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SLC25A4 SLC25A4 BIRC2 BIRC2 TNF TNF CD44 CD44 CD8A CD8A TNFRSF1B TNFRSF1B H2BC21 H2BC21 FASLG FASLG CD55 CD55 CASP8 CASP8 TRADD TRADD CASP9 CASP9 CD28 CD28 CASP3 CASP3 CD34 CD34 PCSK1 PCSK1 FADD FADD ANXA5 ANXA5 BAX BAX FAS FAS CD4 CD4 TNFRSF1A TNFRSF1A RIPK3 RIPK3 IL2 IL2 IFNG IFNG TRAF2 TRAF2 RIPK1 RIPK1 TRAF5 TRAF5 TYR TYR SELL SELL TNFRSF8 TNFRSF8 PMEL PMEL
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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
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a 3D structure is known or predicted
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from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
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SLC25A4ADP/ATP translocase 1; Involved in mitochondrial ADP/ATP transport. Catalyzes the exchange of cytoplasmic ADP with mitochondrial ATP across the mitochondrial inner membrane. (298 aa)
BIRC2Baculoviral IAP repeat-containing protein 2; Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling, and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and regulates both canonical and non- canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target protein [...] (618 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)
CD44CD44 antigen; Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment. Participates thereby in a wide variety of cellular functions including the activation, recirculation and homing of T-lymphocytes, hematopoiesis, inflammation and response to bacterial infection. Engages, through its ectodomain, extracellular matrix components such as hyaluronan/HA, collagen, growth factors, cytokines or proteases and serves as a platform for signal transduction by assembling, via its c [...] (742 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)
TNFRSF1BTumor necrosis factor receptor superfamily member 1b, membrane form; Receptor with high affinity for TNFSF2/TNF-alpha and approximately 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha. The TRAF1/TRAF2 complex recruits the apoptotic suppressors BIRC2 and BIRC3 to TNFRSF1B/TNFR2. This receptor mediates most of the metabolic effects of TNF-alpha. Isoform 2 blocks TNF-alpha-induced apoptosis, which suggests that it regulates TNF-alpha function by antagonizing its biological activity. (461 aa)
H2BC21Histone H2B type 2-E; Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. (126 aa)
FASLGTumor necrosis factor ligand superfamily member 6, membrane form; Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells. Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development. Initiates fratricidal/suicidal activation-induced cell death (AICD) in antigen- activated T-cells contributing to the termination of immune responses (By similarity). TNFRSF6/FAS-mediated apoptosis has also a role in the induction of peripheral tolerance (By similarity). Binds to TNFRSF6B/DcR3, a decoy receptor th [...] (281 aa)
CD55Complement decay-accelerating factor; This protein recognizes C4b and C3b fragments that condense with cell-surface hydroxyl or amino groups when nascent C4b and C3b are locally generated during C4 and c3 activation. Interaction of daf with cell-associated C4b and C3b polypeptides interferes with their ability to catalyze the conversion of C2 and factor B to enzymatically active C2a and Bb and thereby prevents the formation of C4b2a and C3bBb, the amplification convertases of the complement cascade. Inhibits complement activation by destabilizing and preventing the formation of C3 and [...] (444 aa)
CASP8Caspase-8 subunit p10; Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either receptor. The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC. Cleaves and activates CASP3, CA [...] (538 aa)
TRADDTumor necrosis factor receptor type 1-associated DEATH domain protein; The nuclear form acts as a tumor suppressor by preventing ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A by TRIP12: acts by interacting with TRIP12, leading to disrupt interaction between TRIP12 and isoform p19ARF/ARF of CDKN2A (By similarity). Adapter molecule for TNFRSF1A/TNFR1 that specifically associates with the cytoplasmic domain of activated TNFRSF1A/TNFR1 mediating its interaction with FADD. Overexpression of TRADD leads to two major TNF- induced responses, apoptosis and activation of NF-kappa-B. (312 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); Belongs to the peptidase C14A family. (416 aa)
CD28T-cell-specific surface glycoprotein CD28; Involved in T-cell activation, the induction of cell proliferation and cytokine production and promotion of T-cell survival. Enhances the production of IL4 and IL10 in T-cells in conjunction with TCR/CD3 ligation and CD40L costimulation. Isoform 3 enhances CD40L-mediated activation of NF-kappa-B and kinases MAPK8 and PAK2 in T-cells. (220 aa)
CASP3Caspase-3 subunit p12; Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage. (277 aa)
CD34Hematopoietic progenitor cell antigen CD34; Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold for the attachment of lineage specific glycans, allowing stem cells to bind to lectins expressed by stromal cells or other marrow components. Presents carbohydrate ligands to selectins. (385 aa)
PCSK1Neuroendocrine convertase 1; Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Substrates include POMC, renin, enkephalin, dynorphin, somatostatin, insulin and AGRP; Belongs to the peptidase S8 family. Furin subfamily. (753 aa)
FADDFAS-associated death domain protein; Apoptotic adaptor molecule that recruits caspase-8 or caspase-10 to the activated Fas (CD95) or TNFR-1 receptors. The resulting aggregate called the death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation. Active caspase-8 initiates the subsequent cascade of caspases mediating apoptosis. Involved in interferon-mediated antiviral immune response, playing a role in the positive regulation of interferon signaling. (208 aa)
ANXA5Annexin A5; This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade. (320 aa)
BAXApoptosis regulator BAX; Plays a role in the mitochondrial apoptotic process. Under normal conditions, BAX is largely cytosolic via constant retrotranslocation from mitochondria to the cytosol mediated by BCL2L1/Bcl-xL, which avoids accumulation of toxic BAX levels at the mitochondrial outer membrane (MOM). Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis. Promotes activation of CASP3, and thereby apoptosis. (218 aa)
FASTumor necrosis factor receptor superfamily member 6; Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen- stimulated suicide of mature T-cells, or both. The secreted isoforms 2 to 6 block apoptosis (in vitro). (335 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)
TNFRSF1ATumor necrosis factor receptor superfamily member 1A, membrane form; Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase. (455 aa)
RIPK3Receptor-interacting serine/threonine-protein kinase 3; Essential for necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members. Upon induction of necrosis, RIPK3 interacts with, and phosphorylates RIPK1 and MLKL to form a necrosis-inducing complex. RIPK3 binds to and enhances the activity of three metabolic enzymes: GLUL, GLUD1, and PYGL. These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production. Belongs to the protein kinase superfamily. TKL Ser/T [...] (518 aa)
IL2Interleukin-2; Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells. (153 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)
TRAF2TNF receptor-associated factor 2; Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'-linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin-protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein levels [...] (501 aa)
RIPK1Receptor-interacting serine/threonine-protein kinase 1; Serine-threonine kinase which is a key regulator of both cell death and cell survival. Exhibits kinase activity- dependent functions that trigger cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival. Initiates ripoptocide which describes cell death that is dependent on RIPK1, be it apoptosis or necroptosis. Upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, [...] (671 aa)
TRAF5TNF receptor-associated factor 5; Adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases. Mediates activation of NF-kappa-B and probably JNK. Seems to be involved in apoptosis. Plays a role in mediating activation of NF- kappa-B by EIF2AK2/PKR. (557 aa)
TYRTyrosinase; This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reactions leading to melanin production from tyrosine. In addition to hydroxylating tyrosine to DOPA (3,4-dihydroxyphenylalanine), also catalyzes the oxidation of DOPA to DOPA-quinone, and possibly the oxidation of DHI (5,6-dihydroxyindole) to indole-5,6 quinone. Belongs to the tyrosinase family. (529 aa)
SELLL-selectin; Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells. Mediates the adherence of lymphocytes to endothelial cells of high endothelial venules in peripheral lymph nodes. Promotes initial tethering and rolling of leukocytes in endothelia. Belongs to the selectin/LECAM family. (385 aa)
TNFRSF8Tumor necrosis factor receptor superfamily member 8; Receptor for TNFSF8/CD30L. May play a role in the regulation of cellular growth and transformation of activated lymphoblasts. Regulates gene expression through activation of NF-kappa- B ; Belongs to the TNFR8 family. (595 aa)
PMELMelanocyte protein PMEL; Plays a central role in the biogenesis of melanosomes. Involved in the maturation of melanosomes from stage I to II. The transition from stage I melanosomes to stage II melanosomes involves an elongation of the vesicle, and the appearance within of distinct fibrillar structures. Release of the soluble form, ME20-S, could protect tumor cells from antibody mediated immunity. (668 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
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