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Conserved domains on  [gi|7549775|ref|NP_034866|]
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tumor necrosis factor receptor superfamily member 3 precursor [Mus musculus]

Protein Classification

TNFRSF3 and TNFRSF domain-containing protein( domain architecture ID 10180442)

TNFRSF3 and TNFRSF domain-containing protein

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
TNFRSF3 cd10578
Tumor necrosis factor receptor superfamily member 3 (TNFRSF3), also known as lymphotoxin beta ...
11-170 3.33e-88

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.


:

Pssm-ID: 276904 [Multi-domain]  Cd Length: 158  Bit Score: 264.32  E-value: 3.33e-88
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   11 GLAWGPLLLGLSGLLVASQPQLVPPYRIENQTCWDQDKEYYEPMHDVCCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNE 90
Cdd:cd10578   1 GLAWGPLLLGLCGLLAASQPQLVPPYRTENQTCWDQEKEYYEPRHQVCCSRCPPGTHVSAECSRSQDTVCATCPENSYNE 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   91 HWNHLSTCQLCRPCDIVLGFEEVAPCTSDRKAECRCQPGMSCVYLDNECVHCeeERLVLCQPGTEAEVTDEIMDTDVNCV 170
Cdd:cd10578  81 HWNHLSICQLCRPCDPVLGFEEVAPCTSDRKTQCRCQPGMFCVHWDNECEHC--EPLSDCPPGTEAELTDEVGEADNNCV 158
TNFRSF super family cl22855
Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) ...
148-212 7.46e-06

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.


The actual alignment was detected with superfamily member cd13419:

Pssm-ID: 451430  Cd Length: 91  Bit Score: 43.94  E-value: 7.46e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 7549775  148 VLCQPGTE-AEVTDEIMDTDVNCVPCKPGHFQNTSSPRArCQPHTRCEIQGLVEAAPGTSYSDTIC 212
Cdd:cd13419   5 LQCPPGQEpDRACGQGQGLGVLCRSCPPGTFSDSLGSEP-CRPHTSCEVLKRKVATSGTATSDAVC 69
 
Name Accession Description Interval E-value
TNFRSF3 cd10578
Tumor necrosis factor receptor superfamily member 3 (TNFRSF3), also known as lymphotoxin beta ...
11-170 3.33e-88

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.


Pssm-ID: 276904 [Multi-domain]  Cd Length: 158  Bit Score: 264.32  E-value: 3.33e-88
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   11 GLAWGPLLLGLSGLLVASQPQLVPPYRIENQTCWDQDKEYYEPMHDVCCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNE 90
Cdd:cd10578   1 GLAWGPLLLGLCGLLAASQPQLVPPYRTENQTCWDQEKEYYEPRHQVCCSRCPPGTHVSAECSRSQDTVCATCPENSYNE 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   91 HWNHLSTCQLCRPCDIVLGFEEVAPCTSDRKAECRCQPGMSCVYLDNECVHCeeERLVLCQPGTEAEVTDEIMDTDVNCV 170
Cdd:cd10578  81 HWNHLSICQLCRPCDPVLGFEEVAPCTSDRKTQCRCQPGMFCVHWDNECEHC--EPLSDCPPGTEAELTDEVGEADNNCV 158
TNFRSF19L cd13419
tumor necrosis factor receptor superfamily member 19-like (TNFRSF19L), also known as receptor ...
148-212 7.46e-06

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.


Pssm-ID: 276924  Cd Length: 91  Bit Score: 43.94  E-value: 7.46e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 7549775  148 VLCQPGTE-AEVTDEIMDTDVNCVPCKPGHFQNTSSPRArCQPHTRCEIQGLVEAAPGTSYSDTIC 212
Cdd:cd13419   5 LQCPPGQEpDRACGQGQGLGVLCRSCPPGTFSDSLGSEP-CRPHTSCEVLKRKVATSGTATSDAVC 69
PHA02637 PHA02637
TNF-alpha-receptor-like protein; Provisional
33-101 1.84e-05

TNF-alpha-receptor-like protein; Provisional


Pssm-ID: 222913  Cd Length: 127  Bit Score: 43.98  E-value: 1.84e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 7549775    33 VPPYRIENQTCwdQDKEYYEpmHDVCCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLC 101
Cdd:PHA02637  22 IAPHAPSDGKC--KDNEYKR--HNLCCLSCPPGTYASRLCDIKTNTQCTPCGSGTFTSHNNHLPACLSC 86
TNFR_c6 pfam00020
TNFR/NGFR cysteine-rich region;
83-124 5.17e-05

TNFR/NGFR cysteine-rich region;


Pssm-ID: 425425 [Multi-domain]  Cd Length: 39  Bit Score: 40.00  E-value: 5.17e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 7549775     83 CPHNSYNEHWNHLStCQLCRPCDIvlGFEEVAPCTSDRKAEC 124
Cdd:pfam00020   1 CPPGTYTDSWNGLE-CLPCTVCPP--GQVVKRPCTATSDTVC 39
TNFR smart00208
Tumor necrosis factor receptor / nerve growth factor receptor repeats; Repeats in growth ...
83-124 3.72e-03

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


Pssm-ID: 214558  Cd Length: 39  Bit Score: 34.75  E-value: 3.72e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 7549775      83 CPHNSYNEHWNHlSTCQLCRPCDivLGFEEVAPCTSDRKAEC 124
Cdd:smart00208   1 CKEGTYCSDGNH-SSCLRCRRCP--PGLVVKQPCTATSDTVC 39
 
Name Accession Description Interval E-value
TNFRSF3 cd10578
Tumor necrosis factor receptor superfamily member 3 (TNFRSF3), also known as lymphotoxin beta ...
11-170 3.33e-88

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.


Pssm-ID: 276904 [Multi-domain]  Cd Length: 158  Bit Score: 264.32  E-value: 3.33e-88
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   11 GLAWGPLLLGLSGLLVASQPQLVPPYRIENQTCWDQDKEYYEPMHDVCCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNE 90
Cdd:cd10578   1 GLAWGPLLLGLCGLLAASQPQLVPPYRTENQTCWDQEKEYYEPRHQVCCSRCPPGTHVSAECSRSQDTVCATCPENSYNE 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   91 HWNHLSTCQLCRPCDIVLGFEEVAPCTSDRKAECRCQPGMSCVYLDNECVHCeeERLVLCQPGTEAEVTDEIMDTDVNCV 170
Cdd:cd10578  81 HWNHLSICQLCRPCDPVLGFEEVAPCTSDRKTQCRCQPGMFCVHWDNECEHC--EPLSDCPPGTEAELTDEVGEADNNCV 158
TNFRSF5 cd13407
Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40; TNFRSF5 ...
47-212 4.86e-30

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.


Pssm-ID: 276912 [Multi-domain]  Cd Length: 161  Bit Score: 113.65  E-value: 4.86e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   47 DKEYyePMHDVCCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLCRPCDIVLGFEEVAPCTSDRKAECRC 126
Cdd:cd13407   3 EKQY--LHNGRCCSLCPPGQKLVSDCTEATDTECLPCEEGEFQDTWNRERHCHQHRYCDPNLGLRVQTEGTAETDTTCTC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775  127 QPGMSCVylDNECVHCEEERlvLCQPGTE-AEVTDEIMDTdvNCVPCKPGHFQNTSSPRARCQPHTRCEIQGLVEAAPGT 205
Cdd:cd13407  81 QEGQHCT--SEACETCALHT--SCKPGFGvKQIATGVSDT--ICEPCPVGFFSNVSSAFEKCHPWTSCETKGLVELQAGT 154

                ....*..
gi 7549775  206 SYSDTIC 212
Cdd:cd13407 155 NKTDVVC 161
TNFRSF1B cd10577
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B), also known as TNFR2; TNFRSF1B ...
48-212 5.80e-27

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).


Pssm-ID: 276903 [Multi-domain]  Cd Length: 163  Bit Score: 105.25  E-value: 5.80e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   48 KEYYEPMHDVCCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLCR-PCDivLGFEEVAPCTSDRKAECRC 126
Cdd:cd10577   5 KEYYDEKAQMCCSKCPPGQHVKHSCTKTSDTVCAPCEESTYTQLWNWVPECLSCSsPCS--SDQVETQACTRQQNRICSC 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775  127 QPGMSCVY-LDNECVHCeeERLVLCQPGTEAeVTDEIMDTDVNCVPCKPGHFQNTSSPRARCQPHTRCEIQglveAAPGT 205
Cdd:cd10577  83 KPGWYCVLkLQEGCRQC--RPLKKCGPGFGV-ARPGTASSDVECKPCAPGTFSDTTSSTDTCRPHRICSSV----AIPGN 155

                ....*..
gi 7549775  206 SYSDTIC 212
Cdd:cd10577 156 ASMDAVC 162
TNFRSF6B cd10575
Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B), also known as decoy receptor ...
57-212 1.10e-24

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.


Pssm-ID: 276901 [Multi-domain]  Cd Length: 163  Bit Score: 99.40  E-value: 1.10e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   57 VCCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLCRpcdiVLGFE---EVAPCTSDRKAECRCQPGMscv 133
Cdd:cd10575  14 LTCDQCPPGTFVAKHCTRDRPTVCGPCPDLHYTQFWNYLEKCRYCN----VFCTErqvEKRQCNATHNRVCECKPGY--- 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775  134 YLDNE-CVHCEEerlvlCQPGTEAEVTDEiMDTDVNCVPCKPGHFQNTSSPRARCQPHTRCEIQGLVEAAPGTSYSDTIC 212
Cdd:cd10575  87 YMEHGfCLRHSS-----CPPGEGVIKLGT-PYSDTQCEPCPPGFFSASSSSTEPCQPHTNCTQGGLETNVPGNDYHDTLC 160
TNFRSF1B_teleost cd15835
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) in teleost; also known as ...
39-169 7.15e-24

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.


Pssm-ID: 276931 [Multi-domain]  Cd Length: 130  Bit Score: 95.96  E-value: 7.15e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   39 ENQTCWDQDKEYYEPMHDVCCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLCRPCDIVLGFEEVAPCTS 118
Cdd:cd15835   1 SDGNCRNTTTEYYNDGSNLCCSKCRPGTRLKTKCSETSDTVCEPCPSGQYSENWNYYPNCFSCPKCKERKGLQYAQNCSS 80
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 7549775  119 DRKAECRCQPGMSCV--YLDNECVHCEEERlvLCQPGTEAEVTDEiMDTDVNC 169
Cdd:cd15835  81 TTNAVCVCKPGMYCImgFDHPSCSECKKYR--TCKPGYGVSVPGT-PTSDVKC 130
TNFRSF4 cd13406
Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as CD134 or OXO40; ...
53-215 8.02e-20

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.


Pssm-ID: 276911 [Multi-domain]  Cd Length: 142  Bit Score: 85.14  E-value: 8.02e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   53 PMHDVCCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHlSTCQLCRPCDIVLGFEEVAPCTSDRKAECRCQPGMsc 132
Cdd:cd13406   9 PSGEKCCHECPPGEGMESRCTGTQDTVCSPCEPGFYNEAVNY-EPCKPCTQCNQRSGSEEKQKCTKTSDTVCRCRPGT-- 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775  133 vyldnecvhceeerlvlcQPGTEAEVTdeimdtdVNCVPCKPGHFQNTSSprARCQPHTRCEIQGLVEAAPGTSYSDTIC 212
Cdd:cd13406  86 ------------------QPLDSYKPG-------VDCVPCPPGHFSRGDN--QACKPWTNCSLAGKRTLRPGSSTSDAVC 138

                ...
gi 7549775  213 KNP 215
Cdd:cd13406 139 EDR 141
TNFRSF21 cd10583
Tumor necrosis factor receptor superfamily member 21 (TNFRSF21), also known as death receptor ...
59-212 1.13e-19

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.


Pssm-ID: 276909 [Multi-domain]  Cd Length: 159  Bit Score: 85.19  E-value: 1.13e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   59 CSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLCR-PCdiVLGFEEVAPCTSDRKAECRCQPGMscVYLDN 137
Cdd:cd10583  15 CDKCPAGTYVSKHCTETSLRECSPCPNGTFTRHENGIEQCHRCRkPC--PAPMIEKTPCTALTDRECTCPPGT--FLSND 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775  138 ECVhceeeRLVLCQPG-------TEAEvtdeimdtDVNCVPCKPGHFQNTSSPRARCQPHTRCEIQGLVEAAPGTSYSDT 210
Cdd:cd10583  91 TCV-----PHSVCPVGwgvrkkgTETE--------DVRCKPCPRGTFSDVPSSVLKCKTYTDCLGLGLVVIKPGTKETDN 157

                ..
gi 7549775  211 IC 212
Cdd:cd10583 158 VC 159
TNFRSF cd00185
Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) ...
58-143 1.40e-19

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.


Pssm-ID: 276900 [Multi-domain]  Cd Length: 87  Bit Score: 82.64  E-value: 1.40e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   58 CCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLCRPCDIVlGFEEVAPCTSDRKAECRCQPGMSCVYLDN 137
Cdd:cd00185   1 CCQRCPPGEYLSSDCTATTDTVCSPCPPGTYSESWNSLSKCLPCTTCGGG-NQVEKTPCTATDNRCCTCKPGFYCDEGTN 79

                ....*...
gi 7549775  138 --ECVHCE 143
Cdd:cd00185  80 veECKPCT 87
TNFRSF11A cd13411
Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor ...
58-213 8.66e-18

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.


Pssm-ID: 276916 [Multi-domain]  Cd Length: 163  Bit Score: 80.22  E-value: 8.66e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   58 CCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLCRPCDIVLGFEEVAPCTSDRKAECRCQPGMscvYLDN 137
Cdd:cd13411  14 CCSKCEPGKYMSSKCTVTSDSVCLPCGPDEYLDTWNEEDKCLLHKVCDAGKALVAVDPGNSTAPRRCACTAGY---HWSE 90
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 7549775  138 ECVHCEEERLvlCQPGTEAEVTDEiMDTDVNCVPCKPGHFQNTSSPRARCQPHTRCEIQGLVEAAPGTSYSDTICK 213
Cdd:cd13411  91 DCDCCRRNTE--CAPGFGAQHPVQ-LNKDTVCEPCLVGYFSDVFSSTDKCKPWTNCTILGLEEAVPGTNKSDVVCS 163
TNFRSF11A_teleost cd15836
Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) in teleost; also known as ...
58-172 7.01e-17

Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) in teleost; also known as 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. This 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.


Pssm-ID: 276932 [Multi-domain]  Cd Length: 122  Bit Score: 76.38  E-value: 7.01e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   58 CCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLCRPCDIVLGFEEVAPCTSDRKAECRCQPGMSCVYLDn 137
Cdd:cd15836  15 CCRKCEPGSFVFAHCSGSSDTICRDCGRNEYQPDWTSEMKCIPQKFCDEGKGFNRTRPHNPTALEPCQCKPGFQCSPLN- 93
                        90       100       110
                ....*....|....*....|....*....|....*
gi 7549775  138 eCVHCeeERLVLCQPGTeaEVTDEIMDTDVnCVPC 172
Cdd:cd15836  94 -CEFC--EKIPTCPPGY--GLEGEENGRKI-CVPC 122
TNFRSF5_teleost cd13422
Tumor necrosis factor receptor superfamily member 5 (TNFRSF5) in teleosts; also known as CD40; ...
47-212 4.55e-15

Tumor necrosis factor receptor superfamily member 5 (TNFRSF5) in teleosts; 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. Salmon CD40 and CD40L are widely expressed, particularly in immune tissues, and their importance for the immune response is indicated by their relatively high expression in salmon lymphoid organs and gills.


Pssm-ID: 276927 [Multi-domain]  Cd Length: 161  Bit Score: 72.46  E-value: 4.55e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   47 DKEYYEPMHDVCCSRCPPGeFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLCRPCDIVLGFEEVAPCTSDRKAECRC 126
Cdd:cd13422   2 DPETQYEKDGECCKMCGPG-TRMSSDSGCLDPQCQPCGEDEYQDKYTKENKCKRQPYCDPNKNFEISVNKSKTSRSVCKC 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775  127 QPGMSCVylDNECVHCEEERlvLCQPGTEAEVT-DEIMDTDvnCVPCKPGHFQNTSSPRARCQPHTRCEiQGLVEAAPGT 205
Cdd:cd13422  81 KPGFHCS--SEECLTCVPHT--TCGPGQGVKSKgNHIRDTV--CEECPDGTFSNNSSAEGVCKKWTECE-SGYKVEAAGT 153

                ....*..
gi 7549775  206 SYSDTIC 212
Cdd:cd13422 154 NTSDNIC 160
TNFRSF16 cd13416
Tumor necrosis factor receptor superfamily member 16 (TNFRSF16), also known as p75 ...
58-212 6.41e-15

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.


Pssm-ID: 276921 [Multi-domain]  Cd Length: 159  Bit Score: 71.95  E-value: 6.41e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   58 CCSRCPPGEFVFAVCSRSQdTVCKTCPHN-SYNEHWNHLSTCQLCRPCDIVLGFEevAPCTSDRKAECRCQPGMSCVYLD 136
Cdd:cd13416  14 CCEQCPPGEGVARPCGDNQ-TVCEPCLDGvTFSDVVSHTEPCQPCTRCPGLMSMR--APCTATHDTVCECAYGYYLDEDS 90
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 7549775  137 NECVHCEeerlvLCQPGTEAEVTDEImDTDVNCVPCKPGHFQNTSSPRARCQPHTRCEiQGLVEAAPGTSYSDTIC 212
Cdd:cd13416  91 GTCEPCT-----VCPPGQGVVQSCGP-NQDTVCEACPEGTYSDEDSSTDPCLPCTVCE-DGEVELRECTPVSDTVC 159
TNFRSF9 cd13410
Tumor necrosis factor receptor superfamily member 9 (TNFRSF9), also known as CD137; TNFRSF9 ...
59-212 1.49e-13

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.


Pssm-ID: 276915 [Multi-domain]  Cd Length: 138  Bit Score: 67.45  E-value: 1.49e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   59 CSRCPPGEFvfavCSRSQDTVCKTCPHNSYNEHWNHLsTCQLCRPCDIVLGFEEvaPCTSDRKAECRCQPGMSCvyLDNE 138
Cdd:cd13410   6 CSNCPAGTF----CGKNKDQTCIPCPPNSFSSTGGQQ-TCDICRKCEGVFRTKK--PCSSTSNAECECVPGFHC--LGPG 76
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 7549775  139 CVHCEEErlvlCQPGTEAEVTDeimdtdvnCVPCKPGHFQNTSspRARCQPHTRCEIQGLVEAAPGTSYSDTIC 212
Cdd:cd13410  77 CSMCEPD----CKQGQELTKEG--------CKDCSFGTFNDQE--GGVCRPWTNCSLDGKSVLVNGTKERDVVC 136
TNFRSF14_teleost cd13405
Tumor necrosis factor receptor superfamily member 14 (TNFRSF14) in teleost; also known as ...
58-153 2.94e-13

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.


Pssm-ID: 276910 [Multi-domain]  Cd Length: 111  Bit Score: 65.81  E-value: 2.94e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   58 CCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLCRPCDIVLGFEEVAPCTSDRKAECRCQPGMSCV-YLD 136
Cdd:cd13405  12 CCPMCPPGSRVSRHCTEDTSTSCVPCPDGTYMDEPNGLEKCFPCTNCDPGFGLRVKQGCTYTSDTVCEPLEGFYCIdSTK 91
                        90
                ....*....|....*..
gi 7549775  137 NECVHCEEERlvLCQPG 153
Cdd:cd13405  92 DGCSAAQRHS--SCKPG 106
TNFRSF1A cd10576
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), also known as TNFR1; TNFRSF1A ...
46-177 2.40e-11

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.


Pssm-ID: 276902 [Multi-domain]  Cd Length: 130  Bit Score: 60.83  E-value: 2.40e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   46 QDKEYYEPMHDVCCSRCPPGEFVFAVCSRS-QDTVCKTCPHNSYNEHWNHLSTCQLCRPCDIVLGFEEVAPCTSDRKAEC 124
Cdd:cd10576   2 PQGKYLHPNNNHCCTKCHKGTYLYNDCPGPgQDTVCRECENGTFTASENYLRKCLSCSRCRKEMGQVEISPCTVDQDTVC 81
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 7549775  125 RCQPGMSCVYLDNE--CVHCEeerlvLCQPGTEAEVTDEIMDTDVNcvpCKPGHF 177
Cdd:cd10576  82 GCRKNQYQHYWSSLfqCKNCS-----LCLNGTIRQPCQEKQDTICT---CHTGFF 128
TNFRSF14 cd10582
Tumor necrosis factor receptor superfamily member 14 (TNFRSF14), also known as herpes virus ...
53-143 2.24e-10

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.


Pssm-ID: 276908 [Multi-domain]  Cd Length: 101  Bit Score: 57.05  E-value: 2.24e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   53 PMHDVCCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLCRPCDIVLGFEEVAPCTSDRKAECRCQPGMSC 132
Cdd:cd10582   7 PVGSECCPKCSPGYRVKKACGELTGTVCEPCPPGTYTAHLNGLSKCLQCRVCDPAMGLVTRRNCSSTENTVCGCIPGHFC 86
                        90
                ....*....|..
gi 7549775  133 -VYLDNECVHCE 143
Cdd:cd10582  87 sAQDGDHCVECV 98
TNFRSF6 cd10579
Tumor necrosis factor receptor superfamily member 6 (TNFRSF6), also known as fas cell surface ...
58-159 4.62e-10

Tumor necrosis factor receptor superfamily member 6 (TNFRSF6), also known as fas cell surface death receptor (Fas); TNFRSF6 (also known as fas cell surface death receptor (FasR) or Fas, APT1, CD95, FAS1, APO-1, FASTM, ALPS1A) contains a death domain and plays a central role in the physiological regulation of programmed cell death. It has been implicated in the pathogenesis of various malignancies and diseases of the immune system. The receptor interactions with the Fas ligand (FasL), allowing the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10; autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, leading to apoptosis. This receptor has also been shown to activate NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is involved in transducing the proliferating signals in normal diploid fibroblast and T cells. Of the several alternatively spliced transcript variants, some are candidates for nonsense-mediated mRNA decay (NMD). Isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform.


Pssm-ID: 276905 [Multi-domain]  Cd Length: 129  Bit Score: 57.00  E-value: 4.62e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   58 CCSRCPPGEFVFAVC-SRSQDTVCKTCPH-NSYNEHWNHLSTCQLCRPCDIVLGFEEVAPCTSDRKAECRCQPGMSCVyl 135
Cdd:cd10579  21 CCQPCPPGTRKAIDCtTNGGKPDCVPCTEgKEYTDKKHYSDKCRRCKICDEEHGLEVEKNCTRTQNTKCRCKSNFFCN-- 98
                        90       100
                ....*....|....*....|....
gi 7549775  136 DNECVHCeeERLVLCQPGTEAEVT 159
Cdd:cd10579  99 SSPCEHC--DPCTTCEHGIIEECT 120
TNFRSF26 cd15837
Tumor necrosis factor receptor superfamily member 26 (TNFRSF26), also known as tumor necrosis ...
56-151 8.66e-10

Tumor necrosis factor receptor superfamily member 26 (TNFRSF26), also known as tumor necrosis factor receptor homolog 3 (TNFRH3); TNFRSF26 (also known as tumor necrosis factor receptor homolog 3 (TNFRH3) or TNFRSF24) is predominantly expressed in embryos and lymphoid cell types, along with its closely related TNFRSF22 and TNFRSF23 orthologs, and is developmentally regulated. Unlike TNFRSF22/23, TNFRSF26 does not serve as a TRAIL decoy receptor; it remains an orphan receptor.


Pssm-ID: 276933 [Multi-domain]  Cd Length: 118  Bit Score: 55.83  E-value: 8.66e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   56 DVCCSRCPPGEFVFAVCSRSQD-TVCKTCPHNSYNEHWNHLSTCQLCRPCDIvlGFEEVAPCTSDRKAECRCQPG----- 129
Cdd:cd15837  10 NLCCQLCPAGHYVSEPCQENHGvGECAPCEPGTFTAHPNGETSCFPCSQCRD--DQEVVAECSATSDRQCQCKQGhfycd 87
                        90       100
                ....*....|....*....|..
gi 7549775  130 MSCVYLDNECVHCEEERLVLCQ 151
Cdd:cd15837  88 ENCLESCFRCSRCPGGRVVLQP 109
TNFRSF_viral cd15839
Tumor necrosis factor receptor superfamily members, virus-encoded; This family contains viral ...
46-142 1.01e-09

Tumor necrosis factor receptor superfamily members, virus-encoded; This family contains viral TNFR homologs that include vaccinia virus (VACV) cytokine response modifier E (CrmE), an encoded TNFR that shares significant sequence similarity with mammalian type 2 TNF receptors (TNFSFR1B, p75, TNFR type 2), a cowpox virus encoded cytokine-response modifier B (crmB), which is a secreted form of TNF receptor that can contribute to the modification of TNF-mediated antiviral processes, and a myxoma virus (MYXV) T2 (M-T2) protein that binds and inhibits rabbit TNF-alpha. The CrmE structure confirms that the canonical TNFR fold is adopted, but only one of the two "ligand-binding" loops of TNFRSF1A is conserved, suggesting a mechanism for the higher affinity of poxvirus TNFRs for TNFalpha over lymphotoxin-alpha. CrmB protein specifically binds TNF-alpha and TNF-beta indicating that cowpox virus seeks to invade antiviral processes mediated by TNF. Intracellular M-T2 blocks virus-induced lymphocyte apoptosis via a highly conserved viral preligand assembly domain (vPLAD), which controls receptor signaling competency prior to ligand binding.


Pssm-ID: 276935 [Multi-domain]  Cd Length: 125  Bit Score: 56.03  E-value: 1.01e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   46 QDKEYYEPMHDVCCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLCR-PCDIVLgfEEVAPCTSDRKAEC 124
Cdd:cd15839   2 NGNDYNSNSNNLCCKSCPPGTYASHLCDTTSNTKCDPCPSDTFTSIPNHIPACLSCRgRCSSNQ--VETKSCSNTQNRIC 79
                        90
                ....*....|....*....
gi 7549775  125 RCQPGMSCVY-LDNECVHC 142
Cdd:cd15839  80 SCAPGYYCLLkGSDGCVAC 98
TNFRSF6_teleost cd13423
Tumor necrosis factor receptor superfamily member 6 (TNFRSF6) in teleosts; also known as fas ...
59-132 1.83e-09

Tumor necrosis factor receptor superfamily member 6 (TNFRSF6) in teleosts; also known as fas cell surface death receptor (FasR); This subfamily of TNFRSF6 (also known as fas cell surface death receptor (FasR) or Fas; APT1; CD95; FAS1; APO-1; FASTM; ALPS1A) is found in teleosts. It contains a death domain and plays a central role in the physiological regulation of programmed cell death. In humans, it has been implicated in the pathogenesis of various malignancies and diseases of the immune system. The receptor interactions with the Fas ligand (FasL), allowing the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10; autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, leading to apoptosis. This receptor has also been shown to activate NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is involved in transducing the proliferating signals in normal diploid fibroblast and T cells. In channel catfish and the Japanese rice fish, medaka, homologs of Fas receptor (FasR), as well as FADD and caspase 8, have been identified and characterized, and likely constitute the teleost equivalent of the death-inducing signaling complex (DISC). FasL/FasR are involved in the initiation of apoptosis and suggest that mechanisms of cell-mediated cytotoxicity in teleosts are similar to those used by mammals; presumably, the mechanism of apoptosis induction via death receptors was evolutionarily established during the appearance of vertebrates.


Pssm-ID: 276928 [Multi-domain]  Cd Length: 103  Bit Score: 54.74  E-value: 1.83e-09
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 7549775   59 CSRCPPGEFVFAVCSRS-QDTVCKTCPHNSYNEHWNHLSTCQLCRPCDIVLGFEEVAPCTSDRKAECRCQPGMSC 132
Cdd:cd13423  14 CCLCPAGQHVEKHCTNNgTDGECEACEDGTYNSHPNSLDSCEPCTSCDPNANLEVEERCTPSSDTVCRCKEGHYC 88
TNFRSF1A_teleost cd15834
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) in teleosts; also known as ...
51-196 1.89e-09

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.


Pssm-ID: 276930 [Multi-domain]  Cd Length: 150  Bit Score: 55.96  E-value: 1.89e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   51 YEPMHDVCCSRCPPGEFVFAVCSRS-QDTVCKTCPHNSYNEHWNHLSTCQLCRPCDIVLGfEEVAPCTSDRKAECRCQPG 129
Cdd:cd15834   6 YLSENGICCNKCHPGYKLKEECTAPgERSQCTPCPEGTYLEQINYSPNCRRCTLCKVKNE-EEVSPCKKSSNTVCRCKKG 84
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775  130 MSCVYLDN---ECVHCEEerlvlCQPGtEAEVTDEIMDTDVNCVpCKPGHFQNTSSprarCQPHTRCEIQ 196
Cdd:cd15834  85 YYKSRIDSetrECLKCKT-----CGPG-EIEIQPCTPESNTVCE-CKDNYYRNNNK----CKPCQKCSLD 143
TNFRSF11B cd10581
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B), also known as ...
50-179 2.06e-09

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.


Pssm-ID: 276907 [Multi-domain]  Cd Length: 147  Bit Score: 55.55  E-value: 2.06e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   50 YYEPM--HDVCCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLCRPCDIVLGFEEVApCTSDRKAECRCQ 127
Cdd:cd10581  25 HYDPVtsRQLMCDQCPPGTYVKQHCSASRKTVCAPCPDHHYADDWNSNDECQYCNTVCKELQYVKQE-CNSTHNRVCECV 103
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 7549775  128 PGMscvYLDNE-CVhceeeRLVLCQPGTEAeVTDEIMDTDVNCVPCKPGHFQN 179
Cdd:cd10581 104 EGR---YLELEfCL-----KHTECPPGFGV-VQPGTPESDTVCERCPEGFFSN 147
TNFRSF10 cd10580
Tumor necrosis factor receptor superfamily member 10 (TNFRSF10), includes TNFRSF10A (DR4), ...
58-132 2.90e-08

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.


Pssm-ID: 276906 [Multi-domain]  Cd Length: 103  Bit Score: 51.11  E-value: 2.90e-08
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 7549775   58 CCSRCPPGEFVfavcsrSQDT-VCKTCPHNS-YNEHWNHLSTCQLCRPCDIvlGFEEVAPCTSDRKAECRCQPGMSC 132
Cdd:cd10580   1 SCGLCPAGTYV------SEDSgDCIPCKEGVdYTEHPNGLPSCLPCTVCKS--DEEELSPCTTTRNTECQCKPGTFC 69
TNFRSF11B_teleost cd13412
Tumor necrosis factor receptor superfamily 11B (TNFRSF11B) in teleost; also known as ...
59-129 3.16e-07

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.


Pssm-ID: 276917 [Multi-domain]  Cd Length: 129  Bit Score: 49.02  E-value: 3.16e-07
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 7549775   59 CSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLCRP-CDIVLGFEEVAPCTSDRKaeCRCQPG 129
Cdd:cd13412  22 CKKCPPGTHMAAHCTATTQTKCLPCPAAHYTELWNYLPRCLYCNNfCSENQEVEIECSATNNRV--CRCKEG 91
TNFRSF19L cd13419
tumor necrosis factor receptor superfamily member 19-like (TNFRSF19L), also known as receptor ...
148-212 7.46e-06

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.


Pssm-ID: 276924  Cd Length: 91  Bit Score: 43.94  E-value: 7.46e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 7549775  148 VLCQPGTE-AEVTDEIMDTDVNCVPCKPGHFQNTSSPRArCQPHTRCEIQGLVEAAPGTSYSDTIC 212
Cdd:cd13419   5 LQCPPGQEpDRACGQGQGLGVLCRSCPPGTFSDSLGSEP-CRPHTSCEVLKRKVATSGTATSDAVC 69
TNFRSF cd00185
Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) ...
149-212 8.95e-06

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.


Pssm-ID: 276900 [Multi-domain]  Cd Length: 87  Bit Score: 43.74  E-value: 8.95e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 7549775  149 LCQPGTEAeVTDEIMDTDVNCVPCKPGHFQNTSSPRARCQPHTRCEIQGLVEAAPGTSYSDTIC 212
Cdd:cd00185   4 RCPPGEYL-SSDCTATTDTVCSPCPPGTYSESWNSLSKCLPCTTCGGGNQVEKTPCTATDNRCC 66
TNFRSF18 cd13417
Tumor necrosis factor receptor superfamily member 18 (TNFRSF18), also known as ...
111-218 1.41e-05

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.


Pssm-ID: 276922 [Multi-domain]  Cd Length: 130  Bit Score: 44.30  E-value: 1.41e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775  111 EEVAPCTSDRKAECRC-QPGMSCVylDNECVHCEEERlvlCQPGTEAEVTDEImDTDVNCVPCKPGHFQNTSspRARCQP 189
Cdd:cd13417   9 EEADAPCCDAEGDCKCvQPGFHCG--DPQCKTCKKHP---CPPGQEVQRQGKF-DFGFECVPCANGTFSDGH--DGHCKP 80
                        90       100
                ....*....|....*....|....*....
gi 7549775  190 HTRCEIQGLVEAAPGTSYSDTICKNPPEP 218
Cdd:cd13417  81 WTDCSQFGFLTIFPGNKTHNAVCGPGPPP 109
PHA02637 PHA02637
TNF-alpha-receptor-like protein; Provisional
33-101 1.84e-05

TNF-alpha-receptor-like protein; Provisional


Pssm-ID: 222913  Cd Length: 127  Bit Score: 43.98  E-value: 1.84e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 7549775    33 VPPYRIENQTCwdQDKEYYEpmHDVCCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLC 101
Cdd:PHA02637  22 IAPHAPSDGKC--KDNEYKR--HNLCCLSCPPGTYASRLCDIKTNTQCTPCGSGTFTSHNNHLPACLSC 86
TNFR_c6 pfam00020
TNFR/NGFR cysteine-rich region;
83-124 5.17e-05

TNFR/NGFR cysteine-rich region;


Pssm-ID: 425425 [Multi-domain]  Cd Length: 39  Bit Score: 40.00  E-value: 5.17e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 7549775     83 CPHNSYNEHWNHLStCQLCRPCDIvlGFEEVAPCTSDRKAEC 124
Cdd:pfam00020   1 CPPGTYTDSWNGLE-CLPCTVCPP--GQVVKRPCTATSDTVC 39
TNFRSF8 cd13409
Tumor necrosis factor receptor superfamily member 8 (TNFRSF8), also known as CD30; TNFRSF8 ...
57-142 1.36e-04

Tumor necrosis factor receptor superfamily member 8 (TNFRSF8), also known as CD30; TNFRSF8 (also known as CD30, Ki-1, D1S166E) is expressed by activated T and B cells. It transduces signals that lead to the activation of NF-kappaB, mediated by the adaptor proteins TRAF2 and TRAF5. This receptor is a positive regulator of apoptosis, and has been shown to limit the proliferative potential of auto-reactive CD8 effector T cells and protect the body against autoimmunity. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. CD30 is expressed in malignant Hodgkin and Reed-Sternberg cells on the surface of extracellular vesicles, facilitating CD30-CD30L interaction between cell types. This receptor is also associated with anaplastic large cell lymphoma. It is expressed in embryonal carcinoma, but not in seminoma, making it a useful marker in distinguishing between these germ cell tumors. Since CD30 has restricted expression in normal tissues, it is an optimal target for selectively eliminating CD30-expressing neoplastic cells by specific toxin-conjugated monoclonal antibodies (mAbs).


Pssm-ID: 276914  Cd Length: 130  Bit Score: 41.52  E-value: 1.36e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   57 VCCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHWNHLSTCQLCRPCDIVlgfeEVAPCTSDRKAECRCQPGMSCVY-L 135
Cdd:cd13409  42 KCCYRCPPGLSPQQPCPQGSADCRKQCEPDYYLDEDGRCTACVSCSGDDLV----EKAPCSWNSSRVCECRPGMFCATsA 117

                ....*..
gi 7549775  136 DNECVHC 142
Cdd:cd13409 118 TNSCARC 124
TNFRSF9_teleost cd13424
Tumor necrosis factor receptor superfamily member 9 (TNFRSF9) in teleosts; also known as CD137; ...
56-212 2.75e-04

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.


Pssm-ID: 276929 [Multi-domain]  Cd Length: 150  Bit Score: 40.97  E-value: 2.75e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   56 DVCCSRCPPGEFVFAVCSRSQDTVCKTCPHNSYNEHwnhlSTCQLCRPCDIVLGFEEVAP-CTSDRKAECRCQPGMSCVy 134
Cdd:cd13424  11 YVCCESCHPGNRLVERCGPDPAELCKPCEPGTYTVK----PLDYSCYICTQCIGAQVLLKnCTPSSDTVCGCKEGLRCG- 85
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 7549775  135 lDNECVHCEEErlvlCQPGTEAEVtdeimdtDVNCVPCKPGHFQNTSspRARCQP-HTRCEIQGLVEAAPGTSYSDTIC 212
Cdd:cd13424  86 -DAECSFCVTE----CGKGQEPLG-------KRDCRQCPVGTFNDQI--HSKCKEwSTSCPDPNELIVFKGDATSDITC 150
TNFRSF25 cd13420
tumor necrosis factor receptor superfamily member 25 (TNFRSF25), also known as death receptor ...
57-152 4.68e-04

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.


Pssm-ID: 276925 [Multi-domain]  Cd Length: 114  Bit Score: 39.40  E-value: 4.68e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7549775   57 VCCSRCPPGEFVFAVCSR-SQDTVCKTCPHNSYNEHWNHLST-CQLCRPCDIVLGFEEVAPCTSDRKAECRCQPGMscvy 134
Cdd:cd13420  15 FCCRGCPAGHYLKAPCTEpCGNSTCLPCPRGTFLARENHHKTdCTRCQACDEQASQVALENCSAVSDTHCGCESGW---- 90
                        90
                ....*....|....*...
gi 7549775  135 ldneCVHCEEERLVLCQP 152
Cdd:cd13420  91 ----FVECSVKDCVSSSP 104
TNFR smart00208
Tumor necrosis factor receptor / nerve growth factor receptor repeats; Repeats in growth ...
83-124 3.72e-03

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


Pssm-ID: 214558  Cd Length: 39  Bit Score: 34.75  E-value: 3.72e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 7549775      83 CPHNSYNEHWNHlSTCQLCRPCDivLGFEEVAPCTSDRKAEC 124
Cdd:smart00208   1 CKEGTYCSDGNH-SSCLRCRRCP--PGLVVKQPCTATSDTVC 39
TNFR_c6 pfam00020
TNFR/NGFR cysteine-rich region;
57-80 8.31e-03

TNFR/NGFR cysteine-rich region;


Pssm-ID: 425425 [Multi-domain]  Cd Length: 39  Bit Score: 33.83  E-value: 8.31e-03
                          10        20
                  ....*....|....*....|....
gi 7549775     57 VCCSRCPPGEFVFAVCSRSQDTVC 80
Cdd:pfam00020  16 LPCTVCPPGQVVKRPCTATSDTVC 39
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.20
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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