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Database: UniProt
Entry: P46531
LinkDB: P46531
Original site: P46531 
ID   NOTC1_HUMAN             Reviewed;        2555 AA.
AC   P46531; Q59ED8; Q5SXM3;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   23-SEP-2008, sequence version 4.
DT   17-JUN-2020, entry version 238.
DE   RecName: Full=Neurogenic locus notch homolog protein 1;
DE            Short=Notch 1;
DE            Short=hN1;
DE   AltName: Full=Translocation-associated notch protein TAN-1;
DE   Contains:
DE     RecName: Full=Notch 1 extracellular truncation;
DE              Short=NEXT;
DE   Contains:
DE     RecName: Full=Notch 1 intracellular domain;
DE              Short=NICD;
DE   Flags: Precursor;
GN   Name=NOTCH1; Synonyms=TAN1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Brain;
RA   Mann R.S., Blaumueller C.M., Zagouras P.;
RT   "Complete human notch 1 (hN1) cDNA sequence.";
RL   Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164053; DOI=10.1038/nature02465;
RA   Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA   Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA   Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA   Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA   Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA   Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA   Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA   Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA   Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA   Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA   Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA   Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA   Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA   Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA   Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA   McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA   Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA   Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA   Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA   Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA   West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA   Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA   Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA   Dunham I.;
RT   "DNA sequence and analysis of human chromosome 9.";
RL   Nature 429:369-374(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-2443.
RX   PubMed=1831692; DOI=10.1016/0092-8674(91)90111-b;
RA   Ellisen L.W., Bird J., West D.C., Soreng A.L., Reynolds T.C., Smith S.D.,
RA   Sklar J.;
RT   "TAN-1, the human homolog of the Drosophila notch gene, is broken by
RT   chromosomal translocations in T lymphoblastic neoplasms.";
RL   Cell 66:649-661(1991).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 489-2555.
RC   TISSUE=Aortic endothelium;
RA   Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA   Ohara O., Nagase T., Kikuno R.F.;
RL   Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   PROTEIN SEQUENCE OF 1947-1962, INTERACTION WITH HIF1AN, HYDROXYLATION AT
RP   ASN-1955, AND IDENTIFICATION BY MASS SPECTROMETRY.
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   IDENTIFICATION OF LIGANDS.
RX   PubMed=10079256; DOI=10.1016/s0002-9440(10)65325-4;
RA   Gray G.E., Mann R.S., Mitsiadis E., Henrique D., Carcangiu M.-L., Banks A.,
RA   Leiman J., Ward D., Ish-Horowitz D., Artavanis-Tsakonas S.;
RT   "Human ligands of the Notch receptor.";
RL   Am. J. Pathol. 154:785-794(1999).
RN   [7]
RP   INTERACTION WITH DTX1.
RX   PubMed=9590294; DOI=10.1038/ng0598-74;
RA   Matsuno K., Eastman D., Mitsiades T., Quinn A.M., Carcanciu M.L.,
RA   Ordentlich P., Kadesch T., Artavanis-Tsakonas S.;
RT   "Human deltex is a conserved regulator of Notch signalling.";
RL   Nat. Genet. 19:74-78(1998).
RN   [8]
RP   INTERACTION WITH SNW1.
RX   PubMed=10713164; DOI=10.1128/mcb.20.7.2400-2410.2000;
RA   Zhou S., Fujimuro M., Hsieh J.J., Chen L., Miyamoto A., Weinmaster G.,
RA   Hayward S.D.;
RT   "SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain
RT   of NotchIC To facilitate NotchIC function.";
RL   Mol. Cell. Biol. 20:2400-2410(2000).
RN   [9]
RP   INTERACTION WITH MAML1.
RX   PubMed=11101851; DOI=10.1038/82644;
RA   Wu L., Aster J.C., Blacklow S.C., Lake R., Artavanis-Tsakonas S.,
RA   Griffin J.D.;
RT   "MAML1, a human homologue of Drosophila mastermind, is a transcriptional
RT   co-activator for NOTCH receptors.";
RL   Nat. Genet. 26:484-489(2000).
RN   [10]
RP   INTERACTION WITH MAML2 AND MAML3.
RX   PubMed=12370315; DOI=10.1128/mcb.22.21.7688-7700.2002;
RA   Wu L., Sun T., Kobayashi K., Gao P., Griffin J.D.;
RT   "Identification of a family of mastermind-like transcriptional coactivators
RT   for mammalian notch receptors.";
RL   Mol. Cell. Biol. 22:7688-7700(2002).
RN   [11]
RP   INTERACTION WITH CCN3.
RX   PubMed=12050162; DOI=10.1074/jbc.m203727200;
RA   Sakamoto K., Yamaguchi S., Ando R., Miyawaki A., Kabasawa Y., Takagi M.,
RA   Li C.L., Perbal B., Katsube K.;
RT   "The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with
RT   Notch1 extracellular domain and inhibits myoblast differentiation via Notch
RT   signaling pathway.";
RL   J. Biol. Chem. 277:29399-29405(2002).
RN   [12]
RP   INVOLVEMENT IN AOVD1.
RX   PubMed=16025100; DOI=10.1038/nature03940;
RA   Garg V., Muth A.N., Ransom J.F., Schluterman M.K., Barnes R., King I.N.,
RA   Grossfeld P.D., Srivastava D.;
RT   "Mutations in NOTCH1 cause aortic valve disease.";
RL   Nature 437:270-274(2005).
RN   [13]
RP   UBIQUITINATION BY ITCH.
RX   PubMed=18628966; DOI=10.1371/journal.pone.0002735;
RA   Chastagner P., Israel A., Brou C.;
RT   "AIP4/Itch regulates Notch receptor degradation in the absence of ligand.";
RL   PLoS ONE 3:E2735-E2735(2008).
RN   [14]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [15]
RP   FUNCTION.
RX   PubMed=20616313; DOI=10.1161/circresaha.110.217257;
RA   Brutsch R., Liebler S.S., Wustehube J., Bartol A., Herberich S.E.,
RA   Adam M.G., Telzerow A., Augustin H.G., Fischer A.;
RT   "Integrin cytoplasmic domain-associated protein-1 attenuates sprouting
RT   angiogenesis.";
RL   Circ. Res. 107:592-601(2010).
RN   [16]
RP   INTERACTION WITH SNAI1 AND MDM2A.
RX   PubMed=22128911; DOI=10.1186/1741-7007-9-83;
RA   Lim S.O., Kim H.S., Quan X., Ahn S.M., Kim H., Hsieh D., Seong J.K.,
RA   Jung G.;
RT   "Notch1 binds and induces degradation of Snail in hepatocellular
RT   carcinoma.";
RL   BMC Biol. 9:83-83(2011).
RN   [17]
RP   INTERACTION WITH AAK1.
RX   PubMed=21464124; DOI=10.1074/jbc.m110.190769;
RA   Gupta-Rossi N., Ortica S., Meas-Yedid V., Heuss S., Moretti J.,
RA   Olivo-Marin J.C., Israel A.;
RT   "The adaptor-associated kinase 1, AAK1, is a positive regulator of the
RT   Notch pathway.";
RL   J. Biol. Chem. 286:18720-18730(2011).
RN   [18]
RP   INTERACTION WITH SGK1 AND FBXW7.
RX   PubMed=21147854; DOI=10.1242/jcs.073924;
RA   Mo J.S., Ann E.J., Yoon J.H., Jung J., Choi Y.H., Kim H.Y., Ahn J.S.,
RA   Kim S.M., Kim M.Y., Hong J.A., Seo M.S., Lang F., Choi E.J., Park H.S.;
RT   "Serum- and glucocorticoid-inducible kinase 1 (SGK1) controls Notch1
RT   signaling by downregulation of protein stability through Fbw7 ubiquitin
RT   ligase.";
RL   J. Cell Sci. 124:100-112(2011).
RN   [19]
RP   INTERACTION WITH SNW1.
RX   PubMed=21245387; DOI=10.1128/mcb.00360-10;
RA   Vasquez-Del Carpio R., Kaplan F.M., Weaver K.L., VanWye J.D.,
RA   Alves-Guerra M.C., Robbins D.J., Capobianco A.J.;
RT   "Assembly of a Notch transcriptional activation complex requires
RT   multimerization.";
RL   Mol. Cell. Biol. 31:1396-1408(2011).
RN   [20]
RP   UBIQUITINATION BY ITCH.
RX   PubMed=23886940; DOI=10.1242/jcs.130500;
RA   Puca L., Chastagner P., Meas-Yedid V., Israel A., Brou C.;
RT   "Alpha-arrestin 1 (ARRDC1) and beta-arrestins cooperate to mediate Notch
RT   degradation in mammals.";
RL   J. Cell Sci. 126:4457-4468(2013).
RN   [21]
RP   GLYCOSYLATION AT THR-232; THR-1402 AND THR-1725, AND PROTEOLYTIC
RP   PROCESSING.
RX   PubMed=24226769; DOI=10.1038/nature12723;
RA   Boskovski M.T., Yuan S., Pedersen N.B., Goth C.K., Makova S., Clausen H.,
RA   Brueckner M., Khokha M.K.;
RT   "The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type
RT   and laterality.";
RL   Nature 504:456-459(2013).
RN   [22]
RP   ANKYRIN REPEATS.
RX   PubMed=25547411; DOI=10.1186/s12859-014-0440-9;
RA   Chakrabarty B., Parekh N.;
RT   "Identifying tandem Ankyrin repeats in protein structures.";
RL   BMC Bioinformatics 15:6599-6599(2014).
RN   [23]
RP   INTERACTION WITH ZMIZ1.
RX   PubMed=26522984; DOI=10.1016/j.immuni.2015.10.007;
RA   Pinnell N., Yan R., Cho H.J., Keeley T., Murai M.J., Liu Y., Alarcon A.S.,
RA   Qin J., Wang Q., Kuick R., Elenitoba-Johnson K.S., Maillard I.,
RA   Samuelson L.C., Cierpicki T., Chiang M.Y.;
RT   "The PIAS-like coactivator Zmiz1 is a direct and selective cofactor of
RT   Notch1 in T cell development and leukemia.";
RL   Immunity 43:870-883(2015).
RN   [24]
RP   GLYCOSYLATION AT SER-435.
RX   PubMed=30127001; DOI=10.1073/pnas.1804005115;
RA   Takeuchi H., Schneider M., Williamson D.B., Ito A., Takeuchi M.,
RA   Handford P.A., Haltiwanger R.S.;
RT   "Two novel protein O-glucosyltransferases that modify sites distinct from
RT   POGLUT1 and affect Notch trafficking and signaling.";
RL   Proc. Natl. Acad. Sci. U.S.A. 115:E8395-E8402(2018).
RN   [25]
RP   STRUCTURE BY NMR OF 1446-1480 IN COMPLEX WITH CALCIUM IONS, AND DISULFIDE
RP   BONDS.
RX   PubMed=12795601; DOI=10.1021/bi034156y;
RA   Vardar D., North C.L., Sanchez-Irizarry C., Aster J.C., Blacklow S.C.;
RT   "Nuclear magnetic resonance structure of a prototype Lin12-Notch repeat
RT   module from human Notch1.";
RL   Biochemistry 42:7061-7067(2003).
RN   [26]
RP   STRUCTURE BY NMR OF 411-526.
RX   PubMed=15576031; DOI=10.1016/j.str.2004.09.012;
RA   Hambleton S., Valeyev N.V., Muranyi A., Knott V., Werner J.M.,
RA   McMichael A.J., Handford P.A., Downing A.K.;
RT   "Structural and functional properties of the human notch-1 ligand binding
RT   region.";
RL   Structure 12:2173-2183(2004).
RN   [27]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1872-2114.
RX   PubMed=16011479; DOI=10.1042/bj20050515;
RA   Ehebauer M.T., Chirgadze D.Y., Hayward P., Martinez Arias A.,
RA   Blundell T.L.;
RT   "High-resolution crystal structure of the human Notch 1 ankyrin domain.";
RL   Biochem. J. 392:13-20(2005).
RN   [28]
RP   X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 1872-2126 IN COMPLEX WITH RBPSUH
RP   AND MAML1.
RX   PubMed=16530044; DOI=10.1016/j.cell.2005.12.037;
RA   Nam Y., Sliz P., Song L., Aster J.C., Blacklow S.C.;
RT   "Structural basis for cooperativity in recruitment of MAML coactivators to
RT   Notch transcription complexes.";
RL   Cell 124:973-983(2006).
RN   [29]
RP   STRUCTURE BY NMR OF 1721-1771, AND TOPOLOGY.
RX   PubMed=28439555; DOI=10.1126/sciadv.1602794;
RA   Deatherage C.L., Lu Z., Kroncke B.M., Ma S., Smith J.A., Voehler M.W.,
RA   McFeeters R.L., Sanders C.R.;
RT   "Structural and biochemical differences between the Notch and the amyloid
RT   precursor protein transmembrane domains.";
RL   Sci. Adv. 3:E1602794-E1602794(2017).
RN   [30]
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.70 ANGSTROMS) OF 1721-1821 IN COMPLEX
RP   WITH GAMMA-SECRETASE, SUBUNIT, TOPOLOGY, INTERACTION WITH PSEN1,
RP   PROTEOLYTIC CLEAVAGE BY PSEN1, DOMAIN, AND MUTAGENESIS OF PRO-1728 AND
RP   1755-LEU--ARG-1761.
RX   PubMed=30598546; DOI=10.1038/s41586-018-0813-8;
RA   Yang G., Zhou R., Zhou Q., Guo X., Yan C., Ke M., Lei J., Shi Y.;
RT   "Structural basis of Notch recognition by human gamma-secretase.";
RL   Nature 565:192-197(2019).
RN   [31]
RP   INVOLVEMENT IN AOS5, AND VARIANTS AOS5 ARG-429; TYR-1496 AND ASN-1989.
RX   PubMed=25132448; DOI=10.1016/j.ajhg.2014.07.011;
RA   Stittrich A.B., Lehman A., Bodian D.L., Ashworth J., Zong Z., Li H.,
RA   Lam P., Khromykh A., Iyer R.K., Vockley J.G., Baveja R., Silva E.S.,
RA   Dixon J., Leon E.L., Solomon B.D., Glusman G., Niederhuber J.E.,
RA   Roach J.C., Patel M.S.;
RT   "Mutations in NOTCH1 cause Adams-Oliver syndrome.";
RL   Am. J. Hum. Genet. 95:275-284(2014).
CC   -!- FUNCTION: Functions as a receptor for membrane-bound ligands Jagged-1
CC       (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate
CC       determination. Upon ligand activation through the released notch
CC       intracellular domain (NICD) it forms a transcriptional activator
CC       complex with RBPJ/RBPSUH and activates genes of the enhancer of split
CC       locus. Affects the implementation of differentiation, proliferation and
CC       apoptotic programs. Involved in angiogenesis; negatively regulates
CC       endothelial cell proliferation and migration and angiogenic sprouting.
CC       Involved in the maturation of both CD4(+) and CD8(+) cells in the
CC       thymus. Important for follicular differentiation and possibly cell fate
CC       selection within the follicle. During cerebellar development, functions
CC       as a receptor for neuronal DNER and is involved in the differentiation
CC       of Bergmann glia. Represses neuronal and myogenic differentiation. May
CC       play an essential role in postimplantation development, probably in
CC       some aspect of cell specification and/or differentiation. May be
CC       involved in mesoderm development, somite formation and neurogenesis.
CC       May enhance HIF1A function by sequestering HIF1AN away from HIF1A.
CC       Required for the THBS4 function in regulating protective astrogenesis
CC       from the subventricular zone (SVZ) niche after injury. Involved in
CC       determination of left/right symmetry by modulating the balance between
CC       motile and immotile (sensory) cilia at the left-right organiser (LRO).
CC       {ECO:0000269|PubMed:20616313}.
CC   -!- SUBUNIT: Heterodimer of a C-terminal fragment N(TM) and an N-terminal
CC       fragment N(EC) which are probably linked by disulfide bonds. Interacts
CC       with DNER, DTX1, DTX2 and RBPJ/RBPSUH. Also interacts with MAML1, MAML2
CC       and MAML3 which act as transcriptional coactivators for NOTCH1
CC       (PubMed:11101851, PubMed:12370315). The NOTCH1 intracellular domain
CC       interacts with SNW1; the interaction involves multimerized NOTCH1 NICD
CC       and is implicated in a formation of an intermediate preactivation
CC       complex which associates with DNA-bound CBF-1/RBPJ (PubMed:10713164).
CC       The activated membrane-bound form interacts with AAK1 which promotes
CC       NOTCH1 stabilization. Forms a trimeric complex with FBXW7 and SGK1.
CC       Interacts with HIF1AN. HIF1AN negatively regulates the function of
CC       notch intracellular domain (NICD), accelerating myogenic
CC       differentiation (PubMed:17573339). Interacts (via NICD) with SNAI1 (via
CC       zinc fingers); the interaction induces SNAI1 degradation via MDM2-
CC       mediated ubiquitination and inhibits SNAI1-induced cell invasion.
CC       Interacts (via NICD) with MDM2A. Interacts (via NICD) with BCL6; the
CC       interaction decreases MAML1 recruitment by NOTCH1 NICD on target genes
CC       DNA and inhibits NOTCH1 transcractivation activity. Interacts with
CC       THBS4 (By similarity). Interacts (via the EGF-like repeat region) with
CC       CCN3 (via CTCK domain) (PubMed:12050162). Interacts (via EGF-like
CC       domains) with DLL4 (via N-terminal DSL and MNNL domains) (By
CC       similarity). Interacts with ZMIZ1. Interacts (via NICD domain) with
CC       MEGF10 (via the cytoplasmic domain). Interacts with DLL1 and JAG1 (By
CC       similarity). Interacts (via NICD domain) with PRAG1 (By similarity).
CC       Forms a complex with PRAG1, N1ICD and MAML1, in a MAML1-dependent
CC       manner (By similarity). Interacts (via transmembrane region) with
CC       PSEN1; the interaction is direct (PubMed:30598546).
CC       {ECO:0000250|UniProtKB:Q01705, ECO:0000250|UniProtKB:Q07008,
CC       ECO:0000269|PubMed:10713164, ECO:0000269|PubMed:11101851,
CC       ECO:0000269|PubMed:12050162, ECO:0000269|PubMed:12370315,
CC       ECO:0000269|PubMed:17573339, ECO:0000269|PubMed:26522984,
CC       ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:9590294}.
CC   -!- INTERACTION:
CC       P46531; Q13315: ATM; NbExp=8; IntAct=EBI-636374, EBI-495465;
CC       P46531; Q969H0: FBXW7; NbExp=10; IntAct=EBI-636374, EBI-359574;
CC       P46531; Q16665: HIF1A; NbExp=2; IntAct=EBI-636374, EBI-447269;
CC       P46531; P78504: JAG1; NbExp=6; IntAct=EBI-636374, EBI-2847071;
CC       P46531; O60341: KDM1A; NbExp=8; IntAct=EBI-636374, EBI-710124;
CC       P46531; Q8N423: LILRB2; NbExp=8; IntAct=EBI-636374, EBI-2816428;
CC       P46531; Q92585: MAML1; NbExp=14; IntAct=EBI-636374, EBI-908250;
CC       P46531; P19838: NFKB1; NbExp=2; IntAct=EBI-636374, EBI-300010;
CC       P46531; Q13526: PIN1; NbExp=9; IntAct=EBI-636374, EBI-714158;
CC       P46531; Q06330: RBPJ; NbExp=12; IntAct=EBI-636374, EBI-632552;
CC       P46531; Q06330-6: RBPJ; NbExp=6; IntAct=EBI-636374, EBI-12599287;
CC       P46531; Q13573: SNW1; NbExp=3; IntAct=EBI-636374, EBI-632715;
CC       P46531; P98170: XIAP; NbExp=4; IntAct=EBI-636374, EBI-517127;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q01705};
CC       Single-pass type I membrane protein {ECO:0000305|PubMed:30598546}.
CC   -!- SUBCELLULAR LOCATION: [Notch 1 intracellular domain]: Nucleus
CC       {ECO:0000250|UniProtKB:Q01705}. Note=Following proteolytical processing
CC       NICD is translocated to the nucleus. Nuclear location may require
CC       MEGF10. {ECO:0000250|UniProtKB:Q01705}.
CC   -!- TISSUE SPECIFICITY: In fetal tissues most abundant in spleen, brain
CC       stem and lung. Also present in most adult tissues where it is found
CC       mainly in lymphoid tissues.
CC   -!- DOMAIN: Interaction with PSEN1 causes partial unwinding of the
CC       transmembrane helix, facilitating access to the scissile peptide bond.
CC       {ECO:0000269|PubMed:30598546}.
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 (By similarity). Cleavage results in a C-
CC       terminal fragment N(TM) and a N-terminal fragment N(EC). Following
CC       ligand binding, it is cleaved by ADAM17 to yield a membrane-associated
CC       intermediate fragment called notch extracellular truncation (NEXT)
CC       (PubMed:24226769). Following endocytosis, this fragment is then cleaved
CC       by one of the catalytic subunits of gamma-secretase (PSEN1 or PSEN2),
CC       to release a Notch-derived peptide containing the intracellular domain
CC       (NICD) from the membrane (PubMed:30598546).
CC       {ECO:0000250|UniProtKB:Q01705, ECO:0000269|PubMed:24226769,
CC       ECO:0000269|PubMed:30598546}.
CC   -!- PTM: Phosphorylated. {ECO:0000250}.
CC   -!- PTM: O-glycosylated on the EGF-like domains (PubMed:24226769). O-
CC       glucosylated at Ser-435 by KDELC1 and KDELC2 (PubMed:30127001).
CC       Contains both O-linked fucose and O-linked glucose in the EGF-like
CC       domains 11, 12 and 13, which are interacting with the residues on DLL4
CC       (By similarity). O-linked glycosylation by GALNT11 is involved in
CC       determination of left/right symmetry: glycosylation promotes activation
CC       of NOTCH1, possibly by promoting cleavage by ADAM17, modulating the
CC       balance between motile and immotile (sensory) cilia at the left-right
CC       organiser (LRO) (PubMed:24226769). MFNG-, RFNG- and LFNG-mediated
CC       modification of O-fucose residues at specific EGF-like domains results
CC       in inhibition of its activation by JAG1 and enhancement of its
CC       activation by DLL1 via an increased binding to DLL1 (By similarity).
CC       {ECO:0000250|UniProtKB:Q01705, ECO:0000250|UniProtKB:Q07008,
CC       ECO:0000269|PubMed:24226769, ECO:0000269|PubMed:30127001}.
CC   -!- PTM: Ubiquitinated. Undergoes 'Lys-29'-linked polyubiquitination by
CC       ITCH; promotes the lysosomal degradation of non-activated internalized
CC       NOTCH1 (PubMed:18628966, PubMed:23886940). Monoubiquitination at Lys-
CC       1759 is required for activation by gamma-secretase cleavage, it
CC       promotes interaction with AAK1, which stabilizes it. Deubiquitination
CC       by EIF3F is necessary for nuclear import of activated Notch
CC       (PubMed:24226769). {ECO:0000269|PubMed:18628966,
CC       ECO:0000269|PubMed:23886940, ECO:0000269|PubMed:24226769}.
CC   -!- PTM: Hydroxylated at Asn-1955 by HIF1AN. Hydroxylated at Asn-2022 by
CC       HIF1AN (By similarity). Hydroxylation reduces affinity for HI1AN and
CC       may thus indirectly modulate negative regulation of NICD (By
CC       similarity). {ECO:0000250}.
CC   -!- DISEASE: Aortic valve disease 1 (AOVD1) [MIM:109730]: A common defect
CC       in the aortic valve in which two rather than three leaflets are
CC       present. It is often associated with aortic valve calcification,
CC       stenosis and insufficiency. In extreme cases, the blood flow may be so
CC       restricted that the left ventricle fails to grow, resulting in
CC       hypoplastic left heart syndrome. {ECO:0000269|PubMed:16025100}.
CC       Note=The disease is caused by mutations affecting the gene represented
CC       in this entry.
CC   -!- DISEASE: Adams-Oliver syndrome 5 (AOS5) [MIM:616028]: A form of Adams-
CC       Oliver syndrome, a disorder characterized by the congenital absence of
CC       skin (aplasia cutis congenita) in combination with transverse limb
CC       defects. Aplasia cutis congenita can be located anywhere on the body,
CC       but in the vast majority of the cases, it is present on the posterior
CC       parietal region where it is often associated with an underlying defect
CC       of the parietal bones. Limb abnormalities are typically limb truncation
CC       defects affecting the distal phalanges or entire digits (true
CC       ectrodactyly). Only rarely, metatarsals/metacarpals or more proximal
CC       limb structures are also affected. Apart from transverse limb defects,
CC       syndactyly, most commonly of second and third toes, can also be
CC       observed. The clinical features are highly variable and can also
CC       include cardiovascular malformations, brain abnormalities and vascular
CC       defects such as cutis marmorata and dilated scalp veins.
CC       {ECO:0000269|PubMed:25132448}. Note=The disease is caused by mutations
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the NOTCH family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/NOTCH1ID30ch9q34.html";
DR   EMBL; AF308602; AAG33848.1; -; mRNA.
DR   EMBL; AL592301; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL354671; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; M73980; AAA60614.1; -; mRNA.
DR   EMBL; AB209873; BAD93110.1; -; mRNA.
DR   CCDS; CCDS43905.1; -.
DR   PIR; A40043; A40043.
DR   RefSeq; NP_060087.3; NM_017617.4.
DR   PDB; 1PB5; NMR; -; A=1446-1480.
DR   PDB; 1TOZ; NMR; -; A=411-526.
DR   PDB; 1YYH; X-ray; 1.90 A; A/B=1872-2114.
DR   PDB; 2F8X; X-ray; 3.25 A; K=1872-2126.
DR   PDB; 2F8Y; X-ray; 1.55 A; A/B=1905-2126.
DR   PDB; 2HE0; X-ray; 1.90 A; A/B=1872-2114.
DR   PDB; 2VJ3; X-ray; 2.60 A; A=411-526.
DR   PDB; 3ETO; X-ray; 2.00 A; A/B=1446-1733.
DR   PDB; 3I08; X-ray; 3.20 A; A/C=1446-1664, B/D=1665-1733.
DR   PDB; 3L95; X-ray; 2.19 A; X/Y=1448-1728.
DR   PDB; 3NBN; X-ray; 3.45 A; B/E=1872-2126.
DR   PDB; 3V79; X-ray; 3.85 A; K=1872-2126, R=1759-1777.
DR   PDB; 4CUD; X-ray; 1.85 A; A=411-526.
DR   PDB; 4CUE; X-ray; 3.00 A; A=411-526.
DR   PDB; 4CUF; X-ray; 2.29 A; A=411-526.
DR   PDB; 4D0E; X-ray; 1.61 A; A=411-526.
DR   PDB; 4D0F; X-ray; 2.80 A; A=411-526.
DR   PDB; 5FM9; X-ray; 2.92 A; A=140-294.
DR   PDB; 5FMA; X-ray; 2.46 A; A/B=142-294.
DR   PDB; 5KZO; NMR; -; A=1721-1771.
DR   PDB; 5L0R; X-ray; 1.50 A; B=452-491.
DR   PDB; 5UB5; X-ray; 2.09 A; B=452-491.
DR   PDB; 6IDF; EM; 2.70 A; E=1721-1821.
DR   PDB; 6PY8; X-ray; 3.75 A; F/K=1759-2127.
DR   PDBsum; 1PB5; -.
DR   PDBsum; 1TOZ; -.
DR   PDBsum; 1YYH; -.
DR   PDBsum; 2F8X; -.
DR   PDBsum; 2F8Y; -.
DR   PDBsum; 2HE0; -.
DR   PDBsum; 2VJ3; -.
DR   PDBsum; 3ETO; -.
DR   PDBsum; 3I08; -.
DR   PDBsum; 3L95; -.
DR   PDBsum; 3NBN; -.
DR   PDBsum; 3V79; -.
DR   PDBsum; 4CUD; -.
DR   PDBsum; 4CUE; -.
DR   PDBsum; 4CUF; -.
DR   PDBsum; 4D0E; -.
DR   PDBsum; 4D0F; -.
DR   PDBsum; 5FM9; -.
DR   PDBsum; 5FMA; -.
DR   PDBsum; 5KZO; -.
DR   PDBsum; 5L0R; -.
DR   PDBsum; 5UB5; -.
DR   PDBsum; 6IDF; -.
DR   PDBsum; 6PY8; -.
DR   SMR; P46531; -.
DR   BioGRID; 110913; 234.
DR   CORUM; P46531; -.
DR   DIP; DIP-29919N; -.
DR   IntAct; P46531; 156.
DR   MINT; P46531; -.
DR   STRING; 9606.ENSP00000277541; -.
DR   BindingDB; P46531; -.
DR   ChEMBL; CHEMBL2146346; -.
DR   TCDB; 9.B.87.1.12; the selenoprotein p receptor (selp-receptor) family.
DR   iPTMnet; P46531; -.
DR   PhosphoSitePlus; P46531; -.
DR   BioMuta; NOTCH1; -.
DR   DMDM; 206729936; -.
DR   EPD; P46531; -.
DR   jPOST; P46531; -.
DR   MassIVE; P46531; -.
DR   MaxQB; P46531; -.
DR   PaxDb; P46531; -.
DR   PeptideAtlas; P46531; -.
DR   PRIDE; P46531; -.
DR   ProteomicsDB; 55742; -.
DR   ABCD; P46531; 196 sequenced antibodies.
DR   Antibodypedia; 8424; 1278 antibodies.
DR   Ensembl; ENST00000651671; ENSP00000498587; ENSG00000148400.
DR   GeneID; 4851; -.
DR   KEGG; hsa:4851; -.
DR   UCSC; uc004chz.4; human.
DR   CTD; 4851; -.
DR   DisGeNET; 4851; -.
DR   EuPathDB; HostDB:ENSG00000148400.9; -.
DR   GeneCards; NOTCH1; -.
DR   GeneReviews; NOTCH1; -.
DR   HGNC; HGNC:7881; NOTCH1.
DR   HPA; ENSG00000148400; Low tissue specificity.
DR   MalaCards; NOTCH1; -.
DR   MIM; 109730; phenotype.
DR   MIM; 190198; gene.
DR   MIM; 616028; phenotype.
DR   neXtProt; NX_P46531; -.
DR   OpenTargets; ENSG00000148400; -.
DR   Orphanet; 974; Adams-Oliver syndrome.
DR   Orphanet; 402075; Familial bicuspid aortic valve.
DR   PharmGKB; PA31683; -.
DR   eggNOG; ENOG410IR7G; Eukaryota.
DR   eggNOG; COG0666; LUCA.
DR   GeneTree; ENSGT00940000157157; -.
DR   HOGENOM; CLU_000576_2_0_1; -.
DR   InParanoid; P46531; -.
DR   KO; K02599; -.
DR   OMA; NEGSCLD; -.
DR   OrthoDB; 7525at2759; -.
DR   PhylomeDB; P46531; -.
DR   TreeFam; TF351641; -.
DR   Reactome; R-HSA-1912399; Pre-NOTCH Processing in the Endoplasmic Reticulum.
DR   Reactome; R-HSA-1912408; Pre-NOTCH Transcription and Translation.
DR   Reactome; R-HSA-1912420; Pre-NOTCH Processing in Golgi.
DR   Reactome; R-HSA-210744; Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells.
DR   Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription.
DR   Reactome; R-HSA-2122948; Activated NOTCH1 Transmits Signal to the Nucleus.
DR   Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR   Reactome; R-HSA-2644607; Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling.
DR   Reactome; R-HSA-2660826; Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant.
DR   Reactome; R-HSA-2691232; Constitutive Signaling by NOTCH1 HD Domain Mutants.
DR   Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR   Reactome; R-HSA-350054; Notch-HLH transcription pathway.
DR   Reactome; R-HSA-5083630; Defective LFNG causes SCDO3.
DR   Reactome; R-HSA-8941856; RUNX3 regulates NOTCH signaling.
DR   Reactome; R-HSA-9013508; NOTCH3 Intracellular Domain Regulates Transcription.
DR   Reactome; R-HSA-9013695; NOTCH4 Intracellular Domain Regulates Transcription.
DR   SignaLink; P46531; -.
DR   SIGNOR; P46531; -.
DR   BioGRID-ORCS; 4851; 2 hits in 790 CRISPR screens.
DR   ChiTaRS; NOTCH1; human.
DR   EvolutionaryTrace; P46531; -.
DR   GeneWiki; Notch-1; -.
DR   GenomeRNAi; 4851; -.
DR   Pharos; P46531; Tchem.
DR   PRO; PR:P46531; -.
DR   Proteomes; UP000005640; Chromosome 9.
DR   RNAct; P46531; protein.
DR   Bgee; ENSG00000148400; Expressed in visceral pleura and 218 other tissues.
DR   Genevisible; P46531; HS.
DR   GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl.
DR   GO; GO:0005912; C:adherens junction; ISS:UniProtKB.
DR   GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR   GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0002193; C:MAML1-RBP-Jkappa- ICN1 complex; IDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:BHF-UCL.
DR   GO; GO:0043235; C:receptor complex; IDA:MGI.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:BHF-UCL.
DR   GO; GO:0019899; F:enzyme binding; ISS:UniProtKB.
DR   GO; GO:0004857; F:enzyme inhibitor activity; ISS:UniProtKB.
DR   GO; GO:0005112; F:Notch binding; IEA:Ensembl.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:Ensembl.
DR   GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR   GO; GO:0003180; P:aortic valve morphogenesis; IMP:BHF-UCL.
DR   GO; GO:1902263; P:apoptotic process involved in embryonic digit morphogenesis; IEA:Ensembl.
DR   GO; GO:0060842; P:arterial endothelial cell differentiation; ISS:BHF-UCL.
DR   GO; GO:0048708; P:astrocyte differentiation; IEA:Ensembl.
DR   GO; GO:0003162; P:atrioventricular node development; IEA:Ensembl.
DR   GO; GO:0003181; P:atrioventricular valve morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0009912; P:auditory receptor cell fate commitment; IEA:Ensembl.
DR   GO; GO:0007409; P:axonogenesis; IEA:Ensembl.
DR   GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IEA:Ensembl.
DR   GO; GO:0003209; P:cardiac atrium morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0003207; P:cardiac chamber formation; ISS:BHF-UCL.
DR   GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; ISS:BHF-UCL.
DR   GO; GO:0003214; P:cardiac left ventricle morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0060038; P:cardiac muscle cell proliferation; IEA:Ensembl.
DR   GO; GO:0055008; P:cardiac muscle tissue morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0003213; P:cardiac right atrium morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0003219; P:cardiac right ventricle formation; IEA:Ensembl.
DR   GO; GO:0060411; P:cardiac septum morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0060948; P:cardiac vascular smooth muscle cell development; ISS:BHF-UCL.
DR   GO; GO:0003208; P:cardiac ventricle morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0007050; P:cell cycle arrest; IDA:UniProtKB.
DR   GO; GO:0021515; P:cell differentiation in spinal cord; IEA:Ensembl.
DR   GO; GO:0001708; P:cell fate specification; IEA:Ensembl.
DR   GO; GO:0003273; P:cell migration involved in endocardial cushion formation; ISS:BHF-UCL.
DR   GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IDA:BHF-UCL.
DR   GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IDA:UniProtKB.
DR   GO; GO:0060271; P:cilium assembly; ISS:UniProtKB.
DR   GO; GO:0072044; P:collecting duct development; IEA:Ensembl.
DR   GO; GO:0007386; P:compartment pattern specification; IEA:Ensembl.
DR   GO; GO:0060982; P:coronary artery morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0003182; P:coronary sinus valve morphogenesis; IEA:Ensembl.
DR   GO; GO:0003169; P:coronary vein morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0007368; P:determination of left/right symmetry; ISS:BHF-UCL.
DR   GO; GO:0072017; P:distal tubule development; IEA:Ensembl.
DR   GO; GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Ensembl.
DR   GO; GO:0060956; P:endocardial cell differentiation; ISS:BHF-UCL.
DR   GO; GO:0003203; P:endocardial cushion morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0003157; P:endocardium development; ISS:BHF-UCL.
DR   GO; GO:0003160; P:endocardium morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0007492; P:endoderm development; IEA:Ensembl.
DR   GO; GO:0001837; P:epithelial to mesenchymal transition; IMP:BHF-UCL.
DR   GO; GO:0003198; P:epithelial to mesenchymal transition involved in endocardial cushion formation; ISS:BHF-UCL.
DR   GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR   GO; GO:0007440; P:foregut morphogenesis; IEA:Ensembl.
DR   GO; GO:0072144; P:glomerular mesangial cell development; IEA:Ensembl.
DR   GO; GO:0003241; P:growth involved in heart morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0031069; P:hair follicle morphogenesis; IEA:Ensembl.
DR   GO; GO:0007507; P:heart development; IMP:DFLAT.
DR   GO; GO:0001947; P:heart looping; ISS:BHF-UCL.
DR   GO; GO:0061384; P:heart trabecula morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0048873; P:homeostasis of number of cells within a tissue; ISS:BHF-UCL.
DR   GO; GO:0006959; P:humoral immune response; IEA:Ensembl.
DR   GO; GO:0006955; P:immune response; NAS:UniProtKB.
DR   GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR   GO; GO:0002437; P:inflammatory response to antigenic stimulus; IEA:Ensembl.
DR   GO; GO:0072602; P:interleukin-4 secretion; IEA:Ensembl.
DR   GO; GO:0030216; P:keratinocyte differentiation; IEA:Ensembl.
DR   GO; GO:0070986; P:left/right axis specification; IEA:Ensembl.
DR   GO; GO:0001889; P:liver development; IEA:Ensembl.
DR   GO; GO:0030324; P:lung development; IEA:Ensembl.
DR   GO; GO:0014031; P:mesenchymal cell development; ISS:BHF-UCL.
DR   GO; GO:0003192; P:mitral valve formation; IMP:BHF-UCL.
DR   GO; GO:2000811; P:negative regulation of anoikis; IMP:BHF-UCL.
DR   GO; GO:0070168; P:negative regulation of biomineral tissue development; ISS:BHF-UCL.
DR   GO; GO:0030514; P:negative regulation of BMP signaling pathway; ISS:BHF-UCL.
DR   GO; GO:0045955; P:negative regulation of calcium ion-dependent exocytosis; IEA:Ensembl.
DR   GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR   GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; ISS:BHF-UCL.
DR   GO; GO:0043086; P:negative regulation of catalytic activity; ISS:UniProtKB.
DR   GO; GO:0060354; P:negative regulation of cell adhesion molecule production; IMP:ARUK-UCL.
DR   GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; IDA:UniProtKB.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR   GO; GO:0003252; P:negative regulation of cell proliferation involved in heart valve morphogenesis; ISS:BHF-UCL.
DR   GO; GO:2000048; P:negative regulation of cell-cell adhesion mediated by cadherin; IMP:ARUK-UCL.
DR   GO; GO:0010812; P:negative regulation of cell-substrate adhesion; IDA:BHF-UCL.
DR   GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR   GO; GO:2001027; P:negative regulation of endothelial cell chemotaxis; IDA:UniProtKB.
DR   GO; GO:0003332; P:negative regulation of extracellular matrix constituent secretion; ISS:BHF-UCL.
DR   GO; GO:0010629; P:negative regulation of gene expression; IDA:UniProtKB.
DR   GO; GO:0060253; P:negative regulation of glial cell proliferation; ISS:UniProtKB.
DR   GO; GO:0045967; P:negative regulation of growth rate; IDA:UniProtKB.
DR   GO; GO:0045608; P:negative regulation of inner ear auditory receptor cell differentiation; IEA:Ensembl.
DR   GO; GO:0045662; P:negative regulation of myoblast differentiation; IMP:UniProtKB.
DR   GO; GO:0010832; P:negative regulation of myotube differentiation; ISS:UniProtKB.
DR   GO; GO:0050768; P:negative regulation of neurogenesis; ISS:UniProtKB.
DR   GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; ISS:UniProtKB.
DR   GO; GO:0030279; P:negative regulation of ossification; ISS:BHF-UCL.
DR   GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISS:BHF-UCL.
DR   GO; GO:0046533; P:negative regulation of photoreceptor cell differentiation; IEA:Ensembl.
DR   GO; GO:2000974; P:negative regulation of pro-B cell differentiation; ISS:UniProtKB.
DR   GO; GO:2000737; P:negative regulation of stem cell differentiation; IMP:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:ARUK-UCL.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:BHF-UCL.
DR   GO; GO:0021915; P:neural tube development; IEA:Ensembl.
DR   GO; GO:0097150; P:neuronal stem cell population maintenance; IEP:UniProtKB.
DR   GO; GO:0061314; P:Notch signaling involved in heart development; IMP:BHF-UCL.
DR   GO; GO:0007219; P:Notch signaling pathway; IDA:UniProtKB.
DR   GO; GO:0003270; P:Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation; IEA:Ensembl.
DR   GO; GO:0048709; P:oligodendrocyte differentiation; IEA:Ensembl.
DR   GO; GO:0003151; P:outflow tract morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0003344; P:pericardium morphogenesis; ISS:BHF-UCL.
DR   GO; GO:1903849; P:positive regulation of aorta morphogenesis; IEA:Ensembl.
DR   GO; GO:1902339; P:positive regulation of apoptotic process involved in morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0048711; P:positive regulation of astrocyte differentiation; ISS:UniProtKB.
DR   GO; GO:0030513; P:positive regulation of BMP signaling pathway; ISS:UniProtKB.
DR   GO; GO:0062043; P:positive regulation of cardiac epithelial to mesenchymal transition; ISS:BHF-UCL.
DR   GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; ISS:BHF-UCL.
DR   GO; GO:0030335; P:positive regulation of cell migration; ISS:BHF-UCL.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR   GO; GO:0045603; P:positive regulation of endothelial cell differentiation; IEA:Ensembl.
DR   GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISS:BHF-UCL.
DR   GO; GO:0045618; P:positive regulation of keratinocyte differentiation; IEA:Ensembl.
DR   GO; GO:0002052; P:positive regulation of neuroblast proliferation; IEA:Ensembl.
DR   GO; GO:0045747; P:positive regulation of Notch signaling pathway; TAS:Reactome.
DR   GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IDA:UniProtKB.
DR   GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; ISS:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR   GO; GO:0061419; P:positive regulation of transcription from RNA polymerase II promoter in response to hypoxia; ISS:UniProtKB.
DR   GO; GO:0007221; P:positive regulation of transcription of Notch receptor target; ISS:BHF-UCL.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR   GO; GO:0045070; P:positive regulation of viral genome replication; IEA:Ensembl.
DR   GO; GO:0060740; P:prostate gland epithelium morphogenesis; IEA:Ensembl.
DR   GO; GO:0003184; P:pulmonary valve morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0060768; P:regulation of epithelial cell proliferation involved in prostate gland development; IEA:Ensembl.
DR   GO; GO:1901201; P:regulation of extracellular matrix assembly; ISS:BHF-UCL.
DR   GO; GO:0014807; P:regulation of somitogenesis; IEA:Ensembl.
DR   GO; GO:0003256; P:regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation; ISS:BHF-UCL.
DR   GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:UniProtKB.
DR   GO; GO:0031960; P:response to corticosteroid; IEA:Ensembl.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR   GO; GO:0032495; P:response to muramyl dipeptide; IEA:Ensembl.
DR   GO; GO:0060528; P:secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development; IEA:Ensembl.
DR   GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl.
DR   GO; GO:0048103; P:somatic stem cell division; IEA:Ensembl.
DR   GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR   GO; GO:0002040; P:sprouting angiogenesis; IEA:Ensembl.
DR   GO; GO:0042246; P:tissue regeneration; IEA:Ensembl.
DR   GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome.
DR   GO; GO:0035148; P:tube formation; IMP:UniProtKB.
DR   GO; GO:0060979; P:vasculogenesis involved in coronary vascular morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0060843; P:venous endothelial cell differentiation; ISS:BHF-UCL.
DR   GO; GO:0060412; P:ventricular septum morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; ISS:BHF-UCL.
DR   DisProt; DP01104; -.
DR   Gene3D; 1.25.40.20; -; 1.
DR   IDEAL; IID00199; -.
DR   InterPro; IPR002110; Ankyrin_rpt.
DR   InterPro; IPR020683; Ankyrin_rpt-contain_dom.
DR   InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR   InterPro; IPR024600; DUF3454_notch.
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; IPR022362; Notch_1.
DR   InterPro; IPR000800; Notch_dom.
DR   InterPro; IPR010660; Notch_NOD_dom.
DR   InterPro; IPR011656; Notch_NODP_dom.
DR   Pfam; PF12796; Ank_2; 2.
DR   Pfam; PF11936; DUF3454; 1.
DR   Pfam; PF00008; EGF; 25.
DR   Pfam; PF07645; EGF_CA; 4.
DR   Pfam; PF12661; hEGF; 2.
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; PR01984; NOTCH1.
DR   SMART; SM00248; ANK; 6.
DR   SMART; SM01334; DUF3454; 1.
DR   SMART; SM00181; EGF; 36.
DR   SMART; SM00179; EGF_CA; 33.
DR   SMART; SM00004; NL; 3.
DR   SMART; SM01338; NOD; 1.
DR   SMART; SM01339; NODP; 1.
DR   SUPFAM; SSF48403; SSF48403; 1.
DR   SUPFAM; SSF57184; SSF57184; 6.
DR   SUPFAM; SSF90193; SSF90193; 3.
DR   PROSITE; PS50297; ANK_REP_REGION; 1.
DR   PROSITE; PS50088; ANK_REPEAT; 4.
DR   PROSITE; PS00010; ASX_HYDROXYL; 22.
DR   PROSITE; PS00022; EGF_1; 35.
DR   PROSITE; PS01186; EGF_2; 27.
DR   PROSITE; PS50026; EGF_3; 36.
DR   PROSITE; PS01187; EGF_CA; 20.
DR   PROSITE; PS50258; LNR; 3.
PE   1: Evidence at protein level;
KW   3D-structure; Activator; Angiogenesis; ANK repeat; Calcium; Cell membrane;
KW   Developmental protein; Differentiation; Direct protein sequencing;
KW   Disease mutation; Disulfide bond; EGF-like domain; Glycoprotein;
KW   Hydroxylation; Isopeptide bond; Membrane; Metal-binding;
KW   Notch signaling pathway; Nucleus; Phosphoprotein; Polymorphism; Receptor;
KW   Reference proteome; Repeat; Signal; Transcription;
KW   Transcription regulation; Transmembrane; Transmembrane helix;
KW   Ubl conjugation.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   CHAIN           19..2555
FT                   /note="Neurogenic locus notch homolog protein 1"
FT                   /id="PRO_0000007674"
FT   CHAIN           1721..2555
FT                   /note="Notch 1 extracellular truncation"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000007675"
FT   CHAIN           1754..2555
FT                   /note="Notch 1 intracellular domain"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000007676"
FT   TOPO_DOM        19..1735
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305|PubMed:28439555,
FT                   ECO:0000305|PubMed:30598546"
FT   TRANSMEM        1736..1756
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:28439555,
FT                   ECO:0000269|PubMed:30598546"
FT   TOPO_DOM        1757..2555
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305|PubMed:28439555,
FT                   ECO:0000305|PubMed:30598546"
FT   DOMAIN          20..58
FT                   /note="EGF-like 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          59..99
FT                   /note="EGF-like 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          102..139
FT                   /note="EGF-like 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          140..176
FT                   /note="EGF-like 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          178..216
FT                   /note="EGF-like 5; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          218..255
FT                   /note="EGF-like 6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          257..293
FT                   /note="EGF-like 7; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          295..333
FT                   /note="EGF-like 8; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          335..371
FT                   /note="EGF-like 9; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          372..410
FT                   /note="EGF-like 10"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          412..450
FT                   /note="EGF-like 11; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          452..488
FT                   /note="EGF-like 12; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          490..526
FT                   /note="EGF-like 13; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          528..564
FT                   /note="EGF-like 14; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          566..601
FT                   /note="EGF-like 15; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          603..639
FT                   /note="EGF-like 16; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          641..676
FT                   /note="EGF-like 17; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          678..714
FT                   /note="EGF-like 18; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          716..751
FT                   /note="EGF-like 19; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          753..789
FT                   /note="EGF-like 20"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          791..827
FT                   /note="EGF-like 21; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          829..867
FT                   /note="EGF-like 22"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          869..905
FT                   /note="EGF-like 23; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          907..943
FT                   /note="EGF-like 24"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          945..981
FT                   /note="EGF-like 25; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          983..1019
FT                   /note="EGF-like 26"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          1021..1057
FT                   /note="EGF-like 27"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          1059..1095
FT                   /note="EGF-like 28"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          1097..1143
FT                   /note="EGF-like 29"
FT                   /evidence="ECO:0000305"
FT   DOMAIN          1145..1181
FT                   /note="EGF-like 30"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          1183..1219
FT                   /note="EGF-like 31; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          1221..1265
FT                   /note="EGF-like 32; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          1267..1305
FT                   /note="EGF-like 33"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          1307..1346
FT                   /note="EGF-like 34"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          1348..1384
FT                   /note="EGF-like 35"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          1387..1426
FT                   /note="EGF-like 36"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   REPEAT          1449..1489
FT                   /note="LNR 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT   REPEAT          1490..1531
FT                   /note="LNR 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT   REPEAT          1532..1571
FT                   /note="LNR 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT   REPEAT          1927..1956
FT                   /note="ANK 1"
FT                   /evidence="ECO:0000255"
FT   REPEAT          1960..1990
FT                   /note="ANK 2"
FT                   /evidence="ECO:0000255"
FT   REPEAT          1994..2023
FT                   /note="ANK 3"
FT                   /evidence="ECO:0000255"
FT   REPEAT          2027..2056
FT                   /note="ANK 4"
FT                   /evidence="ECO:0000255"
FT   REPEAT          2060..2089
FT                   /note="ANK 5"
FT                   /evidence="ECO:0000255"
FT   REPEAT          2095..2122
FT                   /note="ANK 6"
FT   REGION          420..421
FT                   /note="Interaction with DLL4"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   REGION          448..452
FT                   /note="Interaction with DLL4"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   REGION          1728..1760
FT                   /note="Interaction with PSEN1"
FT                   /evidence="ECO:0000269|PubMed:30598546"
FT   REGION          1947..1955
FT                   /note="HIF1AN-binding"
FT                   /evidence="ECO:0000250"
FT   REGION          2014..2022
FT                   /note="HIF1AN-binding"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        1575..1578
FT                   /note="Poly-Val"
FT   COMPBIAS        1661..1664
FT                   /note="Poly-Arg"
FT   COMPBIAS        1728..1731
FT                   /note="Poly-Pro"
FT   COMPBIAS        1740..1743
FT                   /note="Poly-Ala"
FT   COMPBIAS        1901..1904
FT                   /note="Poly-Glu"
FT   COMPBIAS        2259..2262
FT                   /note="Poly-Gly"
FT   COMPBIAS        2403..2406
FT                   /note="Poly-Gln"
FT   COMPBIAS        2410..2417
FT                   /note="Poly-Pro"
FT   COMPBIAS        2521..2524
FT                   /note="Poly-Ser"
FT   METAL           432
FT                   /note="Calcium 1; via carbonyl oxygen"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   METAL           435
FT                   /note="Calcium 1; via amide nitrogen"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   METAL           452
FT                   /note="Calcium 2"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   METAL           453
FT                   /note="Calcium 2; via carbonyl oxygen"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   METAL           455
FT                   /note="Calcium 2"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   METAL           469
FT                   /note="Calcium 2"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   METAL           470
FT                   /note="Calcium 2; via carbonyl oxygen"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   METAL           490
FT                   /note="Calcium 3"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   METAL           491
FT                   /note="Calcium 3; via carbonyl oxygen"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   METAL           493
FT                   /note="Calcium 3"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   METAL           507
FT                   /note="Calcium 3"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   METAL           508
FT                   /note="Calcium 3; via carbonyl oxygen"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   METAL           1457
FT                   /note="Calcium 4; via carbonyl oxygen"
FT   METAL           1460
FT                   /note="Calcium 4"
FT   METAL           1475
FT                   /note="Calcium 4"
FT   METAL           1478
FT                   /note="Calcium 4"
FT   SITE            469
FT                   /note="Interaction with DLL4"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   SITE            1664..1665
FT                   /note="Cleavage; by furin-like protease"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   SITE            1710..1711
FT                   /note="Cleavage; by ADAM17"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   MOD_RES         1861
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   MOD_RES         1955
FT                   /note="(3S)-3-hydroxyasparagine; by HIF1AN; partial"
FT                   /evidence="ECO:0000269|PubMed:17573339"
FT   MOD_RES         2022
FT                   /note="(3S)-3-hydroxyasparagine; by HIF1AN"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        41
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        65
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        73
FT                   /note="O-linked (Fuc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        116
FT                   /note="O-linked (Fuc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        146
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        194
FT                   /note="O-linked (Fuc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        232
FT                   /note="O-linked (Fuc...) threonine; alternate"
FT                   /evidence="ECO:0000269|PubMed:24226769"
FT   CARBOHYD        232
FT                   /note="O-linked (GalNAc...) threonine; alternate"
FT                   /evidence="ECO:0000269|PubMed:24226769"
FT   CARBOHYD        311
FT                   /note="O-linked (Fuc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        341
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        349
FT                   /note="O-linked (Fuc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        378
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        435
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000269|PubMed:30127001"
FT   CARBOHYD        458
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   CARBOHYD        466
FT                   /note="O-linked (Fuc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   CARBOHYD        496
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   CARBOHYD        534
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        609
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        617
FT                   /note="O-linked (Fuc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        647
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        692
FT                   /note="O-linked (Fuc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        722
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        759
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        767
FT                   /note="O-linked (Fuc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        784
FT                   /note="O-linked (GlcNAc) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        797
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        805
FT                   /note="O-linked (Fuc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        921
FT                   /note="O-linked (Fuc) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        951
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        959
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        997
FT                   /note="O-linked (Fuc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        1027
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        1035
FT                   /note="O-linked (Fuc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        1065
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        1159
FT                   /note="O-linked (Fuc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        1179
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1189
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        1197
FT                   /note="O-linked (Fuc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        1241
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1273
FT                   /note="O-linked (Glc...) serine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        1362
FT                   /note="O-linked (Fuc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        1379
FT                   /note="O-linked (GlcNAc...) threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   CARBOHYD        1402
FT                   /note="O-linked (Fuc...) threonine; alternate"
FT                   /evidence="ECO:0000269|PubMed:24226769"
FT   CARBOHYD        1402
FT                   /note="O-linked (GalNAc...) threonine; alternate"
FT                   /evidence="ECO:0000269|PubMed:24226769"
FT   CARBOHYD        1489
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1587
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1725
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:24226769"
FT   DISULFID        24..37
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        31..46
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        48..57
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        63..74
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        68..87
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        89..98
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        106..117
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        111..127
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        129..138
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        144..155
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        149..164
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        166..175
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        182..195
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        189..204
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        206..215
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        222..233
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        227..243
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        245..254
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        261..272
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        266..281
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        283..292
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        299..312
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        306..321
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        323..332
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        339..350
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        344..359
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        361..370
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        376..387
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        381..398
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        400..409
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        416..429
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   DISULFID        423..438
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   DISULFID        440..449
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   DISULFID        456..467
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   DISULFID        461..476
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   DISULFID        478..487
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   DISULFID        494..505
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   DISULFID        499..514
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   DISULFID        516..525
FT                   /evidence="ECO:0000250|UniProtKB:Q07008"
FT   DISULFID        532..543
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        537..552
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        554..563
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        570..580
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        575..589
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        591..600
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        607..618
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        612..627
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        629..638
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        645..655
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        650..664
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        666..675
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        682..693
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        687..702
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        704..713
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        720..730
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        725..739
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        741..750
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        757..768
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        762..777
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        779..788
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        795..806
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        800..815
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        817..826
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        833..844
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        838..855
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        857..866
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        873..884
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        878..893
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        895..904
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        911..922
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        916..931
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        933..942
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        949..960
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        954..969
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        971..980
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        987..998
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        992..1007
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1009..1018
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1025..1036
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1030..1045
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1047..1056
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1063..1074
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1068..1083
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1085..1094
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1101..1122
FT                   /evidence="ECO:0000305"
FT   DISULFID        1116..1131
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1133..1142
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1149..1160
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1154..1169
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1171..1180
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1187..1198
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1192..1207
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1209..1218
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1238..1253
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1255..1264
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1271..1284
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1276..1293
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1295..1304
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1311..1322
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1316..1334
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1336..1345
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1352..1363
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1357..1372
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1374..1383
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1391..1403
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1397..1414
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1416..1425
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        1449..1472
FT                   /evidence="ECO:0000269|PubMed:12795601"
FT   DISULFID        1454..1467
FT                   /evidence="ECO:0000269|PubMed:12795601"
FT   DISULFID        1463..1479
FT                   /evidence="ECO:0000269|PubMed:12795601"
FT   DISULFID        1490..1514
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT   DISULFID        1496..1509
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT   DISULFID        1505..1521
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT   DISULFID        1536..1549
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT   DISULFID        1545..1561
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT   CROSSLNK        1759
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:Q01705"
FT   VARIANT         300
FT                   /note="Q -> R (in dbSNP:rs11574885)"
FT                   /id="VAR_034898"
FT   VARIANT         429
FT                   /note="C -> R (in AOS5; dbSNP:rs587777736)"
FT                   /evidence="ECO:0000269|PubMed:25132448"
FT                   /id="VAR_071960"
FT   VARIANT         879
FT                   /note="R -> W (in dbSNP:rs11574895)"
FT                   /id="VAR_048990"
FT   VARIANT         1496
FT                   /note="C -> Y (in AOS5; dbSNP:rs587781259)"
FT                   /evidence="ECO:0000269|PubMed:25132448"
FT                   /id="VAR_071961"
FT   VARIANT         1671
FT                   /note="V -> I (in dbSNP:rs2229968)"
FT                   /id="VAR_046618"
FT   VARIANT         1989
FT                   /note="D -> N (in AOS5; dbSNP:rs587777734)"
FT                   /evidence="ECO:0000269|PubMed:25132448"
FT                   /id="VAR_071962"
FT   MUTAGEN         1728
FT                   /note="P->C: Formation of an artifactual disulfide bond
FT                   with PSEN1."
FT                   /evidence="ECO:0000269|PubMed:30598546"
FT   MUTAGEN         1755..1761
FT                   /note="Missing: Loss of proteolytic cleavage by gamma-
FT                   secretase."
FT                   /evidence="ECO:0000269|PubMed:30598546"
FT   CONFLICT        187
FT                   /note="G -> R (in Ref. 1; AAG33848 and 3; AAA60614)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        282
FT                   /note="R -> P (in Ref. 1; AAG33848 and 3; AAA60614)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        477
FT                   /note="I -> M (in Ref. 1; AAG33848 and 3; AAA60614)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        614..615
FT                   /note="HG -> LR (in Ref. 1; AAG33848 and 3; AAA60614)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        621
FT                   /note="R -> P (in Ref. 1; AAG33848 and 3; AAA60614)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        677
FT                   /note="I -> S (in Ref. 1; AAG33848 and 3; AAA60614)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        775
FT                   /note="Y -> I (in Ref. 1; AAG33848 and 3; AAA60614)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        803
FT                   /note="Q -> K (in Ref. 1; AAG33848 and 3; AAA60614)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        860..862
FT                   /note="GWQ -> AGAK (in Ref. 1; AAG33848 and 3; AAA60614)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1021
FT                   /note="D -> V (in Ref. 1; AAG33848 and 3; AAA60614)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1028
FT                   /note="Q -> R (in Ref. 1; AAG33848 and 3; AAA60614)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1032
FT                   /note="H -> L (in Ref. 1; AAG33848 and 3; AAA60614)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1040..1043
FT                   /note="CGSY -> RGLH (in Ref. 1; AAG33848 and 3; AAA60614)"
FT                   /evidence="ECO:0000305"
FT   HELIX           143..146
FT                   /evidence="ECO:0000244|PDB:5FMA"
FT   STRAND          154..157
FT                   /evidence="ECO:0000244|PDB:5FMA"
FT   STRAND          162..165
FT                   /evidence="ECO:0000244|PDB:5FMA"
FT   STRAND          170..175
FT                   /evidence="ECO:0000244|PDB:5FMA"
FT   HELIX           181..184
FT                   /evidence="ECO:0000244|PDB:5FMA"
FT   TURN            190..192
FT                   /evidence="ECO:0000244|PDB:5FMA"
FT   STRAND          194..198
FT                   /evidence="ECO:0000244|PDB:5FMA"
FT   STRAND          201..205
FT                   /evidence="ECO:0000244|PDB:5FMA"
FT   STRAND          210..212
FT                   /evidence="ECO:0000244|PDB:5FMA"
FT   STRAND          232..235
FT                   /evidence="ECO:0000244|PDB:5FMA"
FT   STRAND          237..239
FT                   /evidence="ECO:0000244|PDB:5FMA"
FT   STRAND          241..244
FT                   /evidence="ECO:0000244|PDB:5FMA"
FT   STRAND          249..254
FT                   /evidence="ECO:0000244|PDB:5FMA"
FT   STRAND          271..274
FT                   /evidence="ECO:0000244|PDB:5FMA"
FT   STRAND          279..282
FT                   /evidence="ECO:0000244|PDB:5FMA"
FT   STRAND          289..292
FT                   /evidence="ECO:0000244|PDB:5FMA"
FT   HELIX           415..417
FT                   /evidence="ECO:0000244|PDB:4D0E"
FT   STRAND          418..420
FT                   /evidence="ECO:0000244|PDB:4D0E"
FT   STRAND          422..424
FT                   /evidence="ECO:0000244|PDB:4D0E"
FT   STRAND          428..432
FT                   /evidence="ECO:0000244|PDB:4D0E"
FT   STRAND          435..439
FT                   /evidence="ECO:0000244|PDB:4D0E"
FT   STRAND          444..446
FT                   /evidence="ECO:0000244|PDB:4D0E"
FT   HELIX           455..458
FT                   /evidence="ECO:0000244|PDB:5L0R"
FT   STRAND          466..470
FT                   /evidence="ECO:0000244|PDB:5L0R"
FT   STRAND          473..477
FT                   /evidence="ECO:0000244|PDB:5L0R"
FT   STRAND          482..484
FT                   /evidence="ECO:0000244|PDB:5L0R"
FT   TURN            493..496
FT                   /evidence="ECO:0000244|PDB:4D0E"
FT   TURN            500..502
FT                   /evidence="ECO:0000244|PDB:2VJ3"
FT   STRAND          504..507
FT                   /evidence="ECO:0000244|PDB:4D0E"
FT   STRAND          512..515
FT                   /evidence="ECO:0000244|PDB:4D0E"
FT   STRAND          520..522
FT                   /evidence="ECO:0000244|PDB:4D0E"
FT   HELIX           1448..1450
FT                   /evidence="ECO:0000244|PDB:3L95"
FT   HELIX           1452..1457
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   STRAND          1460..1462
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   HELIX           1465..1467
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   HELIX           1470..1472
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   HELIX           1473..1476
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   TURN            1477..1482
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   TURN            1486..1489
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   HELIX           1492..1494
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   HELIX           1496..1498
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   TURN            1499..1501
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   STRAND          1502..1504
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   HELIX           1507..1509
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   HELIX           1512..1519
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   TURN            1530..1532
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   HELIX           1533..1539
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   STRAND          1542..1544
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   HELIX           1547..1549
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   HELIX           1552..1559
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   STRAND          1563..1565
FT                   /evidence="ECO:0000244|PDB:3L95"
FT   STRAND          1571..1580
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   HELIX           1582..1587
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   HELIX           1589..1600
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   STRAND          1602..1606
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   STRAND          1616..1620
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   STRAND          1672..1681
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   HELIX           1685..1688
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   HELIX           1696..1708
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   STRAND          1714..1716
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   STRAND          1718..1724
FT                   /evidence="ECO:0000244|PDB:3ETO"
FT   STRAND          1733..1735
FT                   /evidence="ECO:0000244|PDB:6IDF"
FT   HELIX           1736..1741
FT                   /evidence="ECO:0000244|PDB:6IDF"
FT   HELIX           1743..1746
FT                   /evidence="ECO:0000244|PDB:6IDF"
FT   TURN            1747..1752
FT                   /evidence="ECO:0000244|PDB:6IDF"
FT   STRAND          1755..1760
FT                   /evidence="ECO:0000244|PDB:6IDF"
FT   STRAND          1767..1769
FT                   /evidence="ECO:0000244|PDB:5KZO"
FT   HELIX           1884..1890
FT                   /evidence="ECO:0000244|PDB:2F8X"
FT   HELIX           1909..1914
FT                   /evidence="ECO:0000244|PDB:2F8X"
FT   TURN            1925..1927
FT                   /evidence="ECO:0000244|PDB:2F8Y"
FT   HELIX           1931..1937
FT                   /evidence="ECO:0000244|PDB:2F8Y"
FT   HELIX           1941..1949
FT                   /evidence="ECO:0000244|PDB:2F8Y"
FT   HELIX           1964..1970
FT                   /evidence="ECO:0000244|PDB:2F8Y"
FT   HELIX           1974..1982
FT                   /evidence="ECO:0000244|PDB:2F8Y"
FT   STRAND          1983..1985
FT                   /evidence="ECO:0000244|PDB:2F8X"
FT   HELIX           1998..2005
FT                   /evidence="ECO:0000244|PDB:2F8Y"
FT   HELIX           2008..2016
FT                   /evidence="ECO:0000244|PDB:2F8Y"
FT   HELIX           2031..2037
FT                   /evidence="ECO:0000244|PDB:2F8Y"
FT   HELIX           2041..2049
FT                   /evidence="ECO:0000244|PDB:2F8Y"
FT   HELIX           2064..2071
FT                   /evidence="ECO:0000244|PDB:2F8Y"
FT   HELIX           2074..2082
FT                   /evidence="ECO:0000244|PDB:2F8Y"
FT   HELIX           2097..2103
FT                   /evidence="ECO:0000244|PDB:2F8Y"
FT   HELIX           2107..2115
FT                   /evidence="ECO:0000244|PDB:2F8Y"
SQ   SEQUENCE   2555 AA;  272505 MW;  E173C872D195F028 CRC64;
     MPPLLAPLLC LALLPALAAR GPRCSQPGET CLNGGKCEAA NGTEACVCGG AFVGPRCQDP
     NPCLSTPCKN AGTCHVVDRR GVADYACSCA LGFSGPLCLT PLDNACLTNP CRNGGTCDLL
     TLTEYKCRCP PGWSGKSCQQ ADPCASNPCA NGGQCLPFEA SYICHCPPSF HGPTCRQDVN
     ECGQKPGLCR HGGTCHNEVG SYRCVCRATH TGPNCERPYV PCSPSPCQNG GTCRPTGDVT
     HECACLPGFT GQNCEENIDD CPGNNCKNGG ACVDGVNTYN CRCPPEWTGQ YCTEDVDECQ
     LMPNACQNGG TCHNTHGGYN CVCVNGWTGE DCSENIDDCA SAACFHGATC HDRVASFYCE
     CPHGRTGLLC HLNDACISNP CNEGSNCDTN PVNGKAICTC PSGYTGPACS QDVDECSLGA
     NPCEHAGKCI NTLGSFECQC LQGYTGPRCE IDVNECVSNP CQNDATCLDQ IGEFQCICMP
     GYEGVHCEVN TDECASSPCL HNGRCLDKIN EFQCECPTGF TGHLCQYDVD ECASTPCKNG
     AKCLDGPNTY TCVCTEGYTG THCEVDIDEC DPDPCHYGSC KDGVATFTCL CRPGYTGHHC
     ETNINECSSQ PCRHGGTCQD RDNAYLCFCL KGTTGPNCEI NLDDCASSPC DSGTCLDKID
     GYECACEPGY TGSMCNINID ECAGNPCHNG GTCEDGINGF TCRCPEGYHD PTCLSEVNEC
     NSNPCVHGAC RDSLNGYKCD CDPGWSGTNC DINNNECESN PCVNGGTCKD MTSGYVCTCR
     EGFSGPNCQT NINECASNPC LNQGTCIDDV AGYKCNCLLP YTGATCEVVL APCAPSPCRN
     GGECRQSEDY ESFSCVCPTG WQGQTCEVDI NECVLSPCRH GASCQNTHGG YRCHCQAGYS
     GRNCETDIDD CRPNPCHNGG SCTDGINTAF CDCLPGFRGT FCEEDINECA SDPCRNGANC
     TDCVDSYTCT CPAGFSGIHC ENNTPDCTES SCFNGGTCVD GINSFTCLCP PGFTGSYCQH
     DVNECDSQPC LHGGTCQDGC GSYRCTCPQG YTGPNCQNLV HWCDSSPCKN GGKCWQTHTQ
     YRCECPSGWT GLYCDVPSVS CEVAAQRQGV DVARLCQHGG LCVDAGNTHH CRCQAGYTGS
     YCEDLVDECS PSPCQNGATC TDYLGGYSCK CVAGYHGVNC SEEIDECLSH PCQNGGTCLD
     LPNTYKCSCP RGTQGVHCEI NVDDCNPPVD PVSRSPKCFN NGTCVDQVGG YSCTCPPGFV
     GERCEGDVNE CLSNPCDARG TQNCVQRVND FHCECRAGHT GRRCESVING CKGKPCKNGG
     TCAVASNTAR GFICKCPAGF EGATCENDAR TCGSLRCLNG GTCISGPRSP TCLCLGPFTG
     PECQFPASSP CLGGNPCYNQ GTCEPTSESP FYRCLCPAKF NGLLCHILDY SFGGGAGRDI
     PPPLIEEACE LPECQEDAGN KVCSLQCNNH ACGWDGGDCS LNFNDPWKNC TQSLQCWKYF
     SDGHCDSQCN SAGCLFDGFD CQRAEGQCNP LYDQYCKDHF SDGHCDQGCN SAECEWDGLD
     CAEHVPERLA AGTLVVVVLM PPEQLRNSSF HFLRELSRVL HTNVVFKRDA HGQQMIFPYY
     GREEELRKHP IKRAAEGWAA PDALLGQVKA SLLPGGSEGG RRRRELDPMD VRGSIVYLEI
     DNRQCVQASS QCFQSATDVA AFLGALASLG SLNIPYKIEA VQSETVEPPP PAQLHFMYVA
     AAAFVLLFFV GCGVLLSRKR RRQHGQLWFP EGFKVSEASK KKRREPLGED SVGLKPLKNA
     SDGALMDDNQ NEWGDEDLET KKFRFEEPVV LPDLDDQTDH RQWTQQHLDA ADLRMSAMAP
     TPPQGEVDAD CMDVNVRGPD GFTPLMIASC SGGGLETGNS EEEEDAPAVI SDFIYQGASL
     HNQTDRTGET ALHLAARYSR SDAAKRLLEA SADANIQDNM GRTPLHAAVS ADAQGVFQIL
     IRNRATDLDA RMHDGTTPLI LAARLAVEGM LEDLINSHAD VNAVDDLGKS ALHWAAAVNN
     VDAAVVLLKN GANKDMQNNR EETPLFLAAR EGSYETAKVL LDHFANRDIT DHMDRLPRDI
     AQERMHHDIV RLLDEYNLVR SPQLHGAPLG GTPTLSPPLC SPNGYLGSLK PGVQGKKVRK
     PSSKGLACGS KEAKDLKARR KKSQDGKGCL LDSSGMLSPV DSLESPHGYL SDVASPPLLP
     SPFQQSPSVP LNHLPGMPDT HLGIGHLNVA AKPEMAALGG GGRLAFETGP PRLSHLPVAS
     GTSTVLGSSS GGALNFTVGG STSLNGQCEW LSRLQSGMVP NQYNPLRGSV APGPLSTQAP
     SLQHGMVGPL HSSLAASALS QMMSYQGLPS TRLATQPHLV QTQQVQPQNL QMQQQNLQPA
     NIQQQQSLQP PPPPPQPHLG VSSAASGHLG RSFLSGEPSQ ADVQPLGPSS LAVHTILPQE
     SPALPTSLPS SLVPPVTAAQ FLTPPSQHSY SSPVDNTPSH QLQVPEHPFL TPSPESPDQW
     SSSSPHSNVS DWSEGVSSPP TSMQSQIARI PEAFK
//
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