Protein detail

NOTC2

Neurogenic locus notch homolog protein 2 (Notch 2) (hN2) [Cleaved into: Notch 2 extracellular truncation (N2ECD); Notch 2 intracellular domain (N2ICD)]

Entry name
NOTC2
UniProt ID
EVMP confidence score
0.60
Supporting publications (n)
16
Transmembrane count
1
Protein classification
Cancer-related genesDisease related genesHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteins
Basic Information
Protein Names
Neurogenic locus notch homolog protein 2 (Notch 2) (hN2) [Cleaved into: Notch 2 extracellular truncation (N2ECD); Notch 2 intracellular domain (N2ICD)]
Protein Class (6)
Cancer-related genesDisease related genesHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteins
Protein Function (6)
  • Predicted intracellular proteins
  • Human disease related genes:Endocrine and metabolic diseases:Diabetes
  • Human disease related genes:Congenital malformations:Congenital malformations of the digestive system
  • Human disease related genes:Musculoskeletal diseases:Skeletal diseases
  • Cancer-related genes:Candidate cancer biomarkers
  • Disease related genes
Transmembrane
1678..1698; Helical
Transmembrane Count
1
Entrez Gene Symbol
Gene Description
Notch receptor 2
Chromosome
1
Position
119911553-120100779
Supporting publications (n)
16
EVMP confidence score
0.60
Fluorescence & Localization
Tissue SpecificbrainCell SpecificAstrocytesBlood Cell SpecificNK-cellBlood Lineage SpecificNK-cells
Function & Pathway
Protein Function (6)
  • Predicted intracellular proteins
  • Human disease related genes:Endocrine and metabolic diseases:Diabetes
  • Human disease related genes:Congenital malformations:Congenital malformations of the digestive system
  • Human disease related genes:Musculoskeletal diseases:Skeletal diseases
  • Cancer-related genes:Candidate cancer biomarkers
  • Disease related genes
Mediation Categories (3)
Clinical-translation mediationImmune mediationReceptor-signaling mediation
Relations & Evidence101

Enzyme-Mediated Modification (8)

8 records.

Substrate Gene SymbolEnzyme Gene SymbolEnzyme UniProt IDResidue TypeResidue OffsetModificationDatabaseReferences
NOTCH2GSK3BP49841S2,070phosphorylationphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperHPRDKEASIGNOR_ProtMapperKEA:15302935SIGNOR:12794074KEA:12794074HPRD:15302935HPRD:20068231ProtMapper:12794074HPRD:18669648
NOTCH2GSK3BP49841S2,093phosphorylationPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperHPRDKEASIGNOR_ProtMapperSIGNOR:12794074ProtMapper:12794074KEA:12794074HPRD:12794074
NOTCH2GSK3BP49841T2,068phosphorylationMIMPHPRD_MIMPSIGNORProtMapperHPRDKEASIGNOR_ProtMapperSIGNOR:12794074ProtMapper:12794074KEA:12794074HPRD:12794074
NOTCH2GSK3BP49841T2,074phosphorylationphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperHPRDKEASIGNOR_ProtMapperSIGNOR:12794074KEA:12794074ProtMapper:12794074HPRD:18669648HPRD:12794074
NOTCH2GSK3BP49841T1,808phosphorylationKEAKEA:17570479
NOTCH2CDK1P06493T1,808phosphorylationKEAKEA:17570479
NOTCH2CDK2P24941S2,070phosphorylationKEAKEA:17570479
NOTCH2MAPK14Q16539T1,808phosphorylationKEAKEA:17570479

Ligand-Receptor Signaling (62)

62 records.

CategoryParentDatabaseTransmitterReceiverSecretedPlasma Membrane (Transmembrane)Plasma Membrane (Peripheral)
receptorreceptorSignaLink_functionYesYes
notchreceptorAlmen2009YesYes
growth_factorreceptorBaccin2019YesYes
notchreceptorHPMRYesYes
notchreceptorSurfaceomeYesYes
notch_pathwayreceptorICELLNETYesYes
receptorreceptorOmniPathYesYes
extracellularextracellularHPMRYes
extracellularextracellularOmniPathYes
intracellularintracellularLOCATEYes
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Regulatory Interaction Network (21)

21 records.

Source Protein SymbolSource UniProt IDTarget Protein SymbolTarget UniProt IDIs DirectedIs StimulationIs InhibitionDatabaseReferences
LFNGQ8NES3NOTC2Q04721YesYesYesWangSIGNORHPRDCui2007SPIKE_LCSPIKECellCallSPIKE_LC:11346656SPIKE:11346656HPRD:11346656SIGNOR:11346656
MFNGO00587NOTC2Q04721YesYesYesWangFantom5_LRdbCellTalkDBHPRD_LRdbiTALKKEGG-MEDICUStalklrRamilowski2015SIGNORconnectomeDB2020HPRDCui2007HPRD_talklrCancerCellMapSPIKE_LCLRdbSPIKECellCallSPIKE_LC:11346656CancerCellMap:11346656LRdb:11346656HPRD:11346656SIGNOR:11346656SPIKE:11346656connectomeDB2020:11346656
GSK3BP49841NOTC2Q04721YesYesYesHPRD_MIMPSIGNORProtMapperPhosphoSite_KEAphosphoELM_KEAHPRDCancerCellMapWangNetworKIN_KEAHPRD-phosphosphoELM_MIMPPhosphoSite_MIMPMIMPiPTMnetPhosphoPointKEAHPRD_KEASIGNOR_ProtMapperNetPathACSNSPIKE_LCSPIKEKEA:15302935ACSN:15020233CancerCellMap:12794074KEA:12794074ACSN:11967263NetPath:12794074ACSN:16944320HPRD-phos:18669648ACSN:21828089ProtMapper:15302935ProtMapper:12794074HPRD-phos:20068231HPRD-phos:12794074ACSN:8524413SIGNOR:12794074ACSN:14663202HPRD-phos:15302935SPIKE:12794074SPIKE_LC:12794074ACSN:15465828ProtMapper:20068231HPRD:12794074ProtMapper:18669648KEA:17570479ACSN:9832503
JAG1P78504NOTC2Q04721YesYesYesiTALKKEGG-MEDICUSICELLNETSIGNORHINTCellPhoneDB_CellinkerSignaLink3UniProt_LRdbHPMR_talklrHPMRCellChatDBHPRD_LRdbDLRP_CellinkertalklrHPRDCui2007Ramilowski2015_Baccin2019DLRP_talklrWangRamilowski2015HPMR_LRdbCellPhoneDBHPRD_talklrBaccin2019CellinkerSTRING_talklrCellCallCellTalkDBFantom5_LRdbHPMR_CellinkerNetPathconnectomeDB2020ACSNSPIKE_LCLRdbSPIKECellinker:10958687NetPath:10958687ACSN:22330899Baccin2019:10958687Cellinker:10551863HPRD:10958687HINT:10958687SignaLink3:10551863HINT:10551863connectomeDB2020:10551863CellChatDB:22353464LRdb:11ACSN:22363130connectomeDB2020:10958687SIGNOR:10958687ICELLNET:16921404SignaLink3:18988627SPIKE:10958687Cellinker:22353464SignaLink3:10958687SIGNOR:18660822LRdb:10551863SignaLink3:23331499SignaLink3:21071413HPRD:10551863Baccin2019:10551863SIGNOR:10551863HPMR:10551863SPIKE_LC:10958687
JAG2Q9Y219NOTC2Q04721YesYesYesiTALKKEGG-MEDICUSICELLNETSIGNORCellPhoneDB_CellinkerSignaLink3UniProt_LRdbCellChatDBHPRD_LRdbDLRP_CellinkertalklrHPRDCui2007Ramilowski2015_Baccin2019DLRP_talklrWangRamilowski2015CellPhoneDBHPRD_talklrBaccin2019CellinkerSTRING_talklrCellCallCellTalkDBFantom5_LRdbNetPathconnectomeDB2020SPIKE_LCLRdbSPIKECellinker:10958687NetPath:10958687Baccin2019:10958687HPRD:10958687CellChatDB:22353464CellTalkDB:22353464connectomeDB2020:10958687SIGNOR:10958687ICELLNET:16921404SignaLink3:18988627SPIKE:10958687Cellinker:22353464SignaLink3:10958687LRdb:10958687SignaLink3:23331499SignaLink3:21071413SPIKE:16713569SPIKE_LC:16713569SPIKE_LC:10958687
MAML2Q8IZL2NOTC2Q04721YesYesWangNetPathHPRDCui2007SignaLink3SPIKE_LCSPIKENetPath:12370315SPIKE:12370315SignaLink3:12370315SPIKE_LC:12370315HPRD:12370315SignaLink3:23331499
NOTC2Q04721SUHQ06330YesYesWangNetPathHPRDCui2007HINTSignaLink3BioGRIDSPIKE_LCLit-BM-17SPIKENetPath:12370315Lit-BM-17:26186194HPRD:9032325Lit-BM-17:25609649Lit-BM-17:26496610SignaLink3:9032325BioGRID:9032325SignaLink3:23331499HINT:9032325SPIKE:11518718NetPath:11518718HINT:26496610Lit-BM-17:9032325HINT:33961781SPIKE_LC:11518718
MAML3Q96JK9NOTC2Q04721YesYesWangNetPathSIGNORHPRDCui2007SignaLink3CancerCellMapSPIKE_LCSPIKENetPath:12370315SPIKE:12370315SIGNOR:12370315SignaLink3:12370315SPIKE_LC:12370315HPRD:12370315SignaLink3:23331499CancerCellMap:12370315
MAML1Q92585NOTC2Q04721YesYesWangNetPathSIGNORHPRDCui2007CancerCellMapSPIKE_LCSPIKESPIKE_LC:11101851SPIKE:11101851NetPath:11101851CancerCellMap:11101851SIGNOR:11101851HPRD:11101851
DLL1O00548NOTC2Q04721YesYesiTALKKEGG-MEDICUSICELLNETSIGNORCellPhoneDB_CellinkerUniProt_LRdbCellChatDBHPRD_LRdbDLRP_CellinkertalklrHPRDCui2007Ramilowski2015_Baccin2019DLRP_talklrWangRamilowski2015CellPhoneDBHPRD_talklrBioGRIDBaccin2019CellinkerSTRING_talklrCellCallCellTalkDBFantom5_LRdbNetPathconnectomeDB2020SPIKE_LCLRdbSPIKESIGNOR:23111325Cellinker:10958687NetPath:10958687CellTalkDB:10958687BioGRID:9244302SPIKE:10958687Cellinker:22353464Baccin2019:10958687ICELLNET:21685328LRdb:10958687HPRD:10958687connectomeDB2020:10958687SPIKE_LC:10958687CellChatDB:22353464
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Protein Complex Composition (9)

9 records.

Component NameComponent Gene SymbolsComponent UniProt IDStoichiometryDatabaseDatabase IDsReferences
MAML1-RBP-Jkappa-Notch2 complexMAML1NOTCH2RBPJQ04721Q06330Q925851:1:1CompleatCompleat:HC240311101851
MAML2-RBP-Jkappa-Notch2 complexMAML2NOTCH2RBPJQ04721Q06330Q8IZL21:1:1CompleatCompleat:HC72612370315
MAML3-RBP-Jkappa-Notch2 complexMAML3NOTCH2RBPJQ04721Q06330Q96JK91:1:1CompleatCompleat:HC56412370315
ARPC2MED10MED11MED14MED16MED18MED20MED27MED28MED30MED4MED6MED8MED9NOTCH2O15144O60244O75586Q04721Q6P2C8Q96G25Q96HR3Q9BTT4Q9BUE0Q9H204Q9H944Q9NPJ6Q9NWA0Q9P086Q9Y2X01:1:1:1:1:1:1:1:1:1:1:1:1:1:1NetworkBlastCompleatCompleat:HC4124
FBXO28NOTCH2PSMB1SPENP20618Q04721Q96T58Q9NVF70:0:0:0Havugimana2012Havugimana2012:C_392
NOTCH2Q047212PDBPDB:2oo4
MAML1NOTCH2RBPJZNF589Q04721Q06330Q86UQ0Q925850:0:0:0hu.MAP
ANKRD44NOTCH2Q04721Q8N8A20:0hu.MAP2
ANKRD44NOTCH2PPP6R1Q04721Q8N8A2Q9UPN70:0:0hu.MAP2

Isolation & Detection Technology (1)

1 record.

EV Isolation MethodDetection MethodNumber of ReferencesReferences
Differential UltracentrifugationSize Exclusion ChromatographyImmunoaffinity CaptureMass spectrometry438113368401894973614683438207106
Sequence, Structure & Domains

Sequences

Length
2,471
Mass
265,405
Sequence
MPALRPALLWALLALWLCCAAPAHALQCRDGYEPCVNEGMCVTYHNGTGYCKCPEGFLGEYCQHRDPCEKNRCQNGGTCVAQAMLGKATCRCASGFTGEDCQYSTSHPCFVSRPCLNGGTCHMLSRDTYECTCQVGFTGKECQWTDACLSHPCANGSTCTTVANQFSCKCLTGFTGQKCETDVNECDIPGHCQHGGTCLNLPGSYQCQCPQGFTGQYCDSLYVPCAPSPCVNGGTCRQTGDFTFECNCLPGFEGSTCERNIDDCPNHRCQNGGVCVDGVNTYNCRCPPQWTGQFCTEDVDECLLQPNACQNGGTCANRNGGYGCVCVNGWSGDDCSENIDDCAFASCTPGSTCIDRVASFSCMCPEGKAGLLCHLDDACISNPCHKGALCDTNPLNGQYICTCPQGYKGADCTEDVDECAMANSNPCEHAGKCVNTDGAFHCECLKGYAGPRCEMDINECHSDPCQNDATCLDKIGGFTCLCMPGFKGVHCELEINECQSNPCVNNGQCVDKVNRFQCLCPPGFTGPVCQIDIDDCSSTPCLNGAKCIDHPNGYECQCATGFTGVLCEENIDNCDPDPCHHGQCQDGIDSYTCICNPGYMGAICSDQIDECYSSPCLNDGRCIDLVNGYQCNCQPGTSGVNCEINFDDCASNPCIHGICMDGINRYSCVCSPGFTGQRCNIDIDECASNPCRKGATCINGVNGFRCICPEGPHHPSCYSQVNECLSNPCIHGNCTGGLSGYKCLCDAGWVGINCEVDKNECLSNPCQNGGTCDNLVNGYRCTCKKGFKGYNCQVNIDECASNPCLNQGTCFDDISGYTCHCVLPYTGKNCQTVLAPCSPNPCENAAVCKESPNFESYTCLCAPGWQGQRCTIDIDECISKPCMNHGLCHNTQGSYMCECPPGFSGMDCEEDIDDCLANPCQNGGSCMDGVNTFSCLCLPGFTGDKCQTDMNECLSEPCKNGGTCSDYVNSYTCKCQAGFDGVHCENNINECTESSCFNGGTCVDGINSFSCLCPVGFTGSFCLHEINECSSHPCLNEGTCVDGLGTYRCSCPLGYTGKNCQTLVNLCSRSPCKNKGTCVQKKAESQCLCPSGWAGAYCDVPNVSCDIAASRRGVLVEHLCQHSGVCINAGNTHYCQCPLGYTGSYCEEQLDECASNPCQHGATCSDFIGGYRCECVPGYQGVNCEYEVDECQNQPCQNGGTCIDLVNHFKCSCPPGTRGLLCEENIDDCARGPHCLNGGQCMDRIGGYSCRCLPGFAGERCEGDINECLSNPCSSEGSLDCIQLTNDYLCVCRSAFTGRHCETFVDVCPQMPCLNGGTCAVASNMPDGFICRCPPGFSGARCQSSCGQVKCRKGEQCVHTASGPRCFCPSPRDCESGCASSPCQHGGSCHPQRQPPYYSCQCAPPFSGSRCELYTAPPSTPPATCLSQYCADKARDGVCDEACNSHACQWDGGDCSLTMENPWANCSSPLPCWDYINNQCDELCNTVECLFDNFECQGNSKTCKYDKYCADHFKDNHCDQGCNSEECGWDGLDCAADQPENLAEGTLVIVVLMPPEQLLQDARSFLRALGTLLHTNLRIKRDSQGELMVYPYYGEKSAAMKKQRMTRRSLPGEQEQEVAGSKVFLEIDNRQCVQDSDHCFKNTDAAAALLASHAIQGTLSYPLVSVVSESLTPERTQLLYLLAVAVVIILFIILLGVIMAKRKRKHGSLWLPEGFTLRRDASNHKRREPVGQDAVGLKNLSVQVSEANLIGTGTSEHWVDDEGPQPKKVKAEDEALLSEEDDPIDRRPWTQQHLEAADIRRTPSLALTPPQAEQEVDVLDVNVRGPDGCTPLMLASLRGGSSDLSDEDEDAEDSSANIITDLVYQGASLQAQTDRTGEMALHLAARYSRADAAKRLLDAGADANAQDNMGRCPLHAAVAADAQGVFQILIRNRVTDLDARMNDGTTPLILAARLAVEGMVAELINCQADVNAVDDHGKSALHWAAAVNNVEATLLLLKNGANRDMQDNKEETPLFLAAREGSYEAAKILLDHFANRDITDHMDRLPRDVARDRMHHDIVRLLDEYNVTPSPPGTVLTSALSPVICGPNRSFLSLKHTPMGKKSRRPSAKSTMPTSLPNLAKEAKDAKGSRRKKSLSEKVQLSESSVTLSPVDSLESPHTYVSDTTSSPMITSPGILQASPNPMLATAAPPAPVHAQHALSFSNLHEMQPLAHGASTVLPSVSQLLSHHHIVSPGSGSAGSLSRLHPVPVPADWMNRMEVNETQYNEMFGMVLAPAEGTHPGIAPQSRPPEGKHITTPREPLPPIVTFQLIPKGSIAQPAGAPQPQSTCPPAVAGPLPTMYQIPEMARLPSVAFPTAMMPQQDGQVAQTILPAYHPFPASVGKYPTPPSQHSYASSNAAERTPSHSGHLQGEHPYLTPSPESPDQWSSSSPHSASDWSDVTTSPTPGGAGGGQRGPGTHMSEPPHNNMQVYA

3D Structural Models

Turn
418..420; 1446..1448; 1453..1458; 1462..1465; 1487..1490
Helix
459..462; 497..500; 1428..1433; 1441..1443; 1449..1452; 1472..1474; 1482..1484; 1491..1494; 1506..1512; 1520..1522; 1525..1532; 1555..1560; 1562..1573; 1632..1635; 1643..1656
Beta Strand
426..428; 432..436; 439..443; 448..450; 470..474; 477..481; 486..488; 508..512; 515..519; 1436..1438; 1477..1479; 1515..1517; 1544..1553; 1575..1579; 1589..1595; 1618..1628; 1663..1670
3D Structure
X-ray crystallography (2)

Domain & Motif Annotations

Compositional Bias
1774..1783; Acidic residues; 2098..2107; Basic residues; 2108..2117; Polar residues; 2137..2150; Polar residues; 2159..2168; Polar residues; 2388..2406; Polar residues; 2417..2445; Low complexity
Repeat
1425..1465; LNR 1; 1466..1502; LNR 2; 1503..1544; LNR 3; 1827..1871; ANK 1; 1876..1905; ANK 2; 1909..1939; ANK 3; 1943..1972; ANK 4; 1976..2005; ANK 5; 2009..2038; ANK 6
Domain (FT)
26..63; EGF-like 1; 64..102; EGF-like 2; 105..143; EGF-like 3; 144..180; EGF-like 4; 182..219; EGF-like 5; calcium-binding; 221..258; EGF-like 6; 260..296; EGF-like 7; calcium-binding; 298..336; EGF-like 8; calcium-binding; 338..374; EGF-like 9; calcium-binding; 375..413; EGF-like 10; 415..454; EGF-like 11; calcium-binding; 456..492; EGF-like 12; calcium-binding; 494..530; EGF-like 13; calcium-binding; 532..568; EGF-like 14; calcium-binding; 570..605; EGF-like 15; calcium-binding; 607..643; EGF-like 16; calcium-binding; 645..680; EGF-like 17; calcium-binding; 682..718; EGF-like 18; calcium-binding; 720..755; EGF-like 19; 757..793; EGF-like 20; calcium-binding; 795..831; EGF-like 21; calcium-binding; 833..871; EGF-like 22; 873..909; EGF-like 23; calcium-binding; 911..947; EGF-like 24; calcium-binding; 949..985; EGF-like 25; calcium-binding; 987..1023; EGF-like 26; calcium-binding; 1025..1061; EGF-like 27; calcium-binding; 1063..1099; EGF-like 28; 1101..1147; EGF-like 29; 1149..1185; EGF-like 30; calcium-binding; 1187..1223; EGF-like 31; calcium-binding; 1225..1262; EGF-like 32; calcium-binding; 1264..1302; EGF-like 33; 1304..1343; EGF-like 34; 1374..1412; EGF-like 35
Region
1425..1677; Negative regulatory region (NRR); 1754..1788; Disordered; 2091..2168; Disordered; 2380..2471; Disordered
Protein Families
NOTCH family
Sequence Similarities
Belongs to the NOTCH family.
Clinical Relevance
Disease Involvement (3)
Cancer-related genesDisease variantOsteoporosis
Biomarker
Phase 2
Antibody
Interaction Protein (2)
ENSG00000149418ENSG00000206560
Interaction Count
2
Interaction Dataset
intact_biogrid
Supporting Publications16
PMIDTitleRelated sentences
24769233Proteomic analysis of cerebrospinal fluid extracellular vesicles: a comprehensive dataset.Most interestingly, the involvement of extracellular vesicles in transferring toxic proteins such as α-synuclein and β-amyloid has been postulated as one of the mechanisms involved in the spreading of neurodegeneration to different brain areas.
25475747Identification of Biomarkers for PKD1 Using Urinary Exosomes.No related sentences available
25844599Molecular profiling of prostate cancer derived exosomes may reveal a predictive signature for response to docetaxel.No related sentences available
29562735Altered Proteome of Extracellular Vesicles Derived from Bladder Cancer Patients Urine.No related sentences available
30760538Microvesicle Proteomic Profiling of Uterine Liquid Biopsy for Ovarian Cancer Early Detection.No related sentences available
32284825Unravelling the proteomic landscape of extracellular vesicles in prostate cancer by density-based fractionation of urine.No related sentences available
32795414Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers.
33114768Proteomic Profiling of Two Distinct Populations of Extracellular Vesicles Isolated from Human Seminal Plasma.No related sentences available
33709510Unbiased proteomic profiling of host cell extracellular vesicle composition and dynamics upon HIV-1 infection.No related sentences available
36635400Proteomic profiling of urinary small extracellular vesicles in children with pneumonia: a pilot study.No related sentences available
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