Protein detail
NOTC1
Neurogenic locus notch homolog protein 1 (Notch 1) (hN1) (Translocation-associated notch protein TAN-1) [Cleaved into: Notch 1 extracellular truncation (NEXT); Notch 1 intracellular domain (NICD)]
Protein symbol NOTC1 | UniProt ID | EVMP score 0.25 |
Frequency 2 | Transmembrane count 1 | Protein classification Cancer-related genesDisease related genesHuman disease related genesPlasma proteinsPotential drug targetsPredicted membrane proteinsTransporters |
Basic Information
Protein Names
Neurogenic locus notch homolog protein 1 (Notch 1) (hN1) (Translocation-associated notch protein TAN-1) [Cleaved into: Notch 1 extracellular truncation (NEXT); Notch 1 intracellular domain (NICD)]
Protein Class
Cancer-related genesDisease related genesHuman disease related genesPlasma proteinsPotential drug targetsPredicted membrane proteinsTransporters
Protein Function
- Cancer-related genes:Mutational cancer driver genes
- Transporters
- Human disease related genes:Cancers:Cancers of the breast and female genital organs
- Cancer-related genes:Mutated cancer genes
- Potential drug targets
- Human disease related genes:Congenital malformations:Congenital malformations of the circulatory system
- Cancer-related genes:Candidate cancer biomarkers
- Human disease related genes:Cancers:Cancers of haematopoietic and lymphoid tissues
- Disease related genes
- Human disease related genes:Congenital malformations:Other congenital malformations
Transmembrane
1736..1756; Helical
Transmembrane Count
1
Ensembl
Entrez Gene Symbol
Gene Synonym
TAN1
Gene Description
Notch receptor 1
Chromosome
9
Position
136494433-136546048
Frequency
2
EVMP Score
0.25
Fluorescence & Localization
Tissue SpecificintestineCell SpecificB-cellsSingle-Nuclei Brain SpecificleukocyteSecretome LocationSecreted to bloodSecretome FunctionReceptor
Function & Pathway
Protein Function
- Cancer-related genes:Mutational cancer driver genes
- Transporters
- Human disease related genes:Cancers:Cancers of the breast and female genital organs
- Cancer-related genes:Mutated cancer genes
- Potential drug targets
- Human disease related genes:Congenital malformations:Congenital malformations of the circulatory system
- Cancer-related genes:Candidate cancer biomarkers
- Human disease related genes:Cancers:Cancers of haematopoietic and lymphoid tissues
- Disease related genes
- Human disease related genes:Congenital malformations:Other congenital malformations
Cellular Component
- GO:0000139 Golgi membrane
- GO:0001669 acrosomal vesicle
- GO:0002193 MAML1-RBP-Jkappa- ICN1 complex
- GO:0005576 extracellular region
- GO:0005634 nucleus
- GO:0005654 nucleoplasm
- GO:0005789 endoplasmic reticulum membrane
- GO:0005829 cytosol
- GO:0005886 plasma membrane
- GO:0005912 adherens junction
- GO:0009986 cell surface
- GO:0010008 endosome membrane
- GO:0016324 apical plasma membrane
- GO:0043235 receptor complex
- GO:0098685 Schaffer collateral - CA1 synapse
- GO:0098839 postsynaptic density membrane
- GO:0098978 glutamatergic synapse
Molecular Function
- GO:0000987 cis-regulatory region sequence-specific DNA binding
- GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
- GO:0003713 transcription coactivator activity
- GO:0004857 enzyme inhibitor activity
- GO:0004888 transmembrane signaling receptor activity
- GO:0005112 Notch binding
- GO:0005509 calcium ion binding
- GO:0005515 protein binding
- GO:0019899 enzyme binding
- GO:0031490 chromatin DNA binding
- GO:0042802 identical protein binding
- GO:0140537 transcription regulator activator activity
Biological Process
KEGG
- hsa01522 Endocrine resistance
- KEGG:hsa04330 Notch signaling pathway
- KEGG:hsa04658 Th1 and Th2 cell differentiation
- KEGG:hsa04919 Thyroid hormone signaling pathway
- KEGG:hsa05020 Prion disease
- KEGG:hsa05165 Human papillomavirus infection
- KEGG:hsa05200 Pathways in cancer
- KEGG:hsa05206 MicroRNAs in cancer
- KEGG:hsa05224 Breast cancer
Reactome
- R-hsa-2122948 activated notch1 transmits signal to the nucleus
- R-hsa-8953897 cellular responses to stimuli
- R-hsa-9711123 cellular response to chemical stress
- R-hsa-5083630 defective lfng causes scdo3
- R-hsa-3906995 diseases associated with o glycosylation of proteins
- R-hsa-3781865 diseases of glycosylation
- R-hsa-5668914 diseases of metabolism
- R-hsa-5663202 diseases of signal transduction by growth factor receptors and second messengers
- R-hsa-2644605 fbxw7 mutants and notch1 in cancer
- R-hsa-9793380 formation of paraxial mesoderm
- R-hsa-9758941 gastrulation
- R-hsa-9755511 keap1 nfe2l2 pathway
- R-hsa-9022699 mecp2 regulates neuronal receptors and channels
- R-hsa-9818030 nfe2l2 regulating tumorigenic genes
- R-hsa-2122947 notch1 intracellular domain regulates transcription
- R-hsa-9013508 notch3 intracellular domain regulates transcription
- R-hsa-9013695 notch4 intracellular domain regulates transcription
- R-hsa-350054 notch hlh transcription pathway
- R-hsa-9759194 nuclear events mediated by nfe2l2
- R-hsa-9725371 nuclear events stimulated by alk signaling in cancer
- R-hsa-1912422 pre notch expression and processing
- R-hsa-1912420 pre notch processing in golgi
- R-hsa-1912399 pre notch processing in the endoplasmic reticulum
- R-hsa-186712 regulation of beta cell development
- R-hsa-210744 regulation of gene expression in late stage branching morphogenesis pancreatic bud precursor cells
- R-hsa-9818749 regulation of nfe2l2 gene expression
- R-hsa-73857 rna polymerase ii transcription
- R-hsa-8941856 runx3 regulates notch signaling
- R-hsa-9700206 signaling by alk in cancer
- R-hsa-157118 signaling by notch
- R-hsa-1980143 signaling by notch1
- R-hsa-2691230 signaling by notch1 hd domain mutants in cancer
- R-hsa-2644602 signaling by notch1 pest domain mutants in cancer
- R-hsa-2660825 signaling by notch1 t 7 9 notch1 m1580 k2555 translocation mutant
- R-hsa-9012852 signaling by notch3
- R-hsa-9013694 signaling by notch4
- R-hsa-9824272 somitogenesis
- R-hsa-8986944 transcriptional regulation by mecp2
- R-hsa-8878159 transcriptional regulation by runx3
Mediation Categories
Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationImmune mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
24 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| NOTCH1 | CDK3 | Q00526 | T | 2,511 | phosphorylation | PhosphoSite | |
| NOTCH1 | CDK3 | Q00526 | S | 2,516 | phosphorylation | PhosphoSite | |
| NOTCH1 | PLK1 | P53350 | S | 1,791 | phosphorylation | PhosphoSite | |
| NOTCH1 | PLK1 | P53350 | S | 2,439 | phosphorylation | PhosphoSite | |
| NOTCH1 | CDK19 | Q9BWU1 | S | 2,513 | phosphorylation | PhosphoSite | |
| NOTCH1 | CDK19 | Q9BWU1 | T | 2,511 | phosphorylation | PhosphoSite | |
| NOTCH1 | CDK19 | Q9BWU1 | S | 2,516 | phosphorylation | PhosphoSite | |
| NOTCH1 | CDK8 | P49336 | S | 2,513 | phosphorylation | PhosphoSite | |
| NOTCH1 | CDK8 | P49336 | T | 2,511 | phosphorylation | PhosphoSite | |
| NOTCH1 | CDK8 | P49336 | S | 2,516 | phosphorylation | PhosphoSite |
Ligand-Receptor Signaling
67 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| receptor | receptor | CellPhoneDB | No | Yes | No | Yes | No |
| receptor | receptor | GO_Intercell | No | Yes | No | Yes | No |
| receptor | receptor | HPMR | No | Yes | No | Yes | No |
| receptor | receptor | ICELLNET | No | Yes | No | Yes | No |
| receptor | receptor | CellChatDB | No | Yes | No | Yes | No |
| receptor | receptor | CellTalkDB | No | Yes | No | Yes | No |
| receptor | receptor | Surfaceome | No | Yes | No | Yes | No |
| receptor | receptor | Ramilowski2015 | No | Yes | No | Yes | No |
| receptor | receptor | Kirouac2010 | No | Yes | No | Yes | No |
| receptor | receptor | Guide2Pharma | No | Yes | No | Yes | No |
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Regulatory Interaction Network
90 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| NOTC1 | P46531 | TFE2 | P15923 | Yes | No | Yes | SIGNOR | SIGNOR:9528794 |
| PIN1 | Q13526 | NOTC1 | P46531 | Yes | Yes | No | SIGNORELMIntActLMPIDLit-BM-17 | LMPID:19151708SIGNOR:19151708IntAct:19151708IntAct:38891776Lit-BM-17:19151708ELM:19151708 |
| CTNB1 | P35222 | NOTC1 | P46531 | Yes | Yes | No | HINTSIGNOR | HINT:19000719SIGNOR:19000719HINT:33189893 |
| GXLT1 | Q4G148 | NOTC1 | P46531 | Yes | Yes | No | SIGNOR | SIGNOR:22117070 |
| KCC4 | Q16566 | NOTC1 | P46531 | Yes | Yes | No | SIGNOR | SIGNOR:23103515 |
| CSK | P41240 | NOTC1 | P46531 | Yes | Yes | No | SIGNOR | SIGNOR:22479394 |
| KAT5 | Q92993 | NOTC1 | P46531 | Yes | Yes | Yes | WangCui2007SIGNOR | SIGNOR:17636029 |
| CNTN6 | Q9UQ52 | NOTC1 | P46531 | Yes | Yes | No | connectomeDB2020SIGNOR | connectomeDB2020:15082708SIGNOR:15082708 |
| XXLT1 | Q8NBI6 | NOTC1 | P46531 | Yes | Yes | No | SIGNOR | SIGNOR:22117070 |
| DYRK2 | Q92630 | NOTC1 | P46531 | Yes | No | Yes | SIGNORPhosphoSitePhosphoSite_ProtMapperProtMapper | PhosphoSite:25344755PhosphoSite:27335110SIGNOR:31605148PhosphoSite:31605148PhosphoSite:27806347 |
Protein Complex Composition
18 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| KAT2BMAPK7MEF2CMEF2DMYO18ANOTCH1TAF1TAF10TAF11TAF12TAF2TAF4TAF5TAF7TAF8 | O00268P21675P46531Q06413Q12962Q13164Q14814Q15542Q15544Q15545Q16514Q6P1X5Q7Z7C8Q92614Q92831 | 1:1:1:1:1:1:1:1:1:1:1:1:1:1:1 | NetworkBlastCompleat | Compleat:HC6335 | ||
| BTRCMDM2NOTCH1RELASNAI1 | O95863P46531Q00987Q04206Q9Y297 | 1:1:1:1:1 | CompleatCFinder | Compleat:HC5120 | ||
| NOTCH1 | P46531 | 2 | PDB | PDB:3etoPDB:2f8yPDB:5fmaPDB:2he0PDB:3i08PDB:1yyhPDB:3l95 | ||
| APH1ANCSTNNOTCH1PSEN1PSENEN | P46531P49768Q92542Q96BI3Q9NZ42 | 1:1:1:1:1 | PDB | PDB:6idf | ||
| NOTCH1NRARPRBPJ | P46531Q06330Q7Z6K4 | 2:2:2 | PDB | PDB:6py8 | ||
| MAML1NOTCH1RBPJZNF589 | P46531Q06330Q86UQ0Q92585 | 0:0:0:0 | hu.MAP | |||
| MAML3MEF2CNOTCH1 | P46531Q06413Q96JK9 | 1:1:1 | CompleatCFinder | Compleat:HC7997 | ||
| NOTCH1POGLUT1 | P46531Q8NBL1 | 1:1 | PDB | PDB:5ub5PDB:5l0r |
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Isolation & Detection Technology
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Size Exclusion Chromatography | R Sequencing | 1 | 28211531 |
Sequence, Structure & Domains
Sequences
Length
2,555
Mass
272,505
Sequence
MPPLLAPLLCLALLPALAARGPRCSQPGETCLNGGKCEAANGTEACVCGGAFVGPRCQDPNPCLSTPCKNAGTCHVVDRRGVADYACSCALGFSGPLCLTPLDNACLTNPCRNGGTCDLLTLTEYKCRCPPGWSGKSCQQADPCASNPCANGGQCLPFEASYICHCPPSFHGPTCRQDVNECGQKPGLCRHGGTCHNEVGSYRCVCRATHTGPNCERPYVPCSPSPCQNGGTCRPTGDVTHECACLPGFTGQNCEENIDDCPGNNCKNGGACVDGVNTYNCRCPPEWTGQYCTEDVDECQLMPNACQNGGTCHNTHGGYNCVCVNGWTGEDCSENIDDCASAACFHGATCHDRVASFYCECPHGRTGLLCHLNDACISNPCNEGSNCDTNPVNGKAICTCPSGYTGPACSQDVDECSLGANPCEHAGKCINTLGSFECQCLQGYTGPRCEIDVNECVSNPCQNDATCLDQIGEFQCICMPGYEGVHCEVNTDECASSPCLHNGRCLDKINEFQCECPTGFTGHLCQYDVDECASTPCKNGAKCLDGPNTYTCVCTEGYTGTHCEVDIDECDPDPCHYGSCKDGVATFTCLCRPGYTGHHCETNINECSSQPCRHGGTCQDRDNAYLCFCLKGTTGPNCEINLDDCASSPCDSGTCLDKIDGYECACEPGYTGSMCNINIDECAGNPCHNGGTCEDGINGFTCRCPEGYHDPTCLSEVNECNSNPCVHGACRDSLNGYKCDCDPGWSGTNCDINNNECESNPCVNGGTCKDMTSGYVCTCREGFSGPNCQTNINECASNPCLNQGTCIDDVAGYKCNCLLPYTGATCEVVLAPCAPSPCRNGGECRQSEDYESFSCVCPTGWQGQTCEVDINECVLSPCRHGASCQNTHGGYRCHCQAGYSGRNCETDIDDCRPNPCHNGGSCTDGINTAFCDCLPGFRGTFCEEDINECASDPCRNGANCTDCVDSYTCTCPAGFSGIHCENNTPDCTESSCFNGGTCVDGINSFTCLCPPGFTGSYCQHDVNECDSQPCLHGGTCQDGCGSYRCTCPQGYTGPNCQNLVHWCDSSPCKNGGKCWQTHTQYRCECPSGWTGLYCDVPSVSCEVAAQRQGVDVARLCQHGGLCVDAGNTHHCRCQAGYTGSYCEDLVDECSPSPCQNGATCTDYLGGYSCKCVAGYHGVNCSEEIDECLSHPCQNGGTCLDLPNTYKCSCPRGTQGVHCEINVDDCNPPVDPVSRSPKCFNNGTCVDQVGGYSCTCPPGFVGERCEGDVNECLSNPCDARGTQNCVQRVNDFHCECRAGHTGRRCESVINGCKGKPCKNGGTCAVASNTARGFICKCPAGFEGATCENDARTCGSLRCLNGGTCISGPRSPTCLCLGPFTGPECQFPASSPCLGGNPCYNQGTCEPTSESPFYRCLCPAKFNGLLCHILDYSFGGGAGRDIPPPLIEEACELPECQEDAGNKVCSLQCNNHACGWDGGDCSLNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQRAEGQCNPLYDQYCKDHFSDGHCDQGCNSAECEWDGLDCAEHVPERLAAGTLVVVVLMPPEQLRNSSFHFLRELSRVLHTNVVFKRDAHGQQMIFPYYGREEELRKHPIKRAAEGWAAPDALLGQVKASLLPGGSEGGRRRRELDPMDVRGSIVYLEIDNRQCVQASSQCFQSATDVAAFLGALASLGSLNIPYKIEAVQSETVEPPPPAQLHFMYVAAAAFVLLFFVGCGVLLSRKRRRQHGQLWFPEGFKVSEASKKKRREPLGEDSVGLKPLKNASDGALMDDNQNEWGDEDLETKKFRFEEPVVLPDLDDQTDHRQWTQQHLDAADLRMSAMAPTPPQGEVDADCMDVNVRGPDGFTPLMIASCSGGGLETGNSEEEEDAPAVISDFIYQGASLHNQTDRTGETALHLAARYSRSDAAKRLLEASADANIQDNMGRTPLHAAVSADAQGVFQILIRNRATDLDARMHDGTTPLILAARLAVEGMLEDLINSHADVNAVDDLGKSALHWAAAVNNVDAAVVLLKNGANKDMQNNREETPLFLAAREGSYETAKVLLDHFANRDITDHMDRLPRDIAQERMHHDIVRLLDEYNLVRSPQLHGAPLGGTPTLSPPLCSPNGYLGSLKPGVQGKKVRKPSSKGLACGSKEAKDLKARRKKSQDGKGCLLDSSGMLSPVDSLESPHGYLSDVASPPLLPSPFQQSPSVPLNHLPGMPDTHLGIGHLNVAAKPEMAALGGGGRLAFETGPPRLSHLPVASGTSTVLGSSSGGALNFTVGGSTSLNGQCEWLSRLQSGMVPNQYNPLRGSVAPGPLSTQAPSLQHGMVGPLHSSLAASALSQMMSYQGLPSTRLATQPHLVQTQQVQPQNLQMQQQNLQPANIQQQQSLQPPPPPPQPHLGVSSAASGHLGRSFLSGEPSQADVQPLGPSSLAVHTILPQESPALPTSLPSSLVPPVTAAQFLTPPSQHSYSSPVDNTPSHQLQVPEHPFLTPSPESPDQWSSSSPHSNVSDWSEGVSSPPTSMQSQIARIPEAFK
3D Structural Models
Turn
190..192; 493..496; 500..502; 832..835; 1477..1482; 1486..1489; 1499..1501; 1530..1532; 1747..1752; 1925..1927
Helix
143..146; 181..184; 415..417; 455..458; 756..759; 794..797; 872..875; 1448..1450; 1452..1457; 1465..1467; 1470..1472; 1473..1476; 1492..1494; 1496..1498; 1507..1509; 1512..1519; 1533..1539; 1547..1549; 1552..1559; 1582..1587; 1589..1600; 1685..1688; 1696..1708; 1736..1741; 1743..1746; 1884..1890; 1909..1914; 1931..1937; 1941..1949; 1964..1970; 1974..1982; 1998..2005; 2008..2016; 2031..2037; 2041..2049; 2064..2071; 2074..2082; 2097..2103; 2107..2115
Beta Strand
154..157; 162..165; 170..175; 194..198; 201..205; 210..212; 232..235; 237..239; 241..244; 249..254; 271..274; 279..282; 289..292; 418..420; 422..424; 428..432; 435..439; 444..446; 466..470; 473..477; 482..484; 504..507; 512..515; 520..522; 767..771; 774..778; 783..785; 805..809; 812..816; 821..823; 843..846; 853..856; 861..863; 883..887; 890..894; 899..901; 921..925; 928..932; 937..939; 1460..1462; 1502..1504; 1542..1544; 1563..1565; 1571..1580; 1602..1606; 1616..1620; 1672..1681; 1714..1716; 1718..1724; 1733..1735; 1755..1760; 1767..1769; 1983..1985
3D Structure
Electron microscopy (1); NMR spectroscopy (6); X-ray crystallography (22)
Domain & Motif Annotations
Compositional Bias
2379..2408; Low complexity; 2483..2502; Polar residues; 2512..2527; Low complexity; 2528..2547; Polar residues
Repeat
1449..1489; LNR 1; 1490..1531; LNR 2; 1532..1571; LNR 3; 1927..1956; ANK 1; 1960..1990; ANK 2; 1994..2023; ANK 3; 2027..2056; ANK 4; 2060..2089; ANK 5; 2095..2122; ANK 6
Domain (CC)
Interaction with PSEN1 causes partial unwinding of the transmembrane helix, facilitating access to the scissile peptide bond.
Domain (FT)
20..58; EGF-like 1; 59..99; EGF-like 2; 102..139; EGF-like 3; 140..176; EGF-like 4; 178..216; EGF-like 5; calcium-binding; 218..255; EGF-like 6; 257..293; EGF-like 7; calcium-binding; 295..333; EGF-like 8; calcium-binding; 335..371; EGF-like 9; calcium-binding; 372..410; EGF-like 10; 412..450; EGF-like 11; calcium-binding; 452..488; EGF-like 12; calcium-binding; 490..526; EGF-like 13; calcium-binding; 528..564; EGF-like 14; calcium-binding; 566..601; EGF-like 15; calcium-binding; 603..639; EGF-like 16; calcium-binding; 641..676; EGF-like 17; calcium-binding; 678..714; EGF-like 18; calcium-binding; 716..751; EGF-like 19; calcium-binding; 753..789; EGF-like 20; 791..827; EGF-like 21; calcium-binding; 829..867; EGF-like 22; 869..905; EGF-like 23; calcium-binding; 907..943; EGF-like 24; 945..981; EGF-like 25; calcium-binding; 983..1019; EGF-like 26; 1021..1057; EGF-like 27; 1059..1095; EGF-like 28; 1097..1143; EGF-like 29; 1145..1181; EGF-like 30; 1183..1219; EGF-like 31; calcium-binding; 1221..1265; EGF-like 32; calcium-binding; 1267..1305; EGF-like 33; 1307..1346; EGF-like 34; 1348..1384; EGF-like 35; 1387..1426; EGF-like 36
Region
420..421; Interaction with DLL4; 448..452; Interaction with DLL4; 1728..1760; Interaction with PSEN1; 1780..1808; Disordered; 1947..1955; HIF1AN-binding; 2014..2022; HIF1AN-binding; 2151..2194; Disordered; 2379..2447; Disordered; 2483..2555; Disordered
Protein Families
NOTCH family
Sequence Similarities
Belongs to the NOTCH family.
Clinical Relevance
Disease Involvement
Cancer-related genesDisease variant
Related Diseases
Biomarker
Phase 1; Phase 1/2
Drugs
Interaction Protein
ENSG00000004487ENSG00000100603ENSG00000101384ENSG00000109670ENSG00000161021ENSG00000168214ENSG00000196782
Interaction Count
7
Interaction Dataset
intact_biogrid