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NOTCH3 NOTCH3 NOTCH4 NOTCH4 NOTCH1 NOTCH1 APPL2 APPL2 APPL1 APPL1 NOTCH2 NOTCH2 ZAP70 ZAP70 SYK SYK LDLRAP1 LDLRAP1 LRP6 LRP6 DKK1 DKK1 CRIM1 CRIM1 GULP1 GULP1 KREMEN2 KREMEN2 DKK2 DKK2
Nodes:
Network nodes represent proteins
splice isoforms or post-translational modifications are collapsed, i.e. each node represents all the proteins produced by a single, protein-coding gene locus.
Node Size
small protein node
small nodes:
protein of unknown 3D structure
large protein node
large nodes:
some 3D structure is known or predicted
Node Color
colored protein node
colored nodes:
query proteins and first shell of interactors
non-colored protein node
white nodes:
second shell of interactors
Edges:
Edges represent protein-protein associations
associations are meant to be specific and meaningful, i.e. proteins jointly contribute to a shared function; this does not necessarily mean they are physically binding each other.
Known Interactions
database edge
from curated databases
experiment edge
experimentally determined
Predicted Interactions
neighborhood edge
gene neighborhood
fusion edge
gene fusions
cooccurrence edge
gene co-occurrence
Others
textmining edge
textmining
coexpression edge
co-expression
homology edge
protein homology
Your Input:
NOTCH2notch 2 (2471 aa)
APPL2adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 2; Required for the regulation of cell proliferation in response to extracellular signals mediated by an early endosomal compartment. Links Rab5 to nuclear signal transduction (664 aa)
LRP6low density lipoprotein receptor-related protein 6; Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor- ligand complexes into ribosome-sized signalsomes. Cell-surface coreceptor of Wnt/beta-catenin signaling, which plays a pivotal role in bone formation. The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1 polymers to the plasma membrane which, in turn, recruits the AXIN1/GSK3B-complex to the cell surface promoting the formation of signalsomes and inhibiting AXIN1/GSK3- mediated phosphorylation and destruction o [...] (1613 aa)
NOTCH3notch 3; Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity) (2321 aa)
ZAP70zeta-chain (TCR) associated protein kinase 70kDa; Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization t [...] (619 aa)
NOTCH1notch 1; Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. May be important for normal lymphocyte function. In altered form, may contribute to transformation or progression in some T-cell neoplasms. Involved in the maturation of both CD4+ and CD8+ c [...] (2555 aa)
CRIM1cysteine rich transmembrane BMP regulator 1 (chordin-like); May play a role in CNS development by interacting with growth factors implicated in motor neuron differentiation and survival. May play a role in capillary formation and maintenance during angiogenesis. Modulates BMP activity by affecting its processing and delivery to the cell surface (1036 aa)
DKK2dickkopf 2 homolog (Xenopus laevis); Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero- posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease (By similarity) (259 aa)
APPL1adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1; Required for the regulation of cell proliferation in response to extracellular signals from an early endosomal compartment. Links Rab5 to nuclear signal transduction (709 aa)
KREMEN2kringle containing transmembrane protein 2; Receptor for Dickkopf protein. Cooperates with Dickkopf to block Wnt/beta-catenin signaling. Forms a ternary complex with Dkk1 and LRP6 and induces rapid endocytosis and removal of the Wnt receptor LRP6 from the plasma membrane (By similarity) (462 aa)
GULP1GULP, engulfment adaptor PTB domain containing 1 (304 aa)
DKK1dickkopf 1 homolog (Xenopus laevis); Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero- posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease (266 aa)
LDLRAP1low density lipoprotein receptor adaptor protein 1; Adapter protein (clathrin-associated sorting protein (CLASP)) required for efficient endocytosis of the LDL receptor (LDLR) in polarized cells such as hepatocytes and lymphocytes, but not in non-polarized cells (fibroblasts). May be required for LDL binding and internalization but not for receptor clustering in coated pits. May facilitate the endocytocis of LDLR and LDLR-LDL complexes from coated pits by stabilizing the interaction between the receptor and the structural components of the pits. May also be involved in the internalizat [...] (308 aa)
NOTCH4notch 4 (2003 aa)
SYKspleen tyrosine kinase; Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine- phosphorylated ITAM domains. The association with the receptor can also [...] (635 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, Homo, Homo sapiens, human, man
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