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Conserved domains on  [gi|568950850|ref|XP_006508002|]
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tumor necrosis factor receptor superfamily member 19L isoform X2 [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
TNFRSF19L cd13419
tumor necrosis factor receptor superfamily member 19-like (TNFRSF19L), also known as receptor ...
73-159 5.25e-37

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: 129.84  E-value: 5.25e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950850  73 PITPWLCPPGKEPDPD----PGQGTLCRTCPPGTFSASWNSYPCQPHYRCSLQKRLEAQAGTATHDTMCGDCQHGWFGPQ 148
Cdd:cd13419    1 CVPCLQCPPGQEPDRAcgqgQGLGVLCRSCPPGTFSDSLGSEPCRPHTSCEVLKRKVATSGTATSDAVCGDCLPGFHSPA 80
                         90
                 ....*....|.
gi 568950850 149 GVPHVPCQPCS 159
Cdd:cd13419   81 APPPSTCLPCS 91
RELT super family cl13980
Tumour necrosis factor receptor superfamily member 19; This family of proteins is found in ...
210-245 4.38e-16

Tumour necrosis factor receptor superfamily member 19; This family of proteins is found in eukaryotes. Proteins in this family are typically between 49 and 288 amino acids in length. There are two completely conserved residues (K and Y) that may be functionally important. The members of tumor necrosis factor receptor (TNFR) superfamily have been designated as the 'guardians of the immune system' due to their roles in immune cell proliferation, differentiation, activation, and death (apoptosis). The messenger RNA of RELT is especially abundant in hematologic tissues such as spleen, lymph node, and peripheral blood leukocytes as well as in leukemias and lymphomas. RELT is able to activate the NF-kappaB pathway and selectively binds tumor necrosis factor receptor-associated factor 1. RELT is a TNF receptor family member that is expressed in hematological tissues and can stimulate the proliferation of T-cells, the p38 and JNK MAPK pathways, and serves as a substrate for the closely related kinases OSR1 and SPAK. Furthermore, family members include the homologs RELL1 and RELL2 (RELT-like protein 1 and 2 respectively). RELT, RELL1 and RELL2 bind to each other in vitro and co-localize with one another at the plasma membrane. Functional studies of the role of RELT, show that overexpression of RELT in epithelial cells induces cell death by promoting cell rounding and DNA fragmentation.


The actual alignment was detected with superfamily member pfam12606:

Pssm-ID: 403713  Cd Length: 42  Bit Score: 71.54  E-value: 4.38e-16
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 568950850  210 YAVIAIVPVFCLMGLLGILVCNLLKRKGYHCTAQKE 245
Cdd:pfam12606   1 YIAFALVPIFFLMGLLGVLICHVLKKKGYRCTTEKE 36
 
Name Accession Description Interval E-value
TNFRSF19L cd13419
tumor necrosis factor receptor superfamily member 19-like (TNFRSF19L), also known as receptor ...
73-159 5.25e-37

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: 129.84  E-value: 5.25e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950850  73 PITPWLCPPGKEPDPD----PGQGTLCRTCPPGTFSASWNSYPCQPHYRCSLQKRLEAQAGTATHDTMCGDCQHGWFGPQ 148
Cdd:cd13419    1 CVPCLQCPPGQEPDRAcgqgQGLGVLCRSCPPGTFSDSLGSEPCRPHTSCEVLKRKVATSGTATSDAVCGDCLPGFHSPA 80
                         90
                 ....*....|.
gi 568950850 149 GVPHVPCQPCS 159
Cdd:cd13419   81 APPPSTCLPCS 91
RELT pfam12606
Tumour necrosis factor receptor superfamily member 19; This family of proteins is found in ...
210-245 4.38e-16

Tumour necrosis factor receptor superfamily member 19; This family of proteins is found in eukaryotes. Proteins in this family are typically between 49 and 288 amino acids in length. There are two completely conserved residues (K and Y) that may be functionally important. The members of tumor necrosis factor receptor (TNFR) superfamily have been designated as the 'guardians of the immune system' due to their roles in immune cell proliferation, differentiation, activation, and death (apoptosis). The messenger RNA of RELT is especially abundant in hematologic tissues such as spleen, lymph node, and peripheral blood leukocytes as well as in leukemias and lymphomas. RELT is able to activate the NF-kappaB pathway and selectively binds tumor necrosis factor receptor-associated factor 1. RELT is a TNF receptor family member that is expressed in hematological tissues and can stimulate the proliferation of T-cells, the p38 and JNK MAPK pathways, and serves as a substrate for the closely related kinases OSR1 and SPAK. Furthermore, family members include the homologs RELL1 and RELL2 (RELT-like protein 1 and 2 respectively). RELT, RELL1 and RELL2 bind to each other in vitro and co-localize with one another at the plasma membrane. Functional studies of the role of RELT, show that overexpression of RELT in epithelial cells induces cell death by promoting cell rounding and DNA fragmentation.


Pssm-ID: 403713  Cd Length: 42  Bit Score: 71.54  E-value: 4.38e-16
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 568950850  210 YAVIAIVPVFCLMGLLGILVCNLLKRKGYHCTAQKE 245
Cdd:pfam12606   1 YIAFALVPIFFLMGLLGVLICHVLKKKGYRCTTEKE 36
TNFR_c6 pfam00020
TNFR/NGFR cysteine-rich region;
98-137 1.31e-05

TNFR/NGFR cysteine-rich region;


Pssm-ID: 459633 [Multi-domain]  Cd Length: 39  Bit Score: 41.91  E-value: 1.31e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 568950850   98 CPPGTFSASWNSYPCQPHYRCSLQKRlEAQAGTATHDTMC 137
Cdd:pfam00020   1 CPPGTYTDNWNGLKCLPCTVCPPGQV-VVRPCTPTSDTVC 39
TNFR smart00208
Tumor necrosis factor receptor / nerve growth factor receptor repeats; Repeats in growth ...
98-137 1.93e-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: 35.91  E-value: 1.93e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 568950850    98 CPPGTFSASWNSYPCQPHYRCSLQKRlEAQAGTATHDTMC 137
Cdd:smart00208   1 CKEGTYCSDGNHSSCLRCRRCPPGLV-VKQPCTATSDTVC 39
 
Name Accession Description Interval E-value
TNFRSF19L cd13419
tumor necrosis factor receptor superfamily member 19-like (TNFRSF19L), also known as receptor ...
73-159 5.25e-37

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: 129.84  E-value: 5.25e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950850  73 PITPWLCPPGKEPDPD----PGQGTLCRTCPPGTFSASWNSYPCQPHYRCSLQKRLEAQAGTATHDTMCGDCQHGWFGPQ 148
Cdd:cd13419    1 CVPCLQCPPGQEPDRAcgqgQGLGVLCRSCPPGTFSDSLGSEPCRPHTSCEVLKRKVATSGTATSDAVCGDCLPGFHSPA 80
                         90
                 ....*....|.
gi 568950850 149 GVPHVPCQPCS 159
Cdd:cd13419   81 APPPSTCLPCS 91
RELT pfam12606
Tumour necrosis factor receptor superfamily member 19; This family of proteins is found in ...
210-245 4.38e-16

Tumour necrosis factor receptor superfamily member 19; This family of proteins is found in eukaryotes. Proteins in this family are typically between 49 and 288 amino acids in length. There are two completely conserved residues (K and Y) that may be functionally important. The members of tumor necrosis factor receptor (TNFR) superfamily have been designated as the 'guardians of the immune system' due to their roles in immune cell proliferation, differentiation, activation, and death (apoptosis). The messenger RNA of RELT is especially abundant in hematologic tissues such as spleen, lymph node, and peripheral blood leukocytes as well as in leukemias and lymphomas. RELT is able to activate the NF-kappaB pathway and selectively binds tumor necrosis factor receptor-associated factor 1. RELT is a TNF receptor family member that is expressed in hematological tissues and can stimulate the proliferation of T-cells, the p38 and JNK MAPK pathways, and serves as a substrate for the closely related kinases OSR1 and SPAK. Furthermore, family members include the homologs RELL1 and RELL2 (RELT-like protein 1 and 2 respectively). RELT, RELL1 and RELL2 bind to each other in vitro and co-localize with one another at the plasma membrane. Functional studies of the role of RELT, show that overexpression of RELT in epithelial cells induces cell death by promoting cell rounding and DNA fragmentation.


Pssm-ID: 403713  Cd Length: 42  Bit Score: 71.54  E-value: 4.38e-16
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 568950850  210 YAVIAIVPVFCLMGLLGILVCNLLKRKGYHCTAQKE 245
Cdd:pfam12606   1 YIAFALVPIFFLMGLLGVLICHVLKKKGYRCTTEKE 36
TNFRSF cd00185
Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) ...
78-159 6.35e-13

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: 64.15  E-value: 6.35e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950850  78 LCPPGKEPDPD--PGQGTLCRTCPPGTFSASWNSYP-CQPHYRCSLQKRLEAQAGTATHDTmCGDCQHGWFGPQGVPHVP 154
Cdd:cd00185    4 RCPPGEYLSSDctATTDTVCSPCPPGTYSESWNSLSkCLPCTTCGGGNQVEKTPCTATDNR-CCTCKPGFYCDEGTNVEE 82

                 ....*
gi 568950850 155 CQPCS 159
Cdd:cd00185   83 CKPCT 87
TNFRSF6B cd10575
Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B), also known as decoy receptor ...
79-140 3.50e-09

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: 55.49  E-value: 3.50e-09
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568950850  79 CPPGK--EPDPDPGQGTLCRTCPPGTFSASWNSY-PCQPHYRCSLQKRLEAQAGTATHDTMCGDC 140
Cdd:cd10575   99 CPPGEgvIKLGTPYSDTQCEPCPPGFFSASSSSTePCQPHTNCTQGGLETNVPGNDYHDTLCTSC 163
TNFRSF27 cd15838
Tumor necrosis factor receptor superfamily member 27 (TNFRSF27), also known as ectodysplasin ...
79-165 5.21e-09

Tumor necrosis factor receptor superfamily member 27 (TNFRSF27), also known as ectodysplasin A2 receptor (EDA2R) or X-linked ectodermal dysplasia receptor (XEDAR); TNFRSF27 (also known as ectodysplasin A2 receptor (EDA2R), X-linked ectodermal dysplasia receptor (XEDAR), EDAA2R, EDA-A2R) has two isoforms, EDA-A1 and EDA-A2, that are encoded by the anhidrotic ectodermal dysplasia (EDA) gene. It is highly expressed during embryonic development and binds to ectodysplasin-A2 (EDA-A2), playing a crucial role in the p53-signaling pathway. EDA2R is a direct p53 target that is frequently down-regulated in colorectal cancer tissues due to its epigenetic alterations or through the p53 gene mutations. Mutations in the EDA-A2/XEDAR signaling give rise to ectodermal dysplasia, characterized by loss of hair, sweat glands, and teeth. A non-synonymous SNP on EDA2R, along with genetic variants in human androgen receptor is associated with androgenetic alopecia (AGA).


Pssm-ID: 276934  Cd Length: 116  Bit Score: 53.74  E-value: 5.21e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950850  79 CPPGKEPDPDPGQG----TLCRTCPPGTFSASWNSYPCQPHYRCSLQKRLEAQAGTATHDTMCGDCQHGWFGPQ---GVP 151
Cdd:cd15838   19 CGPGQELSKDCGYGeggdAYCTACPPRRFKDSWGHHGCKTCLSCALINRVQKSNCTATSNAVCGDCLPGFYRKTrigGLQ 98
                         90
                 ....*....|....
gi 568950850 152 HVPCQPCSKAPPST 165
Cdd:cd15838   99 DQECIPCTKQTPSS 112
TNFRSF19 cd13418
Tumor necrosis factor receptor superfamily member 19 (TNFRSF19), also known as TROY; TNFRSF19 ...
79-163 2.14e-08

Tumor necrosis factor receptor superfamily member 19 (TNFRSF19), also known as TROY; TNFRSF19 (also known as TAJ; TROY; TRADE; TAJ-alpha) is expressed in progenitor cells of the hippocampus, thalamus, and cerebral cortex and highly expressed during embryonic development. It has been shown to interact with TRAF family members, and to activate JNK signaling pathway when overexpressed in cells. It is frequently overexpressed in colorectal cancer cell lines and primary colorectal carcinomas. TNFRSF19 is a beta-catenin target gene, in mesenchymal stem cells, and also activates NF-kappaB signaling, showing that beta-catenin regulates NF-kappaB activity via TNFRSF19. Since Wnt/beta-catenin signaling plays a crucial role in the regulation of colon tissue regeneration and the development of colon tumors, TNFRSF19 may contribute to the development of colorectal tumors. These findings define a role for death receptors DR6 and TROY in CNS-specific vascular development. TNFRSF19 has been shown to promote glioblastoma (GBM) survival signaling and therefore targeting it may increase tumor vulnerability and improve therapeutic response in glioblastoma. It may play an important role in myelin-associated inhibitory factors (MAIFs)-induced inhibition of neurite outgrowth in the postnatal central nervous system (CNS) or on axon regeneration following CNS injury.


Pssm-ID: 276923  Cd Length: 117  Bit Score: 52.17  E-value: 2.14e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950850  79 CPPGKEPDPDPGQG----TLCRTCPPGTFSASWNSYPCQPHYRCSLQKRLEAQAGTATHDTMCGDCQHGWFGPQ---GVP 151
Cdd:cd13418   20 CGPGMELSKECGFGygedAQCVPCRPNRFKEDWGFQKCKPCLDCALLNRFQKANCSATSNAVCGDCLPGFYRKTklvGFQ 99
                         90
                 ....*....|..
gi 568950850 152 HVPCQPCSKAPP 163
Cdd:cd13418  100 DMECVPCGDPPP 111
TNFRSF4 cd13406
Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as CD134 or OXO40; ...
70-139 1.35e-06

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: 47.39  E-value: 1.35e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950850  70 TPTPITPWLCPPGKEPDPDPGQGTLCRTCPPGTFSASWNSyPCQPHYRCSLQKRLEAQAGTATHDTMCGD 139
Cdd:cd13406   72 TKTSDTVCRCRPGTQPLDSYKPGVDCVPCPPGHFSRGDNQ-ACKPWTNCSLAGKRTLRPGSSTSDAVCED 140
TNFRSF5 cd13407
Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40; TNFRSF5 ...
78-157 1.72e-06

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: 47.78  E-value: 1.72e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950850  78 LCPPGK--EPDPDPGQGTLCRTCPPGTFSASWN-SYPCQPHYRCSLQKRLEAQA-GTATHDTMCGdCQHGWFGPQG---- 149
Cdd:cd13407   15 LCPPGQklVSDCTEATDTECLPCEEGEFQDTWNrERHCHQHRYCDPNLGLRVQTeGTAETDTTCT-CQEGQHCTSEacet 93

                 ....*....
gi 568950850 150 -VPHVPCQP 157
Cdd:cd13407   94 cALHTSCKP 102
TNFRSF4 cd13406
Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as CD134 or OXO40; ...
79-168 2.53e-06

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: 46.62  E-value: 2.53e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950850  79 CPPGKEPDP--DPGQGTLCRTCPPGTFSASWNSYPCQPHYRCSLQKRLEA-QAGTATHDTMCGD-----CQHGWfgPQGV 150
Cdd:cd13406   18 CPPGEGMESrcTGTQDTVCSPCEPGFYNEAVNYEPCKPCTQCNQRSGSEEkQKCTKTSDTVCRCrpgtqPLDSY--KPGV 95
                         90
                 ....*....|....*...
gi 568950850 151 PHVPCQPCSKAPPSTGGC 168
Cdd:cd13406   96 DCVPCPPGHFSRGDNQAC 113
TNFRSF1B_teleost cd15835
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) in teleost; also known as ...
93-160 6.62e-06

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: 45.12  E-value: 6.62e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950850  93 TLCRTCPPGTFSASWNSYP-CQPHYRCSLQKRLE-AQAGTATHDTMCGdCQHGWFGPQGVPHVPCQPCSK 160
Cdd:cd15835   40 TVCEPCPSGQYSENWNYYPnCFSCPKCKERKGLQyAQNCSSTTNAVCV-CKPGMYCIMGFDHPSCSECKK 108
TNFRSF1A cd10576
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), also known as TNFR1; TNFRSF1A ...
87-159 1.07e-05

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: 44.65  E-value: 1.07e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568950850  87 PDPGQGTLCRTCPPGTFSASWNSYP-CQPHYRCSLQ-KRLEAQAGTATHDTMCGdCQHGWFGPQGVPHVPCQPCS 159
Cdd:cd10576   29 PGPGQDTVCRECENGTFTASENYLRkCLSCSRCRKEmGQVEISPCTVDQDTVCG-CRKNQYQHYWSSLFQCKNCS 102
TNFR_c6 pfam00020
TNFR/NGFR cysteine-rich region;
98-137 1.31e-05

TNFR/NGFR cysteine-rich region;


Pssm-ID: 459633 [Multi-domain]  Cd Length: 39  Bit Score: 41.91  E-value: 1.31e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 568950850   98 CPPGTFSASWNSYPCQPHYRCSLQKRlEAQAGTATHDTMC 137
Cdd:pfam00020   1 CPPGTYTDNWNGLKCLPCTVCPPGQV-VVRPCTPTSDTVC 39
TNFRSF3 cd10578
Tumor necrosis factor receptor superfamily member 3 (TNFRSF3), also known as lymphotoxin beta ...
79-165 9.75e-05

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: 42.45  E-value: 9.75e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950850  79 CPPGK--EPDPDPGQGTLCRTCPPGTFSASWNSYP-CQPHYRC-SLQKRLEAQAGTATHDTMCGdCQHGWFGPQGVPHVP 154
Cdd:cd10578   52 CPPGThvSAECSRSQDTVCATCPENSYNEHWNHLSiCQLCRPCdPVLGFEEVAPCTSDRKTQCR-CQPGMFCVHWDNECE 130
                         90
                 ....*....|..
gi 568950850 155 -CQPCSKAPPST 165
Cdd:cd10578  131 hCEPLSDCPPGT 142
TNFRSF18 cd13417
Tumor necrosis factor receptor superfamily member 18 (TNFRSF18), also known as ...
79-138 2.13e-04

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: 40.83  E-value: 2.13e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568950850  79 CPPGKEPDPdpgQGTL-----CRTCPPGTFSASWNSYpCQPHYRCSLQKRLEAQAGTATHDTMCG 138
Cdd:cd13417   44 CPPGQEVQR---QGKFdfgfeCVPCANGTFSDGHDGH-CKPWTDCSQFGFLTIFPGNKTHNAVCG 104
TNFRSF16 cd13416
Tumor necrosis factor receptor superfamily member 16 (TNFRSF16), also known as p75 ...
89-137 6.37e-04

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: 39.98  E-value: 6.37e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 568950850  89 PGQGTLCRTCPPGTFSASWNSY-PCQPHYRCSlQKRLEAQAGTATHDTMC 137
Cdd:cd13416  111 PNQDTVCEACPEGTYSDEDSSTdPCLPCTVCE-DGEVELRECTPVSDTVC 159
TNFRSF16 cd13416
Tumor necrosis factor receptor superfamily member 16 (TNFRSF16), also known as p75 ...
95-166 8.96e-04

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: 39.59  E-value: 8.96e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950850  95 CRTCPPG---------------------TFSASWN-SYPCQPHYRCSLQKRLEAQAgTATHDTMCgDCQHGWFgpQGVPH 152
Cdd:cd13416   15 CEQCPPGegvarpcgdnqtvcepcldgvTFSDVVShTEPCQPCTRCPGLMSMRAPC-TATHDTVC-ECAYGYY--LDEDS 90
                         90
                 ....*....|....
gi 568950850 153 VPCQPCSKAPPSTG 166
Cdd:cd13416   91 GTCEPCTVCPPGQG 104
TNFRSF1B cd10577
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B), also known as TNFR2; TNFRSF1B ...
79-137 1.11e-03

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: 39.38  E-value: 1.11e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568950850  79 CPPG---KEPDPDPGQgTLCRTCPPGTFSASWNSY-PCQPHYRCSLQkrleAQAGTATHDTMC 137
Cdd:cd10577  105 CGPGfgvARPGTASSD-VECKPCAPGTFSDTTSSTdTCRPHRICSSV----AIPGNASMDAVC 162
TNFRSF_EDAR cd13421
Tumor necrosis factor receptor superfamily member ectodysplasin A receptor (EDAR); ...
79-168 1.37e-03

Tumor necrosis factor receptor superfamily member ectodysplasin A receptor (EDAR); Ectodysplasin A receptor (EDAR, also known as DL, ED3, ED5, ED1R, EDA3, HRM1, EDA1R, ECTD10A, ECTD10B, EDA-A1R) binds the soluble ligand ectodysplasin A and can activate the nuclear factor-kappaB, JNK, and caspase-independent cell death pathways. It is required for the development of hair, teeth, and other ectodermal derivatives. Mutations in this gene result in autosomal dominant and recessive forms of hypohidrotic ectodermal dysplasia. Patients present defects in the development of ectoderm-derived structures resulting in sparse hair, too few teeth (oligodontia), the absence or reduction in the ability to sweat as well as problems with mucous and saliva and the production and formation of pigment cells.


Pssm-ID: 276926  Cd Length: 136  Bit Score: 38.70  E-value: 1.37e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950850  79 CPPGKEPDPDPGQGTL-----CRTCPPGTFSASWNSYpCQPHYRC-SLQKRLEAQAGTATHDTMCGDCQHGWF----GPQ 148
Cdd:cd13421   38 CRPGEEPYMSCGYGTKdedygCVPCPAEKFSKGGYQI-CRRHKDCeGFFRATVLTPGDMENDAECGPCLPGYYmlenRPR 116
                         90       100
                 ....*....|....*....|
gi 568950850 149 GVPHVPCQPCSKAPPSTGGC 168
Cdd:cd13421  117 NIYGMVCYSCLLAPPNTKEC 136
TNFRSF6_teleost cd13423
Tumor necrosis factor receptor superfamily member 6 (TNFRSF6) in teleosts; also known as fas ...
78-160 1.38e-03

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: 37.79  E-value: 1.38e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950850  78 LCPPG---KEPDPDPGQGTLCRTCPPGTFSASWNS-YPCQPHYRCSLQKRLE-AQAGTATHDTMCGdCQHGWFGPQGVPH 152
Cdd:cd13423   16 LCPAGqhvEKHCTNNGTDGECEACEDGTYNSHPNSlDSCEPCTSCDPNANLEvEERCTPSSDTVCR-CKEGHYCDKGEEC 94

                 ....*...
gi 568950850 153 VPCQPCSK 160
Cdd:cd13423   95 KVCYPCDT 102
TNFR smart00208
Tumor necrosis factor receptor / nerve growth factor receptor repeats; Repeats in growth ...
98-137 1.93e-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: 35.91  E-value: 1.93e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 568950850    98 CPPGTFSASWNSYPCQPHYRCSLQKRlEAQAGTATHDTMC 137
Cdd:smart00208   1 CKEGTYCSDGNHSSCLRCRRCPPGLV-VKQPCTATSDTVC 39
TNFRSF5 cd13407
Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40; TNFRSF5 ...
93-137 3.91e-03

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: 37.77  E-value: 3.91e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 568950850  93 TLCRTCPPGTFS-ASWNSYPCQPHYRCSLQKRLEAQAGTATHDTMC 137
Cdd:cd13407  116 TICEPCPVGFFSnVSSAFEKCHPWTSCETKGLVELQAGTNKTDVVC 161
TNFRSF1B cd10577
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B), also known as TNFR2; TNFRSF1B ...
93-166 4.47e-03

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: 37.84  E-value: 4.47e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950850  93 TLCRTCPPGTFSASWNSYP----CQPhyRCSlQKRLEAQAGTATHDTMCGdCQHGWFGPQGVPH--VPCQPCSKAPPSTG 166
Cdd:cd10577   35 TVCAPCEESTYTQLWNWVPeclsCSS--PCS-SDQVETQACTRQQNRICS-CKPGWYCVLKLQEgcRQCRPLKKCGPGFG 110
 
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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