STRINGSTRING
Hras Hras Bmi1 Bmi1 Ccn1 Ccn1 Ihh Ihh Hspg2 Hspg2 Pgr Pgr Gas1 Gas1 Shh Shh Vtn Vtn Mdm2 Mdm2 Ptch1 Ptch1 Bmp1 Bmp1 Snai2 Snai2 Dhh Dhh Igfbp6 Igfbp6 Gli1 Gli1 Angptl1 Angptl1 Cdh1 Cdh1 Rem1 Rem1 Smo Smo Ptch2 Ptch2 Casp9 Casp9 Kras Kras Mki67 Mki67 Muc5ac Muc5ac Mycn Mycn Hhat Hhat Snai1 Snai1 Pthlh Pthlh Erbb2 Erbb2 Gli2 Gli2 Foxc2 Foxc2 Cd24a Cd24a Epcam Epcam Gpc3 Gpc3 Foxm1 Foxm1 Jag2 Jag2 Hhip Hhip Lrp2 Lrp2 Spp1 Spp1 Itgb1 Itgb1 Ccnd1 Ccnd1 Scube2 Scube2 Trp53 Trp53 Gli3 Gli3 Sufu Sufu Itga6 Itga6 Bcl2 Bcl2 Runx2 Runx2 Pik3c3 Pik3c3 Vegfa Vegfa
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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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query proteins and first shell of interactors
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second shell of interactors
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proteins of unknown 3D structure
filled nodes:
a 3D structure is known or predicted
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Known Interactions
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
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textmining
co-expression
protein homology
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HrasGTPase HRas, N-terminally processed; Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. (189 aa)
Bmi1Polycomb complex protein BMI-1; Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. The complex composed of RNF2, UB2D3 and BMI1 binds nucleosomes, and has activity only with nucleosomal histone H2A. In the PRC1-like complex, regulates the E3 ub [...] (324 aa)
Ccn1CCN family member 1; Promotes cell proliferation, chemotaxis, angiogenesis and cell adhesion. Appears to play a role in wound healing by up- regulating, in skin fibroblasts, the expression of a number of genes involved in angiogenesis, inflammation and matrix remodeling including VEGA-A, VEGA-C, MMP1, MMP3, TIMP1, uPA, PAI-1 and integrins alpha-3 and alpha-5 (By similarity). CCN1-mediated gene regulation is dependent on heparin-binding (By similarity). Down-regulates the expression of alpha-1 and alpha-2 subunits of collagen type-1 (By similarity). Promotes cell adhesion and adhesive s [...] (379 aa)
IhhIndian hedgehog protein C-product; Intercellular signal essential for a variety of patterning events during development. Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes. Implicated in endochondral ossification: may regulate the balance between growth and ossification of the developing bones. Induces the expression of parathyroid hormone-related protein (PTHRP). (411 aa)
Hspg2Basement membrane-specific heparan sulfate proteoglycan core protein; Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development (By similarity). The LG3 peptide has anti-angiogenic propert [...] (4383 aa)
PgrProgesterone 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. Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor. [Isoform B]: Transcriptional activator of several progesteron-dependent promoters in a variety of cell types. Involved in activation of SRC-dependent MAPK signaling on hormone stimulation. Belongs to the nuclear hormone receptor family. NR3 subfamily. (926 aa)
Gas1Growth arrest-specific protein 1; Specific growth arrest protein involved in growth suppression. Blocks entry to S phase. Prevents cycling of normal and transformed cells. (384 aa)
ShhSonic hedgehog protein N-product; [Sonic hedgehog protein]: The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity. Both activities result in the cleavage of the full-length protein into two parts (ShhN and ShhC) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated ShhN. Both activities occur in the reticulum endoplasmic. Once cleaved, ShhC is degraded in the endoplasmic reticulum. (437 aa)
VtnVitronectin; Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family and serves as a cell-to-substrate adhesion molecule. Inhibitor of the membrane-damaging effect of the terminal cytolytic complement pathway. (478 aa)
Mdm2E3 ubiquitin-protein ligase Mdm2; E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73- mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain (By similarity). Also acts as a ubiquitin ligase E3 toward itself, ARRB1 and ARBB2. Permits the nuclear export of p53/TP53 (By similarity). Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein (By similarity). Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and [...] (489 aa)
Ptch1Protein patched homolog 1; Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH). Associates with the smoothened protein (SMO) to transduce the hedgehog's proteins signal. Seems to have a tumor suppressor function, as inactivation of this protein is probably a necessary, if not sufficient step for tumorigenesis. (1434 aa)
Bmp1Bone morphogenetic protein 1; Cleaves the C-terminal propeptides of procollagen I, II and III. Induces cartilage and bone formation. May participate in dorsoventral patterning during early development by cleaving chordin (CHRD) (By similarity). Responsible for the proteolytic activation of lysyl oxidase LOX. (991 aa)
Snai2Zinc finger protein SNAI2; Transcriptional repressor that modulates both activator- dependent and basal transcription. Involved in the generation and migration of neural crest cells. Plays a role in mediating RAF1-induced transcriptional repression of the TJ protein, occludin (OCLN) and subsequent oncogenic transformation of epithelial cells. Represses BRCA2 expression by binding to its E2-box-containing silencer and recruiting CTBP1 and HDAC1 in breast cells. In epidermal keratinocytes, binds to the E-box in ITGA3 promoter and represses its transcription. Involved in the regulation of [...] (269 aa)
DhhDesert hedgehog protein C-product; Intercellular signal essential for a variety of patterning events during development. May function as a spermatocyte survival factor in the testes. Essential for testes development. (396 aa)
Igfbp6Insulin-like growth factor-binding protein 6; IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. (238 aa)
Gli1Zinc finger protein GLI1; Acts as a transcriptional activator. Binds to the DNA consensus sequence 5'-GACCACCCA-3'. Regulates the transcription of specific genes during normal development. Plays a role in craniofacial development and digital development, as well as development of the central nervous system and gastrointestinal tract. Mediates SHH signaling. Plays a role in cell proliferation and differentiation via its role in SHH signaling; Belongs to the GLI C2H2-type zinc-finger protein family. (1111 aa)
Angptl1Angiopoietin-related protein 1. (490 aa)
Cdh1Cadherin-1; Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility and proliferation of epithelial cells. Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7 (By similarity). (Microbial infection) Does not function as a receptor for L.monocytogenes internalin A (InlA); mutating a single surface-exposed residue confers recep [...] (884 aa)
Rem1GTP-binding protein REM 1; Promotes endothelial cell sprouting and actin cytoskeletal reorganization (By similarity). May be involved in angiogenesis. May function in Ca(2+) signaling; Belongs to the small GTPase superfamily. RGK family. (297 aa)
SmoSmoothened homolog; G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO) (By similarity). Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia. Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation. (793 aa)
Ptch2Protein patched homolog 2; Plays a role in the control of cellular growth (By similarity). May have a role in epidermal development. May act as a receptor for Sonic hedgehog (SHH); Belongs to the patched family. (1182 aa)
Casp9Caspase-9 subunit p10; Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates caspase-3. Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) (By similarity). (454 aa)
KrasGTPase KRas, N-terminally processed; Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (By similarity). Plays an important role in the regulation of cell proliferation. Plays a role in promoting oncogenic events by inducing transcriptional silencing of tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a ZNF304-dependent manner (By similarity). (188 aa)
Mki67Proliferation marker protein Ki-67; Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly. Associates with the surface of the mitotic chromosome, the perichromosomal layer, and covers a substantial fraction of the chromosome surface. Prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility. Binds DNA, with a preference for s [...] (3177 aa)
Muc5acMucin 5, subtypes A and C, tracheobronchial/gastric. (2751 aa)
MycnN-myc proto-oncogene protein; Positively regulates the transcription of MYCNOS in neuroblastoma cells. (462 aa)
HhatProtein-cysteine N-palmitoyltransferase HHAT; Catalyzes N-terminal palmitoylation of SHH; which is required for SHH signaling during limb development. May bind GTP. (499 aa)
Snai1Zinc finger protein SNAI1; Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration. Binds to 3 E-boxes of the E-cadherin gene promoter and to the promoters of CLDN7 and KRT8 and, in association with histone demethylase KDM1A which it recruits to the promoters, causes a decrease in dimethylated H3K4 levels and represses transcription. Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival a [...] (264 aa)
PthlhParathyroid hormone-related protein; Neuroendocrine peptide which is a critical regulator of cellular and organ growth, development, migration, differentiation and survival and of epithelial calcium ion transport. Regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. Required for skeletal homeostasis. Promotes mammary mesenchyme differentiation and bud outgrowth by modulating mesenchymal cell responsiveness to BMPs. Upregulates BMPR1A expression in the mammary mesenchyme and this increases the sensitivity o [...] (175 aa)
Erbb2Receptor tyrosine-protein kinase erbB-2; Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and [...] (1256 aa)
Gli2Zinc finger protein GLI2; Functions as transcription regulator in the hedgehog (Hh) pathway. Functions as transcriptional activator. May also function as transcriptional repressor. Requires STK36 for full transcriptional activator activity. Binds to the DNA sequence 5'-GAACCACCCA-3' which is part of the TRE-2S regulatory element (By similarity). Is involved in the smoothened (SHH) signaling pathway. Required for normal skeleton development. Belongs to the GLI C2H2-type zinc-finger protein family. (1544 aa)
Foxc2Forkhead box protein C2; Transcriptional activator. Might be involved in the formation of special mesenchymal tissues. (494 aa)
Cd24aSignal transducer CD24; May have a pivotal role in cell differentiation of different cell types. May have a specific role in early thymocyte development. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of second messengers derived from the GPI-anchor. Modulates B-cell activation responses (By similarity). In association with SIGLEC10 may be involved in the selective suppression of the immune response to danger- associated molecular patterns (DAMPs) such as HMGB1, HSP70 and HSP90. Plays a role in the control of [...] (76 aa)
EpcamEpithelial cell adhesion molecule; May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosal infection. Plays a role in embryonic stem cells proliferation and differentiation. Up-regulates the expression of FABP5, MYC and cyclins A and E (By similarity). Belongs to the EPCAM family. (315 aa)
Gpc3Glypican-3 alpha subunit; Cell surface proteoglycan that bears heparan sulfate (By similarity). Negatively regulates the hedgehog signaling pathway when attached via the GPI-anchor to the cell surface by competing with the hedgehog receptor PTC1 for binding to hedgehog proteins. Binding to the hedgehog protein SHH triggers internalization of the complex by endocytosis and its subsequent lysosomal degradation. Positively regulates the canonical Wnt signaling pathway by binding to the Wnt receptor Frizzled and stimulating the binding of the Frizzled receptor to Wnt ligands (By similarity [...] (579 aa)
Foxm1Forkhead box protein M1; Transcriptional factor regulating the expression of cell cycle genes essential for DNA replication and mitosis. Plays a role in the control of cell proliferation. Plays also a role in DNA breaks repair participating in the DNA damage checkpoint response. (757 aa)
Jag2Protein jagged-2; Putative Notch ligand involved in the mediation of Notch signaling. Plays an essential role during limb, craniofacial and thymic development. May be involved in myogenesis and in the development of peripheral and central nervous systems. (1247 aa)
HhipHedgehog-interacting protein; Modulates hedgehog signaling in several cell types, including brain and lung through direct interaction with members of the hedgehog family. Soluble forms inhibit Shh-induced differentiation in the fibroblast cell line C3H/10T1/2; Belongs to the HHIP family. (700 aa)
Lrp2Low-density lipoprotein receptor-related protein 2; Multiligand endocytic receptor. Acts together with CUBN to mediate endocytosis of high-density lipoproteins. Mediates receptor-mediated uptake of polybasic drugs such as aprotinin, aminoglycosides and polymyxin B (By similarity). In the kidney, mediates the tubular uptake and clearance of leptin. Also mediates transport of leptin across the blood-brain barrier through endocytosis at the choroid plexus epithelium (By similarity). Endocytosis of leptin in neuronal cells is required for hypothalamic leptin signaling and leptin-mediated r [...] (4660 aa)
Spp1Osteopontin; Binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction; Belongs to the osteopontin family. (295 aa)
Itgb1Integrin beta-1; Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-G- E-R in collagen. Integrins alpha-2/beta-1, alpha-3/beta-1, alpha- 4/beta-1, alpha-5/beta-1, alpha-8/beta-1, alpha-10/beta-1, alpha- 11/beta-1 and alpha-V/beta-1 are receptors for fibronectin. Alpha- 4/beta-1 recognizes one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. Integrin alpha-5/beta-1 is a receptor for fibrinogen. Integrin [...] (798 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 [...] (295 aa)
Scube2Signal peptide, CUB and EGF-like domain-containing protein 2; Lipid-binding protein required for SHH long-range signaling by binding to the dually lipid-modified SHH (ShhNp) and by promoting ShhNp mobilization, solubilization and release from the cell membrane. Acts by enhancing the proteolytic processing (shedding) of the lipid-modified N- and C- terminal of ShhNp at the cell surface. Synergizes with DISP1 to cause an increase in SHH secretion. Probable cell surface coreceptor for VEGFR2 involved in VEGFR2-mediated angiogenesis. (968 aa)
Trp53Cellular 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 [...] (390 aa)
Gli3Transcriptional repressor GLI3R; Has a dual function as a transcriptional activator and a repressor of the sonic hedgehog (Shh) pathway, and plays a role in limb development. The full-length GLI3 form (GLI3FL) after phosphorylation and nuclear translocation, acts as an activator (GLI3A) while GLI3R, its C-terminally truncated form, acts as a repressor. A proper balance between the GLI3 activator and the repressor GLI3R, rather than the repressor gradient itself or the activator/repressor ratio gradient, specifies limb digit number and identity. In concert with TRPS1, plays a role in re [...] (1583 aa)
SufuSuppressor of fused homolog; Negative regulator in the hedgehog/smoothened signaling pathway. Down-regulates GLI1- mediated transactivation of target genes. Part of a corepressor complex that acts on DNA-bound GLI1. May also act by linking GLI1 to BTRC and thereby targeting GLI1 to degradation by the proteasome (By similarity). Sequesters GLI1, GLI2 and GLI3 in the cytoplasm, this effect is overcome by binding of STK36 to both SUFU and a GLI protein. Negative regulator of beta-catenin signaling. Regulates the formation of either the repressor form (GLI3R) or the activator form (GLI3A) [...] (485 aa)
Itga6Integrin alpha-6 heavy chain; Integrin alpha-6/beta-1 (ITGA6:ITGB1) is a receptor for laminin on platelets. Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion. Integrin alpha-6/beta-4 (ITGA6:ITGB4) is a receptor for laminin in epithelial cells and it plays a critical structural role in the hemidesmosome. ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (By similarity). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (By similarity). ITGA6:ITGB4 binds to IGF2 and this [...] (1091 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). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release. (236 aa)
Runx2Runt-related transcription factor 2; Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis. Essential for the maturation of osteoblasts and both intramembranous and endochondral ossification. CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, osteocalcin, osteopontin, bone sialoprotein, alpha 1(I) collagen, LCK, IL-3 and GM-CSF promoters. Inhibits KAT6B-dependent transcriptional activation (By similarity). In osteoblasts, supports transc [...] (528 aa)
Pik3c3Phosphatidylinositol 3-kinase catalytic subunit type 3; Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2. Involved in the transport of lysosomal enzyme precursors to lysosomes. Requ [...] (887 aa)
VegfaVascular endothelial growth factor A; Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. May play a role in increasing vascular permeability during lactation, when increased transport of molecules from the blood is required for efficient milk protein synthesis (By similarity). Binding to NRP1 receptor initiates a signaling pathway needed for motor [...] (392 aa)
Your Current Organism:
Mus musculus
NCBI taxonomy Id: 10090
Other names: LK3 transgenic mice, M. musculus, Mus sp. 129SV, house mouse, mouse, nude mice, transgenic mice
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