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Conserved domains on  [gi|768037983|ref|XP_011529304|]
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tumor necrosis factor receptor superfamily member 27 isoform X7 [Homo sapiens]

Protein Classification

tumor necrosis factor receptor family protein( domain architecture ID 10205116)

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

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
TNFRSF27 cd15838
Tumor necrosis factor receptor superfamily member 27 (TNFRSF27), also known as ectodysplasin ...
3-118 6.04e-77

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: 228.24  E-value: 6.04e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983   3 CQENEYWDQWGRCVTCQRCGPGQELSKDCGYGEGGDAYCTACPPRRYKSSWGHHRCQSCITCAVINRVQKVNCTATSNAV 82
Cdd:cd15838    1 CQEKEYLDEHGKCVPCRECGPGQELSKDCGYGEGGDAYCTACPPRRFKDSWGHHGCKTCLSCALINRVQKSNCTATSNAV 80
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 768037983  83 CGDCLPRFYRKTRIGGLQDQECIPCTKQTPTSEVQC 118
Cdd:cd15838   81 CGDCLPGFYRKTRIGGLQDQECIPCTKQTPSSEVQC 116
 
Name Accession Description Interval E-value
TNFRSF27 cd15838
Tumor necrosis factor receptor superfamily member 27 (TNFRSF27), also known as ectodysplasin ...
3-118 6.04e-77

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: 228.24  E-value: 6.04e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983   3 CQENEYWDQWGRCVTCQRCGPGQELSKDCGYGEGGDAYCTACPPRRYKSSWGHHRCQSCITCAVINRVQKVNCTATSNAV 82
Cdd:cd15838    1 CQEKEYLDEHGKCVPCRECGPGQELSKDCGYGEGGDAYCTACPPRRFKDSWGHHGCKTCLSCALINRVQKSNCTATSNAV 80
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 768037983  83 CGDCLPRFYRKTRIGGLQDQECIPCTKQTPTSEVQC 118
Cdd:cd15838   81 CGDCLPGFYRKTRIGGLQDQECIPCTKQTPSSEVQC 116
TNFR_c6 pfam00020
TNFR/NGFR cysteine-rich region;
44-83 1.15e-05

TNFR/NGFR cysteine-rich region;


Pssm-ID: 459633 [Multi-domain]  Cd Length: 39  Bit Score: 41.53  E-value: 1.15e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 768037983   44 CPPRRYKSSWGHHRCQSCITCAViNRVQKVNCTATSNAVC 83
Cdd:pfam00020   1 CPPGTYTDNWNGLKCLPCTVCPP-GQVVVRPCTPTSDTVC 39
TNFR smart00208
Tumor necrosis factor receptor / nerve growth factor receptor repeats; Repeats in growth ...
44-83 1.47e-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: 35.52  E-value: 1.47e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 768037983    44 CPPRRYKSSWGHHRCQSCITCAVINRVqKVNCTATSNAVC 83
Cdd:smart00208   1 CKEGTYCSDGNHSSCLRCRRCPPGLVV-KQPCTATSDTVC 39
 
Name Accession Description Interval E-value
TNFRSF27 cd15838
Tumor necrosis factor receptor superfamily member 27 (TNFRSF27), also known as ectodysplasin ...
3-118 6.04e-77

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: 228.24  E-value: 6.04e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983   3 CQENEYWDQWGRCVTCQRCGPGQELSKDCGYGEGGDAYCTACPPRRYKSSWGHHRCQSCITCAVINRVQKVNCTATSNAV 82
Cdd:cd15838    1 CQEKEYLDEHGKCVPCRECGPGQELSKDCGYGEGGDAYCTACPPRRFKDSWGHHGCKTCLSCALINRVQKSNCTATSNAV 80
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 768037983  83 CGDCLPRFYRKTRIGGLQDQECIPCTKQTPTSEVQC 118
Cdd:cd15838   81 CGDCLPGFYRKTRIGGLQDQECIPCTKQTPSSEVQC 116
TNFRSF19 cd13418
Tumor necrosis factor receptor superfamily member 19 (TNFRSF19), also known as TROY; TNFRSF19 ...
2-118 6.77e-46

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: 149.24  E-value: 6.77e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983   2 DCQENEYWDQWGRCVTCQRCGPGQELSKDCGYGEGGDAYCTACPPRRYKSSWGHHRCQSCITCAVINRVQKVNCTATSNA 81
Cdd:cd13418    1 DCREQEYRDKAGNCIPCRQCGPGMELSKECGFGYGEDAQCVPCRPNRFKEDWGFQKCKPCLDCALLNRFQKANCSATSNA 80
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 768037983  82 VCGDCLPRFYRKTRIGGLQDQECIPCTKQTPTSEVQC 118
Cdd:cd13418   81 VCGDCLPGFYRKTKLVGFQDMECVPCGDPPPPYEPHC 117
TNFRSF cd00185
Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) ...
17-108 3.51e-19

Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) interactions with TNF superfamily (TNFSF) ligands (TNFL) control key cellular processes such as differentiation, proliferation, apoptosis, and cell growth. Dysregulation of these pathways has been shown to result in a wide range of pathological conditions, including autoimmune diseases, inflammation, cancer, and viral infection. There are 29 very diverse family members of TNFRSF reported in humans: 22 are type I transmembrane receptors (single pass with the N terminus on extracellular side of the cell membrane) and have a clear signal peptide; the remaining 7 members are either type III transmembrane receptors (single pass with the N terminus on extracellular side of the membrane but no signal sequence; TNFR13B, TNFR13C, TNFR17, and XEDAR), or attached to the membrane via a glycosylphosphatidylinositol (GPI) linker (TNFR10C), or secreted as soluble receptors (TNFR11B and TNFR6B). All TNFRs contain relatively short cysteine-rich domains (CRDs) in the ectodomain, and are involved in interaction with the TNF homology domain (THD) of their ligands. TNFRs often have multiple CRDs (between one and six), with the most frequent configurations of three or four copies; most CRDs possess three disulfide bridges, but could have between one and four. Localized or genome-wide duplication and evolution of the TNFRSF members appear to have paralleled the emergence of the adaptive immune system; teleosts (i.e. ray-finned, bony fish), which possess an immune system with B and T cells, possess primary and secondary lymphoid organs, and are capable of adaptive responses to pathogens also display several characteristics that are different from the mammalian immune system, making teleost TNFSF orthologs and paralogs of interest to better understand immune system evolution and the immunological pathways elicited to pathogens.


Pssm-ID: 276900 [Multi-domain]  Cd Length: 87  Bit Score: 79.56  E-value: 3.51e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983  17 TCQRCGPGQELSKDCGYGegGDAYCTACPPRRYKSSWGH-HRCQSCITCAVINRVQKVNCTATSNAVCgDCLPRFYRKTr 95
Cdd:cd00185    1 CCQRCPPGEYLSSDCTAT--TDTVCSPCPPGTYSESWNSlSKCLPCTTCGGGNQVEKTPCTATDNRCC-TCKPGFYCDE- 76
                         90
                 ....*....|...
gi 768037983  96 igGLQDQECIPCT 108
Cdd:cd00185   77 --GTNVEECKPCT 87
TNFRSF19L cd13419
tumor necrosis factor receptor superfamily member 19-like (TNFRSF19L), also known as receptor ...
15-108 8.03e-18

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: 75.91  E-value: 8.03e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983  15 CVTCQRCGPGQELSKDCGYGEGGDAYCTACPPRRYKSSWGHHRCQSCITCAVINRVQKVNCTATSNAVCGDCLPRFYrkt 94
Cdd:cd13419    1 CVPCLQCPPGQEPDRACGQGQGLGVLCRSCPPGTFSDSLGSEPCRPHTSCEVLKRKVATSGTATSDAVCGDCLPGFH--- 77
                         90
                 ....*....|....
gi 768037983  95 RIGGLQDQECIPCT 108
Cdd:cd13419   78 SPAAPPPSTCLPCS 91
TNFRSF1B_teleost cd15835
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) in teleost; also known as ...
8-118 4.70e-09

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: 53.21  E-value: 4.70e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983   8 YWDQWGRCvtCQRCGPGQELSKDCgyGEGGDAYCTACPPRRYKSSWGHH-RCQSCITCAVINRVQKV-NCTATSNAVCGd 85
Cdd:cd15835   13 YNDGSNLC--CSKCRPGTRLKTKC--SETSDTVCEPCPSGQYSENWNYYpNCFSCPKCKERKGLQYAqNCSSTTNAVCV- 87
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 768037983  86 CLPRFYrktRIGGLQDQECIPCTKQ-------------TPTSEVQC 118
Cdd:cd15835   88 CKPGMY---CIMGFDHPSCSECKKYrtckpgygvsvpgTPTSDVKC 130
TNFRSF1A_teleost cd15834
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) in teleosts; also known as ...
3-113 7.07e-09

Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) in teleosts; also known as TNFR1; This subfamily of TNFRSF1 ((also known as type I TNFR, TNFR1, DR1, TNFRSF1A, CD120a, p55) is found in teleosts. It binds TNF-alpha, through the death domain (DD), and activates NF-kappaB, mediates apoptosis and activates signaling pathways controlling inflammatory, immune, and stress responses. It mediates signal transduction by interacting with antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRAF2 and TRADD that play regulatory roles. The human genetic disorder called tumor necrosis factor associated periodic syndrome (TRAPS), or periodic fever syndrome, is associated with germline mutations of the extracellular domains of this receptor, possibly due to impaired receptor clearance. Serum levels of TNFRSF1A are elevated in schizophrenia and bipolar disorder, and high levels are also associated with cognitive impairment and dementia. Knockout studies in zebrafish embryos have shown that a signaling balance between TNFRSF1A and TNFRSF1B is required for endothelial cell integrity. TNFRSF1A signals apoptosis through caspase-8, whereas TNFRSF1B signals survival via NF-kappaB in endothelial cells. Thus, this apoptotic pathway seems to be evolutionarily conserved, as TNFalpha promotes apoptosis of human endothelial cells and triggers caspase-2 and P53 activation in these cells via TNFRSF1A.


Pssm-ID: 276930 [Multi-domain]  Cd Length: 150  Bit Score: 53.26  E-value: 7.07e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983   3 CQENEYWDQWGRCvtCQRCGPGQELSKDCgYGEGGDAYCTACPPRRYKSSWGHH-RCQSCITCAVINRVQKVNCTATSNA 81
Cdd:cd15834    1 CLDSEYLSENGIC--CNKCHPGYKLKEEC-TAPGERSQCTPCPEGTYLEQINYSpNCRRCTLCKVKNEEEVSPCKKSSNT 77
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 768037983  82 VCgDCLPRFYRKT-----------RIGGLQDQECIPCTKQTPT 113
Cdd:cd15834   78 VC-RCKKGYYKSRidsetreclkcKTCGPGEIEIQPCTPESNT 119
TNFRSF_EDAR cd13421
Tumor necrosis factor receptor superfamily member ectodysplasin A receptor (EDAR); ...
2-91 8.51e-09

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: 52.57  E-value: 8.51e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983   2 DCQENEYWDQW-GRCVTCQRCGPGQELSKDCGYGEGGDAY-CTACPPRRYkSSWGHHRCQSCITCAVINRVQKVN-CTAT 78
Cdd:cd13421   18 NCGENEYYNQTtGLCQQCPPCRPGEEPYMSCGYGTKDEDYgCVPCPAEKF-SKGGYQICRRHKDCEGFFRATVLTpGDME 96
                         90
                 ....*....|...
gi 768037983  79 SNAVCGDCLPRFY 91
Cdd:cd13421   97 NDAECGPCLPGYY 109
TNFRSF6B cd10575
Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B), also known as decoy receptor ...
13-119 1.07e-07

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: 50.10  E-value: 1.07e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983  13 GRCVTCQRCGPGQELSKDCGYGEGGDayCTACPPRRYKSSWGH-HRCQSCITCAVINRVQKVNCTATSNAVCGdCLPRFY 91
Cdd:cd10575   11 GESLTCDQCPPGTFVAKHCTRDRPTV--CGPCPDLHYTQFWNYlEKCRYCNVFCTERQVEKRQCNATHNRVCE-CKPGYY 87
                         90       100       110
                 ....*....|....*....|....*....|..
gi 768037983  92 RKTRIgGLQDQECIP----CTKQTPTSEVQCA 119
Cdd:cd10575   88 MEHGF-CLRHSSCPPgegvIKLGTPYSDTQCE 118
TNFRSF9_teleost cd13424
Tumor necrosis factor receptor superfamily member 9 (TNFRSF9) in teleosts; also known as CD137; ...
16-84 5.70e-06

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: 45.21  E-value: 5.70e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768037983  16 VTCQRCGPGQELSKDCGYGEggDAYCTACPPRRYKSSWGHHRCQSCITCaVINRVQKVNCTATSNAVCG 84
Cdd:cd13424   12 VCCESCHPGNRLVERCGPDP--AELCKPCEPGTYTVKPLDYSCYICTQC-IGAQVLLKNCTPSSDTVCG 77
TNFRSF7 cd13408
Tumor necrosis factor receptor superfamily member 7 (TNFRSF7), also known as CD27; TNFRSF7 ...
3-84 6.60e-06

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: 44.41  E-value: 6.60e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983   3 CQENEYWDQWGRCvtCQRCGPGQELSKDCGyGEGGDAYCTACPPRRYKSSWGHHR--CQSCITCAVINRVQkvNCTATSN 80
Cdd:cd13408   24 CPERHYWAQGKLC--CQMCEPGTFLVKDCD-QHGKAAQCDPCIPGVSFSPDHHARphCESCRHCNSGLLIR--NCTITAN 98

                 ....
gi 768037983  81 AVCG 84
Cdd:cd13408   99 TECA 102
TNFRSF3 cd10578
Tumor necrosis factor receptor superfamily member 3 (TNFRSF3), also known as lymphotoxin beta ...
3-107 9.15e-06

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: 44.76  E-value: 9.15e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983   3 CQENEYWDQWGRcVTCQRCGPGQELSKDCGYGEggDAYCTACPPRRYKSSWGH-HRCQSCITC-AVINRVQKVNCTATSN 80
Cdd:cd10578   35 DQEKEYYEPRHQ-VCCSRCPPGTHVSAECSRSQ--DTVCATCPENSYNEHWNHlSICQLCRPCdPVLGFEEVAPCTSDRK 111
                         90       100
                 ....*....|....*....|....*..
gi 768037983  81 AVCGdCLPRFYrktriGGLQDQECIPC 107
Cdd:cd10578  112 TQCR-CQPGMF-----CVHWDNECEHC 132
TNFR_c6 pfam00020
TNFR/NGFR cysteine-rich region;
44-83 1.15e-05

TNFR/NGFR cysteine-rich region;


Pssm-ID: 459633 [Multi-domain]  Cd Length: 39  Bit Score: 41.53  E-value: 1.15e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 768037983   44 CPPRRYKSSWGHHRCQSCITCAViNRVQKVNCTATSNAVC 83
Cdd:pfam00020   1 CPPGTYTDNWNGLKCLPCTVCPP-GQVVVRPCTPTSDTVC 39
TNFRSF16 cd13416
Tumor necrosis factor receptor superfamily member 16 (TNFRSF16), also known as p75 ...
2-83 2.05e-05

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: 43.44  E-value: 2.05e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983   2 DCQENEYWDQW-GRCVTCQRCGPGQELSKDCgyGEGGDAYCTACPPRRY---KSSWghHRCQSCITCAViNRVQKVNCTA 77
Cdd:cd13416   79 ECAYGYYLDEDsGTCEPCTVCPPGQGVVQSC--GPNQDTVCEACPEGTYsdeDSST--DPCLPCTVCED-GEVELRECTP 153

                 ....*.
gi 768037983  78 TSNAVC 83
Cdd:cd13416  154 VSDTVC 159
TNFRSF9 cd13410
Tumor necrosis factor receptor superfamily member 9 (TNFRSF9), also known as CD137; TNFRSF9 ...
41-90 3.87e-05

Tumor necrosis factor receptor superfamily member 9 (TNFRSF9), also known as CD137; TNFRSF9 (also known as CD137, ILA, 4-1BB) plays a role in the immunobiology of human cancer where it is preferentially expressed on tumor-reactive subset of tumor-infiltrating lymphocytes. It can be expressed by activated T cells, but to a larger extent on CD8 than on CD4 T cells. In addition, CD137 expression is found on dendritic cells, follicular dendritic cells, natural killer cells, granulocytes and cells of blood vessel walls at sites of inflammation. It transduces signals that lead to the activation of NF-kappaB, mediated by the TRAF adaptor proteins. CD137 contributes to the clonal expansion, survival, and development of T cells. It can also induce proliferation in peripheral monocytes, enhance T cell apoptosis induced by TCR/CD3 triggered activation, and regulate CD28 co-stimulation to promote Th1 cell responses. CD137 is modulated by SAHA treatment in breast cancer cells, suggesting that the combination of SAHA with this receptor could be a new therapeutic approach for the treatment of tumors.


Pssm-ID: 276915 [Multi-domain]  Cd Length: 138  Bit Score: 42.41  E-value: 3.87e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 768037983  41 CTACPPRRYKSSWGHHRCQSCITCAVINRVQKVnCTATSNAVCGdCLPRF 90
Cdd:cd13410   23 CIPCPPNSFSSTGGQQTCDICRKCEGVFRTKKP-CSSTSNAECE-CVPGF 70
TNFRSF1A cd10576
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), also known as TNFR1; TNFRSF1A ...
18-113 6.67e-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: 41.57  E-value: 6.67e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983  18 CQRCGPGQELSKDCGyGEGGDAYCTACPPRRYKSSWGHH-RCQSCITC-AVINRVQKVNCTATSNAVCGdCLPRFYRKTR 95
Cdd:cd10576   15 CTKCHKGTYLYNDCP-GPGQDTVCRECENGTFTASENYLrKCLSCSRCrKEMGQVEISPCTVDQDTVCG-CRKNQYQHYW 92
                         90
                 ....*....|....*...
gi 768037983  96 IGGLQDQECIPCTKQTPT 113
Cdd:cd10576   93 SSLFQCKNCSLCLNGTIR 110
TNFRSF16 cd13416
Tumor necrosis factor receptor superfamily member 16 (TNFRSF16), also known as p75 ...
13-109 2.64e-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: 40.36  E-value: 2.64e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983  13 GRCvtCQRCGPGQELSKDCGygeGGDAYCTACPP-RRYKSSWGH-HRCQSCITCaVINRVQKVNCTATSNAVCgDCLPRF 90
Cdd:cd13416   12 GEC--CEQCPPGEGVARPCG---DNQTVCEPCLDgVTFSDVVSHtEPCQPCTRC-PGLMSMRAPCTATHDTVC-ECAYGY 84
                         90
                 ....*....|....*....
gi 768037983  91 YRktrigGLQDQECIPCTK 109
Cdd:cd13416   85 YL-----DEDSGTCEPCTV 98
TNFRSF11B_teleost cd13412
Tumor necrosis factor receptor superfamily 11B (TNFRSF11B) in teleost; also known as ...
13-83 3.88e-04

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: 39.39  E-value: 3.88e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 768037983  13 GRCVTCQRCGPGQELSKDCGYGEggDAYCTACPPRRYKSSWGH-HRCQSCITCAVINRVQKVNCTATSNAVC 83
Cdd:cd13412   17 GKILTCKKCPPGTHMAAHCTATT--QTKCLPCPAAHYTELWNYlPRCLYCNNFCSENQEVEIECSATNNRVC 86
TNFRSF_viral cd15839
Tumor necrosis factor receptor superfamily members, virus-encoded; This family contains viral ...
3-110 5.72e-04

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: 38.70  E-value: 5.72e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983   3 CQENEY-WDQWGRCvtCQRCGPGQELSKDCGygEGGDAYCTACPPRRYKSSWGHH-RCQSCITCAVINRVQKVNCTATSN 80
Cdd:cd15839    1 CNGNDYnSNSNNLC--CKSCPPGTYASHLCD--TTSNTKCDPCPSDTFTSIPNHIpACLSCRGRCSSNQVETKSCSNTQN 76
                         90       100       110
                 ....*....|....*....|....*....|
gi 768037983  81 AVCgDCLPRFYRKTRiGGLQDQECIPCTKQ 110
Cdd:cd15839   77 RIC-SCAPGYYCLLK-GSDGCVACAPKTKC 104
TNFRSF1B cd10577
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B), also known as TNFR2; TNFRSF1B ...
3-119 7.75e-04

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: 39.00  E-value: 7.75e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983   3 CQEN-EYWDQ-WGRCvtCQRCGPGQELSKDCGygEGGDAYCTACPPRRYKSSWGHHR-CQSCITCAVINRVQKVNCTATS 79
Cdd:cd10577    1 CRNSkEYYDEkAQMC--CSKCPPGQHVKHSCT--KTSDTVCAPCEESTYTQLWNWVPeCLSCSSPCSSDQVETQACTRQQ 76
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 768037983  80 NAVCGdCLPRFYrktRIGGLQD--QECIPCTK----------QTPTSEVQCA 119
Cdd:cd10577   77 NRICS-CKPGWY---CVLKLQEgcRQCRPLKKcgpgfgvarpGTASSDVECK 124
TNFR smart00208
Tumor necrosis factor receptor / nerve growth factor receptor repeats; Repeats in growth ...
44-83 1.47e-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: 35.52  E-value: 1.47e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 768037983    44 CPPRRYKSSWGHHRCQSCITCAVINRVqKVNCTATSNAVC 83
Cdd:smart00208   1 CKEGTYCSDGNHSSCLRCRRCPPGLVV-KQPCTATSDTVC 39
TNFRSF4 cd13406
Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as CD134 or OXO40; ...
1-85 2.26e-03

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: 37.38  E-value: 2.26e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983   1 MDCQENEYwDQWGRCvtCQRCGPGQELSKDCGYGEggDAYCTACPPRRYKSSWGHHRCQSCITCAVIN-RVQKVNCTATS 79
Cdd:cd13406    1 LHCVGDTY-PSGEKC--CHECPPGEGMESRCTGTQ--DTVCSPCEPGFYNEAVNYEPCKPCTQCNQRSgSEEKQKCTKTS 75

                 ....*.
gi 768037983  80 NAVCGD 85
Cdd:cd13406   76 DTVCRC 81
TNFRSF1B cd10577
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B), also known as TNFR2; TNFRSF1B ...
2-88 4.29e-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: 37.07  E-value: 4.29e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983   2 DCQENEY---WDQWGRCVTCQ-RCGPGQELSKDCGYGEggDAYCTaCPPRRYKSSWGHHRCQSCI---TCAVINRVQKVN 74
Cdd:cd10577   39 PCEESTYtqlWNWVPECLSCSsPCSSDQVETQACTRQQ--NRICS-CKPGWYCVLKLQEGCRQCRplkKCGPGFGVARPG 115
                         90
                 ....*....|....
gi 768037983  75 cTATSNAVCGDCLP 88
Cdd:cd10577  116 -TASSDVECKPCAP 128
TNFR_c6 pfam00020
TNFR/NGFR cysteine-rich region;
3-31 7.32e-03

TNFR/NGFR cysteine-rich region;


Pssm-ID: 459633 [Multi-domain]  Cd Length: 39  Bit Score: 33.44  E-value: 7.32e-03
                          10        20        30
                  ....*....|....*....|....*....|.
gi 768037983    3 CQENEYWDQWG--RCVTCQRCGPGQELSKDC 31
Cdd:pfam00020   1 CPPGTYTDNWNglKCLPCTVCPPGQVVVRPC 31
TNFRSF14_teleost cd13405
Tumor necrosis factor receptor superfamily member 14 (TNFRSF14) in teleost; also known as ...
13-91 8.57e-03

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: 34.99  E-value: 8.57e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983  13 GRCvtCQRCGPGQELSKDCGygEGGDAYCTACPPRRYKS-SWGHHRCQSCITC-AVINRVQKVNCTATSNAVCgDCLPRF 90
Cdd:cd13405   10 GEC--CPMCPPGSRVSRHCT--EDTSTSCVPCPDGTYMDePNGLEKCFPCTNCdPGFGLRVKQGCTYTSDTVC-EPLEGF 84

                 .
gi 768037983  91 Y 91
Cdd:cd13405   85 Y 85
TNFRSF21 cd10583
Tumor necrosis factor receptor superfamily member 21 (TNFRSF21), also known as death receptor ...
16-118 9.06e-03

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: 35.88  E-value: 9.06e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983  16 VTCQRCGPGQELSKDCGygEGGDAYCTACPPRRY-KSSWGHHRCQSCITCAVINRVQKVNCTATSNAVCgDCLPRFYrkt 94
Cdd:cd10583   13 LTCDKCPAGTYVSKHCT--ETSLRECSPCPNGTFtRHENGIEQCHRCRKPCPAPMIEKTPCTALTDREC-TCPPGTF--- 86
                         90       100       110
                 ....*....|....*....|....*....|....
gi 768037983  95 riggLQDQECIPCT----------KQTPTSEVQC 118
Cdd:cd10583   87 ----LSNDTCVPHSvcpvgwgvrkKGTETEDVRC 116
TNFRSF5 cd13407
Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40; TNFRSF5 ...
3-107 9.24e-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: 35.84  E-value: 9.24e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983   3 CQENEYWDQwGRCvtCQRCGPGQELSKDCgyGEGGDAYCTACPPRRYKSSWghHRCQSCITCAVIN-----RVQKvNCTA 77
Cdd:cd13407    1 CREKQYLHN-GRC--CSLCPPGQKLVSDC--TEATDTECLPCEEGEFQDTW--NRERHCHQHRYCDpnlglRVQT-EGTA 72
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 768037983  78 TSNAVCG-------------------DCLPRFYRKTRIGGLQDQECIPC 107
Cdd:cd13407   73 ETDTTCTcqegqhctseacetcalhtSCKPGFGVKQIATGVSDTICEPC 121
TNFRSF11B cd10581
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B), also known as ...
14-91 9.47e-03

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: 35.52  E-value: 9.47e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768037983  14 RCVTCQRCGPGQELSKDCGYGEggDAYCTACPPRRYKSSW-GHHRCQSCIT-CAVINRVqKVNCTATSNAVCgDCLPRFY 91
Cdd:cd10581   32 RQLMCDQCPPGTYVKQHCSASR--KTVCAPCPDHHYADDWnSNDECQYCNTvCKELQYV-KQECNSTHNRVC-ECVEGRY 107
 
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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