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UniProtKB - Q04721 (NOTC2_HUMAN)

Entry version 233 (07 Oct 2020)
Sequence version 3 (03 Apr 2007)
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Protein

Neurogenic locus notch homolog protein 2

Gene

NOTCH2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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 (PubMed:21378985, PubMed:21378989). 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 (PubMed:29149593). Positively regulates self-renewal of liver cancer cells (PubMed:25985737).By similarity4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei614Essential for O-xylosylationBy similarity1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionActivator, Developmental protein, Receptor
Biological processDifferentiation, Notch signaling pathway, Transcription, Transcription regulation

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		Q04721

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-1912399, Pre-NOTCH Processing in the Endoplasmic Reticulum
R-HSA-1912408, Pre-NOTCH Transcription and Translation
R-HSA-1912420, Pre-NOTCH Processing in Golgi
R-HSA-2197563, NOTCH2 intracellular domain regulates transcription
R-HSA-2979096, NOTCH2 Activation and Transmission of Signal to the Nucleus
R-HSA-350054, Notch-HLH transcription pathway
R-HSA-5083630, Defective LFNG causes SCDO3
R-HSA-9013695, NOTCH4 Intracellular Domain Regulates Transcription

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		Q04721

SIGNOR Signaling Network Open Resource

More...SIGNORi		Q04721

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Neurogenic locus notch homolog protein 2Curated
Short name:
Notch 2
Short name:
hN2
Cleaved into the following 2 chains:
Notch 2 extracellular truncation
Short name:
N2ECD1 Publication
Notch 2 intracellular domain
Short name:
N2ICD1 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:NOTCH2Imported
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 1

Organism-specific databases

Eukaryotic Pathogen Database Resources

More...EuPathDBi		HostDB:ENSG00000134250.17

Human Gene Nomenclature Database

More...HGNCi		HGNC:7882, NOTCH2

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		600275, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q04721

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini26 – 1677ExtracellularSequence analysisAdd BLAST1652
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei1678 – 1698HelicalSequence analysisAdd BLAST21
Topological domaini1699 – 2471CytoplasmicSequence analysisAdd BLAST773

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Alagille syndrome 2 (ALGS2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Alagille syndrome, an autosomal dominant multisystem disorder. It is clinically defined by hepatic bile duct paucity and cholestasis in association with cardiac, skeletal, and ophthalmologic manifestations. There are characteristic facial features and less frequent clinical involvement of the renal and vascular systems.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_029361444C → Y in ALGS2. 1 PublicationCorresponds to variant dbSNP:rs111033632EnsemblClinVar.1
Hajdu-Cheney syndrome (HJCYS)7 Publications
The disease is caused by mutations affecting the gene represented in this entry. NOTCH2 nonsense and frameshift mutations associated with Hajdu-Cheney syndrome cluster to the last coding exon of the gene. Mutant mRNA products escape nonsense-mediated decay and the resulting truncated NOTCH2 proteins act in a gain-of-function manner (PubMed:21378989). The pathological mechanism at cellular level involves disruption of a high affinity degron recognized by FBXW7 at the C-terminus, loss of interaction with FBXW7, reduced ubiquitination and degradation, and increased NOTCH2 levels. Bone marrow cells derived from HJCYS patients have an enhanced capacity of osteoclastogenesis due to sustained NOTCH2 activity (PubMed:29149593).2 Publications
Disease descriptionA rare, autosomal dominant skeletal disorder characterized by the association of facial anomalies, acro-osteolysis, general osteoporosis, insufficient ossification of the skull, and periodontal disease (premature loss of permanent teeth). Other features include cleft palate, congenital heart defects, polycystic kidneys, orthopedic problems and anomalies of the genitalia, intestines and eyes.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0801952140 – 2471Missing in HJCYS. 1 PublicationAdd BLAST332
Natural variantiVAR_0801962196 – 2471Missing in HJCYS. 1 PublicationAdd BLAST276
Natural variantiVAR_0801972208 – 2471Missing in HJCYS. 2 PublicationsAdd BLAST264
Natural variantiVAR_0801982223 – 2471Missing in HJCYS. 1 PublicationAdd BLAST249
Natural variantiVAR_0801992285 – 2471Missing in HJCYS. 1 PublicationAdd BLAST187
Natural variantiVAR_0802002299 – 2471Missing in HJCYS. 1 PublicationAdd BLAST173
Natural variantiVAR_0802012317 – 2471Missing in HJCYS; loss of interaction with FBW7; decreased ubiquitination. 2 PublicationsAdd BLAST155
Natural variantiVAR_0802022325 – 2471Missing in HJCYS. 1 PublicationAdd BLAST147
Natural variantiVAR_0802032360 – 2471Missing in HJCYS. 1 PublicationAdd BLAST112
Natural variantiVAR_0802042373 – 2471Missing in HJCYS. 1 PublicationAdd BLAST99
Natural variantiVAR_0802052389 – 2471Missing in HJCYS. 1 PublicationAdd BLAST83
Natural variantiVAR_0802062400 – 2471Missing in HJCYS. 3 PublicationsAdd BLAST72

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi2416T → A: Loss of interaction with FBW7. Results in decreased ubiquitination and degradation. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...DisGeNETi		4853

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...GeneReviewsi		NOTCH2

MalaCards human disease database

More...MalaCardsi		NOTCH2
MIMi102500, phenotype
610205, phenotype

Open Targets

More...OpenTargetsi		ENSG00000134250

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		955, Acroosteolysis dominant type
261629, Alagille syndrome due to a NOTCH2 point mutation

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA31684

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		Q04721, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL3407320

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		2859

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		NOTCH2

Domain mapping of disease mutations (DMDM)

More...DMDMi		143811429

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 25Sequence analysisAdd BLAST25
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000000768326 – 2471Neurogenic locus notch homolog protein 2Add BLAST2446
ChainiPRO_00000076841666 – 2471Notch 2 extracellular truncationBy similarityAdd BLAST806
ChainiPRO_00000076851697 – 2471Notch 2 intracellular domainBy similarityAdd BLAST775

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi28 ↔ 41By similarity
Disulfide bondi35 ↔ 51By similarity
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi46N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi53 ↔ 62By similarity
Disulfide bondi68 ↔ 79By similarity
Disulfide bondi73 ↔ 90By similarity
Disulfide bondi92 ↔ 101By similarity
Disulfide bondi109 ↔ 121By similarity
Disulfide bondi115 ↔ 131By similarity
Disulfide bondi133 ↔ 142By similarity
Disulfide bondi148 ↔ 159By similarity
Disulfide bondi153 ↔ 168By similarity
Glycosylationi155N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi170 ↔ 179By similarity
Disulfide bondi186 ↔ 198By similarity
Disulfide bondi192 ↔ 207By similarity
Disulfide bondi209 ↔ 218By similarity
Disulfide bondi225 ↔ 236By similarity
Disulfide bondi230 ↔ 246By similarity
Disulfide bondi248 ↔ 257By similarity
Disulfide bondi264 ↔ 275By similarity
Disulfide bondi269 ↔ 284By similarity
Disulfide bondi286 ↔ 295By similarity
Disulfide bondi302 ↔ 315By similarity
Disulfide bondi309 ↔ 324By similarity
Disulfide bondi326 ↔ 335By similarity
Disulfide bondi342 ↔ 353By similarity
Disulfide bondi347 ↔ 362By similarity
Disulfide bondi364 ↔ 373By similarity
Disulfide bondi379 ↔ 390By similarity
Disulfide bondi384 ↔ 401By similarity
Disulfide bondi403 ↔ 412By similarity
Disulfide bondi419 ↔ 433By similarity
Disulfide bondi427 ↔ 442By similarity
Disulfide bondi444 ↔ 453By similarity
Disulfide bondi460 ↔ 471By similarity
Disulfide bondi465 ↔ 480By similarity
Disulfide bondi482 ↔ 491By similarity
Disulfide bondi498 ↔ 509By similarity
Disulfide bondi503 ↔ 518By similarity
Disulfide bondi520 ↔ 529By similarity
Disulfide bondi536 ↔ 547By similarity
Disulfide bondi541 ↔ 556By similarity
Disulfide bondi558 ↔ 567By similarity
Disulfide bondi574 ↔ 584By similarity
Disulfide bondi579 ↔ 593By similarity
Disulfide bondi595 ↔ 604By similarity
Disulfide bondi611 ↔ 622By similarity
Glycosylationi613O-linked (Glc...) serine; alternateBy similarity1
Glycosylationi613O-linked (Xyl...) serine; alternateBy similarity1
Disulfide bondi616 ↔ 631By similarity
Disulfide bondi633 ↔ 642By similarity
Disulfide bondi649 ↔ 659By similarity
Disulfide bondi654 ↔ 668By similarity
Disulfide bondi670 ↔ 679By similarity
Disulfide bondi686 ↔ 697By similarity
Disulfide bondi691 ↔ 706By similarity
Disulfide bondi708 ↔ 717By similarity
Disulfide bondi724 ↔ 734By similarity
Disulfide bondi729 ↔ 743By similarity
Glycosylationi733N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi745 ↔ 754By similarity
Disulfide bondi761 ↔ 772By similarity
Disulfide bondi766 ↔ 781By similarity
Disulfide bondi783 ↔ 792By similarity
Disulfide bondi799 ↔ 810By similarity
Disulfide bondi804 ↔ 819By similarity
Disulfide bondi821 ↔ 830By similarity
Disulfide bondi837 ↔ 848By similarity
Disulfide bondi842 ↔ 859By similarity
Disulfide bondi861 ↔ 870By similarity
Disulfide bondi877 ↔ 888By similarity
Disulfide bondi882 ↔ 897By similarity
Disulfide bondi899 ↔ 908By similarity
Disulfide bondi915 ↔ 926By similarity
Disulfide bondi920 ↔ 935By similarity
Disulfide bondi937 ↔ 946By similarity
Disulfide bondi953 ↔ 964By similarity
Disulfide bondi958 ↔ 973By similarity
Disulfide bondi975 ↔ 984By similarity
Disulfide bondi991 ↔ 1002By similarity
Disulfide bondi996 ↔ 1011By similarity
Disulfide bondi1013 ↔ 1022By similarity
Disulfide bondi1029 ↔ 1040By similarity
Disulfide bondi1034 ↔ 1049By similarity
Disulfide bondi1051 ↔ 1060By similarity
Disulfide bondi1067 ↔ 1078By similarity
Disulfide bondi1072 ↔ 1087By similarity
Disulfide bondi1089 ↔ 1098By similarity
Glycosylationi1102N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1105 ↔ 1126Curated
Disulfide bondi1120 ↔ 1135By similarity
Disulfide bondi1137 ↔ 1146By similarity
Disulfide bondi1153 ↔ 1164By similarity
Disulfide bondi1158 ↔ 1173By similarity
Disulfide bondi1175 ↔ 1184By similarity
Disulfide bondi1191 ↔ 1202By similarity
Disulfide bondi1196 ↔ 1211By similarity
Disulfide bondi1213 ↔ 1222By similarity
Disulfide bondi1229 ↔ 1241By similarity
Disulfide bondi1235 ↔ 1250By similarity
Disulfide bondi1252 ↔ 1261By similarity
Disulfide bondi1268 ↔ 1281By similarity
Disulfide bondi1273 ↔ 1290By similarity
Disulfide bondi1292 ↔ 1301By similarity
Disulfide bondi1308 ↔ 1319By similarity
Disulfide bondi1313 ↔ 1331By similarity
Disulfide bondi1333 ↔ 1342By similarity
Disulfide bondi1378 ↔ 1389By similarity
Disulfide bondi1383 ↔ 1400By similarity
Disulfide bondi1402 ↔ 1411By similarity
Disulfide bondi1425 ↔ 14481 Publication
Disulfide bondi1430 ↔ 14431 Publication
Disulfide bondi1439 ↔ 14551 Publication
Glycosylationi1465N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1466 ↔ 14891 Publication
Disulfide bondi1472 ↔ 14841 Publication
Disulfide bondi1480 ↔ 14961 Publication
Disulfide bondi1503 ↔ 15271 Publication
Disulfide bondi1509 ↔ 15221 Publication
Disulfide bondi1518 ↔ 15341 Publication
Disulfide bondi1632 ↔ 16391 Publication
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei1716PhosphothreonineCombined sources1
Modified residuei1778PhosphoserineCombined sources1
Modified residuei1802PhosphothreonineCombined sources1
Modified residuei1804PhosphoserineCombined sources1
Modified residuei1808PhosphothreonineCombined sources1
Modified residuei1842PhosphoserineBy similarity1
Modified residuei1845PhosphoserineCombined sources1
Modified residuei2070PhosphoserineCombined sources1
Modified residuei2078PhosphoserineBy similarity1
Modified residuei2081PhosphoserineCombined sources1
Modified residuei2097PhosphothreonineCombined sources1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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 (By similarity). Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC) (By similarity). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT) (By similarity). 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).By similarity
Hydroxylated by HIF1AN.1 Publication
Can be either O-glucosylated or O-xylosylated at Ser-613 by POGLUT1.By similarity
Phosphorylated by GSK3. GSK3-mediated phosphorylation is necessary for NOTCH2 recognition by FBXW7, ubiquitination and degradation via the ubiquitin proteasome pathway.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		Q04721

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q04721

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		Q04721

MaxQB - The MaxQuant DataBase

More...MaxQBi		Q04721

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		Q04721

PeptideAtlas

More...PeptideAtlasi		Q04721

PRoteomics IDEntifications database

More...PRIDEi		Q04721

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		58265

PTM databases

GlyConnect protein glycosylation platform

More...GlyConnecti		1553, 2 N-Linked glycans (1 site)

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		Q04721, 8 sites, 1 O-linked glycan (2 sites)

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q04721

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		Q04721

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in the brain, heart, kidney, lung, skeletal muscle and liver. Ubiquitously expressed in the embryo.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000134250, Expressed in testis and 248 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		Q04721, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q04721, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000134250, Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Heterodimer of a C-terminal fragment N(TM) and an N-terminal fragment N(EC) which are probably linked by disulfide bonds (By similarity).

Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH2.

Interacts with RELA/p65 (By similarity).

Interacts with HIF1AN.

Interacts (via ANK repeats) with TCIM, the interaction inhibits the nuclear translocation of NOTCH2 N2ICD (PubMed:25985737).

Interacts with CUL1, RBX1, SKP1 and FBXW7 that are SCF(FBXW7) E3 ubiquitin-protein ligase complex components (PubMed:29149593).

Interacts with MINAR1; this interaction increases MINAR1 stability and function (PubMed:29329397).

Interacts with NOTCH2NL (NOTCH2NLA, NOTCH2NLB and/or NOTCH2NLC); leading to enhance Notch signaling pathway in a non-cell-autonomous manner (PubMed:29856954).

Interacts with MDK; this interaction mediates a nuclear accumulation of NOTCH2 and therefore activation of NOTCH2 signaling leading to interaction between HES1 and STAT3 (PubMed:18469519).

By similarity8 Publications

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		110915, 72 interactors

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		Q04721

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...ELMi		Q04721

Protein interaction database and analysis system

More...IntActi		Q04721, 46 interactors

Molecular INTeraction database

More...MINTi		Q04721

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000256646

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		Q04721

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		Q04721, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

12471
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		Q04721

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		Q04721

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini26 – 63EGF-like 1PROSITE-ProRule annotationAdd BLAST38
Domaini64 – 102EGF-like 2PROSITE-ProRule annotationAdd BLAST39
Domaini105 – 143EGF-like 3PROSITE-ProRule annotationAdd BLAST39
Domaini144 – 180EGF-like 4PROSITE-ProRule annotationAdd BLAST37
Domaini182 – 219EGF-like 5; calcium-bindingPROSITE-ProRule annotationAdd BLAST38
Domaini221 – 258EGF-like 6PROSITE-ProRule annotationAdd BLAST38
Domaini260 – 296EGF-like 7; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini298 – 336EGF-like 8; calcium-bindingPROSITE-ProRule annotationAdd BLAST39
Domaini338 – 374EGF-like 9; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini375 – 413EGF-like 10PROSITE-ProRule annotationAdd BLAST39
Domaini415 – 454EGF-like 11; calcium-bindingPROSITE-ProRule annotationAdd BLAST40
Domaini456 – 492EGF-like 12; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini494 – 530EGF-like 13; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini532 – 568EGF-like 14; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini570 – 605EGF-like 15; calcium-bindingPROSITE-ProRule annotationAdd BLAST36
Domaini607 – 643EGF-like 16; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini645 – 680EGF-like 17; calcium-bindingPROSITE-ProRule annotationAdd BLAST36
Domaini682 – 718EGF-like 18; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini720 – 755EGF-like 19PROSITE-ProRule annotationAdd BLAST36
Domaini757 – 793EGF-like 20; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini795 – 831EGF-like 21; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini833 – 871EGF-like 22PROSITE-ProRule annotationAdd BLAST39
Domaini873 – 909EGF-like 23; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini911 – 947EGF-like 24; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini949 – 985EGF-like 25; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini987 – 1023EGF-like 26; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini1025 – 1061EGF-like 27; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini1063 – 1099EGF-like 28PROSITE-ProRule annotationAdd BLAST37
Domaini1101 – 1147EGF-like 29CuratedAdd BLAST47
Domaini1149 – 1185EGF-like 30; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini1187 – 1223EGF-like 31; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini1225 – 1262EGF-like 32; calcium-bindingPROSITE-ProRule annotationAdd BLAST38
Domaini1264 – 1302EGF-like 33PROSITE-ProRule annotationAdd BLAST39
Domaini1304 – 1343EGF-like 34PROSITE-ProRule annotationAdd BLAST40
Domaini1374 – 1412EGF-like 35PROSITE-ProRule annotationAdd BLAST39
<p>This subsection of the 'Family and Domains' section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>Repeati1425 – 1465LNR 1Add BLAST41
Repeati1466 – 1502LNR 2Add BLAST37
Repeati1503 – 1544LNR 3Add BLAST42
Repeati1827 – 1871ANK 1Add BLAST45
Repeati1876 – 1905ANK 2Add BLAST30
Repeati1909 – 1939ANK 3Add BLAST31
Repeati1943 – 1972ANK 4Add BLAST30
Repeati1976 – 2005ANK 5Add BLAST30
Repeati2009 – 2038ANK 6Add BLAST30

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1425 – 1677Negative regulatory region (NRR)Add BLAST253

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi1645 – 1648Poly-Ala4
Compositional biasi1994 – 1997Poly-Leu4
Compositional biasi2426 – 2429Poly-Ser4

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the NOTCH family.Curated

Keywords - Domaini

ANK repeat, EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG1217, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000155030

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_000576_0_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q04721

KEGG Orthology (KO)

More...KOi		K20994

Identification of Orthologs from Complete Genome Data

More...OMAi		VSKPCLN

Database of Orthologous Groups

More...OrthoDBi		7525at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q04721

TreeFam database of animal gene trees

More...TreeFami		TF351641

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		1.25.40.20, 1 hit

Intrinsically Disordered proteins with Extensive Annotations and Literature

More...IDEALi		IID00463

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR002110, Ankyrin_rpt
IPR020683, Ankyrin_rpt-contain_dom
IPR036770, Ankyrin_rpt-contain_sf
IPR024600, DUF3454_notch
IPR001881, EGF-like_Ca-bd_dom
IPR013032, EGF-like_CS
IPR000742, EGF-like_dom
IPR000152, EGF-type_Asp/Asn_hydroxyl_site
IPR018097, EGF_Ca-bd_CS
IPR009030, Growth_fac_rcpt_cys_sf
IPR008297, Notch
IPR035993, Notch-like_dom_sf
IPR022336, Notch_2
IPR000800, Notch_dom
IPR010660, Notch_NOD_dom
IPR011656, Notch_NODP_dom

Pfam protein domain database

More...Pfami		View protein in Pfam
PF12796, Ank_2, 1 hit
PF11936, DUF3454, 1 hit
PF00008, EGF, 24 hits
PF07645, EGF_CA, 4 hits
PF12661, hEGF, 3 hits
PF06816, NOD, 1 hit
PF07684, NODP, 1 hit
PF00066, Notch, 3 hits

PIRSF; a whole-protein classification database

More...PIRSFi		PIRSF002279, Notch, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR01452, LNOTCHREPEAT
PR01985, NOTCH2

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00248, ANK, 6 hits
SM01334, DUF3454, 1 hit
SM00181, EGF, 36 hits
SM00179, EGF_CA, 34 hits
SM00004, NL, 3 hits
SM01338, NOD, 1 hit
SM01339, NODP, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF48403, SSF48403, 1 hit
SSF57184, SSF57184, 6 hits
SSF90193, SSF90193, 2 hits

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS50297, ANK_REP_REGION, 1 hit
PS50088, ANK_REPEAT, 4 hits
PS00010, ASX_HYDROXYL, 22 hits
PS00022, EGF_1, 34 hits
PS01186, EGF_2, 29 hits
PS50026, EGF_3, 35 hits
PS01187, EGF_CA, 22 hits
PS50258, LNR, 3 hits

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 7 potential isoforms that are computationally mapped.Show allAlign All

Q04721-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MPALRPALLW ALLALWLCCA APAHALQCRD GYEPCVNEGM CVTYHNGTGY 
        60         70         80         90        100
CKCPEGFLGE YCQHRDPCEK NRCQNGGTCV AQAMLGKATC RCASGFTGED 
       110        120        130        140        150
CQYSTSHPCF VSRPCLNGGT CHMLSRDTYE CTCQVGFTGK ECQWTDACLS 
       160        170        180        190        200
HPCANGSTCT TVANQFSCKC LTGFTGQKCE TDVNECDIPG HCQHGGTCLN 
       210        220        230        240        250
LPGSYQCQCP QGFTGQYCDS LYVPCAPSPC VNGGTCRQTG DFTFECNCLP 
       260        270        280        290        300
GFEGSTCERN IDDCPNHRCQ NGGVCVDGVN TYNCRCPPQW TGQFCTEDVD 
       310        320        330        340        350
ECLLQPNACQ NGGTCANRNG GYGCVCVNGW SGDDCSENID DCAFASCTPG 
       360        370        380        390        400
STCIDRVASF SCMCPEGKAG LLCHLDDACI SNPCHKGALC DTNPLNGQYI 
       410        420        430        440        450
CTCPQGYKGA DCTEDVDECA MANSNPCEHA GKCVNTDGAF HCECLKGYAG 
       460        470        480        490        500
PRCEMDINEC HSDPCQNDAT CLDKIGGFTC LCMPGFKGVH CELEINECQS 
       510        520        530        540        550
NPCVNNGQCV DKVNRFQCLC PPGFTGPVCQ IDIDDCSSTP CLNGAKCIDH 
       560        570        580        590        600
PNGYECQCAT GFTGVLCEEN IDNCDPDPCH HGQCQDGIDS YTCICNPGYM 
       610        620        630        640        650
GAICSDQIDE CYSSPCLNDG RCIDLVNGYQ CNCQPGTSGV NCEINFDDCA 
       660        670        680        690        700
SNPCIHGICM DGINRYSCVC SPGFTGQRCN IDIDECASNP CRKGATCING 
       710        720        730        740        750
VNGFRCICPE GPHHPSCYSQ VNECLSNPCI HGNCTGGLSG YKCLCDAGWV 
       760        770        780        790        800
GINCEVDKNE CLSNPCQNGG TCDNLVNGYR CTCKKGFKGY NCQVNIDECA 
       810        820        830        840        850
SNPCLNQGTC FDDISGYTCH CVLPYTGKNC QTVLAPCSPN PCENAAVCKE 
       860        870        880        890        900
SPNFESYTCL CAPGWQGQRC TIDIDECISK PCMNHGLCHN TQGSYMCECP 
       910        920        930        940        950
PGFSGMDCEE DIDDCLANPC QNGGSCMDGV NTFSCLCLPG FTGDKCQTDM 
       960        970        980        990       1000
NECLSEPCKN GGTCSDYVNS YTCKCQAGFD GVHCENNINE CTESSCFNGG 
      1010       1020       1030       1040       1050
TCVDGINSFS CLCPVGFTGS FCLHEINECS SHPCLNEGTC VDGLGTYRCS 
      1060       1070       1080       1090       1100
CPLGYTGKNC QTLVNLCSRS PCKNKGTCVQ KKAESQCLCP SGWAGAYCDV 
      1110       1120       1130       1140       1150
PNVSCDIAAS RRGVLVEHLC QHSGVCINAG NTHYCQCPLG YTGSYCEEQL 
      1160       1170       1180       1190       1200
DECASNPCQH GATCSDFIGG YRCECVPGYQ GVNCEYEVDE CQNQPCQNGG 
      1210       1220       1230       1240       1250
TCIDLVNHFK CSCPPGTRGL LCEENIDDCA RGPHCLNGGQ CMDRIGGYSC 
      1260       1270       1280       1290       1300
RCLPGFAGER CEGDINECLS NPCSSEGSLD CIQLTNDYLC VCRSAFTGRH 
      1310       1320       1330       1340       1350
CETFVDVCPQ MPCLNGGTCA VASNMPDGFI CRCPPGFSGA RCQSSCGQVK 
      1360       1370       1380       1390       1400
CRKGEQCVHT ASGPRCFCPS PRDCESGCAS SPCQHGGSCH PQRQPPYYSC 
      1410       1420       1430       1440       1450
QCAPPFSGSR CELYTAPPST PPATCLSQYC ADKARDGVCD EACNSHACQW 
      1460       1470       1480       1490       1500
DGGDCSLTME NPWANCSSPL PCWDYINNQC DELCNTVECL FDNFECQGNS 
      1510       1520       1530       1540       1550
KTCKYDKYCA DHFKDNHCDQ GCNSEECGWD GLDCAADQPE NLAEGTLVIV 
      1560       1570       1580       1590       1600
VLMPPEQLLQ DARSFLRALG TLLHTNLRIK RDSQGELMVY PYYGEKSAAM 
      1610       1620       1630       1640       1650
KKQRMTRRSL PGEQEQEVAG SKVFLEIDNR QCVQDSDHCF KNTDAAAALL 
      1660       1670       1680       1690       1700
ASHAIQGTLS YPLVSVVSES LTPERTQLLY LLAVAVVIIL FIILLGVIMA 
      1710       1720       1730       1740       1750
KRKRKHGSLW LPEGFTLRRD ASNHKRREPV GQDAVGLKNL SVQVSEANLI 
      1760       1770       1780       1790       1800
GTGTSEHWVD DEGPQPKKVK AEDEALLSEE DDPIDRRPWT QQHLEAADIR 
      1810       1820       1830       1840       1850
RTPSLALTPP QAEQEVDVLD VNVRGPDGCT PLMLASLRGG SSDLSDEDED 
      1860       1870       1880       1890       1900
AEDSSANIIT DLVYQGASLQ AQTDRTGEMA LHLAARYSRA DAAKRLLDAG 
      1910       1920       1930       1940       1950
ADANAQDNMG RCPLHAAVAA DAQGVFQILI RNRVTDLDAR MNDGTTPLIL 
      1960       1970       1980       1990       2000
AARLAVEGMV AELINCQADV NAVDDHGKSA LHWAAAVNNV EATLLLLKNG 
      2010       2020       2030       2040       2050
ANRDMQDNKE ETPLFLAARE GSYEAAKILL DHFANRDITD HMDRLPRDVA 
      2060       2070       2080       2090       2100
RDRMHHDIVR LLDEYNVTPS PPGTVLTSAL SPVICGPNRS FLSLKHTPMG 
      2110       2120       2130       2140       2150
KKSRRPSAKS TMPTSLPNLA KEAKDAKGSR RKKSLSEKVQ LSESSVTLSP 
      2160       2170       2180       2190       2200
VDSLESPHTY VSDTTSSPMI TSPGILQASP NPMLATAAPP APVHAQHALS 
      2210       2220       2230       2240       2250
FSNLHEMQPL AHGASTVLPS VSQLLSHHHI VSPGSGSAGS LSRLHPVPVP 
      2260       2270       2280       2290       2300
ADWMNRMEVN ETQYNEMFGM VLAPAEGTHP GIAPQSRPPE GKHITTPREP 
      2310       2320       2330       2340       2350
LPPIVTFQLI PKGSIAQPAG APQPQSTCPP AVAGPLPTMY QIPEMARLPS 
      2360       2370       2380       2390       2400
VAFPTAMMPQ QDGQVAQTIL PAYHPFPASV GKYPTPPSQH SYASSNAAER 
      2410       2420       2430       2440       2450
TPSHSGHLQG EHPYLTPSPE SPDQWSSSSP HSASDWSDVT TSPTPGGAGG 
      2460       2470 
GQRGPGTHMS EPPHNNMQVY A
Length:2,471
Mass (Da):265,405
Last modified:April 3, 2007 - v3
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i605B1B963C812BE1
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A494C1U9A0A494C1U9_HUMAN
Neurogenic locus notch homolog prot...
NOTCH2
274Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
D2WEZ3D2WEZ3_HUMAN
Neurogenic locus notch homolog prot...
NOTCH2
863Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A494C1F1A0A494C1F1_HUMAN
Neurogenic locus notch homolog prot...
NOTCH2
114Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
R4GN02R4GN02_HUMAN
Neurogenic locus notch homolog prot...
NOTCH2
236Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A1W2PQQ5A0A1W2PQQ5_HUMAN
Neurogenic locus notch homolog prot...
NOTCH2
31Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A494C1H8A0A494C1H8_HUMAN
Neurogenic locus notch homolog prot...
NOTCH2
12Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A494C049A0A494C049_HUMAN
Neurogenic locus notch homolog prot...
NOTCH2
25Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti21A → T in AAG37073 (Ref. 2) Curated1
Sequence conflicti210P → L in AAG37073 (Ref. 2) Curated1
Sequence conflicti1037E → D in AAB19224 (Ref. 4) Curated1
Sequence conflicti1084 – 1085ES → SP in AAB19224 (Ref. 4) Curated2
Sequence conflicti1094A → V in AAB19224 (Ref. 4) Curated1
Sequence conflicti1139L → V in AAB19224 (Ref. 4) Curated1
Sequence conflicti1519D → N in AAA36377 (Ref. 1) Curated1
Sequence conflicti2053R → H in AAG37073 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029361444C → Y in ALGS2. 1 PublicationCorresponds to variant dbSNP:rs111033632EnsemblClinVar.1
Natural variantiVAR_0314631667V → F. Corresponds to variant dbSNP:rs17024517EnsemblClinVar.1
Natural variantiVAR_0801952140 – 2471Missing in HJCYS. 1 PublicationAdd BLAST332
Natural variantiVAR_0801962196 – 2471Missing in HJCYS. 1 PublicationAdd BLAST276
Natural variantiVAR_0801972208 – 2471Missing in HJCYS. 2 PublicationsAdd BLAST264
Natural variantiVAR_0801982223 – 2471Missing in HJCYS. 1 PublicationAdd BLAST249
Natural variantiVAR_0801992285 – 2471Missing in HJCYS. 1 PublicationAdd BLAST187
Natural variantiVAR_0802002299 – 2471Missing in HJCYS. 1 PublicationAdd BLAST173
Natural variantiVAR_0802012317 – 2471Missing in HJCYS; loss of interaction with FBW7; decreased ubiquitination. 2 PublicationsAdd BLAST155
Natural variantiVAR_0802022325 – 2471Missing in HJCYS. 1 PublicationAdd BLAST147
Natural variantiVAR_0802032360 – 2471Missing in HJCYS. 1 PublicationAdd BLAST112
Natural variantiVAR_0802042373 – 2471Missing in HJCYS. 1 PublicationAdd BLAST99
Natural variantiVAR_0802052389 – 2471Missing in HJCYS. 1 PublicationAdd BLAST83
Natural variantiVAR_0802062400 – 2471Missing in HJCYS. 3 PublicationsAdd BLAST72

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
AF308601 mRNA Translation: AAA36377.2
AF315356 mRNA Translation: AAG37073.1
AL359752, AL512503, AL596222 Genomic DNA Translation: CAI18974.1
AL512503, AL359752, AL596222 Genomic DNA Translation: CAH72483.1
AL596222, AL359752, AL512503 Genomic DNA Translation: CAH70182.1
U77493 mRNA Translation: AAB19224.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS908.1

NCBI Reference Sequences

More...RefSeqi		NP_001186930.1, NM_001200001.1
NP_077719.2, NM_024408.3

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000256646; ENSP00000256646; ENSG00000134250

Database of genes from NCBI RefSeq genomes

More...GeneIDi		4853

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:4853

UCSC genome browser

More...UCSCi		uc001eik.4, human

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF308601 mRNA Translation: AAA36377.2
AF315356 mRNA Translation: AAG37073.1
AL359752, AL512503, AL596222 Genomic DNA Translation: CAI18974.1
AL512503, AL359752, AL596222 Genomic DNA Translation: CAH72483.1
AL596222, AL359752, AL512503 Genomic DNA Translation: CAH70182.1
U77493 mRNA Translation: AAB19224.1
CCDSiCCDS908.1
RefSeqiNP_001186930.1, NM_001200001.1
NP_077719.2, NM_024408.3

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2OO4X-ray2.00A/B1423-1677[»]
5MWBX-ray1.86A414-532[»]
SMRiQ04721
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi110915, 72 interactors
CORUMiQ04721
ELMiQ04721
IntActiQ04721, 46 interactors
MINTiQ04721
STRINGi9606.ENSP00000256646

Chemistry databases

BindingDBiQ04721
ChEMBLiCHEMBL3407320
GuidetoPHARMACOLOGYi2859

PTM databases

GlyConnecti1553, 2 N-Linked glycans (1 site)
GlyGeniQ04721, 8 sites, 1 O-linked glycan (2 sites)
iPTMnetiQ04721
PhosphoSitePlusiQ04721

Polymorphism and mutation databases

BioMutaiNOTCH2
DMDMi143811429

Proteomic databases

EPDiQ04721
jPOSTiQ04721
MassIVEiQ04721
MaxQBiQ04721
PaxDbiQ04721
PeptideAtlasiQ04721
PRIDEiQ04721
ProteomicsDBi58265

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...ABCDi		Q04721, 25 sequenced antibodies

Antibodypedia a portal for validated antibodies

More...Antibodypediai		20208, 617 antibodies

Genome annotation databases

EnsembliENST00000256646; ENSP00000256646; ENSG00000134250
GeneIDi4853
KEGGihsa:4853
UCSCiuc001eik.4, human

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		4853
DisGeNETi4853
EuPathDBiHostDB:ENSG00000134250.17

GeneCards: human genes, protein and diseases

More...GeneCardsi		NOTCH2
GeneReviewsiNOTCH2
HGNCiHGNC:7882, NOTCH2
HPAiENSG00000134250, Low tissue specificity
MalaCardsiNOTCH2
MIMi102500, phenotype
600275, gene
610205, phenotype
neXtProtiNX_Q04721
OpenTargetsiENSG00000134250
Orphaneti955, Acroosteolysis dominant type
261629, Alagille syndrome due to a NOTCH2 point mutation
PharmGKBiPA31684

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG1217, Eukaryota
GeneTreeiENSGT00940000155030
HOGENOMiCLU_000576_0_0_1
InParanoidiQ04721
KOiK20994
OMAiVSKPCLN
OrthoDBi7525at2759
PhylomeDBiQ04721
TreeFamiTF351641

Enzyme and pathway databases

PathwayCommonsiQ04721
ReactomeiR-HSA-1912399, Pre-NOTCH Processing in the Endoplasmic Reticulum
R-HSA-1912408, Pre-NOTCH Transcription and Translation
R-HSA-1912420, Pre-NOTCH Processing in Golgi
R-HSA-2197563, NOTCH2 intracellular domain regulates transcription
R-HSA-2979096, NOTCH2 Activation and Transmission of Signal to the Nucleus
R-HSA-350054, Notch-HLH transcription pathway
R-HSA-5083630, Defective LFNG causes SCDO3
R-HSA-9013695, NOTCH4 Intracellular Domain Regulates Transcription
SignaLinkiQ04721
SIGNORiQ04721

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		4853, 8 hits in 880 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		NOTCH2, human
EvolutionaryTraceiQ04721

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		Notch-2

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		4853
PharosiQ04721, Tchem

Protein Ontology

More...PROi		PR:Q04721
RNActiQ04721, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000134250, Expressed in testis and 248 other tissues
ExpressionAtlasiQ04721, baseline and differential
GenevisibleiQ04721, HS

Family and domain databases

Gene3Di1.25.40.20, 1 hit
IDEALiIID00463
InterProiView protein in InterPro
IPR002110, Ankyrin_rpt
IPR020683, Ankyrin_rpt-contain_dom
IPR036770, Ankyrin_rpt-contain_sf
IPR024600, DUF3454_notch
IPR001881, EGF-like_Ca-bd_dom
IPR013032, EGF-like_CS
IPR000742, EGF-like_dom
IPR000152, EGF-type_Asp/Asn_hydroxyl_site
IPR018097, EGF_Ca-bd_CS
IPR009030, Growth_fac_rcpt_cys_sf
IPR008297, Notch
IPR035993, Notch-like_dom_sf
IPR022336, Notch_2
IPR000800, Notch_dom
IPR010660, Notch_NOD_dom
IPR011656, Notch_NODP_dom
PfamiView protein in Pfam
PF12796, Ank_2, 1 hit
PF11936, DUF3454, 1 hit
PF00008, EGF, 24 hits
PF07645, EGF_CA, 4 hits
PF12661, hEGF, 3 hits
PF06816, NOD, 1 hit
PF07684, NODP, 1 hit
PF00066, Notch, 3 hits
PIRSFiPIRSF002279, Notch, 1 hit
PRINTSiPR01452, LNOTCHREPEAT
PR01985, NOTCH2
SMARTiView protein in SMART
SM00248, ANK, 6 hits
SM01334, DUF3454, 1 hit
SM00181, EGF, 36 hits
SM00179, EGF_CA, 34 hits
SM00004, NL, 3 hits
SM01338, NOD, 1 hit
SM01339, NODP, 1 hit
SUPFAMiSSF48403, SSF48403, 1 hit
SSF57184, SSF57184, 6 hits
SSF90193, SSF90193, 2 hits
PROSITEiView protein in PROSITE
PS50297, ANK_REP_REGION, 1 hit
PS50088, ANK_REPEAT, 4 hits
PS00010, ASX_HYDROXYL, 22 hits
PS00022, EGF_1, 34 hits
PS01186, EGF_2, 29 hits
PS50026, EGF_3, 35 hits
PS01187, EGF_CA, 22 hits
PS50258, LNR, 3 hits

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiNOTC2_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q04721
Secondary accession number(s): Q5T3X7, Q99734, Q9H240
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: April 3, 2007
Last modified: October 7, 2020
This is version 233 of the entry and version 3 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

  1. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families
  5. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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