Tumor necrosis factor receptor superfamily member 8 (TNFRSF8), also known as CD30; TNFRSF8 (also known as CD30, Ki-1, D1S166E) is expressed by activated T and B cells. It transduces signals that lead to the activation of NF-kappaB, mediated by the adaptor proteins TRAF2 and TRAF5. This receptor is a positive regulator of apoptosis, and has been shown to limit the proliferative potential of auto-reactive CD8 effector T cells and protect the body against autoimmunity. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. CD30 is expressed in malignant Hodgkin and Reed-Sternberg cells on the surface of extracellular vesicles, facilitating CD30-CD30L interaction between cell types. This receptor is also associated with anaplastic large cell lymphoma. It is expressed in embryonal carcinoma, but not in seminoma, making it a useful marker in distinguishing between these germ cell tumors. Since CD30 has restricted expression in normal tissues, it is an optimal target for selectively eliminating CD30-expressing neoplastic cells by specific toxin-conjugated monoclonal antibodies (mAbs).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597709797  62 TIPQAKPTPVSPATSSASTMPVRggtrLAQEAASKLTRAPDSPSSVGRPSSDPGLSPTQPCPEGSGDCRKQCEPDYYLDE 141
Cdd:cd13409    1 LSLRAKLTLFSPGTLRAPTMRRA----SAATCDGDPSRYYDEASSKCCYRCPPGLSPQQPCPQGSADCRKQCEPDYYLDE 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 597709797 142 AGRCTACVSCSRDDLVEKTPCAWNSSRTCECRPGMICATSATNSCARCVPYPIC 195
Cdd:cd13409   77 DGRCTACVSCSGDDLVEKAPCSWNSSRVCECRPGMFCATSATNSCARCVPHSVC 130

Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) interactions with TNF superfamily (TNFSF) ligands (TNFL) control key cellular processes such as differentiation, proliferation, apoptosis, and cell growth. Dysregulation of these pathways has been shown to result in a wide range of pathological conditions, including autoimmune diseases, inflammation, cancer, and viral infection. There are 29 very diverse family members of TNFRSF reported in humans: 22 are type I transmembrane receptors (single pass with the N terminus on extracellular side of the cell membrane) and have a clear signal peptide; the remaining 7 members are either type III transmembrane receptors (single pass with the N terminus on extracellular side of the membrane but no signal sequence; TNFR13B, TNFR13C, TNFR17, and XEDAR), or attached to the membrane via a glycosylphosphatidylinositol (GPI) linker (TNFR10C), or secreted as soluble receptors (TNFR11B and TNFR6B). All TNFRs contain relatively short cysteine-rich domains (CRDs) in the ectodomain, and are involved in interaction with the TNF homology domain (THD) of their ligands. TNFRs often have multiple CRDs (between one and six), with the most frequent configurations of three or four copies; most CRDs possess three disulfide bridges, but could have between one and four. Localized or genome-wide duplication and evolution of the TNFRSF members appear to have paralleled the emergence of the adaptive immune system; teleosts (i.e. ray-finned, bony fish), which possess an immune system with B and T cells, possess primary and secondary lymphoid organs, and are capable of adaptive responses to pathogens also display several characteristics that are different from the mammalian immune system, making teleost TNFSF orthologs and paralogs of interest to better understand immune system evolution and the immunological pathways elicited to pathogens.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 597709797  14 CFFHSVCPAGMIVKFPGTAQKNTVCEPASPGV-SPACASPENCKE 57
Cdd:cd10575   93 CLRHSSCPPGEGVIKLGTPYSDTQCEPCPPGFfSASSSSTEPCQP 137

Tumor necrosis factor receptor superfamily member 8 (TNFRSF8), also known as CD30; TNFRSF8 (also known as CD30, Ki-1, D1S166E) is expressed by activated T and B cells. It transduces signals that lead to the activation of NF-kappaB, mediated by the adaptor proteins TRAF2 and TRAF5. This receptor is a positive regulator of apoptosis, and has been shown to limit the proliferative potential of auto-reactive CD8 effector T cells and protect the body against autoimmunity. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. CD30 is expressed in malignant Hodgkin and Reed-Sternberg cells on the surface of extracellular vesicles, facilitating CD30-CD30L interaction between cell types. This receptor is also associated with anaplastic large cell lymphoma. It is expressed in embryonal carcinoma, but not in seminoma, making it a useful marker in distinguishing between these germ cell tumors. Since CD30 has restricted expression in normal tissues, it is an optimal target for selectively eliminating CD30-expressing neoplastic cells by specific toxin-conjugated monoclonal antibodies (mAbs).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597709797  62 TIPQAKPTPVSPATSSASTMPVRggtrLAQEAASKLTRAPDSPSSVGRPSSDPGLSPTQPCPEGSGDCRKQCEPDYYLDE 141
Cdd:cd13409    1 LSLRAKLTLFSPGTLRAPTMRRA----SAATCDGDPSRYYDEASSKCCYRCPPGLSPQQPCPQGSADCRKQCEPDYYLDE 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 597709797 142 AGRCTACVSCSRDDLVEKTPCAWNSSRTCECRPGMICATSATNSCARCVPYPIC 195
Cdd:cd13409   77 DGRCTACVSCSGDDLVEKAPCSWNSSRVCECRPGMFCATSATNSCARCVPHSVC 130

Tumor necrosis factor receptor superfamily member 8 (TNFRSF8), also known as CD30; TNFRSF8 (also known as CD30, Ki-1, D1S166E) is expressed by activated T and B cells. It transduces signals that lead to the activation of NF-kappaB, mediated by the adaptor proteins TRAF2 and TRAF5. This receptor is a positive regulator of apoptosis, and has been shown to limit the proliferative potential of auto-reactive CD8 effector T cells and protect the body against autoimmunity. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. CD30 is expressed in malignant Hodgkin and Reed-Sternberg cells on the surface of extracellular vesicles, facilitating CD30-CD30L interaction between cell types. This receptor is also associated with anaplastic large cell lymphoma. It is expressed in embryonal carcinoma, but not in seminoma, making it a useful marker in distinguishing between these germ cell tumors. Since CD30 has restricted expression in normal tissues, it is an optimal target for selectively eliminating CD30-expressing neoplastic cells by specific toxin-conjugated monoclonal antibodies (mAbs).

                         10        20
                 ....*....|....*....|
gi 597709797   1 MFCSTSAVNSCARCFFHSVC 20
Cdd:cd13409  111 MFCATSATNSCARCVPHSVC 130

Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B), also known as decoy receptor 3 (DcR3); The subfamily TNFRSF6B is also known as decoy receptor 3 (DcR3), M68, or TR6. This protein is a soluble receptor without death domain and cytoplasmic domain, and secreted by cells. It acts as a decoy receptor that competes with death receptors for ligand binding. It is a pleiotropic immunomodulator and biomarker for inflammatory diseases, autoimmune diseases, and cancer. Over-expression of this gene has been noted in several cancers, including pancreatic carcinoma, and gastrointestinal tract tumors. It can neutralize the biological effects of three tumor necrosis factor superfamily (TNFSF) members: TNFSF6 (Fas ligand/FasL/CD95L) and TNFSF14 (LIGHT) which are both involved in apoptosis and inflammation, and TNFSF15 (TNF-like molecule 1A/TL1A), which is a T cell co-stimulator and involved in gut inflammation. DcR3 is a novel inflammatory marker; higher DcR3 levels strongly correlate with inflammation and independently predict cardiovascular and all-cause mortality in chronic kidney disease (CKD) patients on hemodialysis. Increased synovial inflammatory cells infiltration in rheumatoid arthritis and ankylosing spondylitis is also associated with the elevated DcR3 expression. In cartilaginous fish, mRNA expression of DcR3 in the thymus and leydig, which are the representative lymphoid tissues of elasmobranchs, suggests that DcR3 may act as a modulator in the immune system. Interestingly, in banded dogfish (Triakis scyllia), DcR3 mRNA is strongly expressed in the gill, compared with human expression in the normal lung; both are respiratory organs, suggesting potential relevance of DcR3 to respiratory function.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 597709797  14 CFFHSVCPAGMIVKFPGTAQKNTVCEPASPGV-SPACASPENCKE 57
Cdd:cd10575   93 CLRHSSCPPGEGVIKLGTPYSDTQCEPCPPGFfSASSSSTEPCQP 137

Tumor necrosis factor receptor superfamily member 8 (TNFRSF8), also known as CD30; TNFRSF8 (also known as CD30, Ki-1, D1S166E) is expressed by activated T and B cells. It transduces signals that lead to the activation of NF-kappaB, mediated by the adaptor proteins TRAF2 and TRAF5. This receptor is a positive regulator of apoptosis, and has been shown to limit the proliferative potential of auto-reactive CD8 effector T cells and protect the body against autoimmunity. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. CD30 is expressed in malignant Hodgkin and Reed-Sternberg cells on the surface of extracellular vesicles, facilitating CD30-CD30L interaction between cell types. This receptor is also associated with anaplastic large cell lymphoma. It is expressed in embryonal carcinoma, but not in seminoma, making it a useful marker in distinguishing between these germ cell tumors. Since CD30 has restricted expression in normal tissues, it is an optimal target for selectively eliminating CD30-expressing neoplastic cells by specific toxin-conjugated monoclonal antibodies (mAbs).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597709797  62 TIPQAKPTPVSPATSSASTMPVRggtrLAQEAASKLTRAPDSPSSVGRPSSDPGLSPTQPCPEGSGDCRKQCEPDYYLDE 141
Cdd:cd13409    1 LSLRAKLTLFSPGTLRAPTMRRA----SAATCDGDPSRYYDEASSKCCYRCPPGLSPQQPCPQGSADCRKQCEPDYYLDE 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 597709797 142 AGRCTACVSCSRDDLVEKTPCAWNSSRTCECRPGMICATSATNSCARCVPYPIC 195
Cdd:cd13409   77 DGRCTACVSCSGDDLVEKAPCSWNSSRVCECRPGMFCATSATNSCARCVPHSVC 130

Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) interactions with TNF superfamily (TNFSF) ligands (TNFL) control key cellular processes such as differentiation, proliferation, apoptosis, and cell growth. Dysregulation of these pathways has been shown to result in a wide range of pathological conditions, including autoimmune diseases, inflammation, cancer, and viral infection. There are 29 very diverse family members of TNFRSF reported in humans: 22 are type I transmembrane receptors (single pass with the N terminus on extracellular side of the cell membrane) and have a clear signal peptide; the remaining 7 members are either type III transmembrane receptors (single pass with the N terminus on extracellular side of the membrane but no signal sequence; TNFR13B, TNFR13C, TNFR17, and XEDAR), or attached to the membrane via a glycosylphosphatidylinositol (GPI) linker (TNFR10C), or secreted as soluble receptors (TNFR11B and TNFR6B). All TNFRs contain relatively short cysteine-rich domains (CRDs) in the ectodomain, and are involved in interaction with the TNF homology domain (THD) of their ligands. TNFRs often have multiple CRDs (between one and six), with the most frequent configurations of three or four copies; most CRDs possess three disulfide bridges, but could have between one and four. Localized or genome-wide duplication and evolution of the TNFRSF members appear to have paralleled the emergence of the adaptive immune system; teleosts (i.e. ray-finned, bony fish), which possess an immune system with B and T cells, possess primary and secondary lymphoid organs, and are capable of adaptive responses to pathogens also display several characteristics that are different from the mammalian immune system, making teleost TNFSF orthologs and paralogs of interest to better understand immune system evolution and the immunological pathways elicited to pathogens.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597709797 114 PGLSPTQPCPEGSGDCRKQCEPDYYLDEAG---RCTACVSCSRDDLVEKTPCAWNSSRTCECRPGMICATS-ATNSCARC 189
Cdd:cd00185    7 PGEYLSSDCTATTDTVCSPCPPGTYSESWNslsKCLPCTTCGGGNQVEKTPCTATDNRCCTCKPGFYCDEGtNVEECKPC 86

Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B), also known as TNFR2; TNFRSF1B (also known as TNFR2, type 2 TNFR, TNFBR, TNFR80, TNF-R75, TNF-R-II, p75, CD120b) binds TNF-alpha, but lacks the death domain (DD) that is associated with the cytoplasmic domain of TNFRSF1A (TNFR1). It is inducible and expressed exclusively by oligodendrocytes, astrocytes, T cells, thymocytes, myocytes, endothelial cells, and in human mesenchymal stem cells. TNFRSF1B protects oligodendrocyte progenitor cells (OLGs) against oxidative stress, and induces the up-regulation of cell survival genes. While pro-inflammatory and pathogen-clearing activities of TNF are mediated mainly through activation of TNFRSF1A, a strong activator of NF-kappaB, TNFRSF1B is more responsible for suppression of inflammation. Although the affinities of both receptors for soluble TNF are similar, TNFRSF1B is sometimes more abundantly expressed and thought to associate with TNF, thereby increasing its concentration near TNFRSF1A receptors, and making TNF available to activate TNFRSF1A (a ligand-passing mechanism).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597709797 114 PGLSPTQPCPEGSGDCRKQCEPDYYLDEAGRCTACVSCS---RDDLVEKTPCAWNSSRTCECRPGMICATSATNSCARCV 190
Cdd:cd10577   21 PGQHVKHSCTKTSDTVCAPCEESTYTQLWNWVPECLSCSspcSSDQVETQACTRQQNRICSCKPGWYCVLKLQEGCRQCR 100

                 ....*.
gi 597709797 191 PYPICA 196
Cdd:cd10577  101 PLKKCG 106

Tumor necrosis factor receptor superfamily members, virus-encoded; This family contains viral TNFR homologs that include vaccinia virus (VACV) cytokine response modifier E (CrmE), an encoded TNFR that shares significant sequence similarity with mammalian type 2 TNF receptors (TNFSFR1B, p75, TNFR type 2), a cowpox virus encoded cytokine-response modifier B (crmB), which is a secreted form of TNF receptor that can contribute to the modification of TNF-mediated antiviral processes, and a myxoma virus (MYXV) T2 (M-T2) protein that binds and inhibits rabbit TNF-alpha. The CrmE structure confirms that the canonical TNFR fold is adopted, but only one of the two "ligand-binding" loops of TNFRSF1A is conserved, suggesting a mechanism for the higher affinity of poxvirus TNFRs for TNFalpha over lymphotoxin-alpha. CrmB protein specifically binds TNF-alpha and TNF-beta indicating that cowpox virus seeks to invade antiviral processes mediated by TNF. Intracellular M-T2 blocks virus-induced lymphocyte apoptosis via a highly conserved viral preligand assembly domain (vPLAD), which controls receptor signaling competency prior to ligand binding.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597709797 111 SSDPGLSPTQPCPEGSGDCRKQCEPDYYLDEAGRCTACVSCS---RDDLVEKTPCAWNSSRTCECRPGMICATSATNSCA 187
Cdd:cd15839   17 SCPPGTYASHLCDTTSNTKCDPCPSDTFTSIPNHIPACLSCRgrcSSNQVETKSCSNTQNRICSCAPGYYCLLKGSDGCV 96

                         90
                 ....*....|
gi 597709797 188 RCVPYPICAA 197
Cdd:cd15839   97 ACAPKTKCGV 106

Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B), also known as decoy receptor 3 (DcR3); The subfamily TNFRSF6B is also known as decoy receptor 3 (DcR3), M68, or TR6. This protein is a soluble receptor without death domain and cytoplasmic domain, and secreted by cells. It acts as a decoy receptor that competes with death receptors for ligand binding. It is a pleiotropic immunomodulator and biomarker for inflammatory diseases, autoimmune diseases, and cancer. Over-expression of this gene has been noted in several cancers, including pancreatic carcinoma, and gastrointestinal tract tumors. It can neutralize the biological effects of three tumor necrosis factor superfamily (TNFSF) members: TNFSF6 (Fas ligand/FasL/CD95L) and TNFSF14 (LIGHT) which are both involved in apoptosis and inflammation, and TNFSF15 (TNF-like molecule 1A/TL1A), which is a T cell co-stimulator and involved in gut inflammation. DcR3 is a novel inflammatory marker; higher DcR3 levels strongly correlate with inflammation and independently predict cardiovascular and all-cause mortality in chronic kidney disease (CKD) patients on hemodialysis. Increased synovial inflammatory cells infiltration in rheumatoid arthritis and ankylosing spondylitis is also associated with the elevated DcR3 expression. In cartilaginous fish, mRNA expression of DcR3 in the thymus and leydig, which are the representative lymphoid tissues of elasmobranchs, suggests that DcR3 may act as a modulator in the immune system. Interestingly, in banded dogfish (Triakis scyllia), DcR3 mRNA is strongly expressed in the gill, compared with human expression in the normal lung; both are respiratory organs, suggesting potential relevance of DcR3 to respiratory function.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 597709797  14 CFFHSVCPAGMIVKFPGTAQKNTVCEPASPGV-SPACASPENCKE 57
Cdd:cd10575   93 CLRHSSCPPGEGVIKLGTPYSDTQCEPCPPGFfSASSSSTEPCQP 137

Tumor necrosis factor receptor superfamily member 3 (TNFRSF3), also known as lymphotoxin beta receptor (LTBR); TNFRSF3 (also known as lymphotoxin beta receptor, LTbetaR, CD18, TNFCR, TNFR3, D12S370, TNFR-RP, TNFR2-RP, LT-BETA-R, TNF-R-III) plays a role in signaling during development of lymphoid and other organs, lipid metabolism, immune response, and programmed cell death. Its ligands include lymphotoxin (LT) alpha/beta membrane form (heterotrimer) and tumor necrosis factor ligand superfamily member 14 (also known as LIGHT). TNFRSF3 agonism by these ligands initiates canonical, as well as non-canonical nuclear factor-kappaB (NF-kappaB) signaling, and preferentially results in the translocation of p52-RELB complexes into the nucleus. While these ligands are often expressed by T and B cells, TNFRSF3 is conspicuous absence on T and B lymphocytes and NK cells, suggesting that signaling may be unidirectional for TNFRSF3. Activity of this receptor has also been linked to carcinogenesis; it helps trigger apoptosis and can also lead to release of the interleukin 8 (IL8). Alternatively spliced transcript variants encoding multiple isoforms have been observed.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 597709797 131 KQCEPDYYLDEAGRCTACVSCSRDDLV----EKTPCAWNSSRTCECRPGMICATSAtNSCARCVPYPIC 195
Cdd:cd10578   71 ATCPENSYNEHWNHLSICQLCRPCDPVlgfeEVAPCTSDRKTQCRCQPGMFCVHWD-NECEHCEPLSDC 138