NOTC4_MOUSE
ID NOTC4_MOUSE Reviewed; 1964 AA.
AC P31695; A2CG28; O35442; O88314; O88316; Q62389; Q62390; Q9R1W9; Q9R1X0;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 10-APR-2019, sequence version 3.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Neurogenic locus notch homolog protein 4 {ECO:0000250|UniProtKB:Q99466};
DE Short=Notch 4;
DE Contains:
DE RecName: Full=Transforming protein Int-3;
DE Contains:
DE RecName: Full=Notch 4 extracellular truncation;
DE Contains:
DE RecName: Full=Notch 4 intracellular domain;
DE Flags: Precursor;
GN Name=Notch4 {ECO:0000312|MGI:MGI:107471}; Synonyms=Int-3, Int3;
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].
RX PubMed=1312643; DOI=10.1128/jvi.66.4.2594-2599.1992;
RA Robbins J., Blondel B.J., Gallahan D., Callahan R.;
RT "Mouse mammary tumor gene int-3: a member of the notch gene family
RT transforms mammary epithelial cells.";
RL J. Virol. 66:2594-2599(1992).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=9150355; DOI=10.1038/sj.onc.1201035;
RA Gallahan D., Callahan R.;
RT "The mouse mammary tumor associated gene INT3 is a unique member of the
RT NOTCH gene family (NOTCH4).";
RL Oncogene 14:1883-1890(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INVOLVEMENT IN MAMMARY CARCINOMA.
RC TISSUE=Lung, and Testis;
RX PubMed=8681805; DOI=10.1242/dev.122.7.2251;
RA Uyttendaele H., Marazzi G., Wu G., Yan Q., Sassoon D., Kitajewski J.;
RT "Notch4/int-3, a mammary proto-oncogene, is an endothelial cell-specific
RT mammalian Notch gene.";
RL Development 122:2251-2259(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=129;
RX PubMed=14656967; DOI=10.1101/gr.1736803;
RA Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D.,
RA Hood L.;
RT "Analysis of the gene-dense major histocompatibility complex class III
RT region and its comparison to mouse.";
RL Genome Res. 13:2621-2636(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [6]
RP PROTEIN SEQUENCE OF 1463-1964, PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF
RP VAL-1463.
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1466-1600.
RX PubMed=10233982; DOI=10.1128/jvi.73.6.5166-5171.1999;
RA Lee J.-S., Haruna T., Ishimoto A., Honjo T., Yanagawa S.;
RT "Intracisternal type A particle-mediated activation of the Notch4/int3 gene
RT in a mouse mammary tumor: generation of truncated Notch4/int3 mRNAs by
RT retroviral splicing events.";
RL J. Virol. 73:5166-5171(1999).
RN [8]
RP FUNCTION.
RX PubMed=11344305; DOI=10.1073/pnas.091584598;
RA Uyttendaele H., Ho J., Rossant J., Kitajewski J.;
RT "Vascular patterning defects associated with expression of activated Notch4
RT in embryonic endothelium.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:5643-5648(2001).
RN [9]
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 [10]
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 [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 regulate branching morphogenesis in the developing
CC vascular system. {ECO:0000250, ECO:0000269|PubMed:11344305}.
CC -!- SUBUNIT: Heterodimer of a C-terminal fragment N(TM) and a N-terminal
CC fragment N(EC) which are probably linked by disulfide bonds. Interacts
CC with MAML1, MAML2 and MAML3 which act as transcriptional coactivators
CC for NOTCH4. {ECO:0000269|PubMed:15019995}.
CC -!- INTERACTION:
CC P31695; Q93794: sel-10; Xeno; NbExp=2; IntAct=EBI-643670, EBI-323098;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein.
CC -!- SUBCELLULAR LOCATION: [Notch 4 intracellular domain]: Nucleus.
CC Note=Following proteolytical processing NICD is translocated to the
CC nucleus.
CC -!- TISSUE SPECIFICITY: Highly expressed in lung, moderately in heart
CC kidney, and at lower levels in the ovary and skeletal muscle. A very
CC low expression is seen in the brain, intestine, liver and testis.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in endothelial cells during
CC embryonic development from 9.0 dpc.
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 -!- DISEASE: Note=Loss of the extracellular domain causes constitutive
CC activation of the Notch protein, which leads to hyperproliferation of
CC glandular epithelial tissues and development of mammary carcinomas.
CC {ECO:0000303|PubMed:8681805}.
CC -!- SIMILARITY: Belongs to the NOTCH family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA32281.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin.; Evidence={ECO:0000305};
CC Sequence=BAA32283.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA32284.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA32285.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; M80456; AAB38377.1; -; mRNA.
DR EMBL; U43691; AAC52630.1; -; mRNA.
DR EMBL; U43691; AAC52631.1; -; mRNA.
DR EMBL; AF030001; AAB82004.1; -; Genomic_DNA.
DR EMBL; CT009767; CAM18615.1; -; Genomic_DNA.
DR EMBL; AB016771; BAA32281.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AB016772; BAA32283.1; ALT_INIT; mRNA.
DR EMBL; AB016773; BAA32284.1; ALT_INIT; mRNA.
DR EMBL; AB016774; BAA32285.1; ALT_INIT; mRNA.
DR CCDS; CCDS28647.1; -.
DR PIR; A38072; TVMVT3.
DR PIR; T09059; T09059.
DR RefSeq; NP_035059.2; NM_010929.2.
DR AlphaFoldDB; P31695; -.
DR SMR; P31695; -.
DR BioGRID; 201812; 11.
DR CORUM; P31695; -.
DR IntAct; P31695; 2.
DR STRING; 10090.ENSMUSP00000015612; -.
DR GlyGen; P31695; 3 sites.
DR iPTMnet; P31695; -.
DR PhosphoSitePlus; P31695; -.
DR MaxQB; P31695; -.
DR PaxDb; P31695; -.
DR PRIDE; P31695; -.
DR ProteomicsDB; 293706; -.
DR ProteomicsDB; 338653; -.
DR DNASU; 18132; -.
DR Ensembl; ENSMUST00000015612; ENSMUSP00000015612; ENSMUSG00000015468.
DR GeneID; 18132; -.
DR KEGG; mmu:18132; -.
DR UCSC; uc008ccs.1; mouse.
DR CTD; 4855; -.
DR MGI; MGI:107471; Notch4.
DR VEuPathDB; HostDB:ENSMUSG00000015468; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000155030; -.
DR HOGENOM; CLU_000576_0_0_1; -.
DR InParanoid; P31695; -.
DR OMA; SKEPDAC; -.
DR OrthoDB; 7525at2759; -.
DR PhylomeDB; P31695; -.
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-9013700; NOTCH4 Activation and Transmission of Signal to the Nucleus.
DR Reactome; R-MMU-9604323; Negative regulation of NOTCH4 signaling.
DR BioGRID-ORCS; 18132; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Notch4; mouse.
DR PRO; PR:P31695; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; P31695; protein.
DR Bgee; ENSMUSG00000015468; Expressed in external carotid artery and 153 other tissues.
DR ExpressionAtlas; P31695; baseline and differential.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005112; F:Notch binding; IPI:MGI.
DR GO; GO:0038023; F:signaling receptor activity; IEA:InterPro.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IMP:UniProtKB.
DR GO; GO:0045446; P:endothelial cell differentiation; ISO:MGI.
DR GO; GO:0001886; P:endothelial cell morphogenesis; ISO:MGI.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISO:MGI.
DR GO; GO:0030879; P:mammary gland development; ISO:MGI.
DR GO; GO:0001763; P:morphogenesis of a branching structure; IMP:UniProtKB.
DR GO; GO:0060354; P:negative regulation of cell adhesion molecule production; ISO:MGI.
DR GO; GO:2000048; P:negative regulation of cell-cell adhesion mediated by cadherin; ISO:MGI.
DR GO; GO:0045602; P:negative regulation of endothelial cell differentiation; IMP:UniProtKB.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IDA:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0007219; P:Notch signaling pathway; TAS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:MGI.
DR GO; GO:1903849; P:positive regulation of aorta morphogenesis; IMP:MGI.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; IGI:MGI.
DR GO; GO:0032880; P:regulation of protein localization; IDA:MGI.
DR GO; GO:0070613; P:regulation of protein processing; IDA:MGI.
DR GO; GO:0001944; P:vasculature development; IMP:UniProtKB.
DR GO; GO:0048845; P:venous blood vessel morphogenesis; IMP: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; IPR022355; Notch_4.
DR InterPro; IPR000800; Notch_dom.
DR InterPro; IPR010660; Notch_NOD_dom.
DR InterPro; IPR011656; Notch_NODP_dom.
DR Pfam; PF00023; Ank; 1.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF00008; EGF; 17.
DR Pfam; PF07645; EGF_CA; 3.
DR Pfam; PF12661; hEGF; 3.
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; PR01987; NOTCH4.
DR SMART; SM00248; ANK; 6.
DR SMART; SM00181; EGF; 28.
DR SMART; SM00179; EGF_CA; 21.
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; 2.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 5.
DR PROSITE; PS00010; ASX_HYDROXYL; 11.
DR PROSITE; PS00022; EGF_1; 28.
DR PROSITE; PS01186; EGF_2; 21.
DR PROSITE; PS50026; EGF_3; 27.
DR PROSITE; PS01187; EGF_CA; 9.
DR PROSITE; PS50258; LNR; 3.
PE 1: Evidence at protein level;
KW Activator; ANK repeat; Cell membrane; Developmental protein;
KW Differentiation; Direct protein sequencing; Disulfide bond;
KW EGF-like domain; Glycoprotein; Membrane; Notch signaling pathway; Nucleus;
KW Phosphoprotein; Proto-oncogene; Receptor; Reference proteome; Repeat;
KW Signal; Transcription; Transcription regulation; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..1964
FT /note="Neurogenic locus notch homolog protein 4"
FT /id="PRO_0000007704"
FT CHAIN 1411..1964
FT /note="Transforming protein Int-3"
FT /id="PRO_0000007705"
FT CHAIN 1428..1964
FT /note="Notch 4 extracellular truncation"
FT /id="PRO_0000007706"
FT CHAIN 1463..1964
FT /note="Notch 4 intracellular domain"
FT /id="PRO_0000007707"
FT TOPO_DOM 21..1443
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1444..1464
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1465..1964
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 21..60
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 61..112
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 115..152
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 153..189
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 191..229
FT /note="EGF-like 5; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 231..271
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 273..309
FT /note="EGF-like 7; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 311..350
FT /note="EGF-like 8; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 352..388
FT /note="EGF-like 9; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 389..427
FT /note="EGF-like 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 429..470
FT /note="EGF-like 11; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 472..508
FT /note="EGF-like 12; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 510..546
FT /note="EGF-like 13; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 548..584
FT /note="EGF-like 14; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 586..622
FT /note="EGF-like 15; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 623..656
FT /note="EGF-like 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 658..686
FT /note="EGF-like 17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 688..724
FT /note="EGF-like 18"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 726..762
FT /note="EGF-like 19"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 764..800
FT /note="EGF-like 20"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 803..839
FT /note="EGF-like 21"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 841..877
FT /note="EGF-like 22"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 878..924
FT /note="EGF-like 23"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 926..962
FT /note="EGF-like 24"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 964..1000
FT /note="EGF-like 25"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1002..1040
FT /note="EGF-like 26"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1042..1081
FT /note="EGF-like 27"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1083..1122
FT /note="EGF-like 28"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1126..1167
FT /note="EGF-like 29"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 1166..1209
FT /note="LNR 1"
FT REPEAT 1210..1241
FT /note="LNR 2"
FT REPEAT 1247..1287
FT /note="LNR 3"
FT REPEAT 1628..1657
FT /note="ANK 1"
FT REPEAT 1661..1691
FT /note="ANK 2"
FT REPEAT 1695..1724
FT /note="ANK 3"
FT REPEAT 1728..1757
FT /note="ANK 4"
FT REPEAT 1761..1790
FT /note="ANK 5"
FT REGION 1345..1369
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1516..1535
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1879..1907
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 711
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 960
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1139
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 25..38
FT /evidence="ECO:0000250"
FT DISULFID 32..48
FT /evidence="ECO:0000250"
FT DISULFID 50..59
FT /evidence="ECO:0000250"
FT DISULFID 65..77
FT /evidence="ECO:0000250"
FT DISULFID 71..100
FT /evidence="ECO:0000250"
FT DISULFID 102..111
FT /evidence="ECO:0000250"
FT DISULFID 119..130
FT /evidence="ECO:0000250"
FT DISULFID 124..140
FT /evidence="ECO:0000250"
FT DISULFID 142..151
FT /evidence="ECO:0000250"
FT DISULFID 157..168
FT /evidence="ECO:0000250"
FT DISULFID 162..177
FT /evidence="ECO:0000250"
FT DISULFID 179..188
FT /evidence="ECO:0000250"
FT DISULFID 195..208
FT /evidence="ECO:0000250"
FT DISULFID 202..217
FT /evidence="ECO:0000250"
FT DISULFID 219..228
FT /evidence="ECO:0000250"
FT DISULFID 235..246
FT /evidence="ECO:0000250"
FT DISULFID 240..259
FT /evidence="ECO:0000250"
FT DISULFID 261..270
FT /evidence="ECO:0000250"
FT DISULFID 277..288
FT /evidence="ECO:0000250"
FT DISULFID 282..297
FT /evidence="ECO:0000250"
FT DISULFID 299..308
FT /evidence="ECO:0000250"
FT DISULFID 315..329
FT /evidence="ECO:0000250"
FT DISULFID 323..338
FT /evidence="ECO:0000250"
FT DISULFID 340..349
FT /evidence="ECO:0000250"
FT DISULFID 356..367
FT /evidence="ECO:0000250"
FT DISULFID 361..376
FT /evidence="ECO:0000250"
FT DISULFID 378..387
FT /evidence="ECO:0000250"
FT DISULFID 393..404
FT /evidence="ECO:0000250"
FT DISULFID 398..415
FT /evidence="ECO:0000250"
FT DISULFID 417..426
FT /evidence="ECO:0000250"
FT DISULFID 433..449
FT /evidence="ECO:0000250"
FT DISULFID 443..458
FT /evidence="ECO:0000250"
FT DISULFID 460..469
FT /evidence="ECO:0000250"
FT DISULFID 476..487
FT /evidence="ECO:0000250"
FT DISULFID 481..496
FT /evidence="ECO:0000250"
FT DISULFID 498..507
FT /evidence="ECO:0000250"
FT DISULFID 514..525
FT /evidence="ECO:0000250"
FT DISULFID 519..534
FT /evidence="ECO:0000250"
FT DISULFID 536..545
FT /evidence="ECO:0000250"
FT DISULFID 552..563
FT /evidence="ECO:0000250"
FT DISULFID 557..572
FT /evidence="ECO:0000250"
FT DISULFID 574..583
FT /evidence="ECO:0000250"
FT DISULFID 590..601
FT /evidence="ECO:0000250"
FT DISULFID 595..610
FT /evidence="ECO:0000250"
FT DISULFID 612..621
FT /evidence="ECO:0000250"
FT DISULFID 626..637
FT /evidence="ECO:0000250"
FT DISULFID 631..646
FT /evidence="ECO:0000250"
FT DISULFID 648..655
FT /evidence="ECO:0000250"
FT DISULFID 662..669
FT /evidence="ECO:0000250"
FT DISULFID 664..674
FT /evidence="ECO:0000250"
FT DISULFID 676..685
FT /evidence="ECO:0000250"
FT DISULFID 692..703
FT /evidence="ECO:0000250"
FT DISULFID 697..712
FT /evidence="ECO:0000250"
FT DISULFID 714..723
FT /evidence="ECO:0000250"
FT DISULFID 730..741
FT /evidence="ECO:0000250"
FT DISULFID 735..750
FT /evidence="ECO:0000250"
FT DISULFID 752..761
FT /evidence="ECO:0000250"
FT DISULFID 768..779
FT /evidence="ECO:0000250"
FT DISULFID 773..788
FT /evidence="ECO:0000250"
FT DISULFID 790..799
FT /evidence="ECO:0000250"
FT DISULFID 807..818
FT /evidence="ECO:0000250"
FT DISULFID 812..827
FT /evidence="ECO:0000250"
FT DISULFID 829..838
FT /evidence="ECO:0000250"
FT DISULFID 845..856
FT /evidence="ECO:0000250"
FT DISULFID 850..865
FT /evidence="ECO:0000250"
FT DISULFID 867..876
FT /evidence="ECO:0000250"
FT DISULFID 882..903
FT /evidence="ECO:0000250"
FT DISULFID 897..912
FT /evidence="ECO:0000250"
FT DISULFID 914..923
FT /evidence="ECO:0000250"
FT DISULFID 930..941
FT /evidence="ECO:0000250"
FT DISULFID 935..950
FT /evidence="ECO:0000250"
FT DISULFID 952..961
FT /evidence="ECO:0000250"
FT DISULFID 968..979
FT /evidence="ECO:0000250"
FT DISULFID 973..988
FT /evidence="ECO:0000250"
FT DISULFID 990..999
FT /evidence="ECO:0000250"
FT DISULFID 1006..1019
FT /evidence="ECO:0000250"
FT DISULFID 1011..1028
FT /evidence="ECO:0000250"
FT DISULFID 1030..1039
FT /evidence="ECO:0000250"
FT DISULFID 1046..1057
FT /evidence="ECO:0000250"
FT DISULFID 1051..1069
FT /evidence="ECO:0000250"
FT DISULFID 1071..1080
FT /evidence="ECO:0000250"
FT DISULFID 1087..1098
FT /evidence="ECO:0000250"
FT DISULFID 1092..1110
FT /evidence="ECO:0000250"
FT DISULFID 1112..1121
FT /evidence="ECO:0000250"
FT DISULFID 1130..1142
FT /evidence="ECO:0000250"
FT DISULFID 1136..1155
FT /evidence="ECO:0000250"
FT DISULFID 1157..1166
FT /evidence="ECO:0000250"
FT DISULFID 1174..1187
FT /evidence="ECO:0000250"
FT DISULFID 1183..1199
FT /evidence="ECO:0000250"
FT DISULFID 1210..1234
FT /evidence="ECO:0000250"
FT DISULFID 1216..1229
FT /evidence="ECO:0000250"
FT DISULFID 1225..1241
FT /evidence="ECO:0000250"
FT DISULFID 1247..1273
FT /evidence="ECO:0000250"
FT DISULFID 1255..1268
FT /evidence="ECO:0000250"
FT DISULFID 1264..1280
FT /evidence="ECO:0000250"
FT MUTAGEN 1463
FT /note="V->L: NICD processing severely reduced."
FT /evidence="ECO:0000269|PubMed:11518718"
FT CONFLICT 43
FT /note="R -> Q (in Ref. 1; AAB38377)"
FT /evidence="ECO:0000305"
FT CONFLICT 298
FT /note="L -> P (in Ref. 3; AAC52630)"
FT /evidence="ECO:0000305"
FT CONFLICT 884
FT /note="K -> M (in Ref. 1; AAB38377)"
FT /evidence="ECO:0000305"
FT CONFLICT 927
FT /note="V -> M (in Ref. 1; AAB38377)"
FT /evidence="ECO:0000305"
FT CONFLICT 966
FT /note="D -> E (in Ref. 1; AAB38377)"
FT /evidence="ECO:0000305"
FT CONFLICT 1245
FT /note="L -> P (in Ref. 3; AAC52630)"
FT /evidence="ECO:0000305"
FT CONFLICT 1437
FT /note="S -> P (in Ref. 3; AAC52631/AAC52630 and 1;
FT AAB38377)"
FT /evidence="ECO:0000305"
FT CONFLICT 1469
FT /note="R -> Q (in Ref. 7; BAA32283/BAA32284)"
FT /evidence="ECO:0000305"
FT CONFLICT 1489
FT /note="T -> A (in Ref. 1; AAB38377)"
FT /evidence="ECO:0000305"
FT CONFLICT 1549
FT /note="G -> S (in Ref. 1; AAB38377)"
FT /evidence="ECO:0000305"
FT CONFLICT 1688
FT /note="T -> S (in Ref. 1; AAB38377)"
FT /evidence="ECO:0000305"
FT CONFLICT 1836
FT /note="A -> S (in Ref. 3; AAC52630/AAC52631)"
FT /evidence="ECO:0000305"
FT CONFLICT 1838
FT /note="P -> A (in Ref. 1; AAB38377)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1964 AA; 206702 MW; 53D7F86394FC40BD CRC64;
MQPQLLLLLL LPLNFPVILT RELLCGGSPE PCANGGTCLR LSRGQGICQC APGFLGETCQ
FPDPCRDTQL CKNGGSCQAL LPTPPSSRSP TSPLTPHFSC TCPSGFTGDR CQTHLEELCP
PSFCSNGGHC YVQASGRPQC SCEPGWTGEQ CQLRDFCSAN PCANGGVCLA TYPQIQCRCP
PGFEGHTCER DINECFLEPG PCPQGTSCHN TLGSYQCLCP VGQEGPQCKL RKGACPPGSC
LNGGTCQLVP EGHSTFHLCL CPPGFTGLDC EMNPDDCVRH QCQNGATCLD GLDTYTCLCP
KTWKGWDCSE DIDECEARGP PRCRNGGTCQ NTAGSFHCVC VSGWGGAGCE ENLDDCAAAT
CAPGSTCIDR VGSFSCLCPP GRTGLLCHLE DMCLSQPCHV NAQCSTNPLT GSTLCICQPG
YSGSTCHQDL DECQMAQQGP SPCEHGGSCI NTPGSFNCLC LPGYTGSRCE ADHNECLSQP
CHPGSTCLDL LATFHCLCPP GLEGRLCEVE VNECTSNPCL NQAACHDLLN GFQCLCLPGF
TGARCEKDMD ECSSTPCANG GRCRDQPGAF YCECLPGFEG PHCEKEVDEC LSDPCPVGAS
CLDLPGAFFC LCRPGFTGQL CEVPLCTPNM CQPGQQCQGQ EHRAPCLCPD GSPGCVPAED
NCPCHHGHCQ RSLCVCDEGW TGPECETELG GCISTPCAHG GTCHPQPSGY NCTCPAGYMG
LTCSEEVTAC HSGPCLNGGS CSIRPEGYSC TCLPSHTGRH CQTAVDHCVS ASCLNGGTCV
NKPGTFFCLC ATGFQGLHCE EKTNPSCADS PCRNKATCQD TPRGARCLCS PGYTGSSCQT
LIDLCARKPC PHTARCLQSG PSFQCLCLQG WTGALCDFPL SCQKAAMSQG IEISGLCQNG
GLCIDTGSSY FCRCPPGFQG KLCQDNVNPC EPNPCHHGST CVPQPSGYVC QCAPGYEGQN
CSKVLDACQS QPCHNHGTCT SRPGGFHCAC PPGFVGLRCE GDVDECLDRP CHPSGTAACH
SLANAFYCQC LPGHTGQRCE VEMDLCQSQP CSNGGSCEIT TGPPPGFTCH CPKGFEGPTC
SHKALSCGIH HCHNGGLCLP SPKPGSPPLC ACLSGFGGPD CLTPPAPPGC GPPSPCLHNG
TCTETPGLGN PGFQCTCPPD SPGPRCQRPG ASGCEGRGGD GTCDAGCSGP GGDWDGGDCS
LGVPDPWKGC PPHSQCWLLF RDGRCHPQCD SEECLFDGYD CEIPLTCIPA YDQYCRDHFH
NGHCEKGCNN AECGWDGGDC RPEGEDSEGR PSLALLVVLR PPALDQQLLA LARVLSLTLR
VGLWVRKDSE GRNMVFPYPG TRAKEELSGA RDSSSWERQA PPTQPLGKET ESLGAGFVVV
MGVDLSRCGP EHPASRCPWD SGLLLRFLAA MAAVGALEPL LPGPLLAAHP QAGTRPSANQ
LPWPILCSPV VGVLLLALGA LLVLQLIRRR RREHGALWLP PGFIRRPQTQ QAPHRRRPPL
GEDNIGLKAL KPEAEVDEDG VAMCSGPEEG EAEETASASR CQLWPLNSGC GELPQAAMLT
PPQECESEVL DVDTCGPDGV TPLMSAVFCG GVQSTTGASP QRLGLGNLEP WEPLLDRGAC
PQAHTVGTGE TPLHLAARFS RPTAARRLLE AGANPNQPDR AGRTPLHTAV AADAREVCQL
LLASRQTTVD ARTEDGTTPL MLAARLAVED LVEELIAARA DVGARDKRGK TALHWAAAVN
NARAARSLLQ AGADKDAQDS REQTPLFLAA REGAVEVAQL LLELGAARGL RDQAGLAPGD
VARQRSHWDL LTLLEGAGPT TQEARAHART TPGGGAAPRC RTLSAGARPR GGGACLQART
WSVDLGARGG KVYARCRSRS GSCGGPTTRG RRFSAGSRGR RGARASQDDW PRDWVALEAC
GSACSAPIPP PSLTPSPERG SPQVAWGLPV HQEIPLNSVV RNLN
