STRINGSTRING
CD4 CD4 LAG3 LAG3 GADD45B GADD45B GZMK GZMK DUSP1 DUSP1 EGR1 EGR1 FOSB FOSB CCR7 CCR7 CD68 CD68 NT5E NT5E ZAP70 ZAP70 CD3D CD3D IL7R IL7R CCL19 CCL19 CLU CLU APOL1 APOL1 EPSTI1 EPSTI1 IFI6 IFI6 FYN FYN STAT1 STAT1 CD247 CD247 DUSP12 DUSP12 CD244 CD244 IFI16 IFI16 IFI44 IFI44 IFI44L IFI44L SRC SRC RSAD2 RSAD2 CXCL12 CXCL12 IRF7 IRF7 MX1 MX1 CD8A CD8A OAS1 OAS1 EOMES EOMES TNF TNF NR4A1 NR4A1 LCK LCK IFI27 IFI27 CCL15 CCL15 BCL10 BCL10
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:
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)
LAG3Secreted lymphocyte activation gene 3 protein; Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells. Delivers inhibitory signals upon binding to ligands, such as FGL1 (By similarity). FGL1 constitutes a major ligand of LAG3 and is responsible for LAG3 T-cell inhibitory function (By similarity). Following TCR engagement, LAG3 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (By similarity). May inhibit antigen-specific T-cell activation in synergy with PDCD1/PD-1, possibly by acting as a coreceptor for PDCD1/P [...] (525 aa)
GADD45BGrowth arrest and DNA damage-inducible protein GADD45 beta; Involved in the regulation of growth and apoptosis. Mediates activation of stress-responsive MTK1/MEKK4 MAPKKK. (160 aa)
GZMKGranzyme K; Belongs to the peptidase S1 family. Granzyme subfamily. (264 aa)
DUSP1Dual specificity protein phosphatase 1; Dual specificity phosphatase that dephosphorylates MAP kinase MAPK1/ERK2 on both 'Thr-183' and 'Tyr-185', regulating its activity during the meiotic cell cycle. (367 aa)
EGR1Early growth response protein 1; Transcriptional regulator. Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes (By similarity). Binds double-stranded target DNA, irrespective of the cytosine methylation status. Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia. Plays a role in the regulation of cell survival, proliferation and cell death. Activates expression of p53/TP53 and TGFB1, and thereby helps prevent tumor forma [...] (543 aa)
FOSBProtein fosB; FosB interacts with Jun proteins enhancing their DNA binding activity. (338 aa)
CCR7C-C chemokine receptor type 7; Receptor for the MIP-3-beta chemokine. Probable mediator of EBV effects on B-lymphocytes or of normal lymphocyte functions; Belongs to the G-protein coupled receptor 1 family. (378 aa)
CD68Macrosialin; Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-specific lectins or selectins, allowing homing of macrophage subsets to particular sites. Rapid recirculation of CD68 from endosomes and lysosomes to the plasma membrane may allow macrophages to crawl over selectin-bearing substrates or other cells. (354 aa)
NT5E5'-nucleotidase; Hydrolyzes extracellular nucleotides into membrane permeable nucleosides. Exhibits AMP-, NAD-, and NMN-nucleosidase activities. (574 aa)
ZAP70Tyrosine-protein kinase ZAP-70; Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also to the development and activation of primary B- lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated [...] (619 aa)
CD3DT-cell surface glycoprotein CD3 delta chain; Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR- mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of [...] (171 aa)
IL7RInterleukin-7 receptor subunit alpha; Receptor for interleukin-7. Also acts as a receptor for thymic stromal lymphopoietin (TSLP); Belongs to the type I cytokine receptor family. Type 4 subfamily. (459 aa)
CCL19C-C motif chemokine 19; May play a role not only in inflammatory and immunological responses but also in normal lymphocyte recirculation and homing. May play an important role in trafficking of T-cells in thymus, and T-cell and B-cell migration to secondary lymphoid organs. Binds to chemokine receptor CCR7. Recombinant CCL19 shows potent chemotactic activity for T-cells and B-cells but not for granulocytes and monocytes. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta- arrestin (ARRB1/2) to ACKR4; Belongs to the intercrine beta (chemokine CC) family. (98 aa)
CLUClusterin alpha chain; [Isoform 1]: Functions as extracellular chaperone that prevents aggregation of non native proteins. Prevents stress-induced aggregation of blood plasma proteins. Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro). Does not require ATP. Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70. Does not refold proteins by itself. Binding to cell surface receptors triggers internalization of the chaperone-client complex and sub [...] (449 aa)
APOL1Apolipoprotein L1; May play a role in lipid exchange and transport throughout the body. May participate in reverse cholesterol transport from peripheral cells to the liver. (414 aa)
EPSTI1Epithelial-stromal interaction protein 1; Plays a role in M1 macrophage polarization and is required for the proper regulation of gene expression during M1 versus M2 macrophage differentiation (By similarity). Might play a role in RELA/p65 and STAT1 phosphorylation and nuclear localization upon activation of macrophages (By similarity). (410 aa)
IFI6Interferon alpha-inducible protein 6; Plays a role in apoptosis, negatively regulating the intrinsinc apoptotic signaling pathway and TNFSF10-induced apoptosis. However, it has also been shown to have a pro-apoptotic activity. Has an antiviral activity towards hepatitis C virus/HCV by inhibiting the EGFR signaling pathway, which activation is required for entry of the virus into cells. Belongs to the IFI6/IFI27 family. (138 aa)
FYNTyrosine-protein kinase Fyn; Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through [...] (537 aa)
STAT1Signal transducer and activator of transcription 1-alpha/beta; Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors. Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF [...] (750 aa)
CD247T-cell surface glycoprotein CD3 zeta chain; Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR- mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of d [...] (164 aa)
DUSP12Dual specificity protein phosphatase 12; Dual specificity phosphatase; can dephosphorylate both phosphotyrosine and phosphoserine or phosphothreonine residues. Can dephosphorylate glucokinase (in vitro) (By similarity). Has phosphatase activity with the synthetic substrate 6,8-difluoro-4-methylumbelliferyl phosphate and other in vitro substrates. (340 aa)
CD244Natural killer cell receptor 2B4; Heterophilic receptor of the signaling lymphocytic activation molecule (SLAM) family; its ligand is CD48. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Acts as activating natural killer (NK) cell receptor. Activating functi [...] (370 aa)
IFI16Gamma-interferon-inducible protein 16; Binds double-stranded DNA. Binds preferentially to supercoiled DNA and cruciform DNA structures. Seems to be involved in transcriptional regulation. May function as a transcriptional repressor. Could have a role in the regulation of hematopoietic differentiation through activation of unknown target genes. Controls cellular proliferation by modulating the functions of cell cycle regulatory factors including p53/TP53 and the retinoblastoma protein. May be involved in TP53-mediated transcriptional activation by enhancing TP53 sequence-specific DNA bi [...] (729 aa)
IFI44Interferon-induced protein 44; This protein aggregates to form microtubular structures. Belongs to the IFI44 family. (444 aa)
IFI44LInterferon-induced protein 44-like; Exhibits a low antiviral activity against hepatitis C virus. Belongs to the IFI44 family. (452 aa)
SRCProto-oncogene tyrosine-protein kinase Src; Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy bet [...] (536 aa)
RSAD2Radical S-adenosyl methionine domain-containing protein 2; Interferon-inducible iron-sulfur (4FE-4S) cluster-binding antiviral protein which plays a major role in the cell antiviral state induced by type I and type II interferon. Can inhibit a wide range of DNA and RNA viruses, including human cytomegalovirus (HCMV), hepatitis C virus (HCV), west Nile virus (WNV), dengue virus, sindbis virus, influenza A virus, sendai virus, vesicular stomatitis virus (VSV), and human immunodeficiency virus (HIV-1). Displays antiviral activity against influenza A virus by inhibiting the budding of the [...] (361 aa)
CXCL12Stromal cell-derived factor 1; Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. SDF-1-beta(3-72) and SDF-1-alpha(3-67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on local sites. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. Bi [...] (140 aa)
IRF7Interferon regulatory factor 7; Key transcriptional regulator of type I interferon (IFN)- dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN- stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependen [...] (516 aa)
MX1Interferon-induced GTP-binding protein Mx1, N-terminally processed; Interferon-induced dynamin-like GTPase with antiviral activity against a wide range of RNA viruses and some DNA viruses. Its target viruses include negative-stranded RNA viruses and HBV through binding and inactivation of their ribonucleocapsid. May also antagonize reoviridae and asfarviridae replication. Inhibits thogoto virus (THOV) replication by preventing the nuclear import of viral nucleocapsids. Inhibits La Crosse virus (LACV) replication by sequestering viral nucleoprotein in perinuclear complexes, preventing g [...] (662 aa)
CD8AT-cell surface glycoprotein CD8 alpha chain; 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 I molecule:peptide complex. The antigens presented by class I peptides are derived from cytosolic proteins while class II derived from extracellular proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class I proteins presented by antigen presenting cells (APCs). In turn, recruits the Sr [...] (235 aa)
OAS12'-5'-oligoadenylate synthase 1; Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition [...] (414 aa)
EOMESEomesodermin homolog; Functions as a transcriptional activator playing a crucial role during development. Functions in trophoblast differentiation and later in gastrulation, regulating both mesoderm delamination and endoderm specification. Plays a role in brain development being required for the specification and the proliferation of the intermediate progenitor cells and their progeny in the cerebral cortex. Also involved in the differentiation of CD8+ T-cells during immune response regulating the expression of lytic effector genes. (705 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)
NR4A1Nuclear receptor subfamily 4 group A member 1; Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2. Participates in energy homeostasis by sequestrating the kinase STK11 in the nucleus, thereby attenuating cytoplasmic AMPK activation. Plays a role in the vascular response to injury (By similarity). ECO:0000250|UniProtKB:P12813. (652 aa)
LCKTyrosine-protein kinase Lck; Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T- cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen- bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein [...] (509 aa)
IFI27Interferon alpha-inducible protein 27, mitochondrial; Probable adapter protein involved in different biological processes. Part of the signaling pathways that lead to apoptosis. Involved in type-I interferon-induced apoptosis characterized by a rapid and robust release of cytochrome C from the mitochondria and activation of BAX and caspases 2, 3, 6, 8 and 9. Also functions in TNFSF10-induced apoptosis. May also have a function in the nucleus, where it may be involved in the interferon-induced negative regulation of the transcriptional activity of NR4A1, NR4A2 and NR4A3 through the enha [...] (122 aa)
CCL15C-C motif chemokine 15; Chemotactic factor that attracts T-cells and monocytes, but not neutrophils, eosinophils, or B-cells. Acts mainly via CC chemokine receptor CCR1. Also binds to CCR3. CCL15(22-92), CCL15(25-92) and CCL15(29-92) are more potent chemoattractants than the small-inducible cytokine A15; Belongs to the intercrine beta (chemokine CC) family. (113 aa)
BCL10B-cell lymphoma/leukemia 10; Involved in adaptive immune response. Promotes apoptosis, pro-caspase-9 maturation and activation of NF- kappa-B via NIK and IKK. May be an adapter protein between upstream TNFR1-TRADD-RIP complex and the downstream NIK-IKK-IKAP complex. Is a substrate for MALT1. (233 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.