Dll1
entrez
13388
canonical
uniprot
Q61483
canonical
ensembl
ENSMUSG00000014773
resolver
ensp
ENSMUSP00000014917
resolver
enst
ENSMUST00000014917
resolver
genesymbol
Dll1
resolver
uniprot
Q6PFV7
resolver
uniprot_entry
DLL1_MOUSE
resolver
uniprot_sec
Q6PFV7
resolver
amino_acid_sequence
MGRRSALALAVVSALLCQVWSSGVFELKLQEFVNKKGLLGNRNCCRGGSGPPCACRTFFRVCLKHYQASVSPEPPCTYGSAVTPVLGVDSFSLPDGAGIDPAFSNPIRFPFGFTWPGTFSLIIEALHTDSPDDLATENPERLISRLTTQRHLTVGEEWSQDLHSSGRTDLRYSYRFVCDEHYYGEGCSVFCRPRDDAFGHFTCGDRGEKMCDPGWKGQYCTDPICLPGCDDQHGYCDKPGECKCRVGWQGRYCDECIRYPGCLHGTCQQPWQCNCQEGWGGLFCNQDLNYCTHHKPCRNGATCTNTGQGSYTCSCRPGYTGANCELEVDECAPSPCKNGASCTDLEDSFSCTCPPGFYGKVCELSAMTCADGPCFNGGRCSDNPDGGYTCHCPLGFSGFNCEKKMDLCGSSPCSNGAKCVDLGNSYLCRCQAGFSGRYCEDNVDDCASSPCANGGTCRDSVNDFSCTCPPGYTGKNCSAPVSRCEHAPCHNGATCHQRGQRYMCECAQGYGGPNCQFLLPEPPPGPMVVDLSERHMESQGGPFPWVAVCAGVVLVLLLLLGCAAVVVCVRLKLQKHQPPPEPCGGETETMNNLANCQREKDVSVSIIGATQIKNTNKKADFHGDHGAEKSSFKVRYPTVDYNLVRDLKGDEATVRDTHSKRDTKCQSQSSAGEEKIAPTLRGGEIPDRKRPESVYSTSKDTKYQSVYVLSAEKDECVIATEV
uniprot
proteins
function
FUNCTION: 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:10958687, PubMed:21985982). Following transinteraction, ligand cells produce mechanical force that depends of a clathrin-mediated endocytosis, requiring ligand ubiquitination, EPN1 interaction, and actin polymerization; 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:16495313, PubMed:17194759, PubMed:17960184, PubMed:18997111, PubMed:19144989, PubMed:19389377, PubMed:19562077, PubMed:20081190, PubMed:21238454, PubMed:21572390, PubMed:22096075, PubMed:22282195, PubMed:22529374, PubMed:22940113, PubMed:23688253, PubMed:23695674, PubMed:23699523, PubMed:23806616, PubMed:25220152, PubMed:26114479, PubMed:7671806). 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:18997111, PubMed:7671806). 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 through 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). {ECO:0000250|UniProtKB:O00548, ECO:0000250|UniProtKB:P97677, ECO:0000269|PubMed:10958687, ECO:0000269|PubMed:15146182, ECO:0000269|PubMed:16495313, ECO:0000269|PubMed:17194759, ECO:0000269|PubMed:17960184, ECO:0000269|PubMed:18676613, ECO:0000269|PubMed:18997111, ECO:0000269|PubMed:19144989, ECO:0000269|PubMed:19217325, ECO:0000269|PubMed:19389377, ECO:0000269|PubMed:19562077, ECO:0000269|PubMed:20081190, ECO:0000269|PubMed:21238454, ECO:0000269|PubMed:21572390, ECO:0000269|PubMed:21915337, ECO:0000269|PubMed:21985982, ECO:0000269|PubMed:22096075, ECO:0000269|PubMed:22282195, ECO:0000269|PubMed:22529374, ECO:0000269|PubMed:22940113, ECO:0000269|PubMed:23688253, ECO:0000269|PubMed:23695674, ECO:0000269|PubMed:23699523, ECO:0000269|PubMed:23806616, ECO:0000269|PubMed:25220152, ECO:0000269|PubMed:26114479, ECO:0000269|PubMed:7671806}.
uniprot
proteins
mass_dalton
78449
uniprot
proteins
mutagenesis
MUTAGEN 613..618; /note="KNTNKK->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."; /evidence="ECO:0000269|PubMed:21985982"; MUTAGEN 613; /note="K->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."; /evidence="ECO:0000269|PubMed:21985982"; MUTAGEN 638; /note="T->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."; /evidence="ECO:0000269|PubMed:24449764"; MUTAGEN 689; /note="K->R: Decreases Notch signaling pathway."; /evidence="ECO:0000269|PubMed:21985982"; MUTAGEN 693; /note="S->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."; /evidence="ECO:0000269|PubMed:24449764"; MUTAGEN 696; /note="S->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."; /evidence="ECO:0000269|PubMed:24449764"; MUTAGEN 699; /note="K->R: Decreases Notch signaling pathway."; /evidence="ECO:0000269|PubMed:21985982"; MUTAGEN 713; /note="K->R: Decreases Notch signaling pathway."; /evidence="ECO:0000269|PubMed:21985982
uniprot
proteins
post_translational_modification
PTM: 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). {ECO:0000250|UniProtKB:P10041, ECO:0000269|PubMed:17003037, ECO:0000269|PubMed:18676613, ECO:0000269|PubMed:21985982}.; PTM: 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. {ECO:0000269|PubMed:24449764}.; PTM: 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 intracellular membrane-anchored form, followed by a gamma-secretase cleavage releasing an intracellular fragment (PubMed:12794186). {ECO:0000269|PubMed:12794186, ECO:0000269|PubMed:21572390}.; PTM: O-fucosylated. Can be elongated to a disaccharide by MFNG. {ECO:0000250|UniProtKB:P97677}.
uniprot
proteins
pubmed
10958687
uniprot
proteins
pubmed
12794186
uniprot
proteins
pubmed
15146182
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15788413
uniprot
proteins
pubmed
15908431
uniprot
proteins
pubmed
16495313
uniprot
proteins
pubmed
17003037
uniprot
proteins
pubmed
17194759
uniprot
proteins
pubmed
17960184
uniprot
proteins
pubmed
18676613
uniprot
proteins
pubmed
18997111
uniprot
proteins
pubmed
19144989
uniprot
proteins
pubmed
19217325
uniprot
proteins
pubmed
19389377
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
19562077
uniprot
proteins
pubmed
19723503
uniprot
proteins
pubmed
20081190
uniprot
proteins
pubmed
21238454
uniprot
proteins
pubmed
21572390
uniprot
proteins
pubmed
21915337
uniprot
proteins
pubmed
21985982
uniprot
proteins
pubmed
22015720
uniprot
proteins
pubmed
22096075
uniprot
proteins
pubmed
22282195
uniprot
proteins
pubmed
22529374
uniprot
proteins
pubmed
22940113
uniprot
proteins
pubmed
23688253
uniprot
proteins
pubmed
23695674
uniprot
proteins
pubmed
23699523
uniprot
proteins
pubmed
23806616
uniprot
proteins
pubmed
24449764
uniprot
proteins
pubmed
24715457
uniprot
proteins
pubmed
25220152
uniprot
proteins
pubmed
26114479
uniprot
proteins
pubmed
7671806
uniprot
proteins
sequence_length
722
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Apical cell membrane {ECO:0000269|PubMed:24715457}; Single-pass type I membrane protein {ECO:0000269|PubMed:24715457}. Cell junction, adherens junction {ECO:0000269|PubMed:15908431, ECO:0000269|PubMed:24715457}. Membrane raft {ECO:0000269|PubMed:18676613, ECO:0000269|PubMed:21985982}. Note=Distributed around adherens junction in the apical endfeet through interactions with MAGI1. {ECO:0000269|PubMed:15908431, ECO:0000269|PubMed:24715457}.; SUBCELLULAR LOCATION: [Dll1-derived cell-associated form]: Cell membrane {ECO:0000269|PubMed:12794186}.; SUBCELLULAR LOCATION: [Dll1-intracellular form]: Nucleus {ECO:0000269|PubMed:12794186}.
uniprot
proteins
transmembrane_region
TRANSMEM 546..568; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins