EV MemProt Atlas

Basic Information12

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

Ensembl

ENSG00000134250

Entrez Gene Symbol

NOTCH2

Gene Description

Notch receptor 2

Chromosome

1

Position

119911553-120100779

Supporting publications (n)

16

EVMP confidence score

0.60

Fluorescence & Localization4

Tissue SpecificbrainCell SpecificAstrocytesBlood Cell SpecificNK-cellBlood Lineage SpecificNK-cells

Function & Pathway7

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

Cellular Component (10)

Molecular Function (7)

Biological Process (3)

KEGG (9)

Reactome (15)

Page 1 of 2

Mediation Categories (3)

Clinical-translation mediationImmune mediationReceptor-signaling mediation

Relations & Evidence101

Enzyme-Mediated Modification (8)

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)

62 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
transmembrane	transmembrane	UniProt_topology	No	No	No	Yes	No
transmembrane	transmembrane	UniProt_keyword	No	No	No	Yes	No
transmembrane_predicted	transmembrane	OmniPath	No	No	No	Yes	No
transmembrane	transmembrane	CellPhoneDB	No	No	No	Yes	No
transmembrane	transmembrane	TopDB	No	No	No	Yes	No
transmembrane	transmembrane	LOCATE	No	No	No	Yes	No
transmembrane	transmembrane	Ramilowski_location	No	No	No	Yes	No
transmembrane	transmembrane	OmniPath	No	No	No	Yes	No
plasma_membrane	plasma_membrane	UniProt_location	No	No	No	Yes	No
plasma_membrane	plasma_membrane	Cellinker	No	No	No	Yes	No

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Regulatory Interaction Network (21)

21 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
NOTC2	Q04721	DLL1	O00548	Yes	Yes	No	NetPathHPRDCui2007SignaLink3BioGRIDBaccin2019Ramilowski2015_Baccin2019SPIKE_LCSPIKECellCall	Baccin2019:22390640 NetPath:10958687 BioGRID:9244302 SPIKE:10958687 SignaLink3:22390640 HPRD:10958687 SPIKE_LC:10958687
ADA10	O14672	NOTC2	Q04721	Yes	Yes	No	WangCellTalkDBSignaLink3ACSN	ACSN:19601831 ACSN:19726682 SignaLink3:10423016 SignaLink3:23331499 ACSN:19704010 CellTalkDB:24842903
LTC4S	Q16873	NOTC2	Q04721	Yes	Yes	No	SignaLink3	SignaLink3:11101851 SignaLink3:23331499
DLL3	Q9NYJ7	NOTC2	Q04721	Yes	Yes	No	CellChatDBCellTalkDBDLRP_CellinkeriTALKCellPhoneDBKEGG-MEDICUStalklrICELLNETconnectomeDB2020CellPhoneDB_CellinkerSignaLink3DLRP_talklrCellinkerWangLRdbCellCall	ICELLNET:16921404 LRdb:22353464 CellTalkDB:22353464 SignaLink3:11823422 Cellinker:22353464 Cellinker:29910816 SignaLink3:23331499 connectomeDB2020:22353464 CellChatDB:22353464
MK	P21741	NOTC2	Q04721	Yes	Yes	No	connectomeDB2020ICELLNETSIGNORSignaLink3	ICELLNET:18469519 connectomeDB2020:18469519 SignaLink3:23331499 SIGNOR:18469519 SignaLink3:18469519
GXLT1	Q4G148	NOTC2	Q04721	Yes	Yes	No	SIGNOR	SIGNOR:22117070
NOTC2	Q04721	TRAF6	Q9Y4K3	Yes	No	Yes	SIGNOR	SIGNOR:31699119
PGLT1	Q8NBL1	NOTC2	Q04721	Yes	Yes	No	SIGNOR	SIGNOR:22872643
GXLT2	A0PJZ3	NOTC2	Q04721	Yes	Yes	No	SIGNOR	SIGNOR:22117070
	COMPLEX:P49768_Q92542_Q96BI3_Q9NZ42	NOTC2	Q04721	Yes	Yes	No	SIGNOR	SIGNOR:25610395

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Protein Complex Composition (9)

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)

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 & Domains13

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 Relevance8

Disease Involvement (3)

Cancer-related genesDisease variantOsteoporosis

Related Diseases (2)

Lung cancer Pancreatic cancer

Biomarker

Phase 2

Drugs (7)

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

Antibody

HPA048743

Interaction Protein (2)

ENSG00000149418ENSG00000206560

Interaction Count

2

Interaction Dataset

intact_biogrid

Supporting Publications16

PMID	Title	Abstract
37686366	Identification of a Non-Invasive Urinary Exosomal Biomarker for Diabetic Nephropathy Using Data-Independent Acquisition Proteomics.	No abstract available
38490958	Proteomic analysis of ascitic extracellular vesicles describes tumour microenvironment and predicts patient survival in ovarian cancer.	No abstract available
39478498	Proteomic analysis of plasma total exosomes and placenta-derived exosomes in patients with gestational diabetes mellitus in the first and second trimesters.	No abstract available
39873726	Size-Dependent Separation of Extracellular Vesicle Subtypes with Exodisc Enabling Proteomic Analysis in Prostate Cancer.	No abstract available
40091455	Potential Role of Menstrual Fluid-Derived Small Extracellular Vesicle Proteins in Endometriosis Pathogenesiss.	No abstract available
40545963	Extracellular Vesicle Proteome Analysis Improves Diagnosis of Recurrence in Triple-Negative Breast Cancer.	No abstract available

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Entry name NOTC2	UniProt ID Q04721	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

NOTC2