3ALQ,1D0G,3QD6,4HT1,4KGQ,2X29,3MI8,1RJ8,4MSV,2HEV,1U5X,4G4F,4MXW,1A8M,4DOU,6ZT0,7KX0,1KXG


Conserved Protein Domain Family
TNFSF
?
cd00184: TNFSF (This model is not part of the current CDD release)
tumor necrosis factor superfamily (TNFSF)
The tumor necrosis factor superfamily (TNFSF) includes a set of ligands that bind to one or more TNF receptor superfamily (TNFRSF) molecules. These superfamily members initiate numerous physiological functions. They play crucial roles in regulating development and homeostasis of the immune system, nervous system, bone and ectodermal organs in mammals. All members are either membrane-associated or soluble trimeric forms that cluster their cognate receptors to initiate signal transduction. TNFSF proteins that promote survival or inflammatory signaling include TNF-alpha (TNFSF2), lymphotoxins alpha and beta (TNFSF1 and TNFSF3), OX40L (TNFSF4), CD40L (TNFSF5) and B-cell activating factor or BAFF (TNFSF13), while those that induce cell death include FasL (TNFSF6) and TRAIL (TNFSF10). These ligands are essential to many aspects of normal B cell biology from development in the bone marrow to maturation in the periphery, as well as for activation and differentiation into germinal center, memory or plasma cells. Other aspects of B cell biology such as their ability to present antigens or regulate immune responses are also influenced by the TNF ligands; inadequate regulation of many of these ligands is associated with B cell disorders, including autoimmunity and cancers. Inhibitors of TNF ligands are among the most successful protein-based drugs and have been shown to be clinically efficacious at reducing inflammation that is associated with several autoimmune diseases. Many TNF superfamily members have been identified recently in teleost fish, such as TNF-alpha, CD40L (TNFSF5), FasL (TNFSF6), proliferation-inducing ligand or APRIL (TNFSF12), TNF-like weak inducer of apoptosis or TWEAK (TNFSF12), BAFF (TNFSF13), ectodysplasin A or EDA, LIGHT (TNFSF14), and receptor activator of nuclear factor kappa-B ligand or RANKL (TNFSF10), with some members existing as multiple isoforms (e.g., four TRAIL-like genes are present in teleosts). However, no TNF-b gene has been identified in any fish species, despite its important role in mammals.
Links
?
Statistics
?
PSSM-Id: 512934
Aligned: 77 rows
Threshold Bit Score: 41.2656
Created: 1-Nov-2000
Updated: 4-Apr-2025
Structure
?
Program:
Drawing:
Aligned Rows:
Download Cn3D
 
trimer
Conserved site includes 28 residues -Click on image for an interactive view with Cn3D
Feature 1:trimer interface [polypeptide binding site]
Evidence:
  • Structure:1A8M: Human TNF-alpha forms a trimer; contacts at 4A
  • Comment:conserved ring of hydrophobic residues aids in trimeric self-assembly of monomers.
  • Structure:1D0G: Human Apo2L (TRAIL) forms a trimer; contacts at 4A
Scroll to Sequence Alignment Display
Sequence Alignment
?
Format: Row Display: Color Bits: Type Selection: 
Feature 1      # #                                                #                         # 
3ALQ_A     12 PVAHVVAnpqa-------------------------egqLQWLNrr---anALLAn-----gVELRD--NQLVVPseGLY 56  human
4HT1_T     12 IAAHYEVhprpgqdga---------------qagvdgtvSGWEE-------ARINss---spLRYNRqiGEFIVTraGLY 66  human
2X29_A     12 XFAQLVAqnvll-----------------------idgpLSWYSdpg-lagVSLTg-----gLSYKEdtKELVVAkaGVY 62  human
4G4F_A      8 CLAKFELl------------------------------tSKWQM-------TSRKpp----cVNSLPe-GKLKILqdGLY 45  small-eared galago
1A8M_A     12 PVAHVVAnpqa-------------------------egqLQWLNdr---anALLAn-----gVELRD--NQLVVPseGLY 56  human
4DOU_A     27 SAFSVGLetyvt----------------------ipnmpIRFTKi------FYNQq------NHYDGstGKFHCNipGLY 72  human
6ZT0_A      6 PAAHFHLssrrrhqg----------------smgyhgdmYIGNDne----rNSYQg-----hFQTRD--GVLTVTntGLY 58  fruit fly
NP_033429 103 SWAYLQVskhl------------------------nntkLSWNEd------GTIHg------LIYQD--GNLIVQfpGLY 144 house mouse
ELT90633  144 VEVSVIGgtfhrirgf--------------qpglekglrGLWKVdqehslqGHIGpnqlfddSQIDN--GKVIVQesGIY 207 Capitella teleta
ESO96178  168 KCIELSGktvcrnrtiimpkndklngllkfpstdsrydfLHPASw-----yQEKHgp----lMQLNEk-GTFIVQktGIY 237 owl limpet

Feature 1     # # # #                  #         #########                       # #######    
3ALQ_A     57 LIYSQVLFsgqgcpsthvlLTHTISRIavsy-qtpVNLLSAIRSpcqretpeg------aeanpwyePIYLGGVFQLep- 128 human
4HT1_T     67 YLYCQVHFdegk----avyLKLDLLVDg-------VLALRCLEEfsataas---------slgpqlrLCQVSGLLALrp- 125 human
2X29_A     63 YVFFQXELrrvvagegsgsVSLALHLXplrs-aagAAALALTVDlppass-----------earnsaFGFQGRLLHLsa- 129 human
4G4F_A     46 LIYGQVAPstayk--gvapFAVQLRKNe-------AMLQTLTSNs---------------------tIYDVGGTYEFha- 94  small-eared galago
1A8M_A     57 LIYSQVLFkgqgcpsthvlLTHTISRIavsy-qtkVNLLSAIKSpcqretpeg------aeakpwyePIYLGGVFQLek- 128 human
4DOU_A     73 YFAYHITVym-------kdVKVSLFKKd-------KAMLFTYDQyqen----------------nvdQASGSVLLHLev- 121 human
6ZT0_A     59 YVYAQICYnns-----hdqNGFIVFQGd-------TPFLQCLNTvptnm-------------phkvhTCHTSGLIHLer- 112 fruit fly
NP_033429 145 FIVCQLQFlvqcs-nhsvdLTLQLLINski---kkQTLVTVCESgvqs---------------kniyQNLSQFLLHYlqv 205 house mouse
ELT90633  208 LIYFQVIFqtsa----ernLHQSVDLMngddslasCVVLESFSRdnptsntpsltnsgdshvssvfqPCASTIVVHLre- 282 Capitella teleta
ESO96178  238 LIYSTTHYfds-----kllLAQTVQINg-------ETKFRCLDGidfvknqe-------ptlnrrhkTCSVSGVTRLkk- 297 owl limpet

Feature 1                              #   #
3ALQ_A    129 gDRLSAEInrpdyld---faesgqVYFGII 155 human
4HT1_T    126 gSSLRIRTlpwahl----kaapflTYFGLF 151 human
2X29_A    130 gQRLGVHLhteararhawqltqgaTVLGLF 159 human
4G4F_A     95 gDIIDLIFddehq------vlknnTYWGIV 118 small-eared galago
1A8M_A    129 gDRLSAEInrpdyld---faesgqVYFGII 155 human
4DOU_A    122 gDQVWLQVygegernglyadndndSTFTGF 151 human
6ZT0_A    113 nERIHLKDihndrnav-lregnnrSYFGIF 141 fruit fly
NP_033429 206 nSTISVRVdnfqyvd--tntfpldNVLSVF 233 house mouse
ELT90633  283 gSSLGLSNlyhnrwi---lpaehlTFWGIT 309 Capitella teleta
ESO96178  298 gDKLEIQNvfhdvii---ditkdrTYFGVV 324 owl limpet

| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap