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DKK4 DKK4 KREMEN1 KREMEN1 DKK2 DKK2 ZDHHC13 ZDHHC13 LDLRAP1 LDLRAP1 KREMEN2 KREMEN2 LRP5 LRP5 LRP6 LRP6 GULP1 GULP1 DKK1 DKK1 SNX6 SNX6 FZD1 FZD1 FZD2 FZD2 APPL2 APPL2 APPL1 APPL1 DNAJC10 DNAJC10 CRIM1 CRIM1 TP53 TP53 NOTCH2 NOTCH2 SNX32 SNX32 NOTCH1 NOTCH1 NOTCH3 NOTCH3 RIPK4 RIPK4 SNX5 SNX5 NOTCH4 NOTCH4 HACE1 HACE1
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
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gene neighborhood
fusion edge
gene fusions
cooccurrence edge
gene co-occurrence
Others
textmining edge
textmining
coexpression edge
co-expression
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protein homology
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DKK4dickkopf homolog 4 (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) (224 aa)
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)
HACE1HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (909 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)
DNAJC10DnaJ (Hsp40) homolog, subfamily C, member 10 (793 aa)
TP53tumor protein p53; Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression (By similarity) (393 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)
FZD1frizzled family receptor 1; Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK- 3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both p [...] (647 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)
LRP5low density lipoprotein receptor-related protein 5; 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 [...] (1615 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)
SNX32sorting nexin 32; May be involved in several stages of intracellular trafficking (By similarity) (403 aa)
FZD2frizzled family receptor 2; Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK- 3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both p [...] (565 aa)
KREMEN1kringle containing transmembrane protein 1 (492 aa)
RIPK4receptor-interacting serine-threonine kinase 4; Involved in stratified epithelial development. It is a direct transcriptional target of TP63. Plays a role in NF-kappa-B activation (784 aa)
GULP1GULP, engulfment adaptor PTB domain containing 1 (304 aa)
SNX6sorting nexin 6; May be involved in several stages of intracellular trafficking. Promotes lysosomal degradation of CDKN1B (By similarity). Plays a role in retrograde protein transport from endosomes to the trans-Golgi network. May function as link between transport vesicles and dynactin. Negatively regulates retrograde transport of BACE1 from the cell surface to the trans-Golgi network. May contribute to transcription regulation (418 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)
SNX5sorting nexin 5; May be involved in several stages of intracellular trafficking. Plays a role in macropinocytosis. Plays a role in the internalization of EGFR after EGF stimulation (404 aa)
ZDHHC13zinc finger, DHHC-type containing 13; Palmitoyltransferase for HD and GAD2 (By similarity). Mediates Mg(2+) transport (By similarity) (622 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, Homo, Homo sapiens, human, man
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