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 238637342   3 CQENEYRDQWGRCVTCQQCGPGQELSKDCGYGEGGDAHCIVCPPRKYKSTWGHHRCQTCITCAVINRVQKANCTNTSNAI 82
Cdd:cd15838    1 CQEKEYLDEHGKCVPCRECGPGQELSKDCGYGEGGDAYCTACPPRRFKDSWGHHGCKTCLSCALINRVQKSNCTATSNAV 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 238637342  83 CGDCLPRFYRKTRIGGLQDQECIPCTKQTPSSEVQC 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 238637342   3 CQENEYRDQWGRCVTCQQCGPGQELSKDCGYGEGGDAHCIVCPPRKYKSTWGHHRCQTCITCAVINRVQKANCTNTSNAI 82
Cdd:cd15838    1 CQEKEYLDEHGKCVPCRECGPGQELSKDCGYGEGGDAYCTACPPRRFKDSWGHHGCKTCLSCALINRVQKSNCTATSNAV 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 238637342  83 CGDCLPRFYRKTRIGGLQDQECIPCTKQTPSSEVQC 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 238637342   3 CQENEYRDQWGRCVTCQQCGPGQELSKDCGYGEGGDAHCIVCPPRKYKSTWGHHRCQTCITCAVINRVQKANCTNTSNAI 82
Cdd:cd15838    1 CQEKEYLDEHGKCVPCRECGPGQELSKDCGYGEGGDAYCTACPPRRFKDSWGHHGCKTCLSCALINRVQKSNCTATSNAV 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 238637342  83 CGDCLPRFYRKTRIGGLQDQECIPCTKQTPSSEVQC 118
Cdd:cd15838   81 CGDCLPGFYRKTRIGGLQDQECIPCTKQTPSSEVQC 116

tumor necrosis factor receptor superfamily member 19-like (TNFRSF19L), also known as receptor expressed in lymphoid tissues (RELT); TNFRSF19L (also known as receptor expressed in lymphoid tissues (RELT)) is especially abundant in hematologic tissues and can stimulate the proliferation of T-cells. It serves as a substrate for the closely related kinases, odd-skipped related transcription factor 1 (OSR1) and STE20/SPS1-related proline/alanine-rich kinase (SPAK); RELT binds SPAK and uses it to mediate p38 and JNK activation, rather than rely on the canonical TRAF pathways for its function. RELT is capable of stimulating T-cell proliferation in the presence of CD3 signaling, which suggests its regulatory role in immune response. It interacts with phospholipid scramblase 1 (PLSCR1), an interferon-inducible protein that mediates antiviral activity against DNA and RNA viruses; PLSCR1 is a regulator of hepatitis B virus X (HBV X) protein. RELT and PLSCR1 co-localize in intracellular regions of human embryonic kidney-293 cells, with RELT over-expression appearing to alter the localization of PLSCR1.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 238637342  15 CVTCQQCGPGQELSKDCGYGEGGDAHCIVCPPRKYKSTWGHHRCQTCITCAVINRVQKANCTNTSNAICGDCLPRFYrkt 94
Cdd:cd13419    1 CVPCLQCPPGQEPDRACGQGQGLGVLCRSCPPGTFSDSLGSEPCRPHTSCEVLKRKVATSGTATSDAVCGDCLPGFH--- 77

                         90
                 ....*....|....
gi 238637342  95 RIGGLQDQECIPCT 108
Cdd:cd13419   78 SPAAPPPSTCLPCS 91

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 238637342   2 DCQENEYRDQW-GRCVTCQQCGPGQELSKDCGYGEGGDAH-CIVCPPRKYkSTWGHHRCQTCITCAVINRVQ-KANCTNT 78
Cdd:cd13421   18 NCGENEYYNQTtGLCQQCPPCRPGEEPYMSCGYGTKDEDYgCVPCPAEKF-SKGGYQICRRHKDCEGFFRATvLTPGDME 96

                         90
                 ....*....|...
gi 238637342  79 SNAICGDCLPRFY 91
Cdd:cd13421   97 NDAECGPCLPGYY 109

Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) in teleost; also known as TNFR2; This subfamily of TNFRSF1B (also known as TNFR2, type 2 TNFR, TNFBR, TNFR80, TNF-R75, TNF-R-II, p75, CD120b) is found in teleosts. It 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). 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-kB in endothelial cells. In goldfish (Carassius aurutus L.), TNFRSF1B expression is substantially higher than that of TNFRSF1 in tissues and various immune cell types. Both receptors are most robustly expressed in monocytes; mRNA levels of TNFRSF1B are lowest in peripheral blood leukocytes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 238637342   8 YRDQWGRCvtCQQCGPGQELSKDCGygEGGDAHCIVCPPRKYKSTWGHH-RCQTCITCAVINRVQKA-NCTNTSNAICGd 85
Cdd:cd15835   13 YNDGSNLC--CSKCRPGTRLKTKCS--ETSDTVCEPCPSGQYSENWNYYpNCFSCPKCKERKGLQYAqNCSSTTNAVCV- 87

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 238637342  86 CLPRFYrktRIGGLQDQECIPCTKQ-------------TPSSEVQC 118
Cdd:cd15835   88 CKPGMY---CIMGFDHPSCSECKKYrtckpgygvsvpgTPTSDVKC 130

Tumor necrosis factor receptor superfamily member 9 (TNFRSF9), also known as CD137; TNFRSF9 (also known as CD137, ILA, 4-1BB) 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 238637342  41 CIVCPPRKYKSTWGHHRCQTCITCAVINRVQKAnCTNTSNAICGdCLPRF 90
Cdd:cd13410   23 CIPCPPNSFSSTGGQQTCDICRKCEGVFRTKKP-CSSTSNAECE-CVPGF 70

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 238637342   3 CQENEYRDQWGRCvtCQQCGPGQELSKDCGyGEGGDAHCIVCPPRKYKSTWGHHR--CQTCITCAviNRVQKANCTNTSN 80
Cdd:cd13408   24 CPERHYWAQGKLC--CQMCEPGTFLVKDCD-QHGKAAQCDPCIPGVSFSPDHHARphCESCRHCN--SGLLIRNCTITAN 98

                 ....
gi 238637342  81 AICG 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 238637342   3 CQENEYRDQWGRcVTCQQCGPGQELSKDCGYGEggDAHCIVCPPRKYKSTWGH-HRCQTCITC-AVINRVQKANCTNTSN 80
Cdd:cd10578   35 DQEKEYYEPRHQ-VCCSRCPPGTHVSAECSRSQ--DTVCATCPENSYNEHWNHlSICQLCRPCdPVLGFEEVAPCTSDRK 111

                         90       100
                 ....*....|....*....|....*..
gi 238637342  81 AICGdCLPRFYrktriGGLQDQECIPC 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 238637342   2 DCQENEYRDQW-GRCVTCQQCGPGQELSKDCgyGEGGDAHCIVCPPRKYKSTWGHH-RCQTCITCAViNRVQKANCTNTS 79
Cdd:cd13416   79 ECAYGYYLDEDsGTCEPCTVCPPGQGVVQSC--GPNQDTVCEACPEGTYSDEDSSTdPCLPCTVCED-GEVELRECTPVS 155

                 ....
gi 238637342  80 NAIC 83
Cdd:cd13416  156 DTVC 159