Protein detail

NOTC2

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

Protein symbol NOTC2	UniProt ID Q04721	EVMP score 0.60
Frequency 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

Cancer-related genesDisease related genesHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteins

Protein Function

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

Ensembl

ENSG00000134250

Entrez Gene Symbol

NOTCH2

Gene Description

Notch receptor 2

Chromosome

Position

119911553-120100779

Frequency

EVMP Score

0.60

Fluorescence & Localization

Tissue SpecificbrainCell SpecificAstrocytesBlood Cell SpecificNK-cellBlood Lineage SpecificNK-cells

Function & Pathway

Protein Function

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

Cellular Component

Molecular Function

Biological Process

KEGG

Reactome

Mediation Categories

Clinical-translation mediationImmune mediationReceptor-signaling mediation

Relations & Evidence

Enzyme-Mediated Modification

8 records.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database	References
NOTCH2	GSK3B	P49841	S	2,070	phosphorylation	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperHPRDKEASIGNOR_ProtMapper	KEA:15302935 SIGNOR:12794074 KEA:12794074 HPRD:15302935 HPRD:20068231 ProtMapper:12794074 HPRD:18669648
NOTCH2	GSK3B	P49841	S	2,093	phosphorylation	PhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperHPRDKEASIGNOR_ProtMapper	SIGNOR:12794074 ProtMapper:12794074 KEA:12794074 HPRD:12794074
NOTCH2	GSK3B	P49841	T	2,068	phosphorylation	MIMPHPRD_MIMPSIGNORProtMapperHPRDKEASIGNOR_ProtMapper	SIGNOR:12794074 ProtMapper:12794074 KEA:12794074 HPRD:12794074
NOTCH2	GSK3B	P49841	T	2,074	phosphorylation	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperHPRDKEASIGNOR_ProtMapper	SIGNOR:12794074 KEA:12794074 ProtMapper:12794074 HPRD:18669648 HPRD:12794074
NOTCH2	GSK3B	P49841	T	1,808	phosphorylation	KEA	KEA:17570479
NOTCH2	CDK1	P06493	T	1,808	phosphorylation	KEA	KEA:17570479
NOTCH2	CDK2	P24941	S	2,070	phosphorylation	KEA	KEA:17570479
NOTCH2	MAPK14	Q16539	T	1,808	phosphorylation	KEA	KEA:17570479

Ligand-Receptor Signaling

62 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
receptor	receptor	SignaLink_function	No	Yes	No	Yes	No
notch	receptor	Almen2009	No	Yes	No	Yes	No
growth_factor	receptor	Baccin2019	No	Yes	No	Yes	No
notch	receptor	HPMR	No	Yes	No	Yes	No
notch	receptor	Surfaceome	No	Yes	No	Yes	No
notch_pathway	receptor	ICELLNET	No	Yes	No	Yes	No
receptor	receptor	OmniPath	No	Yes	No	Yes	No
extracellular	extracellular	HPMR	No	No	No	Yes	No
extracellular	extracellular	OmniPath	No	No	No	Yes	No
intracellular	intracellular	LOCATE	No	No	No	Yes	No

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Regulatory Interaction Network

21 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
LFNG	Q8NES3	NOTC2	Q04721	Yes	Yes	Yes	WangSIGNORHPRDCui2007SPIKE_LCSPIKECellCall	SPIKE_LC:11346656 SPIKE:11346656 HPRD:11346656 SIGNOR:11346656
MFNG	O00587	NOTC2	Q04721	Yes	Yes	Yes	WangFantom5_LRdbCellTalkDBHPRD_LRdbiTALKKEGG-MEDICUStalklrRamilowski2015SIGNORconnectomeDB2020HPRDCui2007HPRD_talklrCancerCellMapSPIKE_LCLRdbSPIKECellCall	SPIKE_LC:11346656 CancerCellMap:11346656 LRdb:11346656 HPRD:11346656 SIGNOR:11346656 SPIKE:11346656 connectomeDB2020:11346656
GSK3B	P49841	NOTC2	Q04721	Yes	Yes	Yes	HPRD_MIMPSIGNORProtMapperPhosphoSite_KEAphosphoELM_KEAHPRDCancerCellMapWangNetworKIN_KEAHPRD-phosphosphoELM_MIMPPhosphoSite_MIMPMIMPiPTMnetPhosphoPointKEAHPRD_KEASIGNOR_ProtMapperNetPathACSNSPIKE_LCSPIKE	KEA:15302935 ACSN:15020233 CancerCellMap:12794074 KEA:12794074 ACSN:11967263 NetPath:12794074 ACSN:16944320 HPRD-phos:18669648 ACSN:21828089 ProtMapper:15302935 ProtMapper:12794074 HPRD-phos:20068231 HPRD-phos:12794074 ACSN:8524413 SIGNOR:12794074 ACSN:14663202 HPRD-phos:15302935 SPIKE:12794074 SPIKE_LC:12794074 ACSN:15465828 ProtMapper:20068231 HPRD:12794074 ProtMapper:18669648 KEA:17570479 ACSN:9832503
JAG1	P78504	NOTC2	Q04721	Yes	Yes	Yes	iTALKKEGG-MEDICUSICELLNETSIGNORHINTCellPhoneDB_CellinkerSignaLink3UniProt_LRdbHPMR_talklrHPMRCellChatDBHPRD_LRdbDLRP_CellinkertalklrHPRDCui2007Ramilowski2015_Baccin2019DLRP_talklrWangRamilowski2015HPMR_LRdbCellPhoneDBHPRD_talklrBaccin2019CellinkerSTRING_talklrCellCallCellTalkDBFantom5_LRdbHPMR_CellinkerNetPathconnectomeDB2020ACSNSPIKE_LCLRdbSPIKE	Cellinker:10958687 NetPath:10958687 ACSN:22330899 Baccin2019:10958687 Cellinker:10551863 HPRD:10958687 HINT:10958687 SignaLink3:10551863 HINT:10551863 connectomeDB2020:10551863 CellChatDB:22353464LRdb:11ACSN:22363130 connectomeDB2020:10958687 SIGNOR:10958687 ICELLNET:16921404 SignaLink3:18988627 SPIKE:10958687 Cellinker:22353464 SignaLink3:10958687 SIGNOR:18660822 LRdb:10551863 SignaLink3:23331499 SignaLink3:21071413 HPRD:10551863 Baccin2019:10551863 SIGNOR:10551863 HPMR:10551863 SPIKE_LC:10958687
JAG2	Q9Y219	NOTC2	Q04721	Yes	Yes	Yes	iTALKKEGG-MEDICUSICELLNETSIGNORCellPhoneDB_CellinkerSignaLink3UniProt_LRdbCellChatDBHPRD_LRdbDLRP_CellinkertalklrHPRDCui2007Ramilowski2015_Baccin2019DLRP_talklrWangRamilowski2015CellPhoneDBHPRD_talklrBaccin2019CellinkerSTRING_talklrCellCallCellTalkDBFantom5_LRdbNetPathconnectomeDB2020SPIKE_LCLRdbSPIKE	Cellinker:10958687 NetPath:10958687 Baccin2019:10958687 HPRD:10958687 CellChatDB:22353464 CellTalkDB:22353464 connectomeDB2020:10958687 SIGNOR:10958687 ICELLNET:16921404 SignaLink3:18988627 SPIKE:10958687 Cellinker:22353464 SignaLink3:10958687 LRdb:10958687 SignaLink3:23331499 SignaLink3:21071413 SPIKE:16713569 SPIKE_LC:16713569 SPIKE_LC:10958687
MAML2	Q8IZL2	NOTC2	Q04721	Yes	Yes	No	WangNetPathHPRDCui2007SignaLink3SPIKE_LCSPIKE	NetPath:12370315 SPIKE:12370315 SignaLink3:12370315 SPIKE_LC:12370315 HPRD:12370315 SignaLink3:23331499
NOTC2	Q04721	SUH	Q06330	Yes	Yes	No	WangNetPathHPRDCui2007HINTSignaLink3BioGRIDSPIKE_LCLit-BM-17SPIKE	NetPath:12370315 Lit-BM-17:26186194 HPRD:9032325 Lit-BM-17:25609649 Lit-BM-17:26496610 SignaLink3:9032325 BioGRID:9032325 SignaLink3:23331499 HINT:9032325 SPIKE:11518718 NetPath:11518718 HINT:26496610 Lit-BM-17:9032325 HINT:33961781 SPIKE_LC:11518718
MAML3	Q96JK9	NOTC2	Q04721	Yes	Yes	No	WangNetPathSIGNORHPRDCui2007SignaLink3CancerCellMapSPIKE_LCSPIKE	NetPath:12370315 SPIKE:12370315 SIGNOR:12370315 SignaLink3:12370315 SPIKE_LC:12370315 HPRD:12370315 SignaLink3:23331499 CancerCellMap:12370315
MAML1	Q92585	NOTC2	Q04721	Yes	Yes	No	WangNetPathSIGNORHPRDCui2007CancerCellMapSPIKE_LCSPIKE	SPIKE_LC:11101851 SPIKE:11101851 NetPath:11101851 CancerCellMap:11101851 SIGNOR:11101851 HPRD:11101851
DLL1	O00548	NOTC2	Q04721	Yes	Yes	No	iTALKKEGG-MEDICUSICELLNETSIGNORCellPhoneDB_CellinkerUniProt_LRdbCellChatDBHPRD_LRdbDLRP_CellinkertalklrHPRDCui2007Ramilowski2015_Baccin2019DLRP_talklrWangRamilowski2015CellPhoneDBHPRD_talklrBioGRIDBaccin2019CellinkerSTRING_talklrCellCallCellTalkDBFantom5_LRdbNetPathconnectomeDB2020SPIKE_LCLRdbSPIKE	SIGNOR:23111325 Cellinker:10958687 NetPath:10958687 CellTalkDB:10958687 BioGRID:9244302 SPIKE:10958687 Cellinker:22353464 Baccin2019:10958687 ICELLNET:21685328 LRdb:10958687 HPRD:10958687 connectomeDB2020:10958687 SPIKE_LC:10958687 CellChatDB:22353464

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Protein Complex Composition

9 records.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
MAML1-RBP-Jkappa-Notch2 complex	MAML1 NOTCH2 RBPJ	Q04721 Q06330 Q92585	1:1:1	Compleat	Compleat:HC2403	11101851
MAML2-RBP-Jkappa-Notch2 complex	MAML2 NOTCH2 RBPJ	Q04721 Q06330 Q8IZL2	1:1:1	Compleat	Compleat:HC726	12370315
MAML3-RBP-Jkappa-Notch2 complex	MAML3 NOTCH2 RBPJ	Q04721 Q06330 Q96JK9	1:1:1	Compleat	Compleat:HC564	12370315
	ARPC2 MED10 MED11 MED14 MED16 MED18 MED20 MED27 MED28 MED30 MED4 MED6 MED8 MED9 NOTCH2	O15144 O60244 O75586 Q04721 Q6P2C8 Q96G25 Q96HR3 Q9BTT4 Q9BUE0 Q9H204 Q9H944 Q9NPJ6 Q9NWA0 Q9P086 Q9Y2X0	1:1:1:1:1:1:1:1:1:1:1:1:1:1:1	NetworkBlastCompleat	Compleat:HC4124
	FBXO28 NOTCH2 PSMB1 SPEN	P20618 Q04721 Q96T58 Q9NVF7	0:0:0:0	Havugimana2012	Havugimana2012:C_392
	NOTCH2	Q04721	2	PDB	PDB:2oo4
	MAML1 NOTCH2 RBPJ ZNF589	Q04721 Q06330 Q86UQ0 Q92585	0:0:0:0	hu.MAP
	ANKRD44 NOTCH2	Q04721 Q8N8A2	0:0	hu.MAP2
	ANKRD44 NOTCH2 PPP6R1	Q04721 Q8N8A2 Q9UPN7	0:0:0	hu.MAP2

Isolation & Detection Technology

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationSize Exclusion ChromatographyImmunoaffinity Capture	Mass spectrometry	4	38113368 40189497 36146834 38207106

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

Cancer-related genesDisease variantOsteoporosis

Related Diseases

Lung cancer Pancreatic cancer

Biomarker

Phase 2

Drugs

MK-0752 ODEVIXIBAT RO4929097 TAREXTUMAB NIROGACESTAT NOTCH SIGNALING PATHWAY INHIBITOR MK0752 ENOTICUMAB

Antibody

HPA048743

Interaction Protein

ENSG00000149418ENSG00000206560

Interaction Count

Interaction Dataset

intact_biogrid