Tumor necrosis factor receptor superfamily member 18 (TNFRSF18), also known as glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR); TNFRSF18 (also known as activation-inducible TNF receptor (AITR), glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR), CD357, GITR-D) has increased expression upon T-cell activation, and is thought to play a key role in dominant immunological self-tolerance maintained by CD25(+)CD4(+) regulatory T cells. In inflammatory cells, GITR expression indicates a possible molecular link between steroid use and complicated acute sigmoid diverticulitis; increased MMP-9 expression by GITR signaling might explain morphological changes in the colonic wall in diverticulitis. Its ligand, GITRL, activates GITR which could then influence the activity of effector and regulatory T cells, participating in the development of several autoimmune and inflammatory diseases, including autoimmune thyroid disease and rheumatoid arthritis. In systemic lupus erythematosus (SLE) patients, serum GITRL levels are increased compared with healthy controls. GITR and its ligand, GITRL, are possibly involved in the pathogenesis of primary Sjogren's syndrome (pSS). GITR is inactivated during tumor progression in Multiple Myeloma (MM); restoration of GITR expression in GITR deficient MM cells leads to inhibition of MM proliferation and induction of apoptosis, thus playing a pivotal role in MM pathogenesis and disease progression. Regulatory T-cells (Tregs) in liver tumor up-regulate the expression of GITR compared with Tregs in tumor-free liver tissue and blood. Regulatory single nucleotide polymorphisms (SNPs) in the promoter regions of the TNFRSF18 gene have been identified in a group of male Gabonese individuals exposed to a wide array of parasitic diseases such as malaria, filariasis and schistosomiasis, and may serve as a basis to study parasite susceptibility in association studies.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23238194  56 RCCRDYPGEECCSEW-----DCMCVQPEFHCGDPCCTTCRHHPCPPGQGVQSQGKFSFGFQCIDCASGTFSGGHEGHCKP 130
Cdd:cd13417   1 RCCRKCPSEEADAPCcdaegDCKCVQPGFHCGDPQCKTCKKHPCPPGQEVQRQGKFDFGFECVPCANGTFSDGHDGHCKP 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 23238194 131 WTDCCWrCRRRPKTPEAASsprksgasdrqrrrgGWETCGCEPGRPPG 178
Cdd:cd13417  81 WTDCSQ-FGFLTIFPGNKT---------------HNAVCGPGPPPPEE 112

Tumor necrosis factor receptor superfamily member 18 (TNFRSF18), also known as glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR); TNFRSF18 (also known as activation-inducible TNF receptor (AITR), glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR), CD357, GITR-D) has increased expression upon T-cell activation, and is thought to play a key role in dominant immunological self-tolerance maintained by CD25(+)CD4(+) regulatory T cells. In inflammatory cells, GITR expression indicates a possible molecular link between steroid use and complicated acute sigmoid diverticulitis; increased MMP-9 expression by GITR signaling might explain morphological changes in the colonic wall in diverticulitis. Its ligand, GITRL, activates GITR which could then influence the activity of effector and regulatory T cells, participating in the development of several autoimmune and inflammatory diseases, including autoimmune thyroid disease and rheumatoid arthritis. In systemic lupus erythematosus (SLE) patients, serum GITRL levels are increased compared with healthy controls. GITR and its ligand, GITRL, are possibly involved in the pathogenesis of primary Sjogren's syndrome (pSS). GITR is inactivated during tumor progression in Multiple Myeloma (MM); restoration of GITR expression in GITR deficient MM cells leads to inhibition of MM proliferation and induction of apoptosis, thus playing a pivotal role in MM pathogenesis and disease progression. Regulatory T-cells (Tregs) in liver tumor up-regulate the expression of GITR compared with Tregs in tumor-free liver tissue and blood. Regulatory single nucleotide polymorphisms (SNPs) in the promoter regions of the TNFRSF18 gene have been identified in a group of male Gabonese individuals exposed to a wide array of parasitic diseases such as malaria, filariasis and schistosomiasis, and may serve as a basis to study parasite susceptibility in association studies.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23238194  56 RCCRDYPGEECCSEW-----DCMCVQPEFHCGDPCCTTCRHHPCPPGQGVQSQGKFSFGFQCIDCASGTFSGGHEGHCKP 130
Cdd:cd13417   1 RCCRKCPSEEADAPCcdaegDCKCVQPGFHCGDPQCKTCKKHPCPPGQEVQRQGKFDFGFECVPCANGTFSDGHDGHCKP 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 23238194 131 WTDCCWrCRRRPKTPEAASsprksgasdrqrrrgGWETCGCEPGRPPG 178
Cdd:cd13417  81 WTDCSQ-FGFLTIFPGNKT---------------HNAVCGPGPPPPEE 112

Tumor necrosis factor receptor superfamily member 18 (TNFRSF18), also known as glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR); TNFRSF18 (also known as activation-inducible TNF receptor (AITR), glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR), CD357, GITR-D) has increased expression upon T-cell activation, and is thought to play a key role in dominant immunological self-tolerance maintained by CD25(+)CD4(+) regulatory T cells. In inflammatory cells, GITR expression indicates a possible molecular link between steroid use and complicated acute sigmoid diverticulitis; increased MMP-9 expression by GITR signaling might explain morphological changes in the colonic wall in diverticulitis. Its ligand, GITRL, activates GITR which could then influence the activity of effector and regulatory T cells, participating in the development of several autoimmune and inflammatory diseases, including autoimmune thyroid disease and rheumatoid arthritis. In systemic lupus erythematosus (SLE) patients, serum GITRL levels are increased compared with healthy controls. GITR and its ligand, GITRL, are possibly involved in the pathogenesis of primary Sjogren's syndrome (pSS). GITR is inactivated during tumor progression in Multiple Myeloma (MM); restoration of GITR expression in GITR deficient MM cells leads to inhibition of MM proliferation and induction of apoptosis, thus playing a pivotal role in MM pathogenesis and disease progression. Regulatory T-cells (Tregs) in liver tumor up-regulate the expression of GITR compared with Tregs in tumor-free liver tissue and blood. Regulatory single nucleotide polymorphisms (SNPs) in the promoter regions of the TNFRSF18 gene have been identified in a group of male Gabonese individuals exposed to a wide array of parasitic diseases such as malaria, filariasis and schistosomiasis, and may serve as a basis to study parasite susceptibility in association studies.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23238194  56 RCCRDYPGEECCSEW-----DCMCVQPEFHCGDPCCTTCRHHPCPPGQGVQSQGKFSFGFQCIDCASGTFSGGHEGHCKP 130
Cdd:cd13417   1 RCCRKCPSEEADAPCcdaegDCKCVQPGFHCGDPQCKTCKKHPCPPGQEVQRQGKFDFGFECVPCANGTFSDGHDGHCKP 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 23238194 131 WTDCCWrCRRRPKTPEAASsprksgasdrqrrrgGWETCGCEPGRPPG 178
Cdd:cd13417  81 WTDCSQ-FGFLTIFPGNKT---------------HNAVCGPGPPPPEE 112

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 23238194  72 CMCVQPEfHCGDPCCTTCRHH-PCPPGQGVQSQGKFSFGFQCIDCASGTFSGGHEGH--CKPWTDC 134
Cdd:cd13407  78 CTCQEGQ-HCTSEACETCALHtSCKPGFGVKQIATGVSDTICEPCPVGFFSNVSSAFekCHPWTSC 142

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 23238194  72 CMCVqPEFHCGDPCCTTCRHHpCPPGQGVQSQGkfsfgfqCIDCASGTFSGGHEGHCKPWTDCCW 136
Cdd:cd13410  64 CECV-PGFHCLGPGCSMCEPD-CKQGQELTKEG-------CKDCSFGTFNDQEGGVCRPWTNCSL 119

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23238194   137 RCRRRPKTPEAASSPRKSGASDRQRRRGGWETCGC--------EPGRPPGPP----TAASPSPGAPQAAGALRSALGRAL 204
Cdd:PHA03247 2660 RVSRPRRARRLGRAAQASSPPQRPRRRAARPTVGSltsladppPPPPTPEPAphalVSATPLPPGPAAARQASPALPAAP 2739

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 23238194   205 LPwqqkwvqeggsdqRPGPCSSAAAAGPCRRERETQSWPPSSLAGPDG 252
Cdd:PHA03247 2740 AP-------------PAVPAGPATPGGPARPARPPTTAGPPAPAPPAA 2774