Tumor necrosis factor receptor superfamily member 10 (TNFRSF10), includes TNFRSF10A (DR4), TNFRSF10B (DR5), TNFRSF10C (DcR1) and TNFRSF10D (DcR2); TNFRSF10 family contains TNFRSF10A (also known as DR4, Apo2, TRAIL-R1, CD261), TNFRSF10B (also known as DR5, KILLER, TRICK2A, TRAIL-R2, TRICKB, CD262), TNFRSF10C (also known as DcR1, TRAIL-R3, LIT, TRID, CD263), and TNFRSF10D (also known as DcR2, TRUNDD, TRAIL-R4, CD264). Tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL) binds to all 4 receptors. DR4 (TRAIL-R1) and DR5 (TRAIL-R2) are membrane-bound and contain a death domain in their intracellular portion, which is able to transmit an apoptotic signal, thus often called death receptors. In contrast, DcR1 (TRAIL-R3), which lacks the complete intracellular portion and DcR2 (TRAIL-R4), which has a truncated cytoplasmic death domain, do not transmit an apoptotic signal, thus known as decoy receptors. Apoptosis mediated by DR4 and DR5 requires Fas (TNFRSF6)-associated via death domain (FADD), a death domain containing adaptor protein. Two transcript variants encoding different isoforms and one non-coding transcript have been found for TNFRSF10B/DR5. DcR1 appears to function as an antagonistic receptor that protects cells from TRAIL-induced apoptosis; it has been found to be a p53-regulated DNA damage-inducible gene. The expression of this gene is detected in many normal tissues but not in most cancer cell lines, which may explain the specific sensitivity of cancer cells to the apoptosis-inducing activity of TRAIL. DcR2 has been shown to play an inhibitory role in TRAIL-induced cell apoptosis. The membrane expression of all of these receptors (DR4, DR5, DcR1, and DcR2) is greater in normal endometrium (NE) than in endometrioid adenocarcinoma (EAC). In EAC patients, membrane expression of these receptors are not independent predictors of survival. DcR1 and DcR2 expression is critical in cell growth and apoptosis in cutaneous or uveal melanoma; DcR1 and DcR2 are frequently methylated in both, leading to loss of gene expression and melanomagenesis. On the other hand, DR4 and DR5 methylation is rare in cutaneous melanoma and frequent in uveal melanoma; their expression is wholly independent of the promoter methylation status. DcR1 and DcR2 genes are also reported to be hyper-methylated in prostate cancer. The TRAIL ligand, a potent and specific inducer of apoptosis in cancer cells, has been explored as a therapeutic drug; experimental data has shown that DR4 specific TRAIL variants are more efficacious than wild-type TRAIL in pancreatic cancer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779541885  50 GEECPAGSHRSEHTGACNPCTEGVDYTNASNNEPSCFPCTVCKSDQKHKSSCTMTRDTVCQCKEGTFRNENSPEMCRKCS 129
Cdd:cd10580     2 CGLCPAGTYVSEDSGDCIPCKEGVDYTEHPNGLPSCLPCTVCKSDEEELSPCTTTRNTECQCKPGTFCDPDSPEVCQKCS 81

                          90       100
                  ....*....|....*....|..
gi 1779541885 130 -RCPSGEVQVSNCTSWDDIQCV 150
Cdd:cd10580    82 tRCPEGMVEVSPCTPWSDLKCV 103

Tumor necrosis factor receptor superfamily member 10 (TNFRSF10), includes TNFRSF10A (DR4), TNFRSF10B (DR5), TNFRSF10C (DcR1) and TNFRSF10D (DcR2); TNFRSF10 family contains TNFRSF10A (also known as DR4, Apo2, TRAIL-R1, CD261), TNFRSF10B (also known as DR5, KILLER, TRICK2A, TRAIL-R2, TRICKB, CD262), TNFRSF10C (also known as DcR1, TRAIL-R3, LIT, TRID, CD263), and TNFRSF10D (also known as DcR2, TRUNDD, TRAIL-R4, CD264). Tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL) binds to all 4 receptors. DR4 (TRAIL-R1) and DR5 (TRAIL-R2) are membrane-bound and contain a death domain in their intracellular portion, which is able to transmit an apoptotic signal, thus often called death receptors. In contrast, DcR1 (TRAIL-R3), which lacks the complete intracellular portion and DcR2 (TRAIL-R4), which has a truncated cytoplasmic death domain, do not transmit an apoptotic signal, thus known as decoy receptors. Apoptosis mediated by DR4 and DR5 requires Fas (TNFRSF6)-associated via death domain (FADD), a death domain containing adaptor protein. Two transcript variants encoding different isoforms and one non-coding transcript have been found for TNFRSF10B/DR5. DcR1 appears to function as an antagonistic receptor that protects cells from TRAIL-induced apoptosis; it has been found to be a p53-regulated DNA damage-inducible gene. The expression of this gene is detected in many normal tissues but not in most cancer cell lines, which may explain the specific sensitivity of cancer cells to the apoptosis-inducing activity of TRAIL. DcR2 has been shown to play an inhibitory role in TRAIL-induced cell apoptosis. The membrane expression of all of these receptors (DR4, DR5, DcR1, and DcR2) is greater in normal endometrium (NE) than in endometrioid adenocarcinoma (EAC). In EAC patients, membrane expression of these receptors are not independent predictors of survival. DcR1 and DcR2 expression is critical in cell growth and apoptosis in cutaneous or uveal melanoma; DcR1 and DcR2 are frequently methylated in both, leading to loss of gene expression and melanomagenesis. On the other hand, DR4 and DR5 methylation is rare in cutaneous melanoma and frequent in uveal melanoma; their expression is wholly independent of the promoter methylation status. DcR1 and DcR2 genes are also reported to be hyper-methylated in prostate cancer. The TRAIL ligand, a potent and specific inducer of apoptosis in cancer cells, has been explored as a therapeutic drug; experimental data has shown that DR4 specific TRAIL variants are more efficacious than wild-type TRAIL in pancreatic cancer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779541885  50 GEECPAGSHRSEHTGACNPCTEGVDYTNASNNEPSCFPCTVCKSDQKHKSSCTMTRDTVCQCKEGTFRNENSPEMCRKCS 129
Cdd:cd10580     2 CGLCPAGTYVSEDSGDCIPCKEGVDYTEHPNGLPSCLPCTVCKSDEEELSPCTTTRNTECQCKPGTFCDPDSPEVCQKCS 81

                          90       100
                  ....*....|....*....|..
gi 1779541885 130 -RCPSGEVQVSNCTSWDDIQCV 150
Cdd:cd10580    82 tRCPEGMVEVSPCTPWSDLKCV 103

TNFR/NGFR cysteine-rich region;

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1779541885 111 CKEGTFRNENSPEMCRKCSRCPSGEVQVSNCTSWDDIQC 149
Cdd:pfam00020   1 CPPGTYTDNWNGLKCLPCTVCPPGQVVVRPCTPTSDTVC 39

UV excision repair protein Rad23; All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. In humans, Rad23 complexes with the XPC protein. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1779541885 157 ATVETPAAEETmntSPGTPAPAAEETMNTSPGTPAPAAEETMTTSPGTPAPAAEETMTTSPGTPAPAAEETMIT 230
Cdd:TIGR00601  82 GKVAPPAATPT---SAPTPTPSPPASPASGMSAAPASAVEEKSPSEESATATAPESPSTSVPSSGSDAASTLVV 152

Tumor necrosis factor receptor superfamily member 10 (TNFRSF10), includes TNFRSF10A (DR4), TNFRSF10B (DR5), TNFRSF10C (DcR1) and TNFRSF10D (DcR2); TNFRSF10 family contains TNFRSF10A (also known as DR4, Apo2, TRAIL-R1, CD261), TNFRSF10B (also known as DR5, KILLER, TRICK2A, TRAIL-R2, TRICKB, CD262), TNFRSF10C (also known as DcR1, TRAIL-R3, LIT, TRID, CD263), and TNFRSF10D (also known as DcR2, TRUNDD, TRAIL-R4, CD264). Tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL) binds to all 4 receptors. DR4 (TRAIL-R1) and DR5 (TRAIL-R2) are membrane-bound and contain a death domain in their intracellular portion, which is able to transmit an apoptotic signal, thus often called death receptors. In contrast, DcR1 (TRAIL-R3), which lacks the complete intracellular portion and DcR2 (TRAIL-R4), which has a truncated cytoplasmic death domain, do not transmit an apoptotic signal, thus known as decoy receptors. Apoptosis mediated by DR4 and DR5 requires Fas (TNFRSF6)-associated via death domain (FADD), a death domain containing adaptor protein. Two transcript variants encoding different isoforms and one non-coding transcript have been found for TNFRSF10B/DR5. DcR1 appears to function as an antagonistic receptor that protects cells from TRAIL-induced apoptosis; it has been found to be a p53-regulated DNA damage-inducible gene. The expression of this gene is detected in many normal tissues but not in most cancer cell lines, which may explain the specific sensitivity of cancer cells to the apoptosis-inducing activity of TRAIL. DcR2 has been shown to play an inhibitory role in TRAIL-induced cell apoptosis. The membrane expression of all of these receptors (DR4, DR5, DcR1, and DcR2) is greater in normal endometrium (NE) than in endometrioid adenocarcinoma (EAC). In EAC patients, membrane expression of these receptors are not independent predictors of survival. DcR1 and DcR2 expression is critical in cell growth and apoptosis in cutaneous or uveal melanoma; DcR1 and DcR2 are frequently methylated in both, leading to loss of gene expression and melanomagenesis. On the other hand, DR4 and DR5 methylation is rare in cutaneous melanoma and frequent in uveal melanoma; their expression is wholly independent of the promoter methylation status. DcR1 and DcR2 genes are also reported to be hyper-methylated in prostate cancer. The TRAIL ligand, a potent and specific inducer of apoptosis in cancer cells, has been explored as a therapeutic drug; experimental data has shown that DR4 specific TRAIL variants are more efficacious than wild-type TRAIL in pancreatic cancer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779541885  50 GEECPAGSHRSEHTGACNPCTEGVDYTNASNNEPSCFPCTVCKSDQKHKSSCTMTRDTVCQCKEGTFRNENSPEMCRKCS 129
Cdd:cd10580     2 CGLCPAGTYVSEDSGDCIPCKEGVDYTEHPNGLPSCLPCTVCKSDEEELSPCTTTRNTECQCKPGTFCDPDSPEVCQKCS 81

                          90       100
                  ....*....|....*....|..
gi 1779541885 130 -RCPSGEVQVSNCTSWDDIQCV 150
Cdd:cd10580    82 tRCPEGMVEVSPCTPWSDLKCV 103

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 1779541885  51 EECPAGSHRSEhtgaCNPCTEGvDYTNASNNEPSCFPCTVCKSDQKHKSS-CTMTRDTVCQCKEGTFRNENSPEM--CRK 127
Cdd:cd15834    25 EECTAPGERSQ----CTPCPEG-TYLEQINYSPNCRRCTLCKVKNEEEVSpCKKSSNTVCRCKKGYYKSRIDSETreCLK 99

                          90       100
                  ....*....|....*....|...
gi 1779541885 128 CSRCPSGEVQVSNCTSWDDIQCV 150
Cdd:cd15834   100 CKTCGPGEIEIQPCTPESNTVCE 122

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 1779541885  53 CPAGSHRSEHTGA------CNPCTEGVdYTNASNNEPSCFPCTVCKS--DQKHKSSCTMTRDTVCQCKEGTFRNENSPEM 124
Cdd:cd10576    18 CHKGTYLYNDCPGpgqdtvCRECENGT-FTASENYLRKCLSCSRCRKemGQVEISPCTVDQDTVCGCRKNQYQHYWSSLF 96

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1779541885 125 -CRKCSRCPSGEVQVsNCTSWDDIQCVEEFG 154
Cdd:cd10576    97 qCKNCSLCLNGTIRQ-PCQEKQDTICTCHTG 126

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 1779541885  53 CPAGSHRSEHTGA-----CNPCTEGVdYTNASNNEPSCFPCTVCKSDQ--KHKSSCTMTRDTVCQCKEGTF---RNENSP 122
Cdd:cd13405    16 CPPGSRVSRHCTEdtstsCVPCPDGT-YMDEPNGLEKCFPCTNCDPGFglRVKQGCTYTSDTVCEPLEGFYcidSTKDGC 94

                          90
                  ....*....|...
gi 1779541885 123 EMCRKCSRCPSGE 135
Cdd:cd13405    95 SAAQRHSSCKPGQ 107

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779541885  51 EECPAGSHRSEHTGA-----CNPCTEgVDYTNASNNEPSCFPCTV-CKSDQKHKSSCTMTRDTVCQCKEGTFRNEnspEM 124
Cdd:cd10575    17 DQCPPGTFVAKHCTRdrptvCGPCPD-LHYTQFWNYLEKCRYCNVfCTERQVEKRQCNATHNRVCECKPGYYMEH---GF 92

                          90       100
                  ....*....|....*....|....*
gi 1779541885 125 CRKCSRCPSGEVQVSNCTSWDDIQC 149
Cdd:cd10575    93 CLRHSSCPPGEGVIKLGTPYSDTQC 117

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
                   ....*....|....*....|....*....|....*....
gi 1779541885  111 CKEGTFRNENSPEMCRKCSRCPSGEVQVSNCTSWDDIQC 149
Cdd:smart00208   1 CKEGTYCSDGNHSSCLRCRRCPPGLVVKQPCTATSDTVC 39

TNFR/NGFR cysteine-rich region;

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1779541885 111 CKEGTFRNENSPEMCRKCSRCPSGEVQVSNCTSWDDIQC 149
Cdd:pfam00020   1 CPPGTYTDNWNGLKCLPCTVCPPGQVVVRPCTPTSDTVC 39

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 1779541885  51 EECPAGSHRSEHTGA-----CNPCTEGVDYTNASnnEPSCFPCTVCKSDQKHKSSCTMTRDTVCQCKEGtFRNENSpemc 125
Cdd:cd13424    15 ESCHPGNRLVERCGPdpaelCKPCEPGTYTVKPL--DYSCYICTQCIGAQVLLKNCTPSSDTVCGCKEG-LRCGDA---- 87

                  ....*.
gi 1779541885 126 rKCSRC 131
Cdd:cd13424    88 -ECSFC 92

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779541885  52 ECPAGSHRSEHTGA-----CNPCTEGvDYTNASNNEPSCFPC-TVCKSDQKHKSSCTMTRDTVCQCKEGTFRNEnspEMC 125
Cdd:cd13412    24 KCPPGTHMAAHCTAttqtkCLPCPAA-HYTELWNYLPRCLYCnNFCSENQEVEIECSATNNRVCRCKEGYYMDS---DFC 99

                          90       100
                  ....*....|....*....|....*
gi 1779541885 126 RKCSRCPSGEVQVSNCTSWDDIQCV 150
Cdd:cd13412   100 IRHTECGPGYGVKTKGTTKQDTVCE 124

Tumor necrosis factor receptor superfamily member 21 (TNFRSF21), also known as death receptor (DR6); TNFRSF21 (also known as death receptor 6 (DR6), CD358, BM-018) is highly expressed in differentiating neurons as well as in the adult brain, and is upregulated in injured neurons. DR6 negatively regulates neurondendrocyte, axondendrocyte, and oligodendrocyte survival, hinders axondendrocyte and oligodendrocyte regeneration and its inhibition has a neuro-protective effect in nerve injury. It activates nuclear factor kappa-B (NFkB) and mitogen-activated protein kinase 8 (MAPK8, also called c-Jun N-terminal kinase 1), 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. TNFRSF21 plays a role in T-helper cell activation, and may be involved in inflammation and immune regulation. Its possible ligand is alpha-amyloid precursor protein (APP), hence probably involved in the development of Alzheimer's disease; when released, APP binds in an autocrine/paracrine manner to activate a caspase-dependent self-destruction program that removes unnecessary or connectionless axons. Increasing beta-catenin levels in brain endothelium upregulates TNFRSF21 and TNFRSF19, indicating that these death receptors are downstream target genes of Wnt/beta-catenin signaling, which has been shown to be required for blood-brain barrier development. DR6 is up-regulated in numerous solid tumors as well as in tumor vascular cells, including ovarian cancer and may be a clinically useful diagnostic and predictive serum biomarker for some adult sarcoma subtypes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779541885  51 EECPAGSHRSEHTGA-----CNPCTEGVdYTNASNNEPSCFPCTV-CKSDQKHKSSCTMTRDTVCQCKEGTFRNENSpem 124
Cdd:cd10583    16 DKCPAGTYVSKHCTEtslreCSPCPNGT-FTRHENGIEQCHRCRKpCPAPMIEKTPCTALTDRECTCPPGTFLSNDT--- 91

                          90       100
                  ....*....|....*....|....*
gi 1779541885 125 CRKCSRCPSGEVQVSNCTSWDDIQC 149
Cdd:cd10583    92 CVPHSVCPVGWGVRKKGTETEDVRC 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 1779541885   69 CTEGvDYTNaSNNEPSCFPCTVCKSDQKHKSSCTMTRDTVC 109
Cdd:smart00208   1 CKEG-TYCS-DGNHSSCLRCRRCPPGLVVKQPCTATSDTVC 39

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1779541885  66 CNPCTEGVdYTNASNNEPsCFPCTVCK--SDQKHKSSCTMTRDTVCQCKEGTfRNENSPEMCRKCSRCPSG 134
Cdd:cd13406    36 CSPCEPGF-YNEAVNYEP-CKPCTQCNqrSGSEEKQKCTKTSDTVCRCRPGT-QPLDSYKPGVDCVPCPPG 103

Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B), also known as Osteoprotegerin (OPG); TNFRSF11B (also known as Osteoprotegerin, OPG, TR1, OCIF) 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779541885  51 EECPAGSHRSEHTGA-----CNPCTEGvDYTNASNNEPSCFPC-TVCKSDQKHKSSCTMTRDTVCQCKEGTFRNensPEM 124
Cdd:cd10581    37 DQCPPGTYVKQHCSAsrktvCAPCPDH-HYADDWNSNDECQYCnTVCKELQYVKQECNSTHNRVCECVEGRYLE---LEF 112

                          90
                  ....*....|
gi 1779541885 125 CRKCSRCPSG 134
Cdd:cd10581   113 CLKHTECPPG 122

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 1779541885  65 ACNPCTEGvDYTNASNNEPSCFPCTVCKSDQ--KHKSSCTMTRDTVCQCKEGTFRNENSPEMCRKCSRCPSGEVQVSNCT 142
Cdd:cd13407    33 ECLPCEEG-EFQDTWNRERHCHQHRYCDPNLglRVQTEGTAETDTTCTCQEGQHCTSEACETCALHTSCKPGFGVKQIAT 111

                  ....*..
gi 1779541885 143 SWDDIQC 149
Cdd:cd13407   112 GVSDTIC 118

ribonuclease E; Reviewed

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779541885  121 SPEMCrkcsrcpSGEVQVS-NCTSWDDIQCVEEFGANATVETPAAEEtmntspgTPAPAAEETMNTSPGTPAPAA--EET 197
Cdd:PRK10811   833 SPEMA-------SGKVWIRyPVVRPQDVQVEEQREAEEVQVQPVVAE-------VPVAAAVEPVVSAPVVEAVAEvvEEP 898

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1779541885  198 MTTSPGTPAPAAEETMTTSPGTPAPAAEETMITSP 232
Cdd:PRK10811   899 VVVAEPQPEEVVVVETTHPEVIAAPVTEQPQVITE 933

multifunctional oxoglutarate decarboxylase/oxoglutarate dehydrogenase thiamine pyrophosphate-binding subunit/dihydrolipoyllysine-residue succinyltransferase subunit;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1779541885  171 SPGTPAPAAEETMNTSPGTPAPAAEETMTTSPGTPAPAAEETMTTSPGTPAPAAEETMITSPGTPAS 237
Cdd:PRK12270    38 PGSTAAPTAAAAAAAAAASAPAAAPAAKAPAAPAPAPPAAAAPAAPPKPAAAAAAAAAPAAPPAAAA 104

multifunctional oxoglutarate decarboxylase/oxoglutarate dehydrogenase thiamine pyrophosphate-binding subunit/dihydrolipoyllysine-residue succinyltransferase subunit;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1779541885  154 GANATVETPAAEETMNTSPGTPAPAAEETMNTSPGTPAPAAEETMTTSPGTPAPAAEETMTTSPGTPAPAAEET 227
Cdd:PRK12270    39 GSTAAPTAAAAAAAAAASAPAAAPAAKAPAAPAPAPPAAAAPAAPPKPAAAAAAAAAPAAPPAAAAAAAPAAAA 112

multifunctional oxoglutarate decarboxylase/oxoglutarate dehydrogenase thiamine pyrophosphate-binding subunit/dihydrolipoyllysine-residue succinyltransferase subunit;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779541885  152 EFGANATVETPAAEETMNTSPGTPAPAAEETMNTSPGTPAPAAEETMTTSPGTPAPAAEETMTTSPGTPAPAAEETMITS 231
Cdd:PRK12270    31 EFFADYGPGSTAAPTAAAAAAAAAASAPAAAPAAKAPAAPAPAPPAAAAPAAPPKPAAAAAAAAAPAAPPAAAAAAAPAA 110

                   ....*..
gi 1779541885  232 PGTPASS 238
Cdd:PRK12270   111 AAVEDEV 117

envelope glycoprotein I; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779541885 155 ANATVETPAaeeTMNTSPGTPAPAAEETMNTSPGTPAPAAEETMTTSPGTPAPAAEETMTTSPGTPAPAAEETMITS--P 232
Cdd:PHA03291  198 GPADVFVPA---TPRPTPRTTASPETTPTPSTTTSPPSTTIPAPSTTIAAPQAGTTPEAEGTPAPPTPGGGEAPPANatP 274

                          90
                  ....*....|..
gi 1779541885 233 GTPASSHYLSCT 244
Cdd:PHA03291  275 APEASRYELTVT 286

Tumor necrosis factor receptor superfamily member 21 (TNFRSF21), also known as death receptor (DR6); TNFRSF21 (also known as death receptor 6 (DR6), CD358, BM-018) is highly expressed in differentiating neurons as well as in the adult brain, and is upregulated in injured neurons. DR6 negatively regulates neurondendrocyte, axondendrocyte, and oligodendrocyte survival, hinders axondendrocyte and oligodendrocyte regeneration and its inhibition has a neuro-protective effect in nerve injury. It activates nuclear factor kappa-B (NFkB) and mitogen-activated protein kinase 8 (MAPK8, also called c-Jun N-terminal kinase 1), 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. TNFRSF21 plays a role in T-helper cell activation, and may be involved in inflammation and immune regulation. Its possible ligand is alpha-amyloid precursor protein (APP), hence probably involved in the development of Alzheimer's disease; when released, APP binds in an autocrine/paracrine manner to activate a caspase-dependent self-destruction program that removes unnecessary or connectionless axons. Increasing beta-catenin levels in brain endothelium upregulates TNFRSF21 and TNFRSF19, indicating that these death receptors are downstream target genes of Wnt/beta-catenin signaling, which has been shown to be required for blood-brain barrier development. DR6 is up-regulated in numerous solid tumors as well as in tumor vascular cells, including ovarian cancer and may be a clinically useful diagnostic and predictive serum biomarker for some adult sarcoma subtypes.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1779541885  78 ASNNEPSCFPCTVCKSDQKHkssCTMTRDTVCQ-CKEGTF-RNENSPEMCRKCSR-CPSGEVQVSNCTSWDDIQCV 150
Cdd:cd10583     8 ATGTQLTCDKCPAGTYVSKH---CTETSLRECSpCPNGTFtRHENGIEQCHRCRKpCPAPMIEKTPCTALTDRECT 80

ribonuclease E; Reviewed

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779541885  157 ATVETPAAEETMNTSPGTPAPAAEETMNTSPGTPAPAAEETMTTS-PGTPAPAAEETMTTSPGTPAPAAEETMITSPGTP 235
Cdd:PRK10811   918 EVIAAPVTEQPQVITESDVAVAQEVAEHAEPVVEPQDETADIEEAaETAEVVVAEPEVVAQPAAPVVAEVAAEVETVTAV 997

                   ...
gi 1779541885  236 ASS 238
Cdd:PRK10811   998 EPE 1000