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Conserved domains on  [gi|1074585809|emb|SBP27778|]
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SRC kinase signaling inhibitor 1, partial [Iconisemion striatum]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
TNFRSF16 cd13416
Tumor necrosis factor receptor superfamily member 16 (TNFRSF16), also known as p75 ...
1136-1295 6.04e-79

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: 257.23  E-value: 6.04e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1136 DCVSGHYTDSGECCLECPTGEGVVKECGATQTVCAQCLDSETFSENDSHTEKCKPCTQCTGLMRMETPCTDSNDARCVCN 1215
Cdd:cd13416      2 ACPSGQYTSSGECCEQCPPGEGVARPCGDNQTVCEPCLDGVTFSDVVSHTEPCQPCTRCPGLMSMRAPCTATHDTVCECA 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1216 YNYYYNKLSGQCELCTVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTICDEelDETLIAECTPNSDSVC 1295
Cdd:cd13416     82 YGYYLDEDSGTCEPCTVCPPGQGVVQSCGPNQDTVCEACPEGTYSDEDSSTDPCLPCTVCED--GEVELRECTPVSDTVC 159
TNFR_16_TM pfam18422
Tumor necrosis factor receptor member 16 trans-membrane domain; This is the helical ...
1345-1382 1.75e-17

Tumor necrosis factor receptor member 16 trans-membrane domain; This is the helical trans-membrane domain found in tumor necrosis factor receptor superfamily member 16 (also known as p75 neurotrophin receptor, and nerve growth factor receptor-NGFR). p75 plays prominent biological functions such the induction of cell death, and it demonstrates several other activities, like survival, axonal growth, and cell migration. The trans-membrane (TM) domain of p75 stabilizes the receptor dimers through a disulfide bond, essential for the NGF signalling Structural and mutational analysis indicate that Cys257 plays the key role in this stabilization process. Furthermore, although the p75-C257A mutant is still capable to form dimers and bind to NGF, it is unable to transduce the signals triggered by NGF binding in some cell signalling paradigms.


:

Pssm-ID: 436489  Cd Length: 38  Bit Score: 77.16  E-value: 1.75e-17
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1074585809 1345 GLNENLIPIYCSILAAVVVGLVAYIVFKRWNSCKQNKQ 1382
Cdd:pfam18422    1 GTSDNLIPVYCSILAAVVLGLVAYIAFKRWNSCKQNKQ 38
EnvC super family cl34844
Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, ...
564-747 2.29e-06

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];


The actual alignment was detected with superfamily member COG4942:

Pssm-ID: 443969 [Multi-domain]  Cd Length: 377  Bit Score: 51.69  E-value: 2.29e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  564 LQNLQQNTNALRKQLSQLRNIQLENQDSVLSLLR--QTESELSLMMLdaMRPQEDPLQRQRLLveeERLKYLNQEelLIQ 641
Cdd:COG4942     78 LAALEAELAELEKEIAELRAELEAQKEELAELLRalYRLGRQPPLAL--LLSPEDFLDAVRRL---QYLKYLAPA--RRE 150
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  642 QLHDLEKSVEELQRnssinhglvTEQDVDQKSKELRmlgETLTELKNQFPSLQSKMRVVLRVEVEAVKFLKEEPHRLEAL 721
Cdd:COG4942    151 QAEELRADLAELAA---------LRAELEAERAELE---ALLAELEEERAALEALKAERQKLLARLEKELAELAAELAEL 218
                          170       180
                   ....*....|....*....|....*.
gi 1074585809  722 LKRCNTMTDALSSLRRQVTEGVWKTP 747
Cdd:COG4942    219 QQEAEELEALIARLEAEAAAAAERTP 244
AIP3 super family cl38141
Actin interacting protein 3;
92-163 6.40e-06

Actin interacting protein 3;


The actual alignment was detected with superfamily member pfam03915:

Pssm-ID: 427585 [Multi-domain]  Cd Length: 407  Bit Score: 50.22  E-value: 6.40e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1074585809   92 FLQLGEEIRRVHLTHELTsLETLRALIVHMFPQrltmamlrSPSTALL----IKDETRNIFYELEDPRDVQDRCVI 163
Cdd:pfam03915    1 FLQLGRKVKKVVLPLPLT-IASLRLLFVEKFAY--------SPGGDDFpeiyIQDPVSGVRYELEDLSDVKDGSVL 67
sbcc super family cl31020
exonuclease SbcC; All proteins in this family for which functions are known are part of an ...
486-864 1.57e-03

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]


The actual alignment was detected with superfamily member TIGR00618:

Pssm-ID: 129705 [Multi-domain]  Cd Length: 1042  Bit Score: 43.03  E-value: 1.57e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  486 ETRERMEAMEKQIASLTGLLQRV----LTRAPEADSPEKMESASDGSAADPlTPSAPLALMPPPSLGSSQPITVSRMQMQ 561
Cdd:TIGR00618  463 ESAQSLKEREQQLQTKEQIHLQEtrkkAVVLARLLELQEEPCPLCGSCIHP-NPARQDIDNPGPLTRRMQRGEQTYAQLE 541
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  562 LHLQNLQQNTNALRKQLSQLRN-IQLENQDsvLSLLRQTESELSLMMLDAMRPQEDPLQRQRLLVEEERLKYLNQEELLI 640
Cdd:TIGR00618  542 TSEEDVYHQLTSERKQRASLKEqMQEIQQS--FSILTQCDNRSKEDIPNLQNITVRLQDLTEKLSEAEDMLACEQHALLR 619
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  641 Q---QLHDLEKSVEELQRnssinhglvtEQDVDQKSKELRMLGETLTELKNQFPSLQSKMRVVLRVEVEAVKfLKEEPHR 717
Cdd:TIGR00618  620 KlqpEQDLQDVRLHLQQC----------SQELALKLTALHALQLTLTQERVREHALSIRVLPKELLASRQLA-LQKMQSE 688
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  718 LEALLKRCNTMTDALSSLRRQVT--EGVWKTPEDIYSQTQKRPEDLsrSSDLDILNSPPLSLADL-------STSAGLAN 788
Cdd:TIGR00618  689 KEQLTYWKEMLAQCQTLLRELEThiEEYDREFNEIENASSSLGSDL--AAREDALNQSLKELMHQartvlkaRTEAHFNN 766
                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1074585809  789 WIPVSSEVNTSGPEQDVQSSMAFRNRVLDElpsRRPAEKAVSAEVRLAAERDWEEKRAS---LTQFSAQDINRLLEETQ 864
Cdd:TIGR00618  767 NEEVTAALQTGAELSHLAAEIQFFNRLREE---DTHLLKTLEAEIGQEIPSDEDILNLQcetLVQEEEQFLSRLEEKSA 842
 
Name Accession Description Interval E-value
TNFRSF16 cd13416
Tumor necrosis factor receptor superfamily member 16 (TNFRSF16), also known as p75 ...
1136-1295 6.04e-79

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: 257.23  E-value: 6.04e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1136 DCVSGHYTDSGECCLECPTGEGVVKECGATQTVCAQCLDSETFSENDSHTEKCKPCTQCTGLMRMETPCTDSNDARCVCN 1215
Cdd:cd13416      2 ACPSGQYTSSGECCEQCPPGEGVARPCGDNQTVCEPCLDGVTFSDVVSHTEPCQPCTRCPGLMSMRAPCTATHDTVCECA 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1216 YNYYYNKLSGQCELCTVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTICDEelDETLIAECTPNSDSVC 1295
Cdd:cd13416     82 YGYYLDEDSGTCEPCTVCPPGQGVVQSCGPNQDTVCEACPEGTYSDEDSSTDPCLPCTVCED--GEVELRECTPVSDTVC 159
TNFR_16_TM pfam18422
Tumor necrosis factor receptor member 16 trans-membrane domain; This is the helical ...
1345-1382 1.75e-17

Tumor necrosis factor receptor member 16 trans-membrane domain; This is the helical trans-membrane domain found in tumor necrosis factor receptor superfamily member 16 (also known as p75 neurotrophin receptor, and nerve growth factor receptor-NGFR). p75 plays prominent biological functions such the induction of cell death, and it demonstrates several other activities, like survival, axonal growth, and cell migration. The trans-membrane (TM) domain of p75 stabilizes the receptor dimers through a disulfide bond, essential for the NGF signalling Structural and mutational analysis indicate that Cys257 plays the key role in this stabilization process. Furthermore, although the p75-C257A mutant is still capable to form dimers and bind to NGF, it is unable to transduce the signals triggered by NGF binding in some cell signalling paradigms.


Pssm-ID: 436489  Cd Length: 38  Bit Score: 77.16  E-value: 1.75e-17
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1074585809 1345 GLNENLIPIYCSILAAVVVGLVAYIVFKRWNSCKQNKQ 1382
Cdd:pfam18422    1 GTSDNLIPVYCSILAAVVLGLVAYIAFKRWNSCKQNKQ 38
TNFR_c6 pfam00020
TNFR/NGFR cysteine-rich region;
1214-1251 6.54e-07

TNFR/NGFR cysteine-rich region;


Pssm-ID: 459633 [Multi-domain]  Cd Length: 39  Bit Score: 46.92  E-value: 6.54e-07
                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1074585809 1214 CNYNYYYNKLSG-QCELCTVCPVGQGVYTHCDHYHDTVC 1251
Cdd:pfam00020    1 CPPGTYTDNWNGlKCLPCTVCPPGQVVVRPCTPTSDTVC 39
EnvC COG4942
Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, ...
564-747 2.29e-06

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 443969 [Multi-domain]  Cd Length: 377  Bit Score: 51.69  E-value: 2.29e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  564 LQNLQQNTNALRKQLSQLRNIQLENQDSVLSLLR--QTESELSLMMLdaMRPQEDPLQRQRLLveeERLKYLNQEelLIQ 641
Cdd:COG4942     78 LAALEAELAELEKEIAELRAELEAQKEELAELLRalYRLGRQPPLAL--LLSPEDFLDAVRRL---QYLKYLAPA--RRE 150
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  642 QLHDLEKSVEELQRnssinhglvTEQDVDQKSKELRmlgETLTELKNQFPSLQSKMRVVLRVEVEAVKFLKEEPHRLEAL 721
Cdd:COG4942    151 QAEELRADLAELAA---------LRAELEAERAELE---ALLAELEEERAALEALKAERQKLLARLEKELAELAAELAEL 218
                          170       180
                   ....*....|....*....|....*.
gi 1074585809  722 LKRCNTMTDALSSLRRQVTEGVWKTP 747
Cdd:COG4942    219 QQEAEELEALIARLEAEAAAAAERTP 244
AIP3 pfam03915
Actin interacting protein 3;
92-163 6.40e-06

Actin interacting protein 3;


Pssm-ID: 427585 [Multi-domain]  Cd Length: 407  Bit Score: 50.22  E-value: 6.40e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1074585809   92 FLQLGEEIRRVHLTHELTsLETLRALIVHMFPQrltmamlrSPSTALL----IKDETRNIFYELEDPRDVQDRCVI 163
Cdd:pfam03915    1 FLQLGRKVKKVVLPLPLT-IASLRLLFVEKFAY--------SPGGDDFpeiyIQDPVSGVRYELEDLSDVKDGSVL 67
TNFR smart00208
Tumor necrosis factor receptor / nerve growth factor receptor repeats; Repeats in growth ...
1214-1251 1.71e-05

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: 43.23  E-value: 1.71e-05
                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 1074585809  1214 CNYNYYYNKLS-GQCELCTVCPVGQGVYTHCDHYHDTVC 1251
Cdd:smart00208    1 CKEGTYCSDGNhSSCLRCRRCPPGLVVKQPCTATSDTVC 39
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
559-741 4.12e-05

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 48.51  E-value: 4.12e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  559 QMQLHLQNLQQNTNALRKQLSQLRN-------------IQLENQDSVLSLLRQTESELSLMMldamrpqeDPLQRQRLLV 625
Cdd:TIGR02168  688 ELEEKIAELEKALAELRKELEELEEeleqlrkeleelsRQISALRKDLARLEAEVEQLEERI--------AQLSKELTEL 759
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  626 EEERLKYLNQEELLIQQLHDLEKSVEELQR---NSSINHGLVTEQdVDQKSKELRMLGETLTELKNQFPSLQSKMRVVLR 702
Cdd:TIGR02168  760 EAEIEELEERLEEAEEELAEAEAEIEELEAqieQLKEELKALREA-LDELRAELTLLNEEAANLRERLESLERRIAATER 838
                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1074585809  703 VEVEAVKFLKEEPHRLEALLKRCNTMTDALSSLRRQVTE 741
Cdd:TIGR02168  839 RLEDLEEQIEELSEDIESLAAEIEELEELIEELESELEA 877
MAP65_ASE1 pfam03999
Microtubule associated protein (MAP65/ASE1 family);
569-763 1.06e-04

Microtubule associated protein (MAP65/ASE1 family);


Pssm-ID: 427641 [Multi-domain]  Cd Length: 477  Bit Score: 46.53  E-value: 1.06e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  569 QNTNALRKQLSQLRNIQLENQDSVLSLLRQTeseLSLMMLDAMRPQEDPlqRQRLLVEEERLKYLNQEelLIQQLHDLEK 648
Cdd:pfam03999  143 EELESFRKHLENLRNEKERRLEEVNELKKQI---KLLMEELDLVPGTDF--EEDLLCESEDNFCLSRE--NIDKLRKLIK 215
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  649 SVEELqrnssinhglvteqdVDQKSKELRMLGETLTELKN--QFPSLQSKMRVVLRVE--VEAVKFLKEEPHRLEAlLKR 724
Cdd:pfam03999  216 QLEEQ---------------KAEREEKIDDLREKILELWNrlQVPQEEQESFVRENNSlsQDTIDALREELQRLEE-LKK 279
                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1074585809  725 CNtMTDALSSLRRQVTEgVWKTpediysqTQKRPEDLSR 763
Cdd:pfam03999  280 KN-IKKLIEDLRVEIEE-LWDK-------LFYSTEQRKR 309
AIP3 smart00806
Actin interacting protein 3; Aip3p/Bud6p is a regulator of cell and cytoskeletal polarity in ...
92-206 1.38e-04

Actin interacting protein 3; Aip3p/Bud6p is a regulator of cell and cytoskeletal polarity in Saccharomyces cerevisiae that was previously identified as an actin-interacting protein. Actin-interacting protein 3 (Aip3p) localizes at the cell cortex where cytoskeleton assembly must be achieved to execute polarized cell growth, and deletion of AIP3 causes gross defects in cell and cytoskeletal polarity. Aip3p localization is mediated by the secretory pathway, mutations in early- or late-acting components of the secretory apparatus lead to Aip3p mislocalization.


Pssm-ID: 214826 [Multi-domain]  Cd Length: 426  Bit Score: 46.20  E-value: 1.38e-04
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809    92 FLQLGEEIRRVHLTHELTsLETLRALIVHMFPQrltmamlrSPSTA----LLIKDETRNIFYELED--PRDVQDRCVIKI 165
Cdd:smart00806    1 FLRIGNKTKKVVVSSPLT-FNALRLLFIEKFAY--------SPGGDdfpdIYIQDPVSGVSYELEElsLHDIKDGSVLVL 71
                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*.
gi 1074585809   166 ycKEPVYGTYPGHHNPHLAngDLRREMVHAPQ--DSPN---RRLSN 206
Cdd:smart00806   72 --NVEELDEVKKHIDDEID--TLQNELDEVKQalESQReaiQRLKE 113
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
567-763 6.72e-04

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 44.28  E-value: 6.72e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  567 LQQNTNALRKQLSQLRNIQ--LENQDSVLSL------LRQTESELSLMMLDAMRPQEDPLQ-----------RQRLLVEE 627
Cdd:PRK03918   468 LKEIEEKERKLRKELRELEkvLKKESELIKLkelaeqLKELEEKLKKYNLEELEKKAEEYEklkekliklkgEIKSLKKE 547
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  628 -ERLKYLNQE-ELLIQQLHDLEKSVEELQRNSSiNHGLVTEQDVDQKSKELRMLGETLTELKNQFPSLQSKMRVVLRVEV 705
Cdd:PRK03918   548 lEKLEELKKKlAELEKKLDELEEELAELLKELE-ELGFESVEELEERLKELEPFYNEYLELKDAEKELEREEKELKKLEE 626
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1074585809  706 EAVKFLKEephrLEALLKRcntmtdaLSSLRRQVTEGVWKTPEDIYSQTQKRPEDLSR 763
Cdd:PRK03918   627 ELDKAFEE----LAETEKR-------LEELRKELEELEKKYSEEEYEELREEYLELSR 673
sbcc TIGR00618
exonuclease SbcC; All proteins in this family for which functions are known are part of an ...
486-864 1.57e-03

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]


Pssm-ID: 129705 [Multi-domain]  Cd Length: 1042  Bit Score: 43.03  E-value: 1.57e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  486 ETRERMEAMEKQIASLTGLLQRV----LTRAPEADSPEKMESASDGSAADPlTPSAPLALMPPPSLGSSQPITVSRMQMQ 561
Cdd:TIGR00618  463 ESAQSLKEREQQLQTKEQIHLQEtrkkAVVLARLLELQEEPCPLCGSCIHP-NPARQDIDNPGPLTRRMQRGEQTYAQLE 541
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  562 LHLQNLQQNTNALRKQLSQLRN-IQLENQDsvLSLLRQTESELSLMMLDAMRPQEDPLQRQRLLVEEERLKYLNQEELLI 640
Cdd:TIGR00618  542 TSEEDVYHQLTSERKQRASLKEqMQEIQQS--FSILTQCDNRSKEDIPNLQNITVRLQDLTEKLSEAEDMLACEQHALLR 619
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  641 Q---QLHDLEKSVEELQRnssinhglvtEQDVDQKSKELRMLGETLTELKNQFPSLQSKMRVVLRVEVEAVKfLKEEPHR 717
Cdd:TIGR00618  620 KlqpEQDLQDVRLHLQQC----------SQELALKLTALHALQLTLTQERVREHALSIRVLPKELLASRQLA-LQKMQSE 688
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  718 LEALLKRCNTMTDALSSLRRQVT--EGVWKTPEDIYSQTQKRPEDLsrSSDLDILNSPPLSLADL-------STSAGLAN 788
Cdd:TIGR00618  689 KEQLTYWKEMLAQCQTLLRELEThiEEYDREFNEIENASSSLGSDL--AAREDALNQSLKELMHQartvlkaRTEAHFNN 766
                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1074585809  789 WIPVSSEVNTSGPEQDVQSSMAFRNRVLDElpsRRPAEKAVSAEVRLAAERDWEEKRAS---LTQFSAQDINRLLEETQ 864
Cdd:TIGR00618  767 NEEVTAALQTGAELSHLAAEIQFFNRLREE---DTHLLKTLEAEIGQEIPSDEDILNLQcetLVQEEEQFLSRLEEKSA 842
 
Name Accession Description Interval E-value
TNFRSF16 cd13416
Tumor necrosis factor receptor superfamily member 16 (TNFRSF16), also known as p75 ...
1136-1295 6.04e-79

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: 257.23  E-value: 6.04e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1136 DCVSGHYTDSGECCLECPTGEGVVKECGATQTVCAQCLDSETFSENDSHTEKCKPCTQCTGLMRMETPCTDSNDARCVCN 1215
Cdd:cd13416      2 ACPSGQYTSSGECCEQCPPGEGVARPCGDNQTVCEPCLDGVTFSDVVSHTEPCQPCTRCPGLMSMRAPCTATHDTVCECA 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1216 YNYYYNKLSGQCELCTVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTICDEelDETLIAECTPNSDSVC 1295
Cdd:cd13416     82 YGYYLDEDSGTCEPCTVCPPGQGVVQSCGPNQDTVCEACPEGTYSDEDSSTDPCLPCTVCED--GEVELRECTPVSDTVC 159
TNFRSF5 cd13407
Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), also known as CD40; TNFRSF5 ...
1137-1295 9.69e-21

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: 90.54  E-value: 9.69e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1137 CVSGHYTDSGECCLECPTGEGVVKEC-GATQTVCAQCLDSEtFSENDSHTEKCKPCTQC---TGLmRMETPCTDSNDARC 1212
Cdd:cd13407      1 CREKQYLHNGRCCSLCPPGQKLVSDCtEATDTECLPCEEGE-FQDTWNRERHCHQHRYCdpnLGL-RVQTEGTAETDTTC 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1213 VCNYNYYYNklSGQCELC---TVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTICdEELDETLIAECTP 1289
Cdd:cd13407     79 TCQEGQHCT--SEACETCalhTSCKPGFGVKQIATGVSDTICEPCPVGFFSNVSSAFEKCHPWTSC-ETKGLVELQAGTN 155

                   ....*.
gi 1074585809 1290 NSDSVC 1295
Cdd:cd13407    156 KTDVVC 161
TNFRSF5_teleost cd13422
Tumor necrosis factor receptor superfamily member 5 (TNFRSF5) in teleosts; also known as CD40; ...
1141-1295 4.85e-19

Tumor necrosis factor receptor superfamily member 5 (TNFRSF5) in teleosts; also known as CD40; TNFRSF5 (commonly known as CD40 and also as CDW40, p50, Bp50) is widely expressed in diverse cell types including B lymphocytes, dendritic cells, platelets, monocytes, endothelial cells, and fibroblasts. It is essential in mediating a wide variety of immune and inflammatory responses, including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. Its natural immunomodulating ligand is CD40L, and a primary defect in the CD40/CD40L system is associated with X-linked hyper-IgM (XHIM) syndrome. It is also involved in tumorigenesis; CD40 expression is significantly higher in gastric carcinomas and it is associated with the lymphatic metastasis of cancer cells and their tumor node metastasis (TNM) classification. Upregulated levels of CD40/CD40L on B cells and T cells may play an important role in the immune pathogenesis of breast cancer. Consequently, the CD40/CD40L system serves as a link between tumorigenesis, atherosclerosis, and the immune system, and offers a potential target for drug therapy for related diseases, such as cancer, atherosclerosis, diabetes mellitus, and immunological rejection. Salmon CD40 and CD40L are widely expressed, particularly in immune tissues, and their importance for the immune response is indicated by their relatively high expression in salmon lymphoid organs and gills.


Pssm-ID: 276927 [Multi-domain]  Cd Length: 161  Bit Score: 85.56  E-value: 4.85e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1141 HYTDSGECCLECPTGEGVVKECGATQTVCAQCLDSETfseNDSHTEK--CKPCTQCTGLMRMETPCTDSNDARCVCNYNY 1218
Cdd:cd13422      6 QYEKDGECCKMCGPGTRMSSDSGCLDPQCQPCGEDEY---QDKYTKEnkCKRQPYCDPNKNFEISVNKSKTSRSVCKCKP 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1219 YYNKLSGQCELC---TVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTICDEelDETLIAECTPNSDSVC 1295
Cdd:cd13422     83 GFHCSSEECLTCvphTTCGPGQGVKSKGNHIRDTVCEECPDGTFSNNSSAEGVCKKWTECES--GYKVEAAGTNTSDNIC 160
TNFRSF1A_teleost cd15834
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) in teleosts; also known as ...
1137-1288 1.14e-18

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: 84.08  E-value: 1.14e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1137 CVSGHY-TDSGECCLECPTGEGVVKECGA--TQTVCAQClDSETFSENDSHTEKCKPCTQCTG-LMRMETPCTDSNDARC 1212
Cdd:cd15834      1 CLDSEYlSENGICCNKCHPGYKLKEECTApgERSQCTPC-PEGTYLEQINYSPNCRRCTLCKVkNEEEVSPCKKSSNTVC 79
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1074585809 1213 VCNYNYYYNKLSG---QCELCTVCPVGQGVYTHCDHYHDTVCeECLDETYSDRESslepCLPCTICDEELDEtliaECT 1288
Cdd:cd15834     80 RCKKGYYKSRIDSetrECLKCKTCGPGEIEIQPCTPESNTVC-ECKDNYYRNNNK----CKPCQKCSLDCQH----LCT 149
TNFRSF21 cd10583
Tumor necrosis factor receptor superfamily member 21 (TNFRSF21), also known as death receptor ...
1149-1295 1.51e-18

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: 84.03  E-value: 1.51e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1149 CLECPTGEGVVKECgaTQT---VCAQCLDSeTFSENDSHTEKCKPCTQ-CTGLMRMETPCTDSNDARCVCNYNYYynKLS 1224
Cdd:cd10583     15 CDKCPAGTYVSKHC--TETslrECSPCPNG-TFTRHENGIEQCHRCRKpCPAPMIEKTPCTALTDRECTCPPGTF--LSN 89
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1074585809 1225 GQCELCTVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTICdEELDETLIAECTPNSDSVC 1295
Cdd:cd10583     90 DTCVPHSVCPVGWGVRKKGTETEDVRCKPCPRGTFSDVPSSVLKCKTYTDC-LGLGLVVIKPGTKETDNVC 159
TNFRSF cd00185
Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) ...
1148-1233 5.43e-18

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: 79.95  E-value: 5.43e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1148 CCLECPTGEGVVKECGATQ-TVCAQClDSETFSENDSHTEKCKPCTQCT-GLMRMETPCTDSNDARCVCNYNYYYNkLSG 1225
Cdd:cd00185      1 CCQRCPPGEYLSSDCTATTdTVCSPC-PPGTYSESWNSLSKCLPCTTCGgGNQVEKTPCTATDNRCCTCKPGFYCD-EGT 78

                   ....*...
gi 1074585809 1226 QCELCTVC 1233
Cdd:cd00185     79 NVEECKPC 86
TNFRSF14_teleost cd13405
Tumor necrosis factor receptor superfamily member 14 (TNFRSF14) in teleost; also known as ...
1225-1296 1.75e-17

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: 79.68  E-value: 1.75e-17
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1074585809 1225 GQCelCTVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTICDEELDETLIAECTPNSDSVCH 1296
Cdd:cd13405     10 GEC--CPMCPPGSRVSRHCTEDTSTSCVPCPDGTYMDEPNGLEKCFPCTNCDPGFGLRVKQGCTYTSDTVCE 79
TNFR_16_TM pfam18422
Tumor necrosis factor receptor member 16 trans-membrane domain; This is the helical ...
1345-1382 1.75e-17

Tumor necrosis factor receptor member 16 trans-membrane domain; This is the helical trans-membrane domain found in tumor necrosis factor receptor superfamily member 16 (also known as p75 neurotrophin receptor, and nerve growth factor receptor-NGFR). p75 plays prominent biological functions such the induction of cell death, and it demonstrates several other activities, like survival, axonal growth, and cell migration. The trans-membrane (TM) domain of p75 stabilizes the receptor dimers through a disulfide bond, essential for the NGF signalling Structural and mutational analysis indicate that Cys257 plays the key role in this stabilization process. Furthermore, although the p75-C257A mutant is still capable to form dimers and bind to NGF, it is unable to transduce the signals triggered by NGF binding in some cell signalling paradigms.


Pssm-ID: 436489  Cd Length: 38  Bit Score: 77.16  E-value: 1.75e-17
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1074585809 1345 GLNENLIPIYCSILAAVVVGLVAYIVFKRWNSCKQNKQ 1382
Cdd:pfam18422    1 GTSDNLIPVYCSILAAVVLGLVAYIAFKRWNSCKQNKQ 38
TNFRSF6B cd10575
Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B), also known as decoy receptor ...
1149-1284 7.39e-16

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: 76.68  E-value: 7.39e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1149 CLECPTGEGVVKECGAT-QTVCAQCLDSEtFSENDSHTEKCKPCTQ-CTGLMRMETPCTDSNDARCVCNYNYYYNklSGQ 1226
Cdd:cd10575     16 CDQCPPGTFVAKHCTRDrPTVCGPCPDLH-YTQFWNYLEKCRYCNVfCTERQVEKRQCNATHNRVCECKPGYYME--HGF 92
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1074585809 1227 CELCTVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTICDEELDETLI 1284
Cdd:cd10575     93 CLRHSSCPPGEGVIKLGTPYSDTQCEPCPPGFFSASSSSTEPCQPHTNCTQGGLETNV 150
TNFRSF cd00185
Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) ...
1230-1295 1.14e-15

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: 73.40  E-value: 1.14e-15
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1074585809 1230 CTVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTICDEElDETLIAECTPNSDSVC 1295
Cdd:cd00185      2 CQRCPPGEYLSSDCTATTDTVCSPCPPGTYSESWNSLSKCLPCTTCGGG-NQVEKTPCTATDNRCC 66
TNFRSF26 cd15837
Tumor necrosis factor receptor superfamily member 26 (TNFRSF26), also known as tumor necrosis ...
1137-1251 1.77e-15

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


Pssm-ID: 276933 [Multi-domain]  Cd Length: 118  Bit Score: 73.94  E-value: 1.77e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1137 CVSGHYTDSGECCLECPTGEGVVKEC--GATQTVCAQClDSETFSENDSHTEKCKPCTQCTGLMRMETPCTDSNDARCVC 1214
Cdd:cd15837      1 CGPGEYKSANLCCQLCPAGHYVSEPCqeNHGVGECAPC-EPGTFTAHPNGETSCFPCSQCRDDQEVVAECSATSDRQCQC 79
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1074585809 1215 NYNYYYNKLSG--QCELCTVCPVGQGVYTHCDHYHDTVC 1251
Cdd:cd15837     80 KQGHFYCDENCleSCFRCSRCPGGRVVLQPCNATRDTVC 118
TNFRSF1A cd10576
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), also known as TNFR1; TNFRSF1A ...
1137-1252 5.32e-15

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: 73.16  E-value: 5.32e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1137 CVSGHY--TDSGECCLECPTGEGVVKECGATQ--TVCAQClDSETFSENDSHTEKCKPCTQCTGLMRM--ETPCTDSNDA 1210
Cdd:cd10576      1 CPQGKYlhPNNNHCCTKCHKGTYLYNDCPGPGqdTVCREC-ENGTFTASENYLRKCLSCSRCRKEMGQveISPCTVDQDT 79
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1074585809 1211 RCVCNYNYYYNKLSG--QCELCTVCPVGQgVYTHCDHYHDTVCE 1252
Cdd:cd10576     80 VCGCRKNQYQHYWSSlfQCKNCSLCLNGT-IRQPCQEKQDTICT 122
TNFRSF14_teleost cd13405
Tumor necrosis factor receptor superfamily member 14 (TNFRSF14) in teleost; also known as ...
1137-1239 5.40e-15

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: 72.36  E-value: 5.40e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1137 CVSGHYTDSGECCLECPTGEGVVKEC-GATQTVCAQCLDSeTFSENDSHTEKCKPCTQCT---GLmRMETPCTDSNDARC 1212
Cdd:cd13405      1 CGPAEYEINGECCPMCPPGSRVSRHCtEDTSTSCVPCPDG-TYMDEPNGLEKCFPCTNCDpgfGL-RVKQGCTYTSDTVC 78
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1074585809 1213 VCNYNYY-YNKLSGQCELC---TVCPVGQGV 1239
Cdd:cd13405     79 EPLEGFYcIDSTKDGCSAAqrhSSCKPGQYI 109
TNFRSF6 cd10579
Tumor necrosis factor receptor superfamily member 6 (TNFRSF6), also known as fas cell surface ...
1137-1295 6.01e-15

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


Pssm-ID: 276905 [Multi-domain]  Cd Length: 129  Bit Score: 72.79  E-value: 6.01e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1137 CVSGHYTDSGECCLECPTGEGVVKECGAT--QTVCAQCLDSETFSENDSHTEKCKPCTQCTGL--MRMETPCTDSNDARC 1212
Cdd:cd10579     10 CSEGLYRGGQFCCQPCPPGTRKAIDCTTNggKPDCVPCTEGKEYTDKKHYSDKCRRCKICDEEhgLEVEKNCTRTQNTKC 89
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1213 VCNYNYYYNklSGQCElctvcpvgqgvytHCDhyhdtvceecldetysdresslepclPCTICDEELDEtliaECTPNSD 1292
Cdd:cd10579     90 RCKSNFFCN--SSPCE-------------HCD--------------------------PCTTCEHGIIE----ECTPTSN 124

                   ...
gi 1074585809 1293 SVC 1295
Cdd:cd10579    125 TKC 127
TNFRSF1B cd10577
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B), also known as TNFR2; TNFRSF1B ...
1148-1296 1.33e-14

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: 72.89  E-value: 1.33e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1148 CCLECPTGEGVVKECGAT-QTVCAQCLDSeTFSENDSHTEKCKPC-TQCT-GLMRMETpCTDSNDARCVCNYNYY-YNKL 1223
Cdd:cd10577     15 CCSKCPPGQHVKHSCTKTsDTVCAPCEES-TYTQLWNWVPECLSCsSPCSsDQVETQA-CTRQQNRICSCKPGWYcVLKL 92
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1074585809 1224 SGQCELCTV---CPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTICdeeldETLIAECTPNSDSVCH 1296
Cdd:cd10577     93 QEGCRQCRPlkkCGPGFGVARPGTASSDVECKPCAPGTFSDTTSSTDTCRPHRIC-----SSVAIPGNASMDAVCA 163
TNFRSF_viral cd15839
Tumor necrosis factor receptor superfamily members, virus-encoded; This family contains viral ...
1141-1254 2.05e-14

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: 71.44  E-value: 2.05e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1141 HYTDSGECCLECPTGEGVVKECGAT-QTVCAQClDSETFSENDSHTEKCKPCT-QCTGLMRMETPCTDSNDARCVCNYNY 1218
Cdd:cd15839      7 NSNSNNLCCKSCPPGTYASHLCDTTsNTKCDPC-PSDTFTSIPNHIPACLSCRgRCSSNQVETKSCSNTQNRICSCAPGY 85
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1074585809 1219 YYN-KLSGQCELC---TVCPVGQGVYTHcDHYHDTVCEEC 1254
Cdd:cd15839     86 YCLlKGSDGCVACapkTKCGVGYGVSGH-TSTGDVICKKC 124
TNFRSF6_teleost cd13423
Tumor necrosis factor receptor superfamily member 6 (TNFRSF6) in teleosts; also known as fas ...
1230-1295 2.90e-14

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: 70.15  E-value: 2.90e-14
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1074585809 1230 CTVCPVGQGVYTHC-DHYHDTVCEECLDETYSDRESSLEPCLPCTICDEELDETLIAECTPNSDSVC 1295
Cdd:cd13423     14 CCLCPAGQHVEKHCtNNGTDGECEACEDGTYNSHPNSLDSCEPCTSCDPNANLEVEERCTPSSDTVC 80
TNFRSF6_teleost cd13423
Tumor necrosis factor receptor superfamily member 6 (TNFRSF6) in teleosts; also known as fas ...
1136-1233 4.24e-14

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: 69.76  E-value: 4.24e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1136 DCVSGHYTDSG-ECCLeCPTGEGVVKEC--GATQTVCAQClDSETFSENDSHTEKCKPCTQCT--GLMRMETPCTDSNDA 1210
Cdd:cd13423      1 SCEDGTYQHEGlTCCL-CPAGQHVEKHCtnNGTDGECEAC-EDGTYNSHPNSLDSCEPCTSCDpnANLEVEERCTPSSDT 78
                           90       100
                   ....*....|....*....|...
gi 1074585809 1211 RCVCNYNYYYNKlSGQCELCTVC 1233
Cdd:cd13423     79 VCRCKEGHYCDK-GEECKVCYPC 100
TNFRSF11A cd13411
Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor ...
1139-1295 2.16e-13

Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A), also known as receptor activator of nuclear factor-kappaB (RANK); TNFRSF11A (also known as RANK, FEO, OFE, ODFR, OSTS, PDB2, CD26, OPTB7, TRANCER, LOH18CR1) induces the activation of NF-kappa B and MAPK8/JNK through interactions with various TRAF adaptor proteins. This receptor and its ligand are important regulators of the interaction between T cells and dendritic cells. The receptor is also an essential mediator for osteoclast and lymph node development. Mutations at this locus have been associated with familial expansile osteolysis, autosomal recessive osteopetrosis, and Juvenile Paget's disease (JPD) of bone. Alternatively spliced transcript variants have been described for this locus. Mutation analysis may improve diagnosis, prognostication, recurrence risk assessment, and perhaps treatment selection among the monogenic disorders of RANKL/OPG/RANK activation.


Pssm-ID: 276916 [Multi-domain]  Cd Length: 163  Bit Score: 69.43  E-value: 2.16e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1139 SGHYTDSGECCLECPTGEGVVKECGAT-QTVCAQCLDSETFSE-NDShtEKC---KPCTQCTGLMRMEtPCTDSNDARCV 1213
Cdd:cd13411      5 ERHYEYSGRCCSKCEPGKYMSSKCTVTsDSVCLPCGPDEYLDTwNEE--DKCllhKVCDAGKALVAVD-PGNSTAPRRCA 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1214 CNYNYYYNKlsgQCELC---TVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTICDEELDETLIAEcTPN 1290
Cdd:cd13411     82 CTAGYHWSE---DCDCCrrnTECAPGFGAQHPVQLNKDTVCEPCLVGYFSDVFSSTDKCKPWTNCTILGLEEAVPG-TNK 157

                   ....*
gi 1074585809 1291 SDSVC 1295
Cdd:cd13411    158 SDVVC 162
TNFRSF4 cd13406
Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as CD134 or OXO40; ...
1135-1214 2.66e-13

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: 68.58  E-value: 2.66e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1135 PDCVSGHYTDSGECCLECPTGEGVVKECGATQ-TVCAQClDSETFSENDSHtEKCKPCTQC---TGLMRmETPCTDSNDA 1210
Cdd:cd13406      1 LHCVGDTYPSGEKCCHECPPGEGMESRCTGTQdTVCSPC-EPGFYNEAVNY-EPCKPCTQCnqrSGSEE-KQKCTKTSDT 77

                   ....
gi 1074585809 1211 RCVC 1214
Cdd:cd13406     78 VCRC 81
TNFRSF1B_teleost cd15835
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) in teleost; also known as ...
1143-1239 2.89e-12

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: 65.15  E-value: 2.89e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1143 TDSGECCLECPTGEGVVKECGAT-QTVCAQClDSETFSENDSHTEKCKPCTQCT---GLMRMETpCTDSNDARCVCNYNY 1218
Cdd:cd15835     15 DGSNLCCSKCRPGTRLKTKCSETsDTVCEPC-PSGQYSENWNYYPNCFSCPKCKerkGLQYAQN-CSSTTNAVCVCKPGM 92
                           90       100
                   ....*....|....*....|....*.
gi 1074585809 1219 Y--YNKLSGQCELC---TVCPVGQGV 1239
Cdd:cd15835     93 YciMGFDHPSCSECkkyRTCKPGYGV 118
TNFRSF1B_teleost cd15835
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) in teleost; also known as ...
1208-1295 1.29e-10

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: 60.53  E-value: 1.29e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1208 NDARCVCNYNYYYNKLSGQCelCTVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTICDEELDETLIAEC 1287
Cdd:cd15835      1 SDGNCRNTTTEYYNDGSNLC--CSKCRPGTRLKTKCSETSDTVCEPCPSGQYSENWNYYPNCFSCPKCKERKGLQYAQNC 78

                   ....*...
gi 1074585809 1288 TPNSDSVC 1295
Cdd:cd15835     79 SSTTNAVC 86
TNFRSF4 cd13406
Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as CD134 or OXO40; ...
1230-1298 1.62e-10

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: 60.49  E-value: 1.62e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1074585809 1230 CTVCPVGQGVYTHCDHYHDTVCEECLDETYSDrESSLEPCLPCTICDEELDETLIAECTPNSDSVCHNP 1298
Cdd:cd13406     15 CHECPPGEGMESRCTGTQDTVCSPCEPGFYNE-AVNYEPCKPCTQCNQRSGSEEKQKCTKTSDTVCRCR 82
TNFRSF10 cd10580
Tumor necrosis factor receptor superfamily member 10 (TNFRSF10), includes TNFRSF10A (DR4), ...
1148-1252 4.50e-10

Tumor necrosis factor receptor superfamily member 10 (TNFRSF10), includes TNFRSF10A (DR4), TNFRSF10B (DR5), TNFRSF10C (DcR1) and TNFRSF10D (DcR2); TNFRSF10 family contains TNFRSF10A (also known as DR4, Apo2, TRAIL-R1, CD261), TNFRSF10B (also known as DR5, KILLER, TRICK2A, TRAIL-R2, TRICKB, CD262), TNFRSF10C (also known as DcR1, TRAIL-R3, LIT, TRID, CD263), and TNFRSF10D (also known as DcR2, TRUNDD, TRAIL-R4, CD264). Tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL) binds to all 4 receptors. DR4 (TRAIL-R1) and DR5 (TRAIL-R2) are membrane-bound and contain a death domain in their intracellular portion, which is able to transmit an apoptotic signal, thus often called death receptors. In contrast, DcR1 (TRAIL-R3), which lacks the complete intracellular portion and DcR2 (TRAIL-R4), which has a truncated cytoplasmic death domain, do not transmit an apoptotic signal, thus known as decoy receptors. Apoptosis mediated by DR4 and DR5 requires Fas (TNFRSF6)-associated via death domain (FADD), a death domain containing adaptor protein. Two transcript variants encoding different isoforms and one non-coding transcript have been found for TNFRSF10B/DR5. DcR1 appears to function as an antagonistic receptor that protects cells from TRAIL-induced apoptosis; it has been found to be a p53-regulated DNA damage-inducible gene. The expression of this gene is detected in many normal tissues but not in most cancer cell lines, which may explain the specific sensitivity of cancer cells to the apoptosis-inducing activity of TRAIL. DcR2 has been shown to play an inhibitory role in TRAIL-induced cell apoptosis. The membrane expression of all of these receptors (DR4, DR5, DcR1, and DcR2) is greater in normal endometrium (NE) than in endometrioid adenocarcinoma (EAC). In EAC patients, membrane expression of these receptors are not independent predictors of survival. DcR1 and DcR2 expression is critical in cell growth and apoptosis in cutaneous or uveal melanoma; DcR1 and DcR2 are frequently methylated in both, leading to loss of gene expression and melanomagenesis. On the other hand, DR4 and DR5 methylation is rare in cutaneous melanoma and frequent in uveal melanoma; their expression is wholly independent of the promoter methylation status. DcR1 and DcR2 genes are also reported to be hyper-methylated in prostate cancer. The TRAIL ligand, a potent and specific inducer of apoptosis in cancer cells, has been explored as a therapeutic drug; experimental data has shown that DR4 specific TRAIL variants are more efficacious than wild-type TRAIL in pancreatic cancer.


Pssm-ID: 276906 [Multi-domain]  Cd Length: 103  Bit Score: 58.04  E-value: 4.50e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1148 CCLECPTGEGVVKECGatqtVCAQCLDSETFSENDSHTEKCKPCTQCTGLMRMETPCTDSNDARCVCNYNYYYNKLSgqC 1227
Cdd:cd10580      1 SCGLCPAGTYVSEDSG----DCIPCKEGVDYTEHPNGLPSCLPCTVCKSDEEELSPCTTTRNTECQCKPGTFCDPDS--P 74
                           90       100
                   ....*....|....*....|....*....
gi 1074585809 1228 ELC----TVCPVGQGVYTHCDHYHDTVCE 1252
Cdd:cd10580     75 EVCqkcsTRCPEGMVEVSPCTPWSDLKCV 103
TNFRSF26 cd15837
Tumor necrosis factor receptor superfamily member 26 (TNFRSF26), also known as tumor necrosis ...
1214-1295 1.06e-09

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


Pssm-ID: 276933 [Multi-domain]  Cd Length: 118  Bit Score: 57.38  E-value: 1.06e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1214 CNYNYYynKLSGQCelCTVCPVGQGVYTHCD-HYHDTVCEECLDETYSDRESSLEPCLPCTICDEelDETLIAECTPNSD 1292
Cdd:cd15837      1 CGPGEY--KSANLC--CQLCPAGHYVSEPCQeNHGVGECAPCEPGTFTAHPNGETSCFPCSQCRD--DQEVVAECSATSD 74

                   ...
gi 1074585809 1293 SVC 1295
Cdd:cd15837     75 RQC 77
TNFRSF1A cd10576
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), also known as TNFR1; TNFRSF1A ...
1214-1295 1.22e-09

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: 57.75  E-value: 1.22e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1214 CNYNYYYNKLSGQCelCTVCPVGQGVYTHCDHY-HDTVCEECLDETYSDRESSLEPCLPCTICDEELDETLIAECTPNSD 1292
Cdd:cd10576      1 CPQGKYLHPNNNHC--CTKCHKGTYLYNDCPGPgQDTVCRECENGTFTASENYLRKCLSCSRCRKEMGQVEISPCTVDQD 78

                   ...
gi 1074585809 1293 SVC 1295
Cdd:cd10576     79 TVC 81
TNFRSF11A_teleost cd15836
Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) in teleost; also known as ...
1214-1277 3.90e-09

Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) in teleost; also known as RANK; TNFRSF11A (also known as RANK, FEO, OFE, ODFR, OSTS, PDB2, CD26, OPTB7, TRANCER, LOH18CR1) induces the activation of NF-kappa B and MAPK8/JNK through interactions with various TRAF adaptor proteins. This receptor and its ligand are important regulators of the interaction between T cells and dendritic cells. This receptor is also an essential mediator for osteoclast and lymph node development. Mutations at this locus have been associated with familial expansile osteolysis, autosomal recessive osteopetrosis, and Juvenile Paget's disease (JPD) of bone. Alternatively spliced transcript variants have been described for this locus. Mutation analysis may improve diagnosis, prognostication, recurrence risk assessment, and perhaps treatment selection among the monogenic disorders of RANKL/OPG/RANK activation.


Pssm-ID: 276932 [Multi-domain]  Cd Length: 122  Bit Score: 55.97  E-value: 3.90e-09
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1074585809 1214 CNYNYYYNklSGQCelCTVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTICDE 1277
Cdd:cd15836      4 CNQTQYLK--DGKC--CRKCEPGSFVFAHCSGSSDTICRDCGRNEYQPDWTSEMKCIPQKFCDE 63
TNFRSF11B_teleost cd13412
Tumor necrosis factor receptor superfamily 11B (TNFRSF11B) in teleost; also known as ...
1149-1256 5.12e-09

Tumor necrosis factor receptor superfamily 11B (TNFRSF11B) in teleost; also known as Osteoprotegerin (OPG); This subfamily of TNFRSF11B (also known as Osteoprotegerin, OPG, TR1, OCIF) is found in teleosts. It is a secreted glycoprotein that regulates bone resorption. It binds to two ligands, RANKL (receptor activator of nuclear factor kappaB ligand, also known as osteoprotegerin ligand, OPGL, TRANCE, TNF-related activation induced cytokine), a critical cytokine for osteoclast differentiation, and TRAIL (TNF-related apoptosis-inducing ligand), involved in immune surveillance. Therefore, acting as a decoy receptor for RANKL and TRAIL, OPG inhibits the regulatory effects of nuclear factor-kappaB on inflammation, skeletal, and vascular systems, and prevents TRAIL-induced apoptosis. Studies in mice counterparts suggest that this protein and its ligand also play a role in lymph-node organogenesis and vascular calcification. Circulating OPG levels have emerged as independent biomarkers of cardiovascular disease (CVD) in patients with acute or chronic heart disease. OPG has also been implicated in various inflammations and linked to diabetes and poor glycemic control. Alternatively spliced transcript variants of this gene have been reported, although their full length nature has not been determined. Genetic analysis of the Japanese rice fish medaka (Oryzias latipes) has shown that entire networks for bone formation are conserved between teleosts and mammals; enabling medaka to be used as a genetic model to monitor bone homeostasis in vivo.


Pssm-ID: 276917 [Multi-domain]  Cd Length: 129  Bit Score: 55.96  E-value: 5.12e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1149 CLECPTGEGVVKECGA-TQTVCAQCLDSEtFSENDSHTEKCKPCTQ-CTGLMRMETPCTDSNDARCVCNYNYYYNklSGQ 1226
Cdd:cd13412     22 CKKCPPGTHMAAHCTAtTQTKCLPCPAAH-YTELWNYLPRCLYCNNfCSENQEVEIECSATNNRVCRCKEGYYMD--SDF 98
                           90       100       110
                   ....*....|....*....|....*....|
gi 1074585809 1227 CELCTVCPVGQGVYTHCDHYHDTVCEECLD 1256
Cdd:cd13412     99 CIRHTECGPGYGVKTKGTTKQDTVCEKCPS 128
TNFRSF1B cd10577
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B), also known as TNFR2; TNFRSF1B ...
1219-1295 8.95e-09

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: 56.33  E-value: 8.95e-09
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1074585809 1219 YYNKLSGQCelCTVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTI-CDEELDETliAECTPNSDSVC 1295
Cdd:cd10577      7 YYDEKAQMC--CSKCPPGQHVKHSCTKTSDTVCAPCEESTYTQLWNWVPECLSCSSpCSSDQVET--QACTRQQNRIC 80
TNFRSF3 cd10578
Tumor necrosis factor receptor superfamily member 3 (TNFRSF3), also known as lymphotoxin beta ...
1148-1236 9.41e-09

Tumor necrosis factor receptor superfamily member 3 (TNFRSF3), also known as lymphotoxin beta receptor (LTBR); TNFRSF3 (also known as lymphotoxin beta receptor, LTbetaR, CD18, TNFCR, TNFR3, D12S370, TNFR-RP, TNFR2-RP, LT-BETA-R, TNF-R-III) plays a role in signaling during development of lymphoid and other organs, lipid metabolism, immune response, and programmed cell death. Its ligands include lymphotoxin (LT) alpha/beta membrane form (heterotrimer) and tumor necrosis factor ligand superfamily member 14 (also known as LIGHT). TNFRSF3 agonism by these ligands initiates canonical, as well as non-canonical nuclear factor-kappaB (NF-kappaB) signaling, and preferentially results in the translocation of p52-RELB complexes into the nucleus. While these ligands are often expressed by T and B cells, TNFRSF3 is conspicuous absence on T and B lymphocytes and NK cells, suggesting that signaling may be unidirectional for TNFRSF3. Activity of this receptor has also been linked to carcinogenesis; it helps trigger apoptosis and can also lead to release of the interleukin 8 (IL8). Alternatively spliced transcript variants encoding multiple isoforms have been observed.


Pssm-ID: 276904 [Multi-domain]  Cd Length: 158  Bit Score: 55.93  E-value: 9.41e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1148 CCLECPTGEGVVKECGATQ-TVCAQCLDSeTFSENDSHTEKCKPCTQCTGLMRME--TPCTDSNDARCVCN---YNYYYN 1221
Cdd:cd10578     48 CCSRCPPGTHVSAECSRSQdTVCATCPEN-SYNEHWNHLSICQLCRPCDPVLGFEevAPCTSDRKTQCRCQpgmFCVHWD 126
                           90
                   ....*....|....*
gi 1074585809 1222 KLSGQCELCTVCPVG 1236
Cdd:cd10578    127 NECEHCEPLSDCPPG 141
TNFRSF5_teleost cd13422
Tumor necrosis factor receptor superfamily member 5 (TNFRSF5) in teleosts; also known as CD40; ...
1127-1213 1.42e-08

Tumor necrosis factor receptor superfamily member 5 (TNFRSF5) in teleosts; also known as CD40; TNFRSF5 (commonly known as CD40 and also as CDW40, p50, Bp50) is widely expressed in diverse cell types including B lymphocytes, dendritic cells, platelets, monocytes, endothelial cells, and fibroblasts. It is essential in mediating a wide variety of immune and inflammatory responses, including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. Its natural immunomodulating ligand is CD40L, and a primary defect in the CD40/CD40L system is associated with X-linked hyper-IgM (XHIM) syndrome. It is also involved in tumorigenesis; CD40 expression is significantly higher in gastric carcinomas and it is associated with the lymphatic metastasis of cancer cells and their tumor node metastasis (TNM) classification. Upregulated levels of CD40/CD40L on B cells and T cells may play an important role in the immune pathogenesis of breast cancer. Consequently, the CD40/CD40L system serves as a link between tumorigenesis, atherosclerosis, and the immune system, and offers a potential target for drug therapy for related diseases, such as cancer, atherosclerosis, diabetes mellitus, and immunological rejection. Salmon CD40 and CD40L are widely expressed, particularly in immune tissues, and their importance for the immune response is indicated by their relatively high expression in salmon lymphoid organs and gills.


Pssm-ID: 276927 [Multi-domain]  Cd Length: 161  Bit Score: 55.51  E-value: 1.42e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1127 SKTERALFpDCVSGHYTDSGEC--CLE---CPTGEGV-VKECGATQTVCAQCLDSeTFSENDSHTEKCKPCTQCTGLMRM 1200
Cdd:cd13422     71 SKTSRSVC-KCKPGFHCSSEECltCVPhttCGPGQGVkSKGNHIRDTVCEECPDG-TFSNNSSAEGVCKKWTECESGYKV 148
                           90
                   ....*....|...
gi 1074585809 1201 ETPCTDSNDARCV 1213
Cdd:cd13422    149 EAAGTNTSDNICV 161
TNFRSF_viral cd15839
Tumor necrosis factor receptor superfamily members, virus-encoded; This family contains viral ...
1214-1296 3.44e-08

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: 53.33  E-value: 3.44e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1214 CNYNYYYNKLSGQCelCTVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCT-ICDEELDETliAECTPNSD 1292
Cdd:cd15839      1 CNGNDYNSNSNNLC--CKSCPPGTYASHLCDTTSNTKCDPCPSDTFTSIPNHIPACLSCRgRCSSNQVET--KSCSNTQN 76

                   ....
gi 1074585809 1293 SVCH 1296
Cdd:cd15839     77 RICS 80
TNFRSF9_teleost cd13424
Tumor necrosis factor receptor superfamily member 9 (TNFRSF9) in teleosts; also known as CD137; ...
1148-1262 7.20e-08

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: 53.29  E-value: 7.20e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1148 CCLECPTGEGVVKECGAT-QTVCAQClDSETFSENDShTEKCKPCTQCTGLMRMETPCTDSNDARCVCNYNYYYNklSGQ 1226
Cdd:cd13424     13 CCESCHPGNRLVERCGPDpAELCKPC-EPGTYTVKPL-DYSCYICTQCIGAQVLLKNCTPSSDTVCGCKEGLRCG--DAE 88
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1074585809 1227 CELC-TVCPVGQgvythcDHYHDTVCEECLDETYSDR 1262
Cdd:cd13424     89 CSFCvTECGKGQ------EPLGKRDCRQCPVGTFNDQ 119
TNFRSF3 cd10578
Tumor necrosis factor receptor superfamily member 3 (TNFRSF3), also known as lymphotoxin beta ...
1212-1296 1.00e-07

Tumor necrosis factor receptor superfamily member 3 (TNFRSF3), also known as lymphotoxin beta receptor (LTBR); TNFRSF3 (also known as lymphotoxin beta receptor, LTbetaR, CD18, TNFCR, TNFR3, D12S370, TNFR-RP, TNFR2-RP, LT-BETA-R, TNF-R-III) plays a role in signaling during development of lymphoid and other organs, lipid metabolism, immune response, and programmed cell death. Its ligands include lymphotoxin (LT) alpha/beta membrane form (heterotrimer) and tumor necrosis factor ligand superfamily member 14 (also known as LIGHT). TNFRSF3 agonism by these ligands initiates canonical, as well as non-canonical nuclear factor-kappaB (NF-kappaB) signaling, and preferentially results in the translocation of p52-RELB complexes into the nucleus. While these ligands are often expressed by T and B cells, TNFRSF3 is conspicuous absence on T and B lymphocytes and NK cells, suggesting that signaling may be unidirectional for TNFRSF3. Activity of this receptor has also been linked to carcinogenesis; it helps trigger apoptosis and can also lead to release of the interleukin 8 (IL8). Alternatively spliced transcript variants encoding multiple isoforms have been observed.


Pssm-ID: 276904 [Multi-domain]  Cd Length: 158  Bit Score: 52.85  E-value: 1.00e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1212 CVCNYNYYYNKLSGQCelCTVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTICDEELDETLIAECTPNS 1291
Cdd:cd10578     33 CWDQEKEYYEPRHQVC--CSRCPPGTHVSAECSRSQDTVCATCPENSYNEHWNHLSICQLCRPCDPVLGFEEVAPCTSDR 110

                   ....*
gi 1074585809 1292 DSVCH 1296
Cdd:cd10578    111 KTQCR 115
TNFRSF11A_teleost cd15836
Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) in teleost; also known as ...
1135-1239 5.34e-07

Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) in teleost; also known as RANK; TNFRSF11A (also known as RANK, FEO, OFE, ODFR, OSTS, PDB2, CD26, OPTB7, TRANCER, LOH18CR1) induces the activation of NF-kappa B and MAPK8/JNK through interactions with various TRAF adaptor proteins. This receptor and its ligand are important regulators of the interaction between T cells and dendritic cells. This receptor is also an essential mediator for osteoclast and lymph node development. Mutations at this locus have been associated with familial expansile osteolysis, autosomal recessive osteopetrosis, and Juvenile Paget's disease (JPD) of bone. Alternatively spliced transcript variants have been described for this locus. Mutation analysis may improve diagnosis, prognostication, recurrence risk assessment, and perhaps treatment selection among the monogenic disorders of RANKL/OPG/RANK activation.


Pssm-ID: 276932 [Multi-domain]  Cd Length: 122  Bit Score: 49.80  E-value: 5.34e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1135 PDCVSGHYTDSGECCLECPTGEGVVKEC-GATQTVCAQCLDSETFSENDSHtEKCKP---CTQCTGLMRmETPCTDSNDA 1210
Cdd:cd15836      2 PTCNQTQYLKDGKCCRKCEPGSFVFAHCsGSSDTICRDCGRNEYQPDWTSE-MKCIPqkfCDEGKGFNR-TRPHNPTALE 79
                           90       100       110
                   ....*....|....*....|....*....|..
gi 1074585809 1211 RCVCNYNYYYNKLSgqCELCT---VCPVGQGV 1239
Cdd:cd15836     80 PCQCKPGFQCSPLN--CEFCEkipTCPPGYGL 109
TNFR_c6 pfam00020
TNFR/NGFR cysteine-rich region;
1214-1251 6.54e-07

TNFR/NGFR cysteine-rich region;


Pssm-ID: 459633 [Multi-domain]  Cd Length: 39  Bit Score: 46.92  E-value: 6.54e-07
                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1074585809 1214 CNYNYYYNKLSG-QCELCTVCPVGQGVYTHCDHYHDTVC 1251
Cdd:pfam00020    1 CPPGTYTDNWNGlKCLPCTVCPPGQVVVRPCTPTSDTVC 39
EnvC COG4942
Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, ...
564-747 2.29e-06

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 443969 [Multi-domain]  Cd Length: 377  Bit Score: 51.69  E-value: 2.29e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  564 LQNLQQNTNALRKQLSQLRNIQLENQDSVLSLLR--QTESELSLMMLdaMRPQEDPLQRQRLLveeERLKYLNQEelLIQ 641
Cdd:COG4942     78 LAALEAELAELEKEIAELRAELEAQKEELAELLRalYRLGRQPPLAL--LLSPEDFLDAVRRL---QYLKYLAPA--RRE 150
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  642 QLHDLEKSVEELQRnssinhglvTEQDVDQKSKELRmlgETLTELKNQFPSLQSKMRVVLRVEVEAVKFLKEEPHRLEAL 721
Cdd:COG4942    151 QAEELRADLAELAA---------LRAELEAERAELE---ALLAELEEERAALEALKAERQKLLARLEKELAELAAELAEL 218
                          170       180
                   ....*....|....*....|....*.
gi 1074585809  722 LKRCNTMTDALSSLRRQVTEGVWKTP 747
Cdd:COG4942    219 QQEAEELEALIARLEAEAAAAAERTP 244
TNFR_c6 pfam00020
TNFR/NGFR cysteine-rich region;
1254-1295 2.93e-06

TNFR/NGFR cysteine-rich region;


Pssm-ID: 459633 [Multi-domain]  Cd Length: 39  Bit Score: 45.38  E-value: 2.93e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1074585809 1254 CLDETYSDRESSLEpCLPCTICDEelDETLIAECTPNSDSVC 1295
Cdd:pfam00020    1 CPPGTYTDNWNGLK-CLPCTVCPP--GQVVVRPCTPTSDTVC 39
AIP3 pfam03915
Actin interacting protein 3;
92-163 6.40e-06

Actin interacting protein 3;


Pssm-ID: 427585 [Multi-domain]  Cd Length: 407  Bit Score: 50.22  E-value: 6.40e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1074585809   92 FLQLGEEIRRVHLTHELTsLETLRALIVHMFPQrltmamlrSPSTALL----IKDETRNIFYELEDPRDVQDRCVI 163
Cdd:pfam03915    1 FLQLGRKVKKVVLPLPLT-IASLRLLFVEKFAY--------SPGGDDFpeiyIQDPVSGVRYELEDLSDVKDGSVL 67
TNFRSF9 cd13410
Tumor necrosis factor receptor superfamily member 9 (TNFRSF9), also known as CD137; TNFRSF9 ...
1149-1275 6.63e-06

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: 47.04  E-value: 6.63e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1149 CLECPTGegvvKECGATQT-VCAQClDSETFSENDSHtEKCKPCTQCTGLMRMETPCTDSNDARCVCNYNYYYnkLSGQC 1227
Cdd:cd13410      6 CSNCPAG----TFCGKNKDqTCIPC-PPNSFSSTGGQ-QTCDICRKCEGVFRTKKPCSSTSNAECECVPGFHC--LGPGC 77
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1074585809 1228 ELCTV-CPVGQGVYthcdhyhDTVCEECLDETYSDRESslEPCLPCTIC 1275
Cdd:cd13410     78 SMCEPdCKQGQELT-------KEGCKDCSFGTFNDQEG--GVCRPWTNC 117
TNFRSF11B_teleost cd13412
Tumor necrosis factor receptor superfamily 11B (TNFRSF11B) in teleost; also known as ...
1224-1295 7.03e-06

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: 47.10  E-value: 7.03e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1074585809 1224 SGQCELCTVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPC-TICDEelDETLIAECTPNSDSVC 1295
Cdd:cd13412     16 TGKILTCKKCPPGTHMAAHCTATTQTKCLPCPAAHYTELWNYLPRCLYCnNFCSE--NQEVEIECSATNNRVC 86
TNFRSF cd00185
Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) ...
1136-1192 8.59e-06

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


Pssm-ID: 276900 [Multi-domain]  Cd Length: 87  Bit Score: 45.28  E-value: 8.59e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1074585809 1136 DCVSGHYTDS----GEC--CLECPTGEGVVK-ECGATQTVCAQCLDSeTFSENDSHTEKCKPCT 1192
Cdd:cd00185     25 PCPPGTYSESwnslSKClpCTTCGGGNQVEKtPCTATDNRCCTCKPG-FYCDEGTNVEECKPCT 87
TNFRSF10 cd10580
Tumor necrosis factor receptor superfamily member 10 (TNFRSF10), includes TNFRSF10A (DR4), ...
1230-1296 1.39e-05

Tumor necrosis factor receptor superfamily member 10 (TNFRSF10), includes TNFRSF10A (DR4), TNFRSF10B (DR5), TNFRSF10C (DcR1) and TNFRSF10D (DcR2); TNFRSF10 family contains TNFRSF10A (also known as DR4, Apo2, TRAIL-R1, CD261), TNFRSF10B (also known as DR5, KILLER, TRICK2A, TRAIL-R2, TRICKB, CD262), TNFRSF10C (also known as DcR1, TRAIL-R3, LIT, TRID, CD263), and TNFRSF10D (also known as DcR2, TRUNDD, TRAIL-R4, CD264). Tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL) binds to all 4 receptors. DR4 (TRAIL-R1) and DR5 (TRAIL-R2) are membrane-bound and contain a death domain in their intracellular portion, which is able to transmit an apoptotic signal, thus often called death receptors. In contrast, DcR1 (TRAIL-R3), which lacks the complete intracellular portion and DcR2 (TRAIL-R4), which has a truncated cytoplasmic death domain, do not transmit an apoptotic signal, thus known as decoy receptors. Apoptosis mediated by DR4 and DR5 requires Fas (TNFRSF6)-associated via death domain (FADD), a death domain containing adaptor protein. Two transcript variants encoding different isoforms and one non-coding transcript have been found for TNFRSF10B/DR5. DcR1 appears to function as an antagonistic receptor that protects cells from TRAIL-induced apoptosis; it has been found to be a p53-regulated DNA damage-inducible gene. The expression of this gene is detected in many normal tissues but not in most cancer cell lines, which may explain the specific sensitivity of cancer cells to the apoptosis-inducing activity of TRAIL. DcR2 has been shown to play an inhibitory role in TRAIL-induced cell apoptosis. The membrane expression of all of these receptors (DR4, DR5, DcR1, and DcR2) is greater in normal endometrium (NE) than in endometrioid adenocarcinoma (EAC). In EAC patients, membrane expression of these receptors are not independent predictors of survival. DcR1 and DcR2 expression is critical in cell growth and apoptosis in cutaneous or uveal melanoma; DcR1 and DcR2 are frequently methylated in both, leading to loss of gene expression and melanomagenesis. On the other hand, DR4 and DR5 methylation is rare in cutaneous melanoma and frequent in uveal melanoma; their expression is wholly independent of the promoter methylation status. DcR1 and DcR2 genes are also reported to be hyper-methylated in prostate cancer. The TRAIL ligand, a potent and specific inducer of apoptosis in cancer cells, has been explored as a therapeutic drug; experimental data has shown that DR4 specific TRAIL variants are more efficacious than wild-type TRAIL in pancreatic cancer.


Pssm-ID: 276906 [Multi-domain]  Cd Length: 103  Bit Score: 45.33  E-value: 1.39e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1074585809 1230 CTVCPVGQGVythcdHYHDTVCEECLDE-TYSDRESSLEPCLPCTICDEelDETLIAECTPNSDSVCH 1296
Cdd:cd10580      2 CGLCPAGTYV-----SEDSGDCIPCKEGvDYTEHPNGLPSCLPCTVCKS--DEEELSPCTTTRNTECQ 62
TNFRSF19L cd13419
tumor necrosis factor receptor superfamily member 19-like (TNFRSF19L), also known as receptor ...
1149-1220 1.59e-05

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: 44.71  E-value: 1.59e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1074585809 1149 CLECPTGEGVVKECGATQ---TVCAQClDSETFSeNDSHTEKCKPCTQCTGLMRME-TPCTDSNDARC-VCNYNYYY 1220
Cdd:cd13419      4 CLQCPPGQEPDRACGQGQglgVLCRSC-PPGTFS-DSLGSEPCRPHTSCEVLKRKVaTSGTATSDAVCgDCLPGFHS 78
TNFR smart00208
Tumor necrosis factor receptor / nerve growth factor receptor repeats; Repeats in growth ...
1214-1251 1.71e-05

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: 43.23  E-value: 1.71e-05
                            10        20        30
                    ....*....|....*....|....*....|....*....
gi 1074585809  1214 CNYNYYYNKLS-GQCELCTVCPVGQGVYTHCDHYHDTVC 1251
Cdd:smart00208    1 CKEGTYCSDGNhSSCLRCRRCPPGLVVKQPCTATSDTVC 39
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
559-741 4.12e-05

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 48.51  E-value: 4.12e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  559 QMQLHLQNLQQNTNALRKQLSQLRN-------------IQLENQDSVLSLLRQTESELSLMMldamrpqeDPLQRQRLLV 625
Cdd:TIGR02168  688 ELEEKIAELEKALAELRKELEELEEeleqlrkeleelsRQISALRKDLARLEAEVEQLEERI--------AQLSKELTEL 759
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  626 EEERLKYLNQEELLIQQLHDLEKSVEELQR---NSSINHGLVTEQdVDQKSKELRMLGETLTELKNQFPSLQSKMRVVLR 702
Cdd:TIGR02168  760 EAEIEELEERLEEAEEELAEAEAEIEELEAqieQLKEELKALREA-LDELRAELTLLNEEAANLRERLESLERRIAATER 838
                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1074585809  703 VEVEAVKFLKEEPHRLEALLKRCNTMTDALSSLRRQVTE 741
Cdd:TIGR02168  839 RLEDLEEQIEELSEDIESLAAEIEELEELIEELESELEA 877
TNFR_c6 pfam00020
TNFR/NGFR cysteine-rich region;
1177-1212 4.36e-05

TNFR/NGFR cysteine-rich region;


Pssm-ID: 459633 [Multi-domain]  Cd Length: 39  Bit Score: 41.91  E-value: 4.36e-05
                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1074585809 1177 TFSENDSHtEKCKPCTQCTGLMRMETPCTDSNDARC 1212
Cdd:pfam00020    5 TYTDNWNG-LKCLPCTVCPPGQVVVRPCTPTSDTVC 39
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
559-707 4.88e-05

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 47.59  E-value: 4.88e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  559 QMQLHLQNLQQNTNALRKQLSQLRNiQLENQDSVLSLLRQTESELSLmMLDAMRPQEDPLQRQRLLVEEERLKYLNQEEL 638
Cdd:COG4372     42 KLQEELEQLREELEQAREELEQLEE-ELEQARSELEQLEEELEELNE-QLQAAQAELAQAQEELESLQEEAEELQEELEE 119
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1074585809  639 LIQQLHDLEKSVEELQRNSSinhglVTEQDVDQKSKELRMLGETLTELKNQFPSLQSKMRVVLRVEVEA 707
Cdd:COG4372    120 LQKERQDLEQQRKQLEAQIA-----ELQSEIAEREEELKELEEQLESLQEELAALEQELQALSEAEAEQ 183
TNFRSF11B cd10581
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B), also known as ...
1219-1295 5.01e-05

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: 44.77  E-value: 5.01e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1074585809 1219 YYNKLSGQCELCTVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTICDEELdETLIAECTPNSDSVC 1295
Cdd:cd10581     25 HYDPVTSRQLMCDQCPPGTYVKQHCSASRKTVCAPCPDHHYADDWNSNDECQYCNTVCKEL-QYVKQECNSTHNRVC 100
TNFRSF14 cd10582
Tumor necrosis factor receptor superfamily member 14 (TNFRSF14), also known as herpes virus ...
1228-1296 5.05e-05

Tumor necrosis factor receptor superfamily member 14 (TNFRSF14), also known as herpes virus entry mediator (HVEM); TNFRSF14 (also known as herpes virus entry mediator or HVEM, ATAR, CD270, HVEA, LIGHTR, TR2) regulates T-cell immune responses by activating inflammatory, as well as inhibitory signaling pathways. HVEM acts as a receptor for the canonical TNF-related ligand LIGHT (lymphotoxin-like), which exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for HVEM. It also acts as a ligand for the immunoglobulin superfamily proteins BTLA (B and T lymphocyte attenuator) and CD160, a feature distinguishing HVEM from other immune regulatory molecules, thus, creating a functionally diverse set of intrinsic and bidirectional signaling pathways. HVEM is highly expressed in the gut epithelium. Genome-wide association studies have shown that Hvem is an inflammatory bowel disease (IBD) risk gene, suggesting that HVEM could have a regulatory role influencing the regulation of epithelial barrier, host defense, and the microbiota. Mouse models have revealed that HVEM is involved in colitis pathogenesis, mucosal host defense, and epithelial immunity, thus acting as a mucosal gatekeeper with multiple regulatory functions in the mucosa. HVEM plays a critical role in both tumor progression and resistance to antitumor immune responses, possibly through direct and indirect mechanisms. It is known to be expressed in several human malignancies, including esophageal squamous cell carcinoma, follicular lymphoma and melanoma. HVEM network may therefore be an attractive target for drug intervention.


Pssm-ID: 276908 [Multi-domain]  Cd Length: 101  Bit Score: 43.57  E-value: 5.05e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1074585809 1228 ELCTVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTICDEELDETLIAECTPNSDSVCH 1296
Cdd:cd10582     11 ECCPKCSPGYRVKKACGELTGTVCEPCPPGTYTAHLNGLSKCLQCRVCDPAMGLVTRRNCSSTENTVCG 79
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
485-745 5.35e-05

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 48.13  E-value: 5.35e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  485 TETRERMEAMEKQIASLTGLLQRVLTRAPEADSPEKMESASDGSAADpltpsaplalmpppslgSSQPITVSRMQMQLHL 564
Cdd:TIGR02168  270 EELRLEVSELEEEIEELQKELYALANEISRLEQQKQILRERLANLER-----------------QLEELEAQLEELESKL 332
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  565 QNLQQNTNALRKQLSQLRNiQLENQDSVLSLLRQTESELSlmmlDAMRPQEDPLQRQRllveEERLKYLNQEELLIQQLH 644
Cdd:TIGR02168  333 DELAEELAELEEKLEELKE-ELESLEAELEELEAELEELE----SRLEELEEQLETLR----SKVAQLELQIASLNNEIE 403
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  645 DLEKSVEELQRNSSINHGLVTEQDVDQKSKELRMLGETLTELKNQFPSLQSKMRVV----------LRVEVEAVKFLKEE 714
Cdd:TIGR02168  404 RLEARLERLEDRRERLQQEIEELLKKLEEAELKELQAELEELEEELEELQEELERLeealeelreeLEEAEQALDAAERE 483
                          250       260       270
                   ....*....|....*....|....*....|.
gi 1074585809  715 PHRLEALLKRCNTMTDALSSLRRQVTEgVWK 745
Cdd:TIGR02168  484 LAQLQARLDSLERLQENLEGFSEGVKA-LLK 513
Mplasa_alph_rch TIGR04523
helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of ...
564-734 7.10e-05

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.


Pssm-ID: 275316 [Multi-domain]  Cd Length: 745  Bit Score: 47.32  E-value: 7.10e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  564 LQNLQQNTNALRKQL----SQLRNIQLENQ---DSVLSLLRQTES-ELSLMMLDAMRPQEDP----LQRQRLLVEEE--R 629
Cdd:TIGR04523  351 LTNSESENSEKQRELeekqNEIEKLKKENQsykQEIKNLESQINDlESKIQNQEKLNQQKDEqikkLQQEKELLEKEieR 430
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  630 LKYL---NQEEL--LIQQLHDLEKSVEELQRN---------------SSINHGL-VTEQDVDQKSKELRMLGETLTELKN 688
Cdd:TIGR04523  431 LKETiikNNSEIkdLTNQDSVKELIIKNLDNTresletqlkvlsrsiNKIKQNLeQKQKELKSKEKELKKLNEEKKELEE 510
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1074585809  689 QFPSLQSKmrvvlrveveaVKFLKEEPHRLEALLKRCNTMTDALSS 734
Cdd:TIGR04523  511 KVKDLTKK-----------ISSLKEKIEKLESEKKEKESKISDLED 545
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
561-739 8.02e-05

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 46.82  E-value: 8.02e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  561 QLHLQNLQQNTNALRKQLSQLRNIQLENQDSVLSLLRQTESELSLmmldamrpqedplQRQRLLVEEERLKYLNQE-ELL 639
Cdd:COG4372     12 RLSLFGLRPKTGILIAALSEQLRKALFELDKLQEELEQLREELEQ-------------AREELEQLEEELEQARSElEQL 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  640 IQQLHDLEKSVEELQRNSSinhglVTEQDVDQKSKELRMLGETLTELKNQFPSLQSKMRVVLRVEVEAVKFLKEEPHRLE 719
Cdd:COG4372     79 EEELEELNEQLQAAQAELA-----QAQEELESLQEEAEELQEELEELQKERQDLEQQRKQLEAQIAELQSEIAEREEELK 153
                          170       180
                   ....*....|....*....|
gi 1074585809  720 ALLKRCNTMTDALSSLRRQV 739
Cdd:COG4372    154 ELEEQLESLQEELAALEQEL 173
TNFRSF1A_teleost cd15834
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) in teleosts; also known as ...
1214-1295 9.42e-05

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


Pssm-ID: 276930 [Multi-domain]  Cd Length: 150  Bit Score: 44.02  E-value: 9.42e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1214 CNYNYYYNKlSGQCelCTVCPVGQGVYTHCDHY-HDTVCEECLDETYSDRESSLEPCLPCTICDEELDETlIAECTPNSD 1292
Cdd:cd15834      1 CLDSEYLSE-NGIC--CNKCHPGYKLKEECTAPgERSQCTPCPEGTYLEQINYSPNCRRCTLCKVKNEEE-VSPCKKSSN 76

                   ...
gi 1074585809 1293 SVC 1295
Cdd:cd15834     77 TVC 79
MAP65_ASE1 pfam03999
Microtubule associated protein (MAP65/ASE1 family);
569-763 1.06e-04

Microtubule associated protein (MAP65/ASE1 family);


Pssm-ID: 427641 [Multi-domain]  Cd Length: 477  Bit Score: 46.53  E-value: 1.06e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  569 QNTNALRKQLSQLRNIQLENQDSVLSLLRQTeseLSLMMLDAMRPQEDPlqRQRLLVEEERLKYLNQEelLIQQLHDLEK 648
Cdd:pfam03999  143 EELESFRKHLENLRNEKERRLEEVNELKKQI---KLLMEELDLVPGTDF--EEDLLCESEDNFCLSRE--NIDKLRKLIK 215
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  649 SVEELqrnssinhglvteqdVDQKSKELRMLGETLTELKN--QFPSLQSKMRVVLRVE--VEAVKFLKEEPHRLEAlLKR 724
Cdd:pfam03999  216 QLEEQ---------------KAEREEKIDDLREKILELWNrlQVPQEEQESFVRENNSlsQDTIDALREELQRLEE-LKK 279
                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1074585809  725 CNtMTDALSSLRRQVTEgVWKTpediysqTQKRPEDLSR 763
Cdd:pfam03999  280 KN-IKKLIEDLRVEIEE-LWDK-------LFYSTEQRKR 309
TNFR smart00208
Tumor necrosis factor receptor / nerve growth factor receptor repeats; Repeats in growth ...
1181-1212 1.31e-04

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: 40.53  E-value: 1.31e-04
                            10        20        30
                    ....*....|....*....|....*....|..
gi 1074585809  1181 NDSHTEKCKPCTQCTGLMRMETPCTDSNDARC 1212
Cdd:smart00208    8 SDGNHSSCLRCRRCPPGLVVKQPCTATSDTVC 39
AIP3 smart00806
Actin interacting protein 3; Aip3p/Bud6p is a regulator of cell and cytoskeletal polarity in ...
92-206 1.38e-04

Actin interacting protein 3; Aip3p/Bud6p is a regulator of cell and cytoskeletal polarity in Saccharomyces cerevisiae that was previously identified as an actin-interacting protein. Actin-interacting protein 3 (Aip3p) localizes at the cell cortex where cytoskeleton assembly must be achieved to execute polarized cell growth, and deletion of AIP3 causes gross defects in cell and cytoskeletal polarity. Aip3p localization is mediated by the secretory pathway, mutations in early- or late-acting components of the secretory apparatus lead to Aip3p mislocalization.


Pssm-ID: 214826 [Multi-domain]  Cd Length: 426  Bit Score: 46.20  E-value: 1.38e-04
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809    92 FLQLGEEIRRVHLTHELTsLETLRALIVHMFPQrltmamlrSPSTA----LLIKDETRNIFYELED--PRDVQDRCVIKI 165
Cdd:smart00806    1 FLRIGNKTKKVVVSSPLT-FNALRLLFIEKFAY--------SPGGDdfpdIYIQDPVSGVSYELEElsLHDIKDGSVLVL 71
                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*.
gi 1074585809   166 ycKEPVYGTYPGHHNPHLAngDLRREMVHAPQ--DSPN---RRLSN 206
Cdd:smart00806   72 --NVEELDEVKKHIDDEID--TLQNELDEVKQalESQReaiQRLKE 113
TNFRSF1A cd10576
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), also known as TNFR1; TNFRSF1A ...
1137-1219 1.89e-04

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: 42.73  E-value: 1.89e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1137 CVSGHYTDSG---ECCLECPT-----GEGVVKECGATQ-TVCAqCLDSEtFSENDSHTEKCKPCTQCT-GLMRMetPCTD 1206
Cdd:cd10576     40 CENGTFTASEnylRKCLSCSRcrkemGQVEISPCTVDQdTVCG-CRKNQ-YQHYWSSLFQCKNCSLCLnGTIRQ--PCQE 115
                           90
                   ....*....|...
gi 1074585809 1207 SNDARCVCNYNYY 1219
Cdd:cd10576    116 KQDTICTCHTGFF 128
TNFRSF11B cd10581
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B), also known as ...
1149-1295 3.37e-04

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: 42.46  E-value: 3.37e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1149 CLECPTGEGVVKECGAT-QTVCAQCLDSEtFSENDSHTEKCKPCTqctglmrmetpctdsndarcvcnynyyynklsgqc 1227
Cdd:cd10581     36 CDQCPPGTYVKQHCSASrKTVCAPCPDHH-YADDWNSNDECQYCN----------------------------------- 79
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1074585809 1228 elcTVCPVGQGVYTHCDHYHDTVCeECLDETYSDressLEPCLPCTICDEELDetLIAECTPNSDSVC 1295
Cdd:cd10581     80 ---TVCKELQYVKQECNSTHNRVC-ECVEGRYLE----LEFCLKHTECPPGFG--VVQPGTPESDTVC 137
TNFRSF14 cd10582
Tumor necrosis factor receptor superfamily member 14 (TNFRSF14), also known as herpes virus ...
1146-1233 3.57e-04

Tumor necrosis factor receptor superfamily member 14 (TNFRSF14), also known as herpes virus entry mediator (HVEM); TNFRSF14 (also known as herpes virus entry mediator or HVEM, ATAR, CD270, HVEA, LIGHTR, TR2) regulates T-cell immune responses by activating inflammatory, as well as inhibitory signaling pathways. HVEM acts as a receptor for the canonical TNF-related ligand LIGHT (lymphotoxin-like), which exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for HVEM. It also acts as a ligand for the immunoglobulin superfamily proteins BTLA (B and T lymphocyte attenuator) and CD160, a feature distinguishing HVEM from other immune regulatory molecules, thus, creating a functionally diverse set of intrinsic and bidirectional signaling pathways. HVEM is highly expressed in the gut epithelium. Genome-wide association studies have shown that Hvem is an inflammatory bowel disease (IBD) risk gene, suggesting that HVEM could have a regulatory role influencing the regulation of epithelial barrier, host defense, and the microbiota. Mouse models have revealed that HVEM is involved in colitis pathogenesis, mucosal host defense, and epithelial immunity, thus acting as a mucosal gatekeeper with multiple regulatory functions in the mucosa. HVEM plays a critical role in both tumor progression and resistance to antitumor immune responses, possibly through direct and indirect mechanisms. It is known to be expressed in several human malignancies, including esophageal squamous cell carcinoma, follicular lymphoma and melanoma. HVEM network may therefore be an attractive target for drug intervention.


Pssm-ID: 276908 [Multi-domain]  Cd Length: 101  Bit Score: 41.26  E-value: 3.57e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1146 GECCLECPTGEGVVKECG-ATQTVCAQClDSETFSENDSHTEKCKPCTQCTGLMRMETPCTDSNDARCVCNYNYYYNKLS 1224
Cdd:cd10582     10 SECCPKCSPGYRVKKACGeLTGTVCEPC-PPGTYTAHLNGLSKCLQCRVCDPAMGLVTRRNCSSTENTVCGCIPGHFCSA 88

                   ....*....
gi 1074585809 1225 GQCELCTVC 1233
Cdd:cd10582     89 QDGDHCVEC 97
EnvC COG4942
Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, ...
564-766 3.69e-04

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 443969 [Multi-domain]  Cd Length: 377  Bit Score: 44.75  E-value: 3.69e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  564 LQNLQQNTNALRKQLSQLRNIQLENQ---DSVLSLLRQTESELSLM--MLDAMRPQEDpLQRQRLLVEEERLKYLNQEel 638
Cdd:COG4942     22 AAEAEAELEQLQQEIAELEKELAALKkeeKALLKQLAALERRIAALarRIRALEQELA-ALEAELAELEKEIAELRAE-- 98
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  639 LIQQLHDLEKSVEELQRNSSINH--GLVTEQDVDQKSKELRMLGETLTELKNQFPSLQSKMRVVLRVEVEavkfLKEEPH 716
Cdd:COG4942     99 LEAQKEELAELLRALYRLGRQPPlaLLLSPEDFLDAVRRLQYLKYLAPARREQAEELRADLAELAALRAE----LEAERA 174
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1074585809  717 RLEALLKRCNTMTDALSSLRRQVTEGVWKTPEDIySQTQKRPEDLSRSSD 766
Cdd:COG4942    175 ELEALLAELEEERAALEALKAERQKLLARLEKEL-AELAAELAELQQEAE 223
YhaN COG4717
Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];
559-721 3.69e-04

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];


Pssm-ID: 443752 [Multi-domain]  Cd Length: 641  Bit Score: 45.14  E-value: 3.69e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  559 QMQLHLQNLQQNTNALRKQLSQLRNI--QLENQDSVLSL---LRQTESELSLMM--LDAMRPQEDPLQRQRllveeerlk 631
Cdd:COG4717     92 ELQEELEELEEELEELEAELEELREEleKLEKLLQLLPLyqeLEALEAELAELPerLEELEERLEELRELE--------- 162
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  632 ylNQEELLIQQLHDLEKSVEELQRNSSinhgLVTEQDVDQKSKELRMLGETLTELKNQFPSLQSKMRvVLRVEVEAVKFL 711
Cdd:COG4717    163 --EELEELEAELAELQEELEELLEQLS----LATEEELQDLAEELEELQQRLAELEEELEEAQEELE-ELEEELEQLENE 235
                          170
                   ....*....|
gi 1074585809  712 KEEPHRLEAL 721
Cdd:COG4717    236 LEAAALEERL 245
TNFR smart00208
Tumor necrosis factor receptor / nerve growth factor receptor repeats; Repeats in growth ...
1254-1295 4.70e-04

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: 38.99  E-value: 4.70e-04
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|..
gi 1074585809  1254 CLDETYSDRESSlEPCLPCTICDEelDETLIAECTPNSDSVC 1295
Cdd:smart00208    1 CKEGTYCSDGNH-SSCLRCRRCPP--GLVVKQPCTATSDTVC 39
TNFRSF6 cd10579
Tumor necrosis factor receptor superfamily member 6 (TNFRSF6), also known as fas cell surface ...
1135-1212 6.25e-04

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


Pssm-ID: 276905 [Multi-domain]  Cd Length: 129  Bit Score: 41.21  E-value: 6.25e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1135 PDCVS----GHYTD----SGEC--CLECPTGEG--VVKECGATQ-TVCAqCldSETFSENDSHTEKCKPCTQC-TGLmrm 1200
Cdd:cd10579     42 PDCVPctegKEYTDkkhySDKCrrCKICDEEHGleVEKNCTRTQnTKCR-C--KSNFFCNSSPCEHCDPCTTCeHGI--- 115
                           90
                   ....*....|..
gi 1074585809 1201 ETPCTDSNDARC 1212
Cdd:cd10579    116 IEECTPTSNTKC 127
TNFR_c6 pfam00020
TNFR/NGFR cysteine-rich region;
1137-1169 6.32e-04

TNFR/NGFR cysteine-rich region;


Pssm-ID: 459633 [Multi-domain]  Cd Length: 39  Bit Score: 38.83  E-value: 6.32e-04
                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1074585809 1137 CVSGHYTDSG---EC--CLECPTGEGVVKECGATQ-TVC 1169
Cdd:pfam00020    1 CPPGTYTDNWnglKClpCTVCPPGQVVVRPCTPTSdTVC 39
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
567-763 6.72e-04

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 44.28  E-value: 6.72e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  567 LQQNTNALRKQLSQLRNIQ--LENQDSVLSL------LRQTESELSLMMLDAMRPQEDPLQ-----------RQRLLVEE 627
Cdd:PRK03918   468 LKEIEEKERKLRKELRELEkvLKKESELIKLkelaeqLKELEEKLKKYNLEELEKKAEEYEklkekliklkgEIKSLKKE 547
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  628 -ERLKYLNQE-ELLIQQLHDLEKSVEELQRNSSiNHGLVTEQDVDQKSKELRMLGETLTELKNQFPSLQSKMRVVLRVEV 705
Cdd:PRK03918   548 lEKLEELKKKlAELEKKLDELEEELAELLKELE-ELGFESVEELEERLKELEPFYNEYLELKDAEKELEREEKELKKLEE 626
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1074585809  706 EAVKFLKEephrLEALLKRcntmtdaLSSLRRQVTEGVWKTPEDIYSQTQKRPEDLSR 763
Cdd:PRK03918   627 ELDKAFEE----LAETEKR-------LEELRKELEELEKKYSEEEYEELREEYLELSR 673
TNFRSF21 cd10583
Tumor necrosis factor receptor superfamily member 21 (TNFRSF21), also known as death receptor ...
1218-1298 1.47e-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: 40.89  E-value: 1.47e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1218 YYYNKLSGQCELCTVCPVGQGVYTHCDHYHDTVCEECLDETYSDRESSLEPCLPCTI-CDEELDETLiaECTPNSDSVCH 1296
Cdd:cd10583      3 RHVDPATGTQLTCDKCPAGTYVSKHCTETSLRECSPCPNGTFTRHENGIEQCHRCRKpCPAPMIEKT--PCTALTDRECT 80

                   ..
gi 1074585809 1297 NP 1298
Cdd:cd10583     81 CP 82
sbcc TIGR00618
exonuclease SbcC; All proteins in this family for which functions are known are part of an ...
486-864 1.57e-03

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]


Pssm-ID: 129705 [Multi-domain]  Cd Length: 1042  Bit Score: 43.03  E-value: 1.57e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  486 ETRERMEAMEKQIASLTGLLQRV----LTRAPEADSPEKMESASDGSAADPlTPSAPLALMPPPSLGSSQPITVSRMQMQ 561
Cdd:TIGR00618  463 ESAQSLKEREQQLQTKEQIHLQEtrkkAVVLARLLELQEEPCPLCGSCIHP-NPARQDIDNPGPLTRRMQRGEQTYAQLE 541
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  562 LHLQNLQQNTNALRKQLSQLRN-IQLENQDsvLSLLRQTESELSLMMLDAMRPQEDPLQRQRLLVEEERLKYLNQEELLI 640
Cdd:TIGR00618  542 TSEEDVYHQLTSERKQRASLKEqMQEIQQS--FSILTQCDNRSKEDIPNLQNITVRLQDLTEKLSEAEDMLACEQHALLR 619
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  641 Q---QLHDLEKSVEELQRnssinhglvtEQDVDQKSKELRMLGETLTELKNQFPSLQSKMRVVLRVEVEAVKfLKEEPHR 717
Cdd:TIGR00618  620 KlqpEQDLQDVRLHLQQC----------SQELALKLTALHALQLTLTQERVREHALSIRVLPKELLASRQLA-LQKMQSE 688
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  718 LEALLKRCNTMTDALSSLRRQVT--EGVWKTPEDIYSQTQKRPEDLsrSSDLDILNSPPLSLADL-------STSAGLAN 788
Cdd:TIGR00618  689 KEQLTYWKEMLAQCQTLLRELEThiEEYDREFNEIENASSSLGSDL--AAREDALNQSLKELMHQartvlkaRTEAHFNN 766
                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1074585809  789 WIPVSSEVNTSGPEQDVQSSMAFRNRVLDElpsRRPAEKAVSAEVRLAAERDWEEKRAS---LTQFSAQDINRLLEETQ 864
Cdd:TIGR00618  767 NEEVTAALQTGAELSHLAAEIQFFNRLREE---DTHLLKTLEAEIGQEIPSDEDILNLQcetLVQEEEQFLSRLEEKSA 842
TNFRSF27 cd15838
Tumor necrosis factor receptor superfamily member 27 (TNFRSF27), also known as ectodysplasin ...
1137-1231 3.14e-03

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: 39.11  E-value: 3.14e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1137 CVSGHYTDS-GEC--CLECPTGEGVVKECGATQTVCAQCLDSETFSENDS-HTEKCKPCTQCTGLMRME-TPCTDSNDAR 1211
Cdd:cd15838      1 CQEKEYLDEhGKCvpCRECGPGQELSKDCGYGEGGDAYCTACPPRRFKDSwGHHGCKTCLSCALINRVQkSNCTATSNAV 80
                           90       100
                   ....*....|....*....|....*.
gi 1074585809 1212 CVCNYNYYYNK--LSGQ----CELCT 1231
Cdd:cd15838     81 CGDCLPGFYRKtrIGGLqdqeCIPCT 106
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
559-723 5.38e-03

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 41.04  E-value: 5.38e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  559 QMQLHLQNLQQNTNALRKQLSQLRN--IQLENQ-DSVLSLLRQTESELSLMMLDAMRPQED--PLQRQRLLVEEERLKYL 633
Cdd:COG4372     56 QAREELEQLEEELEQARSELEQLEEelEELNEQlQAAQAELAQAQEELESLQEEAEELQEEleELQKERQDLEQQRKQLE 135
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  634 NQEELLIQQLHDLEKSVEELQRNSSINHGLVTEQDVDQKSKELRMLGETLTELKNQFPSLQSKMRVVLRVEVEAVKFLKE 713
Cdd:COG4372    136 AQIAELQSEIAEREEELKELEEQLESLQEELAALEQELQALSEAEAEQALDELLKEANRNAEKEEELAEAEKLIESLPRE 215
                          170
                   ....*....|
gi 1074585809  714 EPHRLEALLK 723
Cdd:COG4372    216 LAEELLEAKD 225
TNFRSF19L cd13419
tumor necrosis factor receptor superfamily member 19-like (TNFRSF19L), also known as receptor ...
1227-1312 5.87e-03

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: 37.39  E-value: 5.87e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1227 CELCTVCPVGQGVYTHCDHYHD--TVCEECLDETYSDRESSlEPCLPCTICdEELDETLIAECTPNSDSVCHNpNLPTYD 1304
Cdd:cd13419      1 CVPCLQCPPGQEPDRACGQGQGlgVLCRSCPPGTFSDSLGS-EPCRPHTSC-EVLKRKVATSGTATSDAVCGD-CLPGFH 77

                   ....*...
gi 1074585809 1305 PTTADPLS 1312
Cdd:cd13419     78 SPAAPPPS 85
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
560-867 6.83e-03

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 41.20  E-value: 6.83e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  560 MQLHLQNLQQNTNALRKQLSQL--------RNIQLENQdsvlslLRQTESELSLMMLDAMRPQEDPLQRQRLLVEEERLK 631
Cdd:TIGR02168  184 TRENLDRLEDILNELERQLKSLerqaekaeRYKELKAE------LRELELALLVLRLEELREELEELQEELKEAEEELEE 257
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  632 Y---LNQEELLIQQL----HDLEKSVEELQrnssinhglvteqdvdqksKELRMLGETLTELKNQFPSLQSKMRVVLRVE 704
Cdd:TIGR02168  258 LtaeLQELEEKLEELrlevSELEEEIEELQ-------------------KELYALANEISRLEQQKQILRERLANLERQL 318
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  705 VEAVKFLKEEPHRLEALLKRCNTMTDALSSLRRQVTEgvwkTPEDIYSQTQKRPEDLSRSSDLDilnspplsladlstsa 784
Cdd:TIGR02168  319 EELEAQLEELESKLDELAEELAELEEKLEELKEELES----LEAELEELEAELEELESRLEELE---------------- 378
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809  785 glANWIPVSSEVNtsGPEQDVQSSMAFRNRVLDELpSRRPAEKAVSAEVRLAAERDWEEKRASLTQFSAQDINRLLEETQ 864
Cdd:TIGR02168  379 --EQLETLRSKVA--QLELQIASLNNEIERLEARL-ERLEDRRERLQQEIEELLKKLEEAELKELQAELEELEEELEELQ 453

                   ...
gi 1074585809  865 AEL 867
Cdd:TIGR02168  454 EEL 456
TNFRSF21 cd10583
Tumor necrosis factor receptor superfamily member 21 (TNFRSF21), also known as death receptor ...
1137-1212 7.45e-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: 38.96  E-value: 7.45e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1074585809 1137 CVSGHYTDSGECCLE--CPTGEGVVKECGATQTV-CAQCLDSeTFSENDSHTEKCKPCTQCTGL-MRMETPCTDSNDARC 1212
Cdd:cd10583     81 CPPGTFLSNDTCVPHsvCPVGWGVRKKGTETEDVrCKPCPRG-TFSDVPSSVLKCKTYTDCLGLgLVVIKPGTKETDNVC 159
 
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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