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  5. TNF Receptor Superfamily

TNF Receptor Superfamily

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TNF Receptor Superfamily

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TNF receptor superfamily (TNFRSF) members are transmembrane proteins cysteine-rich motifs in their extracellular domains that bind to their cognate ligands. About 30 members of TNFRSF members have been identified. Tumor necrosis factor receptors (TNFRs) are primarily type I transmembrane proteins containing an extracellular TNF binding region and a cytoplasmic tail. But BCMA, TACI, BAFFR and XEDAR belong to Type III transmembrane proteins[1]. TNFRs can be divided into three types: (1) receptors containing the death domain (DD) (fatty acid synthase, TNFR1, and DR3) activate caspase cascades via the external apoptotic pathway triggered by DD; (2) the cytoplasmic cauda region contains one or more TRAF interaction mods (TIM), which recruit TRAF family members and ultimately activate key molecules of multiple signal transduction pathways; (3) it does not contain functional intracellular signaling domain or motif, and can competitively bind to the corresponding ligand with the other two groups of receptors[2]. TNFRSF are primarily involved in apoptosis and inflammation, also and are also involved in cell proliferation, differentiation and survival[3][4].

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Cat. No. Product Name / Synonyms Species Source
  • HY-P7168
    Fas/CD95 Protein, Human (HEK293)

    rHuFASR/TNFRSF6; Tumor necrosis factor receptor superfamily member 6; Fas receptor; CD95; APT1; FAS1; Apo-1

    		Human HEK293
    Fas receptor is a cell surface death receptor, can bind to Fas ligand to form death-inducing signaling complexes, such as Fas associated death domain proteins (FADD). Fas receptor participates in the caspase cascade and regulate the activation of JNK and p38-K downstream. It is also involved in the signaling cascade of ERK/JNK MAPKs, activating MAPK3/ERK1, MAPK8/JNK and NF-κB, which has been implicated in the pathogenesis of various malignant tumors and immune system diseases. Human Fas receptor contain a death domain (230-314 a.a.) that plays a key role in regulating programmed death. Fas/CD95 Protein, Human (HEK293) has a full length of 157 amino acids (Q26-S172), produced in HEK293 cells with tag free.
  • HY-P70806
    TRAIL R2/TNFRSF10B Protein, Human (127a.a, HEK293, His)

    Tumor Necrosis Factor Receptor Superfamily Member 10B; Death Receptor 5; TNF-Related Apoptosis-Inducing Ligand Receptor 2; TRAIL Receptor 2; TRAIL-R2; CD262; TNFRSF10B; DR5; KILLER; TRAILR2; TRICK2; ZTNFR9

    		Human HEK293
    TRAIL R2/TNFRSF10B protein is the receptor of TNFSF10/TRAIL and recruits caspase-8 through FADD to initiate cell apoptosis. It forms the death-inducing signaling complex (DISC), activates caspases and mediates apoptosis. TRAIL R2/TNFRSF10B Protein, Human (127a.a, HEK293, His) is the recombinant human-derived TRAIL R2/TNFRSF10B protein, expressed by HEK293 , with C-6*His labeled tag. The total length of TRAIL R2/TNFRSF10B Protein, Human (127a.a, HEK293, His) is 127 a.a., with molecular weight of ~18.0 kDa.
  • HY-P72025
    TNFRII Protein, Human (HEK293, hFc)

    Tumor necrosis factor receptor 2; TNF-R2; Tumor necrosis factor receptor type II; TNF-RII; TNFR-II; p75; p80 TNF-alpha receptor; CD120b; Etanercept; TBP-2; TBPII;

    		Human HEK293
    TNFRII (TNFRSF1B) protein has a high ability to bind with tumor necrosis factor-alpha (TNF-α). TNFRII has pro-apoptotic function. TNFRII recruits TRAF2, induces gene expression and intensively crosstalks with TNF-R1. TNFRII selectively enhances the induction of apoptosis by the death receptor TNFRI. TNFRII Protein, Human (HEK293, hFc) is expressed by HEK293 and has a transmembrane region (L23-D257) with hFc tag at the C-terminus.
  • HY-P7271
    NGFR Protein, Human (HEK293)

    rHuNGFR; Gp80-LNGFR; p75 ICD; CD271; TNFRSF16

    		Human HEK293
    Nerve Growth Factor Receptor (NGFR) also known as CD271, p75NTR, TNFRSF16, is a transmembrane low-affinity receptor for the neurotrophin family. NGFR has no intrinsic tyrosine kinase activity. NGFR can act as a tumour suppressor, negatively regulating cell growth and proliferation. NGF-NGFR cascade activates NF-κB, leading to inhibition of apoptosis, increases survival of schwannoma, and breast cancer cells.  NGFR Protein, Human (HEK293) is a recombinant protein consisting of 222 amino acids (K29-N250) and is produced in HEK293 cells.
  • HY-P72847
    BCMA/TNFRSF17 Protein, Human (HEK293, His)

    Tumor necrosis factor receptor superfamily member 17; CD269; TNFRSF17; BCM; BCMA

    		Human HEK293
    B Cell Maturation Antigen (BCMA) also referred to as TNFRSF17 or CD269, is a transmembrane glycoprotein member of the tumor necrosis factor receptor (TNFR) superfamily. BCMA is used as a biomarker for Multiple myeloma (MM). BCMA mainly plays an important role in B cells for their proliferation, survival and also differentiates them into plasma cells. BCMA/TNFRSF17 Protein, Human (HEK293, His) is a recombinant protein with a C-Terminal His label, It consists of 54 amino acids (M1-A54) and is produced in HEK293 cells.
  • HY-P7317
    4-1BB/TNFRSF9 Protein, Human (CHO, Fc)

    rHu4-1BB, Fc Chimera; CD137; ILA

    		Human CHO
    4-1BB (CD137; TNFRSF9), a receptor of TNFSF9/4-1BBL, belongs to the tumor necrosis factor (TNF) receptor superfamily. 4-1BB is helpful for T cell activation and development, and also induces peripheral mononuclear cell proliferation and migration to the tumor microenvironment. 4-1BB is also involved in enhancing Nrf2 and NF-κB pathway mediated apoptosis of endothelial cells. Human 4-1BB protein is a surface glycoprotein with a transmembrane domain (187-213 a.a.). 4-1BB/TNFRSF9 Protein, Human (CHO, Fc) is the extracellular part (L24-Q186) of 4-1BB protein, produced by HEK293 cells with C-terminal hFc-tag.
  • HY-P7646
    BAFFR/TNFRSF13C Protein, Mouse (HEK293, Fc)

    rMuBAFFR/TNFRSF13C, C-Fc; BAFF R; BAFFR; BR3; CD268; TNFRSF13C

    		Mouse HEK293
    BAFF Receptor (B-cell activating factor receptor, BAFF-R), also known as TNFRSF13C and BR3, is a membrane protein of the TNF receptor superfamily which recognizes BAFF. BAFF Receptor is the crucial receptor for B-cell survival and also is a potent costimulator of both B and T cell activation. BAFFR/TNFRSF13C Protein, Mouse (HEK293, Fc) is a recombinant protein with a C-Terminal Fc label, It consists of 62 amino acids (S10-A71) and is produced in HEK293 cells.
  • HY-P76683
    TNFRII Protein, Human (257a.a, HEK293, His)

    TNF-R2; CD120b; Tumor necrosis factor receptor superfamily member 1b; p75; Tnfr2

    		Human HEK293
    TNFRII (TNFRSF1B) protein has a high ability to bind with tumor necrosis factor-alpha (TNF-α). TNFRII has pro-apoptotic function. TNFRII recruits TRAF2, induces gene expression and intensively crosstalks with TNF-R1. TNFRII selectively enhances the induction of apoptosis by the death receptor TNFRI. TNFRII Protein, Human (257a.a, HEK293, His) is expressed by HEK293 and has a transmembrane region (M1-D257) with His tag at the C-terminus.
  • HY-P77100
    NGFR Protein, Mouse (HEK293, Fc)

    NGFR; Gp80-LNGFR; p75 ICD; CD271; TNFRSF16

    		Mouse HEK293
    Nerve Growth Factor Receptor (NGFR) also known as CD271, p75NTR, TNFRSF16, is a transmembrane low-affinity receptor for the neurotrophin family. NGFR has no intrinsic tyrosine kinase activity. NGFR can act as a tumour suppressor, negatively regulating cell growth and proliferation. NGF-NGFR cascade activates NF-κB, leading to inhibition of apoptosis, increases survival of schwannoma, and breast cancer cells.  NGFR Protein, Mouse (HEK293, Fc) is a recombinant protein with a C-Terminal Fc label, It consists of 243 amino acids (M1-N243) and is produced in HEK293 cells.
  • HY-P78065
    BAFFR/TNFRSF13C Protein, Human (Biotinylated, HEK293, His-Avi)

    CD268; BAFFR; BR3; TNFRSF13C; BROMIX; CVID4; prolixin

    		Human HEK293
    BAFF Receptor (B-cell activating factor receptor, BAFF-R), also known as TNFRSF13C and BR3, is a membrane protein of the TNF receptor superfamily which recognizes BAFF. BAFF Receptor is the crucial receptor for B-cell survival and also is a potent costimulator of both B and T cell activation. BAFFR/TNFRSF13C Protein, Human (Biotinylated, HEK293, His-Avi) is a biotinylated recombinant protein with a C-Terminal Avi label and a C-Terminal His label, It consists of 65 amino acids (S7-A71) and is produced in HEK293 cells.
  • HY-P78070
    BCMA/TNFRSF17 Protein, Human (Biotinylated, HEK293, His-Avi)

    CD269; TNFRSF17; BCMA; BCM; TNFRSF13A

    		Human HEK293
    B Cell Maturation Antigen (BCMA) also referred to as TNFRSF17 or CD269, is a transmembrane glycoprotein member of the tumor necrosis factor receptor (TNFR) superfamily. BCMA is used as a biomarker for Multiple myeloma (MM). BCMA mainly plays an important role in B cells for their proliferation, survival and also differentiates them into plasma cells. BCMA/TNFRSF17 Protein, Human (Biotinylated, HEK293, His-Avi) is a biotinylated recombinant protein with a C-Terminal Avi label and a C-Terminal His label, It consists of 54 amino acids (M1-A54) and is produced in HEK293 cells.
  • HY-P78071
    BCMA/TNFRSF17 Trimer Protein, Human (Biotinylated, HEK293, His-Avi)

    CD269; TNFRSF17; BCMA; BCM; TNFRSF13A

    		Human HEK293
    B Cell Maturation Antigen (BCMA) also referred to as TNFRSF17 or CD269, is a transmembrane glycoprotein member of the tumor necrosis factor receptor (TNFR) superfamily. BCMA is used as a biomarker for Multiple myeloma (MM). BCMA mainly plays an important role in B cells for their proliferation, survival and also differentiates them into plasma cells. BCMA/TNFRSF17 Trimer Protein, Human (Biotinylated, HEK293, His-Avi) is a biotinylated recombinant protein with a C-Terminal Avi label and a C-Terminal His label, It consists of 54 amino acids (M1-A54) and is produced in HEK293 cells.
  • HY-P78091
    CD40 Protein, Human (Biotinylated, HEK293, His-Avi)

    CD40; CD40L receptor; TNFRSF5; B cell surface antigen CD40; B-cell surface antigen CD40; Bp50B cell-associated molecule; CD40 antigen; CD40 molecule, TNF receptor superfamily member 5; CD40 type II isoform; CDw40; MGC9013; nerve growth factor receptor-relat

    		Human HEK293
    CD40 protein is a TNFSF5/CD40LG receptor that transduces signals through TRAF6 and MAP3K8-mediated pathways, activates ERK in macrophages and B cells, and induces immunoglobulin secretion. CD40 exists as monomers and homodimers and interacts with TRAF proteins (TRAF1, TRAF2, TRAF3, TRAF5, and TRAF6). CD40 Protein, Human (Biotinylated, HEK293, His-Avi) is the recombinant human-derived CD40 protein, expressed by HEK293 , with C-Avi, C-His labeled tag. The total length of CD40 Protein, Human (Biotinylated, HEK293, His-Avi) is 173 a.a., with molecular weight of 35-40 kDa.
  • HY-P78189
    OX40/TNFRSF4 Protein, Human (Biotinylated, HEK293, His-Avi)

    CD134; OX40; OX40L receptor; TNFRSF4; ACT-135; Ly-70; OX40 homologue;  TXGP1L; IMD16

    		Human HEK293
    OX40 (TNFRSF4), is a receptor for OX40 Ligand. OX40 is preferentially expressed by T cells. OX40 can be activated by OX40 Ligand, thereby functioning as a T cell co-stimulatory molecule. The OX40-OX40 Ligand interaction promotes effector T-cell survival and effectively induces memory T-cell generation, as well as enhances the helper function of Tfh for B cells, and also promotes the differentiation and maturation of DCs. OX40/TNFRSF4 Protein, Human (Biotinylated, HEK293, His-Avi) is a recombinant biotinylated human OX40 (L29-A216) with C-terminal Avi and His tag, which is produced in HEK293.
  • HY-P78219
    TRAIL R1/TNFRSF10A Protein, Human (Biotinylated, HEK293, His-Avi)

    DR4; CD261; TNFRSF10A; TRAIL-R; APO2; TRAIL R1; MGC9365

    		Human HEK293
    TRAIL R1/TNFRSF10A protein is a receptor for TNFSF10/TRAIL, which recruits caspase-8 through FADD to initiate cell apoptosis and form a death-inducing signaling complex (DISC). It activates NF-kappa-B and interacts with TRADD and RIPK1 in the monomeric state. TRAIL R1/TNFRSF10A Protein, Human (Biotinylated, HEK293, His-Avi) is the recombinant human-derived TRAIL R1/TNFRSF10A protein, expressed by HEK293 , with C-Avi, C-His labeled tag. The total length of TRAIL R1/TNFRSF10A Protein, Human (Biotinylated, HEK293, His-Avi) is 206 a.a., with molecular weight of 25-30 kDa.
  • HY-P78220
    TRAIL R2/TNFRSF10B Protein, Human (Biotinylated, HEK293, His-Avi)

    CD262; DR5; DR5TRICK2B; Fas-like protein; KILLER/DR5; TNFRSF10B; TRAIL R2; TRAIL receptor 2; TRAILR2; TRICK2; TRICK2A; TRICKB; ZTNFR9; KILLER

    		Human HEK293
    TRAIL R2/TNFRSF10B protein is the receptor of TNFSF10/TRAIL and recruits caspase-8 through FADD to initiate cell apoptosis. It forms the death-inducing signaling complex (DISC), activates caspases and mediates apoptosis. TRAIL R2/TNFRSF10B Protein, Human (Biotinylated, HEK293, His-Avi) is the recombinant human-derived TRAIL R2/TNFRSF10B protein, expressed by HEK293 , with C-Avi, C-His labeled tag. The total length of TRAIL R2/TNFRSF10B Protein, Human (Biotinylated, HEK293, His-Avi) is 127 a.a., with molecular weight of 20-25 kDa.
  • HY-P78221
    TRAILR4/TNFRSF10D Protein, Human (Biotinylated, HEK293, His-Avi)

    CD264; RSF10D; TRAILR4; DCR2; TRUNDD; TNFRSF10D

    		Human HEK293
    TRAILR4/TNFRSF10D protein is a receptor for TRAIL and lacks the ability to induce apoptosis due to the truncated death domain. Paradoxically, not only does it fail to induce apoptosis, but it also prevents TRAIL-mediated apoptosis. TRAILR4/TNFRSF10D Protein, Human (Biotinylated, HEK293, His-Avi) is the recombinant human-derived TRAILR4/TNFRSF10D protein, expressed by HEK293 , with C-Avi, C-His labeled tag. The total length of TRAILR4/TNFRSF10D Protein, Human (Biotinylated, HEK293, His-Avi) is 156 a.a., with molecular weight of 38-50 kDa.
  • HY-P73499A
    CD40 Protein, Human (193a.a, HEK293, C-His)

    Tumor Necrosis Factor Receptor Superfamily member 5; Bp50; CD40L Receptor; CDw40; TNFRSF5

    		Human HEK293
    CD40 protein is a TNFSF5/CD40LG receptor that transduces signals through TRAF6 and MAP3K8-mediated pathways, activates ERK in macrophages and B cells, and induces immunoglobulin secretion. CD40 exists as monomers and homodimers and interacts with TRAF proteins (TRAF1, TRAF2, TRAF3, TRAF5, and TRAF6). CD40 Protein, Human (193a.a, HEK293, C-His) is the recombinant human-derived CD40 protein, expressed by HEK293 , with C-6*His labeled tag. The total length of CD40 Protein, Human (193a.a, HEK293, C-His) is 173 a.a., with molecular weight of ~28-32 kDa.
  • HY-P70821
    TRAIL R2/TNFRSF10B Protein, Mouse (HEK293, hFc)

    Tumor necrosis factor receptor superfamily member 10B/Death receptor 5/MK/CD262/Tnfrsf10b/Dr5/Killer

    		Mouse HEK293
    TRAIL R2/TNFRSF10B protein is the receptor of TNFSF10/TRAIL and activates apoptosis through FADD-mediated recruitment of caspase-8 to form death-inducing signaling complex (DISC). It initiates caspase cascade-mediated apoptosis and promotes NF-kappa-B activation, which is critical for ER stress-induced apoptosis. TRAIL R2/TNFRSF10B Protein, Mouse (HEK293, hFc) is the recombinant mouse-derived TRAIL R2/TNFRSF10B protein, expressed by HEK293 , with C-hFc labeled tag. The total length of TRAIL R2/TNFRSF10B Protein, Mouse (HEK293, hFc) is 125 a.a., with molecular weight of 50-75 kDa.
  • HY-P70801
    TNFRSF1A Protein, Human (His)

    Tumor necrosis factor receptor superfamily member 1A; Tumor necrosis factor receptor 1; TNF-R1; Tumor necrosis factor receptor type I; TNF-RI; TNFR-I; TNFAR; TNFR1

    		Human E. coli
    TNFRSF1A (TNF RI) protein has a high ability to bind with tumor necrosis factor-alpha (TNF-α). TNFRSF1A is a STAT3 target gene that regulates the NF-κB pathway. TNFRSF1A activate NF-κB, mediate apoptosis, and function as a regulator of inflammation. TNFRSF1A Protein, Human (His) is expressed by E. coli and has a transmembrane region (I22-T211) with a 6*His tag at the N-terminus.
Cat. No. Product Name Effect Purity
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Download TNF Receptor Signaling Pathway Map.

Following the binding of TNF to TNF receptors, TNFR1 binds to TRADD, which recruits RIPK1, TRAF2/5 and cIAP1/2 to form TNFR1 signaling complex I; TNFR2 binds to TRAF1/2 directly to recruit cIAP1/2. Both cIAP1 and cIAP2 are E3 ubiquitin ligases that add K63 linked polyubiquitin chains to RIPK1 and other components of the signaling complex. The ubiquitin ligase activity of the cIAPs is needed to recruit the LUBAC, which adds M1 linked linear polyubiquitin chains to RIPK1. K63 polyubiquitylated RIPK1 recruits TAB2, TAB3 and TAK1, which activate signaling mediated by JNK and p38, as well as the IκB kinase complex. The IKK complex then activates NF-κB signaling, which leads to the transcription of anti-apoptotic factors-such as FLIP and Bcl-XL-that promote cell survival. 

 

The formation of TNFR1 complex IIa and complex IIb depends on non-ubiquitylated RIPK1. For the formation of complex IIa, ubiquitylated RIPK1 in complex I is deubiquitylated by CYLD. This deubiquitylated RIPK1 dissociates from the membrane-bound complex and moves into the cytosol, where it interacts with TRADD, FADD, Pro-caspase 8 and FLIPL to form complex IIa. By contrast, complex IIb is formed when the RIPK1 in complex I is not ubiquitylated owing to conditions that have resulted in the depletion of cIAPs, which normally ubiquitylate RIPK1. This non-ubiquitylated RIPK1 dissociates from complex I, moves into the cytosol, and assembles with FADD, Pro-caspase 8, FLIPL and RIPK3 (but not TRADD) to form complex IIb. For either complex IIa or complex IIb to prevent necroptosis, both RIPK1 and RIPK3 must be inactivated by the cleavage activity of the Pro-caspase 8-FLIPL heterodimer or fully activated caspase 8. The Pro-caspase 8 homodimer generates active Caspase 8, which is released from complex IIa and complex IIb. This active Caspase 8 then carries out cleavage reactions to activate downstream executioner caspases and thus induce classical apoptosis. 

 

Formation of the complex IIc (necrosome) is initiated either by RIPK1 deubiquitylation mediated by CYLD or by RIPK1 non-ubiquitylation due to depletion of cIAPs, similar to complex IIa and complex IIb formation. RIPK1 recruits numerous RIPK3 molecules. They come together to form amyloid microfilaments called necrosomes. Activated RIPK3 phosphorylates and recruits MLKL, eventually leading to the formation of a supramolecular protein complex at the plasma membrane and necroptosis [1][2].

 

Reference:
[1]. Brenner D, et al. Regulation of tumour necrosis factor signalling: live or let die.Nat Rev Immunol. 2015 Jun;15(6):362-74. 
[2]. Conrad M, et al. Regulated necrosis: disease relevance and therapeutic opportunities.Nat Rev Drug Discov. 2016 May;15(5):348-66.