NOTC3_MOUSE
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 03-AUG-2022, entry version 208.
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}.
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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; 673 antibodies from 44 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 transcription, DNA-templated; 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
