NOTC1_HUMAN
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 03-AUG-2022, entry version 248.
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). Interacts with
CC ZFP64 (By similarity). {ECO:0000250|UniProtKB:Q01705,
CC ECO:0000250|UniProtKB:Q07008, ECO:0000269|PubMed:10713164,
CC ECO:0000269|PubMed:11101851, ECO:0000269|PubMed:12050162,
CC ECO:0000269|PubMed:12370315, ECO:0000269|PubMed:17573339,
CC ECO:0000269|PubMed:26522984, ECO:0000269|PubMed:30598546,
CC ECO:0000269|PubMed:9590294}.
CC -!- INTERACTION:
CC P46531; Q13315: ATM; NbExp=8; IntAct=EBI-636374, EBI-495465;
CC P46531; Q969H0: FBXW7; NbExp=11; 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=15; IntAct=EBI-636374, EBI-908250;
CC P46531; P19838: NFKB1; NbExp=2; IntAct=EBI-636374, EBI-300010;
CC P46531; P46531: NOTCH1; NbExp=6; IntAct=EBI-636374, EBI-636374;
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; Q93009: USP7; NbExp=3; IntAct=EBI-636374, EBI-302474;
CC P46531; P98170: XIAP; NbExp=4; IntAct=EBI-636374, EBI-517127;
CC PRO_0000007676; Q8IZL2: MAML2; NbExp=2; IntAct=EBI-9692333, EBI-2864946;
CC PRO_0000007676; Q96JK9: MAML3; NbExp=2; IntAct=EBI-9692333, EBI-1043855;
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 variants 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 variants
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";
CC ---------------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
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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 AlphaFoldDB; P46531; -.
DR SASBDB; P46531; -.
DR SMR; P46531; -.
DR BioGRID; 110913; 346.
DR CORUM; P46531; -.
DR DIP; DIP-29919N; -.
DR IntAct; P46531; 183.
DR MINT; P46531; -.
DR STRING; 9606.ENSP00000277541; -.
DR BindingDB; P46531; -.
DR ChEMBL; CHEMBL2146346; -.
DR GuidetoPHARMACOLOGY; 2861; -.
DR TCDB; 9.B.87.1.12; the selenoprotein p receptor (selp-receptor) family.
DR GlyGen; P46531; 54 sites, 2 O-linked glycans (9 sites).
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; 1312 antibodies from 54 providers.
DR DNASU; 4851; -.
DR Ensembl; ENST00000651671.1; ENSP00000498587.1; ENSG00000148400.13.
DR GeneID; 4851; -.
DR KEGG; hsa:4851; -.
DR MANE-Select; ENST00000651671.1; ENSP00000498587.1; NM_017617.5; NP_060087.3.
DR UCSC; uc004chz.4; human.
DR CTD; 4851; -.
DR DisGeNET; 4851; -.
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 VEuPathDB; HostDB:ENSG00000148400; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000157157; -.
DR HOGENOM; CLU_000576_2_0_1; -.
DR InParanoid; P46531; -.
DR OMA; IAGYSCE; -.
DR OrthoDB; 7525at2759; -.
DR PhylomeDB; P46531; -.
DR TreeFam; TF351641; -.
DR PathwayCommons; P46531; -.
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 Reactome; R-HSA-9759194; Nuclear events mediated by NFE2L2.
DR SignaLink; P46531; -.
DR SIGNOR; P46531; -.
DR BioGRID-ORCS; 4851; 19 hits in 1089 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 ventricular zone and 195 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:0019899; F:enzyme binding; ISS:UniProtKB.
DR GO; GO:0004857; F:enzyme inhibitor activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005112; F:Notch binding; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:BHF-UCL.
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:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IEA:Ensembl.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; 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:0060379; P:cardiac muscle cell myoblast differentiation; 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:0021515; P:cell differentiation in spinal cord; 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:0071228; P:cellular response to tumor cell; IDA:UniProtKB.
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:0009957; P:epidermal cell fate specification; IEA:Ensembl.
DR GO; GO:0072148; P:epithelial cell fate commitment; IEA:Ensembl.
DR GO; GO:0050673; P:epithelial cell proliferation; 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:0002085; P:inhibition of neuroepithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0097400; P:interleukin-17-mediated signaling pathway; 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:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl.
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: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:0061101; P:neuroendocrine cell differentiation; 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; IEA:Ensembl.
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:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0006606; P:protein import into nucleus; 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:0072091; P:regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; 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:0042670; P:retinal cone cell differentiation; 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:0072538; P:T-helper 17 type immune response; IEA:Ensembl.
DR GO; GO:0042246; P:tissue regeneration; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
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; 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; IPR022362; Notch_1.
DR InterPro; IPR024600; Notch_C.
DR InterPro; IPR000800; Notch_dom.
DR InterPro; IPR010660; Notch_NOD_dom.
DR InterPro; IPR011656; Notch_NODP_dom.
DR Pfam; PF12796; Ank_2; 2.
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 variant; Disulfide bond; EGF-like domain; Glycoprotein;
KW Hydroxylation; Isopeptide bond; Membrane; Metal-binding;
KW Notch signaling pathway; Nucleus; Phosphoprotein; 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 1780..1808
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 REGION 2151..2194
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2379..2447
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2483..2555
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2170..2187
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2379..2405
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2483..2506
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2514..2548
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 432
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 435
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 452
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 453
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 455
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 469
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 470
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 490
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 491
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 493
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 507
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 508
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT BINDING 1457
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT BINDING 1460
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT BINDING 1475
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT BINDING 1478
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="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:0007829|PDB:5FMA"
FT STRAND 154..157
FT /evidence="ECO:0007829|PDB:5FMA"
FT STRAND 162..165
FT /evidence="ECO:0007829|PDB:5FMA"
FT STRAND 170..175
FT /evidence="ECO:0007829|PDB:5FMA"
FT HELIX 181..184
FT /evidence="ECO:0007829|PDB:5FMA"
FT TURN 190..192
FT /evidence="ECO:0007829|PDB:5FMA"
FT STRAND 194..198
FT /evidence="ECO:0007829|PDB:5FMA"
FT STRAND 201..205
FT /evidence="ECO:0007829|PDB:5FMA"
FT STRAND 210..212
FT /evidence="ECO:0007829|PDB:5FMA"
FT STRAND 232..235
FT /evidence="ECO:0007829|PDB:5FMA"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:5FMA"
FT STRAND 241..244
FT /evidence="ECO:0007829|PDB:5FMA"
FT STRAND 249..254
FT /evidence="ECO:0007829|PDB:5FMA"
FT STRAND 271..274
FT /evidence="ECO:0007829|PDB:5FMA"
FT STRAND 279..282
FT /evidence="ECO:0007829|PDB:5FMA"
FT STRAND 289..292
FT /evidence="ECO:0007829|PDB:5FMA"
FT HELIX 415..417
FT /evidence="ECO:0007829|PDB:4D0E"
FT STRAND 418..420
FT /evidence="ECO:0007829|PDB:4D0E"
FT STRAND 422..424
FT /evidence="ECO:0007829|PDB:4D0E"
FT STRAND 428..432
FT /evidence="ECO:0007829|PDB:4D0E"
FT STRAND 435..439
FT /evidence="ECO:0007829|PDB:4D0E"
FT STRAND 444..446
FT /evidence="ECO:0007829|PDB:4D0E"
FT HELIX 455..458
FT /evidence="ECO:0007829|PDB:5L0R"
FT STRAND 466..470
FT /evidence="ECO:0007829|PDB:5L0R"
FT STRAND 473..477
FT /evidence="ECO:0007829|PDB:5L0R"
FT STRAND 482..484
FT /evidence="ECO:0007829|PDB:5L0R"
FT TURN 493..496
FT /evidence="ECO:0007829|PDB:4D0E"
FT TURN 500..502
FT /evidence="ECO:0007829|PDB:2VJ3"
FT STRAND 504..507
FT /evidence="ECO:0007829|PDB:4D0E"
FT STRAND 512..515
FT /evidence="ECO:0007829|PDB:4D0E"
FT STRAND 520..522
FT /evidence="ECO:0007829|PDB:4D0E"
FT HELIX 1448..1450
FT /evidence="ECO:0007829|PDB:3L95"
FT HELIX 1452..1457
FT /evidence="ECO:0007829|PDB:3ETO"
FT STRAND 1460..1462
FT /evidence="ECO:0007829|PDB:3ETO"
FT HELIX 1465..1467
FT /evidence="ECO:0007829|PDB:3ETO"
FT HELIX 1470..1472
FT /evidence="ECO:0007829|PDB:3ETO"
FT HELIX 1473..1476
FT /evidence="ECO:0007829|PDB:3ETO"
FT TURN 1477..1482
FT /evidence="ECO:0007829|PDB:3ETO"
FT TURN 1486..1489
FT /evidence="ECO:0007829|PDB:3ETO"
FT HELIX 1492..1494
FT /evidence="ECO:0007829|PDB:3ETO"
FT HELIX 1496..1498
FT /evidence="ECO:0007829|PDB:3ETO"
FT TURN 1499..1501
FT /evidence="ECO:0007829|PDB:3ETO"
FT STRAND 1502..1504
FT /evidence="ECO:0007829|PDB:3ETO"
FT HELIX 1507..1509
FT /evidence="ECO:0007829|PDB:3ETO"
FT HELIX 1512..1519
FT /evidence="ECO:0007829|PDB:3ETO"
FT TURN 1530..1532
FT /evidence="ECO:0007829|PDB:3ETO"
FT HELIX 1533..1539
FT /evidence="ECO:0007829|PDB:3ETO"
FT STRAND 1542..1544
FT /evidence="ECO:0007829|PDB:3ETO"
FT HELIX 1547..1549
FT /evidence="ECO:0007829|PDB:3ETO"
FT HELIX 1552..1559
FT /evidence="ECO:0007829|PDB:3ETO"
FT STRAND 1563..1565
FT /evidence="ECO:0007829|PDB:3L95"
FT STRAND 1571..1580
FT /evidence="ECO:0007829|PDB:3ETO"
FT HELIX 1582..1587
FT /evidence="ECO:0007829|PDB:3ETO"
FT HELIX 1589..1600
FT /evidence="ECO:0007829|PDB:3ETO"
FT STRAND 1602..1606
FT /evidence="ECO:0007829|PDB:3ETO"
FT STRAND 1616..1620
FT /evidence="ECO:0007829|PDB:3ETO"
FT STRAND 1672..1681
FT /evidence="ECO:0007829|PDB:3ETO"
FT HELIX 1685..1688
FT /evidence="ECO:0007829|PDB:3ETO"
FT HELIX 1696..1708
FT /evidence="ECO:0007829|PDB:3ETO"
FT STRAND 1714..1716
FT /evidence="ECO:0007829|PDB:3ETO"
FT STRAND 1718..1724
FT /evidence="ECO:0007829|PDB:3ETO"
FT STRAND 1733..1735
FT /evidence="ECO:0007829|PDB:6IDF"
FT HELIX 1736..1741
FT /evidence="ECO:0007829|PDB:6IDF"
FT HELIX 1743..1746
FT /evidence="ECO:0007829|PDB:6IDF"
FT TURN 1747..1752
FT /evidence="ECO:0007829|PDB:6IDF"
FT STRAND 1755..1760
FT /evidence="ECO:0007829|PDB:6IDF"
FT STRAND 1767..1769
FT /evidence="ECO:0007829|PDB:5KZO"
FT HELIX 1884..1890
FT /evidence="ECO:0007829|PDB:2F8X"
FT HELIX 1909..1914
FT /evidence="ECO:0007829|PDB:2F8X"
FT TURN 1925..1927
FT /evidence="ECO:0007829|PDB:2F8Y"
FT HELIX 1931..1937
FT /evidence="ECO:0007829|PDB:2F8Y"
FT HELIX 1941..1949
FT /evidence="ECO:0007829|PDB:2F8Y"
FT HELIX 1964..1970
FT /evidence="ECO:0007829|PDB:2F8Y"
FT HELIX 1974..1982
FT /evidence="ECO:0007829|PDB:2F8Y"
FT STRAND 1983..1985
FT /evidence="ECO:0007829|PDB:2F8X"
FT HELIX 1998..2005
FT /evidence="ECO:0007829|PDB:2F8Y"
FT HELIX 2008..2016
FT /evidence="ECO:0007829|PDB:2F8Y"
FT HELIX 2031..2037
FT /evidence="ECO:0007829|PDB:2F8Y"
FT HELIX 2041..2049
FT /evidence="ECO:0007829|PDB:2F8Y"
FT HELIX 2064..2071
FT /evidence="ECO:0007829|PDB:2F8Y"
FT HELIX 2074..2082
FT /evidence="ECO:0007829|PDB:2F8Y"
FT HELIX 2097..2103
FT /evidence="ECO:0007829|PDB:2F8Y"
FT HELIX 2107..2115
FT /evidence="ECO:0007829|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
