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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-Experimental evidence at protein leveli

Functioni

Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). Involved in bone remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation. Positively regulates self-renewal of liver cancer cells (PubMed:25985737).By similarity3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei614Essential for O-xylosylationBy similarity1

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • receptor activity Source: UniProtKB
  • transcription factor activity, ligand-activated RNA polymerase II transcription factor binding Source: UniProtKB

GO - Biological processi

  • animal organ morphogenesis Source: UniProtKB
  • apoptotic process Source: UniProtKB
  • atrial septum morphogenesis Source: BHF-UCL
  • bone remodeling Source: UniProtKB
  • cell cycle arrest Source: UniProtKB
  • cell fate determination Source: UniProtKB
  • cell growth Source: UniProtKB
  • hemopoiesis Source: UniProtKB
  • marginal zone B cell differentiation Source: UniProtKB
  • multicellular organism development Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • nervous system development Source: UniProtKB
  • Notch signaling involved in heart development Source: BHF-UCL
  • Notch signaling pathway Source: UniProtKB
  • positive regulation of Ras protein signal transduction Source: UniProtKB
  • pulmonary valve morphogenesis Source: BHF-UCL
  • regulation of developmental process Source: InterPro
  • regulation of transcription, DNA-templated Source: UniProtKB
  • stem cell population maintenance Source: UniProtKB
  • transcription initiation from RNA polymerase II promoter Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein, Receptor

Keywords - Biological processi

Differentiation, Notch signaling pathway, Transcription, Transcription regulation

Enzyme and pathway databases

BioCyciZFISH:ENSG00000134250-MONOMER.
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.
SignaLinkiQ04721.
SIGNORiQ04721.

Names & Taxonomyi

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
Gene namesi
Name:NOTCH2Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:7882. NOTCH2.

Subcellular locationi

Notch 2 extracellular truncation :
Notch 2 intracellular domain :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini26 – 1677ExtracellularSequence analysisAdd BLAST1652
Transmembranei1678 – 1698HelicalSequence analysisAdd BLAST21
Topological domaini1699 – 2471CytoplasmicSequence analysisAdd BLAST773

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • endoplasmic reticulum membrane Source: Reactome
  • extracellular region Source: Reactome
  • Golgi membrane Source: Reactome
  • integral component of plasma membrane Source: UniProtKB
  • membrane Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • plasma membrane Source: HPA
  • receptor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

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
Natural variantiVAR_029361444C → Y in ALGS2. 1 PublicationCorresponds to variant rs111033632dbSNPEnsembl.1
Hajdu-Cheney syndrome (HJCYS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry. NOTCH2 mutations associated with Hajdu-Cheney syndrome cluster to the last coding exon of the gene. This suggests that the mutant mRNA products may escape nonsense-mediated decay and the resulting truncated NOTCH2 proteins act in a gain-of-function manner.
Disease descriptionA rare 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

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi4853.
MalaCardsiNOTCH2.
MIMi102500. phenotype.
610205. phenotype.
OpenTargetsiENSG00000134250.
Orphaneti955. Acroosteolysis dominant type.
261629. Alagille syndrome due to a NOTCH2 point mutation.
PharmGKBiPA31684.

Chemistry databases

ChEMBLiCHEMBL3407320.
GuidetoPHARMACOLOGYi2859.

Polymorphism and mutation databases

BioMutaiNOTCH2.
DMDMi143811429.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
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
Disulfide bondi28 ↔ 41By similarity
Disulfide bondi35 ↔ 51By similarity
Glycosylationi46N-linked (GlcNAc...)Sequence 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...)Sequence 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...); alternateBy similarity1
Glycosylationi613O-linked (Xyl...); 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...)Sequence 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...)Sequence 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...)Sequence 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
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

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. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). 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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ04721.
MaxQBiQ04721.
PaxDbiQ04721.
PeptideAtlasiQ04721.
PRIDEiQ04721.

PTM databases

iPTMnetiQ04721.
PhosphoSitePlusiQ04721.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000134250.
CleanExiHS_NOTCH2.
ExpressionAtlasiQ04721. baseline and differential.
GenevisibleiQ04721. HS.

Organism-specific databases

HPAiHPA046392.
HPA048743.

Interactioni

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 C8orf4, the interaction inhibits the nuclear translocation of NOTCH2 N2ICD (PubMed:25985737).By similarity4 Publications

Protein-protein interaction databases

BioGridi110915. 50 interactors.
IntActiQ04721. 26 interactors.
MINTiMINT-1187009.
STRINGi9606.ENSP00000256646.

Chemistry databases

BindingDBiQ04721.

Structurei

Secondary structure

12471
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi1428 – 1433Combined sources6
Beta strandi1436 – 1438Combined sources3
Helixi1441 – 1443Combined sources3
Turni1446 – 1448Combined sources3
Helixi1449 – 1452Combined sources4
Turni1453 – 1458Combined sources6
Turni1462 – 1465Combined sources4
Helixi1472 – 1474Combined sources3
Beta strandi1477 – 1479Combined sources3
Helixi1482 – 1484Combined sources3
Turni1487 – 1490Combined sources4
Helixi1491 – 1494Combined sources4
Helixi1506 – 1512Combined sources7
Beta strandi1515 – 1517Combined sources3
Helixi1520 – 1522Combined sources3
Helixi1525 – 1532Combined sources8
Beta strandi1544 – 1553Combined sources10
Helixi1555 – 1560Combined sources6
Helixi1562 – 1573Combined sources12
Beta strandi1575 – 1579Combined sources5
Beta strandi1589 – 1594Combined sources6
Beta strandi1617 – 1628Combined sources12
Helixi1632 – 1635Combined sources4
Helixi1643 – 1656Combined sources14
Beta strandi1663 – 1670Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2OO4X-ray2.00A/B1423-1677[»]
ProteinModelPortaliQ04721.
SMRiQ04721.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ04721.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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
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
Regioni1425 – 1677Negative regulatory region (NRR)Add BLAST253

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1645 – 1648Poly-Ala4
Compositional biasi1994 – 1997Poly-Leu4
Compositional biasi2426 – 2429Poly-Ser4

Sequence similaritiesi

Belongs to the NOTCH family.Curated
Contains 6 ANK repeats.PROSITE-ProRule annotation
Contains 35 EGF-like domains.PROSITE-ProRule annotation
Contains 3 LNR (Lin/Notch) repeats.PROSITE-ProRule annotation

Keywords - Domaini

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

Phylogenomic databases

eggNOGiENOG410IR7G. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00810000125346.
HOGENOMiHOG000234369.
HOVERGENiHBG052650.
InParanoidiQ04721.
KOiK02599.
OrthoDBiEOG091G01NU.
PhylomeDBiQ04721.
TreeFamiTF351641.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
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_.
IPR008297. Notch.
IPR022336. Notch_2.
IPR000800. Notch_dom.
IPR010660. Notch_NOD_dom.
IPR011656. Notch_NODP_dom.
[Graphical view]
PfamiPF12796. Ank_2. 2 hits.
PF11936. DUF3454. 1 hit.
PF00008. EGF. 24 hits.
PF07645. EGF_CA. 4 hits.
PF12661. hEGF. 4 hits.
PF06816. NOD. 1 hit.
PF07684. NODP. 1 hit.
PF00066. Notch. 3 hits.
[Graphical view]
PIRSFiPIRSF002279. Notch. 1 hit.
PRINTSiPR01452. LNOTCHREPEAT.
PR01985. NOTCH2.
SMARTiSM00248. 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.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF57184. SSF57184. 6 hits.
SSF90193. SSF90193. 2 hits.
PROSITEiPS50297. 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.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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
Checksum:i605B1B963C812BE1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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 rs111033632dbSNPEnsembl.1
Natural variantiVAR_0314631667V → F.Corresponds to variant rs17024517dbSNPEnsembl.1

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.

Genome annotation databases

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

Cross-referencesi

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:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2OO4X-ray2.00A/B1423-1677[»]
ProteinModelPortaliQ04721.
SMRiQ04721.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110915. 50 interactors.
IntActiQ04721. 26 interactors.
MINTiMINT-1187009.
STRINGi9606.ENSP00000256646.

Chemistry databases

BindingDBiQ04721.
ChEMBLiCHEMBL3407320.
GuidetoPHARMACOLOGYi2859.

PTM databases

iPTMnetiQ04721.
PhosphoSitePlusiQ04721.

Polymorphism and mutation databases

BioMutaiNOTCH2.
DMDMi143811429.

Proteomic databases

EPDiQ04721.
MaxQBiQ04721.
PaxDbiQ04721.
PeptideAtlasiQ04721.
PRIDEiQ04721.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4853.
DisGeNETi4853.
GeneCardsiNOTCH2.
GeneReviewsiNOTCH2.
HGNCiHGNC:7882. NOTCH2.
HPAiHPA046392.
HPA048743.
MalaCardsiNOTCH2.
MIMi102500. phenotype.
600275. gene.
610205. phenotype.
neXtProtiNX_Q04721.
OpenTargetsiENSG00000134250.
Orphaneti955. Acroosteolysis dominant type.
261629. Alagille syndrome due to a NOTCH2 point mutation.
PharmGKBiPA31684.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IR7G. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00810000125346.
HOGENOMiHOG000234369.
HOVERGENiHBG052650.
InParanoidiQ04721.
KOiK02599.
OrthoDBiEOG091G01NU.
PhylomeDBiQ04721.
TreeFamiTF351641.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000134250-MONOMER.
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.
SignaLinkiQ04721.
SIGNORiQ04721.

Miscellaneous databases

ChiTaRSiNOTCH2. human.
EvolutionaryTraceiQ04721.
GeneWikiiNotch-2.
GenomeRNAii4853.
PROiQ04721.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134250.
CleanExiHS_NOTCH2.
ExpressionAtlasiQ04721. baseline and differential.
GenevisibleiQ04721. HS.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
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_.
IPR008297. Notch.
IPR022336. Notch_2.
IPR000800. Notch_dom.
IPR010660. Notch_NOD_dom.
IPR011656. Notch_NODP_dom.
[Graphical view]
PfamiPF12796. Ank_2. 2 hits.
PF11936. DUF3454. 1 hit.
PF00008. EGF. 24 hits.
PF07645. EGF_CA. 4 hits.
PF12661. hEGF. 4 hits.
PF06816. NOD. 1 hit.
PF07684. NODP. 1 hit.
PF00066. Notch. 3 hits.
[Graphical view]
PIRSFiPIRSF002279. Notch. 1 hit.
PRINTSiPR01452. LNOTCHREPEAT.
PR01985. NOTCH2.
SMARTiSM00248. 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.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF57184. SSF57184. 6 hits.
SSF90193. SSF90193. 2 hits.
PROSITEiPS50297. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNOTC2_HUMAN
AccessioniPrimary (citable) accession number: Q04721
Secondary accession number(s): Q5T3X7, Q99734, Q9H240
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: April 3, 2007
Last modified: November 30, 2016
This is version 196 of the entry and version 3 of the sequence. [Complete history]
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.

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.