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Conserved domains on  [gi|768018657|ref|XP_011527411|]
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tumor necrosis factor receptor superfamily member 5 isoform X5 [Homo sapiens]

Protein Classification

tumor necrosis factor receptor family protein( domain architecture ID 366323)

tumor necrosis factor receptor (TNFR) family protein may interact with TNF superfamily (TNFSF) ligands (TNFL) to control key cellular processes such as differentiation, proliferation, apoptosis, and cell growth; similar to Rattus norvegicus tumor necrosis factor receptor superfamily member 8

CATH:  2.10.50.10
Gene Ontology:  GO:0005515
PubMed:  7917108

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
TNFRSF super family cl22855
Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) ...
26-135 2.67e-65

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 cd13407:

Pssm-ID: 473981 [Multi-domain]  Cd Length: 161  Bit Score: 196.86  E-value: 2.67e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  26 CREKQYLINSQCCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTICTC 105
Cdd:cd13407    1 CREKQYLHNGRCCSLCPPGQKLVSDCTEATDTECLPCEEGEFQDTWNRERHCHQHRYCDPNLGLRVQTEGTAETDTTCTC 80
                         90       100       110
                 ....*....|....*....|....*....|
gi 768018657 106 EEGWHCTSEACESCVLHRSCSPGFGVKQIA 135
Cdd:cd13407   81 QEGQHCTSEACETCALHTSCKPGFGVKQIA 110
 
Name Accession Description Interval E-value
TNFRSF5 cd13407
Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40; TNFRSF5 ...
26-135 2.67e-65

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: 196.86  E-value: 2.67e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  26 CREKQYLINSQCCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTICTC 105
Cdd:cd13407    1 CREKQYLHNGRCCSLCPPGQKLVSDCTEATDTECLPCEEGEFQDTWNRERHCHQHRYCDPNLGLRVQTEGTAETDTTCTC 80
                         90       100       110
                 ....*....|....*....|....*....|
gi 768018657 106 EEGWHCTSEACESCVLHRSCSPGFGVKQIA 135
Cdd:cd13407   81 QEGQHCTSEACETCALHTSCKPGFGVKQIA 110
PHA02637 PHA02637
TNF-alpha-receptor-like protein; Provisional
4-77 3.35e-03

TNF-alpha-receptor-like protein; Provisional


Pssm-ID: 222913  Cd Length: 127  Bit Score: 35.89  E-value: 3.35e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 768018657   4 LPLQCVLWGCLLTAVHPEPPTACREKQYLINSQCCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHC 77
Cdd:PHA02637  10 LFLSCIIINGRDIAPHAPSDGKCKDNEYKRHNLCCLSCPPGTYASRLCDIKTNTQCTPCGSGTFTSHNNHLPAC 83
 
Name Accession Description Interval E-value
TNFRSF5 cd13407
Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40; TNFRSF5 ...
26-135 2.67e-65

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: 196.86  E-value: 2.67e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  26 CREKQYLINSQCCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTICTC 105
Cdd:cd13407    1 CREKQYLHNGRCCSLCPPGQKLVSDCTEATDTECLPCEEGEFQDTWNRERHCHQHRYCDPNLGLRVQTEGTAETDTTCTC 80
                         90       100       110
                 ....*....|....*....|....*....|
gi 768018657 106 EEGWHCTSEACESCVLHRSCSPGFGVKQIA 135
Cdd:cd13407   81 QEGQHCTSEACETCALHTSCKPGFGVKQIA 110
TNFRSF14_teleost cd13405
Tumor necrosis factor receptor superfamily member 14 (TNFRSF14) in teleost; also known as ...
26-133 1.53e-24

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: 91.62  E-value: 1.53e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  26 CREKQYLINSQCCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTICTC 105
Cdd:cd13405    1 CGPAEYEINGECCPMCPPGSRVSRHCTEDTSTSCVPCPDGTYMDEPNGLEKCFPCTNCDPGFGLRVKQGCTYTSDTVCEP 80
                         90       100       110
                 ....*....|....*....|....*....|.
gi 768018657 106 EEGWHCTSEACESCVL---HRSCSPGFGVKQ 133
Cdd:cd13405   81 LEGFYCIDSTKDGCSAaqrHSSCKPGQYIKQ 111
TNFRSF5_teleost cd13422
Tumor necrosis factor receptor superfamily member 5 (TNFRSF5) in teleosts; also known as CD40; ...
28-134 2.16e-24

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: 92.49  E-value: 2.16e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  28 EKQYLINSQCCSLCQPGQKLVSDCTeFTETECLPCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTICTCEE 107
Cdd:cd13422    4 ETQYEKDGECCKMCGPGTRMSSDSG-CLDPQCQPCGEDEYQDKYTKENKCKRQPYCDPNKNFEISVNKSKTSRSVCKCKP 82
                         90       100
                 ....*....|....*....|....*..
gi 768018657 108 GWHCTSEACESCVLHRSCSPGFGVKQI 134
Cdd:cd13422   83 GFHCSSEECLTCVPHTTCGPGQGVKSK 109
TNFRSF11A cd13411
Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor ...
28-132 1.93e-22

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: 87.54  E-value: 1.93e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  28 EKQYLINSQCCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTICTCEE 107
Cdd:cd13411    5 ERHYEYSGRCCSKCEPGKYMSSKCTVTSDSVCLPCGPDEYLDTWNEEDKCLLHKVCDAGKALVAVDPGNSTAPRRCACTA 84
                         90       100
                 ....*....|....*....|....*
gi 768018657 108 GWHCtSEACESCVLHRSCSPGFGVK 132
Cdd:cd13411   85 GYHW-SEDCDCCRRNTECAPGFGAQ 108
TNFRSF1B_teleost cd15835
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) in teleost; also known as ...
37-131 4.51e-21

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: 83.25  E-value: 4.51e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  37 CCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTICTCEEGWHCTS--- 113
Cdd:cd15835   20 CCSKCRPGTRLKTKCSETSDTVCEPCPSGQYSENWNYYPNCFSCPKCKERKGLQYAQNCSSTTNAVCVCKPGMYCIMgfd 99
                         90
                 ....*....|....*....
gi 768018657 114 -EACESCVLHRSCSPGFGV 131
Cdd:cd15835  100 hPSCSECKKYRTCKPGYGV 118
TNFRSF11A_teleost cd15836
Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) in teleost; also known as ...
26-132 6.24e-19

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: 77.54  E-value: 6.24e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  26 CREKQYLINSQCCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTICTC 105
Cdd:cd15836    4 CNQTQYLKDGKCCRKCEPGSFVFAHCSGSSDTICRDCGRNEYQPDWTSEMKCIPQKFCDEGKGFNRTRPHNPTALEPCQC 83
                         90       100
                 ....*....|....*....|....*..
gi 768018657 106 EEGWHCTSEACESCVLHRSCSPGFGVK 132
Cdd:cd15836   84 KPGFQCSPLNCEFCEKIPTCPPGYGLE 110
TNFRSF cd00185
Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) ...
37-122 9.10e-16

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: 68.39  E-value: 9.10e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  37 CCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHKYCDPNlGLRVQQKGTSETDTICTCEEGWHC-TSEA 115
Cdd:cd00185    1 CCQRCPPGEYLSSDCTATTDTVCSPCPPGTYSESWNSLSKCLPCTTCGGG-NQVEKTPCTATDNRCCTCKPGFYCdEGTN 79

                 ....*..
gi 768018657 116 CESCVLH 122
Cdd:cd00185   80 VEECKPC 86
TNFRSF1B cd10577
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B), also known as TNFR2; TNFRSF1B ...
37-131 9.61e-16

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: 70.20  E-value: 9.61e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  37 CCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQhkyCDP--NLGLRVQQKGTSETDTICTCEEGWHCTS- 113
Cdd:cd10577   15 CCSKCPPGQHVKHSCTKTSDTVCAPCEESTYTQLWNWVPECLS---CSSpcSSDQVETQACTRQQNRICSCKPGWYCVLk 91
                         90       100
                 ....*....|....*....|
gi 768018657 114 --EACESCVLHRSCSPGFGV 131
Cdd:cd10577   92 lqEGCRQCRPLKKCGPGFGV 111
TNFRSF11B cd10581
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B), also known as ...
38-145 5.31e-13

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: 62.49  E-value: 5.31e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  38 CSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHChqhKYCDP--NLGLRVQQKGTSETDTICTCEEGWHCTsea 115
Cdd:cd10581   36 CDQCPPGTYVKQHCSASRKTVCAPCPDHHYADDWNSNDEC---QYCNTvcKELQYVKQECNSTHNRVCECVEGRYLE--- 109
                         90       100       110
                 ....*....|....*....|....*....|
gi 768018657 116 CESCVLHRSCSPGFGVKQIAVRPKTWLCNR 145
Cdd:cd10581  110 LEFCLKHTECPPGFGVVQPGTPESDTVCER 139
TNFRSF6 cd10579
Tumor necrosis factor receptor superfamily member 6 (TNFRSF6), also known as fas cell surface ...
24-128 6.48e-13

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: 62.01  E-value: 6.48e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  24 TACREKQYLINSQCCSLCQPGQKLVSDCTEFT-ETECLPCGE-SEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDT 101
Cdd:cd10579    8 INCSEGLYRGGQFCCQPCPPGTRKAIDCTTNGgKPDCVPCTEgKEYTDKKHYSDKCRRCKICDEEHGLEVEKNCTRTQNT 87
                         90       100
                 ....*....|....*....|....*..
gi 768018657 102 ICTCEEGWHCTSEACESCVLHRSCSPG 128
Cdd:cd10579   88 KCRCKSNFFCNSSPCEHCDPCTTCEHG 114
TNFRSF14 cd10582
Tumor necrosis factor receptor superfamily member 14 (TNFRSF14), also known as herpes virus ...
26-124 1.64e-11

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: 57.43  E-value: 1.64e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  26 CREKQYLINSQCCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTICTC 105
Cdd:cd10582    1 CKEDEYPVGSECCPKCSPGYRVKKACGELTGTVCEPCPPGTYTAHLNGLSKCLQCRVCDPAMGLVTRRNCSSTENTVCGC 80
                         90
                 ....*....|....*....
gi 768018657 106 EEGWHCTSEACESCVLHRS 124
Cdd:cd10582   81 IPGHFCSAQDGDHCVECVP 99
TNFRSF6_teleost cd13423
Tumor necrosis factor receptor superfamily member 6 (TNFRSF6) in teleosts; also known as fas ...
25-127 3.53e-10

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: 53.97  E-value: 3.53e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  25 ACREKQYLINSQCCSLCQPGQKLVSDCTE-FTETECLPCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTIC 103
Cdd:cd13423    1 SCEDGTYQHEGLTCCLCPAGQHVEKHCTNnGTDGECEACEDGTYNSHPNSLDSCEPCTSCDPNANLEVEERCTPSSDTVC 80
                         90       100
                 ....*....|....*....|....
gi 768018657 104 TCEEGWHCTSEacESCVLHRSCSP 127
Cdd:cd13423   81 RCKEGHYCDKG--EECKVCYPCDT 102
TNFRSF3 cd10578
Tumor necrosis factor receptor superfamily member 3 (TNFRSF3), also known as lymphotoxin beta ...
37-128 2.84e-09

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: 52.85  E-value: 2.84e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  37 CCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTICTCEEGWHCTSEA- 115
Cdd:cd10578   48 CCSRCPPGTHVSAECSRSQDTVCATCPENSYNEHWNHLSICQLCRPCDPVLGFEEVAPCTSDRKTQCRCQPGMFCVHWDn 127
                         90
                 ....*....|....
gi 768018657 116 -CESCVLHRSCSPG 128
Cdd:cd10578  128 eCEHCEPLSDCPPG 141
TNFRSF11B_teleost cd13412
Tumor necrosis factor receptor superfamily 11B (TNFRSF11B) in teleost; also known as ...
38-134 4.16e-09

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: 52.11  E-value: 4.16e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  38 CSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHC-HQHKYCDPNlgLRVQQKGTSETDTICTCEEGWHCTSEAc 116
Cdd:cd13412   22 CKKCPPGTHMAAHCTATTQTKCLPCPAAHYTELWNYLPRClYCNNFCSEN--QEVEIECSATNNRVCRCKEGYYMDSDF- 98
                         90
                 ....*....|....*...
gi 768018657 117 esCVLHRSCSPGFGVKQI 134
Cdd:cd13412   99 --CIRHTECGPGYGVKTK 114
TNFRSF6B cd10575
Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B), also known as decoy receptor ...
38-133 2.68e-08

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: 50.48  E-value: 2.68e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  38 CSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHChqhKYCDPNLGLR--VQQKGTSETDTICTCEEGWHCTSea 115
Cdd:cd10575   16 CDQCPPGTFVAKHCTRDRPTVCGPCPDLHYTQFWNYLEKC---RYCNVFCTERqvEKRQCNATHNRVCECKPGYYMEH-- 90
                         90
                 ....*....|....*...
gi 768018657 116 cESCVLHRSCSPGFGVKQ 133
Cdd:cd10575   91 -GFCLRHSSCPPGEGVIK 107
TNFRSF4 cd13406
Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as CD134 or OXO40; ...
26-108 6.58e-08

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: 48.93  E-value: 6.58e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  26 CREKQYLINSQCCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNREThCHQHKYCDPNLGLRVQQKGTSETDTICTC 105
Cdd:cd13406    3 CVGDTYPSGEKCCHECPPGEGMESRCTGTQDTVCSPCEPGFYNEAVNYEP-CKPCTQCNQRSGSEEKQKCTKTSDTVCRC 81

                 ...
gi 768018657 106 EEG 108
Cdd:cd13406   82 RPG 84
TNFRSF16 cd13416
Tumor necrosis factor receptor superfamily member 16 (TNFRSF16), also known as p75 ...
25-131 3.82e-07

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: 47.30  E-value: 3.82e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  25 ACREKQYLINSQCCSLCQPGQKLVSDCTEfTETECLPCGESE-FLDTWNRETHCHQHKYCDPNlgLRVQQKGTSETDTIC 103
Cdd:cd13416    2 ACPSGQYTSSGECCEQCPPGEGVARPCGD-NQTVCEPCLDGVtFSDVVSHTEPCQPCTRCPGL--MSMRAPCTATHDTVC 78
                         90       100
                 ....*....|....*....|....*...
gi 768018657 104 TCEEGWHcTSEACESCVLHRSCSPGFGV 131
Cdd:cd13416   79 ECAYGYY-LDEDSGTCEPCTVCPPGQGV 105
TNFRSF7 cd13408
Tumor necrosis factor receptor superfamily member 7 (TNFRSF7), also known as CD27; TNFRSF7 ...
8-119 6.41e-07

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


Pssm-ID: 276913 [Multi-domain]  Cd Length: 121  Bit Score: 45.96  E-value: 6.41e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657   8 CVLWGCLLTAVHPEPPTACREKQYLINSQCCSLCQPGQKLVSDCTEF-TETECLPCGES-EFLDTWNRETHCHQHKYCDP 85
Cdd:cd13408    7 WVLGTLAGLSATPAPKSCPERHYWAQGKLCCQMCEPGTFLVKDCDQHgKAAQCDPCIPGvSFSPDHHARPHCESCRHCNS 86
                         90       100       110
                 ....*....|....*....|....*....|....
gi 768018657  86 NLGLRvqqKGTSETDTICTCEEGWHCTSEACESC 119
Cdd:cd13408   87 GLLIR---NCTITANTECACPKGWQCRDKECTEC 117
TNFRSF_viral cd15839
Tumor necrosis factor receptor superfamily members, virus-encoded; This family contains viral ...
26-132 2.71e-06

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: 44.47  E-value: 2.71e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  26 CREKQYLINSQ--CCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHK-YCDPNlglRVQQKGTSET-DT 101
Cdd:cd15839    1 CNGNDYNSNSNnlCCKSCPPGTYASHLCDTTSNTKCDPCPSDTFTSIPNHIPACLSCRgRCSSN---QVETKSCSNTqNR 77
                         90       100       110
                 ....*....|....*....|....*....|....
gi 768018657 102 ICTCEEGWHC---TSEACESCVLHRSCSPGFGVK 132
Cdd:cd15839   78 ICSCAPGYYCllkGSDGCVACAPKTKCGVGYGVS 111
TNFRSF1A_teleost cd15834
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) in teleosts; also known as ...
26-143 5.38e-06

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: 44.02  E-value: 5.38e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  26 CREKQYLI-NSQCCSLCQPGQKLVSDCT-EFTETECLPCGESEFLDTWNRETHCHQHKYCDPNLGlRVQQKGTSETDTIC 103
Cdd:cd15834    1 CLDSEYLSeNGICCNKCHPGYKLKEECTaPGERSQCTPCPEGTYLEQINYSPNCRRCTLCKVKNE-EEVSPCKKSSNTVC 79
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 768018657 104 TCEEGWH---CTSEACEsCVLHRSCSPGFGVKQIAVRPKTWLC 143
Cdd:cd15834   80 RCKKGYYksrIDSETRE-CLKCKTCGPGEIEIQPCTPESNTVC 121
TNFRSF9_teleost cd13424
Tumor necrosis factor receptor superfamily member 9 (TNFRSF9) in teleosts; also known as CD137; ...
37-120 7.22e-05

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: 7.22e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  37 CCSLCQPGQKLVSDCTEFTETECLPCGESEFLdTWNRETHCHQhkyCDPNLGLRVQQKG-TSETDTICTCEEGWHCTSEA 115
Cdd:cd13424   13 CCESCHPGNRLVERCGPDPAELCKPCEPGTYT-VKPLDYSCYI---CTQCIGAQVLLKNcTPSSDTVCGCKEGLRCGDAE 88

                 ....*
gi 768018657 116 CESCV 120
Cdd:cd13424   89 CSFCV 93
TNFRSF21 cd10583
Tumor necrosis factor receptor superfamily member 21 (TNFRSF21), also known as death receptor ...
38-133 2.26e-04

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: 39.35  E-value: 2.26e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  38 CSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQ-HKYCDPnlGLRVQQKGTSETDTICTCEEGwhcTSEAC 116
Cdd:cd10583   15 CDKCPAGTYVSKHCTETSLRECSPCPNGTFTRHENGIEQCHRcRKPCPA--PMIEKTPCTALTDRECTCPPG---TFLSN 89
                         90
                 ....*....|....*..
gi 768018657 117 ESCVLHRSCSPGFGVKQ 133
Cdd:cd10583   90 DTCVPHSVCPVGWGVRK 106
TNFRSF1A cd10576
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), also known as TNFR1; TNFRSF1A ...
26-129 2.22e-03

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: 36.18  E-value: 2.22e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768018657  26 CREKQYL--INSQCCSLCQPGQKLVSDCTEFTE-TECLPCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTI 102
Cdd:cd10576    1 CPQGKYLhpNNNHCCTKCHKGTYLYNDCPGPGQdTVCRECENGTFTASENYLRKCLSCSRCRKEMGQVEISPCTVDQDTV 80
                         90       100
                 ....*....|....*....|....*..
gi 768018657 103 CTCEEGWHCTSEAceSCVLHRSCSPGF 129
Cdd:cd10576   81 CGCRKNQYQHYWS--SLFQCKNCSLCL 105
PHA02637 PHA02637
TNF-alpha-receptor-like protein; Provisional
4-77 3.35e-03

TNF-alpha-receptor-like protein; Provisional


Pssm-ID: 222913  Cd Length: 127  Bit Score: 35.89  E-value: 3.35e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 768018657   4 LPLQCVLWGCLLTAVHPEPPTACREKQYLINSQCCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHC 77
Cdd:PHA02637  10 LFLSCIIINGRDIAPHAPSDGKCKDNEYKRHNLCCLSCPPGTYASRLCDIKTNTQCTPCGSGTFTSHNNHLPAC 83
TNFRSF5_teleost cd13422
Tumor necrosis factor receptor superfamily member 5 (TNFRSF5) in teleosts; also known as CD40; ...
41-103 3.51e-03

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: 36.25  E-value: 3.51e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 768018657  41 CQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHKYCDPnlGLRVQQKGTSETDTIC 103
Cdd:cd13422  100 CGPGQGVKSKGNHIRDTVCEECPDGTFSNNSSAEGVCKKWTECES--GYKVEAAGTNTSDNIC 160
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
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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