STRINGSTRING
HFE HFE ACVR1 ACVR1 TNF TNF IL6 IL6 TMPRSS6 TMPRSS6 INS INS SLC11A2 SLC11A2 TFRC TFRC JAK2 JAK2 BMPR1A BMPR1A FLVCR1 FLVCR1 NEO1 NEO1 IL1A IL1A IL1B IL1B STAT3 STAT3 BMP6 BMP6 EIF5B EIF5B LEP LEP CYBRD1 CYBRD1 OSM OSM HJV HJV SLC40A1 SLC40A1 HAMP HAMP IL22 IL22 CEBPA CEBPA TFR2 TFR2
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:
HFEHereditary hemochromatosis protein; Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin. (348 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 for left-right pattern formation during embryogenesis (By similarity); Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. (509 aa)
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. Impairs regulatory T- cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 [...] (233 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 [...] (212 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. (824 aa)
INSInsulin A chain; Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver. (110 aa)
SLC11A2Natural resistance-associated macrophage protein 2; Important in metal transport, in particular iron. Can also transport manganese, cobalt, cadmium, nickel, vanadium and lead. 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. May serve to import iron into the mitochondria. Belongs to the NRAMP family. (590 aa)
TFRCTransferrin receptor protein 1, serum form; 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). A second ligand, the heditary hemochromatosis protein HFE, competes for binding with tra [...] (760 aa)
JAK2Tyrosine-protein kinase JAK2; Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN- beta, IFN-gamma and multiple interleukins. Following ligand-binding to cell surface receptors [...] (1132 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)
FLVCR1Feline leukemia virus subgroup C receptor-related protein 1; [Isoform 1]: Heme transporter that exports cytoplasmic heme. It can also export coproporphyrin and protoporphyrin IX, which are both intermediate products in the heme biosynthetic pathway. Does not export bilirubin. Heme export depends on the presence of HPX and is required to maintain intracellular free heme balance, protecting cells from heme toxicity. Heme export provides protection from heme or ferrous iron toxicities in liver, brain, sensory neurons and during erythtopoiesis, a process in which heme synthesis intensifies [...] (555 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. Belongs to the immunoglobulin superfamily. DCC family. (1461 aa)
IL1AInterleukin-1 alpha; Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells. (271 aa)
IL1BInterleukin-1 beta; Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B- cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T- helper 1 (Th1) cells. (269 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. Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. Acts as a regulator of inflammatory response by regulating differenti [...] (770 aa)
BMP6Bone morphogenetic protein 6; Induces cartilage and bone formation. (513 aa)
EIF5BEukaryotic translation initiation factor 5B; Plays a role in translation initiation. Translational GTPase that catalyzes the joining of the 40S and 60S subunits to form the 80S initiation complex with the initiator methionine-tRNA in the P-site base paired to the start codon. GTP binding and hydrolysis induces conformational changes in the enzyme that renders it active for productive interactions with the ribosome. The release of the enzyme after formation of the initiation complex is a prerequisite to form elongation-competent ribosomes. (1220 aa)
LEPLeptin; Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in the activation of several major signaling pathways. In the hypothalamus, acts as an appetite-regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo- pituitary-adrenal hormones. In the periphery, increases basal me [...] (167 aa)
CYBRD1Cytochrome b reductase 1; Ferric-chelate reductase that reduces Fe(3+) to Fe(2+). Present at the brush border of duodenal enterocytes where it probably reduces dietary Fe(3+) thereby facilitating its transport into the mucosal cells. Uses ascorbate as electron donor. May be involved in extracellular ascorbate recycling in erythrocyte membranes. May also act as a ferrireductase in airway epithelial cells. (286 aa)
OSMOncostatin-M; Growth regulator. Inhibits the proliferation of a number of tumor cell lines. Stimulates proliferation of AIDS-KS cells. It regulates cytokine production, including IL-6, G-CSF and GM-CSF from endothelial cells. Uses both type I OSM receptor (heterodimers composed of LIFR and IL6ST) and type II OSM receptor (heterodimers composed of OSMR and IL6ST). Involved in the maturation of fetal hepatocytes, thereby promoting liver development and regeneration (By similarity). Belongs to the LIF/OSM family. (252 aa)
HJVHemojuvelin; Acts as a bone morphogenetic protein (BMP) coreceptor. Through enhancement of BMP signaling regulates hepcidin (HAMP) expression and regulates iron homeostasis. Belongs to the repulsive guidance molecule (RGM) family. (426 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); Belongs to the ferroportin (FP) (TC 2.A.100) family. SLC40A subfamily. (571 aa)
HAMPHepcidin-20; 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. (84 aa)
IL22Interleukin-22; Cytokine that contributes to the inflammatory response in vivo. (179 aa)
CEBPACCAAT/enhancer-binding protein alpha; Transcription factor that coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, and cells of the lung and the placenta. Binds directly to the consensus DNA sequence 5'-T[TG]NNGNAA[TG]-3' acting as an activator on distinct target genes. During early embryogenesis, plays essential and redundant functions with CEBPB. Essential for the transition from common myeloid progenitors (CMP) to granulocyte/monocyte progenitors (GMP). Critical for the proper development of the liver and the lung (By similarity [...] (358 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. (801 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
Server load: low (34%) [HD]
STRING is a Core Data Resource as designated by Global Biodata Coalition and ELIXIR.