| IED ID | IndEnz0002007835 |
| Enzyme Type ID | protease007835 |
| Protein Name |
Neurogenic locus notch homolog protein 3 Notch 3 Cleaved into: Notch 3 extracellular truncation; Notch 3 intracellular domain |
| Gene Name | NOTCH3 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MGPGARGRRRRRRPMSPPPPPPPVRALPLLLLLAGPGAAAPPCLDGSPCANGGRCTQLPSREAACLCPPGWVGERCQLEDPCHSGPCAGRGVCQSSVVAGTARFSCRCPRGFRGPDCSLPDPCLSSPCAHGARCSVGPDGRFLCSCPPGYQGRSCRSDVDECRVGEPCRHGGTCLNTPGSFRCQCPAGYTGPLCENPAVPCAPSPCRNGGTCRQSGDLTYDCACLPGFEGQNCEVNVDDCPGHRCLNGGTCVDGVNTYNCQCPPEWTGQFCTEDVDECQLQPNACHNGGTCFNTLGGHSCVCVNGWTGESCSQNIDDCATAVCFHGATCHDRVASFYCACPMGKTGLLCHLDDACVSNPCHEDAICDTNPVNGRAICTCPPGFTGGACDQDVDECSIGANPCEHLGRCVNTQGSFLCQCGRGYTGPRCETDVNECLSGPCRNQATCLDRIGQFTCICMAGFTGTYCEVDIDECQSSPCVNGGVCKDRVNGFSCTCPSGFSGSTCQLDVDECASTPCRNGAKCVDQPDGYECRCAEGFEGTLCDRNVDDCSPDPCHHGRCVDGIASFSCACAPGYTGTRCESQVDECRSQPCRHGGKCLDLVDKYLCRCPSGTTGVNCEVNIDDCASNPCTFGVCRDGINRYDCVCQPGFTGPLCNVEINECASSPCGEGGSCVDGENGFRCLCPPGSLPPLCLPPSHPCAHEPCSHGICYDAPGGFRCVCEPGWSGPRCSQSLARDACESQPCRAGGTCSSDGMGFHCTCPPGVQGRQCELLSPCTPNPCEHGGRCESAPGQLPVCSCPQGWQGPRCQQDVDECAGPAPCGPHGICTNLAGSFSCTCHGGYTGPSCDQDINDCDPNPCLNGGSCQDGVGSFSCSCLPGFAGPRCARDVDECLSNPCGPGTCTDHVASFTCTCPPGYGGFHCEQDLPDCSPSSCFNGGTCVDGVNSFSCLCRPGYTGAHCQHEADPCLSRPCLHGGVCSAAHPGFRCTCLESFTGPQCQTLVDWCSRQPCQNGGRCVQTGAYCLCPPGWSGRLCDIRSLPCREAAAQIGVRLEQLCQAGGQCVDEDSSHYCVCPEGRTGSHCEQEVDPCLAQPCQHGGTCRGYMGGYMCECLPGYNGDNCEDDVDECASQPCQHGGSCIDLVARYLCSCPPGTLGVLCEINEDDCGPGPPLDSGPRCLHNGTCVDLVGGFRCTCPPGYTGLRCEADINECRSGACHAAHTRDCLQDPGGGFRCLCHAGFSGPRCQTVLSPCESQPCQHGGQCRPSPGPGGGLTFTCHCAQPFWGPRCERVARSCRELQCPVGVPCQQTPRGPRCACPPGLSGPSCRSFPGSPPGASNASCAAAPCLHGGSCRPAPLAPFFRCACAQGWTGPRCEAPAAAPEVSEEPRCPRAACQAKRGDQRCDRECNSPGCGWDGGDCSLSVGDPWRQCEALQCWRLFNNSRCDPACSSPACLYDNFDCHAGGRERTCNPVYEKYCADHFADGRCDQGCNTEECGWDGLDCASEVPALLARGVLVLTVLLPPEELLRSSADFLQRLSAILRTSLRFRLDAHGQAMVFPYHRPSPGSEPRARRELAPEVIGSVVMLEIDNRLCLQSPENDHCFPDAQSAADYLGALSAVERLDFPYPLRDVRGEPLEPPEPSVPLLPLLVAGAVLLLVILVLGVMVARRKREHSTLWFPEGFSLHKDVASGHKGRREPVGQDALGMKNMAKGESLMGEVATDWMDTECPEAKRLKVEEPGMGAEEAVDCRQWTQHHLVAADIRVAPAMALTPPQGDADADGMDVNVRGPDGFTPLMLASFCGGALEPMPTEEDEADDTSASIISDLICQGAQLGARTDRTGETALHLAARYARADAAKRLLDAGADTNAQDHSGRTPLHTAVTADAQGVFQILIRNRSTDLDARMADGSTALILAARLAVEGMVEELIASHADVNAVDELGKSALHWAAAVNNVEATLALLKNGANKDMQDSKEETPLFLAAREGSYEAAKLLLDHFANREITDHLDRLPRDVAQERLHQDIVRLLDQPSGPRSPPGPHGLGPLLCPPGAFLPGLKAAQSGSKKSRRPPGKAGLGPQGPRGRGKKLTLACPGPLADSSVTLSPVDSLDSPRPFGGPPASPGGFPLEGPYAAATATAVSLAQLGGPGRAGLGRQPPGGCVLSLGLLNPVAVPLDWARLPPPAPPGPSFLLPLAPGPQLLNPGTPVSPQERPPPYLAVPGHGEEYPAAGAHSSPPKARFLRVPSEHPYLTPSPESPEHWASPSPPSLSDWSESTPSPATATGAMATTTGALPAQPLPLSVPSSLAQAQTQLGPQPEVTPKRQVLA |
| Enzyme Length | 2321 |
| Uniprot Accession Number | Q9UM47 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). 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. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). {ECO:0000250|UniProtKB:Q9R172, ECO:0000269|PubMed:15350543}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (10); Chain (3); Compositional bias (4); Disulfide bond (111); Domain (34); Glycosylation (3); Helix (15); Modified residue (1); Natural variant (122); Region (3); Repeat (8); Signal peptide (1); Site (1); Topological domain (2); Transmembrane (1); Turn (8) |
| Keywords | 3D-structure;ANK repeat;Activator;Cell membrane;Developmental protein;Differentiation;Disease variant;Disulfide bond;EGF-like domain;Glycoprotein;Membrane;Methylation;Notch signaling pathway;Nucleus;Phosphoprotein;Receptor;Reference proteome;Repeat;Signal;Transcription;Transcription regulation;Transmembrane;Transmembrane helix |
| Interact With | Itself; P86480; Q9R1P4 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15350543}; Single-pass type I membrane protein.; SUBCELLULAR LOCATION: [Notch 3 intracellular domain]: Nucleus. Note=Following proteolytical processing NICD is translocated to the nucleus. |
| Modified Residue | MOD_RES 2174; /note=Omega-N-methylarginine; /evidence=ECO:0007744|PubMed:24129315 |
| Post Translational Modification | PTM: 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. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane. {ECO:0000269|PubMed:15350543}.; PTM: Phosphorylated. {ECO:0000250}.; PTM: Hydroxylated by HIF1AN. {ECO:0000269|PubMed:18299578}. |
| Signal Peptide | SIGNAL 1..39; /evidence=ECO:0000255 |
| Structure 3D | X-ray crystallography (5) |
| Cross Reference PDB | 4ZLP; 5CZV; 5CZX; 6WQU; 6XSW; |
| Mapped Pubmed ID | 10075724; 10366590; 10459009; 10545110; 10551863; 10669757; 10734111; 10935626; 10935637; 10964718; 11006133; 11032621; 11044625; 11112321; 11135303; 11413271; 11524432; 11530204; 11707585; 11740940; 11861701; 11866432; 11891328; 11971902; 11978185; 12049766; 12050117; 12210282; 12386158; 12480758; 12486116; 12511775; 12678157; 1295745; 14566327; 14767686; 15096408; 15304596; 15533827; 15546612; 15692013; 15694192; 15760269; 15829515; 15879553; 15987768; 16093323; 16107360; 16385447; 16426270; 16492242; 16717210; 16796587; 16807713; 16833034; 16899352; 16998728; 17157496; 17301032; 17331978; 17332745; 17390743; 17474147; 1764995; 17690848; 17696940; 17804716; 17822320; 17822871; 17853970; 17854869; 17878719; 17920003; 17939118; 17996090; 18022198; 18060036; 18069660; 18075987; 18184405; 18243100; 18339869; 18347015; 18483410; 18499132; 18593473; 18626519; 18632624; 18758477; 18765654; 18941948; 18948701; 18974129; 19006080; 19018300; 19043263; 19054571; 19056668; 19139365; 19150886; 19167727; 19174371; 19208840; 19242647; 19293235; 19372454; 19373490; 19404845; 19417009; 19576955; 19640841; 19701457; 19723635; 19735738; 19816816; 19825845; 19835636; 19855400; 19859875; 19881544; 19913121; 20038773; 20040020; 20069356; 20167921; 20169447; 20170518; 20197277; 20329594; 20359736; 20472562; 20554499; 20614134; 20624166; 20628086; 20628624; 20634891; 20651241; 20671266; 20711500; 20801121; 20804727; 20813781; 20819128; 20935329; 21078731; 21097675; 21103979; 21118965; 21124806; 21169401; 21217157; 21245095; 21409506; 21464368; 21471519; 21490058; 21508102; 21551231; 21602525; 21616505; 21628316; 21673954; 21702048; 21705670; 21743488; 21852154; 21890822; 21900206; 21920521; 21940234; 21940951; 21951372; 21988832; 22006983; 22079340; 22079830; 22082899; 22117196; 22120716; 22133740; 22153798; 22153900; 22157815; 22159056; 22204979; 22218279; 22292737; 22310065; 22367839; 22373597; 22396495; 22422895; 22487239; 22526456; 22623959; 22664156; 22691042; 22705236; 22806125; 22948298; 23010708; 23019585; 23028706; 23036509; 23226563; 23314443; 23319290; 23412372; 23414517; 23444212; 23460375; 23465844; 23468978; 23492684; 23572112; 23587639; 23602593; 23610446; 23637910; 23645556; 23649002; 23649698; 23729168; 23747483; 23773728; 23836039; 23845442; 23847153; 23975424; 23999936; 24026140; 24041655; 24086431; 24138322; 24139282; 24143218; 24151014; 24244701; 24336671; 24367688; 24480794; 24643801; 24671051; 24728738; 24743243; 24788939; 24797362; 24810798; 24816653; 24842903; 24844136; 24905589; 24984200; 25096610; 25098330; 25105908; 25125655; 25150590; 25169943; 25171754; 25260852; 25297585; 25356737; 25368251; 25381438; 25412914; 25416974; 25417103; 25512616; 25572698; 25595846; 25604251; 25609649; 25622783; 25623805; 25668819; 25700162; 25738469; 25807436; 25846406; 25864518; 25870235; 25953367; 25957400; 25982499; 26002683; 26051713; 26270344; 26308724; 26634853; 26640406; 26694515; 26715087; 26838758; 26858125; 26876201; 26912635; 26977885; 27035162; 27035429; 27124156; 27157619; 27241575; 27266621; 27312418; 27370894; 27375140; 27431799; 27445438; 27455010; 27460529; 27633819; 27697639; 27717083; 27749937; 27770607; 27780727; 27781952; 27791012; 27840976; 27841855; 27881154; 27887917; 27941324; 27966788; 27986595; 28013292; 28061457; 28084316; 28108512; 28281965; 28415631; 28416766; 28440410; 28446540; 28476798; 28601945; 28710804; 28714011; 28719575; 28775167; 28867359; 28968839; 29023469; 29170450; 29188607; 29259010; 29304760; 29363903; 29463793; 29532409; 29544907; 29610298; 29643474; 29659670; 29700822; 29781034; 29801872; 29973002; 29980472; 29991510; 30030828; 30081092; 30180881; 30309883; 30321499; 30335896; 30341249; 30355220; 30454692; 30502484; 30545719; 30591475; 30732676; 30806291; 30859180; 31212292; 31288479; 31324198; 31339861; 31346528; 31467432; 31554780; 31566039; 31647781; 31667734; 31720972; 31729093; 31770532; 31792094; 31843982; 31901894; 31915071; 31960911; 32073729; 32122318; 32141180; 32185220; 32210034; 32210188; 32277177; 32313117; 32337960; 32468036; 32470649; 32499639; 32573853; 32662081; 32732295; 32929895; 32980981; 33021719; 33029756; 33091750; 33099573; 33161844; 33169924; 33268848; 33305890; 33452458; 33664344; 33681964; 33712516; 33775697; 33894418; 34006834; 34042293; 34092645; 34257585; 34404235; 34446744; 34688318; 34706522; 34831437; 7918097; 8293978; 8681805; 9187150; 9207795; 9244302; 9604939; 9651681; 9653148; 9727485; |
| Motif | |
| Gene Encoded By | |
| Mass | 243,631 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |