tumor necrosis factor receptor superfamily member 25 (TNFRSF25), also known as death receptor 3 (DR3); TNFRSF25 (also known as death receptor 3 (DR3), death domain receptor 3 (DDR3), apoptosis-mediating receptor, lymphocyte associated receptor of death (LARD), apoptosis inducing receptor (AIR), APO-3, translocating chain-association membrane protein (TRAMP), WSL-1, WSL-LR or TNFRSF12) is preferentially expressed in thymocytes and lymphocytes, and may play a role in regulating lymphocyte homeostasis. It has been detected in lymphocyte-rich tissues such as colon, intestine, thymus and spleen, as well as in the prostate. Various death domain containing adaptor proteins mediate the signal transduction of this receptor; it activates nuclear factor kappa-B (NFkB) and induces cell apoptosis by associating with TNFRSF1A-associated via death domain (TRADD), which is known to mediate signal transduction of tumor necrosis factor receptors. DR3 associates with tumor necrosis factor (TNF)-like cytokine 1A (TL1A also known as TNFSF15) on activated lymphocytes and induces pro-inflammatory signals; TL1A also binds decoy receptor DcR3 (also known as TNFRSF6B). DR3/DcR3/TL1A expression is increased in both serum and inflamed tissues in autoimmune diseases such as in several autoimmune diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), allergic asthma, experimental autoimmune encephalomyelitis, type 1 diabetes, ankylosing spondylitis (AS), and primary biliary cirrhosis (PBC), making modulation of TL1A-DR3 interaction a potential therapeutic target.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568932186  50 RCDCASESQKRYGPFCCRGCPKGHYMKAPCAEPCGNSTCLPCPSDTFLTRDNHFKTDCTRCQVCDEEALQVTLENCSAKS 129
Cdd:cd13420    1 KCDCASEFQKRNGPFCCRGCPAGHYLKAPCTEPCGNSTCLPCPRGTFLARENHHKTDCTRCQACDEQASQVALENCSAVS 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 568932186 130 DTHCGCQSGWCVDCSTEPCGKSSPFSCVPCGATT 163
Cdd:cd13420   81 DTHCGCESGWFVECSVKDCVSSSPFSCKPCLDCG 114

tumor necrosis factor receptor superfamily member 25 (TNFRSF25), also known as death receptor 3 (DR3); TNFRSF25 (also known as death receptor 3 (DR3), death domain receptor 3 (DDR3), apoptosis-mediating receptor, lymphocyte associated receptor of death (LARD), apoptosis inducing receptor (AIR), APO-3, translocating chain-association membrane protein (TRAMP), WSL-1, WSL-LR or TNFRSF12) is preferentially expressed in thymocytes and lymphocytes, and may play a role in regulating lymphocyte homeostasis. It has been detected in lymphocyte-rich tissues such as colon, intestine, thymus and spleen, as well as in the prostate. Various death domain containing adaptor proteins mediate the signal transduction of this receptor; it activates nuclear factor kappa-B (NFkB) and induces cell apoptosis by associating with TNFRSF1A-associated via death domain (TRADD), which is known to mediate signal transduction of tumor necrosis factor receptors. DR3 associates with tumor necrosis factor (TNF)-like cytokine 1A (TL1A also known as TNFSF15) on activated lymphocytes and induces pro-inflammatory signals; TL1A also binds decoy receptor DcR3 (also known as TNFRSF6B). DR3/DcR3/TL1A expression is increased in both serum and inflamed tissues in autoimmune diseases such as in several autoimmune diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), allergic asthma, experimental autoimmune encephalomyelitis, type 1 diabetes, ankylosing spondylitis (AS), and primary biliary cirrhosis (PBC), making modulation of TL1A-DR3 interaction a potential therapeutic target.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568932186  50 RCDCASESQKRYGPFCCRGCPKGHYMKAPCAEPCGNSTCLPCPSDTFLTRDNHFKTDCTRCQVCDEEALQVTLENCSAKS 129
Cdd:cd13420    1 KCDCASEFQKRNGPFCCRGCPAGHYLKAPCTEPCGNSTCLPCPRGTFLARENHHKTDCTRCQACDEQASQVALENCSAVS 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 568932186 130 DTHCGCQSGWCVDCSTEPCGKSSPFSCVPCGATT 163
Cdd:cd13420   81 DTHCGCESGWFVECSVKDCVSSSPFSCKPCLDCG 114

Death domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568932186  341 QLYDVMDAVPA--RRWKEFVRTLGLREAEIEAVEVEICRFRDQQYEMLKRWRQQQP--AGLGAIYAALERMGLEGCAEDL 416
Cdd:pfam00531   3 QLDRLLDPPPPlgKDWRELARKLGLSENEIDEIESENPRLRSQTYELLRLWEQREGknATVGTLLEALRKLGRRDAAEKI 82

                  ....
gi 568932186  417 RSRL 420
Cdd:pfam00531  83 QSIL 86

TNF-alpha-receptor-like protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568932186  53 CASESQKRYGpFCCRGCPKGHYMKAPCaEPCGNSTCLPCPSDTFLTRDNHFKTdCTRCQVCDEEALQVTLENCSAKSD 130
Cdd:PHA02637  32 CKDNEYKRHN-LCCLSCPPGTYASRLC-DIKTNTQCTPCGSGTFTSHNNHLPA-CLSCNGRCDRVTRLTIESVNALEA 106

tumor necrosis factor receptor superfamily member 25 (TNFRSF25), also known as death receptor 3 (DR3); TNFRSF25 (also known as death receptor 3 (DR3), death domain receptor 3 (DDR3), apoptosis-mediating receptor, lymphocyte associated receptor of death (LARD), apoptosis inducing receptor (AIR), APO-3, translocating chain-association membrane protein (TRAMP), WSL-1, WSL-LR or TNFRSF12) is preferentially expressed in thymocytes and lymphocytes, and may play a role in regulating lymphocyte homeostasis. It has been detected in lymphocyte-rich tissues such as colon, intestine, thymus and spleen, as well as in the prostate. Various death domain containing adaptor proteins mediate the signal transduction of this receptor; it activates nuclear factor kappa-B (NFkB) and induces cell apoptosis by associating with TNFRSF1A-associated via death domain (TRADD), which is known to mediate signal transduction of tumor necrosis factor receptors. DR3 associates with tumor necrosis factor (TNF)-like cytokine 1A (TL1A also known as TNFSF15) on activated lymphocytes and induces pro-inflammatory signals; TL1A also binds decoy receptor DcR3 (also known as TNFRSF6B). DR3/DcR3/TL1A expression is increased in both serum and inflamed tissues in autoimmune diseases such as in several autoimmune diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), allergic asthma, experimental autoimmune encephalomyelitis, type 1 diabetes, ankylosing spondylitis (AS), and primary biliary cirrhosis (PBC), making modulation of TL1A-DR3 interaction a potential therapeutic target.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568932186  50 RCDCASESQKRYGPFCCRGCPKGHYMKAPCAEPCGNSTCLPCPSDTFLTRDNHFKTDCTRCQVCDEEALQVTLENCSAKS 129
Cdd:cd13420    1 KCDCASEFQKRNGPFCCRGCPAGHYLKAPCTEPCGNSTCLPCPRGTFLARENHHKTDCTRCQACDEQASQVALENCSAVS 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 568932186 130 DTHCGCQSGWCVDCSTEPCGKSSPFSCVPCGATT 163
Cdd:cd13420   81 DTHCGCESGWFVECSVKDCVSSSPFSCKPCLDCG 114

Death domain of Tumor Necrosis Factor Receptor 1; Death Domain (DD) found in tumor necrosis factor receptor-1 (TNFR-1). TNFR-1 has many names including TNFRSF1A, CD120a, p55, p60, and TNFR60. It activates two major intracellular signaling pathways that lead to the activation of the transcription factor NF-kB and the induction of cell death. Upon binding of its ligand TNF, TNFR-1 trimerizes which leads to the recruitment of an adaptor protein named TNFR-associated death domain protein (TRADD) through a DD/DD interaction. Mutations in the TNFRSF1A gene causes TNFR-associated periodic syndrome (TRAPS), a rare disorder characterized recurrent fever, myalgia, abdominal pain, conjunctivitis and skin eruptions. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568932186 341 QLYDVMDAVPARRWKEFVRTLGLREAEIEAVEVEICRFRDQQYEMLKRWRQQQP---AGLGAIYAALERMGLEGCAEDLR 417
Cdd:cd08313    1 LLYTVLDEVPPRRWKEFVRRLGLSDNEIERVELDHRRCRDAQYQMLKVWKERGPrpyATLQHLLSVLRDMELVGCAEDIE 80

DEATH domain, found in proteins involved in cell death (apoptosis); Alpha-helical domain present in a variety of proteins with apoptotic functions. Some (but not all) of these domains form homotypic and heterotypic dimers.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568932186   336 LQPGPQLYDVMDAVPARRWKEFVRTLGLREAEIEAVEVEICR-FRDQQYEMLKRWRQQQP--AGLGAIYAALERMGLEGC 412
Cdd:smart00005   2 ELTRQKLAKLLDHPLGLDWRELARKLGLSEADIDQIRTEAPRdLAEQSVQLLRLWEQREGknATLGTLLEALRKMGRDDA 81

                   ....*..
gi 568932186   413 AEDLRSR 419
Cdd:smart00005  82 VELLRSE 88

Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), also known as TNFR1; TNFRSF1A (also known as type I TNFR, TNFR1, DR1, TNFRSF1A, CD120a, p55) binds TNF-alpha, through the death domain (DD), and activates NF-kappaB, mediates apoptosis and activates signaling pathways controlling inflammatory, immune, and stress responses. It mediates signal transduction by interacting with antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRAF2 and TRADD that play regulatory roles. The human genetic disorder called tumor necrosis factor associated periodic syndrome (TRAPS), or periodic fever syndrome, is associated with germline mutations of the extracellular domains of this receptor, possibly due to impaired receptor clearance. TNFRSF1A polymorphisms rs1800693 and rs4149584 are associated with elevated risk of multiple sclerosis. Serum levels of TNFRSF1A are elevated in schizophrenia and bipolar disorder, and high levels are also associated with cognitive impairment and dementia. Patients with idiopathic recurrent acute pericarditis (IRAP), presumed to be an autoimmune process, have also been shown to carry rare mutations (R104Q and D12E) in the TNFRSF1A gene.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568932186  64 FCCRGCPKGHYMKAPCAEPCGNSTCLPCPSDTFLTRDNHFkTDCTRCQVCDEEALQVTLENCSAKSDTHCGCQSGWCVDc 143
Cdd:cd10576   13 HCCTKCHKGTYLYNDCPGPGQDTVCRECENGTFTASENYL-RKCLSCSRCRKEMGQVEISPCTVDQDTVCGCRKNQYQH- 90

                         90
                 ....*....|....*.
gi 568932186 144 stepcGKSSPFSCVPC 159
Cdd:cd10576   91 -----YWSSLFQCKNC 101

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 568932186  65 CCRGCPKGHYMKAPCAEPcGNSTCLPCPSDTFLTRDNHFKTdCTRCQVCDEEAlQVTLENCSAKSDTHCGCQSGWCVDCS 144
Cdd:cd00185    1 CCQRCPPGEYLSSDCTAT-TDTVCSPCPPGTYSESWNSLSK-CLPCTTCGGGN-QVEKTPCTATDNRCCTCKPGFYCDEG 77

                         90
                 ....*....|....*
gi 568932186 145 TEpcgkssPFSCVPC 159
Cdd:cd00185   78 TN------VEECKPC 86

Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) in teleosts; also known as TNFR1; This subfamily of TNFRSF1 ((also known as type I TNFR, TNFR1, DR1, TNFRSF1A, CD120a, p55) is found in teleosts. It binds TNF-alpha, through the death domain (DD), and activates NF-kappaB, mediates apoptosis and activates signaling pathways controlling inflammatory, immune, and stress responses. It mediates signal transduction by interacting with antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRAF2 and TRADD that play regulatory roles. The human genetic disorder called tumor necrosis factor associated periodic syndrome (TRAPS), or periodic fever syndrome, is associated with germline mutations of the extracellular domains of this receptor, possibly due to impaired receptor clearance. Serum levels of TNFRSF1A are elevated in schizophrenia and bipolar disorder, and high levels are also associated with cognitive impairment and dementia. Knockout studies in zebrafish embryos have shown that a signaling balance between TNFRSF1A and TNFRSF1B is required for endothelial cell integrity. TNFRSF1A signals apoptosis through caspase-8, whereas TNFRSF1B signals survival via NF-kappaB in endothelial cells. Thus, this apoptotic pathway seems to be evolutionarily conserved, as TNFalpha promotes apoptosis of human endothelial cells and triggers caspase-2 and P53 activation in these cells via TNFRSF1A.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568932186  64 FCCRGCPKGHYMKAPCAEPCGNSTCLPCPSDTFLTRDNHFKTdCTRCQVCDEEaLQVTLENCSAKSDTHCGCQSGW---C 140
Cdd:cd15834   12 ICCNKCHPGYKLKEECTAPGERSQCTPCPEGTYLEQINYSPN-CRRCTLCKVK-NEEEVSPCKKSSNTVCRCKKGYyksR 89

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568932186 141 VDCSTEPCGKsspfsCVPCGATTPVHEAPTPRP-----CLPGFYIRGNDCTSCpTGFSSVCPKACTA 202
Cdd:cd15834   90 IDSETRECLK-----CKTCGPGEIEIQPCTPESntvceCKDNYYRNNNKCKPC-QKCSLDCQHLCTT 150

Tumor necrosis factor receptor superfamily member 14 (TNFRSF14), also known as herpes virus entry mediator (HVEM); TNFRSF14 (also known as herpes virus entry mediator or HVEM, ATAR, CD270, HVEA, LIGHTR, TR2) regulates T-cell immune responses by activating inflammatory, as well as inhibitory signaling pathways. HVEM acts as a receptor for the canonical TNF-related ligand LIGHT (lymphotoxin-like), which exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for HVEM. It also acts as a ligand for the immunoglobulin superfamily proteins BTLA (B and T lymphocyte attenuator) and CD160, a feature distinguishing HVEM from other immune regulatory molecules, thus, creating a functionally diverse set of intrinsic and bidirectional signaling pathways. HVEM is highly expressed in the gut epithelium. Genome-wide association studies have shown that Hvem is an inflammatory bowel disease (IBD) risk gene, suggesting that HVEM could have a regulatory role influencing the regulation of epithelial barrier, host defense, and the microbiota. Mouse models have revealed that HVEM is involved in colitis pathogenesis, mucosal host defense, and epithelial immunity, thus acting as a mucosal gatekeeper with multiple regulatory functions in the mucosa. HVEM plays a critical role in both tumor progression and resistance to antitumor immune responses, possibly through direct and indirect mechanisms. It is known to be expressed in several human malignancies, including esophageal squamous cell carcinoma, follicular lymphoma and melanoma. HVEM network may therefore be an attractive target for drug intervention.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568932186  62 GPFCCRGCPKGHYMKAPCAEPCGnSTCLPCPSDTFLTRDNHFkTDCTRCQVCDEEALQVTLENCSAKSDTHCGCQSG 138
Cdd:cd10582    9 GSECCPKCSPGYRVKKACGELTG-TVCEPCPPGTYTAHLNGL-SKCLQCRVCDPAMGLVTRRNCSSTENTVCGCIPG 83

Tumor necrosis factor receptor superfamily member 14 (TNFRSF14) in teleost; also known as herpes virus entry mediator (HVEM); This subfamily of TNFRSF14 (also known as herpes virus entry mediator or HVEM, ATAR, CD270, HVEA, LIGHTR, TR2) is found in teleosts, many of which are as yet uncharacterized. It regulates T-cell immune responses by activating inflammatory as well as inhibitory signaling pathways. HVEM acts as a receptor for the canonical TNF-related ligand LIGHT (lymphotoxin-like), which exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for HVEM. It also acts as a ligand for the immunoglobulin superfamily proteins BTLA (B and T lymphocyte attenuator) and CD160, a feature distinguishing HVEM from other immune regulatory molecules, thus, creating a functionally diverse set of intrinsic and bidirectional signaling pathways. HVEM is highly expressed in the gut epithelium. Genome-wide association studies have shown that HVEM is an inflammatory bowel disease (IBD) risk gene, suggesting that HVEM could have a regulatory role influencing the regulation of epithelial barrier, host defense, and the microbiota. Mouse models have revealed that HVEM is involved in colitis pathogenesis, mucosal host defense, and epithelial immunity, thus acting as a mucosal gatekeeper with multiple regulatory functions in the mucosa. HVEM plays a critical role in both tumor progression and resistance to antitumor immune responses, possibly through direct and indirect mechanisms. It is known to be expressed in several human malignancies, including esophageal squamous cell carcinoma, follicular lymphoma, and melanoma. HVEM network may therefore be an attractive target for drug intervention. In Asian seabass, the up-regulation of differentially expressed TNFRSF14 gene has been observed.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568932186  65 CCRGCPKGHYMKAPCAEPcGNSTCLPCPSDTFLTRDNHFKTdCTRCQVCDEEALQVTLENCSAKSDTHCGCQSG-WCVDC 143
Cdd:cd13405   12 CCPMCPPGSRVSRHCTED-TSTSCVPCPDGTYMDEPNGLEK-CFPCTNCDPGFGLRVKQGCTYTSDTVCEPLEGfYCIDS 89

                 ....*
gi 568932186 144 STEPC 148
Cdd:cd13405   90 TKDGC 94

Death domain of Tumor necrosis factor-Related Apoptosis-Inducing Ligand Receptors; Death Domain (DD) found in Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL) Receptors. In mammals, this family includes TRAILR1 (also called DR4 or TNFRSF10A) and TRAILR2 (also called DR5, TNFRSF10B, or KILLER). They function as receptors for the cytokine TRAIL and are involved in apoptosis signaling pathways. TRAIL preferentially induces apoptosis in cancer cells while exhibiting little toxicity in normal cells. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568932186 347 DAVPARRWKEFVRTLGLREAEIEAVEVEICRFRDQQYEMLKRWRQQQpaGLGA----IYAALERMGLEGCAEDLRSRL 420
Cdd:cd08315    7 DIVPFKSWKRLMRALGLSDNEIKLAEANDPGSQEPLYQMLNKWLNKT--GRKAsvntLLDALEDLGLRGAAETIADKL 82

Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40; TNFRSF5 (commonly known as CD40 and also as CDW40, p50, Bp50) is widely expressed in diverse cell types including B lymphocytes, dendritic cells, platelets, monocytes, endothelial cells, and fibroblasts. It is essential in mediating a wide variety of immune and inflammatory responses, including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. Its natural immunomodulating ligand is CD40L, and a primary defect in the CD40/CD40L system is associated with X-linked hyper-IgM (XHIM) syndrome. It is also involved in tumorigenesis; CD40 expression is significantly higher in gastric carcinomas and it is associated with the lymphatic metastasis of cancer cells and their tumor node metastasis (TNM) classification. Upregulated levels of CD40/CD40L on B cells and T cells may play an important role in the immune pathogenesis of breast cancer. Consequently, the CD40/CD40L system serves as a link between tumorigenesis, atherosclerosis, and the immune system, and offers a potential target for drug therapy for related diseases, such as cancer, atherosclerosis, diabetes mellitus, and immunological rejection.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568932186  65 CCRGCPKGHYMKAPCAEpCGNSTCLPCPSDTFL---TRDNHfktdCTRCQVCDEEALQVTLENCSAKSDTHCGCQSGWcv 141
Cdd:cd13407   12 CCSLCPPGQKLVSDCTE-ATDTECLPCEEGEFQdtwNRERH----CHQHRYCDPNLGLRVQTEGTAETDTTCTCQEGQ-- 84

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568932186 142 DCSTEPCGksspfSCVPcgattpvheaptPRPCLPGFYIR-------GNDCTSCPTGFSS 194
Cdd:cd13407   85 HCTSEACE-----TCAL------------HTSCKPGFGVKqiatgvsDTICEPCPVGFFS 127

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568932186  65 CCRGCPKGHYMKAPCaEPCGNSTCLPCPSDTFLTRDNHFKTdCTRCQVCDEEALQVTLENCSAKSDTHCGCQSGW-CVDC 143
Cdd:cd10578   48 CCSRCPPGTHVSAEC-SRSQDTVCATCPENSYNEHWNHLSI-CQLCRPCDPVLGFEEVAPCTSDRKTQCRCQPGMfCVHW 125

                         90
                 ....*....|....*..
gi 568932186 144 STEpCGKSSPFSCVPCG 160
Cdd:cd10578  126 DNE-CEHCEPLSDCPPG 141

Tumor necrosis factor receptor superfamily member 9 (TNFRSF9) in teleosts; also known as CD137; This subfamily of TNFRSF9 (also known as CD137, ILA, 4-1BB) is found in teleosts. CD137 plays a role in the immunobiology of human cancer where it is preferentially expressed on tumor-reactive subset of tumor-infiltrating lymphocytes. It can be expressed by activated T cells, but to a larger extent on CD8 than on CD4 T cells. In addition, CD137 expression is found on dendritic cells, follicular dendritic cells, natural killer cells, granulocytes and cells of blood vessel walls at sites of inflammation. It transduces signals that lead to the activation of NF-kappaB, mediated by the TRAF adaptor proteins. CD137 contributes to the clonal expansion, survival, and development of T cells. It can also induce proliferation in peripheral monocytes, enhance T cell apoptosis induced by TCR/CD3 triggered activation, and regulate CD28 co-stimulation to promote Th1 cell responses. CD137 is modulated by SAHA treatment in breast cancer cells, suggesting that the combination of SAHA with this receptor could be a new therapeutic approach for the treatment of tumors. Mostly, CD137 in teleosts have not been characterized.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568932186  53 CASESQKRYGPFCCRGCPKGHYMKAPCAePCGNSTCLPCPSDTFLTRDNHFKtdCTRCQVCdeEALQVTLENCSAKSDTH 132
Cdd:cd13424    1 CKKWEPSGKNYVCCESCHPGNRLVERCG-PDPAELCKPCEPGTYTVKPLDYS--CYICTQC--IGAQVLLKNCTPSSDTV 75

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 568932186 133 CGCQSGWcvdcstePCGKSSPFSCVPCGATTpvhEAPTPRpclpgfyirgNDCTSCPTG 191
Cdd:cd13424   76 CGCKEGL-------RCGDAECSFCVTECGKG---QEPLGK----------RDCRQCPVG 114

Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK); TNFRSF11A (also known as RANK, FEO, OFE, ODFR, OSTS, PDB2, CD26, OPTB7, TRANCER, LOH18CR1) induces the activation of NF-kappa B and MAPK8/JNK through interactions with various TRAF adaptor proteins. This receptor and its ligand are important regulators of the interaction between T cells and dendritic cells. The receptor is also an essential mediator for osteoclast and lymph node development. Mutations at this locus have been associated with familial expansile osteolysis, autosomal recessive osteopetrosis, and Juvenile Paget's disease (JPD) of bone. Alternatively spliced transcript variants have been described for this locus. Mutation analysis may improve diagnosis, prognostication, recurrence risk assessment, and perhaps treatment selection among the monogenic disorders of RANKL/OPG/RANK activation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568932186  53 CASESQKRYGPFCCRGCPKGHYMKAPCAePCGNSTCLPCPSDTFL-TRDNHFKtdCTRCQVCDEEALQVTLENCSAKSDT 131
Cdd:cd13411    2 CSSERHYEYSGRCCSKCEPGKYMSSKCT-VTSDSVCLPCGPDEYLdTWNEEDK--CLLHKVCDAGKALVAVDPGNSTAPR 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 568932186 132 HCGCQSG--WCVDCstEPCGKSSpfSCVP-CGATTPV--HEAPTPRPCLPGFY 179
Cdd:cd13411   79 RCACTAGyhWSEDC--DCCRRNT--ECAPgFGAQHPVqlNKDTVCEPCLVGYF 127

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 568932186  65 CCRGCPKGHYMKAPCAEpCGNSTCLPCPSDTFLTRDNHFKTdctrCQVCDE--EALQVTLENCSAKSDTHCGCQSGW-CV 141
Cdd:cd10577   15 CCSKCPPGQHVKHSCTK-TSDTVCAPCEESTYTQLWNWVPE----CLSCSSpcSSDQVETQACTRQQNRICSCKPGWyCV 89

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 568932186 142 DCSTEPCGKSSPFScvPCGATTPVHEAPTP------RPCLPG 177
Cdd:cd10577   90 LKLQEGCRQCRPLK--KCGPGFGVARPGTAssdvecKPCAPG 129

TNF-alpha-receptor-like protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568932186  53 CASESQKRYGpFCCRGCPKGHYMKAPCaEPCGNSTCLPCPSDTFLTRDNHFKTdCTRCQVCDEEALQVTLENCSAKSD 130
Cdd:PHA02637  32 CKDNEYKRHN-LCCLSCPPGTYASRLC-DIKTNTQCTPCGSGTFTSHNNHLPA-CLSCNGRCDRVTRLTIESVNALEA 106