ID NOTC3_MOUSE Reviewed; 2318 AA. AC Q61982; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 1. DT 12-OCT-2022, entry version 209. DE RecName: Full=Neurogenic locus notch homolog protein 3; DE Short=Notch 3; DE Contains: DE RecName: Full=Notch 3 extracellular truncation; DE Contains: DE RecName: Full=Notch 3 intracellular domain; DE Flags: Precursor; GN Name=Notch3; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=ICR X Swiss Webster; RX PubMed=7918097; DOI=10.1016/0925-4773(94)90081-7; RA Lardelli M., Dalstrand J., Lendahl U.; RT "The novel Notch homologue mouse Notch 3 lacks specific epidermal growth RT factor-repeats and is expressed in proliferating neuroepithelium."; RL Mech. Dev. 46:123-136(1994). RN [2] RP PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF MET-1664. RX PubMed=11518718; DOI=10.1074/jbc.m107234200; RA Saxena M.T., Schroeter E.H., Mumm J.S., Kopan R.; RT "Murine notch homologs (N1-4) undergo presenilin-dependent proteolysis."; RL J. Biol. Chem. 276:40268-40273(2001). RN [3] RP PROTEOLYTIC PROCESSING. RX PubMed=11459941; DOI=10.1073/pnas.161269998; RA Mizutani T., Taniguchi Y., Aoki T., Hashimoto N., Honjo T.; RT "Conservation of the biochemical mechanisms of signal transduction among RT mammalian Notch family members."; RL Proc. Natl. Acad. Sci. U.S.A. 98:9026-9031(2001). RN [4] RP INTERACTION WITH MAML1. RX PubMed=15019995; DOI=10.1016/j.gene.2003.12.007; RA Wu L., Kobayashi K., Sun T., Gao P., Liu J., Nakamura M., Weisberg E., RA Mukhopadhyay N.K., Griffin J.D.; RT "Cloning and functional characterization of the murine mastermind-like 1 RT (Maml1) gene."; RL Gene 328:153-165(2004). RN [5] RP INTERACTION WITH HIF1AN. RX PubMed=17573339; DOI=10.1074/jbc.m704102200; RA Coleman M.L., McDonough M.A., Hewitson K.S., Coles C., Mecinovic J., RA Edelmann M., Cook K.M., Cockman M.E., Lancaster D.E., Kessler B.M., RA Oldham N.J., Ratcliffe P.J., Schofield C.J.; RT "Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor RT inhibiting hypoxia-inducible factor."; RL J. Biol. Chem. 282:24027-24038(2007). RN [6] RP HYDROXYLATION BY HIF1AN. RX PubMed=18299578; DOI=10.1073/pnas.0711591105; RA Zheng X., Linke S., Dias J.M., Zheng X., Gradin K., Wallis T.P., RA Hamilton B.R., Gustafsson M., Ruas J.L., Wilkins S., Bilton R.L., RA Brismar K., Whitelaw M.L., Pereira T., Gorman J.J., Ericson J., Peet D.J., RA Lendahl U., Poellinger L.; RT "Interaction with factor inhibiting HIF-1 defines an additional mode of RT cross-coupling between the Notch and hypoxia signaling pathways."; RL Proc. Natl. Acad. Sci. U.S.A. 105:3368-3373(2008). CC -!- FUNCTION: Functions as a receptor for membrane-bound ligands Jagged1, CC Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand CC activation through the released notch intracellular domain (NICD) it CC forms a transcriptional activator complex with RBPJ/RBPSUH and CC activates genes of the enhancer of split locus. Affects the CC implementation of differentiation, proliferation and apoptotic programs CC (By similarity). May play a role during CNS development. CC {ECO:0000250|UniProtKB:Q9R172, ECO:0000250|UniProtKB:Q9UM47}. CC -!- SUBUNIT: Interacts with PSMA1 (By similarity). Heterodimer of a C- CC terminal fragment N(TM) and a N-terminal fragment N(EC) which are CC probably linked by disulfide bonds. Interacts with MAML1, MAML2 and CC MAML3 which act as transcriptional coactivators for NOTCH3. Interacts CC with HIF1AN. {ECO:0000250, ECO:0000269|PubMed:15019995, CC ECO:0000269|PubMed:17573339}. CC -!- INTERACTION: CC PRO_0000007697; Q77CA8: LRORF2; Xeno; NbExp=3; IntAct=EBI-11292908, EBI-11292862; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9UM47}; CC Single-pass type I membrane protein. CC -!- SUBCELLULAR LOCATION: [Notch 3 intracellular domain]: Nucleus. CC Note=Following proteolytical processing NICD is translocated to the CC nucleus. CC -!- TISSUE SPECIFICITY: Proliferating neuroepithelium. CC -!- DEVELOPMENTAL STAGE: CNS development. CC -!- DOMAIN: The EGF-like domains 10 and 11 are required for binding the CC ligands JAG1 and DLL1. {ECO:0000250|UniProtKB:Q9UM47}. CC -!- PTM: Synthesized in the endoplasmic reticulum as an inactive form which CC is proteolytically cleaved by a furin-like convertase in the trans- CC Golgi network before it reaches the plasma membrane to yield an active, CC ligand-accessible form. Cleavage results in a C-terminal fragment N(TM) CC and a N-terminal fragment N(EC). Following ligand binding, it is CC cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane- CC associated intermediate fragment called notch extracellular truncation CC (NEXT). This fragment is then cleaved by presenilin dependent gamma- CC secretase to release a notch-derived peptide containing the CC intracellular domain (NICD) from the membrane. CC {ECO:0000269|PubMed:11459941, ECO:0000269|PubMed:11518718}. CC -!- PTM: Phosphorylated. CC -!- PTM: Hydroxylated by HIF1AN. {ECO:0000269|PubMed:18299578}. CC -!- SIMILARITY: Belongs to the NOTCH family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X74760; CAA52776.1; -; mRNA. DR CCDS; CCDS28614.1; -. DR PIR; S45306; S45306. DR RefSeq; NP_032742.1; NM_008716.2. DR AlphaFoldDB; Q61982; -. DR SMR; Q61982; -. DR BioGRID; 201811; 11. DR CORUM; Q61982; -. DR IntAct; Q61982; 3. DR MINT; Q61982; -. DR STRING; 10090.ENSMUSP00000085016; -. DR GlyGen; Q61982; 3 sites. DR iPTMnet; Q61982; -. DR PhosphoSitePlus; Q61982; -. DR CPTAC; non-CPTAC-3485; -. DR MaxQB; Q61982; -. DR PaxDb; Q61982; -. DR PeptideAtlas; Q61982; -. DR PRIDE; Q61982; -. DR ProteomicsDB; 293705; -. DR ABCD; Q61982; 2 sequenced antibodies. DR Antibodypedia; 3951; 732 antibodies from 43 providers. DR DNASU; 18131; -. DR Ensembl; ENSMUST00000087723; ENSMUSP00000085016; ENSMUSG00000038146. DR GeneID; 18131; -. DR KEGG; mmu:18131; -. DR UCSC; uc008bvx.1; mouse. DR CTD; 4854; -. DR MGI; MGI:99460; Notch3. DR VEuPathDB; HostDB:ENSMUSG00000038146; -. DR eggNOG; KOG1217; Eukaryota. DR GeneTree; ENSGT00940000160234; -. DR HOGENOM; CLU_000576_0_0_1; -. DR InParanoid; Q61982; -. DR OMA; RDCLQDA; -. DR OrthoDB; 7525at2759; -. DR PhylomeDB; Q61982; -. DR TreeFam; TF351641; -. DR Reactome; R-MMU-1912420; Pre-NOTCH Processing in Golgi. DR Reactome; R-MMU-350054; Notch-HLH transcription pathway. DR Reactome; R-MMU-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus. DR Reactome; R-MMU-9017802; Noncanonical activation of NOTCH3. DR BioGRID-ORCS; 18131; 1 hit in 74 CRISPR screens. DR ChiTaRS; Notch3; mouse. DR PRO; PR:Q61982; -. DR Proteomes; UP000000589; Chromosome 17. DR RNAct; Q61982; protein. DR Bgee; ENSMUSG00000038146; Expressed in external carotid artery and 281 other tissues. DR ExpressionAtlas; Q61982; baseline and differential. DR Genevisible; Q61982; MM. DR GO; GO:0015629; C:actin cytoskeleton; ISO:MGI. DR GO; GO:0009986; C:cell surface; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0005887; C:integral component of plasma membrane; IC:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:AgBase. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0043235; C:receptor complex; ISO:MGI. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0038023; F:signaling receptor activity; ISS:UniProtKB. DR GO; GO:0048844; P:artery morphogenesis; IMP:MGI. DR GO; GO:0007411; P:axon guidance; IBA:GO_Central. DR GO; GO:0030900; P:forebrain development; IGI:MGI. DR GO; GO:0072104; P:glomerular capillary formation; IEP:UniProtKB. DR GO; GO:0045596; P:negative regulation of cell differentiation; IMP:MGI. DR GO; GO:0045665; P:negative regulation of neuron differentiation; IMP:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:MGI. DR GO; GO:0014016; P:neuroblast differentiation; IMP:MGI. DR GO; GO:0030182; P:neuron differentiation; IMP:MGI. DR GO; GO:0048663; P:neuron fate commitment; IGI:MGI. DR GO; GO:0007219; P:Notch signaling pathway; IDA:UniProtKB. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:MGI. DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISO:MGI. DR Gene3D; 1.25.40.20; -; 1. DR InterPro; IPR002110; Ankyrin_rpt. DR InterPro; IPR036770; Ankyrin_rpt-contain_sf. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR013032; EGF-like_CS. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR008297; Notch. DR InterPro; IPR035993; Notch-like_dom_sf. DR InterPro; IPR022331; Notch_3. DR InterPro; IPR024600; Notch_C. DR InterPro; IPR000800; Notch_dom. DR InterPro; IPR010660; Notch_NOD_dom. DR InterPro; IPR011656; Notch_NODP_dom. DR Pfam; PF12796; Ank_2; 1. DR Pfam; PF13857; Ank_5; 1. DR Pfam; PF00008; EGF; 18. DR Pfam; PF07645; EGF_CA; 6. DR Pfam; PF12661; hEGF; 4. DR Pfam; PF06816; NOD; 1. DR Pfam; PF07684; NODP; 1. DR Pfam; PF00066; Notch; 3. DR PIRSF; PIRSF002279; Notch; 1. DR PRINTS; PR01452; LNOTCHREPEAT. DR PRINTS; PR01986; NOTCH3. DR SMART; SM00248; ANK; 6. DR SMART; SM01334; DUF3454; 1. DR SMART; SM00181; EGF; 34. DR SMART; SM00179; EGF_CA; 30. DR SMART; SM00004; NL; 3. DR SMART; SM01338; NOD; 1. DR SMART; SM01339; NODP; 1. DR SUPFAM; SSF48403; SSF48403; 1. DR SUPFAM; SSF57184; SSF57184; 5. DR SUPFAM; SSF90193; SSF90193; 3. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 4. DR PROSITE; PS00010; ASX_HYDROXYL; 18. DR PROSITE; PS00022; EGF_1; 33. DR PROSITE; PS01186; EGF_2; 27. DR PROSITE; PS50026; EGF_3; 34. DR PROSITE; PS01187; EGF_CA; 16. DR PROSITE; PS50258; LNR; 3. PE 1: Evidence at protein level; KW Activator; ANK repeat; Cell membrane; Developmental protein; KW Differentiation; Disulfide bond; EGF-like domain; Glycoprotein; Membrane; KW Methylation; Notch signaling pathway; Nucleus; Phosphoprotein; Receptor; KW Reference proteome; Repeat; Signal; Transcription; KW Transcription regulation; Transmembrane; Transmembrane helix. FT SIGNAL 1..39 FT /evidence="ECO:0000255" FT CHAIN 40..2318 FT /note="Neurogenic locus notch homolog protein 3" FT /id="PRO_0000007695" FT CHAIN 1630..2318 FT /note="Notch 3 extracellular truncation" FT /id="PRO_0000007696" FT CHAIN 1663..2318 FT /note="Notch 3 intracellular domain" FT /id="PRO_0000007697" FT TOPO_DOM 40..1643 FT /note="Extracellular" FT TRANSMEM 1644..1664 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1665..2318 FT /note="Cytoplasmic" FT DOMAIN 40..78 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 79..119 FT /note="EGF-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 120..157 FT /note="EGF-like 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 159..196 FT /note="EGF-like 4; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 198..235 FT /note="EGF-like 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 237..273 FT /note="EGF-like 6; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 275..313 FT /note="EGF-like 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 315..351 FT /note="EGF-like 8; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 352..390 FT /note="EGF-like 9" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 392..430 FT /note="EGF-like 10; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 432..468 FT /note="EGF-like 11; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 470..506 FT /note="EGF-like 12; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 508..544 FT /note="EGF-like 13; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 546..581 FT /note="EGF-like 14; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 583..619 FT /note="EGF-like 15; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 621..656 FT /note="EGF-like 16; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 658..694 FT /note="EGF-like 17; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 696..731 FT /note="EGF-like 18" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 735..771 FT /note="EGF-like 19" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 772..809 FT /note="EGF-like 20" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 811..848 FT /note="EGF-like 21; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 850..886 FT /note="EGF-like 22; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 888..923 FT /note="EGF-like 23; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 925..961 FT /note="EGF-like 24" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 963..999 FT /note="EGF-like 25" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1001..1035 FT /note="EGF-like 26" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1037..1083 FT /note="EGF-like 27" FT /evidence="ECO:0000305" FT DOMAIN 1085..1121 FT /note="EGF-like 28" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1123..1159 FT /note="EGF-like 29; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1161..1204 FT /note="EGF-like 30; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1206..1245 FT /note="EGF-like 31" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1247..1288 FT /note="EGF-like 32" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1290..1326 FT /note="EGF-like 33" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1336..1374 FT /note="EGF-like 34" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REPEAT 1388..1428 FT /note="LNR 1" FT REPEAT 1429..1466 FT /note="LNR 2" FT REPEAT 1468..1506 FT /note="LNR 3" FT REPEAT 1839..1868 FT /note="ANK 1" FT REPEAT 1872..1902 FT /note="ANK 2" FT REPEAT 1906..1935 FT /note="ANK 3" FT REPEAT 1939..1968 FT /note="ANK 4" FT REPEAT 1972..2001 FT /note="ANK 5" FT REGION 1..20 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2025..2045 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2058..2126 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2184..2318 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2242..2261 FT /note="PEST-like" FT COMPBIAS 1..15 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2184..2211 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2257..2284 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2294..2309 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 1572..1573 FT /note="Cleavage; by furin-like protease" FT /evidence="ECO:0000250" FT MOD_RES 2174 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q9UM47" FT CARBOHYD 1180 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1337 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1439 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 43..55 FT /evidence="ECO:0000250" FT DISULFID 49..66 FT /evidence="ECO:0000250" FT DISULFID 68..77 FT /evidence="ECO:0000250" FT DISULFID 83..94 FT /evidence="ECO:0000250" FT DISULFID 88..107 FT /evidence="ECO:0000250" FT DISULFID 109..118 FT /evidence="ECO:0000250" FT DISULFID 124..135 FT /evidence="ECO:0000250" FT DISULFID 129..145 FT /evidence="ECO:0000250" FT DISULFID 147..156 FT /evidence="ECO:0000250" FT DISULFID 163..175 FT /evidence="ECO:0000250" FT DISULFID 169..184 FT /evidence="ECO:0000250" FT DISULFID 186..195 FT /evidence="ECO:0000250" FT DISULFID 202..213 FT /evidence="ECO:0000250" FT DISULFID 207..223 FT /evidence="ECO:0000250" FT DISULFID 225..234 FT /evidence="ECO:0000250" FT DISULFID 241..252 FT /evidence="ECO:0000250" FT DISULFID 246..261 FT /evidence="ECO:0000250" FT DISULFID 263..272 FT /evidence="ECO:0000250" FT DISULFID 279..292 FT /evidence="ECO:0000250" FT DISULFID 286..301 FT /evidence="ECO:0000250" FT DISULFID 303..312 FT /evidence="ECO:0000250" FT DISULFID 319..330 FT /evidence="ECO:0000250" FT DISULFID 324..339 FT /evidence="ECO:0000250" FT DISULFID 341..350 FT /evidence="ECO:0000250" FT DISULFID 356..367 FT /evidence="ECO:0000250" FT DISULFID 361..378 FT /evidence="ECO:0000250" FT DISULFID 380..389 FT /evidence="ECO:0000250" FT DISULFID 396..409 FT /evidence="ECO:0000250" FT DISULFID 403..418 FT /evidence="ECO:0000250" FT DISULFID 420..429 FT /evidence="ECO:0000250" FT DISULFID 436..447 FT /evidence="ECO:0000250" FT DISULFID 441..456 FT /evidence="ECO:0000250" FT DISULFID 458..467 FT /evidence="ECO:0000250" FT DISULFID 474..485 FT /evidence="ECO:0000250" FT DISULFID 479..494 FT /evidence="ECO:0000250" FT DISULFID 496..505 FT /evidence="ECO:0000250" FT DISULFID 512..523 FT /evidence="ECO:0000250" FT DISULFID 517..532 FT /evidence="ECO:0000250" FT DISULFID 534..543 FT /evidence="ECO:0000250" FT DISULFID 550..560 FT /evidence="ECO:0000250" FT DISULFID 555..569 FT /evidence="ECO:0000250" FT DISULFID 571..580 FT /evidence="ECO:0000250" FT DISULFID 587..598 FT /evidence="ECO:0000250" FT DISULFID 592..607 FT /evidence="ECO:0000250" FT DISULFID 609..618 FT /evidence="ECO:0000250" FT DISULFID 625..635 FT /evidence="ECO:0000250" FT DISULFID 630..644 FT /evidence="ECO:0000250" FT DISULFID 646..655 FT /evidence="ECO:0000250" FT DISULFID 662..673 FT /evidence="ECO:0000250" FT DISULFID 667..682 FT /evidence="ECO:0000250" FT DISULFID 684..693 FT /evidence="ECO:0000250" FT DISULFID 700..710 FT /evidence="ECO:0000250" FT DISULFID 705..719 FT /evidence="ECO:0000250" FT DISULFID 721..730 FT /evidence="ECO:0000250" FT DISULFID 739..750 FT /evidence="ECO:0000250" FT DISULFID 744..759 FT /evidence="ECO:0000250" FT DISULFID 761..770 FT /evidence="ECO:0000250" FT DISULFID 776..787 FT /evidence="ECO:0000250" FT DISULFID 781..797 FT /evidence="ECO:0000250" FT DISULFID 799..808 FT /evidence="ECO:0000250" FT DISULFID 815..827 FT /evidence="ECO:0000250" FT DISULFID 821..836 FT /evidence="ECO:0000250" FT DISULFID 838..847 FT /evidence="ECO:0000250" FT DISULFID 854..865 FT /evidence="ECO:0000250" FT DISULFID 859..874 FT /evidence="ECO:0000250" FT DISULFID 876..885 FT /evidence="ECO:0000250" FT DISULFID 892..902 FT /evidence="ECO:0000250" FT DISULFID 897..911 FT /evidence="ECO:0000250" FT DISULFID 913..922 FT /evidence="ECO:0000250" FT DISULFID 929..940 FT /evidence="ECO:0000250" FT DISULFID 934..949 FT /evidence="ECO:0000250" FT DISULFID 951..960 FT /evidence="ECO:0000250" FT DISULFID 967..978 FT /evidence="ECO:0000250" FT DISULFID 972..987 FT /evidence="ECO:0000250" FT DISULFID 989..998 FT /evidence="ECO:0000250" FT DISULFID 1005..1016 FT /evidence="ECO:0000250" FT DISULFID 1010..1023 FT /evidence="ECO:0000250" FT DISULFID 1025..1034 FT /evidence="ECO:0000250" FT DISULFID 1041..1062 FT /evidence="ECO:0000305" FT DISULFID 1056..1071 FT /evidence="ECO:0000250" FT DISULFID 1073..1082 FT /evidence="ECO:0000250" FT DISULFID 1089..1100 FT /evidence="ECO:0000250" FT DISULFID 1094..1109 FT /evidence="ECO:0000250" FT DISULFID 1111..1120 FT /evidence="ECO:0000250" FT DISULFID 1127..1138 FT /evidence="ECO:0000250" FT DISULFID 1132..1147 FT /evidence="ECO:0000250" FT DISULFID 1149..1158 FT /evidence="ECO:0000250" FT DISULFID 1165..1183 FT /evidence="ECO:0000250" FT DISULFID 1177..1192 FT /evidence="ECO:0000250" FT DISULFID 1194..1203 FT /evidence="ECO:0000250" FT DISULFID 1210..1223 FT /evidence="ECO:0000250" FT DISULFID 1215..1233 FT /evidence="ECO:0000250" FT DISULFID 1235..1244 FT /evidence="ECO:0000250" FT DISULFID 1251..1262 FT /evidence="ECO:0000250" FT DISULFID 1256..1276 FT /evidence="ECO:0000250" FT DISULFID 1278..1287 FT /evidence="ECO:0000250" FT DISULFID 1294..1305 FT /evidence="ECO:0000250" FT DISULFID 1299..1314 FT /evidence="ECO:0000250" FT DISULFID 1316..1325 FT /evidence="ECO:0000250" FT DISULFID 1340..1351 FT /evidence="ECO:0000250" FT DISULFID 1345..1362 FT /evidence="ECO:0000250" FT DISULFID 1364..1373 FT /evidence="ECO:0000250" FT DISULFID 1388..1411 FT /evidence="ECO:0000250" FT DISULFID 1393..1406 FT /evidence="ECO:0000250" FT DISULFID 1402..1418 FT /evidence="ECO:0000250" FT DISULFID 1429..1452 FT /evidence="ECO:0000250" FT DISULFID 1434..1447 FT /evidence="ECO:0000250" FT DISULFID 1443..1459 FT /evidence="ECO:0000250" FT DISULFID 1468..1494 FT /evidence="ECO:0000250" FT DISULFID 1476..1489 FT /evidence="ECO:0000250" FT DISULFID 1485..1501 FT /evidence="ECO:0000250" FT MUTAGEN 1664 FT /note="M->L: No effect on NICD processing." FT /evidence="ECO:0000269|PubMed:11518718" SQ SEQUENCE 2318 AA; 244248 MW; A80D1F75AFF0185A CRC64; MGLGARGRRR RRRLMALPPP PPPMRALPLL LLLAGLGAAA PPCLDGSPCA NGGRCTHQQP SLEAACLCLP GWVGERCQLE DPCHSGPCAG RGVCQSSVVA GTARFSCRCL RGFQGPDCSQ PDPCVSRPCV HGAPCSVGPD GRFACACPPG YQGQSCQSDI DECRSGTTCR HGGTCLNTPG SFRCQCPLGY TGLLCENPVV PCAPSPCRNG GTCRQSSDVT YDCACLPGFE GQNCEVNVDD CPGHRCLNGG TCVDGVNTYN CQCPPEWTGQ FCTEDVDECQ LQPNACHNGG TCFNLLGGHS CVCVNGWTGE SCSQNIDDCA TAVCFHGATC HDRVASFYCA CPMGKTGLLC HLDDACVSNP CHEDAICDTN PVSGRAICTC PPGFTGGACD QDVDECSIGA NPCEHLGRCV NTQGSFLCQC GRGYTGPRCE TDVNECLSGP CRNQATCLDR IGQFTCICMA GFTGTYCEVD IDECQSSPCV NGGVCKDRVN GFSCTCPSGF SGSMCQLDVD ECASTPCRNG AKCVDQPDGY ECRCAEGFEG TLCERNVDDC SPDPCHHGRC VDGIASFSCA CAPGYTGIRC ESQVDECRSQ PCRYGGKCLD LVDKYLCRCP PGTTGVNCEV NIDDCASNPC TFGVCRDGIN RYDCVCQPGF TGPLCNVEIN ECASSPCGEG GSCVDGENGF HCLCPPGSLP PLCLPANHPC AHKPCSHGVC HDAPGGFRCV CEPGWSGPRC SQSLAPDACE SQPCQAGGTC TSDGIGFRCT CAPGFQGHQC EVLSPCTPSL CEHGGHCESD PDRLTVCSCP PGWQGPRCQQ DVDECAGASP CGPHGTCTNL PGNFRCICHR GYTGPFCDQD IDDCDPNPCL HGGSCQDGVG SFSCSCLDGF AGPRCARDVD ECLSSPCGPG TCTDHVASFT CACPPGYGGF HCEIDLPDCS PSSCFNGGTC VDGVSSFSCL CRPGYTGTHC QYEADPCFSR PCLHGGICNP THPGFECTCR EGFTGSQCQN PVDWCSQAPC QNGGRCVQTG AYCICPPGWS GRLCDIQSLP CTEAAAQMGV RLEQLCQEGG KCIDKGRSHY CVCPEGRTGS HCEHEVDPCT AQPCQHGGTC RGYMGGYVCE CPAGYAGDSC EDNIDECASQ PCQNGGSCID LVARYLCSCP PGTLGVLCEI NEDDCDLGPS LDSGVQCLHN GTCVDLVGGF RCNCPPGYTG LHCEADINEC RPGACHAAHT RDCLQDPGGH FRCVCHPGFT GPRCQIALSP CESQPCQHGG QCRHSLGRGG GLTFTCHCVP PFWGLRCERV ARSCRELQCP VGIPCQQTAR GPRCACPPGL SGPSCRVSRA SPSGATNASC ASAPCLHGGS CLPVQSVPFF RCVCAPGWGG PRCETPSAAP EVPEEPRCPR AACQAKRGDQ NCDRECNTPG CGWDGGDCSL NVDDPWRQCE ALQCWRLFNN SRCDPACSSP ACLYDNFDCY SGGRDRTCNP VYEKYCADHF ADGRCDQGCN TEECGWDGLD CASEVPALLA RGVLVLTVLL PPEELLRSSA DFLQRLSAIL RTSLRFRLDA RGQAMVFPYH RPSPGSESRV RRELGPEVIG SVVMLEIDNR LCLQSAENDH CFPDAQSAAD YLGALSAVER LDFPYPLRDV RGEPLEAPEQ SVPLLPLLVA GAVFLLIIFI LGVMVARRKR EHSTLWFPEG FALHKDIAAG HKGRREPVGQ DALGMKNMAK GESLMGEVVT DLNDSECPEA KRLKVEEPGM GAEEPEDCRQ WTQHHLVAAD IRVAPATALT PPQGDADADG VDVNVRGPDG FTPLMLASFC GGALEPMPAE EDEADDTSAS IISDLICQGA QLGARTDRTG ETALHLAARY ARADAAKRLL DAGADTNAQD HSGRTPLHTA VTADAQGVFQ ILIRNRSTDL DARMADGSTA LILAARLAVE GMVEELIASH ADVNAVDELG KSALHWAAAV NNVEATLALL KNGANKDMQD SKEETPLFLA AREGSYEAAK LLLDHLANRE ITDHLDRLPR DVAQERLHQD IVRLLDQPSG PRSPSGPHGL GPLLCPPGAF LPGLKAVQSG TKKSRRPPGK TGLGPQGTRG RGKKLTLACP GPLADSSVTL SPVDSLDSPR PFSGPPASPG GFPLEGPYAT TATAVSLAQL GASRAGPLGR QPPGGCVLSF GLLNPVAVPL DWARLPPPAP PGPSFLLPLA PGPQLLNPGA PVSPQERPPP YLAAPGHGEE YPAAGTRSSP TKARFLRVPS EHPYLTPSPE SPEHWASPSP PSLSDWSDST PSPATATNAT ASGALPAQPH PISVPSLPQS QTQLGPQPEV TPKRQVMA //