydroxylation reduces affinity

for HI1AN and may thus indirectly modulate negative regulation of NICD (By similarity)¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P46531

2 DME Specific Peptides for NOTCH1 (P46531)

CFNGGTC

INTLGSF

NOTCH1 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_060087.3

ENSEMBL proteins:

ENSP00000277541

Reactome Protein details: P46531
Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	R&D Systems Recombinant & Natural Proteins for NOTCH1 (Notch-1)
	Browse recombinant and purified proteins available from Enzo Life Sciences
	Browse OriGene full length recombinant human proteins expressed in human HEK293 cells OriGene Protein Over-expression Lysate: NOTCH1 OriGene Custom Protein Services for NOTCH1
	GenScript Custom Purified and Recombinant Proteins Services for NOTCH1
	Novus Biologicals NOTCH1 Proteins Novus Biologicals NOTCH1 Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for NOTCH1

Gene Ontology (GO): 5/11 cellular component terms (GO ID links to tree view) (see all 11): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000139	Golgi membrane	TAS	--
GO:0001669	acrosomal vesicle	--	--
GO:0002193	MAML1-RBP-Jkappa- ICN1 complex	IDA	16510869
GO:0005576	extracellular region	TAS	--
GO:0005634	nucleus	TAS	10713164

NOTCH1 for ontologies About GeneDecksing

NOTCH1 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of NOTCH1
	R&D Systems Antibodies for NOTCH1 (Notch-1)
	Cell Signaling Technology (CST) Antibodies for NOTCH1 (Notch 1)
	OriGene Antibodies (see all 3): NOTCH1 OriGene Custom Antibody Services for NOTCH1
	GenScript Superior Antibodies for NOTCH1
	Novus Biologicals NOTCH1 Antibodies
	Abcam antibodies for NOTCH1
	Uscn Antibodies for NOTCH1
	ThermoFisher Antibodies for NOTCH1

Assay Products for NOTCH1:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for NOTCH1 (Notch-1) (see all)
	GenScript Custom Assay Services for NOTCH1
	Cell Signaling Technology (CST) Sandwich ELISA Kits for NOTCH1 (Notch 1)
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for NOTCH1

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

NOTCH1 for domains About GeneDecksing

5/13 InterPro domains/families (see all 13):

IPR010660 Notch_NOD_dom

IPR022362 Notch_1

IPR024600 DUF3454_notch

IPR001881 EGF-like_Ca-bd

IPR008297 Notch

Graphical View of Domain Structure for InterPro Entry P46531

ProtoNet protein and cluster: P46531

4 Blocks protein families:

IPB000152 Aspartic acid and asparagine hydroxylation site

IPB000800 LIN-12/notch repeat (LNR) signature

IPB001881 EGF-like calcium-binding

IPB002110 Ankyrin repeat signature

UniProtKB/Swiss-Prot: NOTC1_HUMAN, P46531

Similarity: Belongs to the NOTCH family

Similarity: Contains 5 ANK repeats

Similarity: Contains 36 EGF-like domains

Similarity: Contains 3 LNR (Lin/Notch) repeats

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: