DegronMD - O00548(DLL1)

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: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). {ECO:0000250|UniProtKB:P97677, ECO:0000250|UniProtKB:Q61483, ECO:0000269|PubMed:11006133, ECO:0000269|PubMed:11581320}. View more >>

GO - Biological processes (BP): astrocyte development [GO:0014002]; cell differentiation [GO:0030154]; cell fate determination [GO:0001709]; cerebellar molecular layer formation [GO:0021688]; cerebellar Purkinje cell layer structural organization [GO:0021693]; clathrin-dependent endocytosis [GO:0072583]; compartment pattern specification [GO:0007386]; determination of left/right symmetry [GO:0007368]; endothelial tip cell fate specification [GO:0097102]; energy homeostasis [GO:0097009]; heart looping [GO:0001947]; hemopoiesis [GO:0030097]; inner ear development [GO:0048839]; lateral inhibition [GO:0046331]; left/right axis specification [GO:0070986]; loop of Henle development [GO:0072070]; marginal zone B cell differentiation [GO:0002315]; negative regulation of cardiac muscle cell differentiation [GO:2000726]; negative regulation of cell differentiation [GO:0045596]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of epidermal cell differentiation [GO:0045605]; negative regulation of epithelial cell differentiation [GO:0030857]; negative regulation of glial cell apoptotic process [GO:0034351]; negative regulation of inner ear auditory receptor cell differentiation [GO:0045608]; negative regulation of interleukin-10 production [GO:0032693]; negative regulation of myeloid cell differentiation [GO:0045638]; negative regulation of myoblast differentiation [GO:0045662]; negative regulation of neuron differentiation [GO:0045665]; negative regulation of Notch signaling pathway [GO:0045746]; nephron development [GO:0072006]; neuronal stem cell population maintenance [GO:0097150]; neuron fate specification [GO:0048665]; Notch signaling pathway [GO:0007219]; Notch signaling pathway involved in arterial endothelial cell fate commitment [GO:0060853]; organ growth [GO:0035265]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of endocytosis [GO:0045807]; positive regulation of gene expression [GO:0010628]; positive regulation of Notch signaling pathway [GO:0045747]; positive regulation of skeletal muscle tissue growth [GO:0048633]; positive regulation of sprouting angiogenesis [GO:1903672]; positive regulation of transcription by RNA polymerase II [GO:0045944]; proximal/distal pattern formation [GO:0009954]; proximal tubule development [GO:0072014]; regulation of blood pressure [GO:0008217]; regulation of cell adhesion [GO:0030155]; regulation of cell division [GO:0051302]; regulation of growth [GO:0040008]; regulation of neurogenesis [GO:0050767]; regulation of skeletal muscle tissue growth [GO:0048631]; regulation of somitogenesis [GO:0014807]; regulation of vascular endothelial growth factor signaling pathway [GO:1900746]; retina development in camera-type eye [GO:0060041]; retina morphogenesis in camera-type eye [GO:0060042]; skeletal muscle tissue growth [GO:0048630]; skin epidermis development [GO:0098773]; somite specification [GO:0001757]; somitogenesis [GO:0001756]; spinal cord development [GO:0021510]; type B pancreatic cell development [GO:0003323] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.K700N	TCGA-77-7335	LUSC	TCGA	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation rewiring degron network	0.3056
p.K700N	DO26707	LUSC	ICGC	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation rewiring degron network	0.3056
p.S694L	TCGA-AJ-A3BG	UCEC	TCGA	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation altering degron motif	0.7667
p.S694L	TCGA-FD-A3B3	BLCA	TCGA	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation altering degron motif	0.7667
p.S694L	DO749	BLCA	ICGC	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation altering degron motif	0.7667
p.S694L	DO42633	UCEC	ICGC	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation altering degron motif	0.7667
p.S694L	SIDM00120	Prostate Carcinoma	GDSC	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation altering degron motif	0.7667
p.S694L	ACH-000979	Prostate Cancer	CCLE	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation altering degron motif	0.7667
p.S694L	DU-145	prostate	COSMIC	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation altering degron motif	0.7667
p.R689I	TCGA-AX-A2HC	UCEC	TCGA	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation rewiring degron network	0.2222
p.R689I	DO41572	UCEC	ICGC	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation rewiring degron network	0.2222
p.S706L	TCGA-BR-8680	STAD	TCGA	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation blocking phosphorylation signal	0.5833
p.S706L	DO47769	STAD	ICGC	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation blocking phosphorylation signal	0.5833
p.Q705H	DO1121	BRCA	ICGC	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation rewiring degron network	0.1667
p.V709I	DO229389	BTCA	ICGC	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation rewiring degron network	0.0556
p.P692S	DO222418	MELA	ICGC	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation rewiring degron network	0.3056
p.S697L	SIDM01722	Non-Cancerous	GDSC	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation altering degron motif	0.6556
p.S697L	SIDM00174	Head and Neck Carcinoma	GDSC	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation altering degron motif	0.6556
p.S697L	ACH-002213	Head and Neck Cancer	CCLE	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation altering degron motif	0.6556
p.S697L	ACH-002343	Non-Cancerous	CCLE	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation altering degron motif	0.6556
p.D701Y	SIDM01186	Breast Carcinoma	GDSC	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation rewiring degron network	0.2778
p.D701Y	ACH-000554	Breast Cancer	CCLE	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation rewiring degron network	0.2778
p.D701Y	UACC-893	breast	COSMIC	DSGCSTS	DEG_SCF_TRCP1_1	693:699	Mutation rewiring degron network	0.2778

DegronMD: protein-targeted degradation, mutation and drug response to degrons

DLL1

UniProt ID: O00548

Entrez ID: 28514

Protein name: Delta-like protein 1 (Drosophila Delta homolog 1) (Delta1) (H-Delta-1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for DLL1 in