Delta-like 1

Last updated
DLL1
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases DLL1 , DELTA1, DL1, Delta, Delta-like 1, delta like canonical Notch ligand 1, NEDBAS
External IDs OMIM: 606582 MGI: 104659 HomoloGene: 4104 GeneCards: DLL1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005618

NM_007865
NM_001379042

RefSeq (protein)

NP_005609

NP_031891
NP_001365971

Location (UCSC) Chr 6: 170.28 – 170.31 Mb Chr 17: 15.59 – 15.6 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Delta-like protein 1 is a protein that in humans is encoded by the DLL1 gene. [5]

Contents

Function

DLL1 is a human homolog of the Notch Delta ligand and is a member of the delta/serrate/jagged family. It plays a role in mediating cell fate decisions during hematopoiesis. It may play a role in cell-to-cell communication. [5]

Interactions

Delta-like 1 has been shown to interact with NOTCH2 [6] [7] [8]

Related Research Articles

<span class="mw-page-title-main">Notch signaling pathway</span> Series of molecular signals

The Notch signaling pathway is a highly conserved cell signaling system present in most animals. Mammals possess four different notch receptors, referred to as NOTCH1, NOTCH2, NOTCH3, and NOTCH4. The notch receptor is a single-pass transmembrane receptor protein. It is a hetero-oligomer composed of a large extracellular portion, which associates in a calcium-dependent, non-covalent interaction with a smaller piece of the notch protein composed of a short extracellular region, a single transmembrane-pass, and a small intracellular region.

<span class="mw-page-title-main">Gamma secretase</span>

Gamma secretase is a multi-subunit protease complex, itself an integral membrane protein, that cleaves single-pass transmembrane proteins at residues within the transmembrane domain. Proteases of this type are known as intramembrane proteases. The most well-known substrate of gamma secretase is amyloid precursor protein, a large integral membrane protein that, when cleaved by both gamma and beta secretase, produces a short 37-43 amino acid peptide called amyloid beta whose abnormally folded fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients. Gamma secretase is also critical in the related processing of several other type I integral membrane proteins, such as Notch, ErbB4, E-cadherin, N-cadherin, ephrin-B2, or CD44.

<span class="mw-page-title-main">Presenilin</span>

Presenilins are a family of related multi-pass transmembrane proteins which constitute the catalytic subunits of the gamma-secretase intramembrane protease protein complex. They were first identified in screens for mutations causing early onset forms of familial Alzheimer's disease by Peter St George-Hyslop. Vertebrates have two presenilin genes, called PSEN1 that codes for presenilin 1 (PS-1) and PSEN2 that codes for presenilin 2 (PS-2). Both genes show conservation between species, with little difference between rat and human presenilins. The nematode worm C. elegans has two genes that resemble the presenilins and appear to be functionally similar, sel-12 and hop-1.

<span class="mw-page-title-main">Alpha secretase</span> Family of proteolytic enzymes

Alpha secretases are a family of proteolytic enzymes that cleave amyloid precursor protein (APP) in its transmembrane region. Specifically, alpha secretases cleave within the fragment that gives rise to the Alzheimer's disease-associated peptide amyloid beta when APP is instead processed by beta secretase and gamma secretase. The alpha-secretase pathway is the predominant APP processing pathway. Thus, alpha-secretase cleavage precludes amyloid beta formation and is considered to be part of the non-amyloidogenic pathway in APP processing. Alpha secretases are members of the ADAM family, which are expressed on the surfaces of cells and anchored in the cell membrane. Several such proteins, notably ADAM10, have been identified as possessing alpha-secretase activity. Upon cleavage by alpha secretases, APP releases its extracellular domain - a fragment known as APPsα - into the extracellular environment in a process known as ectodomain shedding.

<span class="mw-page-title-main">TGFBR3</span> Protein-coding gene in the species Homo sapiens

Betaglycan also known as Transforming growth factor beta receptor III (TGFBR3), is a cell-surface chondroitin sulfate / heparan sulfate proteoglycan >300 kDa in molecular weight. Betaglycan binds to various members of the TGF-beta superfamily of ligands via its core protein, and bFGF via its heparan sulfate chains. TGFBR3 is the most widely expressed type of TGF-beta receptor. Its affinity towards all individual isoforms of TGF-beta is similarly high and therefore it plays an important role as a coreceptor mediating the binding of TGF-beta to its other receptors - specifically TGFBR2. The intrinsic kinase activity of this receptor has not yet been described. In regard of TGF-beta signalling it is generally considered a non-signaling receptor or a coreceptor. By binding to various member of the TGF-beta superfamily at the cell surface it acts as a reservoir of TGF-beta.

<span class="mw-page-title-main">Low-density lipoprotein receptor-related protein 8</span> Cell surface receptor, part of the low-density lipoprotein receptor family

Low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), is a protein that in humans is encoded by the LRP8 gene. ApoER2 is a cell surface receptor that is part of the low-density lipoprotein receptor family. These receptors function in signal transduction and endocytosis of specific ligands. Through interactions with one of its ligands, reelin, ApoER2 plays an important role in embryonic neuronal migration and postnatal long-term potentiation. Another LDL family receptor, VLDLR, also interacts with reelin, and together these two receptors influence brain development and function. Decreased expression of ApoER2 is associated with certain neurological diseases.

<span class="mw-page-title-main">NOTCH3</span> Protein-coding gene in the species Homo sapiens

Neurogenic locus notch homolog protein 3(Notch 3) is a protein that in humans is encoded by the NOTCH3 gene.

<span class="mw-page-title-main">JAG1</span> Protein-coding gene in the species Homo sapiens

Jagged1 (JAG1) is one of five cell surface proteins (ligands) that interact with four receptors in the mammalian Notch signaling pathway. The Notch Signaling Pathway is a highly conserved pathway that functions to establish and regulate cell fate decisions in many organ systems. Once the JAG1-NOTCH (receptor-ligand) interactions take place, a cascade of proteolytic cleavages is triggered resulting in activation of the transcription for downstream target genes. Located on human chromosome 20, the JAG1 gene is expressed in multiple organ systems in the body and causes the autosomal dominant disorder Alagille syndrome (ALGS) resulting from loss of function mutations within the gene. JAG1 has also been designated as CD339.

<span class="mw-page-title-main">Presenilin-1</span> Protein-coding gene in the species Homo sapiens

Presenilin-1(PS-1) is a presenilin protein that in humans is encoded by the PSEN1 gene. Presenilin-1 is one of the four core proteins in the gamma secretase complex, which is considered to play an important role in generation of amyloid beta (Aβ) from amyloid-beta precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease.

<span class="mw-page-title-main">Notch 1</span> Protein-coding gene in the species Homo sapiens

Neurogenic locus notch homolog protein 1(Notch 1) is a protein encoded in humans by the NOTCH1 gene. Notch 1 is a single-pass transmembrane receptor.

<span class="mw-page-title-main">Notch 4</span> Protein-coding gene in the species Homo sapiens

Neurogenic locus notch homolog 4(Notch 4) is a protein that in humans is encoded by the NOTCH4 gene located on chromosome 6.

<span class="mw-page-title-main">Notch 2</span> Protein-coding gene in the species Homo sapiens

Neurogenic locus notch homolog protein 2 is a protein that in humans is encoded by the NOTCH2 gene.

<span class="mw-page-title-main">NUMB (gene)</span> Protein-coding gene in the species Homo sapiens

Protein numb homolog is a protein that in humans is encoded by the NUMB gene. The protein encoded by this gene plays a role in the determination of cell fates during development. The encoded protein, whose degradation is induced in a proteasome-dependent manner by MDM2, is a membrane-bound protein that has been shown to associate with EPS15, LNX1, and NOTCH1. Four transcript variants encoding different isoforms have been found for this gene.

<span class="mw-page-title-main">PTPRF</span> Protein-coding gene in the species Homo sapiens

Receptor-type tyrosine-protein phosphatase F is an enzyme that in humans is encoded by the PTPRF gene.

<span class="mw-page-title-main">HES1</span> Protein-coding gene in the species Homo sapiens

Transcription factor HES1 is a protein that is encoded by the Hes1 gene, and is the mammalian homolog of the hairy gene in Drosophila. HES1 is one of the seven members of the Hes gene family (HES1-7). Hes genes code nuclear proteins that suppress transcription.

<span class="mw-page-title-main">JAG2</span> Protein-coding gene in the species Homo sapiens

Jagged-2 is a protein that in humans is encoded by the JAG2 gene.

<span class="mw-page-title-main">MFNG</span> Protein-coding gene in the species Homo sapiens

Beta-1,3-N-acetylglucosaminyltransferase manic fringe is an enzyme that in humans is encoded by the MFNG gene, a member of the fringe gene family which also includes the radical fringe (RFNG) and lunatic fringe (LFNG).

<span class="mw-page-title-main">DTX1</span> Protein-coding gene in the species Homo sapiens

Protein deltex-1 is a protein that in humans is encoded by the DTX1 gene.

<span class="mw-page-title-main">Notch proteins</span>

Notch proteins are a family of type-1 transmembrane proteins that form a core component of the Notch signaling pathway, which is highly conserved in metazoans. The Notch extracellular domain mediates interactions with DSL family ligands, allowing it to participate in juxtacrine signaling. The Notch intracellular domain acts as a transcriptional activator when in complex with CSL family transcription factors. Members of this Type 1 transmembrane protein family share several core structures, including an extracellular domain consisting of multiple epidermal growth factor (EGF)-like repeats and an intracellular domain transcriptional activation domain (TAD). Notch family members operate in a variety of different tissues and play a role in a variety of developmental processes by controlling cell fate decisions. Much of what is known about Notch function comes from studies done in Caenorhabditis elegans (C.elegans) and Drosophila melanogaster. Human homologs have also been identified, but details of Notch function and interactions with its ligands are not well known in this context.

<span class="mw-page-title-main">Hes3 signaling axis</span>

The STAT3-Ser/Hes3 signaling axis is a specific type of intracellular signaling pathway that regulates several fundamental properties of cells.

References

  1. 1 2 3 ENSG00000198719 GRCh38: Ensembl release 89: ENSG00000275555, ENSG00000198719 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000014773 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 "Entrez Gene: DLL1 delta-like 1 (Drosophila)".
  6. Shimizu K, Chiba S, Saito T, Kumano K, Takahashi T, Hirai H (July 2001). "Manic fringe and lunatic fringe modify different sites of the Notch2 extracellular region, resulting in different signaling modulation". J. Biol. Chem. 276 (28): 25753–8. doi: 10.1074/jbc.M103473200 . PMID   11346656.
  7. Blaumueller CM, Qi H, Zagouras P, Artavanis-Tsakonas S (July 1997). "Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane". Cell. 90 (2): 281–91. doi: 10.1016/s0092-8674(00)80336-0 . PMID   9244302. S2CID   16544864.
  8. Shimizu K, Chiba S, Hosoya N, Kumano K, Saito T, Kurokawa M, Kanda Y, Hamada Y, Hirai H (September 2000). "Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of Notch2". Mol. Cell. Biol. 20 (18): 6913–22. doi:10.1128/mcb.20.18.6913-6922.2000. PMC   88767 . PMID   10958687.

Further reading