STRINGSTRING
FLG FLG CD4 CD4 TGM1 TGM1 IFNG IFNG IL4 IL4 IL5 IL5 PI3 PI3 LIF LIF KRT5 KRT5 KRT1 KRT1 DSG1 DSG1 DSC1 DSC1 TLR2 TLR2 BLMH BLMH CDH1 CDH1 IL1A IL1A ICAM1 ICAM1 KRT10 KRT10 CA2 CA2 CLDN1 CLDN1 TLR3 TLR3 IL3 IL3 CSF2 CSF2 STAT6 STAT6 DEFB4A DEFB4A HAS3 HAS3 IL13 IL13 CXCL10 CXCL10 CXCL8 CXCL8 TERT TERT KLK5 KLK5 TSLP TSLP OCLN OCLN TJP1 TJP1 SPINK5 SPINK5 CLDN7 CLDN7 S100A7 S100A7 LOR LOR SPRR2B SPRR2B IVL IVL HRNR HRNR IL13RA2 IL13RA2 CDSN CDSN IL31 IL31 CRLF2 CRLF2 FLG2 FLG2 SPRR2A SPRR2A IL4R IL4R IL6 IL6 CASP14 CASP14 TNF TNF CLDN4 CLDN4 NELL2 NELL2 TJP2 TJP2 IL22 IL22 NTF4 NTF4 CCL5 CCL5 KITLG KITLG IL17A IL17A
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:
FLGFilaggrin; Aggregates keratin intermediate filaments and promotes disulfide-bond formation among the intermediate filaments during terminal differentiation of mammalian epidermis. (4061 aa)
CD4T-cell surface glycoprotein CD4; Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class II molecule:peptide complex. The antigens presented by class II peptides are derived from extracellular proteins while class I peptides are derived from cytosolic proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen presenting cells (APCs). In turn, recruits the Src kina [...] (458 aa)
TGM1Protein-glutamine gamma-glutamyltransferase K; Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Responsible for cross-linking epidermal proteins during formation of the stratum corneum. Involved in cell proliferation ; Belongs to the transglutaminase superfamily. Transglutaminase family. (817 aa)
IFNGInterferon gamma; Produced by lymphocytes activated by specific antigens or mitogens. IFN-gamma, in addition to having antiviral activity, has important immunoregulatory functions. It is a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons; Belongs to the type II (or gamma) interferon family. (166 aa)
IL4Interleukin-4; Participates in at least several B-cell activation processes as well as of other cell types. It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1. It also regulates the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes. Positively regulates IL31RA expression in macrophages (By similarity). Stimulates autophagy in dendritic cells by interfering with mTORC1 signaling and through the induction of RUFY4 (By [...] (153 aa)
IL5Interleukin-5; Factor that induces terminal differentiation of late- developing B-cells to immunoglobulin secreting cells; Belongs to the IL-5 family. (134 aa)
PI3Elafin; Neutrophil and pancreatic elastase-specific inhibitor of skin. It may prevent elastase-mediated tissue proteolysis. Has been shown to inhibit the alpha-4-beta-2/CHRNA2-CHRNB2 nicotinic acetylcholine receptor and to produce a weak inhibition on Kv11.1/KCNH2/ERG1 and on the transient receptor potential cation channel subfamily V member 1 (TRPV1). (117 aa)
LIFLeukemia inhibitory factor; LIF has the capacity to induce terminal differentiation in leukemic cells. Its activities include the induction of hematopoietic differentiation in normal and myeloid leukemia cells, the induction of neuronal cell differentiation, and the stimulation of acute-phase protein synthesis in hepatocytes. (202 aa)
KRT5Keratin, type II cytoskeletal 5; Keratin 5; Belongs to the intermediate filament family. (590 aa)
KRT1Keratin, type II cytoskeletal 1; May regulate the activity of kinases such as PKC and SRC via binding to integrin beta-1 (ITB1) and the receptor of activated protein C kinase 1 (RACK1). In complex with C1QBP is a high affinity receptor for kininogen-1/HMWK. (644 aa)
DSG1Desmoglein-1; Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. (1049 aa)
DSC1Desmocollin-1; Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms. Linked to the keratinization of epithelial tissues. (894 aa)
TLR2Toll-like receptor 2; Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. May also activate immune cells and promote apoptosis in response to the lipid moiety of lipoproteins. Recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble [...] (784 aa)
BLMHBleomycin hydrolase; The normal physiological role of BLM hydrolase is unknown, but it catalyzes the inactivation of the antitumor drug BLM (a glycopeptide) by hydrolyzing the carboxamide bond of its B- aminoalaninamide moiety thus protecting normal and malignant cells from BLM toxicity. (455 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. (Microbial infection) Serves as a receptor for Listeria monocytogenes; internalin A (InlA) binds to this protein and promotes uptake of the bacteria. (882 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)
ICAM1Intercellular adhesion molecule 1; ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups through ARHGEF26/SGEF and RHOG activation. (Microbial infection) Acts as a receptor for Coxsackievirus A21 capsid proteins. (532 aa)
KRT10Keratin, type I cytoskeletal 10; Plays a role in the establishment of the epidermal barrier on plantar skin. (Microbial infection) Binds S.pneumoniae PsrP, mediating adherence of the bacteria to lung cell lines. Reduction of levels of KRT10 keratin decrease adherence, overexpression increases adherence. Neither protein has to be glycosylated for the interaction to occur. (584 aa)
CA2Carbonic anhydrase 2; Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton- coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6. (260 aa)
CLDN1Claudin-1; Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermeable barriers, others mediate the permeability to ions and small molecules. Often, several claudin family members are coexpressed and interact with each other, and this determines the overall permeability. CLDN1 is required to prevent the paracellular diffusion of small molecules through tight junctions in the epidermis and is required for the normal barrier function of the skin. [...] (211 aa)
TLR3Toll-like receptor 3; Key component of innate and adaptive immunity. TLRs (Toll- like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the inflammatory response. (904 aa)
IL3Interleukin-3; Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. (152 aa)
CSF2Granulocyte-macrophage colony-stimulating factor; Cytokine that stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes. Belongs to the GM-CSF family. (144 aa)
STAT6Signal transducer and activator of transcription 6; Carries out a dual function: signal transduction and activation of transcription. Involved in IL4/interleukin-4- and IL3/interleukin-3-mediated signaling. (847 aa)
DEFB4ABeta-defensin 4A; Exhibits antimicrobial activity against Gram-negative bacteria and Gram-positive bacteria. May act as a ligand for C-C chemokine receptor CCR6. Can bind to both human and mouse CCR6 and induce chemotactic activity of CCR6-expressing cells. Belongs to the beta-defensin family. LAP/TAP subfamily. (64 aa)
HAS3Hyaluronan synthase 3; Catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer. Therefore, it is essential to hyaluronan synthesis a major component of most extracellular matrices that has a structural role in tissues architectures and regulates cell adhesion, migration and differentiation. This is one of the isozymes catalyzing that reaction (By similarity); Belongs to the NodC/HAS family. (553 aa)
IL13Interleukin-13; Cytokine. Inhibits inflammatory cytokine production. Synergizes with IL2 in regulating interferon-gamma synthesis. May be critical in regulating inflammatory and immune responses. Positively regulates IL31RA expression in macrophages (By similarity). (146 aa)
CXCL10C-X-C motif chemokine 10; Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modulation of angiostatic effects. Plays thereby an important role during viral infections by stimulating the activation and migration of immune cells to the infected sites (By similarity). Mechanistically, binding of CXCL10 to the CXCR3 receptor activates G protein-mediated signaling and results in downstream activation of phospholipase C-dependent pathway, an increas [...] (98 aa)
CXCL8Interleukin-8; IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus. IL-8(6-77) has a 5-10-fold higher activity on neutrophil activation, IL-8(5-77) has increased activity on neutrophil activation and IL-8(7-77) has a higher affinity to receptors CXCR1 and CXCR2 as compared to IL-8(1-77), respectively. (99 aa)
TERTTelomerase reverse transcriptase; Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal somatic cells. Catalytic component of the teleromerase holoenzyme complex whose main activity is the elongation of telomeres by acting as a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. Catalyzes the RNA-dependent extension of 3'-chromosomal termini with the 6-nuc [...] (1132 aa)
KLK5Kallikrein-5; May be involved in desquamation; Belongs to the peptidase S1 family. Kallikrein subfamily. (293 aa)
TSLPThymic stromal lymphopoietin; [Isoform 1]: Cytokine that induces the release of T-cell- attracting chemokines from monocytes and, in particular, enhances the maturation of CD11c(+) dendritic cells. Can induce allergic inflammation by directly activating mast cells. (159 aa)
OCLNOccludin; May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions. (522 aa)
TJP1Tight junction protein ZO-1; TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton. The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Necessary for lumenogenesis, and particularly efficient epithelial polarization and barrier formation (By similarity). Plays a role i [...] (1768 aa)
SPINK5Serine protease inhibitor Kazal-type 5; Serine protease inhibitor, probably important for the anti- inflammatory and/or antimicrobial protection of mucous epithelia. Contribute to the integrity and protective barrier function of the skin by regulating the activity of defense-activating and desquamation- involved proteases. Inhibits KLK5, it's major target, in a pH-dependent manner. Inhibits KLK7, KLK14 CASP14, and trypsin. (1094 aa)
CLDN7Claudin-7; Plays a major role in tight junction-specific obliteration of the intercellular space; Belongs to the claudin family. (211 aa)
S100A7S100 calcium binding protein A7. (101 aa)
LORLoricrin; Major keratinocyte cell envelope protein. (312 aa)
SPRR2BSmall proline-rich protein 2A; Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane; Belongs to the cornifin (SPRR) family. (72 aa)
IVLInvolucrin; Part of the insoluble cornified cell envelope (CE) of stratified squamous epithelia; Belongs to the involucrin family. (585 aa)
HRNRHornerin; Component of the epidermal cornified cell envelopes. Belongs to the S100-fused protein family. (2850 aa)
IL13RA2Interleukin-13 receptor subunit alpha-2; Binds as a monomer with high affinity to interleukin-13 (IL13), but not to interleukin-4 (IL4). (380 aa)
CDSNCorneodesmosin; Important for the epidermal barrier integrity. (529 aa)
IL31Interleukin-31; Activates STAT3 and possibly STAT1 and STAT5 through the IL31 heterodimeric receptor composed of IL31RA and OSMR. May function in skin immunity. Enhances myeloid progenitor cell survival in vitro (By similarity). Induces RETNLA and serum amyloid A protein expression in macrophages (By similarity). (164 aa)
CRLF2Cytokine receptor-like factor 2; Receptor for thymic stromal lymphopoietin (TSLP). Forms a functional complex with TSLP and IL7R which is capable of stimulating cell proliferation through activation of STAT3 and STAT5. Also activates JAK2 (By similarity). Implicated in the development of the hematopoietic system; Belongs to the type I cytokine receptor family. Type 5 subfamily. (371 aa)
FLG2Filaggrin-2; Essential for normal cell-cell adhesion in the cornified cell layers. Important for proper integrity and mechanical strength of the stratum corneum of the epidermis. In the N-terminal section; belongs to the S-100 family. (2391 aa)
SPRR2ASmall proline rich protein 2A. (72 aa)
IL4RSoluble interleukin-4 receptor subunit alpha; Receptor for both interleukin 4 and interleukin 13. Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and, chemokine and mucus production at sites of allergic inflammation. In certain cell types, can signal through activation of insulin receptor substrates, IRS1/IRS2. (825 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)
CASP14Caspase-14 subunit p20, intermediate form; Non-apoptotic caspase involved in epidermal differentiation. Is the predominant caspase in epidermal stratum corneum. Seems to play a role in keratinocyte differentiation and is required for cornification. Regulates maturation of the epidermis by proteolytically processing filaggrin (By similarity). In vitro has a preference for the substrate [WY]-X-X-D motif and is active on the synthetic caspase substrate WEHD-ACF. Involved in processing of prosaposin in the epidermis (By similarity). May be involved in retinal pigment epithelium cell barrie [...] (242 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)
CLDN4Claudin-4; Channel-forming tight junction protein that mediates paracellular chloride transport in the kidney. Plays a critical role in the paracellular reabsorption of filtered chloride in the kidney collecting ducts. Claudins play a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity; Belongs to the claudin family. (209 aa)
NELL2Protein kinase C-binding protein NELL2; Required for neuron survival through the modulation of MAPK pathways (By similarity). Involved in the regulation of hypothalamic GNRH secretion and the control of puberty (By similarity). (866 aa)
TJP2Tight junction protein ZO-2; Plays a role in tight junctions and adherens junctions. (1221 aa)
IL22Interleukin-22; Cytokine that contributes to the inflammatory response in vivo. (179 aa)
NTF4Neurotrophin-4; Target-derived survival factor for peripheral sensory sympathetic neurons. (210 aa)
CCL5C-C motif chemokine 5; Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. May activate several chemokine receptors including CCR1, CCR3, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant RANTES protein induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form RANTES(3-68) acts as a natural chemotaxis inhibitor and is a more potent inhibitor of HIV-1-infection. The second [...] (91 aa)
KITLGSoluble KIT ligand; Ligand for the receptor-type protein-tyrosine kinase KIT. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. KITLG/SCF binding can activate several signaling pathways. Promotes phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and subsequent activation of the kinase AKT1. KITLG/SCF and KIT also transmit signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or M [...] (273 aa)
IL17AInterleukin-17A; Ligand for IL17RA and IL17RC. The heterodimer formed by IL17A and IL17F is a ligand for the heterodimeric complex formed by IL17RA and IL17RC. Involved in inducing stromal cells to produce proinflammatory and hematopoietic cytokines ; Belongs to the IL-17 family. (155 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
Server load: low (26%) [HD]
STRING is a Core Data Resource as designated by Global Biodata Coalition and ELIXIR.