NOTC1_MOUSE
ID NOTC1_MOUSE Reviewed; 2531 AA.
AC Q01705; Q06007; Q3TZW2; Q3U3Y2; Q61905; Q7TQ50; Q7TQ51; Q7TQ52; Q8K428;
AC Q99JC2; Q9QW58; Q9R0X7;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 18-APR-2012, sequence version 3.
DT 03-AUG-2022, entry version 233.
DE RecName: Full=Neurogenic locus notch homolog protein 1;
DE Short=Notch 1;
DE AltName: Full=Motch A {ECO:0000303|PubMed:8440332};
DE AltName: Full=mT14;
DE AltName: Full=p300;
DE Contains:
DE RecName: Full=Notch 1 extracellular truncation {ECO:0000303|PubMed:10882062};
DE Short=NEXT {ECO:0000303|PubMed:10882062};
DE Contains:
DE RecName: Full=Notch 1 intracellular domain;
DE Short=NICD;
DE Flags: Precursor;
GN Name=Notch1; Synonyms=Motch {ECO:0000303|PubMed:8440332};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Embryo;
RX PubMed=8449489; DOI=10.1006/geno.1993.1055;
RA Franco del Amo F., Gendron-Maguire M., Swiatek P.J., Jenkins N.A.,
RA Copeland N.G., Gridley T.;
RT "Cloning, analysis, and chromosomal localization of Notch-1, a mouse
RT homolog of Drosophila Notch.";
RL Genomics 15:259-264(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=BALB/cJ; TISSUE=Thymus;
RX PubMed=7956822; DOI=10.1242/dev.120.9.2421;
RA Nye J.S., Kopan R., Axel R.;
RT "An activated Notch suppresses neurogenesis and myogenesis but not
RT gliogenesis in mammalian cells.";
RL Development 120:2421-2430(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=BALB/cJ; TISSUE=Thymus;
RX PubMed=12123574; DOI=10.1016/s0960-9822(02)00888-6;
RA Foltz D.R., Santiago M.C., Berechid B.E., Nye J.S.;
RT "Glycogen synthase kinase-3beta modulates notch signaling and stability.";
RL Curr. Biol. 12:1006-1011(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=CB-17/SCID; TISSUE=Thymus;
RX PubMed=12807718; DOI=10.1093/carcin/bgg071;
RA Tsuji H., Ishii-Ohba H., Ukai H., Katsube T., Ogiu T.;
RT "Radiation-induced deletions in the 5' end region of Notch1 lead to the
RT formation of truncated proteins and are involved in the development of
RT mouse thymic lymphomas.";
RL Carcinogenesis 24:1257-1268(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 731-1899 (ISOFORM 2), AND DEVELOPMENTAL
RP STAGE.
RC STRAIN=CD-1; TISSUE=Embryo;
RX PubMed=1426644; DOI=10.1016/0012-1606(92)90076-s;
RA Reaume A.G., Conlon R.A., Zirngibl R., Yamaguchi T.P., Rossant J.;
RT "Expression analysis of a Notch homologue in the mouse embryo.";
RL Dev. Biol. 154:377-387(1992).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1161-1547.
RC STRAIN=C57BL/6 X CBA; TISSUE=Embryo;
RX PubMed=8440332; DOI=10.1006/excr.1993.1044;
RA Lardelli M., Lendahl U.;
RT "Motch A and Motch B-two mouse Notch homologues coexpressed in a wide
RT variety of tissues.";
RL Exp. Cell Res. 204:364-372(1993).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1373-2531.
RC STRAIN=NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1551-1647 (ISOFORM 1), AND DEVELOPMENTAL
RP STAGE.
RC TISSUE=Embryo;
RX PubMed=1425352; DOI=10.1242/dev.115.3.737;
RA Franco del Amo F., Smith D.E., Swiatek P.J., Gendron-Maguire M.,
RA Greenspan R.J., McMahon A.P., Gridley T.;
RT "Expression pattern of Motch, a mouse homolog of Drosophila Notch, suggests
RT an important role in early postimplantation mouse development.";
RL Development 115:737-744(1992).
RN [12]
RP PROTEIN SEQUENCE OF 1655-1659, CLEAVAGE BY FURIN-LIKE CONVERTASE, AND
RP MUTAGENESIS OF 1651-ARG--ARG-1654.
RX PubMed=9653148; DOI=10.1073/pnas.95.14.8108;
RA Logeat F., Bessia C., Brou C., LeBail O., Jarriault S., Seidah N.G.,
RA Israel A.;
RT "The Notch1 receptor is cleaved constitutively by a furin-like
RT convertase.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8108-8112(1998).
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1659-1673.
RX PubMed=10437788; DOI=10.1016/s0014-5793(99)00901-1;
RA Lee J.S., Ishimoto A., Yanagawa S.;
RT "Murine leukemia provirus-mediated activation of the Notch1 gene leads to
RT induction of HES-1 in a mouse T lymphoma cell line, DL-3.";
RL FEBS Lett. 455:276-280(1999).
RN [14]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1865-2076, AND DEVELOPMENTAL STAGE IN HAIR
RP FOLLICLES.
RX PubMed=8486742; DOI=10.1083/jcb.121.3.631;
RA Kopan R., Weintraub H.;
RT "Mouse notch: expression in hair follicles correlates with cell fate
RT determination.";
RL J. Cell Biol. 121:631-641(1993).
RN [15]
RP PROTEIN SEQUENCE OF 1937-1952 AND 1995-2019, FUNCTION, INTERACTION WITH
RP HIF1AN, HYDROXYLATION AT ASN-1945 AND ASN-2012 BY HIF1AN, MUTAGENESIS OF
RP ASN-1945 AND ASN-2012, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18299578; DOI=10.1073/pnas.0711591105;
RA Zheng X., Linke S., Dias J.M., Zheng X., Gradin K., Wallis T.P.,
RA Hamilton B.R., Gustafsson M., Ruas J.L., Wilkins S., Bilton R.L.,
RA Brismar K., Whitelaw M.L., Pereira T., Gorman J.J., Ericson J., Peet D.J.,
RA Lendahl U., Poellinger L.;
RT "Interaction with factor inhibiting HIF-1 defines an additional mode of
RT cross-coupling between the Notch and hypoxia signaling pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:3368-3373(2008).
RN [16]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1951-2201.
RX PubMed=9384671;
RA Messerle M., Follo M., Nehls M., Eggert H., Boehm T.;
RT "Dynamic changes in gene expression during in vitro differentiation of
RT mouse embryonic stem cells.";
RL Cytokines Cell. Mol. Ther. 1:139-143(1995).
RN [17]
RP SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF CYS-1675
RP AND CYS-1682.
RX PubMed=10882062; DOI=10.1016/s1097-2765(00)80416-5;
RA Mumm J.S., Schroeter E.H., Saxena M.T., Griesemer A., Tian X., Pan D.J.,
RA Ray W.J., Kopan R.;
RT "A ligand-induced extracellular cleavage regulates gamma-secretase-like
RT proteolytic activation of Notch1.";
RL Mol. Cell 5:197-206(2000).
RN [18]
RP PROTEOLYTIC PROCESSING.
RX PubMed=10882063; DOI=10.1016/s1097-2765(00)80417-7;
RA Brou C., Logeat F., Gupta N., Bessia C., LeBail O., Doedens J.R.,
RA Cumano A., Roux P., Black R.A., Israel A.;
RT "A novel proteolytic cleavage involved in Notch signaling: the role of the
RT disintegrin-metalloprotease TACE.";
RL Mol. Cell 5:207-216(2000).
RN [19]
RP PARTIAL PROTEIN SEQUENCE, AND PROTEOLYTIC PROCESSING.
RX PubMed=11518718; DOI=10.1074/jbc.m107234200;
RA Saxena M.T., Schroeter E.H., Mumm J.S., Kopan R.;
RT "Murine notch homologs (N1-4) undergo presenilin-dependent proteolysis.";
RL J. Biol. Chem. 276:40268-40273(2001).
RN [20]
RP PROTEOLYTIC PROCESSING.
RX PubMed=11459941; DOI=10.1073/pnas.161269998;
RA Mizutani T., Taniguchi Y., Aoki T., Hashimoto N., Honjo T.;
RT "Conservation of the biochemical mechanisms of signal transduction among
RT mammalian Notch family members.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:9026-9031(2001).
RN [21]
RP INTERACTION WITH DTX1 AND DTX2.
RX PubMed=11226752; DOI=10.1016/s0736-5748(00)00071-x;
RA Kishi N., Tang Z., Maeda Y., Hirai A., Mo R., Ito M., Suzuki S., Nakao K.,
RA Kinoshita T., Kadesch T., Hui C.-C., Artavanis-Tsakonas S., Okano H.,
RA Matsuno K.;
RT "Murine homologs of deltex define a novel gene family involved in
RT vertebrate Notch signaling and neurogenesis.";
RL Int. J. Dev. Neurosci. 19:21-35(2001).
RN [22]
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 [23]
RP INTERACTION WITH MAML1.
RX PubMed=15019995; DOI=10.1016/j.gene.2003.12.007;
RA Wu L., Kobayashi K., Sun T., Gao P., Liu J., Nakamura M., Weisberg E.,
RA Mukhopadhyay N.K., Griffin J.D.;
RT "Cloning and functional characterization of the murine mastermind-like 1
RT (Maml1) gene.";
RL Gene 328:153-165(2004).
RN [24]
RP UBIQUITINATION AT LYS-1749, AND ENDOCYTOSIS.
RX PubMed=15240571; DOI=10.1083/jcb.200310098;
RA Gupta-Rossi N., Six E., LeBail O., Logeat F., Chastagner P., Olry A.,
RA Israel A., Brou C.;
RT "Monoubiquitination and endocytosis direct gamma-secretase cleavage of
RT activated Notch receptor.";
RL J. Cell Biol. 166:73-83(2004).
RN [25]
RP INTERACTION WITH DNER, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15965470; DOI=10.1038/nn1492;
RA Eiraku M., Tohgo A., Ono K., Kaneko M., Fujishima K., Hirano T.,
RA Kengaku M.;
RT "DNER acts as a neuron-specific Notch ligand during Bergmann glial
RT development.";
RL Nat. Neurosci. 8:873-880(2005).
RN [26]
RP INTERACTION WITH ZFP64.
RX PubMed=18430783; DOI=10.1242/jcs.023119;
RA Sakamoto K., Tamamura Y., Katsube K., Yamaguchi A.;
RT "Zfp64 participates in Notch signaling and regulates differentiation in
RT mesenchymal cells.";
RL J. Cell Sci. 121:1613-1623(2008).
RN [27]
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 [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1851, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [29]
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 [30]
RP GLYCOSYLATION AT SER-65; THR-73; THR-116; SER-146; THR-194; SER-341;
RP SER-378; SER-458; THR-466; SER-496; SER-534; SER-609; SER-647; SER-722;
RP SER-759; THR-767; SER-797; THR-805; SER-951; SER-1027; THR-1035; SER-1065;
RP SER-1189; THR-1197; SER-1273 AND THR-1362, AND MUTAGENESIS OF SER-65;
RP SER-146; SER-341; SER-378; SER-458; SER-496; SER-534; SER-609; SER-647;
RP SER-722; SER-759; SER-797; SER-951; SER-1027; SER-1065; SER-1189 AND
RP SER-1273.
RX PubMed=21757702; DOI=10.1074/jbc.m111.268243;
RA Rana N.A., Nita-Lazar A., Takeuchi H., Kakuda S., Luther K.B.,
RA Haltiwanger R.S.;
RT "O-glucose trisaccharide is present at high but variable stoichiometry at
RT multiple sites on mouse Notch1.";
RL J. Biol. Chem. 286:31623-31637(2011).
RN [31]
RP FUNCTION AS NEUROGENESIS REPRESSOR, AND INTERACTION WITH BCL6.
RX PubMed=23160044; DOI=10.1038/nn.3264;
RA Tiberi L., van den Ameele J., Dimidschstein J., Piccirilli J., Gall D.,
RA Herpoel A., Bilheu A., Bonnefont J., Iacovino M., Kyba M., Bouschet T.,
RA Vanderhaeghen P.;
RT "BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression
RT of selective Notch targets.";
RL Nat. Neurosci. 15:1627-1635(2012).
RN [32]
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 [33]
RP FUNCTION, AND INTERACTION WITH THBS4.
RX PubMed=23615612; DOI=10.1038/nature12069;
RA Benner E.J., Luciano D., Jo R., Abdi K., Paez-Gonzalez P., Sheng H.,
RA Warner D.S., Liu C., Eroglu C., Kuo C.T.;
RT "Protective astrogenesis from the SVZ niche after injury is controlled by
RT Notch modulator Thbs4.";
RL Nature 497:369-373(2013).
RN [34]
RP INTERACTION WITH PRAG1, AND INTERACTION WITH PRAG1 AND MAML1.
RX PubMed=25038227; DOI=10.1158/0008-5472.can-14-1547;
RA Weaver K.L., Alves-Guerra M.C., Jin K., Wang Z., Han X., Ranganathan P.,
RA Zhu X., DaSilva T., Liu W., Ratti F., Demarest R.M., Tzimas C., Rice M.,
RA Vasquez-Del Carpio R., Dahmane N., Robbins D.J., Capobianco A.J.;
RT "NACK is an integral component of the Notch transcriptional activation
RT complex and is critical for development and tumorigenesis.";
RL Cancer Res. 74:4741-4751(2014).
RN [35]
RP GLYCOSYLATION AT THR-73; THR-116; THR-194; THR-232; THR-311; THR-349;
RP SER-458; THR-466; THR-617; THR-692; SER-759; THR-767; SER-784; SER-797;
RP THR-805; THR-900; SER-921; THR-997; THR-1035; THR-1159; THR-1197; THR-1362;
RP THR-1379 AND THR-1402, MUTAGENESIS OF THR-232; THR-311; THR-349; THR-466;
RP THR-997; THR-1035; THR-1159; THR-1362 AND THR-1402, AND INTERACTION WITH
RP DLL1 AND JAG1.
RX PubMed=28089369; DOI=10.1016/j.devcel.2016.12.013;
RA Kakuda S., Haltiwanger R.S.;
RT "Deciphering the fringe-mediated notch code: identification of activating
RT and inhibiting sites allowing discrimination between ligands.";
RL Dev. Cell 40:193-201(2017).
RN [36]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MEGF10.
RX PubMed=28498977; DOI=10.1093/hmg/ddx189;
RA Saha M., Mitsuhashi S., Jones M.D., Manko K., Reddy H.M., Bruels C.,
RA Cho K.A., Pacak C.A., Draper I., Kang P.B.;
RT "Consequences of MEGF10 deficiency on myoblast function and Notch1
RT interactions.";
RL Hum. Mol. Genet. 26:2984-3000(2017).
RN [37]
RP GLYCOSYLATION AT SER-435, AND MUTAGENESIS OF THR-311 AND 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 [38]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1971-2104.
RX PubMed=15802643; DOI=10.1110/ps.041184105;
RA Lubman O.Y., Kopan R., Waksman G., Korolev S.;
RT "The crystal structure of a partial mouse Notch-1 ankyrin domain: repeats 4
RT through 7 preserve an ankyrin fold.";
RL Protein Sci. 14:1274-1281(2005).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 1899-2106 IN COMPLEX WITH HIF1AN;
RP IRON AND 2-OXOGLUTARATE, HYDROXYLATION AT ASN-1945 AND ASN-2012,
RP MUTAGENESIS OF ASN-1945 AND ASN-2012, AND IDENTIFICATION BY MASS
RP 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).
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:15965470, ECO:0000269|PubMed:18299578,
CC ECO:0000269|PubMed:23160044, ECO:0000269|PubMed:23615612}.
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. Notch 1
CC intracellular domain interacts with SNW1; the interaction involves
CC multimerized NOTCH1 NICD and is implicated in a formation of an
CC intermediate preactivation complex which associates with DNA-bound CBF-
CC 1/RBPJ. The activated membrane-bound form interacts with AAK1 which
CC promotes NOTCH1 stabilization. Forms a trimeric complex with FBXW7 and
CC SGK1. Interacts with HIF1AN. HIF1AN negatively regulates the function
CC of notch intracellular domain (NICD), accelerating myogenic
CC differentiation. Interacts (via NICD) with SNAI1 (via zinc fingers);
CC the interaction induces SNAI1 degradation via MDM2-mediated
CC ubiquitination and inhibits SNAI1-induced cell invasion. Interacts (via
CC NICD) with MDM2A. Interacts (via NICD) with BCL6; the interaction
CC decreases MAML1 recruitment by NOTCH1 NICD on target genes DNA and
CC inhibits NOTCH1 transcractivation activity. Interacts with THBS4.
CC Interacts (via the EGF-like repeat region) with CCN3 (via CTCK domain)
CC (PubMed:12050162). Interacts (via EGF-like domains) with DLL4 (via N-
CC terminal DSL and MNNL domains) (By similarity). Interacts with ZMIZ1.
CC Interacts (via NICD domain) with MEGF10 (via the cytoplasmic domain)
CC (PubMed:28498977). Interacts with DLL1 and JAG1 (PubMed:28089369).
CC Interacts (via NICD domain) with PRAG1 (PubMed:25038227). Forms a
CC complex with PRAG1, N1ICD and MAML1, in a MAML1-dependent manner
CC (PubMed:25038227). Interacts (via transmembrane region) with PSEN1; the
CC interaction is direct (By similarity). Interacts with ZFP64
CC (PubMed:18430783). {ECO:0000250|UniProtKB:P46531,
CC ECO:0000250|UniProtKB:Q07008, ECO:0000269|PubMed:11226752,
CC ECO:0000269|PubMed:12050162, ECO:0000269|PubMed:15019995,
CC ECO:0000269|PubMed:15965470, ECO:0000269|PubMed:17573339,
CC ECO:0000269|PubMed:18299578, ECO:0000269|PubMed:18430783,
CC ECO:0000269|PubMed:21464124, ECO:0000269|PubMed:23160044,
CC ECO:0000269|PubMed:23615612, ECO:0000269|PubMed:25038227,
CC ECO:0000269|PubMed:28089369, ECO:0000269|PubMed:28498977}.
CC -!- INTERACTION:
CC Q01705; P31266: Rbpj; NbExp=8; IntAct=EBI-1392707, EBI-1392666;
CC Q01705; Q3TKT4: Smarca4; NbExp=2; IntAct=EBI-1392707, EBI-1210244;
CC Q01705; Q6P9Z1: Smarcd3; NbExp=2; IntAct=EBI-1392707, EBI-7525857;
CC Q01705; P62991: Ubc; NbExp=3; IntAct=EBI-1392707, EBI-413074;
CC Q01705; Q06330: RBPJ; Xeno; NbExp=3; IntAct=EBI-1392707, EBI-632552;
CC Q01705; P28159: Su(H); Xeno; NbExp=3; IntAct=EBI-1392707, EBI-92180;
CC PRO_0000007679; Q77CA8: LRORF2; Xeno; NbExp=3; IntAct=EBI-11292892, EBI-11292862;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10882062,
CC ECO:0000269|PubMed:28498977}; Single-pass type I membrane protein.
CC -!- SUBCELLULAR LOCATION: [Notch 1 intracellular domain]: Nucleus
CC {ECO:0000269|PubMed:28498977}. Note=Following proteolytical processing
CC NICD is translocated to the nucleus. Nuclear location may require
CC MEGF10. {ECO:0000269|PubMed:28498977}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q01705-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q01705-2; Sequence=VSP_001402, VSP_001403, VSP_001404;
CC Name=3;
CC IsoId=Q01705-3; Sequence=VSP_043064;
CC Name=4;
CC IsoId=Q01705-4; Sequence=VSP_043065;
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain, lung and thymus.
CC Expressed at lower levels in the spleen, bone-marrow, spinal cord,
CC eyes, mammary gland, liver, intestine, skeletal muscle, kidney and
CC heart. In the hair follicle, highly expressed exclusively in the
CC epithelial compartment. {ECO:0000269|PubMed:15965470}.
CC -!- DEVELOPMENTAL STAGE: First detected in the mesoderm at 7.5 dpc By 8.5
CC dpc highly expressed in presomitic mesoderm, mesenchyme and endothelial
CC cells, while much lower levels are seen in the neuroepithelium. Between
CC 9.5-10.5 dpc expressed at high levels in the neuroepithelium. At 13.5
CC dpc expressed in the surface ectoderm, eye and developing whisker
CC follicles. Hair follicle matrix cells expression starts as different
CC cell types become distinguishable in the developing follicle.
CC Expression persists throughout the growth phase of the follicle and
CC maintains the same expression profile in the second hair cycle. The
CC cells in the follicle that undergo a phase of high level expression are
CC in transition from mitotic precursors to several discrete,
CC differentiating cell types. Specifically expressed in cerebellar
CC Bergmann glial cells during postnatal development.
CC {ECO:0000269|PubMed:1425352, ECO:0000269|PubMed:1426644,
CC ECO:0000269|PubMed:8486742}.
CC -!- DOMAIN: Interaction with PSEN1 causes partial unwinding of the
CC transmembrane helix, facilitating access to the scissile peptide bond.
CC {ECO:0000250|UniProtKB:P46531}.
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 (PubMed:10882062, PubMed:10882063). Cleavage
CC results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC).
CC Following ligand binding, it is cleaved by ADAM17 to yield a membrane-
CC associated intermediate fragment called notch extracellular truncation
CC (NEXT) (PubMed:10882062, PubMed:10882063). Following endocytosis, this
CC fragment is then cleaved by one of the catalytic subunits of gamma-
CC secretase (PSEN1 or PSEN2) to release a Notch-derived peptide
CC containing the intracellular domain (NICD) from the membrane
CC (PubMed:10882062, PubMed:11518718, PubMed:11459941).
CC {ECO:0000269|PubMed:10882062, ECO:0000269|PubMed:10882063,
CC ECO:0000269|PubMed:11459941, ECO:0000269|PubMed:11518718}.
CC -!- PTM: Phosphorylated.
CC -!- PTM: O-linked glycosylation by GALNT11 is involved in determination of
CC left/right symmetry: glycosylation promotes activation of NOTCH1,
CC possibly by promoting cleavage by ADAM17, modulating the balance
CC between motile and immotile (sensory) cilia at the left-right organiser
CC (LRO) (By similarity). O-glycosylated on the EGF-like domains
CC (PubMed:21757702). O-glucosylated at Ser-435 by KDELC1 and KDELC2
CC (PubMed:30127001). Contains both O-linked fucose and O-linked glucose
CC in the EGF-like domains 11, 12 and 13, which are interacting with the
CC residues on DLL4 (By similarity). O-glycosylation at Ser-1027 is only
CC partial (PubMed:21757702). MFNG-, RFNG- and LFNG-mediated modification
CC of O-fucose residues at specific EGF-like domains results in inhibition
CC of its activation by JAG1 and enhancement of its activation by DLL1 via
CC an increased binding to DLL1 (PubMed:28089369).
CC {ECO:0000250|UniProtKB:P46531, ECO:0000250|UniProtKB:Q07008,
CC ECO:0000269|PubMed:21757702, ECO:0000269|PubMed:28089369,
CC 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 1749 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:15240571). {ECO:0000269|PubMed:15240571,
CC ECO:0000269|PubMed:18628966, ECO:0000269|PubMed:23886940}.
CC -!- PTM: Hydroxylated at Asn-1945 and Asn-2012 by HIF1AN. Hydroxylation
CC reduces affinity for HI1AN and may thus indirectly modulate negative
CC regulation of NICD. {ECO:0000269|PubMed:17573339,
CC ECO:0000269|PubMed:18299578}.
CC -!- SIMILARITY: Belongs to the NOTCH family. {ECO:0000305}.
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DR EMBL; Z11886; CAA77941.1; -; mRNA.
DR EMBL; AF508809; AAM28905.1; -; mRNA.
DR EMBL; AB100603; BAC77038.1; -; Genomic_DNA.
DR EMBL; AB100603; BAC77039.1; -; Genomic_DNA.
DR EMBL; AB100603; BAC77040.1; -; Genomic_DNA.
DR EMBL; AL732541; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466542; EDL08321.1; -; Genomic_DNA.
DR EMBL; BC138441; AAI38442.1; -; mRNA.
DR EMBL; BC138442; AAI38443.1; -; mRNA.
DR EMBL; L02613; AAK14898.1; -; mRNA.
DR EMBL; X68278; CAA48339.1; -; mRNA.
DR EMBL; AK154528; BAE32653.1; -; mRNA.
DR EMBL; AK157475; BAE34095.1; -; mRNA.
DR EMBL; AJ238029; CAB40733.1; -; mRNA.
DR EMBL; X82562; CAA57909.1; -; mRNA.
DR CCDS; CCDS15806.1; -. [Q01705-1]
DR PIR; A46438; A46438.
DR PIR; B49175; B49175.
DR RefSeq; NP_032740.3; NM_008714.3. [Q01705-1]
DR PDB; 1YMP; X-ray; 2.20 A; A/B=1971-2105.
DR PDB; 2QC9; X-ray; 2.35 A; A/B=1899-2106.
DR PDB; 2RQZ; NMR; -; A=452-489.
DR PDB; 2RR0; NMR; -; A=452-489.
DR PDB; 2RR2; NMR; -; A=452-489.
DR PDB; 3P3N; X-ray; 2.40 A; B=1930-1949.
DR PDB; 3P3P; X-ray; 2.60 A; B=1999-2016.
DR PDB; 5KY0; X-ray; 1.53 A; B=452-491.
DR PDB; 5KY4; X-ray; 1.47 A; B=983-1022.
DR PDB; 5KY8; X-ray; 1.65 A; B=452-491.
DR PDB; 5KY9; X-ray; 1.83 A; B=452-491.
DR PDB; 7ABV; X-ray; 2.06 A; A=1446-1717.
DR PDBsum; 1YMP; -.
DR PDBsum; 2QC9; -.
DR PDBsum; 2RQZ; -.
DR PDBsum; 2RR0; -.
DR PDBsum; 2RR2; -.
DR PDBsum; 3P3N; -.
DR PDBsum; 3P3P; -.
DR PDBsum; 5KY0; -.
DR PDBsum; 5KY4; -.
DR PDBsum; 5KY8; -.
DR PDBsum; 5KY9; -.
DR PDBsum; 7ABV; -.
DR AlphaFoldDB; Q01705; -.
DR SMR; Q01705; -.
DR BioGRID; 201808; 26.
DR CORUM; Q01705; -.
DR DIP; DIP-214N; -.
DR IntAct; Q01705; 11.
DR MINT; Q01705; -.
DR STRING; 10090.ENSMUSP00000028288; -.
DR BindingDB; Q01705; -.
DR ChEMBL; CHEMBL4295799; -.
DR GlyGen; Q01705; 45 sites.
DR iPTMnet; Q01705; -.
DR PhosphoSitePlus; Q01705; -.
DR EPD; Q01705; -.
DR MaxQB; Q01705; -.
DR PaxDb; Q01705; -.
DR PeptideAtlas; Q01705; -.
DR PRIDE; Q01705; -.
DR ProteomicsDB; 252840; -. [Q01705-1]
DR ProteomicsDB; 252841; -. [Q01705-2]
DR ProteomicsDB; 252842; -. [Q01705-3]
DR ProteomicsDB; 252843; -. [Q01705-4]
DR ABCD; Q01705; 29 sequenced antibodies.
DR Antibodypedia; 8424; 1312 antibodies from 54 providers.
DR DNASU; 18128; -.
DR Ensembl; ENSMUST00000028288; ENSMUSP00000028288; ENSMUSG00000026923. [Q01705-1]
DR GeneID; 18128; -.
DR KEGG; mmu:18128; -.
DR UCSC; uc008ivl.2; mouse. [Q01705-1]
DR CTD; 4851; -.
DR MGI; MGI:97363; Notch1.
DR VEuPathDB; HostDB:ENSMUSG00000026923; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000157157; -.
DR HOGENOM; CLU_000576_2_0_1; -.
DR InParanoid; Q01705; -.
DR OMA; IAGYSCE; -.
DR OrthoDB; 7525at2759; -.
DR PhylomeDB; Q01705; -.
DR TreeFam; TF351641; -.
DR Reactome; R-MMU-1912420; Pre-NOTCH Processing in Golgi.
DR Reactome; R-MMU-2122947; NOTCH1 Intracellular Domain Regulates Transcription.
DR Reactome; R-MMU-2122948; Activated NOTCH1 Transmits Signal to the Nucleus.
DR Reactome; R-MMU-350054; Notch-HLH transcription pathway.
DR Reactome; R-MMU-8941856; RUNX3 regulates NOTCH signaling.
DR BioGRID-ORCS; 18128; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Notch1; mouse.
DR EvolutionaryTrace; Q01705; -.
DR PRO; PR:Q01705; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q01705; protein.
DR Bgee; ENSMUSG00000026923; Expressed in hair follicle and 342 other tissues.
DR ExpressionAtlas; Q01705; baseline and differential.
DR Genevisible; Q01705; MM.
DR GO; GO:0001669; C:acrosomal vesicle; ISO:MGI.
DR GO; GO:0005912; C:adherens junction; IDA:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0071944; C:cell periphery; IDA:MGI.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; IC:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0002193; C:MAML1-RBP-Jkappa- ICN1 complex; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:AgBase.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:MGI.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0004857; F:enzyme inhibitor activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005112; F:Notch binding; IPI:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:ARUK-UCL.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISO:MGI.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0003180; P:aortic valve morphogenesis; IMP:BHF-UCL.
DR GO; GO:0006915; P:apoptotic process; IDA:MGI.
DR GO; GO:1902263; P:apoptotic process involved in embryonic digit morphogenesis; IMP:MGI.
DR GO; GO:0060842; P:arterial endothelial cell differentiation; IMP:BHF-UCL.
DR GO; GO:0048708; P:astrocyte differentiation; ISO:MGI.
DR GO; GO:0003162; P:atrioventricular node development; IMP:BHF-UCL.
DR GO; GO:0003181; P:atrioventricular valve morphogenesis; IMP:BHF-UCL.
DR GO; GO:0009912; P:auditory receptor cell fate commitment; IMP:MGI.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0007409; P:axonogenesis; IDA:MGI.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IMP:MGI.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; IMP:MGI.
DR GO; GO:0003209; P:cardiac atrium morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003207; P:cardiac chamber formation; IMP:BHF-UCL.
DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; IMP:BHF-UCL.
DR GO; GO:0003214; P:cardiac left ventricle morphogenesis; IMP:BHF-UCL.
DR GO; GO:0060379; P:cardiac muscle cell myoblast differentiation; IMP:BHF-UCL.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; IMP:BHF-UCL.
DR GO; GO:0055008; P:cardiac muscle tissue morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003213; P:cardiac right atrium morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003219; P:cardiac right ventricle formation; IMP:MGI.
DR GO; GO:0060411; P:cardiac septum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0060948; P:cardiac vascular smooth muscle cell development; IMP:BHF-UCL.
DR GO; GO:0003208; P:cardiac ventricle morphogenesis; IMP:BHF-UCL.
DR GO; GO:0030154; P:cell differentiation; IMP:MGI.
DR GO; GO:0021515; P:cell differentiation in spinal cord; IEA:Ensembl.
DR GO; GO:0003273; P:cell migration involved in endocardial cushion formation; IMP:BHF-UCL.
DR GO; GO:0008283; P:cell population proliferation; IGI:MGI.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; ISO:MGI.
DR GO; GO:0071228; P:cellular response to tumor cell; ISO:MGI.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; ISS:UniProtKB.
DR GO; GO:0072044; P:collecting duct development; IEP:UniProtKB.
DR GO; GO:0007386; P:compartment pattern specification; IMP:MGI.
DR GO; GO:0060982; P:coronary artery morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003182; P:coronary sinus valve morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003169; P:coronary vein morphogenesis; IMP:BHF-UCL.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:MGI.
DR GO; GO:0072017; P:distal tubule development; IEP:UniProtKB.
DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IMP:MGI.
DR GO; GO:0030326; P:embryonic limb morphogenesis; IGI:MGI.
DR GO; GO:0060956; P:endocardial cell differentiation; IMP:BHF-UCL.
DR GO; GO:0003197; P:endocardial cushion development; IMP:MGI.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003157; P:endocardium development; IMP:BHF-UCL.
DR GO; GO:0003160; P:endocardium morphogenesis; IMP:BHF-UCL.
DR GO; GO:0007492; P:endoderm development; IMP:MGI.
DR GO; GO:0009957; P:epidermal cell fate specification; IMP:MGI.
DR GO; GO:0008544; P:epidermis development; IGI:MGI.
DR GO; GO:0072148; P:epithelial cell fate commitment; IMP:MGI.
DR GO; GO:0050673; P:epithelial cell proliferation; IMP:MGI.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; IMP:MGI.
DR GO; GO:0003198; P:epithelial to mesenchymal transition involved in endocardial cushion formation; IMP:BHF-UCL.
DR GO; GO:0030900; P:forebrain development; IMP:MGI.
DR GO; GO:0007440; P:foregut morphogenesis; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IDA:MGI.
DR GO; GO:0010001; P:glial cell differentiation; IMP:MGI.
DR GO; GO:0072144; P:glomerular mesangial cell development; IEP:UniProtKB.
DR GO; GO:0003241; P:growth involved in heart morphogenesis; IMP:BHF-UCL.
DR GO; GO:0031069; P:hair follicle morphogenesis; IMP:MGI.
DR GO; GO:0007507; P:heart development; ISO:MGI.
DR GO; GO:0001947; P:heart looping; IGI:BHF-UCL.
DR GO; GO:0061384; P:heart trabecula morphogenesis; IMP:BHF-UCL.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IGI:BHF-UCL.
DR GO; GO:0006959; P:humoral immune response; IGI:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; IGI:MGI.
DR GO; GO:0002085; P:inhibition of neuroepithelial cell differentiation; IMP:MGI.
DR GO; GO:0097400; P:interleukin-17-mediated signaling pathway; IDA:MGI.
DR GO; GO:0030216; P:keratinocyte differentiation; IMP:MGI.
DR GO; GO:0070986; P:left/right axis specification; IGI:BHF-UCL.
DR GO; GO:0001889; P:liver development; IMP:MGI.
DR GO; GO:0030324; P:lung development; IMP:MGI.
DR GO; GO:0014031; P:mesenchymal cell development; IMP:BHF-UCL.
DR GO; GO:0003192; P:mitral valve formation; ISO:MGI.
DR GO; GO:2000811; P:negative regulation of anoikis; ISO:MGI.
DR GO; GO:0070168; P:negative regulation of biomineral tissue development; IDA:BHF-UCL.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IMP:BHF-UCL.
DR GO; GO:0045955; P:negative regulation of calcium ion-dependent exocytosis; IMP:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:MGI.
DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; IMP:BHF-UCL.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IDA:UniProtKB.
DR GO; GO:0060354; P:negative regulation of cell adhesion molecule production; ISO:MGI.
DR GO; GO:0060548; P:negative regulation of cell death; IMP:MGI.
DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0003252; P:negative regulation of cell proliferation involved in heart valve morphogenesis; IDA:BHF-UCL.
DR GO; GO:2000048; P:negative regulation of cell-cell adhesion mediated by cadherin; ISO:MGI.
DR GO; GO:0010812; P:negative regulation of cell-substrate adhesion; ISO:MGI.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:2001027; P:negative regulation of endothelial cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:0003332; P:negative regulation of extracellular matrix constituent secretion; IMP:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0060253; P:negative regulation of glial cell proliferation; IDA:UniProtKB.
DR GO; GO:0045608; P:negative regulation of inner ear auditory receptor cell differentiation; IMP:MGI.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; ISO:MGI.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; IDA:UniProtKB.
DR GO; GO:0050768; P:negative regulation of neurogenesis; IDA:UniProtKB.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IMP:MGI.
DR GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; IDA:UniProtKB.
DR GO; GO:0030279; P:negative regulation of ossification; IMP:BHF-UCL.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IMP:BHF-UCL.
DR GO; GO:0046533; P:negative regulation of photoreceptor cell differentiation; IMP:MGI.
DR GO; GO:2000974; P:negative regulation of pro-B cell differentiation; IMP:UniProtKB.
DR GO; GO:2000737; P:negative regulation of stem cell differentiation; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0021915; P:neural tube development; IMP:MGI.
DR GO; GO:0061101; P:neuroendocrine cell differentiation; IMP:MGI.
DR GO; GO:0030182; P:neuron differentiation; IMP:MGI.
DR GO; GO:0048663; P:neuron fate commitment; IGI:MGI.
DR GO; GO:0097150; P:neuronal stem cell population maintenance; IEA:Ensembl.
DR GO; GO:0061314; P:Notch signaling involved in heart development; IMP:BHF-UCL.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:MGI.
DR GO; GO:0003270; P:Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation; IMP:MGI.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IMP:MGI.
DR GO; GO:0002051; P:osteoblast fate commitment; NAS:BHF-UCL.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISO:MGI.
DR GO; GO:0003344; P:pericardium morphogenesis; IMP:BHF-UCL.
DR GO; GO:1903849; P:positive regulation of aorta morphogenesis; IMP:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:MGI.
DR GO; GO:1902339; P:positive regulation of apoptotic process involved in morphogenesis; IDA:BHF-UCL.
DR GO; GO:0048711; P:positive regulation of astrocyte differentiation; IDA:UniProtKB.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IDA:UniProtKB.
DR GO; GO:0062043; P:positive regulation of cardiac epithelial to mesenchymal transition; ISO:MGI.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IMP:BHF-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0045603; P:positive regulation of endothelial cell differentiation; ISO:MGI.
DR GO; GO:1901189; P:positive regulation of ephrin receptor signaling pathway; IC:BHF-UCL.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IGI:MGI.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IMP:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IGI:BHF-UCL.
DR GO; GO:0045687; P:positive regulation of glial cell differentiation; ISO:MGI.
DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; IDA:MGI.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; ISO:MGI.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IDA:MGI.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; ISO:MGI.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IDA: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; IDA:UniProtKB.
DR GO; GO:0007221; P:positive regulation of transcription of Notch receptor target; IGI:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0045070; P:positive regulation of viral genome replication; IMP:AgBase.
DR GO; GO:0050434; P:positive regulation of viral transcription; IMP:AgBase.
DR GO; GO:0060740; P:prostate gland epithelium morphogenesis; IMP:MGI.
DR GO; GO:0030163; P:protein catabolic process; IDA:MGI.
DR GO; GO:0006606; P:protein import into nucleus; IDA:MGI.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003264; P:regulation of cardioblast proliferation; ISO:MGI.
DR GO; GO:0061344; P:regulation of cell adhesion involved in heart morphogenesis; IC:BHF-UCL.
DR GO; GO:0030334; P:regulation of cell migration; IMP:BHF-UCL.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:0060768; P:regulation of epithelial cell proliferation involved in prostate gland development; IMP:MGI.
DR GO; GO:1901201; P:regulation of extracellular matrix assembly; IMP:BHF-UCL.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0045607; P:regulation of inner ear auditory receptor cell differentiation; IMP:MGI.
DR GO; GO:0050767; P:regulation of neurogenesis; IMP:MGI.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; IGI:MGI.
DR GO; GO:0014807; P:regulation of somitogenesis; IMP:MGI.
DR GO; GO:0072091; P:regulation of stem cell proliferation; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
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; IDA:BHF-UCL.
DR GO; GO:0042670; P:retinal cone cell differentiation; IMP:MGI.
DR GO; GO:0060528; P:secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development; IMP:MGI.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IMP:MGI.
DR GO; GO:0048103; P:somatic stem cell division; IDA:MGI.
DR GO; GO:0007283; P:spermatogenesis; ISO:MGI.
DR GO; GO:0002040; P:sprouting angiogenesis; IMP:MGI.
DR GO; GO:0072538; P:T-helper 17 type immune response; IDA:MGI.
DR GO; GO:0042246; P:tissue regeneration; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0035148; P:tube formation; ISS:UniProtKB.
DR GO; GO:0060979; P:vasculogenesis involved in coronary vascular morphogenesis; IMP:BHF-UCL.
DR GO; GO:0048845; P:venous blood vessel morphogenesis; IMP:MGI.
DR GO; GO:0060843; P:venous endothelial cell differentiation; IMP:BHF-UCL.
DR GO; GO:0060412; P:ventricular septum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; IMP:BHF-UCL.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR013032; EGF-like_CS.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR008297; Notch.
DR InterPro; IPR035993; Notch-like_dom_sf.
DR InterPro; 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; 21.
DR Pfam; PF07645; EGF_CA; 5.
DR Pfam; PF12661; hEGF; 3.
DR Pfam; PF06816; NOD; 1.
DR Pfam; PF07684; NODP; 1.
DR Pfam; PF00066; Notch; 3.
DR PIRSF; PIRSF002279; Notch; 1.
DR PRINTS; PR01452; LNOTCHREPEAT.
DR PRINTS; 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; 21.
DR PROSITE; PS50258; LNR; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Angiogenesis; ANK repeat;
KW Calcium; Cell membrane; Developmental protein; Differentiation;
KW Direct protein sequencing; 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..2531
FT /note="Neurogenic locus notch homolog protein 1"
FT /id="PRO_0000007677"
FT CHAIN 1711..2531
FT /note="Notch 1 extracellular truncation"
FT /evidence="ECO:0000305|PubMed:10882062,
FT ECO:0000305|PubMed:10882063"
FT /id="PRO_0000007678"
FT CHAIN 1744..2531
FT /note="Notch 1 intracellular domain"
FT /evidence="ECO:0000305|PubMed:10882062,
FT ECO:0000305|PubMed:11459941, ECO:0000305|PubMed:11518718"
FT /id="PRO_0000007679"
FT TOPO_DOM 19..1725
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1726..1746
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P46531"
FT TOPO_DOM 1747..2531
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
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; calcium-binding"
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; calcium-binding"
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; calcium-binding"
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; calcium-binding"
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 REPEAT 1490..1531
FT /note="LNR 2"
FT REPEAT 1532..1571
FT /note="LNR 3"
FT REPEAT 1917..1946
FT /note="ANK 1"
FT REPEAT 1950..1980
FT /note="ANK 2"
FT REPEAT 1984..2013
FT /note="ANK 3"
FT REPEAT 2017..2046
FT /note="ANK 4"
FT REPEAT 2050..2079
FT /note="ANK 5"
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 1718..1750
FT /note="Interaction with PSEN1"
FT /evidence="ECO:0000250|UniProtKB:P46531"
FT REGION 1770..1798
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1937..1945
FT /note="HIF1AN-binding"
FT REGION 2004..2012
FT /note="HIF1AN-binding"
FT REGION 2140..2185
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2382..2428
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2440..2531
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2160..2177
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2382..2404
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2440..2482
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2490..2524
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 /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT BINDING 1460
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT BINDING 1475
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT BINDING 1478
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525"
FT SITE 469
FT /note="Interaction with DLL4"
FT /evidence="ECO:0000250|UniProtKB:Q07008"
FT SITE 1654..1655
FT /note="Cleavage; by furin-like protease"
FT /evidence="ECO:0000269|PubMed:9653148"
FT SITE 1710..1711
FT /note="Cleavage; by ADAM17"
FT /evidence="ECO:0000269|PubMed:10882062,
FT ECO:0000269|PubMed:10882063"
FT MOD_RES 1851
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1945
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN; partial"
FT /evidence="ECO:0000269|PubMed:17573339,
FT ECO:0000269|PubMed:18299578"
FT MOD_RES 2012
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN; partial"
FT /evidence="ECO:0000269|PubMed:17573339,
FT ECO:0000269|PubMed:18299578"
FT CARBOHYD 65
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:21757702"
FT CARBOHYD 73
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000269|PubMed:21757702,
FT ECO:0000269|PubMed:28089369"
FT CARBOHYD 116
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000269|PubMed:21757702,
FT ECO:0000269|PubMed:28089369"
FT CARBOHYD 146
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:21757702"
FT CARBOHYD 194
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000269|PubMed:21757702,
FT ECO:0000269|PubMed:28089369"
FT CARBOHYD 232
FT /note="O-linked (Fuc...) threonine; alternate"
FT /evidence="ECO:0000269|PubMed:28089369"
FT CARBOHYD 232
FT /note="O-linked (GalNAc...) threonine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P46531"
FT CARBOHYD 311
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000269|PubMed:28089369"
FT CARBOHYD 341
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:21757702"
FT CARBOHYD 349
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000269|PubMed:28089369"
FT CARBOHYD 378
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:21757702"
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:0000269|PubMed:21757702,
FT ECO:0000269|PubMed:28089369"
FT CARBOHYD 466
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000269|PubMed:21757702,
FT ECO:0000269|PubMed:28089369"
FT CARBOHYD 496
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:21757702"
FT CARBOHYD 534
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:21757702"
FT CARBOHYD 609
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:21757702"
FT CARBOHYD 617
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000269|PubMed:28089369"
FT CARBOHYD 647
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:21757702"
FT CARBOHYD 692
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000269|PubMed:28089369"
FT CARBOHYD 722
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:21757702"
FT CARBOHYD 759
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:21757702,
FT ECO:0000269|PubMed:28089369"
FT CARBOHYD 767
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000269|PubMed:21757702,
FT ECO:0000269|PubMed:28089369"
FT CARBOHYD 784
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000269|PubMed:28089369"
FT CARBOHYD 797
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:21757702,
FT ECO:0000269|PubMed:28089369"
FT CARBOHYD 805
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000269|PubMed:21757702,
FT ECO:0000269|PubMed:28089369"
FT CARBOHYD 888
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 900
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000269|PubMed:28089369"
FT CARBOHYD 921
FT /note="O-linked (Fuc) serine"
FT /evidence="ECO:0000269|PubMed:28089369"
FT CARBOHYD 951
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:21757702"
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:0000269|PubMed:28089369"
FT CARBOHYD 1027
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:21757702"
FT CARBOHYD 1035
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000269|PubMed:21757702,
FT ECO:0000269|PubMed:28089369"
FT CARBOHYD 1065
FT /note="O-linked (Glc...) serine"
FT /evidence="ECO:0000269|PubMed:21757702"
FT CARBOHYD 1159
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000269|PubMed:28089369"
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:0000269|PubMed:21757702"
FT CARBOHYD 1197
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000269|PubMed:21757702,
FT ECO:0000269|PubMed:28089369"
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:0000269|PubMed:21757702"
FT CARBOHYD 1362
FT /note="O-linked (Fuc...) threonine"
FT /evidence="ECO:0000269|PubMed:21757702,
FT ECO:0000269|PubMed:28089369"
FT CARBOHYD 1379
FT /note="O-linked (GlcNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:28089369"
FT CARBOHYD 1402
FT /note="O-linked (Fuc...) threonine; alternate"
FT /evidence="ECO:0000269|PubMed:28089369"
FT CARBOHYD 1402
FT /note="O-linked (GalNAc...) threonine; alternate"
FT /evidence="ECO:0000269|PubMed:28089369"
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 DISULFID 24..37
FT /evidence="ECO:0000250"
FT DISULFID 31..46
FT /evidence="ECO:0000250"
FT DISULFID 63..74
FT /evidence="ECO:0000250"
FT DISULFID 68..87
FT /evidence="ECO:0000250"
FT DISULFID 89..98
FT /evidence="ECO:0000250"
FT DISULFID 106..117
FT /evidence="ECO:0000250"
FT DISULFID 111..127
FT /evidence="ECO:0000250"
FT DISULFID 129..138
FT /evidence="ECO:0000250"
FT DISULFID 144..155
FT /evidence="ECO:0000250"
FT DISULFID 149..164
FT /evidence="ECO:0000250"
FT DISULFID 166..175
FT /evidence="ECO:0000250"
FT DISULFID 182..195
FT /evidence="ECO:0000250"
FT DISULFID 189..204
FT /evidence="ECO:0000250"
FT DISULFID 206..215
FT /evidence="ECO:0000250"
FT DISULFID 222..233
FT /evidence="ECO:0000250"
FT DISULFID 227..243
FT /evidence="ECO:0000250"
FT DISULFID 245..254
FT /evidence="ECO:0000250"
FT DISULFID 261..272
FT /evidence="ECO:0000250"
FT DISULFID 266..281
FT /evidence="ECO:0000250"
FT DISULFID 283..292
FT /evidence="ECO:0000250"
FT DISULFID 299..312
FT /evidence="ECO:0000250"
FT DISULFID 306..321
FT /evidence="ECO:0000250"
FT DISULFID 323..332
FT /evidence="ECO:0000250"
FT DISULFID 339..350
FT /evidence="ECO:0000250"
FT DISULFID 344..359
FT /evidence="ECO:0000250"
FT DISULFID 361..370
FT /evidence="ECO:0000250"
FT DISULFID 376..387
FT /evidence="ECO:0000250"
FT DISULFID 381..398
FT /evidence="ECO:0000250"
FT DISULFID 400..409
FT /evidence="ECO:0000250"
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:0000250"
FT DISULFID 537..552
FT /evidence="ECO:0000250"
FT DISULFID 554..563
FT /evidence="ECO:0000250"
FT DISULFID 570..580
FT /evidence="ECO:0000250"
FT DISULFID 575..589
FT /evidence="ECO:0000250"
FT DISULFID 591..600
FT /evidence="ECO:0000250"
FT DISULFID 607..618
FT /evidence="ECO:0000250"
FT DISULFID 612..627
FT /evidence="ECO:0000250"
FT DISULFID 629..638
FT /evidence="ECO:0000250"
FT DISULFID 645..655
FT /evidence="ECO:0000250"
FT DISULFID 650..664
FT /evidence="ECO:0000250"
FT DISULFID 666..675
FT /evidence="ECO:0000250"
FT DISULFID 682..693
FT /evidence="ECO:0000250"
FT DISULFID 687..702
FT /evidence="ECO:0000250"
FT DISULFID 704..713
FT /evidence="ECO:0000250"
FT DISULFID 720..730
FT /evidence="ECO:0000250"
FT DISULFID 725..739
FT /evidence="ECO:0000250"
FT DISULFID 741..750
FT /evidence="ECO:0000250"
FT DISULFID 757..768
FT /evidence="ECO:0000250"
FT DISULFID 762..777
FT /evidence="ECO:0000250"
FT DISULFID 779..788
FT /evidence="ECO:0000250"
FT DISULFID 795..806
FT /evidence="ECO:0000250"
FT DISULFID 800..815
FT /evidence="ECO:0000250"
FT DISULFID 817..826
FT /evidence="ECO:0000250"
FT DISULFID 833..844
FT /evidence="ECO:0000250"
FT DISULFID 838..855
FT /evidence="ECO:0000250"
FT DISULFID 857..866
FT /evidence="ECO:0000250"
FT DISULFID 873..884
FT /evidence="ECO:0000250"
FT DISULFID 878..893
FT /evidence="ECO:0000250"
FT DISULFID 895..904
FT /evidence="ECO:0000250"
FT DISULFID 911..922
FT /evidence="ECO:0000250"
FT DISULFID 916..931
FT /evidence="ECO:0000250"
FT DISULFID 933..942
FT /evidence="ECO:0000250"
FT DISULFID 949..960
FT /evidence="ECO:0000250"
FT DISULFID 954..969
FT /evidence="ECO:0000250"
FT DISULFID 971..980
FT /evidence="ECO:0000250"
FT DISULFID 987..998
FT /evidence="ECO:0000250"
FT DISULFID 992..1007
FT /evidence="ECO:0000250"
FT DISULFID 1009..1018
FT /evidence="ECO:0000250"
FT DISULFID 1025..1036
FT /evidence="ECO:0000250"
FT DISULFID 1030..1045
FT /evidence="ECO:0000250"
FT DISULFID 1047..1056
FT /evidence="ECO:0000250"
FT DISULFID 1063..1074
FT /evidence="ECO:0000250"
FT DISULFID 1068..1083
FT /evidence="ECO:0000250"
FT DISULFID 1085..1094
FT /evidence="ECO:0000250"
FT DISULFID 1101..1122
FT /evidence="ECO:0000305"
FT DISULFID 1116..1131
FT /evidence="ECO:0000250"
FT DISULFID 1133..1142
FT /evidence="ECO:0000250"
FT DISULFID 1149..1160
FT /evidence="ECO:0000250"
FT DISULFID 1154..1169
FT /evidence="ECO:0000250"
FT DISULFID 1171..1180
FT /evidence="ECO:0000250"
FT DISULFID 1187..1198
FT /evidence="ECO:0000250"
FT DISULFID 1192..1207
FT /evidence="ECO:0000250"
FT DISULFID 1209..1218
FT /evidence="ECO:0000250"
FT DISULFID 1225..1244
FT /evidence="ECO:0000250"
FT DISULFID 1238..1253
FT /evidence="ECO:0000250"
FT DISULFID 1255..1264
FT /evidence="ECO:0000250"
FT DISULFID 1271..1284
FT /evidence="ECO:0000250"
FT DISULFID 1276..1293
FT /evidence="ECO:0000250"
FT DISULFID 1295..1304
FT /evidence="ECO:0000250"
FT DISULFID 1311..1322
FT /evidence="ECO:0000250"
FT DISULFID 1316..1334
FT /evidence="ECO:0000250"
FT DISULFID 1336..1345
FT /evidence="ECO:0000250"
FT DISULFID 1352..1363
FT /evidence="ECO:0000250"
FT DISULFID 1357..1372
FT /evidence="ECO:0000250"
FT DISULFID 1374..1383
FT /evidence="ECO:0000250"
FT DISULFID 1391..1403
FT /evidence="ECO:0000250"
FT DISULFID 1397..1414
FT /evidence="ECO:0000250"
FT DISULFID 1416..1425
FT /evidence="ECO:0000250"
FT DISULFID 1449..1472
FT /evidence="ECO:0000250"
FT DISULFID 1454..1467
FT /evidence="ECO:0000250"
FT DISULFID 1463..1479
FT /evidence="ECO:0000250"
FT DISULFID 1490..1514
FT /evidence="ECO:0000250"
FT DISULFID 1496..1509
FT /evidence="ECO:0000250"
FT DISULFID 1505..1521
FT /evidence="ECO:0000250"
FT DISULFID 1536..1549
FT /evidence="ECO:0000250"
FT DISULFID 1545..1561
FT /evidence="ECO:0000250"
FT CROSSLNK 1749
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:15240571"
FT VAR_SEQ 1..47
FT /note="MPRLLTPLLCLTLLPALAARGLRCSQPSGTCLNGGRCEVANGTEACV -> M
FT QTPLLSLAGATTELCFLPASVLASSLPGPSL (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_043065"
FT VAR_SEQ 1..21
FT /note="MPRLLTPLLCLTLLPALAARG -> MKNSNTLTNKWRMEQC (in
FT isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_043064"
FT VAR_SEQ 857..914
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1426644"
FT /id="VSP_001402"
FT VAR_SEQ 1329..1355
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1426644"
FT /id="VSP_001403"
FT VAR_SEQ 1636..1854
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1426644"
FT /id="VSP_001404"
FT MUTAGEN 65
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 146
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 232
FT /note="T->V: No significant effect on its binding and
FT activation by DLL1 or JAG1. No significant effect on RFNG-,
FT LFNG- and MFNG-mediated enhancement of its activation by
FT DLL1. Decrease in LFNG- and MFNG-mediated inhibition of its
FT activation by JAG1. Significant decrease in LFNG- and MFNG-
FT mediated inhibition of its activation by JAG1; when
FT associated with V-1402."
FT /evidence="ECO:0000269|PubMed:28089369"
FT MUTAGEN 311
FT /note="T->V: Significant loss of binding and activation by
FT DLL1 or JAG1. Decrease in RFNG-, LFNG- and MFNG-mediated
FT enhancement of its activation by DLL1. Decrease in LFNG-
FT mediated inhibition of its activation by JAG1. Significant
FT loss of binding and activation by DLL1 or JAG1 and complete
FT loss of RFNG- and LFNG-mediated enhancement of its
FT activation by DLL1; when associated with V-466. Decreased
FT localization to the plasma membrane; when associated with
FT A-435."
FT /evidence="ECO:0000269|PubMed:28089369,
FT ECO:0000269|PubMed:30127001"
FT MUTAGEN 341
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 349
FT /note="T->V: Reduced binding and activation by JAG1 but not
FT DLL1. Decrease in MFNG-mediated enhancement of its
FT activation by DLL1."
FT /evidence="ECO:0000269|PubMed:28089369"
FT MUTAGEN 378
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 435
FT /note="S->A: No effect on localization to the plasma
FT membrane. No effect on binding and activation by DLL1.
FT Decreased localization to the plasma membrane; when
FT associated with V-311."
FT /evidence="ECO:0000269|PubMed:30127001"
FT MUTAGEN 458
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 466
FT /note="T->V: Reduced binding and activation by DLL1 but not
FT JAG1. Decrease in RFNG- and LFNG-mediated enhancement of
FT its activation by DLL1. Loss of RFNG-mediated enhancement
FT of its activation by JAG1. Significant loss of binding and
FT activation by DLL1 or JAG1 and complete loss of RFNG- and
FT LFNG-mediated enhancement of its activation by DLL1; when
FT associated with V-311."
FT /evidence="ECO:0000269|PubMed:28089369"
FT MUTAGEN 496
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 534
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 609
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 647
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 722
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 759
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 797
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 951
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 997
FT /note="T->V: Reduced binding and activation by DLL1 but not
FT JAG1. No effect on RFNG-, LFNG- and MFNG-mediated
FT enhancement of its activation by DLL1. No effect on
FT LFNG- and MFNG-mediated inhibition of its activation by
FT JAG1."
FT /evidence="ECO:0000269|PubMed:28089369"
FT MUTAGEN 1027
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 1035
FT /note="T->V: Reduced binding and activation by JAG1 but not
FT DLL1. No effect on RFNG-, LFNG- and MFNG-mediated
FT enhancement of its activation by DLL1. No effect on
FT LFNG- and MFNG-mediated inhibition of its activation by
FT JAG1."
FT /evidence="ECO:0000269|PubMed:28089369"
FT MUTAGEN 1065
FT /note="S->A: Reduced activity."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 1159
FT /note="T->V: No significant effect on its binding and
FT activation by DLL1 or JAG1. No effect on RFNG-, LFNG- and
FT MFNG-mediated enhancement of its activation by DLL1. No
FT effect on LFNG- and MFNG-mediated inhibition of its
FT activation by JAG1."
FT /evidence="ECO:0000269|PubMed:28089369"
FT MUTAGEN 1189
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 1273
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:21757702"
FT MUTAGEN 1362
FT /note="T->V: No significant effect on its binding and
FT activation by DLL1 or JAG1. No effect on RFNG-, LFNG- and
FT MFNG-mediated enhancement of its activation by DLL1. No
FT effect on LFNG- and MFNG-mediated inhibition of its
FT activation by JAG1."
FT /evidence="ECO:0000269|PubMed:28089369"
FT MUTAGEN 1402
FT /note="T->V: No significant effect on its binding and
FT activation by DLL1 or JAG1. No effect on RFNG-, LFNG- and
FT MFNG-mediated enhancement of its activation by DLL1.
FT Decrease in LFNG- and MFNG-mediated inhibition of its
FT activation by JAG1. Significant decrease in LFNG- and MFNG-
FT mediated inhibition of its activation by JAG1; when
FT associated with V-232."
FT /evidence="ECO:0000269|PubMed:28089369"
FT MUTAGEN 1651..1654
FT /note="RQRR->AAAA: Processing by furin-like convertase
FT abolished."
FT /evidence="ECO:0000269|PubMed:9653148"
FT MUTAGEN 1675
FT /note="C->S: Produces an activated, ligand-independent
FT molecule; when associated with S-1682."
FT /evidence="ECO:0000269|PubMed:10882062"
FT MUTAGEN 1682
FT /note="C->S: Produces an activated, ligand-independent
FT molecule; when associated with S-1675."
FT /evidence="ECO:0000269|PubMed:10882062"
FT MUTAGEN 1744
FT /note="V->L: NICD processing severely reduced."
FT MUTAGEN 1945
FT /note="N->A: Reduced ability to promote HIF1AN-dependent 2-
FT oxoglutarate decarboxylation and greatly reduced
FT transactivation capacity. Abolished ability to promote
FT HIF1AN-dependent 2-oxoglutarate decarboxylation; when
FT associated with G-2012. Almost abolished transactivation
FT capacity; when associated with A-2012."
FT /evidence="ECO:0000269|PubMed:17573339,
FT ECO:0000269|PubMed:18299578"
FT MUTAGEN 2012
FT /note="N->A: Slightly reduced ability to promote HIF1AN-
FT dependent 2-oxoglutarate decarboxylation. Abolished ability
FT to promote HIF1AN-dependent 2-oxoglutarate decarboxylation
FT and almost abolished transactivation capacity; when
FT associated with A-1945."
FT /evidence="ECO:0000269|PubMed:17573339,
FT ECO:0000269|PubMed:18299578"
FT MUTAGEN 2012
FT /note="N->G: Reduced ability to promote HIF1AN-dependent 2-
FT oxoglutarate decarboxylation. Abolished ability to promote
FT HIF1AN-dependent 2-oxoglutarate decarboxylation; when
FT associated with A-1945."
FT /evidence="ECO:0000269|PubMed:17573339,
FT ECO:0000269|PubMed:18299578"
FT CONFLICT 17
FT /note="L -> R (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 41
FT /note="N -> S (in Ref. 1; CAA77941 and 3; AAM28905)"
FT /evidence="ECO:0000305"
FT CONFLICT 48
FT /note="C -> A (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 51
FT /note="A -> S (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 60
FT /note="S -> P (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 67
FT /note="P -> R (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 75
FT /note="H -> Y (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 82
FT /note="T -> I (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 104..105
FT /note="NA -> KP (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 130
FT /note="P -> S (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="T -> H (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="R -> C (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 231
FT /note="G -> A (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 287
FT /note="W -> V (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="G -> A (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 373..374
FT /note="ND -> KH (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 396
FT /note="A -> R (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 417
FT /note="A -> D (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 422
FT /note="P -> R (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 448
FT /note="R -> G (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 510
FT /note="N -> H (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 835
FT /note="T -> I (in Ref. 8; AAK14898)"
FT /evidence="ECO:0000305"
FT CONFLICT 933..934
FT /note="CL -> SV (in Ref. 8; AAK14898)"
FT /evidence="ECO:0000305"
FT CONFLICT 1050
FT /note="G -> R (in Ref. 8; AAK14898)"
FT /evidence="ECO:0000305"
FT CONFLICT 1104..1106
FT /note="Missing (in Ref. 8; AAK14898)"
FT /evidence="ECO:0000305"
FT CONFLICT 1155
FT /note="Q -> L (in Ref. 8; AAK14898)"
FT /evidence="ECO:0000305"
FT CONFLICT 1209
FT /note="C -> W (in Ref. 8; AAK14898)"
FT /evidence="ECO:0000305"
FT CONFLICT 1438
FT /note="R -> P (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 1545
FT /note="C -> S (in Ref. 8; AAK14898)"
FT /evidence="ECO:0000305"
FT CONFLICT 1556
FT /note="W -> R (in Ref. 8; AAK14898)"
FT /evidence="ECO:0000305"
FT CONFLICT 1572
FT /note="G -> R (in Ref. 8; AAK14898)"
FT /evidence="ECO:0000305"
FT CONFLICT 1576
FT /note="L -> V (in Ref. 8; AAK14898)"
FT /evidence="ECO:0000305"
FT CONFLICT 1609
FT /note="D -> H (in Ref. 8; AAK14898)"
FT /evidence="ECO:0000305"
FT CONFLICT 1661
FT /note="I -> T (in Ref. 10; BAE32653)"
FT /evidence="ECO:0000305"
FT CONFLICT 1864
FT /note="V -> D (in Ref. 8; AAK14898)"
FT /evidence="ECO:0000305"
FT CONFLICT 1890
FT /note="S -> R (in Ref. 8; AAK14898)"
FT /evidence="ECO:0000305"
FT CONFLICT 1896..1898
FT /note="APA -> RPG (in Ref. 8; AAK14898)"
FT /evidence="ECO:0000305"
FT CONFLICT 1933..1934
FT /note="AA -> RR (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 1938
FT /note="Missing (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 1997
FT /note="V -> L (in Ref. 3; AAM28905)"
FT /evidence="ECO:0000305"
FT CONFLICT 2046..2047
FT /note="MQ -> IE (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 2054
FT /note="P -> S (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 2058..2062
FT /note="AAREG -> SIRRE (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 2075
FT /note="A -> G (in Ref. 16; CAA57909)"
FT /evidence="ECO:0000305"
FT CONFLICT 2086
FT /note="L -> M (in Ref. 10; BAE34095)"
FT /evidence="ECO:0000305"
FT CONFLICT 2136
FT /note="L -> P (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 2172
FT /note="K -> S (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 2179
FT /note="C -> W (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 2185
FT /note="S -> SS (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 2206
FT /note="P -> H (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 2258
FT /note="P -> H (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 2273
FT /note="S -> C (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 2347
FT /note="N -> S (in Ref. 10; BAE34095)"
FT /evidence="ECO:0000305"
FT CONFLICT 2380
FT /note="Q -> P (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT CONFLICT 2483..2484
FT /note="HP -> PT (in Ref. 1; CAA77941)"
FT /evidence="ECO:0000305"
FT HELIX 456..458
FT /evidence="ECO:0007829|PDB:5KY0"
FT STRAND 462..464
FT /evidence="ECO:0007829|PDB:2RQZ"
FT STRAND 466..469
FT /evidence="ECO:0007829|PDB:5KY0"
FT STRAND 470..472
FT /evidence="ECO:0007829|PDB:2RR0"
FT STRAND 474..477
FT /evidence="ECO:0007829|PDB:5KY0"
FT STRAND 482..484
FT /evidence="ECO:0007829|PDB:5KY0"
FT STRAND 997..1000
FT /evidence="ECO:0007829|PDB:5KY4"
FT STRAND 1005..1008
FT /evidence="ECO:0007829|PDB:5KY4"
FT STRAND 1013..1015
FT /evidence="ECO:0007829|PDB:5KY4"
FT HELIX 1453..1457
FT /evidence="ECO:0007829|PDB:7ABV"
FT STRAND 1460..1462
FT /evidence="ECO:0007829|PDB:7ABV"
FT HELIX 1465..1467
FT /evidence="ECO:0007829|PDB:7ABV"
FT TURN 1470..1472
FT /evidence="ECO:0007829|PDB:7ABV"
FT HELIX 1473..1476
FT /evidence="ECO:0007829|PDB:7ABV"
FT TURN 1477..1482
FT /evidence="ECO:0007829|PDB:7ABV"
FT TURN 1486..1489
FT /evidence="ECO:0007829|PDB:7ABV"
FT HELIX 1492..1494
FT /evidence="ECO:0007829|PDB:7ABV"
FT HELIX 1496..1498
FT /evidence="ECO:0007829|PDB:7ABV"
FT TURN 1499..1501
FT /evidence="ECO:0007829|PDB:7ABV"
FT STRAND 1502..1504
FT /evidence="ECO:0007829|PDB:7ABV"
FT HELIX 1507..1509
FT /evidence="ECO:0007829|PDB:7ABV"
FT HELIX 1512..1519
FT /evidence="ECO:0007829|PDB:7ABV"
FT HELIX 1530..1539
FT /evidence="ECO:0007829|PDB:7ABV"
FT STRAND 1542..1544
FT /evidence="ECO:0007829|PDB:7ABV"
FT HELIX 1547..1549
FT /evidence="ECO:0007829|PDB:7ABV"
FT HELIX 1552..1559
FT /evidence="ECO:0007829|PDB:7ABV"
FT STRAND 1571..1580
FT /evidence="ECO:0007829|PDB:7ABV"
FT HELIX 1582..1587
FT /evidence="ECO:0007829|PDB:7ABV"
FT HELIX 1589..1600
FT /evidence="ECO:0007829|PDB:7ABV"
FT STRAND 1602..1606
FT /evidence="ECO:0007829|PDB:7ABV"
FT STRAND 1616..1619
FT /evidence="ECO:0007829|PDB:7ABV"
FT STRAND 1663..1671
FT /evidence="ECO:0007829|PDB:7ABV"
FT HELIX 1675..1678
FT /evidence="ECO:0007829|PDB:7ABV"
FT HELIX 1686..1698
FT /evidence="ECO:0007829|PDB:7ABV"
FT STRAND 1704..1706
FT /evidence="ECO:0007829|PDB:7ABV"
FT STRAND 1708..1714
FT /evidence="ECO:0007829|PDB:7ABV"
FT HELIX 1921..1927
FT /evidence="ECO:0007829|PDB:2QC9"
FT HELIX 1931..1939
FT /evidence="ECO:0007829|PDB:2QC9"
FT HELIX 1954..1961
FT /evidence="ECO:0007829|PDB:2QC9"
FT HELIX 1964..1972
FT /evidence="ECO:0007829|PDB:2QC9"
FT HELIX 1975..1977
FT /evidence="ECO:0007829|PDB:1YMP"
FT HELIX 1988..1995
FT /evidence="ECO:0007829|PDB:1YMP"
FT HELIX 2000..2006
FT /evidence="ECO:0007829|PDB:1YMP"
FT HELIX 2021..2027
FT /evidence="ECO:0007829|PDB:1YMP"
FT HELIX 2031..2039
FT /evidence="ECO:0007829|PDB:1YMP"
FT HELIX 2054..2061
FT /evidence="ECO:0007829|PDB:1YMP"
FT HELIX 2064..2072
FT /evidence="ECO:0007829|PDB:1YMP"
FT HELIX 2087..2093
FT /evidence="ECO:0007829|PDB:1YMP"
FT HELIX 2097..2103
FT /evidence="ECO:0007829|PDB:1YMP"
SQ SEQUENCE 2531 AA; 270835 MW; 97C91F69BABF02BF CRC64;
MPRLLTPLLC LTLLPALAAR GLRCSQPSGT CLNGGRCEVA NGTEACVCSG AFVGQRCQDS
NPCLSTPCKN AGTCHVVDHG GTVDYACSCP LGFSGPLCLT PLDNACLANP CRNGGTCDLL
TLTEYKCRCP PGWSGKSCQQ ADPCASNPCA NGGQCLPFES SYICRCPPGF HGPTCRQDVN
ECSQNPGLCR HGGTCHNEIG SYRCACRATH TGPHCELPYV PCSPSPCQNG GTCRPTGDTT
HECACLPGFA GQNCEENVDD CPGNNCKNGG ACVDGVNTYN CRCPPEWTGQ YCTEDVDECQ
LMPNACQNGG TCHNTHGGYN CVCVNGWTGE DCSENIDDCA SAACFQGATC HDRVASFYCE
CPHGRTGLLC HLNDACISNP CNEGSNCDTN PVNGKAICTC PSGYTGPACS QDVDECALGA
NPCEHAGKCL NTLGSFECQC LQGYTGPRCE IDVNECISNP CQNDATCLDQ IGEFQCICMP
GYEGVYCEIN TDECASSPCL HNGHCMDKIN EFQCQCPKGF NGHLCQYDVD ECASTPCKNG
AKCLDGPNTY TCVCTEGYTG THCEVDIDEC DPDPCHYGSC KDGVATFTCL CQPGYTGHHC
ETNINECHSQ PCRHGGTCQD RDNSYLCLCL KGTTGPNCEI NLDDCASNPC DSGTCLDKID
GYECACEPGY TGSMCNVNID ECAGSPCHNG GTCEDGIAGF TCRCPEGYHD PTCLSEVNEC
NSNPCIHGAC RDGLNGYKCD CAPGWSGTNC DINNNECESN PCVNGGTCKD MTSGYVCTCR
EGFSGPNCQT NINECASNPC LNQGTCIDDV AGYKCNCPLP YTGATCEVVL APCATSPCKN
SGVCKESEDY ESFSCVCPTG WQGQTCEVDI NECVKSPCRH GASCQNTNGS YRCLCQAGYT
GRNCESDIDD CRPNPCHNGG SCTDGINTAF CDCLPGFQGA FCEEDINECA SNPCQNGANC
TDCVDSYTCT CPVGFNGIHC ENNTPDCTES SCFNGGTCVD GINSFTCLCP PGFTGSYCQY
DVNECDSRPC LHGGTCQDSY GTYKCTCPQG YTGLNCQNLV RWCDSAPCKN GGRCWQTNTQ
YHCECRSGWT GVNCDVLSVS CEVAAQKRGI DVTLLCQHGG LCVDEGDKHY CHCQAGYTGS
YCEDEVDECS PNPCQNGATC TDYLGGFSCK CVAGYHGSNC SEEINECLSQ PCQNGGTCID
LTNSYKCSCP RGTQGVHCEI NVDDCHPPLD PASRSPKCFN NGTCVDQVGG YTCTCPPGFV
GERCEGDVNE CLSNPCDPRG TQNCVQRVND FHCECRAGHT GRRCESVING CRGKPCKNGG
VCAVASNTAR GFICRCPAGF EGATCENDAR TCGSLRCLNG GTCISGPRSP TCLCLGSFTG
PECQFPASSP CVGSNPCYNQ GTCEPTSENP FYRCLCPAKF NGLLCHILDY SFTGGAGRDI
PPPQIEEACE LPECQVDAGN KVCNLQCNNH ACGWDGGDCS LNFNDPWKNC TQSLQCWKYF
SDGHCDSQCN SAGCLFDGFD CQLTEGQCNP LYDQYCKDHF SDGHCDQGCN SAECEWDGLD
CAEHVPERLA AGTLVLVVLL PPDQLRNNSF HFLRELSHVL HTNVVFKRDA QGQQMIFPYY
GHEEELRKHP IKRSTVGWAT SSLLPGTSGG RQRRELDPMD IRGSIVYLEI DNRQCVQSSS
QCFQSATDVA AFLGALASLG SLNIPYKIEA VKSEPVEPPL PSQLHLMYVA AAAFVLLFFV
GCGVLLSRKR RRQHGQLWFP EGFKVSEASK KKRREPLGED SVGLKPLKNA SDGALMDDNQ
NEWGDEDLET KKFRFEEPVV LPDLSDQTDH RQWTQQHLDA ADLRMSAMAP TPPQGEVDAD
CMDVNVRGPD GFTPLMIASC SGGGLETGNS EEEEDAPAVI SDFIYQGASL HNQTDRTGET
ALHLAARYSR SDAAKRLLEA SADANIQDNM GRTPLHAAVS ADAQGVFQIL LRNRATDLDA
RMHDGTTPLI LAARLAVEGM LEDLINSHAD VNAVDDLGKS ALHWAAAVNN VDAAVVLLKN
GANKDMQNNK EETPLFLAAR EGSYETAKVL LDHFANRDIT DHMDRLPRDI AQERMHHDIV
RLLDEYNLVR SPQLHGTALG GTPTLSPTLC SPNGYLGNLK SATQGKKARK PSTKGLACGS
KEAKDLKARR KKSQDGKGCL LDSSSMLSPV DSLESPHGYL SDVASPPLLP SPFQQSPSMP
LSHLPGMPDT HLGISHLNVA AKPEMAALAG GSRLAFEPPP PRLSHLPVAS SASTVLSTNG
TGAMNFTVGA PASLNGQCEW LPRLQNGMVP SQYNPLRPGV TPGTLSTQAA GLQHSMMGPL
HSSLSTNTLS PIIYQGLPNT RLATQPHLVQ TQQVQPQNLQ LQPQNLQPPS QPHLSVSSAA
NGHLGRSFLS GEPSQADVQP LGPSSLPVHT ILPQESQALP TSLPSSMVPP MTTTQFLTPP
SQHSYSSSPV DNTPSHQLQV PEHPFLTPSP ESPDQWSSSS PHSNISDWSE GISSPPTTMP
SQITHIPEAF K
