STRINGSTRING
Tnf Tnf Slc11a2 Slc11a2 Tfrc Tfrc Scara5 Scara5 Gdf2 Gdf2 Bmp5 Bmp5 Bmp7 Bmp7 Tgfbr1 Tgfbr1 Acvr1b Acvr1b Tmprss6 Tmprss6 Smad1 Smad1 Smurf1 Smurf1 Erfe Erfe Bmpr2 Bmpr2 Acvr1 Acvr1 Hfe Hfe Smurf2 Smurf2 Hamp2 Hamp2 Tfr2 Tfr2 Rgma Rgma Timd2 Timd2 Slc39a8 Slc39a8 Bmp6 Bmp6 Rgmb Rgmb Mb Mb Nfe2 Nfe2 Stat3 Stat3 Pecam1 Pecam1 Nfe2l2 Nfe2l2 Slc39a14 Slc39a14 Neo1 Neo1 Hamp Hamp Stab2 Stab2 Gdf5 Gdf5 Hjv Hjv Gdf7 Gdf7 Smad6 Smad6 Bmpr1a Bmpr1a Acvrl1 Acvrl1 Mcam Mcam Bmpr1b Bmpr1b Acvr1c Acvr1c Slc40a1 Slc40a1 Smad7 Smad7 Il6 Il6 Lox Lox Smad4 Smad4
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 Color
colored nodes:
query proteins and first shell of interactors
white nodes:
second shell of interactors
Node Content
empty nodes:
proteins of unknown 3D structure
filled nodes:
a 3D structure is known or predicted
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 to 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:
TnfTumor necrosis factor, membrane form; Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation (By similarity). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces [...] (235 aa)
Slc11a2Natural resistance-associated macrophage protein 2; May serve to import iron into the mitochondria (By similarity). Important in metal transport, in particular iron. Involved in apical iron uptake into duodenal enterocytes. Involved in iron transport from acidified endosomes into the cytoplasm of erythroid precursor cells. May play an important role in hepatic iron accumulation and tissue iron distribution. (568 aa)
TfrcTransferrin receptor protein 1; Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes. Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). Upon stimulation, positively regulates T and B cell proliferation through iron uptake ; Belongs to t [...] (763 aa)
Scara5Scavenger receptor class A member 5; Ferritin receptor that mediates non-transferrin-dependent delivery of iron. Mediates cellular uptake of ferritin-bound iron by stimulating ferritin endocytosis from the cell surface with consequent iron delivery within the cell. Delivery of iron to cells by ferritin is required for the development of specific cell types, suggesting the existence of cell type-specific mechanisms of iron traffic in organogenesis, which alternatively utilize transferrin or non- transferrin iron delivery pathways. Ferritin mediates iron uptake in capsule cells of the de [...] (491 aa)
Gdf2Growth/differentiation factor 2; Potent circulating inhibitor of angiogenesis (By similarity). Signals through the type I activin receptor ACVRL1 but not other Alks. Signaling through SMAD1 in endothelial cells requires TGF-beta coreceptor endoglin/ENG. (428 aa)
Bmp5Bone morphogenetic protein 5; Induces cartilage and bone formation; Belongs to the TGF-beta family. (454 aa)
Bmp7Bone morphogenetic protein 7; Induces cartilage and bone formation. May be the osteoinductive factor responsible for the phenomenon of epithelial osteogenesis. Plays a role in calcium regulation and bone homeostasis. (430 aa)
Tgfbr1TGF-beta receptor type-1; Transmembrane serine/threonine kinase forming with the TGF- beta type II serine/threonine kinase receptor, TGFBR2, the non- promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinog [...] (503 aa)
Acvr1bActivin receptor type-1B; Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine [...] (505 aa)
Tmprss6Transmembrane protease serine 6; Serine protease which hydrolyzes a range of proteins including type I collagen, fibronectin and fibrinogen. Can also activate urokinase-type plasminogen activator with low efficiency. May play a specialized role in matrix remodeling processes in liver. Through the cleavage of HJV, a regulator of the expression of the iron absorption-regulating hormone hepicidin/HAMP, plays a role in iron homeostasis. (811 aa)
Smad1Mothers against decapentaplegic homolog 1; Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD1 is a receptor- regulated SMAD (R-SMAD) (By similarity). May play a role in the initiation and maintenance of spermatogenesis. SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1 (By similarity). May act synergistically with SMAD4 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. (465 aa)
Smurf1E3 ubiquitin-protein ligase SMURF1; E3 ubiquitin-protein ligase that acts as a negative regulator of BMP signaling pathway (By similarity). Mediates ubiquitination and degradation of SMAD1 and SMAD5, 2 receptor-regulated SMADs specific for the BMP pathway (By similarity). Promotes ubiquitination and subsequent proteasomal degradation of TRAF family members and RHOA (By similarity). Promotes ubiquitination and subsequent proteasomal degradation of MAVS. Plays a role in dendrite formation by melanocytes (By similarity). (731 aa)
ErfeErythroferrone; Iron-regulatory hormone that acts as an erythroid regulator after hemorrhage: produced by erythroblasts following blood loss and mediates suppression of hepcidin (HAMP) expression in the liver, thereby promoting increased iron absorption and mobilization from stores. Promotes lipid uptake into adipocytes and hepatocytes via transcriptional up-regulation of genes involved in fatty acid uptake. (340 aa)
Bmpr2Bone morphogenetic protein receptor type-2; On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Binds to BMP7, BMP2 and, less efficiently, BMP4. Binding is weak but enhanced by the presence of type I receptors for BMPs. Mediates induction of adipogenesis by GDF6. (1038 aa)
Acvr1Activin receptor type-1; On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for activin. May be involved in left-right pattern formation during embryogenesis; Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. (509 aa)
HfeHereditary hemochromatosis protein homolog; Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin. (359 aa)
Smurf2E3 ubiquitin-protein ligase SMURF2; E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Interacts with SMAD1 and SMAD7 in order to trigger their ubiquitination and proteasome-dependent degradation. In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with SCYE1. Forms a stable complex with the TGF-beta receptor-mediated phosphorylated SMAD2 and SMAD3. In this way, SMAD2 may recruit substrates, such as [...] (748 aa)
Hamp2Hepcidin-2; Seems to act as a signaling molecule involved in the maintenance of iron homeostasis. (84 aa)
Tfr2Transferrin receptor protein 2; Mediates cellular uptake of transferrin-bound iron in a non- iron dependent manner. May be involved in iron metabolism, hepatocyte function and erythrocyte differentiation; Belongs to the peptidase M28 family. M28B subfamily. (798 aa)
RgmaRepulsive guidance molecule A; Member of the repulsive guidance molecule (RGM) family that performs several functions in the developing and adult nervous system. Regulates cephalic neural tube closure, inhibits neurite outgrowth and cortical neuron branching, and the formation of mature synapses. Binding to its receptor NEO1/neogenin induces activation of RHOA- ROCK1/Rho-kinase signaling pathway through UNC5B-ARHGEF12/LARG- PTK2/FAK1 cascade, leading to collapse of the neuronal growth cone and neurite outgrowth inhibition. Furthermore, RGMA binding to NEO1/neogenin leads to HRAS inacti [...] (454 aa)
Timd2T-cell immunoglobulin and mucin domain-containing protein 2; Probable receptor for SEMA4A involved in the regulation of T- cell function. The interaction with SEMA4A enhances T-cell activation. Belongs to the immunoglobulin superfamily. TIM family. (305 aa)
Slc39a8Zinc transporter ZIP8; Acts as a manganese and zinc influx transporter. Plays a role in manganese reabsorption in the proximal tubule of the kidney and in manganese uptake into the brain. (462 aa)
Bmp6Bone morphogenetic protein 6; Induces cartilage and bone formation; Belongs to the TGF-beta family. (510 aa)
RgmbRGM domain family member B; Member of the repulsive guidance molecule (RGM) family that contributes to the patterning of the developing nervous system. Acts as a bone morphogenetic protein (BMP) coreceptor that potentiates BMP signaling. Promotes neuronal adhesion. May inhibit neurite outgrowth (By similarity). (436 aa)
MbMyoglobin; Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles. (154 aa)
Nfe2Transcription factor NF-E2 45 kDa subunit; Component of the NF-E2 complex essential for regulating erythroid and megakaryocytic maturation and differentiation. Binds to the hypersensitive site 2 (HS2) of the beta-globin control region (LCR). This subunit (NFE2) recognizes the TCAT/C sequence of the AP-1- like core palindrome present in a number of erythroid and megakaryocytic gene promoters. Requires MAFK or other small MAF proteins for binding to the NF-E2 motif. May play a role in all aspects of hemoglobin production from globin and heme synthesis to procurement of iron; Belongs to t [...] (373 aa)
Stat3Signal transducer and activator of transcription 3; Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (By similarity). Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene (By similarity). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Binds to the interleukin-6 (IL-6)- responsive elements identified in the promoters of various acute-phase protein genes (By similarity). Activated by IL31 through IL31RA (By s [...] (770 aa)
Pecam1Platelet endothelial cell adhesion molecule; Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (By similarity). Tyr-679 plays a critical role in TEM and is required for efficient trafficking of PECAM1 to and from the lateral border recycling compartment (LBRC) and is also essential for the LBRC membrane to be targeted around migrating leukocytes (By similarity). Trans-homophilic interaction may play a role in endothelial cell-cell adhesion via cell junctions (By similarity). Heterophilic interaction with CD177 pla [...] (727 aa)
Nfe2l2Nuclear factor erythroid 2-related factor 2; Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralizing reactive electrophiles. In normal conditions, ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex. In response to oxidative stress, electrophile metabolites inhibit activity of the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2, hetero [...] (597 aa)
Slc39a14Zinc transporter ZIP14; Broad-scope metal ion transporter with a preference for zinc uptake. Also mediates cellular uptake of nontransferrin-bound iron. (489 aa)
Neo1Neogenin; Multi-functional cell surface receptor regulating cell adhesion in many diverse developmental processes, including neural tube and mammary gland formation, myogenesis and angiogenesis. Receptor for members of the BMP, netrin, and repulsive guidance molecule (RGM) families. Netrin-Neogenin interactions result in a chemoattractive axon guidance response and cell-cell adhesion, the interaction between NEO1/Neogenin and RGMa and RGMb induces a chemorepulsive response. (1492 aa)
HampHepcidin; Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues. Acts by promoting endocytosis and degradation of ferroportin, leading to the retention of iron in iron-exporting cells and decreased flow of iron into plasma. Controls the major flows of iron into plasma: absorption of dietary iron in the intestine, recycling of iron by macrophages, which phagocytose old erythrocytes and other cells, and mobilization of stored iron from hepatocytes; Belongs to the hepcidin family. (83 aa)
Stab2Short form stabilin-2; Phosphatidylserine receptor that enhances the engulfment of apoptotic cells. Hyaluronan receptor that binds to and mediates endocytosis of hyaluronic acid (HA). Acts also, in different species, as a primary systemic scavenger receptor for heparin (Hep), chondroitin sulfate (CS), dermatan sulfate (DS), nonglycosaminoglycan (GAG), acetylated low-density lipoprotein (AcLDL), pro-collagen propeptides and advanced glycation end products (AGE). May serve to maintain tissue integrity by supporting extracellular matrix turnover or it may contribute to maintaining fluidit [...] (2559 aa)
Gdf5Growth/differentiation factor 5; Growth factor involved in bone and cartilage formation. During cartilage development regulates differentiation of chondrogenic tissue through two pathways. Firstly, positively regulates differentiation of chondrogenic tissue through its binding of high affinity with BMPR1B and of less affinity with BMPR1A, leading to induction of SMAD1-SMAD5-SMAD8 complex phosphorylation and then SMAD protein signaling transduction (By similarity). Secondly, negatively regulates chondrogenic differentiation through its interaction with NOG (By similarity). Required to p [...] (495 aa)
HjvHemojuvelin; Acts as a bone morphogenetic protein (BMP) coreceptor. Through enhancement of BMP signaling regulates hepcidin (HAMP) expression and regulates iron homeostasis. (420 aa)
Gdf7Growth/differentiation factor 7. (461 aa)
Smad6Mothers against decapentaplegic homolog 6; Binds to regulatory elements in target promoter regions (By similarity). May block the BMP-SMAD1 signaling pathway by competing with SMAD4 for receptor-activated SMAD1-binding (By similarity). Acts as a mediator of TGF-beta and BMP antiflammatory activity. Suppresses IL1R-TLR signaling through its direct interaction with PEL1, preventing NF-kappa-B activation, nuclear transport and NF-kappa-B-mediated expression of proinflammatory genes. (495 aa)
Bmpr1aBone morphogenetic protein receptor type-1A; On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for BMP2, BMP4, GDF5 and GDF6. Positively regulates chondrocyte differentiation through GDF5 interaction. Mediates induction of adipogenesis by GDF6 ; Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. (532 aa)
Acvrl1Serine/threonine-protein kinase receptor R3; Type I receptor for TGF-beta family ligands BMP9/GDF2 and BMP10 and important regulator of normal blood vessel development. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. May bind activin as well. (502 aa)
McamCell surface glycoprotein MUC18; Plays a role in cell adhesion, and in cohesion of the endothelial monolayer at intercellular junctions in vascular tissue. Its expression may allow melanoma cells to interact with cellular elements of the vascular system, thereby enhancing hematogeneous tumor spread. Could be an adhesion molecule active in neural crest cells during embryonic development. Acts as surface receptor that triggers tyrosine phosphorylation of FYN and PTK2/FAK1, and a transient increase in the intracellular calcium concentration (By similarity). (648 aa)
Bmpr1bBone morphogenetic protein receptor type-1B; On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for BMP7/OP-1. Receptor for GDF5. Positively regulates chondrocyte differentiation through GDF5 interaction. (502 aa)
Acvr1cActivin receptor type-1C; Serine/threonine protein kinase which forms a receptor complex on ligand binding. The receptor complex consisting of 2 type II and 2 type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators, SMAD2 and SMAD3. Receptor for activin AB, activin B and NODAL. Plays a role in cell differentiation, growth arrest and apoptosis. (493 aa)
Slc40a1Solute carrier family 40 member 1; May be involved in iron export from duodenal epithelial cell and also in transfer of iron between maternal and fetal circulation. Mediates iron efflux in the presence of a ferroxidase (hephaestin and/or ceruloplasmin). (570 aa)
Smad7Mothers against decapentaplegic homolog 7; Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members; has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associating with their receptors thus preventing SMAD2 access. Functions as an adapter to recruit SMURF2 to the TGF-beta receptor complex. Also acts by recruiting the PPP1R15A-PP1 complex to TGFBR1, which promotes its dephosphorylation. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a [...] (426 aa)
Il6Interleukin-6; Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Involved in lymphocyte and monocyte differentiation. Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Required for the generation of T(H)17 cells. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance. It induces myeloma and plasm [...] (211 aa)
LoxProtein-lysine 6-oxidase, short form; Responsible for the post-translational oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin. Regulator of Ras expression. May play a role in tumor suppression. Plays a role in the aortic wall architecture. (411 aa)
Smad4Mothers against decapentaplegic homolog 4; Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling. Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for synergistic transcriptional activity in r [...] (551 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
Server load: low (18%) [HD]
STRING is a Core Data Resource as designated by Global Biodata Coalition and ELIXIR.