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Protein

Delta-like protein 1

Gene

Dll1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner (PubMed:21985982, PubMed:10958687). Following transinteraction, ligand cells produce mechanical force that depends of a clathrin-mediated endocytosis, requiring ligand ubiquitination, EPN1 interaction, and actin polymerisation; these events promote Notch receptor extracellular domain (NECD) transendocytosis and triggers Notch signaling through induction of cleavage, hyperphosphorylation, and nuclear accumulation of the intracellular domain of Notch receptors (NICD) (PubMed:10958687, PubMed:18676613). Is required for embryonic development and maintenance of adult stem cells in many different tissues and immune systeme; the DLL1-induced Notch signaling is mediated through an intercellular communication that regulates cell lineage, cell specification, cell patterning and morphogenesis through effects on differentiation and proliferation (PubMed:17194759, PubMed:19562077, PubMed:18997111, PubMed:23695674, PubMed:16495313, PubMed:21238454, PubMed:22282195, PubMed:7671806, PubMed:17960184, PubMed:22529374, PubMed:19389377, PubMed:23699523, PubMed:19144989, PubMed:23688253, PubMed:23806616, PubMed:26114479, PubMed:22940113, PubMed:25220152, PubMed:20081190, PubMed:21572390, PubMed:22096075). Plays a role in brain development at different level, namely by regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner (PubMed:7671806, PubMed:18997111). During neocortex development, Dll1-Notch signaling transmission is mediated by dynamic interactions between intermediate neurogenic progenitors and radial glia; the cell-cell interactions are mediated via dynamic and transient elongation processes, likely to reactivate/maintain Notch activity in neighboring progenitors, and coordinate progenitor cell division and differentiation across radial and zonal boundaries (PubMed:23699523). During cerebellar development, regulates Bergmann glial monolayer formation and its morphological maturation through a Notch signaling pathway (PubMed:23688253). At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway (PubMed:19389377, PubMed:26114479). Also controls neurogenesis of the neural tube in a progenitor domain-specific fashion along the dorsoventral axis (PubMed:20081190). Maintains quiescence of neural stem cells and plays a role as a fate determinant that segregates asymmetrically to one daughter cell during neural stem cells mitosis, resulting in neuronal differentiation in Dll1-inheriting cell (PubMed:23695674). Plays a role in immune systeme development, namely the development of all T cells and marginal zone (MZ) B cells (PubMed:15146182, PubMed:19217325). Blocks the differentiation of progenitor cells into the B-cell lineage while promoting the emergence of a population of cells with the characteristics of a T-cell/NK-cell precursor (By similarity). Upon MMP14 cleavage, negatively regulates Notch signaling in haematopoietic progenitor cells to specifically maintain normal B-cell development in bone marrow (PubMed:21572390). Also plays a role during muscle development. During early development, inhibits myoblasts differentiation from the medial dermomyotomal lip and later regulates progenitor cell differentiation (PubMed:17194759). Directly modulates cell adhesion and basal lamina formation in satellite cells through Notch signaling. Maintains myogenic progenitors pool by suppressing differentiation through down-regulation of MYOD1 and is required for satellite cell homing and PAX7 expression (PubMed:22940113). During craniofacial and trunk myogenesis suppresses differentiation of cranial mesoderm-derived and somite-derived muscle via MYOD1 regulation but in cranial mesoderm-derived progenitors, is neither required for satellite cell homing nor for PAX7 expression (PubMed:25220152). Also plays a role during pancreatic cell development. During type B pancreatic cell development, may be involved in the initiation of proximodistal patterning in the early pancreatic epithelium (PubMed:22529374). Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels (PubMed:22096075). During fetal stages of development, is required to maintain arterial identity and the responsiveness of arterial endothelial cells for VEGFA through regulation of KDR activation and NRP1 expression (PubMed:19144989). Controls sprouting angiogenesis and subsequent vertical branch formation througth regulation on tip cell differentiation (PubMed:22282195). Negatively regulates goblet cell differentiation in intestine and controls secretory fat commitment through lateral inhibition in small intestine (PubMed:21238454, PubMed:21915337). Plays a role during inner ear development; negatively regulates auditory hair cell differentiation (PubMed:16495313). Plays a role during nephron development through Notch signaling pathway (PubMed:23806616). Regulates growth, blood pressure and energy homeostasis (PubMed:19562077).By similarity27 Publications

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • Notch binding Source: UniProtKB
  • scaffold protein binding Source: UniProtKB
  • Tat protein binding Source: MGI

GO - Biological processi

  • astrocyte development Source: UniProtKB
  • auditory receptor cell differentiation Source: UniProtKB
  • auditory receptor cell fate commitment Source: UniProtKB
  • cell-cell signaling Source: MGI
  • cerebellar molecular layer formation Source: UniProtKB
  • cerebellar Purkinje cell layer structural organization Source: UniProtKB
  • clathrin-mediated endocytosis Source: UniProtKB
  • compartment pattern specification Source: MGI
  • determination of left/right symmetry Source: MGI
  • endothelial tip cell fate specification Source: UniProtKB
  • heart looping Source: BHF-UCL
  • inner ear development Source: MGI
  • inner ear morphogenesis Source: UniProtKB
  • in utero embryonic development Source: UniProtKB
  • lateral inhibition Source: UniProtKB
  • left/right axis specification Source: BHF-UCL
  • loop of Henle development Source: UniProtKB
  • marginal zone B cell differentiation Source: UniProtKB
  • negative regulation of auditory receptor cell differentiation Source: MGI
  • negative regulation of cell differentiation Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of epidermal cell differentiation Source: UniProtKB
  • negative regulation of epithelial cell differentiation Source: UniProtKB
  • negative regulation of glial cell apoptotic process Source: UniProtKB
  • negative regulation of interleukin-10 production Source: MGI
  • negative regulation of myeloid cell differentiation Source: MGI
  • negative regulation of myoblast differentiation Source: UniProtKB
  • negative regulation of neuron differentiation Source: UniProtKB
  • nephron development Source: UniProtKB
  • nervous system development Source: UniProtKB
  • neuronal stem cell population maintenance Source: UniProtKB
  • neuron fate specification Source: UniProtKB
  • Notch signaling involved in heart development Source: BHF-UCL
  • Notch signaling pathway Source: UniProtKB
  • Notch signaling pathway involved in arterial endothelial cell fate commitment Source: UniProtKB
  • odontogenesis of dentin-containing tooth Source: UniProtKB
  • organ growth Source: UniProtKB
  • organ morphogenesis Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of endocytosis Source: UniProtKB
  • positive regulation of gene expression Source: MGI
  • positive regulation of Notch signaling pathway Source: UniProtKB
  • positive regulation of skeletal muscle tissue growth Source: UniProtKB
  • positive regulation of sprouting angiogenesis Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • proximal/distal pattern formation Source: UniProtKB
  • proximal tubule development Source: UniProtKB
  • regulation of blood pressure Source: UniProtKB
  • regulation of cell adhesion Source: UniProtKB
  • regulation of cell division Source: UniProtKB
  • regulation of energy homeostasis Source: UniProtKB
  • regulation of growth Source: UniProtKB
  • regulation of neurogenesis Source: UniProtKB
  • regulation of skeletal muscle tissue growth Source: UniProtKB
  • regulation of somitogenesis Source: UniProtKB
  • regulation of vascular endothelial growth factor signaling pathway Source: UniProtKB
  • retina development in camera-type eye Source: UniProtKB
  • retina morphogenesis in camera-type eye Source: UniProtKB
  • skeletal muscle tissue growth Source: UniProtKB
  • skin epidermis development Source: UniProtKB
  • somite specification Source: MGI
  • somitogenesis Source: UniProtKB
  • spinal cord development Source: UniProtKB
  • type B pancreatic cell development Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Notch signaling pathway

Enzyme and pathway databases

ReactomeiR-MMU-1980148. Signaling by NOTCH3.
R-MMU-1980150. Signaling by NOTCH4.

Names & Taxonomyi

Protein namesi
Recommended name:
Delta-like protein 1Curated
Alternative name(s):
Drosophila Delta homolog 1
Short name:
Delta11 Publication
Cleaved into the following 3 chains:
Dll1-soluble form1 Publication
Short name:
Dll1-EC1 Publication
Short name:
Shed form1 Publication
Dll1-derived cell-associated form1 Publication
Short name:
Dll1-TMIC1 Publication
Short name:
Membrane-associated fragment1 Publication
Dll1-intracellular form1 Publication
Short name:
Dll1-IC1 Publication
Gene namesi
Name:Dll1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:104659. Dll1.

Subcellular locationi

Dll1-derived cell-associated form :
Dll1-intracellular form :

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini18 – 545528ExtracellularSequence analysisAdd
BLAST
Transmembranei546 – 56823HelicalSequence analysisAdd
BLAST
Topological domaini569 – 722154CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • adherens junction Source: UniProtKB
  • apical plasma membrane Source: UniProtKB
  • cytoplasmic vesicle Source: MGI
  • integral component of membrane Source: UniProtKB-KW
  • membrane raft Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Heterozygous Dll1 mice mutants are lighter and smaller, with altered fat to lean ratio and have increased blood pressure and a slight bradycardia. The animals have reduced cholesterol and triglyceride levels in blood (PubMed:19562077). Heterozygous Dll1 mice mutants and hypomorphic Dll1 mice mutants survive until birth, despite significantly reduced Notch activity (PubMed:17194759). Conditional knockout in inner ear leads to an early and excessive production of hair cells and have vestibular defects (PubMed:16495313). Conditional knockout in a small proportion of neural precursor cells reduces neurogenesis, whereas conditional knockout in a large proportion promotes premature neurogenesis (PubMed:18997111). Hypomorph Dll1 pups mutant survive until birth but are smaller. Conditional knockout Dll1 mice mutant in epidermis, survive and have no gross abnormalities (PubMed:17960184). Hypomorph Dll1 mice mutant survive until birth and have severe skeletal muscle defects (PubMed:19144989). Heterozygous Dll1 mutant embryos show disrupted muscle growth (PubMed:25220152). Conditional knockout Dll1 mice mutant show disorganization of Bergmann fibers, ectopic localization of Bergmann glia in the molecular layer and a reduction in the number of Bergmann glia (PubMed:23688253).8 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi613 – 6186KNTNKK → RNTNRR: Highly decreases Notch signaling pathway. Multi-ubiquitination pattern is reduced, although it does appear to be mono-ubiquitinated. Interacts with MIB1. Loss of cis interaction with NOTCH1. 1 Publication
Mutagenesisi613 – 6131K → R: Highly decreases Notch signaling pathway. Multi-ubiquitination pattern is reduced, although it does appear to be mono-ubiquitinated. Interacts with MIB1. Loss of cis and trans interaction with NOTCH1. Increases its association with lipid raft microdomains. 1 Publication
Mutagenesisi638 – 6381T → V: Not phosphorylated; when associated with A-693 and A-696. Not phosphorylated and doesn't prevent phosphorylation at S-693 and S-696. Reduces NOTCH1 transactivation; when associated with A-693 and A-696. Reduces cell surface levels of proteins; when associated with A-693 and A-696. Increases ectodomain shedding; when associated with A-693 and A-696. 1 Publication
Mutagenesisi689 – 6891K → R: Decreases Notch signaling pathway. 1 Publication
Mutagenesisi693 – 6931S → A: Not phosphorylated; when associated with V-638 and A-696. Not phosphorylated and prevents phosphorylation at S-696. Reduces NOTCH1 transactivation; when associated with V-638 and A-696. Reduces cell surface levels of proteins; when associated with V-638 and A-696. Increases ectodomain shedding; when associated with V-638 and A-696. 1 Publication
Mutagenesisi696 – 6961S → A: Not phosphorylated; when associated with V-638 and A-693. Not phosphorylated and doesn't prevent phosphorylation at T-638 and S-693, Reduces NOTCH1 transactivation; when associated with V-638 and A-693. Reduces cell surface levels of proteins; when associated with V-638 and A-693. Increases ectodomain shedding; when associated with V-638 and A-693. 1 Publication
Mutagenesisi699 – 6991K → R: Decreases Notch signaling pathway. 1 Publication
Mutagenesisi713 – 7131K → R: Decreases Notch signaling pathway. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 722Dll1-intracellular form1 PublicationPRO_0000434832
Signal peptidei1 – 1717Sequence analysisAdd
BLAST
Chaini18 – 722705Delta-like protein 1PRO_0000007507Add
BLAST
Chaini18 – 535518Dll1-soluble form1 PublicationPRO_0000434830Add
BLAST
Chaini536 – 722187Dll1-derived cell-associated form1 PublicationPRO_0000434831Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi178 ↔ 187By similarity
Disulfide bondi191 ↔ 203By similarity
Disulfide bondi211 ↔ 220By similarity
Disulfide bondi225 ↔ 236By similarity
Disulfide bondi229 ↔ 242By similarity
Disulfide bondi244 ↔ 253By similarity
Disulfide bondi256 ↔ 267By similarity
Disulfide bondi262 ↔ 273By similarity
Disulfide bondi275 ↔ 284By similarity
Disulfide bondi291 ↔ 303By similarity
Disulfide bondi297 ↔ 313By similarity
Disulfide bondi315 ↔ 324By similarity
Disulfide bondi331 ↔ 342By similarity
Disulfide bondi336 ↔ 351By similarity
Disulfide bondi353 ↔ 362By similarity
Disulfide bondi369 ↔ 380By similarity
Disulfide bondi374 ↔ 390By similarity
Disulfide bondi392 ↔ 401By similarity
Disulfide bondi408 ↔ 419By similarity
Disulfide bondi413 ↔ 428By similarity
Disulfide bondi430 ↔ 439By similarity
Disulfide bondi446 ↔ 457By similarity
Disulfide bondi451 ↔ 466By similarity
Disulfide bondi468 ↔ 477By similarity
Glycosylationi476 – 4761N-linked (GlcNAc...)Sequence analysis
Disulfide bondi484 ↔ 495By similarity
Disulfide bondi489 ↔ 504By similarity
Disulfide bondi506 ↔ 515By similarity
Cross-linki613 – 613Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei638 – 6381Phosphothreonine1 Publication
Modified residuei693 – 6931Phosphoserine; by PKB1 Publication
Modified residuei696 – 6961Phosphoserine1 Publication

Post-translational modificationi

Ubiquitinated by MIB (MIB1 or MIB2), leading to its endocytosis and subsequent degradation. Ubiquitinated; promotes recycling back to the plasma membrane and confers a strong affinity for NOTCH1 (PubMed:18676613). Multi-ubiquitination of LYS-613 by MIB1 promotes both cis and trans-interaction with NOTCH1, as well as activation of Notch signaling (PubMed:21985982). Ubiquitinated by NEURL1B (PubMed:17003037).By similarity3 Publications
Phosphorylated in a membrane association-dependent manner. Phosphorylation at Ser-696 requires the presence of Ser-693, whereas phosphorylation at Thr-638 and Ser-693 occurs independently of the other sites. Phosphorylation is required for full ligand activity in vitro and affects surface presentation, ectodomain shedding, and endocytosis.1 Publication
Cleaved by MMP14; negatively regulates DLL1-induced Notch signaling in HPCs, modulating B-lymphocyte differentiation in bone marrow (PubMed:21572390). Undergoes two consecutive processing events: a shedding event, partially by ADAM10, that generates a soluble extracellular form and an intracelular membrane-anchored form, followed by a gamma-secretase cleavage releasing an intracellular fragment (PubMed:12794186).2 Publications
O-fucosylated. Can be elongated to a disaccharide by MFNG.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei527 – 5271Cleavage; by MMP141 Publication
Sitei535 – 5362Cleavage; by ADAM protease1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ61483.
PRIDEiQ61483.

PTM databases

iPTMnetiQ61483.
PhosphoSiteiQ61483.

Miscellaneous databases

PMAP-CutDBQ6PFV7.

Expressioni

Tissue specificityi

In the embryo, expressed in the paraxial mesoderm and nervous system. Expressed at high levels in adult heart and at lower levels, in adult lung. Highly expressed in satellite cells from masseter and tongue than in satellite cells from leg and extraocular muscle.? (PubMed:25220152).2 Publications

Developmental stagei

Expressed until E15. Expression then decreases and increases again in the adult. In differentiating somites, is expressed at low levels in cells emerging from the dorsomedial lip and subsequently throughout myotomes. In the limb buds, is found in myoblasts and myocytes but not in the progenitor cells (PubMed:17194759). Highly expressed in the endothelium and in the smooth muscle layer starting at E13.5 in arterial vessels, but not in veins. At E12.5, there is no detectable expression in arteries or veins. This pattern persists until E18.5 (PubMed:19144989). Strongly expressed in developing muscle of tongue, cheek, and in extraocular muscle at E11.5. Found at E18 and P21 in head muscle (PubMed:25220152). Detected in a subset of cells in the ventricular zone (VZ), the intermediate zone (IZ) and the cortical plate (CP) of neocortex and in the ganglionic eminences at E13.5. At later stages, such as at E16.5, found in the VZ and IZ, but at very low levels in the CP of the neocortex (PubMed:18997111). Highly expressed in embryonic cells located in the ventricular zone (VZ) of the retinal neuroepithelium that form clusters; is first detected in cells located in the central retina. As the retina grows, expression spreads peripherally along the expanding neurogenic region, being always absent from the ciliary margin zone (CMZ) (PubMed:19389377).6 Publications

Inductioni

Induced by PTF1A in multipotent pancreatic progenitor cells (PubMed:22096075). Induced by CDX1 and CDX2 during somitogenesis and goblet cell differentiation (PubMed:22015720).2 Publications

Gene expression databases

BgeeiQ61483.
CleanExiMM_DLL1.
GenevisibleiQ61483. MM.

Interactioni

Subunit structurei

Homodimer (PubMed:12794186). Interacts with TJP1 (PubMed:24715457). Interacts with MMP14; inhibits DLL1-induced Notch signaling (PubMed:21572390). Interacts with MAGI1 (via PDZ domain); forms a complex with CTNNB1 and CDH2 and promotes recruitment to the adherens junction and stabilization on the cell surface (PubMed:15908431). Interacts with PSEN1; undergoes a presenilin-dependent gamma-secretase cleavage that releases a Dll1-intracellular form (PubMed:12794186). Interacts with MFAP5 (PubMed:15788413). Interacts with MIB1 (PubMed:21985982). Interacts with NEURL1B; leads to ubiquitination (PubMed:17003037, PubMed:19723503). Interacts with NEURL1 (PubMed:19723503). Interacts with SYNJ2BP; enhances DLL1 protein stability, and promotes Notch signaling in endothelial cells (By similarity). Interacts with MAGI1, MAGI2, MAGI3 and MPDZ (By similarity). Interacts (via ubiquitin) with EPN1 (via IUM domain); binding with NOTCH1 attached to neighboring cell, promotes ligand ubiquitination and EPN1 interaction, leading to NECD transendocytosis and Notch signaling (By similarity).By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Magi2Q9WVQ12EBI-297125,EBI-297151

GO - Molecular functioni

  • Notch binding Source: UniProtKB
  • scaffold protein binding Source: UniProtKB
  • Tat protein binding Source: MGI

Protein-protein interaction databases

BioGridi199232. 6 interactions.
DIPiDIP-32600N.
IntActiQ61483. 4 interactions.
MINTiMINT-8187263.
STRINGi10090.ENSMUSP00000014917.

Structurei

3D structure databases

ProteinModelPortaliQ61483.
SMRiQ61483. Positions 22-551.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini176 – 22045DSLPROSITE-ProRule annotationAdd
BLAST
Domaini225 – 25329EGF-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini256 – 28429EGF-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini291 – 32434EGF-like 3PROSITE-ProRule annotationAdd
BLAST
Domaini331 – 36232EGF-like 4; calcium-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini369 – 40133EGF-like 5PROSITE-ProRule annotationAdd
BLAST
Domaini408 – 43932EGF-like 6PROSITE-ProRule annotationAdd
BLAST
Domaini446 – 47732EGF-like 7; calcium-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini484 – 51532EGF-like 8PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni719 – 7224Interaction with MAGI11 Publication

Sequence similaritiesi

Contains 1 DSL domain.PROSITE-ProRule annotation
Contains 8 EGF-like domains.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG249767.
GeneTreeiENSGT00810000125346.
HOGENOMiHOG000267024.
HOVERGENiHBG007139.
InParanoidiQ61483.
KOiK06051.
OMAiCQREKDV.
OrthoDBiEOG7GQXZ5.
TreeFamiTF351835.

Family and domain databases

InterProiIPR001774. DSL.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR009030. Growth_fac_rcpt_.
IPR011651. Notch_ligand_N.
[Graphical view]
PfamiPF01414. DSL. 1 hit.
PF00008. EGF. 5 hits.
PF07645. EGF_CA. 1 hit.
PF07657. MNNL. 1 hit.
[Graphical view]
SMARTiSM00051. DSL. 1 hit.
SM00181. EGF. 4 hits.
SM00179. EGF_CA. 4 hits.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 1 hit.
PROSITEiPS00010. ASX_HYDROXYL. 3 hits.
PS51051. DSL. 1 hit.
PS00022. EGF_1. 8 hits.
PS01186. EGF_2. 8 hits.
PS50026. EGF_3. 7 hits.
PS01187. EGF_CA. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q61483-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRRSALALA VVSALLCQVW SSGVFELKLQ EFVNKKGLLG NRNCCRGGSG
60 70 80 90 100
PPCACRTFFR VCLKHYQASV SPEPPCTYGS AVTPVLGVDS FSLPDGAGID
110 120 130 140 150
PAFSNPIRFP FGFTWPGTFS LIIEALHTDS PDDLATENPE RLISRLTTQR
160 170 180 190 200
HLTVGEEWSQ DLHSSGRTDL RYSYRFVCDE HYYGEGCSVF CRPRDDAFGH
210 220 230 240 250
FTCGDRGEKM CDPGWKGQYC TDPICLPGCD DQHGYCDKPG ECKCRVGWQG
260 270 280 290 300
RYCDECIRYP GCLHGTCQQP WQCNCQEGWG GLFCNQDLNY CTHHKPCRNG
310 320 330 340 350
ATCTNTGQGS YTCSCRPGYT GANCELEVDE CAPSPCKNGA SCTDLEDSFS
360 370 380 390 400
CTCPPGFYGK VCELSAMTCA DGPCFNGGRC SDNPDGGYTC HCPLGFSGFN
410 420 430 440 450
CEKKMDLCGS SPCSNGAKCV DLGNSYLCRC QAGFSGRYCE DNVDDCASSP
460 470 480 490 500
CANGGTCRDS VNDFSCTCPP GYTGKNCSAP VSRCEHAPCH NGATCHQRGQ
510 520 530 540 550
RYMCECAQGY GGPNCQFLLP EPPPGPMVVD LSERHMESQG GPFPWVAVCA
560 570 580 590 600
GVVLVLLLLL GCAAVVVCVR LKLQKHQPPP EPCGGETETM NNLANCQREK
610 620 630 640 650
DVSVSIIGAT QIKNTNKKAD FHGDHGAEKS SFKVRYPTVD YNLVRDLKGD
660 670 680 690 700
EATVRDTHSK RDTKCQSQSS AGEEKIAPTL RGGEIPDRKR PESVYSTSKD
710 720
TKYQSVYVLS AEKDECVIAT EV
Length:722
Mass (Da):78,449
Last modified:July 27, 2011 - v2
Checksum:i9D570B9DC7EEC75E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti628 – 6281E → K in CAA56865 (PubMed:7671806).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80903 mRNA. Translation: CAA56865.1.
AY497019 Genomic DNA. Translation: AAR30869.1.
CH466630 Genomic DNA. Translation: EDL20466.1.
BC057400 mRNA. Translation: AAH57400.1.
BC065063 mRNA. Translation: AAH65063.1.
CCDSiCCDS37452.1.
PIRiI48324.
RefSeqiNP_031891.2. NM_007865.3.
UniGeneiMm.4875.

Genome annotation databases

EnsembliENSMUST00000014917; ENSMUSP00000014917; ENSMUSG00000014773.
GeneIDi13388.
KEGGimmu:13388.
UCSCiuc008aoi.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80903 mRNA. Translation: CAA56865.1.
AY497019 Genomic DNA. Translation: AAR30869.1.
CH466630 Genomic DNA. Translation: EDL20466.1.
BC057400 mRNA. Translation: AAH57400.1.
BC065063 mRNA. Translation: AAH65063.1.
CCDSiCCDS37452.1.
PIRiI48324.
RefSeqiNP_031891.2. NM_007865.3.
UniGeneiMm.4875.

3D structure databases

ProteinModelPortaliQ61483.
SMRiQ61483. Positions 22-551.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199232. 6 interactions.
DIPiDIP-32600N.
IntActiQ61483. 4 interactions.
MINTiMINT-8187263.
STRINGi10090.ENSMUSP00000014917.

PTM databases

iPTMnetiQ61483.
PhosphoSiteiQ61483.

Proteomic databases

MaxQBiQ61483.
PRIDEiQ61483.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000014917; ENSMUSP00000014917; ENSMUSG00000014773.
GeneIDi13388.
KEGGimmu:13388.
UCSCiuc008aoi.2. mouse.

Organism-specific databases

CTDi28514.
MGIiMGI:104659. Dll1.

Phylogenomic databases

eggNOGiNOG249767.
GeneTreeiENSGT00810000125346.
HOGENOMiHOG000267024.
HOVERGENiHBG007139.
InParanoidiQ61483.
KOiK06051.
OMAiCQREKDV.
OrthoDBiEOG7GQXZ5.
TreeFamiTF351835.

Enzyme and pathway databases

ReactomeiR-MMU-1980148. Signaling by NOTCH3.
R-MMU-1980150. Signaling by NOTCH4.

Miscellaneous databases

NextBioi283748.
PMAP-CutDBQ6PFV7.
PROiQ61483.
SOURCEiSearch...

Gene expression databases

BgeeiQ61483.
CleanExiMM_DLL1.
GenevisibleiQ61483. MM.

Family and domain databases

InterProiIPR001774. DSL.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR009030. Growth_fac_rcpt_.
IPR011651. Notch_ligand_N.
[Graphical view]
PfamiPF01414. DSL. 1 hit.
PF00008. EGF. 5 hits.
PF07645. EGF_CA. 1 hit.
PF07657. MNNL. 1 hit.
[Graphical view]
SMARTiSM00051. DSL. 1 hit.
SM00181. EGF. 4 hits.
SM00179. EGF_CA. 4 hits.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 1 hit.
PROSITEiPS00010. ASX_HYDROXYL. 3 hits.
PS51051. DSL. 1 hit.
PS00022. EGF_1. 8 hits.
PS01186. EGF_2. 8 hits.
PS50026. EGF_3. 7 hits.
PS01187. EGF_CA. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Transient and restricted expression during mouse embryogenesis of Dll1, a murine gene closely related to Drosophila Delta."
    Bettenhausen B., de Angelis M.H., Simon D., Guenet J.-L., Gossler A.
    Development 121:2407-2418(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, FUNCTION.
    Strain: C57BL/6 X BALB/c.
    Tissue: Embryo.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Embryonic brain.
  5. "MT1-MMP cleaves Dll1 to negatively regulate Notch signalling to maintain normal B-cell development."
    Jin G., Zhang F., Chan K.M., Xavier Wong H.L., Liu B., Cheah K.S., Liu X., Mauch C., Liu D., Zhou Z.
    EMBO J. 30:2281-2293(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 527-534 AND 536-543, PROTEOLYTIC CLEAVAGE BY MMP14, INTERACTION WITH MMP14, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION.
  6. "The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and gamma-secretase."
    Six E., Ndiaye D., Laabi Y., Brou C., Gupta-Rossi N., Israel A., Logeat F.
    Proc. Natl. Acad. Sci. U.S.A. 100:7638-7643(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 536-554, PROTEOLYTIC CLEAVAGE, HOMODIMERIZATION, INTERACTION WITH PSEN1, SUBCELLULAR LOCATION.
  7. "Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of Notch2."
    Shimizu K., Chiba S., Hosoya N., Kumano K., Saito T., Kurokawa M., Kanda Y., Hamada Y., Hirai H.
    Mol. Cell. Biol. 20:6913-6922(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo."
    Hozumi K., Negishi N., Suzuki D., Abe N., Sotomaru Y., Tamaoki N., Mailhos C., Ish-Horowicz D., Habu S., Owen M.J.
    Nat. Immunol. 5:638-644(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "The extracellular matrix protein MAGP-2 interacts with Jagged1 and induces its shedding from the cell surface."
    Nehring L.C., Miyamoto A., Hein P.W., Weinmaster G., Shipley J.M.
    J. Biol. Chem. 280:20349-20355(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MFAP5.
  10. "MAGI1 recruits Dll1 to cadherin-based adherens junctions and stabilizes it on the cell surface."
    Mizuhara E., Nakatani T., Minaki Y., Sakamoto Y., Ono Y., Takai Y.
    J. Biol. Chem. 280:26499-26507(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAGI1, SUBCELLULAR LOCATION.
  11. "Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear."
    Brooker R., Hozumi K., Lewis J.
    Development 133:1277-1286(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  12. Cited for: INTERACTION WITH NEURL1B, UBIQUITINATION.
  13. "Premature myogenic differentiation and depletion of progenitor cells cause severe muscle hypotrophy in Delta1 mutants."
    Schuster-Gossler K., Cordes R., Gossler A.
    Proc. Natl. Acad. Sci. U.S.A. 104:537-542(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, FUNCTION.
  14. "Selection of differentiating cells by different levels of delta-like 1 among neural precursor cells in the developing mouse telencephalon."
    Kawaguchi D., Yoshimatsu T., Hozumi K., Gotoh Y.
    Development 135:3849-3858(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
  15. "Role of the Notch ligand Delta1 in embryonic and adult mouse epidermis."
    Estrach S., Cordes R., Hozumi K., Gossler A., Watt F.M.
    J. Invest. Dermatol. 128:825-832(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  16. "The intracellular region of Notch ligands Dll1 and Dll3 regulates their trafficking and signaling activity."
    Heuss S.F., Ndiaye-Lobry D., Six E.M., Israel A., Logeat F.
    Proc. Natl. Acad. Sci. U.S.A. 105:11212-11217(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION, FUNCTION, SUBCELLULAR LOCATION.
  17. "Neuralized-2: Expression in human and rodents and interaction with Delta-like ligands."
    Rullinkov G., Tamme R., Sarapuu A., Lauren J., Sepp M., Palm K., Timmusk T.
    Biochem. Biophys. Res. Commun. 389:420-425(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NEURL1 AND NEURL1B.
  18. "DLL1-mediated Notch activation regulates endothelial identity in mouse fetal arteries."
    Soerensen I., Adams R.H., Gossler A.
    Blood 113:5680-5688(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, FUNCTION.
  19. "Dll1 and Dll4 function sequentially in the retina and pV2 domain of the spinal cord to regulate neurogenesis and create cell diversity."
    Rocha S.F., Lopes S.S., Gossler A., Henrique D.
    Dev. Biol. 328:54-65(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DEVELOPMENTAL STAGE.
  20. "Lunatic and manic fringe cooperatively enhance marginal zone B cell precursor competition for delta-like 1 in splenic endothelial niches."
    Tan J.B., Xu K., Cretegny K., Visan I., Yuan J.S., Egan S.E., Guidos C.J.
    Immunity 30:254-263(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  21. Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  22. "Domain-specific control of neurogenesis achieved through patterned regulation of Notch ligand expression."
    Marklund U., Hansson E.M., Sundstroem E., de Angelis M.H., Przemeck G.K., Lendahl U., Muhr J., Ericson J.
    Development 137:437-445(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  23. Cited for: MUTAGENESIS OF 613-LYS--LYS-618; LYS-613; LYS-689; LYS-699 AND LYS-713, INTERACTION WITH MIB1, SUBCELLULAR LOCATION, FUNCTION, UBIQUITINATION AT LYS-613.
  24. "Dll1- and dll4-mediated notch signaling are required for homeostasis of intestinal stem cells."
    Pellegrinet L., Rodilla V., Liu Z., Chen S., Koch U., Espinosa L., Kaestner K.H., Kopan R., Lewis J., Radtke F.
    Gastroenterology 140:1230-1240(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  25. "Delta1 expression, cell cycle exit, and commitment to a specific secretory fate coincide within a few hours in the mouse intestinal stem cell system."
    Stamataki D., Holder M., Hodgetts C., Jeffery R., Nye E., Spencer-Dene B., Winton D.J., Lewis J.
    PLoS ONE 6:E24484-E24484(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  26. "Extrinsic Notch ligand Delta-like 1 regulates tip cell selection and vascular branching morphogenesis."
    Napp L.C., Augustynik M., Paesler F., Krishnasamy K., Woiterski J., Limbourg A., Bauersachs J., Drexler H., Le Noble F., Limbourg F.P.
    Circ. Res. 110:530-535(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  27. "Ptf1a-mediated control of Dll1 reveals an alternative to the lateral inhibition mechanism."
    Ahnfelt-Roenne J., Joergensen M.C., Klinck R., Jensen J.N., Fuechtbauer E.M., Deering T., MacDonald R.J., Wright C.V., Madsen O.D., Serup P.
    Development 139:33-45(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION.
  28. Cited for: INDUCTION.
  29. "Colonization of the satellite cell niche by skeletal muscle progenitor cells depends on Notch signals."
    Broehl D., Vasyutina E., Czajkowski M.T., Griger J., Rassek C., Rahn H.P., Purfuerst B., Wende H., Birchmeier C.
    Dev. Cell 23:469-481(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  30. Cited for: FUNCTION.
  31. "The extracellular domain of Notch2 increases its cell-surface abundance and ligand responsiveness during kidney development."
    Liu Z., Chen S., Boyle S., Zhu Y., Zhang A., Piwnica-Worms D.R., Ilagan M.X., Kopan R.
    Dev. Cell 25:585-598(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  32. "Dynamic interactions between intermediate neurogenic progenitors and radial glia in embryonic mouse neocortex: potential role in Dll1-Notch signaling."
    Nelson B.R., Hodge R.D., Bedogni F., Hevner R.F.
    J. Neurosci. 33:9122-9139(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  33. "Delta-like 1 regulates Bergmann glial monolayer formation during cerebellar development."
    Hiraoka Y., Komine O., Nagaoka M., Bai N., Hozumi K., Tanaka K.
    Mol. Brain 6:25-25(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  34. "Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis."
    Kawaguchi D., Furutachi S., Kawai H., Hozumi K., Gotoh Y.
    Nat. Commun. 4:1880-1880(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  35. "Cadherin-based adhesions in the apical endfoot are required for active Notch signaling to control neurogenesis in vertebrates."
    Hatakeyama J., Wakamatsu Y., Nagafuchi A., Kageyama R., Shigemoto R., Shimamura K.
    Development 141:1671-1682(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TJP1, SUBCELLULAR LOCATION.
  36. "Divergent and conserved roles of Dll1 signaling in development of craniofacial and trunk muscle."
    Czajkowski M.T., Rassek C., Lenhard D.C., Broehl D., Birchmeier C.
    Dev. Biol. 395:307-316(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
  37. "S/T phosphorylation of DLL1 is required for full ligand activity in vitro but dispensable for DLL1 function in vivo during embryonic patterning and marginal zone B cell development."
    Braune E.B., Schuster-Gossler K., Lyszkiewicz M., Serth K., Preusse K., Madlung J., Macek B., Krueger A., Gossler A.
    Mol. Cell. Biol. 34:1221-1233(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT THR-638; SER-693 AND SER-696, MUTAGENESIS OF THR-638; SER-693 AND SER-696.
  38. "Context-dependent functional divergence of the Notch ligands DLL1 and DLL4 in vivo."
    Preusse K., Tveriakhina L., Schuster-Gossler K., Gaspar C., Rosa A.I., Henrique D., Gossler A., Stauber M.
    PLoS Genet. 11:E1005328-E1005328(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiDLL1_MOUSE
AccessioniPrimary (citable) accession number: Q61483
Secondary accession number(s): Q6PFV7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: April 13, 2016
This is version 154 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.