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UniProtKB - Q04721 (NOTC2_HUMAN)

Protein

Neurogenic locus notch homolog protein 2

Gene

NOTCH2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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
Sitei614Essential for O-xylosylationBy similarity1

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • signaling receptor activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

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

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

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000134250.17
HGNCiHGNC:7882 NOTCH2
MIMi600275 gene
neXtProtiNX_Q04721

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
Topological domaini26 – 1677ExtracellularSequence analysisAdd BLAST1652
Transmembranei1678 – 1698HelicalSequence analysisAdd BLAST21
Topological domaini1699 – 2471CytoplasmicSequence analysisAdd BLAST773

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 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
Mutagenesisi2416T → A: Loss of interaction with FBW7. Results in decreased ubiquitination and degradation. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi4853
GeneReviewsiNOTCH2
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...) 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
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 (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

EPDiQ04721
MaxQBiQ04721
PaxDbiQ04721
PeptideAtlasiQ04721
PRIDEiQ04721
ProteomicsDBi58265

PTM databases

GlyConnecti1553
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 Expressed in 238 organ(s), highest expression level in testis
CleanExiHS_NOTCH2
ExpressionAtlasiQ04721 baseline and differential
GenevisibleiQ04721 HS

Organism-specific databases

HPAiHPA048743

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 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

BioGridi110915, 54 interactors
CORUMiQ04721
ELMiQ04721
IntActiQ04721, 35 interactors
MINTiQ04721
STRINGi9606.ENSP00000256646

Chemistry databases

BindingDBiQ04721

Structurei

Secondary structure

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

3D structure databases

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

Keywords - Domaini

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

Phylogenomic databases

eggNOGiENOG410IR7G Eukaryota
COG0666 LUCA
GeneTreeiENSGT00810000125346
HOGENOMiHOG000234369
HOVERGENiHBG052650
InParanoidiQ04721
KOiK20994
OrthoDBiEOG091G01NU
PhylomeDBiQ04721
TreeFamiTF351641

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, 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
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

Sequence (1+)i

Sequence statusi: Complete.

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
Checksum:i605B1B963C812BE1
GO

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:
D2WEZ3D2WEZ3_HUMAN
Neurogenic locus notch homolog prot...
NOTCH2
863Annotation score:
A0A1W2PQQ5A0A1W2PQQ5_HUMAN
Neurogenic locus notch homolog prot...
NOTCH2
31Annotation score:

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 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:
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

Similar proteinsi

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[»]
5MWBX-ray1.86A414-532[»]
ProteinModelPortaliQ04721
SMRiQ04721
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110915, 54 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

CTDi4853
DisGeNETi4853
EuPathDBiHostDB:ENSG00000134250.17
GeneCardsiNOTCH2
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
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IR7G Eukaryota
COG0666 LUCA
GeneTreeiENSGT00810000125346
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

ChiTaRSiNOTCH2 human
EvolutionaryTraceiQ04721
GeneWikiiNotch-2
GenomeRNAii4853
PROiPR:Q04721
SOURCEiSearch...

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, 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
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
ProtoNetiSearch...

Entry informationi

Entry nameiNOTC2_HUMAN
AccessioniPrimary (citable) accession number: Q04721
Secondary accession number(s): Q5T3X7, Q99734, Q9H240
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: April 3, 2007
Last modified: October 10, 2018
This is version 216 of the entry and version 3 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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