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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

  • calcium ion binding Source: InterPro
  • signaling receptor activity Source: UniProtKB

GO - Biological processi

<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

Reactome - a knowledgebase of biological pathways and processes

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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

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SignaLinki
Q04721

SIGNOR Signaling Network Open Resource

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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_and_taxonomy_section">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 2
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_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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_manual">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

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EuPathDBi
HostDB:ENSG00000134250.17

Human Gene Nomenclature Database

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HGNCi
HGNC:7882 NOTCH2

Online Mendelian Inheritance in Man (OMIM)

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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; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'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_location_section">'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.
See also OMIM:610205
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.
See also OMIM:102500
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_and_biotech_section">'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.

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GeneReviewsi
NOTCH2

MalaCards human disease database

More...
MalaCardsi
NOTCH2
MIMi102500 phenotype
610205 phenotype

Open Targets

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OpenTargetsi
ENSG00000134250

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

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

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA31684

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL3407320

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
2859

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
NOTCH2

Domain mapping of disease mutations (DMDM)

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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.<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_processing_section">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 ↔ 1126By similarity
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_processing_section">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

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EPDi
Q04721

MaxQB - The MaxQuant DataBase

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MaxQBi
Q04721

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

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PaxDbi
Q04721

PeptideAtlas

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PeptideAtlasi
Q04721

PRoteomics IDEntifications database

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PRIDEi
Q04721

ProteomicsDB human proteome resource

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ProteomicsDBi
58265

PTM databases

GlyConnect protein glycosylation platform

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GlyConnecti
1553

iPTMnet integrated resource for PTMs in systems biology context

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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

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Bgeei
ENSG00000134250 Expressed in 238 organ(s), highest expression level in testis

CleanEx database of gene expression profiles

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CleanExi
HS_NOTCH2

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q04721 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q04721 HS

Organism-specific databases

Human Protein Atlas

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HPAi
HPA048743

<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_section">'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_section">'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).By similarity7 Publications

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
110915, 57 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
Q04721

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
Q04721

Protein interaction database and analysis system

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IntActi
Q04721, 35 interactors

Molecular INTeraction database

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MINTi
Q04721

STRING: functional protein association networks

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STRINGi
9606.ENSP00000256646

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q04721

<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

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

More...
ProteinModelPortali
Q04721

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

More...
SMRi
Q04721

Database of comparative protein structure models

More...
ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
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_and_domains_section">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 29PROSITE-ProRule annotationAdd 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
ENOG410IR7G Eukaryota
COG0666 LUCA

Ensembl GeneTree

More...
GeneTreei
ENSGT00940000155030

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000234369

The HOVERGEN Database of Homologous Vertebrate Genes

More...
HOVERGENi
HBG052650

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
Q04721

KEGG Orthology (KO)

More...
KOi
K20994

Database of Orthologous Groups

More...
OrthoDBi
EOG091G01NU

Database for complete collections of gene phylogenies

More...
PhylomeDBi
Q04721

TreeFam database of animal gene trees

More...
TreeFami
TF351641

Family and domain databases

Conserved Domains Database

More...
CDDi
cd00204 ANK, 2 hits

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
1.25.40.20, 1 hit

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_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<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_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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 3 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 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
R4GN02R4GN02_HUMAN
Neurogenic locus notch homolog prot...
NOTCH2
235Annotation 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>
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>

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

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.487360

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_references_section">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
UniGeneiHs.487360

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[»]
ProteinModelPortaliQ04721
SMRiQ04721
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110915, 57 interactors
CORUMiQ04721
ELMiQ04721
IntActiQ04721, 35 interactors
MINTiQ04721
STRINGi9606.ENSP00000256646

Chemistry databases

BindingDBiQ04721
ChEMBLiCHEMBL3407320
GuidetoPHARMACOLOGYi2859

PTM databases

GlyConnecti1553
iPTMnetiQ04721
PhosphoSitePlusiQ04721

Polymorphism and mutation databases

BioMutaiNOTCH2
DMDMi143811429

Proteomic databases

EPDiQ04721
MaxQBiQ04721
PaxDbiQ04721
PeptideAtlasiQ04721
PRIDEiQ04721
ProteomicsDBi58265

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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
HPAiHPA048743
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

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GenAtlasi
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Phylogenomic databases

eggNOGiENOG410IR7G Eukaryota
COG0666 LUCA
GeneTreeiENSGT00940000155030
HOGENOMiHOG000234369
HOVERGENiHBG052650
InParanoidiQ04721
KOiK20994
OrthoDBiEOG091G01NU
PhylomeDBiQ04721
TreeFamiTF351641

Enzyme and pathway databases

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

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

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ChiTaRSi
NOTCH2 human
EvolutionaryTraceiQ04721

The Gene Wiki collection of pages on human genes and proteins

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GeneWikii
Notch-2

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

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GenomeRNAii
4853

Protein Ontology

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PROi
PR:Q04721

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
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Gene expression databases

BgeeiENSG00000134250 Expressed in 238 organ(s), highest expression level in testis
CleanExiHS_NOTCH2
ExpressionAtlasiQ04721 baseline and differential
GenevisibleiQ04721 HS

Family and domain databases

CDDicd00204 ANK, 2 hits
Gene3Di1.25.40.20, 1 hit
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

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ProtoNeti
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<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_and_isoforms">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: December 5, 2018
This is version 218 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, Complete proteome, Reference proteome

Documents

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