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Database: UniProt
Entry: Q61483
LinkDB: Q61483
Original site: Q61483 
ID   DLL1_MOUSE              Reviewed;         722 AA.
AC   Q61483; Q6PFV7;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   13-FEB-2019, entry version 177.
DE   RecName: Full=Delta-like protein 1 {ECO:0000305};
DE   AltName: Full=Drosophila Delta homolog 1;
DE            Short=Delta1 {ECO:0000303|PubMed:12794186};
DE   Contains:
DE     RecName: Full=Dll1-soluble form {ECO:0000303|PubMed:12794186};
DE              Short=Dll1-EC {ECO:0000305|PubMed:12794186};
DE              Short=Shed form {ECO:0000303|PubMed:12794186};
DE   Contains:
DE     RecName: Full=Dll1-derived cell-associated form {ECO:0000303|PubMed:12794186};
DE              Short=Dll1-TMIC {ECO:0000305|PubMed:12794186};
DE              Short=Membrane-associated fragment {ECO:0000303|PubMed:12794186};
DE   Contains:
DE     RecName: Full=Dll1-intracellular form {ECO:0000303|PubMed:12794186};
DE              Short=Dll1-IC {ECO:0000305|PubMed:12794186};
DE   Flags: Precursor;
GN   Name=Dll1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, TISSUE SPECIFICITY,
RP   AND FUNCTION.
RC   STRAIN=C57BL/6 X BALB/c; TISSUE=Embryo;
RX   PubMed=7671806;
RA   Bettenhausen B., de Angelis M.H., Simon D., Guenet J.-L., Gossler A.;
RT   "Transient and restricted expression during mouse embryogenesis of
RT   Dll1, a murine gene closely related to Drosophila Delta.";
RL   Development 121:2407-2418(1995).
RN   [2]
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.,
RA   She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
RA   Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
RA   Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
RA   Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
RA   Lindblad-Toh K., Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of
RT   the mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Embryonic 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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   PROTEIN SEQUENCE OF 527-534 AND 536-543, PROTEOLYTIC CLEAVAGE BY
RP   MMP14, INTERACTION WITH MMP14, IDENTIFICATION BY MASS SPECTROMETRY,
RP   AND FUNCTION.
RX   PubMed=21572390; DOI=10.1038/emboj.2011.136;
RA   Jin G., Zhang F., Chan K.M., Xavier Wong H.L., Liu B., Cheah K.S.,
RA   Liu X., Mauch C., Liu D., Zhou Z.;
RT   "MT1-MMP cleaves Dll1 to negatively regulate Notch signalling to
RT   maintain normal B-cell development.";
RL   EMBO J. 30:2281-2293(2011).
RN   [6]
RP   PROTEIN SEQUENCE OF 536-554, PROTEOLYTIC CLEAVAGE, HOMODIMERIZATION,
RP   INTERACTION WITH PSEN1, AND SUBCELLULAR LOCATION.
RX   PubMed=12794186; DOI=10.1073/pnas.1230693100;
RA   Six E., Ndiaye D., Laabi Y., Brou C., Gupta-Rossi N., Israel A.,
RA   Logeat F.;
RT   "The Notch ligand Delta1 is sequentially cleaved by an ADAM protease
RT   and gamma-secretase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:7638-7643(2003).
RN   [7]
RP   FUNCTION.
RX   PubMed=10958687; DOI=10.1128/MCB.20.18.6913-6922.2000;
RA   Shimizu K., Chiba S., Hosoya N., Kumano K., Saito T., Kurokawa M.,
RA   Kanda Y., Hamada Y., Hirai H.;
RT   "Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces
RT   cleavage, nuclear translocation, and hyperphosphorylation of Notch2.";
RL   Mol. Cell. Biol. 20:6913-6922(2000).
RN   [8]
RP   FUNCTION.
RX   PubMed=15146182; DOI=10.1038/ni1075;
RA   Hozumi K., Negishi N., Suzuki D., Abe N., Sotomaru Y., Tamaoki N.,
RA   Mailhos C., Ish-Horowicz D., Habu S., Owen M.J.;
RT   "Delta-like 1 is necessary for the generation of marginal zone B cells
RT   but not T cells in vivo.";
RL   Nat. Immunol. 5:638-644(2004).
RN   [9]
RP   INTERACTION WITH MFAP5.
RX   PubMed=15788413; DOI=10.1074/jbc.M500273200;
RA   Nehring L.C., Miyamoto A., Hein P.W., Weinmaster G., Shipley J.M.;
RT   "The extracellular matrix protein MAGP-2 interacts with Jagged1 and
RT   induces its shedding from the cell surface.";
RL   J. Biol. Chem. 280:20349-20355(2005).
RN   [10]
RP   INTERACTION WITH MAGI1, AND SUBCELLULAR LOCATION.
RX   PubMed=15908431; DOI=10.1074/jbc.M500375200;
RA   Mizuhara E., Nakatani T., Minaki Y., Sakamoto Y., Ono Y., Takai Y.;
RT   "MAGI1 recruits Dll1 to cadherin-based adherens junctions and
RT   stabilizes it on the cell surface.";
RL   J. Biol. Chem. 280:26499-26507(2005).
RN   [11]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=16495313; DOI=10.1242/dev.02284;
RA   Brooker R., Hozumi K., Lewis J.;
RT   "Notch ligands with contrasting functions: Jagged1 and Delta1 in the
RT   mouse inner ear.";
RL   Development 133:1277-1286(2006).
RN   [12]
RP   INTERACTION WITH NEURL1B, AND UBIQUITINATION.
RX   PubMed=17003037; DOI=10.1074/jbc.M606601200;
RA   Song R., Koo B.-K., Yoon K.-J., Yoon M.-J., Yoo K.-W., Kim H.-T.,
RA   Oh H.-J., Kim Y.-Y., Han J.-K., Kim C.-H., Kong Y.-Y.;
RT   "Neuralized-2 regulates a Notch ligand in cooperation with Mind bomb-
RT   1.";
RL   J. Biol. Chem. 281:36391-36400(2006).
RN   [13]
RP   DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=17194759; DOI=10.1073/pnas.0608281104;
RA   Schuster-Gossler K., Cordes R., Gossler A.;
RT   "Premature myogenic differentiation and depletion of progenitor cells
RT   cause severe muscle hypotrophy in Delta1 mutants.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:537-542(2007).
RN   [14]
RP   FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX   PubMed=18997111; DOI=10.1242/dev.024570;
RA   Kawaguchi D., Yoshimatsu T., Hozumi K., Gotoh Y.;
RT   "Selection of differentiating cells by different levels of delta-like
RT   1 among neural precursor cells in the developing mouse
RT   telencephalon.";
RL   Development 135:3849-3858(2008).
RN   [15]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=17960184; DOI=10.1038/sj.jid.5701113;
RA   Estrach S., Cordes R., Hozumi K., Gossler A., Watt F.M.;
RT   "Role of the Notch ligand Delta1 in embryonic and adult mouse
RT   epidermis.";
RL   J. Invest. Dermatol. 128:825-832(2008).
RN   [16]
RP   UBIQUITINATION, FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=18676613; DOI=10.1073/pnas.0800695105;
RA   Heuss S.F., Ndiaye-Lobry D., Six E.M., Israel A., Logeat F.;
RT   "The intracellular region of Notch ligands Dll1 and Dll3 regulates
RT   their trafficking and signaling activity.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:11212-11217(2008).
RN   [17]
RP   INTERACTION WITH NEURL1 AND NEURL1B.
RX   PubMed=19723503; DOI=10.1016/j.bbrc.2009.08.147;
RA   Rullinkov G., Tamme R., Sarapuu A., Lauren J., Sepp M., Palm K.,
RA   Timmusk T.;
RT   "Neuralized-2: Expression in human and rodents and interaction with
RT   Delta-like ligands.";
RL   Biochem. Biophys. Res. Commun. 389:420-425(2009).
RN   [18]
RP   DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=19144989; DOI=10.1182/blood-2008-08-174508;
RA   Soerensen I., Adams R.H., Gossler A.;
RT   "DLL1-mediated Notch activation regulates endothelial identity in
RT   mouse fetal arteries.";
RL   Blood 113:5680-5688(2009).
RN   [19]
RP   FUNCTION, AND DEVELOPMENTAL STAGE.
RX   PubMed=19389377; DOI=10.1016/j.ydbio.2009.01.011;
RA   Rocha S.F., Lopes S.S., Gossler A., Henrique D.;
RT   "Dll1 and Dll4 function sequentially in the retina and pV2 domain of
RT   the spinal cord to regulate neurogenesis and create cell diversity.";
RL   Dev. Biol. 328:54-65(2009).
RN   [20]
RP   FUNCTION.
RX   PubMed=19217325; DOI=10.1016/j.immuni.2008.12.016;
RA   Tan J.B., Xu K., Cretegny K., Visan I., Yuan J.S., Egan S.E.,
RA   Guidos C.J.;
RT   "Lunatic and manic fringe cooperatively enhance marginal zone B cell
RT   precursor competition for delta-like 1 in splenic endothelial
RT   niches.";
RL   Immunity 30:254-263(2009).
RN   [21]
RP   DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=19562077; DOI=10.1371/journal.pone.0006054;
RA   Rubio-Aliaga I., Przemeck G.K., Fuchs H., Gailus-Durner V., Adler T.,
RA   Hans W., Horsch M., Rathkolb B., Rozman J., Schrewe A., Wagner S.,
RA   Hoelter S.M., Becker L., Klopstock T., Wurst W., Wolf E.,
RA   Klingenspor M., Ivandic B.T., Busch D.H., Beckers J.,
RA   Hrabe de Angelis M.;
RT   "Dll1 haploinsufficiency in adult mice leads to a complex phenotype
RT   affecting metabolic and immunological processes.";
RL   PLoS ONE 4:E6054-E6054(2009).
RN   [22]
RP   FUNCTION.
RX   PubMed=20081190; DOI=10.1242/dev.036806;
RA   Marklund U., Hansson E.M., Sundstroem E., de Angelis M.H.,
RA   Przemeck G.K., Lendahl U., Muhr J., Ericson J.;
RT   "Domain-specific control of neurogenesis achieved through patterned
RT   regulation of Notch ligand expression.";
RL   Development 137:437-445(2010).
RN   [23]
RP   MUTAGENESIS OF 613-LYS--LYS-618; LYS-613; LYS-689; LYS-699 AND
RP   LYS-713, INTERACTION WITH MIB1, SUBCELLULAR LOCATION, FUNCTION, AND
RP   UBIQUITINATION AT LYS-613.
RX   PubMed=21985982; DOI=10.1016/j.bbamcr.2011.08.019;
RA   Zhang L., Widau R.C., Herring B.P., Gallagher P.J.;
RT   "Delta-like 1-Lysine613 regulates notch signaling.";
RL   Biochim. Biophys. Acta 1813:2036-2043(2011).
RN   [24]
RP   FUNCTION.
RX   PubMed=21238454; DOI=10.1053/j.gastro.2011.01.005;
RA   Pellegrinet L., Rodilla V., Liu Z., Chen S., Koch U., Espinosa L.,
RA   Kaestner K.H., Kopan R., Lewis J., Radtke F.;
RT   "Dll1- and dll4-mediated notch signaling are required for homeostasis
RT   of intestinal stem cells.";
RL   Gastroenterology 140:1230-1240(2011).
RN   [25]
RP   FUNCTION.
RX   PubMed=21915337; DOI=10.1371/journal.pone.0024484;
RA   Stamataki D., Holder M., Hodgetts C., Jeffery R., Nye E.,
RA   Spencer-Dene B., Winton D.J., Lewis J.;
RT   "Delta1 expression, cell cycle exit, and commitment to a specific
RT   secretory fate coincide within a few hours in the mouse intestinal
RT   stem cell system.";
RL   PLoS ONE 6:E24484-E24484(2011).
RN   [26]
RP   FUNCTION.
RX   PubMed=22282195; DOI=10.1161/CIRCRESAHA.111.263319;
RA   Napp L.C., Augustynik M., Paesler F., Krishnasamy K., Woiterski J.,
RA   Limbourg A., Bauersachs J., Drexler H., Le Noble F., Limbourg F.P.;
RT   "Extrinsic Notch ligand Delta-like 1 regulates tip cell selection and
RT   vascular branching morphogenesis.";
RL   Circ. Res. 110:530-535(2012).
RN   [27]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=22096075; DOI=10.1242/dev.071761;
RA   Ahnfelt-Roenne J., Joergensen M.C., Klinck R., Jensen J.N.,
RA   Fuechtbauer E.M., Deering T., MacDonald R.J., Wright C.V.,
RA   Madsen O.D., Serup P.;
RT   "Ptf1a-mediated control of Dll1 reveals an alternative to the lateral
RT   inhibition mechanism.";
RL   Development 139:33-45(2012).
RN   [28]
RP   INDUCTION.
RX   PubMed=22015720; DOI=10.1016/j.ydbio.2011.09.034;
RA   Grainger S., Lam J., Savory J.G., Mears A.J., Rijli F.M., Lohnes D.;
RT   "Cdx regulates Dll1 in multiple lineages.";
RL   Dev. Biol. 361:1-11(2012).
RN   [29]
RP   FUNCTION.
RX   PubMed=22940113; DOI=10.1016/j.devcel.2012.07.014;
RA   Broehl D., Vasyutina E., Czajkowski M.T., Griger J., Rassek C.,
RA   Rahn H.P., Purfuerst B., Wende H., Birchmeier C.;
RT   "Colonization of the satellite cell niche by skeletal muscle
RT   progenitor cells depends on Notch signals.";
RL   Dev. Cell 23:469-481(2012).
RN   [30]
RP   FUNCTION.
RX   PubMed=22529374; DOI=10.1073/pnas.1203605109;
RA   Horn S., Kobberup S., Joergensen M.C., Kalisz M., Klein T.,
RA   Kageyama R., Gegg M., Lickert H., Lindner J., Magnuson M.A.,
RA   Kong Y.Y., Serup P., Ahnfelt-Roenne J., Jensen J.N.;
RT   "Mind bomb 1 is required for pancreatic beta-cell formation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:7356-7361(2012).
RN   [31]
RP   FUNCTION.
RX   PubMed=23806616; DOI=10.1016/j.devcel.2013.05.022;
RA   Liu Z., Chen S., Boyle S., Zhu Y., Zhang A., Piwnica-Worms D.R.,
RA   Ilagan M.X., Kopan R.;
RT   "The extracellular domain of Notch2 increases its cell-surface
RT   abundance and ligand responsiveness during kidney development.";
RL   Dev. Cell 25:585-598(2013).
RN   [32]
RP   FUNCTION.
RX   PubMed=23699523; DOI=10.1523/JNEUROSCI.0791-13.2013;
RA   Nelson B.R., Hodge R.D., Bedogni F., Hevner R.F.;
RT   "Dynamic interactions between intermediate neurogenic progenitors and
RT   radial glia in embryonic mouse neocortex: potential role in Dll1-Notch
RT   signaling.";
RL   J. Neurosci. 33:9122-9139(2013).
RN   [33]
RP   DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=23688253; DOI=10.1186/1756-6606-6-25;
RA   Hiraoka Y., Komine O., Nagaoka M., Bai N., Hozumi K., Tanaka K.;
RT   "Delta-like 1 regulates Bergmann glial monolayer formation during
RT   cerebellar development.";
RL   Mol. Brain 6:25-25(2013).
RN   [34]
RP   FUNCTION.
RX   PubMed=23695674; DOI=10.1038/ncomms2895;
RA   Kawaguchi D., Furutachi S., Kawai H., Hozumi K., Gotoh Y.;
RT   "Dll1 maintains quiescence of adult neural stem cells and segregates
RT   asymmetrically during mitosis.";
RL   Nat. Commun. 4:1880-1880(2013).
RN   [35]
RP   INTERACTION WITH TJP1, AND SUBCELLULAR LOCATION.
RX   PubMed=24715457; DOI=10.1242/dev.102988;
RA   Hatakeyama J., Wakamatsu Y., Nagafuchi A., Kageyama R., Shigemoto R.,
RA   Shimamura K.;
RT   "Cadherin-based adhesions in the apical endfoot are required for
RT   active Notch signaling to control neurogenesis in vertebrates.";
RL   Development 141:1671-1682(2014).
RN   [36]
RP   FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=25220152; DOI=10.1016/j.ydbio.2014.09.005;
RA   Czajkowski M.T., Rassek C., Lenhard D.C., Broehl D., Birchmeier C.;
RT   "Divergent and conserved roles of Dll1 signaling in development of
RT   craniofacial and trunk muscle.";
RL   Dev. Biol. 395:307-316(2014).
RN   [37]
RP   IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT THR-638;
RP   SER-693 AND SER-696, AND MUTAGENESIS OF THR-638; SER-693 AND SER-696.
RX   PubMed=24449764; DOI=10.1128/MCB.00965-13;
RA   Braune E.B., Schuster-Gossler K., Lyszkiewicz M., Serth K.,
RA   Preusse K., Madlung J., Macek B., Krueger A., Gossler A.;
RT   "S/T phosphorylation of DLL1 is required for full ligand activity in
RT   vitro but dispensable for DLL1 function in vivo during embryonic
RT   patterning and marginal zone B cell development.";
RL   Mol. Cell. Biol. 34:1221-1233(2014).
RN   [38]
RP   FUNCTION.
RX   PubMed=26114479; DOI=10.1371/journal.pgen.1005328;
RA   Preusse K., Tveriakhina L., Schuster-Gossler K., Gaspar C., Rosa A.I.,
RA   Henrique D., Gossler A., Stauber M.;
RT   "Context-dependent functional divergence of the Notch ligands DLL1 and
RT   DLL4 in vivo.";
RL   PLoS Genet. 11:E1005328-E1005328(2015).
CC   -!- FUNCTION: Transmembrane ligand protein of NOTCH1, NOTCH2 and
CC       NOTCH3 receptors that binds the extracellular domain (ECD) of
CC       Notch receptor in a cis and trans fashion manner (PubMed:21985982,
CC       PubMed:10958687). Following transinteraction, ligand cells produce
CC       mechanical force that depends of a clathrin-mediated endocytosis,
CC       requiring ligand ubiquitination, EPN1 interaction, and actin
CC       polymerisation; these events promote Notch receptor extracellular
CC       domain (NECD) transendocytosis and triggers Notch signaling
CC       through induction of cleavage, hyperphosphorylation, and nuclear
CC       accumulation of the intracellular domain of Notch receptors (NICD)
CC       (PubMed:10958687, PubMed:18676613). Is required for embryonic
CC       development and maintenance of adult stem cells in many different
CC       tissues and immune systeme; the DLL1-induced Notch signaling is
CC       mediated through an intercellular communication that regulates
CC       cell lineage, cell specification, cell patterning and
CC       morphogenesis through effects on differentiation and proliferation
CC       (PubMed:17194759, PubMed:19562077, PubMed:18997111,
CC       PubMed:23695674, PubMed:16495313, PubMed:21238454,
CC       PubMed:22282195, PubMed:7671806, PubMed:17960184, PubMed:22529374,
CC       PubMed:19389377, PubMed:23699523, PubMed:19144989,
CC       PubMed:23688253, PubMed:23806616, PubMed:26114479,
CC       PubMed:22940113, PubMed:25220152, PubMed:20081190,
CC       PubMed:21572390, PubMed:22096075). Plays a role in brain
CC       development at different level, namely by regulating neuronal
CC       differentiation of neural precursor cells via cell-cell
CC       interaction, most likely through the lateral inhibitory system in
CC       an endogenous level dependent-manner (PubMed:7671806,
CC       PubMed:18997111). During neocortex development, Dll1-Notch
CC       signaling transmission is mediated by dynamic interactions between
CC       intermediate neurogenic progenitors and radial glia; the cell-cell
CC       interactions are mediated via dynamic and transient elongation
CC       processes, likely to reactivate/maintain Notch activity in
CC       neighboring progenitors, and coordinate progenitor cell division
CC       and differentiation across radial and zonal boundaries
CC       (PubMed:23699523). During cerebellar development, regulates
CC       Bergmann glial monolayer formation and its morphological
CC       maturation through a Notch signaling pathway (PubMed:23688253). At
CC       the retina and spinal cord level, regulates neurogenesis by
CC       preventing the premature differentiation of neural progenitors and
CC       also by maintaining progenitors in spinal cord through Notch
CC       signaling pathway (PubMed:19389377, PubMed:26114479). Also
CC       controls neurogenesis of the neural tube in a progenitor domain-
CC       specific fashion along the dorsoventral axis (PubMed:20081190).
CC       Maintains quiescence of neural stem cells and plays a role as a
CC       fate determinant that segregates asymmetrically to one daughter
CC       cell during neural stem cells mitosis, resulting in neuronal
CC       differentiation in Dll1-inheriting cell (PubMed:23695674). Plays a
CC       role in immune systeme development, namely the development of all
CC       T-cells and marginal zone (MZ) B cells (PubMed:15146182,
CC       PubMed:19217325). Blocks the differentiation of progenitor cells
CC       into the B-cell lineage while promoting the emergence of a
CC       population of cells with the characteristics of a T-cell/NK-cell
CC       precursor (By similarity). Upon MMP14 cleavage, negatively
CC       regulates Notch signaling in haematopoietic progenitor cells to
CC       specifically maintain normal B-cell development in bone marrow
CC       (PubMed:21572390). Also plays a role during muscle development.
CC       During early development, inhibits myoblasts differentiation from
CC       the medial dermomyotomal lip and later regulates progenitor cell
CC       differentiation (PubMed:17194759). Directly modulates cell
CC       adhesion and basal lamina formation in satellite cells through
CC       Notch signaling. Maintains myogenic progenitors pool by
CC       suppressing differentiation through down-regulation of MYOD1 and
CC       is required for satellite cell homing and PAX7 expression
CC       (PubMed:22940113). During craniofacial and trunk myogenesis
CC       suppresses differentiation of cranial mesoderm-derived and somite-
CC       derived muscle via MYOD1 regulation but in cranial mesoderm-
CC       derived progenitors, is neither required for satellite cell homing
CC       nor for PAX7 expression (PubMed:25220152). Also plays a role
CC       during pancreatic cell development. During type B pancreatic cell
CC       development, may be involved in the initiation of proximodistal
CC       patterning in the early pancreatic epithelium (PubMed:22529374).
CC       Stimulates multipotent pancreatic progenitor cells proliferation
CC       and pancreatic growth by maintaining HES1 expression and PTF1A
CC       protein levels (PubMed:22096075). During fetal stages of
CC       development, is required to maintain arterial identity and the
CC       responsiveness of arterial endothelial cells for VEGFA through
CC       regulation of KDR activation and NRP1 expression
CC       (PubMed:19144989). Controls sprouting angiogenesis and subsequent
CC       vertical branch formation througth regulation on tip cell
CC       differentiation (PubMed:22282195). Negatively regulates goblet
CC       cell differentiation in intestine and controls secretory fat
CC       commitment through lateral inhibition in small intestine
CC       (PubMed:21238454, PubMed:21915337). Plays a role during inner ear
CC       development; negatively regulates auditory hair cell
CC       differentiation (PubMed:16495313). Plays a role during nephron
CC       development through Notch signaling pathway (PubMed:23806616).
CC       Regulates growth, blood pressure and energy homeostasis
CC       (PubMed:19562077). {ECO:0000250|UniProtKB:O00548,
CC       ECO:0000250|UniProtKB:P97677, ECO:0000269|PubMed:10958687,
CC       ECO:0000269|PubMed:15146182, ECO:0000269|PubMed:16495313,
CC       ECO:0000269|PubMed:17194759, ECO:0000269|PubMed:17960184,
CC       ECO:0000269|PubMed:18676613, ECO:0000269|PubMed:18997111,
CC       ECO:0000269|PubMed:19144989, ECO:0000269|PubMed:19217325,
CC       ECO:0000269|PubMed:19389377, ECO:0000269|PubMed:19562077,
CC       ECO:0000269|PubMed:20081190, ECO:0000269|PubMed:21238454,
CC       ECO:0000269|PubMed:21572390, ECO:0000269|PubMed:21915337,
CC       ECO:0000269|PubMed:21985982, ECO:0000269|PubMed:22096075,
CC       ECO:0000269|PubMed:22282195, ECO:0000269|PubMed:22529374,
CC       ECO:0000269|PubMed:22940113, ECO:0000269|PubMed:23688253,
CC       ECO:0000269|PubMed:23695674, ECO:0000269|PubMed:23699523,
CC       ECO:0000269|PubMed:23806616, ECO:0000269|PubMed:25220152,
CC       ECO:0000269|PubMed:26114479, ECO:0000269|PubMed:7671806}.
CC   -!- SUBUNIT: Homodimer (PubMed:12794186). Interacts with TJP1
CC       (PubMed:24715457). Interacts with MMP14; inhibits DLL1-induced
CC       Notch signaling (PubMed:21572390). Interacts with MAGI1 (via PDZ
CC       domain); forms a complex with CTNNB1 and CDH2 and promotes
CC       recruitment to the adherens junction and stabilization on the cell
CC       surface (PubMed:15908431). Interacts with PSEN1; undergoes a
CC       presenilin-dependent gamma-secretase cleavage that releases a
CC       Dll1-intracellular form (PubMed:12794186). Interacts with MFAP5
CC       (PubMed:15788413). Interacts with MIB1 (PubMed:21985982).
CC       Interacts with NEURL1B; leads to ubiquitination (PubMed:17003037,
CC       PubMed:19723503). Interacts with NEURL1 (PubMed:19723503).
CC       Interacts with SYNJ2BP; enhances DLL1 protein stability, and
CC       promotes Notch signaling in endothelial cells (By similarity).
CC       Interacts with MAGI1, MAGI2, MAGI3 and MPDZ (By similarity).
CC       Interacts (via ubiquitin) with EPN1 (via IUM domain); binding with
CC       NOTCH1 attached to neighboring cell, promotes ligand
CC       ubiquitination and EPN1 interaction, leading to NECD
CC       transendocytosis and Notch signaling. Interacts with NOTCH1 (By
CC       similarity). {ECO:0000250|UniProtKB:O00548,
CC       ECO:0000250|UniProtKB:P97677, ECO:0000269|PubMed:12794186,
CC       ECO:0000269|PubMed:15788413, ECO:0000269|PubMed:15908431,
CC       ECO:0000269|PubMed:17003037, ECO:0000269|PubMed:19723503,
CC       ECO:0000269|PubMed:21572390, ECO:0000269|PubMed:21985982,
CC       ECO:0000269|PubMed:24715457}.
CC   -!- INTERACTION:
CC       Q9WVQ1:Magi2; NbExp=3; IntAct=EBI-297125, EBI-297151;
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane
CC       {ECO:0000269|PubMed:24715457}; Single-pass type I membrane protein
CC       {ECO:0000269|PubMed:24715457}. Cell junction, adherens junction
CC       {ECO:0000269|PubMed:15908431, ECO:0000269|PubMed:24715457}.
CC       Membrane raft {ECO:0000269|PubMed:18676613,
CC       ECO:0000269|PubMed:21985982}. Note=Distributed around adherens
CC       junction in the apical endfeet through interactions with MAGI1.
CC       {ECO:0000269|PubMed:15908431, ECO:0000269|PubMed:24715457}.
CC   -!- SUBCELLULAR LOCATION: Dll1-derived cell-associated form: Cell
CC       membrane {ECO:0000269|PubMed:12794186}.
CC   -!- SUBCELLULAR LOCATION: Dll1-intracellular form: Nucleus
CC       {ECO:0000269|PubMed:12794186}.
CC   -!- TISSUE SPECIFICITY: In the embryo, expressed in the paraxial
CC       mesoderm and nervous system. Expressed at high levels in adult
CC       heart and at lower levels, in adult lung. Highly expressed in
CC       satellite cells from masseter and tongue than in satellite cells
CC       from leg and extraocular muscle.? (PubMed:25220152).
CC       {ECO:0000269|PubMed:25220152, ECO:0000269|PubMed:7671806}.
CC   -!- DEVELOPMENTAL STAGE: Expressed until 15 dpc. Expression then
CC       decreases and increases again in the adult. In differentiating
CC       somites, is expressed at low levels in cells emerging from the
CC       dorsomedial lip and subsequently throughout myotomes. In the limb
CC       buds, is found in myoblasts and myocytes but not in the progenitor
CC       cells (PubMed:17194759). Highly expressed in the endothelium and
CC       in the smooth muscle layer starting at 13.5 dpc in arterial
CC       vessels, but not in veins. At 12.5 dpc, there is no detectable
CC       expression in arteries or veins. This pattern persists until 18.5
CC       dpc (PubMed:19144989). Strongly expressed in developing muscle of
CC       tongue, cheek, and in extraocular muscle at 11.5 dpc. Found at 18
CC       dpc and P21 in head muscle (PubMed:25220152). Detected in a subset
CC       of cells in the ventricular zone (VZ), the intermediate zone (IZ)
CC       and the cortical plate (CP) of neocortex and in the ganglionic
CC       eminences at 13.5 dpc. At later stages, such as at 16.5 dpc, found
CC       in the VZ and IZ, but at very low levels in the CP of the
CC       neocortex (PubMed:18997111). Highly expressed in embryonic cells
CC       located in the ventricular zone (VZ) of the retinal
CC       neuroepithelium that form clusters; is first detected in cells
CC       located in the central retina. As the retina grows, expression
CC       spreads peripherally along the expanding neurogenic region, being
CC       always absent from the ciliary margin zone (CMZ)
CC       (PubMed:19389377). {ECO:0000269|PubMed:17194759,
CC       ECO:0000269|PubMed:18997111, ECO:0000269|PubMed:19144989,
CC       ECO:0000269|PubMed:19389377, ECO:0000269|PubMed:25220152,
CC       ECO:0000269|PubMed:7671806}.
CC   -!- INDUCTION: Induced by PTF1A in multipotent pancreatic progenitor
CC       cells (PubMed:22096075). Induced by CDX1 and CDX2 during
CC       somitogenesis and goblet cell differentiation (PubMed:22015720).
CC       {ECO:0000269|PubMed:22015720, ECO:0000269|PubMed:22096075}.
CC   -!- PTM: Ubiquitinated by MIB (MIB1 or MIB2), leading to its
CC       endocytosis and subsequent degradation. Ubiquitinated; promotes
CC       recycling back to the plasma membrane and confers a strong
CC       affinity for NOTCH1 (PubMed:18676613). Multi-ubiquitination of
CC       LYS-613 by MIB1 promotes both cis and trans-interaction with
CC       NOTCH1, as well as activation of Notch signaling
CC       (PubMed:21985982). Ubiquitinated by NEURL1B (PubMed:17003037).
CC       {ECO:0000250|UniProtKB:P10041, ECO:0000269|PubMed:17003037,
CC       ECO:0000269|PubMed:18676613, ECO:0000269|PubMed:21985982}.
CC   -!- PTM: Phosphorylated in a membrane association-dependent manner.
CC       Phosphorylation at Ser-696 requires the presence of Ser-693,
CC       whereas phosphorylation at Thr-638 and Ser-693 occurs
CC       independently of the other sites. Phosphorylation is required for
CC       full ligand activity in vitro and affects surface presentation,
CC       ectodomain shedding, and endocytosis.
CC       {ECO:0000269|PubMed:24449764}.
CC   -!- PTM: Cleaved by MMP14; negatively regulates DLL1-induced Notch
CC       signaling in HPCs, modulating B-lymphocyte differentiation in bone
CC       marrow (PubMed:21572390). Undergoes two consecutive processing
CC       events: a shedding event, partially by ADAM10, that generates a
CC       soluble extracellular form and an intracellular membrane-anchored
CC       form, followed by a gamma-secretase cleavage releasing an
CC       intracellular fragment (PubMed:12794186).
CC       {ECO:0000269|PubMed:12794186, ECO:0000269|PubMed:21572390}.
CC   -!- PTM: O-fucosylated. Can be elongated to a disaccharide by MFNG.
CC       {ECO:0000250|UniProtKB:P97677}.
CC   -!- DISRUPTION PHENOTYPE: Heterozygous Dll1 mice mutants are lighter
CC       and smaller, with altered fat to lean ratio and have increased
CC       blood pressure and a slight bradycardia. The animals have reduced
CC       cholesterol and triglyceride levels in blood (PubMed:19562077).
CC       Heterozygous Dll1 mice mutants and hypomorphic Dll1 mice mutants
CC       survive until birth, despite significantly reduced Notch activity
CC       (PubMed:17194759). Conditional knockout in inner ear leads to an
CC       early and excessive production of hair cells and have vestibular
CC       defects (PubMed:16495313). Conditional knockout in a small
CC       proportion of neural precursor cells reduces neurogenesis, whereas
CC       conditional knockout in a large proportion promotes premature
CC       neurogenesis (PubMed:18997111). Hypomorph Dll1 pups mutant survive
CC       until birth but are smaller. Conditional knockout Dll1 mice mutant
CC       in epidermis, survive and have no gross abnormalities
CC       (PubMed:17960184). Hypomorph Dll1 mice mutant survive until birth
CC       and have severe skeletal muscle defects (PubMed:19144989).
CC       Heterozygous Dll1 mutant embryos show disrupted muscle growth
CC       (PubMed:25220152). Conditional knockout Dll1 mice mutant show
CC       disorganization of Bergmann fibers, ectopic localization of
CC       Bergmann glia in the molecular layer and a reduction in the number
CC       of Bergmann glia (PubMed:23688253). {ECO:0000269|PubMed:16495313,
CC       ECO:0000269|PubMed:17194759, ECO:0000269|PubMed:17960184,
CC       ECO:0000269|PubMed:18997111, ECO:0000269|PubMed:19144989,
CC       ECO:0000269|PubMed:19562077, ECO:0000269|PubMed:23688253,
CC       ECO:0000269|PubMed:25220152}.
DR   EMBL; X80903; CAA56865.1; -; mRNA.
DR   EMBL; AY497019; AAR30869.1; -; Genomic_DNA.
DR   EMBL; CH466630; EDL20466.1; -; Genomic_DNA.
DR   EMBL; BC057400; AAH57400.1; -; mRNA.
DR   EMBL; BC065063; AAH65063.1; -; mRNA.
DR   CCDS; CCDS37452.1; -.
DR   PIR; I48324; I48324.
DR   RefSeq; NP_031891.2; NM_007865.3.
DR   UniGene; Mm.4875; -.
DR   ProteinModelPortal; Q61483; -.
DR   SMR; Q61483; -.
DR   BioGrid; 199232; 7.
DR   DIP; DIP-32600N; -.
DR   IntAct; Q61483; 8.
DR   MINT; Q61483; -.
DR   STRING; 10090.ENSMUSP00000014917; -.
DR   iPTMnet; Q61483; -.
DR   PhosphoSitePlus; Q61483; -.
DR   PaxDb; Q61483; -.
DR   PRIDE; Q61483; -.
DR   Ensembl; ENSMUST00000014917; ENSMUSP00000014917; ENSMUSG00000014773.
DR   GeneID; 13388; -.
DR   KEGG; mmu:13388; -.
DR   UCSC; uc008aoi.2; mouse.
DR   CTD; 28514; -.
DR   MGI; MGI:104659; Dll1.
DR   eggNOG; ENOG410IR7B; Eukaryota.
DR   eggNOG; ENOG410XUNS; LUCA.
DR   GeneTree; ENSGT00940000159781; -.
DR   HOGENOM; HOG000267024; -.
DR   HOVERGEN; HBG007139; -.
DR   InParanoid; Q61483; -.
DR   KO; K06051; -.
DR   OMA; DKPCHQG; -.
DR   OrthoDB; 406049at2759; -.
DR   TreeFam; TF351835; -.
DR   Reactome; R-MMU-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus.
DR   PRO; PR:Q61483; -.
DR   Proteomes; UP000000589; Chromosome 17.
DR   Bgee; ENSMUSG00000014773; Expressed in 315 organ(s), highest expression level in presomitic mesoderm.
DR   Genevisible; Q61483; MM.
DR   GO; GO:0005912; C:adherens junction; IDA:UniProtKB.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR   GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0005112; F:Notch binding; IPI:UniProtKB.
DR   GO; GO:0097110; F:scaffold protein binding; IPI:UniProtKB.
DR   GO; GO:0030957; F:Tat protein binding; ISO:MGI.
DR   GO; GO:0009887; P:animal organ morphogenesis; NAS:UniProtKB.
DR   GO; GO:0014002; P:astrocyte development; IMP:UniProtKB.
DR   GO; GO:0009912; P:auditory receptor cell fate commitment; NAS:UniProtKB.
DR   GO; GO:0007267; P:cell-cell signaling; IDA:MGI.
DR   GO; GO:0021688; P:cerebellar molecular layer formation; IMP:UniProtKB.
DR   GO; GO:0021693; P:cerebellar Purkinje cell layer structural organization; IMP:UniProtKB.
DR   GO; GO:0072583; P:clathrin-dependent endocytosis; ISS:UniProtKB.
DR   GO; GO:0007386; P:compartment pattern specification; IMP:MGI.
DR   GO; GO:0007368; P:determination of left/right symmetry; IMP:MGI.
DR   GO; GO:0097102; P:endothelial tip cell fate specification; IMP:UniProtKB.
DR   GO; GO:0097009; P:energy homeostasis; IMP:UniProtKB.
DR   GO; GO:0001947; P:heart looping; IMP:BHF-UCL.
DR   GO; GO:0001701; P:in utero embryonic development; NAS:UniProtKB.
DR   GO; GO:0042491; P:inner ear auditory receptor cell differentiation; NAS:UniProtKB.
DR   GO; GO:0048839; P:inner ear development; IMP:MGI.
DR   GO; GO:0042472; P:inner ear morphogenesis; NAS:UniProtKB.
DR   GO; GO:0046331; P:lateral inhibition; IDA:UniProtKB.
DR   GO; GO:0070986; P:left/right axis specification; IMP:BHF-UCL.
DR   GO; GO:0072070; P:loop of Henle development; IEP:UniProtKB.
DR   GO; GO:0002315; P:marginal zone B cell differentiation; IMP:UniProtKB.
DR   GO; GO:2000726; P:negative regulation of cardiac muscle cell differentiation; IMP:BHF-UCL.
DR   GO; GO:0045596; P:negative regulation of cell differentiation; IMP:UniProtKB.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB.
DR   GO; GO:0045605; P:negative regulation of epidermal cell differentiation; IMP:UniProtKB.
DR   GO; GO:0030857; P:negative regulation of epithelial cell differentiation; IMP:UniProtKB.
DR   GO; GO:0034351; P:negative regulation of glial cell apoptotic process; IMP:UniProtKB.
DR   GO; GO:0045608; P:negative regulation of inner ear auditory receptor cell differentiation; IMP:MGI.
DR   GO; GO:0032693; P:negative regulation of interleukin-10 production; ISO:MGI.
DR   GO; GO:0045638; P:negative regulation of myeloid cell differentiation; IDA:MGI.
DR   GO; GO:0045662; P:negative regulation of myoblast differentiation; IMP:UniProtKB.
DR   GO; GO:0045665; P:negative regulation of neuron differentiation; IMP:UniProtKB.
DR   GO; GO:0072006; P:nephron development; IMP:UniProtKB.
DR   GO; GO:0007399; P:nervous system development; NAS:UniProtKB.
DR   GO; GO:0048665; P:neuron fate specification; IDA:UniProtKB.
DR   GO; GO:0097150; P:neuronal stem cell population maintenance; IMP:UniProtKB.
DR   GO; GO:0061314; P:Notch signaling involved in heart development; IC:BHF-UCL.
DR   GO; GO:0007219; P:Notch signaling pathway; IMP:UniProtKB.
DR   GO; GO:0060853; P:Notch signaling pathway involved in arterial endothelial cell fate commitment; IMP:UniProtKB.
DR   GO; GO:0042475; P:odontogenesis of dentin-containing tooth; NAS:UniProtKB.
DR   GO; GO:0035265; P:organ growth; IMP:UniProtKB.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR   GO; GO:0045807; P:positive regulation of endocytosis; IDA:UniProtKB.
DR   GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
DR   GO; GO:0045747; P:positive regulation of Notch signaling pathway; IDA:UniProtKB.
DR   GO; GO:0048633; P:positive regulation of skeletal muscle tissue growth; IMP:UniProtKB.
DR   GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IMP:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR   GO; GO:0072014; P:proximal tubule development; IEP:UniProtKB.
DR   GO; GO:0009954; P:proximal/distal pattern formation; IMP:UniProtKB.
DR   GO; GO:0008217; P:regulation of blood pressure; IMP:UniProtKB.
DR   GO; GO:0030155; P:regulation of cell adhesion; IMP:UniProtKB.
DR   GO; GO:0051302; P:regulation of cell division; IMP:UniProtKB.
DR   GO; GO:0040008; P:regulation of growth; IMP:UniProtKB.
DR   GO; GO:0050767; P:regulation of neurogenesis; IMP:UniProtKB.
DR   GO; GO:0048631; P:regulation of skeletal muscle tissue growth; IMP:UniProtKB.
DR   GO; GO:0014807; P:regulation of somitogenesis; IMP:UniProtKB.
DR   GO; GO:1900746; P:regulation of vascular endothelial growth factor signaling pathway; IMP:UniProtKB.
DR   GO; GO:0060041; P:retina development in camera-type eye; IMP:UniProtKB.
DR   GO; GO:0060042; P:retina morphogenesis in camera-type eye; IMP:UniProtKB.
DR   GO; GO:0048630; P:skeletal muscle tissue growth; IMP:UniProtKB.
DR   GO; GO:0098773; P:skin epidermis development; IMP:UniProtKB.
DR   GO; GO:0001757; P:somite specification; IMP:MGI.
DR   GO; GO:0001756; P:somitogenesis; IMP:UniProtKB.
DR   GO; GO:0021510; P:spinal cord development; IMP:UniProtKB.
DR   GO; GO:0003323; P:type B pancreatic cell development; IMP:UniProtKB.
DR   InterPro; IPR001774; DSL.
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; IPR011651; Notch_ligand_N.
DR   Pfam; PF01414; DSL; 1.
DR   Pfam; PF00008; EGF; 4.
DR   Pfam; PF07645; EGF_CA; 1.
DR   Pfam; PF12661; hEGF; 1.
DR   Pfam; PF07657; MNNL; 1.
DR   SMART; SM00051; DSL; 1.
DR   SMART; SM00181; EGF; 8.
DR   SMART; SM00179; EGF_CA; 6.
DR   SUPFAM; SSF57184; SSF57184; 1.
DR   PROSITE; PS00010; ASX_HYDROXYL; 3.
DR   PROSITE; PS51051; DSL; 1.
DR   PROSITE; PS00022; EGF_1; 8.
DR   PROSITE; PS01186; EGF_2; 8.
DR   PROSITE; PS50026; EGF_3; 7.
DR   PROSITE; PS01187; EGF_CA; 2.
PE   1: Evidence at protein level;
KW   Cell junction; Cell membrane; Complete proteome;
KW   Developmental protein; Differentiation; Direct protein sequencing;
KW   Disulfide bond; EGF-like domain; Glycoprotein; Isopeptide bond;
KW   Membrane; Notch signaling pathway; Nucleus; Phosphoprotein;
KW   Reference proteome; Repeat; Signal; Transmembrane;
KW   Transmembrane helix; Ubl conjugation.
FT   SIGNAL        1     17       {ECO:0000255}.
FT   CHAIN        18    722       Delta-like protein 1.
FT                                /FTId=PRO_0000007507.
FT   CHAIN        18    535       Dll1-soluble form.
FT                                {ECO:0000269|PubMed:12794186}.
FT                                /FTId=PRO_0000434830.
FT   CHAIN       536    722       Dll1-derived cell-associated form.
FT                                {ECO:0000269|PubMed:12794186}.
FT                                /FTId=PRO_0000434831.
FT   CHAIN         ?    722       Dll1-intracellular form.
FT                                {ECO:0000269|PubMed:12794186}.
FT                                /FTId=PRO_0000434832.
FT   TOPO_DOM     18    545       Extracellular. {ECO:0000255}.
FT   TRANSMEM    546    568       Helical. {ECO:0000255}.
FT   TOPO_DOM    569    722       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN      176    220       DSL. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00377}.
FT   DOMAIN      225    253       EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      256    284       EGF-like 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      291    324       EGF-like 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      331    362       EGF-like 4; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      369    401       EGF-like 5. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      408    439       EGF-like 6. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      446    477       EGF-like 7; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      484    515       EGF-like 8. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   REGION      719    722       Interaction with MAGI1.
FT                                {ECO:0000269|PubMed:15908431}.
FT   SITE        527    528       Cleavage; by MMP14.
FT                                {ECO:0000269|PubMed:21572390}.
FT   SITE        535    536       Cleavage; by ADAM protease.
FT                                {ECO:0000269|PubMed:12794186}.
FT   MOD_RES     638    638       Phosphothreonine.
FT                                {ECO:0000269|PubMed:24449764}.
FT   MOD_RES     693    693       Phosphoserine; by PKB.
FT                                {ECO:0000269|PubMed:24449764}.
FT   MOD_RES     696    696       Phosphoserine.
FT                                {ECO:0000269|PubMed:24449764}.
FT   CARBOHYD    476    476       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    178    187       {ECO:0000250}.
FT   DISULFID    191    203       {ECO:0000250}.
FT   DISULFID    211    220       {ECO:0000250}.
FT   DISULFID    225    236       {ECO:0000250}.
FT   DISULFID    229    242       {ECO:0000250}.
FT   DISULFID    244    253       {ECO:0000250}.
FT   DISULFID    256    267       {ECO:0000250}.
FT   DISULFID    262    273       {ECO:0000250}.
FT   DISULFID    275    284       {ECO:0000250}.
FT   DISULFID    291    303       {ECO:0000250}.
FT   DISULFID    297    313       {ECO:0000250}.
FT   DISULFID    315    324       {ECO:0000250}.
FT   DISULFID    331    342       {ECO:0000250}.
FT   DISULFID    336    351       {ECO:0000250}.
FT   DISULFID    353    362       {ECO:0000250}.
FT   DISULFID    369    380       {ECO:0000250}.
FT   DISULFID    374    390       {ECO:0000250}.
FT   DISULFID    392    401       {ECO:0000250}.
FT   DISULFID    408    419       {ECO:0000250}.
FT   DISULFID    413    428       {ECO:0000250}.
FT   DISULFID    430    439       {ECO:0000250}.
FT   DISULFID    446    457       {ECO:0000250}.
FT   DISULFID    451    466       {ECO:0000250}.
FT   DISULFID    468    477       {ECO:0000250}.
FT   DISULFID    484    495       {ECO:0000250}.
FT   DISULFID    489    504       {ECO:0000250}.
FT   DISULFID    506    515       {ECO:0000250}.
FT   CROSSLNK    613    613       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in ubiquitin).
FT                                {ECO:0000269|PubMed:21985982}.
FT   MUTAGEN     613    618       KNTNKK->RNTNRR: Highly decreases Notch
FT                                signaling pathway. Multi-ubiquitination
FT                                pattern is reduced, although it does
FT                                appear to be mono-ubiquitinated.
FT                                Interacts with MIB1. Loss of cis
FT                                interaction with NOTCH1.
FT                                {ECO:0000269|PubMed:21985982}.
FT   MUTAGEN     613    613       K->R: Highly decreases Notch signaling
FT                                pathway. Multi-ubiquitination pattern is
FT                                reduced, although it does appear to be
FT                                mono-ubiquitinated. Interacts with MIB1.
FT                                Loss of cis and trans interaction with
FT                                NOTCH1. Increases its association with
FT                                lipid raft microdomains.
FT                                {ECO:0000269|PubMed:21985982}.
FT   MUTAGEN     638    638       T->V: Not phosphorylated; when associated
FT                                with A-693 and A-696. Not phosphorylated
FT                                and doesn't prevent phosphorylation at S-
FT                                693 and S-696. Reduces NOTCH1
FT                                transactivation; when associated with A-
FT                                693 and A-696. Reduces cell surface
FT                                levels of proteins; when associated with
FT                                A-693 and A-696. Increases ectodomain
FT                                shedding; when associated with A-693 and
FT                                A-696. {ECO:0000269|PubMed:24449764}.
FT   MUTAGEN     689    689       K->R: Decreases Notch signaling pathway.
FT                                {ECO:0000269|PubMed:21985982}.
FT   MUTAGEN     693    693       S->A: Not phosphorylated; when associated
FT                                with V-638 and A-696. Not phosphorylated
FT                                and prevents phosphorylation at S-696.
FT                                Reduces NOTCH1 transactivation; when
FT                                associated with V-638 and A-696. Reduces
FT                                cell surface levels of proteins; when
FT                                associated with V-638 and A-696.
FT                                Increases ectodomain shedding; when
FT                                associated with V-638 and A-696.
FT                                {ECO:0000269|PubMed:24449764}.
FT   MUTAGEN     696    696       S->A: Not phosphorylated; when associated
FT                                with V-638 and A-693. Not phosphorylated
FT                                and doesn't prevent phosphorylation at T-
FT                                638 and S-693, Reduces NOTCH1
FT                                transactivation; when associated with V-
FT                                638 and A-693. Reduces cell surface
FT                                levels of proteins; when associated with
FT                                V-638 and A-693. Increases ectodomain
FT                                shedding; when associated with V-638 and
FT                                A-693. {ECO:0000269|PubMed:24449764}.
FT   MUTAGEN     699    699       K->R: Decreases Notch signaling pathway.
FT                                {ECO:0000269|PubMed:21985982}.
FT   MUTAGEN     713    713       K->R: Decreases Notch signaling pathway.
FT                                {ECO:0000269|PubMed:21985982}.
FT   CONFLICT    628    628       E -> K (in Ref. 1; CAA56865).
FT                                {ECO:0000305}.
SQ   SEQUENCE   722 AA;  78449 MW;  9D570B9DC7EEC75E CRC64;
     MGRRSALALA VVSALLCQVW SSGVFELKLQ EFVNKKGLLG NRNCCRGGSG PPCACRTFFR
     VCLKHYQASV SPEPPCTYGS AVTPVLGVDS FSLPDGAGID PAFSNPIRFP FGFTWPGTFS
     LIIEALHTDS PDDLATENPE RLISRLTTQR HLTVGEEWSQ DLHSSGRTDL RYSYRFVCDE
     HYYGEGCSVF CRPRDDAFGH FTCGDRGEKM CDPGWKGQYC TDPICLPGCD DQHGYCDKPG
     ECKCRVGWQG RYCDECIRYP GCLHGTCQQP WQCNCQEGWG GLFCNQDLNY CTHHKPCRNG
     ATCTNTGQGS YTCSCRPGYT GANCELEVDE CAPSPCKNGA SCTDLEDSFS CTCPPGFYGK
     VCELSAMTCA DGPCFNGGRC SDNPDGGYTC HCPLGFSGFN CEKKMDLCGS SPCSNGAKCV
     DLGNSYLCRC QAGFSGRYCE DNVDDCASSP CANGGTCRDS VNDFSCTCPP GYTGKNCSAP
     VSRCEHAPCH NGATCHQRGQ RYMCECAQGY GGPNCQFLLP EPPPGPMVVD LSERHMESQG
     GPFPWVAVCA GVVLVLLLLL GCAAVVVCVR LKLQKHQPPP EPCGGETETM NNLANCQREK
     DVSVSIIGAT QIKNTNKKAD FHGDHGAEKS SFKVRYPTVD YNLVRDLKGD EATVRDTHSK
     RDTKCQSQSS AGEEKIAPTL RGGEIPDRKR PESVYSTSKD TKYQSVYVLS AEKDECVIAT
     EV
//
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