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 27-MAR-2024, entry version 257. 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; Q13153: PAK1; NbExp=4; IntAct=EBI-636374, EBI-1307; 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 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="https://atlasgeneticsoncology.org/gene/30/NOTCH1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 PDB; 8OR5; NMR; -; A=1734-1760. DR PDB; 8ORY; NMR; -; A=1734-1757. DR PDB; 8ORZ; NMR; -; A=1734-1757. 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 PDBsum; 8OR5; -. DR PDBsum; 8ORY; -. DR PDBsum; 8ORZ; -. DR AlphaFoldDB; P46531; -. DR EMDB; EMD-9648; -. DR SASBDB; P46531; -. DR SMR; P46531; -. DR BioGRID; 110913; 359. DR ComplexPortal; CPX-937; CSL-NOTCH1-MAML transcriptional activation complex. DR CORUM; P46531; -. DR DIP; DIP-29919N; -. DR IntAct; P46531; 187. DR MINT; P46531; -. DR STRING; 9606.ENSP00000498587; -. DR BindingDB; P46531; -. DR ChEMBL; CHEMBL2146346; -. DR GuidetoPHARMACOLOGY; 2861; -. DR TCDB; 9.B.87.1.12; the selenoprotein p receptor (selp-receptor) family. DR GlyCosmos; P46531; 54 sites, 2 glycans. DR GlyGen; P46531; 57 sites, 3 O-linked glycans (13 sites). DR iPTMnet; P46531; -. DR PhosphoSitePlus; P46531; -. DR SwissPalm; P46531; -. DR BioMuta; NOTCH1; -. DR DMDM; 206729936; -. DR EPD; P46531; -. DR jPOST; P46531; -. DR MassIVE; P46531; -. DR MaxQB; P46531; -. DR PaxDb; 9606-ENSP00000277541; -. DR PeptideAtlas; P46531; -. DR ProteomicsDB; 55742; -. DR Pumba; P46531; -. DR ABCD; P46531; 196 sequenced antibodies. DR Antibodypedia; 8424; 1566 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 AGR; HGNC:7881; -. DR CTD; 4851; -. DR DisGeNET; 4851; -. DR GeneCards; 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; TCHEQRD; -. DR OrthoDB; 5473534at2759; -. 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-9793380; Formation of paraxial mesoderm. DR Reactome; R-HSA-9818030; NFE2L2 regulating tumorigenic genes. DR Reactome; R-HSA-9818749; Regulation of NFE2L2 gene expression. DR Reactome; R-HSA-9824272; Somitogenesis. DR SignaLink; P46531; -. DR SIGNOR; P46531; -. DR BioGRID-ORCS; 4851; 23 hits in 1178 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 196 other cell types or tissues. 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:0010008; C:endosome membrane; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. 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:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL. 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; IDA:BHF-UCL. DR GO; GO:0140537; F:transcription regulator activator activity; IEA:Ensembl. DR GO; GO:0004888; F:transmembrane signaling receptor activity; IDA:BHF-UCL. 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:0071456; P:cellular response to hypoxia; ISS:UniProtKB. 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:0001554; P:luteolysis; 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:0032966; P:negative regulation of collagen biosynthetic process; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:BHF-UCL. 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; IEA:Ensembl. 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: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: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:0045893; P:positive regulation of DNA-templated transcription; ISS: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:0051152; P:positive regulation of smooth muscle cell differentiation; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0007221; P:positive regulation of transcription of Notch receptor target; ISS:BHF-UCL. 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:0061344; P:regulation of cell adhesion involved in heart morphogenesis; IEA:Ensembl. DR GO; GO:0006355; P:regulation of DNA-templated transcription; TAS:UniProtKB. 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: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 CDD; cd00054; EGF_CA; 31. DR CDD; cd21702; JMTM_Notch1; 1. DR DisProt; DP01104; -. DR Gene3D; 3.30.300.320; -; 1. DR Gene3D; 3.30.70.3310; -; 1. DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1. DR Gene3D; 2.10.25.10; Laminin; 35. 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 PANTHER; PTHR24044:SF514; ANTERIOR PHARYNX IN EXCESS PROTEIN 1-RELATED; 1. DR PANTHER; PTHR24044; NOTCH LIGAND FAMILY MEMBER; 1. DR Pfam; PF00023; Ank; 1. DR Pfam; PF12796; Ank_2; 1. DR Pfam; PF13637; Ank_4; 1. DR Pfam; PF00008; EGF; 21. DR Pfam; PF07645; EGF_CA; 4. DR Pfam; PF12661; hEGF; 6. 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; PR01983; NOTCH. 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; Ankyrin repeat; 1. DR SUPFAM; SSF57196; EGF/Laminin; 15. DR SUPFAM; SSF57184; Growth factor receptor domain; 6. DR SUPFAM; SSF90193; Notch domain; 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. DR Genevisible; P46531; HS. 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:rs587778563)" 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 FT gamma-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 //