ID DLL1_HUMAN Reviewed; 723 AA. AC O00548; B2RAK7; B5M0B3; Q9NU41; Q9UJV2; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 31-OCT-2006, sequence version 2. DT 13-FEB-2019, entry version 182. DE RecName: Full=Delta-like protein 1; DE AltName: Full=Drosophila Delta homolog 1; DE Short=Delta1; DE Short=H-Delta-1; DE Flags: Precursor; GN Name=DLL1; ORFNames=UNQ146/PRO172; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=10079256; DOI=10.1016/S0002-9440(10)65325-4; RA Gray G.E., Mann R.S., Mitsiadis E., Henrique D., Carcangiu M.-L., RA Banks A., Leiman J., Ward D., Ish-Horowitz D., Artavanis-Tsakonas S.; RT "Human ligands of the Notch receptor."; RL Am. J. Pathol. 154:785-794(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=10688816; RA Han W., Ye Q., Moore M.A.S.; RT "A soluble form of human Delta-like-1 inhibits differentiation of RT hematopoietic progenitor cells."; RL Blood 95:1616-1625(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=19906316; DOI=10.1186/1471-2164-10-518; RA Wang P., Yu P., Gao P., Shi T., Ma D.; RT "Discovery of novel human transcript variants by analysis of intronic RT single-block EST with polyadenylation site."; RL BMC Genomics 10:518-518(2009). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Oda T., Chandrasekharappa S.C.; RT "Human Delta 1 gene sequence."; RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics assessment."; RL Genome Res. 13:2265-2270(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP FUNCTION. RX PubMed=11006133; DOI=10.1006/bbrc.2000.3469; RA Shimizu K., Chiba S., Saito T., Kumano K., Hirai H.; RT "Physical interaction of Delta1, Jagged1, and Jagged2 with Notch1 and RT Notch3 receptors."; RL Biochem. Biophys. Res. Commun. 276:385-389(2000). RN [10] RP FUNCTION. RX PubMed=11581320; DOI=10.1084/jem.194.7.991; RA Jaleco A.C., Neves H., Hooijberg E., Gameiro P., Clode N., Haury M., RA Henrique D., Parreira L.; RT "Differential effects of Notch ligands Delta-1 and Jagged-1 in human RT lymphoid differentiation."; RL J. Exp. Med. 194:991-1001(2001). RN [11] RP INTERACTION WITH MAGI1; MAGI2; MAGI3 AND MPDZ. RX PubMed=15509766; DOI=10.1242/dev.01417; RA Wright G.J., Leslie J.D., Ariza-McNaughton L., Lewis J.; RT "Delta proteins and MAGI proteins: an interaction of Notch ligands RT with intracellular scaffolding molecules and its significance for RT zebrafish development."; RL Development 131:5659-5669(2004). RN [12] RP INTERACTION WITH SYNJ2BP. RX PubMed=24025447; DOI=10.1161/CIRCRESAHA.113.301686; RA Adam M.G., Berger C., Feldner A., Yang W.J., Wuestehube-Lausch J., RA Herberich S.E., Pinder M., Gesierich S., Hammes H.P., Augustin H.G., RA Fischer A.; RT "Synaptojanin-2 binding protein stabilizes the Notch ligands DLL1 and RT DLL4 and inhibits sprouting angiogenesis."; RL Circ. Res. 113:1206-1218(2013). RN [13] RP INTERACTION WITH NOTCH2NLB. RX PubMed=29856955; DOI=10.1016/j.cell.2018.03.067; RA Suzuki I.K., Gacquer D., Van Heurck R., Kumar D., Wojno M., Bilheu A., RA Herpoel A., Lambert N., Cheron J., Polleux F., Detours V., RA Vanderhaeghen P.; RT "Human-specific NOTCH2NL genes expand cortical neurogenesis through RT Delta/Notch regulation."; RL Cell 173:1370-1384(2018). 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 CC (PubMed:11006133). Following transinteraction, ligand cells CC produce mechanical force that depends of a clathrin-mediated CC endocytosis, requiring ligand ubiquitination, EPN1 interaction, CC and actin polymerisation; these events promote Notch receptor CC extracellular domain (NECD) transendocytosis and triggers Notch CC signaling through induction of cleavage, hyperphosphorylation, and CC nuclear accumulation of the intracellular domain of Notch CC receptors (NICD) (By similarity). 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:11581320). Plays a role in brain development at different CC level, namely by regulating neuronal differentiation of neural CC precursor cells via cell-cell interaction, most likely through the CC lateral inhibitory system in an endogenous level dependent-manner. CC During neocortex development, Dll1-Notch signaling transmission is CC mediated by dynamic interactions between intermediate neurogenic CC progenitors and radial glia; the cell-cell interactions are CC mediated via dynamic and transient elongation processes, likely to CC reactivate/maintain Notch activity in neighboring progenitors, and CC coordinate progenitor cell division and differentiation across CC radial and zonal boundaries. During cerebellar development, CC regulates Bergmann glial monolayer formation and its morphological CC maturation through a Notch signaling pathway. At the retina and CC spinal cord level, regulates neurogenesis by preventing the CC premature differentiation of neural progenitors and also by CC maintaining progenitors in spinal cord through Notch signaling CC pathway. Also controls neurogenesis of the neural tube in a CC progenitor domain-specific fashion along the dorsoventral axis. 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. Plays a role in immune CC systeme development, namely the development of all T-cells and CC marginal zone (MZ) B-cells (By similarity). Blocks the CC differentiation of progenitor cells into the B-cell lineage while CC promoting the emergence of a population of cells with the CC characteristics of a T-cell/NK-cell precursor (PubMed:11581320). CC Also plays a role during muscle development. During early CC development, inhibits myoblasts differentiation from the medial CC dermomyotomal lip and later regulates progenitor cell CC differentiation. Directly modulates cell adhesion and basal lamina CC formation in satellite cells through Notch signaling. Maintains CC myogenic progenitors pool by suppressing differentiation through CC down-regulation of MYOD1 and is required for satellite cell homing CC and PAX7 expression. 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. Also plays a role during pancreatic cell CC development. During type B pancreatic cell development, may be CC involved in the initiation of proximodistal patterning in the CC early pancreatic epithelium. Stimulates multipotent pancreatic CC progenitor cells proliferation and pancreatic growth by CC maintaining HES1 expression and PTF1A protein levels. During fetal CC stages of development, is required to maintain arterial identity CC and the responsiveness of arterial endothelial cells for VEGFA CC through regulation of KDR activation and NRP1 expression. Controls CC sprouting angiogenesis and subsequent vertical branch formation CC througth regulation on tip cell differentiation. Negatively CC regulates goblet cell differentiation in intestine and controls CC secretory fat commitment through lateral inhibition in small CC intestine. Plays a role during inner ear development; negatively CC regulates auditory hair cell differentiation. Plays a role during CC nephron development through Notch signaling pathway. Regulates CC growth, blood pressure and energy homeostasis (By similarity). CC {ECO:0000250|UniProtKB:P97677, ECO:0000250|UniProtKB:Q61483, CC ECO:0000269|PubMed:11006133, ECO:0000269|PubMed:11581320}. CC -!- SUBUNIT: Homodimer. Interacts with TJP1. Interacts with MAGI1 (via CC PDZ domain); forms a complex with CTNNB1 and CDH2 and promotes CC recruitment to the adherens junction and stabilization on the cell CC surface. Interacts with PSEN1; undergoes a presenilin-dependent CC gamma-secretase cleavage that releases a Dll1-intracellular form. CC Interacts with MFAP5. Interacts with MIB1. Interacts with NEURL1B; CC leads to ubiquitination. Interacts with NEURL1 (By similarity). CC Interacts with SYNJ2BP; enhances DLL1 protein stability, and CC promotes Notch signaling in endothelial cells (PubMed:24025447). CC Interacts with MAGI1, MAGI2, MAGI3 and MPDZ (PubMed:15509766). 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) (PubMed:15509766, PubMed:24025447). Interacts with CC NOTCH2NLB; leading to promote Notch signaling pathway in a cell- CC autonomous manner through inhibition of cis DLL1-NOTCH2 CC interactions (PubMed:29856955). {ECO:0000250|UniProtKB:P97677, CC ECO:0000250|UniProtKB:Q61483, ECO:0000269|PubMed:15509766, CC ECO:0000269|PubMed:24025447, ECO:0000269|PubMed:29856955}. CC -!- SUBCELLULAR LOCATION: Apical cell membrane CC {ECO:0000250|UniProtKB:Q61483}; Single-pass type I membrane CC protein {ECO:0000250|UniProtKB:Q61483}. Cell junction, adherens CC junction {ECO:0000250|UniProtKB:Q61483}. Membrane raft CC {ECO:0000250|UniProtKB:Q61483}. Note=Distributed around adherens CC junction in the apical endfeet through interactions with MAGI1. CC {ECO:0000250|UniProtKB:Q61483}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O00548-1; Sequence=Displayed; CC Name=2; CC IsoId=O00548-2; Sequence=VSP_057186, VSP_057187; CC -!- TISSUE SPECIFICITY: Expressed in heart and pancreas, with lower CC expression in brain and muscle and almost no expression in CC placenta, lung, liver and kidney. CC -!- PTM: Ubiquitinated by MIB (MIB1 or MIB2), leading to its CC endocytosis and subsequent degradation (By similarity). CC Ubiquitinated; promotes recycling back to the plasma membrane and CC confers a strong affinity for NOTCH1. Multi-ubiquitination of LYS- CC 613 by MIB1 promotes both cis and trans-interaction with NOTCH1, CC as well as activation of Notch signaling. Ubiquitinated by NEURL1B CC (By similarity). {ECO:0000250|UniProtKB:P10041, CC ECO:0000250|UniProtKB:Q61483}. CC -!- PTM: Phosphorylated in a membrane association-dependent manner. CC Phosphorylation at Ser-697 requires the presence of Ser-694, CC whereas phosphorylation at Ser-694 occurs independently of the CC other site. Phosphorylation is required for full ligand activity CC in vitro and affects surface presentation, ectodomain shedding, CC and endocytosis. {ECO:0000250|UniProtKB:Q61483}. CC -!- PTM: O-fucosylated. Can be elongated to a disaccharide by MFNG. CC {ECO:0000250|UniProtKB:P97677}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AF003522; AAB61286.1; -; mRNA. DR EMBL; AF196571; AAF05834.1; -; mRNA. DR EMBL; EU927387; ACH57449.1; -; mRNA. DR EMBL; AF222310; AAG09716.1; -; Genomic_DNA. DR EMBL; AY358892; AAQ89251.1; -; mRNA. DR EMBL; AK314234; BAG36904.1; -; mRNA. DR EMBL; AL078605; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW47425.1; -; Genomic_DNA. DR CCDS; CCDS5313.1; -. [O00548-1] DR RefSeq; NP_005609.3; NM_005618.3. [O00548-1] DR UniGene; Hs.379912; -. DR PDB; 4XBM; X-ray; 3.20 A; A/B=21-545. DR PDBsum; 4XBM; -. DR ProteinModelPortal; O00548; -. DR SMR; O00548; -. DR BioGrid; 118391; 6. DR CORUM; O00548; -. DR IntAct; O00548; 1. DR STRING; 9606.ENSP00000355718; -. DR iPTMnet; O00548; -. DR PhosphoSitePlus; O00548; -. DR BioMuta; DLL1; -. DR EPD; O00548; -. DR PaxDb; O00548; -. DR PeptideAtlas; O00548; -. DR PRIDE; O00548; -. DR ProteomicsDB; 47965; -. DR DNASU; 28514; -. DR Ensembl; ENST00000366756; ENSP00000355718; ENSG00000198719. [O00548-1] DR Ensembl; ENST00000616526; ENSP00000480905; ENSG00000275555. [O00548-1] DR GeneID; 28514; -. DR KEGG; hsa:28514; -. DR UCSC; uc003qxm.4; human. [O00548-1] DR CTD; 28514; -. DR DisGeNET; 28514; -. DR EuPathDB; HostDB:ENSG00000198719.8; -. DR GeneCards; DLL1; -. DR GeneReviews; DLL1; -. DR HGNC; HGNC:2908; DLL1. DR HPA; HPA078298; -. DR MalaCards; DLL1; -. DR MIM; 606582; gene. DR neXtProt; NX_O00548; -. DR OpenTargets; ENSG00000198719; -. DR Orphanet; 93925; Alobar holoprosencephaly. DR Orphanet; 93924; Lobar holoprosencephaly. DR Orphanet; 280200; Microform holoprosencephaly. DR Orphanet; 93926; Midline interhemispheric variant of holoprosencephaly. DR Orphanet; 220386; Semilobar holoprosencephaly. DR Orphanet; 280195; Septopreoptic holoprosencephaly. DR PharmGKB; PA27364; -. DR eggNOG; ENOG410IR7B; Eukaryota. DR eggNOG; ENOG410XUNS; LUCA. DR GeneTree; ENSGT00940000159781; -. DR HOGENOM; HOG000267024; -. DR HOVERGEN; HBG007139; -. DR InParanoid; O00548; -. DR KO; K06051; -. DR OMA; DKPCHQG; -. DR OrthoDB; 406049at2759; -. DR PhylomeDB; O00548; -. DR TreeFam; TF351835; -. DR Reactome; R-HSA-2122948; Activated NOTCH1 Transmits Signal to the Nucleus. DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants. DR Reactome; R-HSA-2660826; Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant. DR Reactome; R-HSA-2691232; Constitutive Signaling by NOTCH1 HD Domain Mutants. DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants. DR Reactome; R-HSA-2979096; NOTCH2 Activation and Transmission of Signal to the Nucleus. DR Reactome; R-HSA-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus. DR Reactome; R-HSA-9022702; MECP2 regulates transcription of neuronal ligands. DR SignaLink; O00548; -. DR SIGNOR; O00548; -. DR ChiTaRS; DLL1; human. DR GeneWiki; Delta-like_1; -. DR GenomeRNAi; 28514; -. DR PRO; PR:O00548; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; ENSG00000198719; Expressed in 178 organ(s), highest expression level in spleen. DR ExpressionAtlas; O00548; baseline and differential. DR Genevisible; O00548; HS. DR GO; GO:0005912; C:adherens junction; ISS:UniProtKB. DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl. DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB. DR GO; GO:0005887; C:integral component of plasma membrane; NAS:UniProtKB. DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. 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; IEA:Ensembl. DR GO; GO:0030957; F:Tat protein binding; IPI:UniProtKB. DR GO; GO:0014002; P:astrocyte development; ISS:UniProtKB. DR GO; GO:0030154; P:cell differentiation; TAS:UniProtKB. DR GO; GO:0001709; P:cell fate determination; NAS:UniProtKB. DR GO; GO:0021688; P:cerebellar molecular layer formation; ISS:UniProtKB. DR GO; GO:0021693; P:cerebellar Purkinje cell layer structural organization; ISS:UniProtKB. DR GO; GO:0072583; P:clathrin-dependent endocytosis; ISS:UniProtKB. DR GO; GO:0007386; P:compartment pattern specification; IEA:Ensembl. DR GO; GO:0007368; P:determination of left/right symmetry; ISS:BHF-UCL. DR GO; GO:0097102; P:endothelial tip cell fate specification; ISS:UniProtKB. DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB. DR GO; GO:0001947; P:heart looping; ISS:BHF-UCL. DR GO; GO:0030097; P:hemopoiesis; NAS:UniProtKB. DR GO; GO:0048839; P:inner ear development; IEA:Ensembl. DR GO; GO:0046331; P:lateral inhibition; ISS:UniProtKB. DR GO; GO:0070986; P:left/right axis specification; IEA:Ensembl. DR GO; GO:0072070; P:loop of Henle development; IEA:Ensembl. DR GO; GO:0002315; P:marginal zone B cell differentiation; ISS:UniProtKB. DR GO; GO:2000726; P:negative regulation of cardiac muscle cell differentiation; IEA:Ensembl. DR GO; GO:0045596; P:negative regulation of cell differentiation; ISS:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB. DR GO; GO:0045605; P:negative regulation of epidermal cell differentiation; ISS:UniProtKB. DR GO; GO:0030857; P:negative regulation of epithelial cell differentiation; ISS:UniProtKB. DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; ISS:UniProtKB. DR GO; GO:0045608; P:negative regulation of inner ear auditory receptor cell differentiation; IEA:Ensembl. DR GO; GO:0032693; P:negative regulation of interleukin-10 production; IMP:UniProtKB. DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; IEA:Ensembl. DR GO; GO:0045662; P:negative regulation of myoblast differentiation; ISS:UniProtKB. DR GO; GO:0045665; P:negative regulation of neuron differentiation; ISS:UniProtKB. DR GO; GO:0072006; P:nephron development; ISS:UniProtKB. DR GO; GO:0048665; P:neuron fate specification; ISS:UniProtKB. DR GO; GO:0097150; P:neuronal stem cell population maintenance; IEP:UniProtKB. 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; ISS:UniProtKB. DR GO; GO:0035265; P:organ growth; ISS:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB. DR GO; GO:0045807; P:positive regulation of endocytosis; ISS:UniProtKB. DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; ISS:UniProtKB. DR GO; GO:0048633; P:positive regulation of skeletal muscle tissue growth; ISS:UniProtKB. DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL. DR GO; GO:0072014; P:proximal tubule development; IEA:Ensembl. DR GO; GO:0009954; P:proximal/distal pattern formation; ISS:UniProtKB. DR GO; GO:0008217; P:regulation of blood pressure; ISS:UniProtKB. DR GO; GO:0030155; P:regulation of cell adhesion; TAS:UniProtKB. DR GO; GO:0051302; P:regulation of cell division; ISS:UniProtKB. DR GO; GO:0040008; P:regulation of growth; ISS:UniProtKB. DR GO; GO:0050767; P:regulation of neurogenesis; ISS:UniProtKB. DR GO; GO:0048631; P:regulation of skeletal muscle tissue growth; ISS:UniProtKB. DR GO; GO:0014807; P:regulation of somitogenesis; ISS:UniProtKB. DR GO; GO:1900746; P:regulation of vascular endothelial growth factor signaling pathway; ISS:UniProtKB. DR GO; GO:0060041; P:retina development in camera-type eye; ISS:UniProtKB. DR GO; GO:0060042; P:retina morphogenesis in camera-type eye; ISS:UniProtKB. DR GO; GO:0048630; P:skeletal muscle tissue growth; ISS:UniProtKB. DR GO; GO:0098773; P:skin epidermis development; ISS:UniProtKB. DR GO; GO:0001757; P:somite specification; IEA:Ensembl. DR GO; GO:0001756; P:somitogenesis; ISS:UniProtKB. DR GO; GO:0021510; P:spinal cord development; ISS:UniProtKB. DR GO; GO:0003323; P:type B pancreatic cell development; ISS: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; 5. 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; 2. 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; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell junction; Cell membrane; KW Complete proteome; Developmental protein; Differentiation; KW Disulfide bond; EGF-like domain; Glycoprotein; Isopeptide bond; KW Membrane; Notch signaling pathway; Phosphoprotein; Polymorphism; KW Reference proteome; Repeat; Signal; Transmembrane; KW Transmembrane helix; Ubl conjugation. FT SIGNAL 1 17 {ECO:0000255}. FT CHAIN 18 723 Delta-like protein 1. FT /FTId=PRO_0000007506. FT TOPO_DOM 18 545 Extracellular. {ECO:0000255}. FT TRANSMEM 546 568 Helical. {ECO:0000255}. FT TOPO_DOM 569 723 Cytoplasmic. {ECO:0000255}. FT DOMAIN 177 221 DSL. {ECO:0000255|PROSITE- FT ProRule:PRU00377}. FT DOMAIN 226 254 EGF-like 1. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 257 285 EGF-like 2. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 292 325 EGF-like 3. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 332 363 EGF-like 4; calcium-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DOMAIN 370 402 EGF-like 5. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 409 440 EGF-like 6. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT DOMAIN 447 478 EGF-like 7; calcium-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00076}. FT DOMAIN 485 516 EGF-like 8. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT REGION 720 723 Interaction with MAGI1. FT {ECO:0000250|UniProtKB:Q61483}. FT MOD_RES 694 694 Phosphoserine; by PKB. FT {ECO:0000250|UniProtKB:Q61483}. FT MOD_RES 697 697 Phosphoserine. FT {ECO:0000250|UniProtKB:Q61483}. FT CARBOHYD 477 477 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 179 188 {ECO:0000250}. FT DISULFID 192 204 {ECO:0000250}. FT DISULFID 212 221 {ECO:0000250}. FT DISULFID 226 237 {ECO:0000250}. FT DISULFID 230 243 {ECO:0000250}. FT DISULFID 245 254 {ECO:0000250}. FT DISULFID 257 268 {ECO:0000250}. FT DISULFID 263 274 {ECO:0000250}. FT DISULFID 276 285 {ECO:0000250}. FT DISULFID 292 304 {ECO:0000250}. FT DISULFID 298 314 {ECO:0000250}. FT DISULFID 316 325 {ECO:0000250}. FT DISULFID 332 343 {ECO:0000250}. FT DISULFID 337 352 {ECO:0000250}. FT DISULFID 354 363 {ECO:0000250}. FT DISULFID 370 381 {ECO:0000250}. FT DISULFID 375 391 {ECO:0000250}. FT DISULFID 393 402 {ECO:0000250}. FT DISULFID 409 420 {ECO:0000250}. FT DISULFID 414 429 {ECO:0000250}. FT DISULFID 431 440 {ECO:0000250}. FT DISULFID 447 458 {ECO:0000250}. FT DISULFID 452 467 {ECO:0000250}. FT DISULFID 469 478 {ECO:0000250}. FT DISULFID 485 496 {ECO:0000250}. FT DISULFID 490 505 {ECO:0000250}. FT DISULFID 507 516 {ECO:0000250}. FT CROSSLNK 613 613 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000250|UniProtKB:Q61483}. FT VAR_SEQ 224 247 PICLPGCDEQHGFCDKPGECKCRV -> RESLGRHRWLTRP FT RTRTTRRDGAS (in isoform 2). FT {ECO:0000303|PubMed:19906316}. FT /FTId=VSP_057186. FT VAR_SEQ 248 723 Missing (in isoform 2). FT {ECO:0000303|PubMed:19906316}. FT /FTId=VSP_057187. FT VARIANT 444 444 V -> M (in dbSNP:rs16901311). FT /FTId=VAR_048976. FT CONFLICT 498 498 E -> Q (in Ref. 2; AAF05834). FT {ECO:0000305}. FT CONFLICT 502 502 R -> G (in Ref. 1; AAB61286, 2; AAF05834 FT and 3; AAG09716). {ECO:0000305}. FT CONFLICT 510 510 G -> S (in Ref. 2; AAF05834). FT {ECO:0000305}. FT STRAND 23 30 {ECO:0000244|PDB:4XBM}. FT STRAND 57 66 {ECO:0000244|PDB:4XBM}. FT STRAND 78 83 {ECO:0000244|PDB:4XBM}. FT STRAND 88 91 {ECO:0000244|PDB:4XBM}. FT STRAND 108 112 {ECO:0000244|PDB:4XBM}. FT STRAND 118 128 {ECO:0000244|PDB:4XBM}. FT STRAND 143 152 {ECO:0000244|PDB:4XBM}. FT STRAND 156 166 {ECO:0000244|PDB:4XBM}. FT STRAND 169 179 {ECO:0000244|PDB:4XBM}. FT STRAND 183 185 {ECO:0000244|PDB:4XBM}. FT STRAND 195 197 {ECO:0000244|PDB:4XBM}. FT STRAND 200 204 {ECO:0000244|PDB:4XBM}. FT STRAND 206 208 {ECO:0000244|PDB:4XBM}. FT STRAND 210 212 {ECO:0000244|PDB:4XBM}. FT STRAND 216 218 {ECO:0000244|PDB:4XBM}. FT STRAND 232 236 {ECO:0000244|PDB:4XBM}. FT STRAND 249 254 {ECO:0000244|PDB:4XBM}. FT STRAND 265 267 {ECO:0000244|PDB:4XBM}. FT STRAND 280 285 {ECO:0000244|PDB:4XBM}. FT STRAND 287 289 {ECO:0000244|PDB:4XBM}. FT HELIX 292 295 {ECO:0000244|PDB:4XBM}. FT STRAND 303 306 {ECO:0000244|PDB:4XBM}. FT STRAND 308 310 {ECO:0000244|PDB:4XBM}. FT STRAND 312 315 {ECO:0000244|PDB:4XBM}. FT TURN 322 325 {ECO:0000244|PDB:4XBM}. FT TURN 331 334 {ECO:0000244|PDB:4XBM}. FT STRAND 342 346 {ECO:0000244|PDB:4XBM}. FT STRAND 349 353 {ECO:0000244|PDB:4XBM}. FT STRAND 358 362 {ECO:0000244|PDB:4XBM}. FT STRAND 365 367 {ECO:0000244|PDB:4XBM}. FT STRAND 380 383 {ECO:0000244|PDB:4XBM}. FT STRAND 385 387 {ECO:0000244|PDB:4XBM}. FT STRAND 389 392 {ECO:0000244|PDB:4XBM}. FT STRAND 399 402 {ECO:0000244|PDB:4XBM}. FT HELIX 408 411 {ECO:0000244|PDB:4XBM}. FT STRAND 419 422 {ECO:0000244|PDB:4XBM}. FT STRAND 427 430 {ECO:0000244|PDB:4XBM}. SQ SEQUENCE 723 AA; 78056 MW; 094B8F235DFD899D CRC64; MGSRCALALA VLSALLCQVW SSGVFELKLQ EFVNKKGLLG NRNCCRGGAG PPPCACRTFF RVCLKHYQAS VSPEPPCTYG SAVTPVLGVD SFSLPDGGGA DSAFSNPIRF PFGFTWPGTF SLIIEALHTD SPDDLATENP ERLISRLATQ RHLTVGEEWS QDLHSSGRTD LKYSYRFVCD EHYYGEGCSV FCRPRDDAFG HFTCGERGEK VCNPGWKGPY CTEPICLPGC DEQHGFCDKP GECKCRVGWQ GRYCDECIRY PGCLHGTCQQ PWQCNCQEGW GGLFCNQDLN YCTHHKPCKN GATCTNTGQG SYTCSCRPGY TGATCELGID ECDPSPCKNG GSCTDLENSY SCTCPPGFYG KICELSAMTC ADGPCFNGGR CSDSPDGGYS CRCPVGYSGF NCEKKIDYCS SSPCSNGAKC VDLGDAYLCR CQAGFSGRHC DDNVDDCASS PCANGGTCRD GVNDFSCTCP PGYTGRNCSA PVSRCEHAPC HNGATCHERG HRYVCECARG YGGPNCQFLL PELPPGPAVV DLTEKLEGQG GPFPWVAVCA GVILVLMLLL GCAAVVVCVR LRLQKHRPPA DPCRGETETM NNLANCQREK DISVSIIGAT QIKNTNKKAD FHGDHSADKN GFKARYPAVD YNLVQDLKGD DTAVRDAHSK RDTKCQPQGS SGEEKGTPTT LRGGEASERK RPDSGCSTSK DTKYQSVYVI SEEKDECVIA TEV //