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Protein

Delta-like protein 1

Gene

Dll1

Organism
Rattus norvegicus (Rat)
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 (By similarity). 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:22658936). 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 (By similarity). 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. 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. During cerebellar development, regulates Bergmann glial monolayer formation and its morphological maturation through a Notch signaling pathway. 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. Also controls neurogenesis of the neural tube in a progenitor domain-specific fashion along the dorsoventral axis. 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. Plays a role in immune systeme development, namely the development of all T-cells and marginal zone (MZ) B cells (By similarity). 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). Also plays a role during muscle development. During early development, inhibits myoblasts differentiation from the medial dermomyotomal lip and later regulates progenitor cell differentiation. 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. 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. 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. Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels. 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. Controls sprouting angiogenesis and subsequent vertical branch formation througth regulation on tip cell differentiation. Negatively regulates goblet cell differentiation in intestine and controls secretory fat commitment through lateral inhibition in small intestine. Plays a role during inner ear development; negatively regulates auditory hair cell differentiation. Plays a role during nephron development through Notch signaling pathway. Regulates growth, blood pressure and energy homeostasis (By similarity).By similarity1 Publication

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • Notch binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Notch signaling pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Delta-like protein 1
Alternative name(s):
Drosophila Delta homolog 1
Short name:
Delta1
Gene namesi
Name:Dll1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi70949. Dll1.

Subcellular locationi

  • Apical cell membrane By similarity; Single-pass type I membrane protein By similarity
  • Cell junctionadherens junction By similarity
  • Membrane raft By similarity

  • Note: Distributed around adherens junction in the apical endfeet through interactions with MAGI1.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini18 – 537520ExtracellularSequence analysisAdd
BLAST
Transmembranei538 – 56023HelicalSequence analysisAdd
BLAST
Topological domaini561 – 714154CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717Sequence analysisAdd
BLAST
Chaini18 – 714697Delta-like protein 1PRO_0000007508Add
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-linki605 – 605Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei630 – 6301PhosphothreonineBy similarity
Modified residuei685 – 6851Phosphoserine; by PKBBy similarity
Modified residuei688 – 6881PhosphoserineBy similarity

Post-translational modificationi

Ubiquitinated by MIB (MIB1 or MIB2), leading to its endocytosis and subsequent degradation (By similarity). Ubiquitinated; promotes recycling back to the plasma membrane and confers a strong affinity for NOTCH1. Mono- and multi-ubiquitinated. Multi-ubiquitination of LYS-605 by MIB1 promotes both cis and trans-interaction with NOTCH1, as well as activation of Notch signaling. Ubiquitinated by NEURL1B (By similarity).By similarity
Phosphorylated in a membrane association-dependent manner. Phosphorylation at Ser-688 requires the presence of Ser-685, whereas phosphorylation at Thr-630 and Ser-685 occur independently of the other sites. Phosphorylation is required for full ligand activity in vitro and affects surface presentation, ectodomain shedding, and endocytosis.By similarity
O-fucosylated. Can be elongated to a disaccharide by MFNG.1 Publication

Keywords - PTMi

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

Proteomic databases

PaxDbiP97677.
PRIDEiP97677.

Interactioni

Subunit structurei

Homodimer. Interacts with TJP1. 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. Interacts with PSEN1; undergoes a presenilin-dependent gamma-secretase cleavage that releases a Dll1-intracellular form. Interacts with MFAP5. Interacts with MIB1. Interacts with NEURL1B; leads to ubiquitination. Interacts with NEURL1 (By similarity). Interacts with SYNJ2BP; enhances DLL1 protein stability, and promotes Notch signaling in endothelial cells. 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 (PubMed:22658936).By similarity1 Publication

GO - Molecular functioni

  • Notch binding Source: UniProtKB

Protein-protein interaction databases

IntActiP97677. 2 interactions.
STRINGi10116.ENSRNOP00000019934.

Structurei

3D structure databases

ProteinModelPortaliP97677.
SMRiP97677. Positions 178-326.
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
Regioni711 – 7144Interaction with MAGI1By similarity

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

eggNOGiENOG410IR7B. Eukaryota.
ENOG410XUNS. LUCA.
HOGENOMiHOG000267024.
HOVERGENiHBG007139.
InParanoidiP97677.
KOiK06051.
PhylomeDBiP97677.

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. 8 hits.
SM00179. EGF_CA. 6 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.

P97677-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRRSALALA VVSALLCQVW SSGVFELKLQ EFVNKKGLLG NRNCCRGGSG
60 70 80 90 100
PPCACRTFFR VCLKHYQASV SPEPPCTYGS AVTAVLGVDS 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
FTCGERGEKM CDPGWKGQYC TDPICLPGCD DQHGYCDKPG ECKCRVGWQG
260 270 280 290 300
RYCDECIRYP GCLHGTCQQP WQCNCQEGWG GLFCNQDLNY CTHHKPCRNG
310 320 330 340 350
ATCTNTGQGS YTCSCRPGYT GANCELEVDE CAPSPCRNGG SCTDLEDSYS
360 370 380 390 400
CTCPPGFYGK VCELSAMTCA DGPCFNGGRC SDNPDGGYTC HCPAGFSGFN
410 420 430 440 450
CEKKIDLCSS SPCSNGAKCV DLGNSYLCRC QTGFSGRYCE DNVDDCASSP
460 470 480 490 500
CANGGTCRDS VNDFSCTCPP GYTGRNCSAP VSRCEHAPCH NGATCHQRGQ
510 520 530 540 550
RYMCECAQGY GGANCQFLLP EPPPDLIVAA QGGSFPWVAV CAGVVLVLLL
560 570 580 590 600
LLGCAAVVVC VRLKLQKHQP PPDPCGGETE TMNNLANCQR EKDVSVSIIG
610 620 630 640 650
ATQIKNTNKK ADFHGDHGAD KSSFKARYPT VDYNLIRDLK GDEATVRDAH
660 670 680 690 700
SKRDTKCQSQ GSVGEEKSTS TLRGGEVPDR KRPESVYSTS KDTKYQSVYV
710
LSAEKDECVI ATEV
Length:714
Mass (Da):77,379
Last modified:May 1, 1997 - v1
Checksum:i4B8EE2272BAEA27E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U78889 mRNA. Translation: AAB37343.1.
RefSeqiNP_114452.1. NM_032063.2.
UniGeneiRn.10628.

Genome annotation databases

GeneIDi84010.
KEGGirno:84010.
UCSCiRGD:70949. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U78889 mRNA. Translation: AAB37343.1.
RefSeqiNP_114452.1. NM_032063.2.
UniGeneiRn.10628.

3D structure databases

ProteinModelPortaliP97677.
SMRiP97677. Positions 178-326.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP97677. 2 interactions.
STRINGi10116.ENSRNOP00000019934.

Proteomic databases

PaxDbiP97677.
PRIDEiP97677.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi84010.
KEGGirno:84010.
UCSCiRGD:70949. rat.

Organism-specific databases

CTDi28514.
RGDi70949. Dll1.

Phylogenomic databases

eggNOGiENOG410IR7B. Eukaryota.
ENOG410XUNS. LUCA.
HOGENOMiHOG000267024.
HOVERGENiHBG007139.
InParanoidiP97677.
KOiK06051.
PhylomeDBiP97677.

Miscellaneous databases

NextBioi616537.
PROiP97677.

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. 8 hits.
SM00179. EGF_CA. 6 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

  1. Disibio G., Hebshi L., Boulter J., Weinmaster G.
    Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Notch ligands are substrates for protein O-fucosyltransferase-1 and Fringe."
    Panin V.M., Shao L., Lei L., Moloney D.J., Irvine K.D., Haltiwanger R.S.
    J. Biol. Chem. 277:29945-29952(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION.
  3. "Notch ligand endocytosis generates mechanical pulling force dependent on dynamin, epsins, and actin."
    Meloty-Kapella L., Shergill B., Kuon J., Botvinick E., Weinmaster G.
    Dev. Cell 22:1299-1312(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH EPN1.

Entry informationi

Entry nameiDLL1_RAT
AccessioniPrimary (citable) accession number: P97677
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 1, 1997
Last modified: May 11, 2016
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.