Tumor necrosis factor receptor superfamily member 27 (TNFRSF27), also known as ectodysplasin A2 receptor (EDA2R) or X-linked ectodermal dysplasia receptor (XEDAR); TNFRSF27 (also known as ectodysplasin A2 receptor (EDA2R), X-linked ectodermal dysplasia receptor (XEDAR), EDAA2R, EDA-A2R) has two isoforms, EDA-A1 and EDA-A2, that are encoded by the anhidrotic ectodermal dysplasia (EDA) gene. It is highly expressed during embryonic development and binds to ectodysplasin-A2 (EDA-A2), playing a crucial role in the p53-signaling pathway. EDA2R is a direct p53 target that is frequently down-regulated in colorectal cancer tissues due to its epigenetic alterations or through the p53 gene mutations. Mutations in the EDA-A2/XEDAR signaling give rise to ectodermal dysplasia, characterized by loss of hair, sweat glands, and teeth. A non-synonymous SNP on EDA2R, along with genetic variants in human androgen receptor is associated with androgenetic alopecia (AGA).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1519312798   3 CQENEYWDQWGRCVTCQRCGPGQELSKDCGYGEGGDAYCTACPPRRYKSSWGHHRCQSCITCAVINRVQKVNCTATSNAV 82
Cdd:cd15838     1 CQEKEYLDEHGKCVPCRECGPGQELSKDCGYGEGGDAYCTACPPRRFKDSWGHHGCKTCLSCALINRVQKSNCTATSNAV 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1519312798  83 CGDCLPRFYRKTRIGGLQDQECIPCTKQTPTSEVQC 118
Cdd:cd15838    81 CGDCLPGFYRKTRIGGLQDQECIPCTKQTPSSEVQC 116

Tumor necrosis factor receptor superfamily member 27 (TNFRSF27), also known as ectodysplasin A2 receptor (EDA2R) or X-linked ectodermal dysplasia receptor (XEDAR); TNFRSF27 (also known as ectodysplasin A2 receptor (EDA2R), X-linked ectodermal dysplasia receptor (XEDAR), EDAA2R, EDA-A2R) has two isoforms, EDA-A1 and EDA-A2, that are encoded by the anhidrotic ectodermal dysplasia (EDA) gene. It is highly expressed during embryonic development and binds to ectodysplasin-A2 (EDA-A2), playing a crucial role in the p53-signaling pathway. EDA2R is a direct p53 target that is frequently down-regulated in colorectal cancer tissues due to its epigenetic alterations or through the p53 gene mutations. Mutations in the EDA-A2/XEDAR signaling give rise to ectodermal dysplasia, characterized by loss of hair, sweat glands, and teeth. A non-synonymous SNP on EDA2R, along with genetic variants in human androgen receptor is associated with androgenetic alopecia (AGA).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1519312798   3 CQENEYWDQWGRCVTCQRCGPGQELSKDCGYGEGGDAYCTACPPRRYKSSWGHHRCQSCITCAVINRVQKVNCTATSNAV 82
Cdd:cd15838     1 CQEKEYLDEHGKCVPCRECGPGQELSKDCGYGEGGDAYCTACPPRRFKDSWGHHGCKTCLSCALINRVQKSNCTATSNAV 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1519312798  83 CGDCLPRFYRKTRIGGLQDQECIPCTKQTPTSEVQC 118
Cdd:cd15838    81 CGDCLPGFYRKTRIGGLQDQECIPCTKQTPSSEVQC 116

Tumor necrosis factor receptor / nerve growth factor receptor repeats; Repeats in growth factor receptors that are involved in growth factor binding. TNF/TNFR

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1519312798   44 CPPRRYKSSWGHHRCQSCITCAVINRVqKVNCTATSNAVC 83
Cdd:smart00208   1 CKEGTYCSDGNHSSCLRCRRCPPGLVV-KQPCTATSDTVC 39

Tumor necrosis factor receptor superfamily member 27 (TNFRSF27), also known as ectodysplasin A2 receptor (EDA2R) or X-linked ectodermal dysplasia receptor (XEDAR); TNFRSF27 (also known as ectodysplasin A2 receptor (EDA2R), X-linked ectodermal dysplasia receptor (XEDAR), EDAA2R, EDA-A2R) has two isoforms, EDA-A1 and EDA-A2, that are encoded by the anhidrotic ectodermal dysplasia (EDA) gene. It is highly expressed during embryonic development and binds to ectodysplasin-A2 (EDA-A2), playing a crucial role in the p53-signaling pathway. EDA2R is a direct p53 target that is frequently down-regulated in colorectal cancer tissues due to its epigenetic alterations or through the p53 gene mutations. Mutations in the EDA-A2/XEDAR signaling give rise to ectodermal dysplasia, characterized by loss of hair, sweat glands, and teeth. A non-synonymous SNP on EDA2R, along with genetic variants in human androgen receptor is associated with androgenetic alopecia (AGA).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1519312798   3 CQENEYWDQWGRCVTCQRCGPGQELSKDCGYGEGGDAYCTACPPRRYKSSWGHHRCQSCITCAVINRVQKVNCTATSNAV 82
Cdd:cd15838     1 CQEKEYLDEHGKCVPCRECGPGQELSKDCGYGEGGDAYCTACPPRRFKDSWGHHGCKTCLSCALINRVQKSNCTATSNAV 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1519312798  83 CGDCLPRFYRKTRIGGLQDQECIPCTKQTPTSEVQC 118
Cdd:cd15838    81 CGDCLPGFYRKTRIGGLQDQECIPCTKQTPSSEVQC 116

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 1519312798  17 TCQRCGPGQELSKDCGYGegGDAYCTACPPRRYKSSWGH-HRCQSCITCAVINRVQKVNCTATSNAVCgDCLPRFYRKTr 95
Cdd:cd00185     1 CCQRCPPGEYLSSDCTAT--TDTVCSPCPPGTYSESWNSlSKCLPCTTCGGGNQVEKTPCTATDNRCC-TCKPGFYCDE- 76

                          90
                  ....*....|...
gi 1519312798  96 igGLQDQECIPCT 108
Cdd:cd00185    77 --GTNVEECKPCT 87

Tumor necrosis factor receptor superfamily member ectodysplasin A receptor (EDAR); Ectodysplasin A receptor (EDAR, also known as DL, ED3, ED5, ED1R, EDA3, HRM1, EDA1R, ECTD10A, ECTD10B, EDA-A1R) binds the soluble ligand ectodysplasin A and can activate the nuclear factor-kappaB, JNK, and caspase-independent cell death pathways. It is required for the development of hair, teeth, and other ectodermal derivatives. Mutations in this gene result in autosomal dominant and recessive forms of hypohidrotic ectodermal dysplasia. Patients present defects in the development of ectoderm-derived structures resulting in sparse hair, too few teeth (oligodontia), the absence or reduction in the ability to sweat as well as problems with mucous and saliva and the production and formation of pigment cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1519312798   2 DCQENEYWDQW-GRCVTCQRCGPGQELSKDCGYGEGGDAY-CTACPPRRYkSSWGHHRCQSCITCAVINRVQKVN-CTAT 78
Cdd:cd13421    18 NCGENEYYNQTtGLCQQCPPCRPGEEPYMSCGYGTKDEDYgCVPCPAEKF-SKGGYQICRRHKDCEGFFRATVLTpGDME 96

                          90
                  ....*....|...
gi 1519312798  79 SNAVCGDCLPRFY 91
Cdd:cd13421    97 NDAECGPCLPGYY 109

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 1519312798   3 CQENEYWDQWGRCvtCQRCGPGQELSKDCgYGEGGDAYCTACPPRRYKSSWGHH-RCQSCITCAVINRVQKVNCTATSNA 81
Cdd:cd15834     1 CLDSEYLSENGIC--CNKCHPGYKLKEEC-TAPGERSQCTPCPEGTYLEQINYSpNCRRCTLCKVKNEEEVSPCKKSSNT 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1519312798  82 VCgDCLPRFYRKT-----------RIGGLQDQECIPCTKQTPT 113
Cdd:cd15834    78 VC-RCKKGYYKSRidsetreclkcKTCGPGEIEIQPCTPESNT 119

Tumor necrosis factor receptor superfamily member 7 (TNFRSF7), also known as CD27; TNFRSF7 (also known as CD27, T14, S152, Tp55, S152, LPFS2) has a key role in the generation of immunological memory via effects on T-cell expansion and survival, and B cell development. It binds to ligand CD70, and plays a key role in regulating B-cell activation and immunoglobulin synthesis. CD27 transduces signals that lead to the activation of NF-kappaB and MAPK8/JNK, and mediates the signaling process through adaptor proteins TRAF2 and TRAF5. CD27-binding protein (SIVA), a pro-apoptotic protein, can bind to CD27 and may play an important role in the apoptosis induced by this receptor. The potential role of the CD27/CD70 pathway in the course of inflammatory diseases, such as arthritis, and inflammatory bowel disease, suggests that CD70 may be a target for immune intervention. The expression of CD27 and CD44 molecules correlates with the differentiation stage of B cell precursors and has been shown to have a biological significance in acute lymphoblastic leukemia.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1519312798   3 CQENEYWDQWGRCvtCQRCGPGQELSKDCGyGEGGDAYCTACPPRRYKSSWGHHR--CQSCITCAVINRVQkvNCTATSN 80
Cdd:cd13408    24 CPERHYWAQGKLC--CQMCEPGTFLVKDCD-QHGKAAQCDPCIPGVSFSPDHHARphCESCRHCNSGLLIR--NCTITAN 98

                  ....
gi 1519312798  81 AVCG 84
Cdd:cd13408    99 TECA 102

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 1519312798   3 CQENEYWDQWGRcVTCQRCGPGQELSKDCGYGEggDAYCTACPPRRYKSSWGH-HRCQSCITC-AVINRVQKVNCTATSN 80
Cdd:cd10578    35 DQEKEYYEPRHQ-VCCSRCPPGTHVSAECSRSQ--DTVCATCPENSYNEHWNHlSICQLCRPCdPVLGFEEVAPCTSDRK 111

                          90       100
                  ....*....|....*....|....*..
gi 1519312798  81 AVCGdCLPRFYrktriGGLQDQECIPC 107
Cdd:cd10578   112 TQCR-CQPGMF-----CVHWDNECEHC 132

Tumor necrosis factor receptor superfamily member 16 (TNFRSF16), also known as p75 neurotrophin receptor (p75NTR) or CD271; TNFRSF16 (also known as nerve growth factor receptor (NGFR) or p75 neurotrophin receptor (p75NTR or p75(NTR)), CD271, Gp80-LNGFR) is a common receptor for both neurotrophins and proneurotrophins, and plays a diverse role in many tissues, including the nervous system. It has been shown to be expressed in various types of stem cells and has been used to prospectively isolate stem cells with different degrees of potency. p75NTR owes its signaling to the recruitment of intracellular binding proteins, leading to the activation of different signaling pathways. It binds nerve growth factor (NGF) and the complex can initiate a signaling cascade which has been associated with both neuronal apoptosis and neuronal survival of discrete populations of neurons, depending on the presence or absence of intracellular signaling molecules downstream of p75NTR (e.g. NF-kB, JNK, or p75NTR intracellular death domain). p75NTR can also bind NGF in concert with the neurotrophic tyrosine kinase receptor type 1 (TrkA) protein where it is thought to modulate the formation of the high-affinity neurotrophin binding complex. On melanoma cell, p75NTR is an immunosuppressive factor, induced by interferon (IFN)-gamma, and mediates down-regulation of melanoma antigens. It can interact with the aggregated form of amyloid beta (Abeta) peptides, and plays an important role in etiopathogenesis of Alzheimer's disease by influencing protein tau hyper-phosphorylation. p75(NTR) is involved in the formation and progression of retina diseases; its expression is induced in retinal pigment epithelium (RPE) cells and its knockdown rescues RPE cell proliferation activity and inhibits RPE apoptosis induced by hypoxia. It can therefore be a potential therapeutic target for RPE hypoxia or oxidative stress diseases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1519312798   2 DCQENEYWDQW-GRCVTCQRCGPGQELSKDCgyGEGGDAYCTACPPRRY---KSSWghHRCQSCITCAViNRVQKVNCTA 77
Cdd:cd13416    79 ECAYGYYLDEDsGTCEPCTVCPPGQGVVQSC--GPNQDTVCEACPEGTYsdeDSST--DPCLPCTVCED-GEVELRECTP 153

                  ....*.
gi 1519312798  78 TSNAVC 83
Cdd:cd13416   154 VSDTVC 159

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 1519312798  18 CQRCGPGQELSKDCGyGEGGDAYCTACPPRRYKSSWGHH-RCQSCITC-AVINRVQKVNCTATSNAVCGdCLPRFYRKTR 95
Cdd:cd10576    15 CTKCHKGTYLYNDCP-GPGQDTVCRECENGTFTASENYLrKCLSCSRCrKEMGQVEISPCTVDQDTVCG-CRKNQYQHYW 92

                          90
                  ....*....|....*...
gi 1519312798  96 IGGLQDQECIPCTKQTPT 113
Cdd:cd10576    93 SSLFQCKNCSLCLNGTIR 110

Tumor necrosis factor receptor superfamily 11B (TNFRSF11B) in teleost; also known as Osteoprotegerin (OPG); This subfamily of TNFRSF11B (also known as Osteoprotegerin, OPG, TR1, OCIF) is found in teleosts. It is a secreted glycoprotein that regulates bone resorption. It binds to two ligands, RANKL (receptor activator of nuclear factor kappaB ligand, also known as osteoprotegerin ligand, OPGL, TRANCE, TNF-related activation induced cytokine), a critical cytokine for osteoclast differentiation, and TRAIL (TNF-related apoptosis-inducing ligand), involved in immune surveillance. Therefore, acting as a decoy receptor for RANKL and TRAIL, OPG inhibits the regulatory effects of nuclear factor-kappaB on inflammation, skeletal, and vascular systems, and prevents TRAIL-induced apoptosis. Studies in mice counterparts suggest that this protein and its ligand also play a role in lymph-node organogenesis and vascular calcification. Circulating OPG levels have emerged as independent biomarkers of cardiovascular disease (CVD) in patients with acute or chronic heart disease. OPG has also been implicated in various inflammations and linked to diabetes and poor glycemic control. Alternatively spliced transcript variants of this gene have been reported, although their full length nature has not been determined. Genetic analysis of the Japanese rice fish medaka (Oryzias latipes) has shown that entire networks for bone formation are conserved between teleosts and mammals; enabling medaka to be used as a genetic model to monitor bone homeostasis in vivo.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1519312798  13 GRCVTCQRCGPGQELSKDCGYGEggDAYCTACPPRRYKSSWGH-HRCQSCITCAVINRVQKVNCTATSNAVC 83
Cdd:cd13412    17 GKILTCKKCPPGTHMAAHCTATT--QTKCLPCPAAHYTELWNYlPRCLYCNNFCSENQEVEIECSATNNRVC 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 1519312798   3 CQEN-EYWDQ-WGRCvtCQRCGPGQELSKDCGygEGGDAYCTACPPRRYKSSWGHHR-CQSCITCAVINRVQKVNCTATS 79
Cdd:cd10577     1 CRNSkEYYDEkAQMC--CSKCPPGQHVKHSCT--KTSDTVCAPCEESTYTQLWNWVPeCLSCSSPCSSDQVETQACTRQQ 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1519312798  80 NAVCGdCLPRFYrktRIGGLQD--QECIPCTK----------QTPTSEVQCA 119
Cdd:cd10577    77 NRICS-CKPGWY---CVLKLQEgcRQCRPLKKcgpgfgvarpGTASSDVECK 124

Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as CD134 or OXO40; TNFRSF4 (also known as OX40, ACT35, CD134, IMD16, TXGP1L) activates NF-kappaB through its interaction with adaptor proteins TRAF2 and TRAF5. It also promotes the expression of apoptosis inhibitors BCL2 and BCL2lL1/BCL2-XL, and thus suppresses apoptosis. It is primarily expressed on activated CD4+ and CD8+ T cells, where it is transiently expressed and upregulated on the most recently antigen-activated T cells within inflammatory lesions. This makes it an attractive target to modulate immune responses, i.e. TNFRSF4 (OX40) blocking agents to inhibit adverse inflammation or agonists to enhance immune responses. An artificially created biologic fusion protein, OX40-immunoglobulin (OX40-Ig), prevents OX40 from reaching the T-cell receptors, thus reducing the T-cell response. Some single nucleotide polymorphisms (SNPs) of its natural ligand OX40 ligand (OX40L, CD252), which is also found on activated T cells, have been associated with systemic lupus erythematosus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1519312798   1 MDCQENEYwDQWGRCvtCQRCGPGQELSKDCGYGEggDAYCTACPPRRYKSSWGHHRCQSCITCAVIN-RVQKVNCTATS 79
Cdd:cd13406     1 LHCVGDTY-PSGEKC--CHECPPGEGMESRCTGTQ--DTVCSPCEPGFYNEAVNYEPCKPCTQCNQRSgSEEKQKCTKTS 75

                  ....*.
gi 1519312798  80 NAVCGD 85
Cdd:cd13406    76 DTVCRC 81