dbPAF Protein Information


Tag Content
dbPAF ID dbPAF-0000126
Uniprot Accession O00548; DLL1_HUMAN; B2RAK7; B5M0B3; Q9NU41; Q9UJV2;
Genbank Protein ID NP_005609.3; XP_011534060.1; XP_011544782.1;
Genbank Nucleotide ID NM_005618.3; XM_011535758.1; XM_011546480.1;
Protein Name Delta-like protein 1
Protein Synonyms/Alias Drosophila Delta homolog 1;Delta1;H-Delta-1;
Gene Name DLL1
Gene Synonyms/Alias UNQ146/PRO172;
Organism Homo sapiens(Human)
NCBI Taxa ID 9606
Functional Description
(View all)
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:11006133). 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) (By similarity). 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:11581320). 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 (PubMed:11581320). 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).
Phosphorylation Sites
dbPAF PTMs: 5
PositionPeptidesSourceReferences ( PMIDs )
603CQREKDISVSIIGATPhosphoSitePlus22135298
641ARYPAVDYNLVQDLKPhosphoSitePlus22135298
702GCSTSKDTKYQSVYVPhosphoSitePlus22135298
704STSKDTKYQSVYVISPhosphoSitePlus22135298
706SKDTKYQSVYVISEEPhosphoSitePlus22135298
Sequence
(Fasta)
MGSRCALALA VLSALLCQVW SSGVFELKLQ EFVNKKGLLG NRNCCRGGAG PPPCACRTFF 60
RVCLKHYQAS VSPEPPCTYG SAVTPVLGVD SFSLPDGGGA DSAFSNPIRF PFGFTWPGTF 120
SLIIEALHTD SPDDLATENP ERLISRLATQ RHLTVGEEWS QDLHSSGRTD LKYSYRFVCD 180
EHYYGEGCSV FCRPRDDAFG HFTCGERGEK VCNPGWKGPY CTEPICLPGC DEQHGFCDKP 240
GECKCRVGWQ GRYCDECIRY PGCLHGTCQQ PWQCNCQEGW GGLFCNQDLN YCTHHKPCKN 300
GATCTNTGQG SYTCSCRPGY TGATCELGID ECDPSPCKNG GSCTDLENSY SCTCPPGFYG 360
KICELSAMTC ADGPCFNGGR CSDSPDGGYS CRCPVGYSGF NCEKKIDYCS SSPCSNGAKC 420
VDLGDAYLCR CQAGFSGRHC DDNVDDCASS PCANGGTCRD GVNDFSCTCP PGYTGRNCSA 480
PVSRCEHAPC HNGATCHERG HRYVCECARG YGGPNCQFLL PELPPGPAVV DLTEKLEGQG 540
GPFPWVAVCA GVILVLMLLL GCAAVVVCVR LRLQKHRPPA DPCRGETETM NNLANCQREK 600
DISVSIIGAT QIKNTNKKAD FHGDHSADKN GFKARYPAVD YNLVQDLKGD DTAVRDAHSK 660
RDTKCQPQGS SGEEKGTPTT LRGGEASERK RPDSGCSTSK DTKYQSVYVI SEEKDECVIA 720
TEV 724
Keyword

KW-0002--3D-structure
KW-0025--Alternative splicing
KW-0965--Cell junction
KW-1003--Cell membrane
KW-0181--Complete proteome
KW-0217--Developmental protein
KW-0221--Differentiation
KW-1015--Disulfide bond
KW-0245--EGF-like domain
KW-0325--Glycoprotein
KW-1017--Isopeptide bond
KW-0472--Membrane
KW-0914--Notch signaling pathway
KW-0597--Phosphoprotein
KW-0621--Polymorphism
KW-1185--Reference proteome
KW-0677--Repeat
KW-0732--Signal
KW-0812--Transmembrane
KW-1133--Transmembrane helix
KW-0832--Ubl conjugation

Interpro

IPR001774--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_N_dom
IPR011651--Notch_ligand_N

PROSITE

PS00010--ASX_HYDROXYL
PS51051--DSL
PS00022--EGF_1
PS01186--EGF_2
PS50026--EGF_3
PS01187--EGF_CA

Pfam

PF01414--DSL
PF00008--EGF
PF07657--MNNL

Gene Ontology

GO:0005912--C:adherens junction
GO:0016324--C:apical plasma membrane
GO:0031410--C:cytoplasmic vesicle
GO:0005576--C:extracellular region
GO:0005887--C:integral component of plasma membrane
GO:0045121--C:membrane raft
GO:0005886--C:plasma membrane
GO:0005509--F:calcium ion binding
GO:0005112--F:Notch binding
GO:0030957--F:Tat protein binding
GO:0014002--P:astrocyte development
GO:0030154--P:cell differentiation
GO:0001709--P:cell fate determination
GO:0021688--P:cerebellar molecular layer formation
GO:0021693--P:cerebellar Purkinje cell layer structural organization
GO:0072583--P:clathrin-mediated endocytosis
GO:0007386--P:compartment pattern specification
GO:0007368--P:determination of left/right symmetry
GO:0097102--P:endothelial tip cell fate specification
GO:0001947--P:heart looping
GO:0030097--P:hemopoiesis
GO:0048839--P:inner ear development
GO:0046331--P:lateral inhibition
GO:0070986--P:left/right axis specification
GO:0072070--P:loop of Henle development
GO:0002315--P:marginal zone B cell differentiation
GO:0045608--P:negative regulation of auditory receptor cell differentiation
GO:0045596--P:negative regulation of cell differentiation
GO:0008285--P:negative regulation of cell proliferation
GO:0045605--P:negative regulation of epidermal cell differentiation
GO:0030857--P:negative regulation of epithelial cell differentiation
GO:0034351--P:negative regulation of glial cell apoptotic process
GO:0032693--P:negative regulation of interleukin-10 production
GO:0045638--P:negative regulation of myeloid cell differentiation
GO:0045662--P:negative regulation of myoblast differentiation
GO:0045665--P:negative regulation of neuron differentiation
GO:0072006--P:nephron development
GO:0048665--P:neuron fate specification
GO:0097150--P:neuronal stem cell population maintenance
GO:0007220--P:Notch receptor processing
GO:0007219--P:Notch signaling pathway
GO:0060853--P:Notch signaling pathway involved in arterial endothelial cell fate commitment
GO:0035265--P:organ growth
GO:0008284--P:positive regulation of cell proliferation
GO:0045807--P:positive regulation of endocytosis
GO:0045747--P:positive regulation of Notch signaling pathway
GO:0048633--P:positive regulation of skeletal muscle tissue growth
GO:1903672--P:positive regulation of sprouting angiogenesis
GO:0045944--P:positive regulation of transcription from RNA polymerase II promoter
GO:0072014--P:proximal tubule development
GO:0009954--P:proximal/distal pattern formation
GO:0008217--P:regulation of blood pressure
GO:0030155--P:regulation of cell adhesion
GO:0051302--P:regulation of cell division
GO:2000505--P:regulation of energy homeostasis
GO:0040008--P:regulation of growth
GO:0050767--P:regulation of neurogenesis
GO:0048631--P:regulation of skeletal muscle tissue growth
GO:0014807--P:regulation of somitogenesis
GO:1900746--P:regulation of vascular endothelial growth factor signaling pathway
GO:0060041--P:retina development in camera-type eye
GO:0060042--P:retina morphogenesis in camera-type eye
GO:0048630--P:skeletal muscle tissue growth
GO:0098773--P:skin epidermis development
GO:0001757--P:somite specification
GO:0001756--P:somitogenesis
GO:0021510--P:spinal cord development
GO:0003323--P:type B pancreatic cell development