STRINGSTRING
TP53 TP53 PIK3R2 PIK3R2 PIK3R3 PIK3R3 SP1 SP1 E2F1 E2F1 JUN JUN FOS FOS ESR2 ESR2 RAF1 RAF1 GRB2 GRB2 ARAF ARAF ADCY6 ADCY6 SOS2 SOS2 RB1 RB1 PIK3CB PIK3CB JAG1 JAG1 CDKN1A CDKN1A MAP2K2 MAP2K2 SRC SRC RPS6KB2 RPS6KB2 ADCY1 ADCY1 NRAS NRAS MAPK13 MAPK13 MAPK1 MAPK1 DLL4 DLL4 DLL3 DLL3 PIK3R1 PIK3R1 CDKN2C CDKN2C SHC3 SHC3 SOS1 SOS1 SHC4 SHC4 BAD BAD NOTCH1 NOTCH1 ADCY8 ADCY8 MTOR MTOR SHC2 SHC2 MAPK3 MAPK3 MAPK11 MAPK11 RPS6KB1 RPS6KB1 GNAS GNAS CCND1 CCND1 AKT1 AKT1 E2F2 E2F2 AKT3 AKT3 CDKN1B CDKN1B ADCY2 ADCY2 MMP2 MMP2 BCL2 BCL2 SHC1 SHC1 MAPK10 MAPK10 MMP9 MMP9 E2F3 E2F3 IGF1R IGF1R HBEGF HBEGF ERBB2 ERBB2 ADCY5 ADCY5 ADCY3 ADCY3 ABCB11 ABCB11 MAP2K1 MAP2K1 PRKACB PRKACB NOTCH4 NOTCH4 CDKN2A CDKN2A MED1 MED1 NOTCH3 NOTCH3 NCOR1 NCOR1 IGF1 IGF1 HRAS HRAS ADCY9 ADCY9 ADCY4 ADCY4 PRKACA PRKACA ADCY7 ADCY7 PIK3CD PIK3CD BRAF BRAF MAPK14 MAPK14 PTK2 PTK2 NCOA3 NCOA3 JAG2 JAG2 PIK3CA PIK3CA EGFR EGFR AKT2 AKT2 CDK4 CDK4 MDM2 MDM2 BAX BAX NOTCH2 NOTCH2 ESR1 ESR1
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query proteins and first shell of interactors
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second shell of interactors
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proteins of unknown 3D structure
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a 3D structure is known or predicted
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experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
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TP53Cellular tumor antigen 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. Its pro-apoptotic activity is activated via its intera [...] (386 aa)
PIK3R2Phosphatidylinositol 3-kinase regulatory subunit beta; Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5- bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Binds to activated (phosphorylated) protein- tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating t [...] (724 aa)
PIK3R3Phosphatidylinositol 3-kinase regulatory subunit gamma; Binds to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulates their kinase activity. During insulin stimulation, it also binds to IRS-1. (461 aa)
SP1Sp1 transcription factor. (786 aa)
E2F1E2F transcription factor 1. (437 aa)
JUNTranscription factor AP-1; Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. Involved in activated KRAS-mediated transcriptional activation of USP28. Binds to the USP28 promoter; Belongs to the bZIP family. Jun subfamily. (303 aa)
FOSProto-oncogene c-Fos; Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex, at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling. Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation (By similarity). In growing cells, activates phospholipid synthesis, possibly by activating CDS1 and [...] (380 aa)
ESR2Estrogen receptor beta; Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1 (ER-alpha), and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. May play a role in ovarian follicular growth and maturation; Belongs to the nuclear hormone receptor family. NR3 subfamily. (527 aa)
RAF1RAF proto-oncogene serine/threonine-protein kinase; Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal- regulated kin [...] (668 aa)
GRB2Growth factor receptor-bound protein 2. (217 aa)
ARAFMetalloproteinase inhibitor 1; Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16. Does not act on MMP14. Also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signaling cascades via CD63 and ITGB1. Plays a role in integrin signaling. (795 aa)
ADCY6Adenylate cyclase type 6; Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. (1166 aa)
SOS2SOS Ras/Rho guanine nucleotide exchange factor 2. (1332 aa)
RB1RB transcriptional corepressor 1. (928 aa)
PIK3CBPhosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta; Belongs to the PI3/PI4-kinase family. (1070 aa)
JAG1Delta-like protein; Putative Notch ligand involved in the mediation of Notch signaling. (1218 aa)
CDKN1ACyclin dependent kinase inhibitor 1A. (161 aa)
MAP2K2Mitogen-activated protein kinase kinase 2; Belongs to the protein kinase superfamily. (447 aa)
SRCTyrosine-protein kinase. (688 aa)
RPS6KB2Ribosomal protein S6 kinase; Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily. (485 aa)
ADCY1Adenylate cyclase type 1; Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. . Mediates responses to increased cellular Ca(2+)/calmodulin levels. May be involved in regulatory processes in the central nervous system. May play a role in memory and learning. Plays a role in the regulation of the circadian rhythm of daytime contrast sensitivity probably by modulating the rhythmic synthesis of cyclic AMP in the retina (By similarity). (1134 aa)
NRASNRAS proto-oncogene, GTPase. (189 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 [...] (366 aa)
MAPK1Mitogen-activated protein kinase 1; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays a [...] (360 aa)
DLL4Delta-like protein; Putative Notch ligand involved in the mediation of Notch signaling. (685 aa)
DLL3Delta like canonical Notch ligand 3. (587 aa)
PIK3R1Phosphatidylinositol 3-kinase regulatory subunit alpha; Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling. Modulates the cellular response to ER stress by promoting nuclear translocation [...] (724 aa)
CDKN2CCyclin dependent kinase inhibitor 2C. (168 aa)
SHC3SHC adaptor protein 3. (583 aa)
SOS1SOS Ras/Rac guanine nucleotide exchange factor 1. (1333 aa)
SHC4Uncharacterized protein. (630 aa)
BADBCL2 associated agonist of cell death. (168 aa)
NOTCH1Notch receptor 1. (2533 aa)
ADCY8Adenylate cyclase type 8; Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. (1253 aa)
MTORSerine/threonine-protein kinase mTOR; Belongs to the PI3/PI4-kinase family. (2550 aa)
SHC2SHC adaptor protein 2. (584 aa)
MAPK3Mitogen-activated protein kinase; Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. MAP kinase subfamily. (456 aa)
MAPK11Mitogen-activated protein kinase. (364 aa)
RPS6KB1Ribosomal protein S6 kinase beta-1; Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTO [...] (525 aa)
GNASNeuroendocrine secretory protein 55; Belongs to the NESP55 family. (241 aa)
CCND1G1/S-specific cyclin-D1; Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. A [...] (428 aa)
AKT1RAC-alpha serine/threonine-protein kinase; AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (By similarity). AKT is responsible of the regulation of glucose uptake by mediating insulin- induced tra [...] (480 aa)
E2F2E2F transcription factor 2. (432 aa)
AKT3Non-specific serine/threonine protein kinase; Belongs to the protein kinase superfamily. (479 aa)
CDKN1BCyclin dependent kinase inhibitor 1B. (198 aa)
ADCY2Adenylate cyclase type 2; Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. (1052 aa)
MMP272 kDa type IV collagenase; Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta- type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3 [...] (661 aa)
BCL2Apoptosis regulator Bcl-2; Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1) (By similarity). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (By similarity). (229 aa)
SHC1SHC-transforming protein 1; Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis (By similarity). (583 aa)
MAPK10Mitogen-activated protein kinase. (426 aa)
MMP9Matrix metalloproteinase-9; Could play a role in bone osteoclastic resorption. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments (By similarity). Belongs to the peptidase M10A family. (712 aa)
E2F3E2F transcription factor 3. (463 aa)
IGF1RInsulin-like growth factor 1 receptor alpha chain; Receptor tyrosine kinase which mediates actions of insulin- like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates ( [...] (1367 aa)
HBEGFHeparin binding EGF like growth factor. (208 aa)
ERBB2Receptor protein-tyrosine kinase. (1255 aa)
ADCY5Adenylate cyclase type 5; Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. (1259 aa)
ADCY3Adenylate cyclase type 3; Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. (1145 aa)
ABCB11ATP binding cassette subfamily B member 11. (1324 aa)
MAP2K1Mitogen-activated protein kinase kinase 1; Belongs to the protein kinase superfamily. (393 aa)
PRKACBcAMP-dependent protein kinase catalytic subunit beta; Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, and differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these [...] (397 aa)
NOTCH4Notch receptor 4. (1989 aa)
CDKN2AUncharacterized protein. (153 aa)
MED1Mediator of RNA polymerase II transcription subunit 1; Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene- specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. (1575 aa)
NOTCH3Notch receptor 3. (2332 aa)
NCOR1Nuclear receptor corepressor 1. (2436 aa)
IGF1Insulin-like growth factor I; The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]- 2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. May play a role in synapse maturation. Ca(2+)-dependent exo [...] (188 aa)
HRASHRas proto-oncogene, GTPase. (199 aa)
ADCY9Adenylate cyclase 9; Belongs to the adenylyl cyclase class-4/guanylyl cyclase family. (1354 aa)
ADCY4Adenylate cyclase type 4; Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. (1077 aa)
PRKACAcAMP-dependent protein kinase catalytic subunit alpha; Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA and VASP. RORA is activated by phosphorylation. Required for glucose- mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the [...] (351 aa)
ADCY7Adenylate cyclase type 7; Catalyzes the formation of cAMP in response to activation of G protein-coupled receptors. Functions in signaling cascades activated namely by thrombin and sphingosine 1-phosphate and mediates regulation of cAMP synthesis through synergistic action of the stimulatory G alpha protein with GNA13 (By similarity). Also, during inflammation, mediates zymosan-induced increase intracellular cAMP, leading to protein kinase A pathway activation in order to modulate innate immune responses through heterotrimeric G proteins G(12/13) (By similarity). Functions in signaling [...] (1100 aa)
PIK3CDPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit. (1044 aa)
BRAFB-Raf proto-oncogene, serine/threonine kinase. (766 aa)
MAPK14Mitogen-activated protein kinase. (571 aa)
PTK2Protein tyrosine kinase 2; Belongs to the protein kinase superfamily. Tyr protein kinase family. (1108 aa)
NCOA3Nuclear receptor coactivator. (1411 aa)
JAG2Delta-like protein; Putative Notch ligand involved in the mediation of Notch signaling. (1069 aa)
PIK3CAPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform; Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to v [...] (1068 aa)
EGFRReceptor protein-tyrosine kinase. (1208 aa)
AKT2Non-specific serine/threonine protein kinase; Belongs to the protein kinase superfamily. (481 aa)
CDK4Cyclin-dependent kinase 4; Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. [...] (303 aa)
MDM2E3 ubiquitin-protein ligase Mdm2; Belongs to the MDM2/MDM4 family. (492 aa)
BAXApoptosis regulator BAX; Accelerates programmed cell death by binding to, and antagonizing the apoptosis repressor BCL2 or its adenovirus homolog E1B 19k protein. Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis. Promotes activation of CASP3, and thereby apoptosis. BAX deficiency leads to lymphoid hyperplasia and male sterility, because of the cessation of sperm production (By similarity). Interacts (via a C-terminal 33 residues) with NOL3 (via CARD domai [...] (355 aa)
NOTCH2Notch receptor 2. (2471 aa)
ESR1Estrogen receptor; Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE- independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial a [...] (596 aa)
Your Current Organism:
Bos taurus
NCBI taxonomy Id: 9913
Other names: B. taurus, Bos bovis, Bos primigenius taurus, Bovidae sp. Adi Nefas, bovine, cattle, cow, dairy cow, domestic cattle, domestic cow
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