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TRAF4 TRAF4 AXIN1 AXIN1 ANXA2 ANXA2 GSK3B GSK3B PTPN11 PTPN11 MAP2K2 MAP2K2 MAP2K1 MAP2K1 PTPN6 PTPN6 UBC UBC MAP2K5 MAP2K5 MAP3K2 MAP3K2 PTK2B PTK2B BTK BTK MAPK13 MAPK13 CDC42 CDC42 MAP3K4 MAP3K4 MAP3K3 MAP3K3 SH3KBP1 SH3KBP1 BUB1B BUB1B RAC1 RAC1 MAP2K3 MAP2K3 MAP2K6 MAP2K6 RACGAP1 RACGAP1 GADD45G GADD45G GADD45B GADD45B GADD45A GADD45A
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.
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colored nodes:
query proteins and first shell of interactors
white nodes:
second shell of interactors
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empty nodes:
proteins of unknown 3D structure
filled nodes:
some 3D structure is known or predicted
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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
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
Others
textmining
co-expression
protein homology
Your Input:
MAP2K5Dual specificity mitogen-activated protein kinase kinase 5; Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis; Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily (448 aa)
MAPK13Mitogen-activated protein kinase 13; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studie [...] (365 aa)
GADD45BGrowth arrest and DNA damage-inducible protein GADD45 beta; Involved in the regulation of growth and apoptosis. Mediates activation of stress-responsive MTK1/MEKK4 MAPKKK (160 aa)
GADD45GGrowth arrest and DNA damage-inducible protein GADD45 gamma; Involved in the regulation of growth and apoptosis. Mediates activation of stress-responsive MTK1/MEKK4 MAPKKK; Belongs to the GADD45 family (159 aa)
AXIN1Axin-1; Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling. Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin li [...] (862 aa)
TRAF4TNF receptor-associated factor 4; Adapter protein and signal transducer that links members of the tumor necrosis factor receptor (TNFR) family to different signaling pathways. Plays a role in the activation of NF-kappa-B and JNK, and in the regulation of cell survival and apoptosis. Regulates activation of NF-kappa-B in response to signaling through Toll-like receptors. Required for normal skeleton development, and for normal development of the respiratory tract (By similarity). Required for activation of RPS6KB1 in response to TNF signaling. Modulates TRAF6 functions (470 aa)
MAP2K2Dual specificity mitogen-activated protein kinase kinase 2; Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity) (400 aa)
BUB1BMitotic checkpoint serine/threonine-protein kinase BUB1 beta; Essential component of the mitotic checkpoint. Required for normal mitosis progression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Nega [...] (1050 aa)
MAP2K1Dual specificity mitogen-activated protein kinase kinase 1; Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine resid [...] (393 aa)
GSK3BGlycogen synthase kinase-3 beta; Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glyc [...] (433 aa)
PTPN11Tyrosine-protein phosphatase non-receptor type 11; Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Positively regulates MAPK signal transduction pathway. Dephosphorylates GAB1, ARHGAP35 and EGFR. Dephosphorylates ROCK2 at ’Tyr-722’ resulting in stimulatation of its RhoA binding activity. Dephosphorylates CDC73; Protein tyrosine phosphatases, non-receptor type (593 aa)
MAP2K3Dual specificity mitogen-activated protein kinase kinase 3; Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14; Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily (347 aa)
ANXA2Annexin A2; Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response. Inhibits PCSK9-enhanced LDLR degradation, probably reduces PCSK9 protein levels via a translational mechanism but also competes with LDLR for binding with PCSK9; Belongs to the annexin family (357 aa)
RAC1Ras-related C3 botulinum toxin substrate 1; Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages. Essential for the SPATA13-mediated [...] (211 aa)
MAP3K3Mitogen-activated protein kinase kinase kinase 3; Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators (657 aa)
GADD45AGrowth arrest and DNA damage-inducible protein GADD45 alpha; In T-cells, functions as a regulator of p38 MAPKs by inhibiting p88 phosphorylation and activity (By similarity). Might affect PCNA interaction with some CDK (cell division protein kinase) complexes; stimulates DNA excision repair in vitro and inhibits entry of cells into S phase; Belongs to the GADD45 family (165 aa)
MAP3K4Mitogen-activated protein kinase kinase kinase 4; Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6 (1608 aa)
PTK2BProtein-tyrosine kinase 2-beta; Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T- cells, and contributes to the regulation of T-cell responses. Promo [...] (1009 aa)
SH3KBP1SH3 domain-containing kinase-binding protein 1; Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through a association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activit [...] (665 aa)
CDC42Cell division control protein 42 homolog; Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Plays a role in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. Mediates CDC42-dependent cell migration. Required for DOCK [...] (191 aa)
MAP3K2Mitogen-activated protein kinase kinase kinase 2; Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and-run dynamics (619 aa)
PTPN6Tyrosine-protein phosphatase non-receptor type 6; Modulates signaling by tyrosine phosphorylated cell surface receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation. Plays a key role in hematopoiesis; Protein tyrosine phosphatases, non-receptor type (624 aa)
RACGAP1Rac GTPase-activating protein 1; Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Required for proper attachment of the midbody to the cell membrane during cytokinesis. Plays key roles in controlling cell growth and differentiation of hematopoietic cells through mechanisms other than regulating Rac GTPase activity. Also involved in the regulation of growth-related processes in adipocytes and myoblasts. May be involved in regulating spermatogene [...] (632 aa)
UBCPolyubiquitin-C; Ubiquitin- Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked- Lys-6-linked may be involved in DNA repair; [...] (685 aa)
MAP2K6Dual specificity mitogen-activated protein kinase kinase 6; Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 i [...] (334 aa)
BTKTyrosine-protein kinase BTK; Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members. PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker prote [...] (693 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, Homo sapiens, human, man
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