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TNF-like superfamily

SCOP classification
Root:   SCOP hierarchy in SUPERFAMILY [ 0] (11)
Class:   All beta proteins [ 48724] (174)
Fold:   TNF-like [ 49841]
Superfamily:   TNF-like [ 49842]
Families:   TNF-like [ 49843] (14)


Superfamily statistics
Genomes (263) Uniprot 2017_06 genome PDB chains (SCOP 1.75)
Domains 4,857 12,497 40
Proteins 4,643 12,174 40


Functional annotation
General category Processes_EC
Detailed category Immune response

Document:
Function annotation of SCOP domain superfamilies

Gene Ontology (high-coverage)

(show details)
GO term FDR (all) SDFO level Annotation (direct or inherited)
Biological Process (BP) response to stimulus 0 Least Informative Direct
Biological Process (BP) biological regulation 0 Least Informative Direct
Biological Process (BP) single-organism cellular process 0.0001994 Least Informative Direct
Biological Process (BP) macromolecule metabolic process 0.0003998 Least Informative Direct
Biological Process (BP) organonitrogen compound metabolic process 0.0006349 Least Informative Direct
Biological Process (BP) single-organism metabolic process 1 Least Informative Inherited
Biological Process (BP) primary metabolic process 0.0265 Least Informative Inherited
Biological Process (BP) cellular component organization or biogenesis 0.8642 Least Informative Inherited
Biological Process (BP) multicellular organismal process 0.03306 Least Informative Inherited
Biological Process (BP) regulation of response to stimulus 0 Moderately Informative Direct
Biological Process (BP) cell communication 0 Moderately Informative Direct
Biological Process (BP) protein complex biogenesis 0 Moderately Informative Direct
Biological Process (BP) immune system process 0 Moderately Informative Direct
Biological Process (BP) single organism signaling 0 Moderately Informative Direct
Biological Process (BP) macromolecular complex subunit organization 0.0000000000002512 Moderately Informative Direct
Biological Process (BP) regulation of protein metabolic process 0.00000000003973 Moderately Informative Direct
Biological Process (BP) regulation of cell communication 0.00000000005157 Moderately Informative Direct
Biological Process (BP) regulation of molecular function 0.0000000002702 Moderately Informative Direct
Biological Process (BP) response to organic substance 0.0000000002968 Moderately Informative Direct
Biological Process (BP) cellular component assembly 0.0000001343 Moderately Informative Direct
Biological Process (BP) defense response 0.0000002759 Moderately Informative Direct
Biological Process (BP) regulation of signaling 0.0000009557 Moderately Informative Direct
Biological Process (BP) animal organ development 0.0000116 Moderately Informative Direct
Biological Process (BP) oxidation-reduction process 0.0001173 Moderately Informative Direct
Biological Process (BP) monocarboxylic acid metabolic process 0.0003938 Moderately Informative Direct
Biological Process (BP) regulation of developmental process 1 Moderately Informative Inherited
Biological Process (BP) regulation of localization 0.2359 Moderately Informative Inherited
Biological Process (BP) regulation of macromolecule biosynthetic process 0.002295 Moderately Informative Inherited
Biological Process (BP) regulation of nucleobase-containing compound metabolic process 0.01897 Moderately Informative Inherited
Biological Process (BP) cellular localization 0.2104 Moderately Informative Inherited
Biological Process (BP) cellular response to chemical stimulus 0.6386 Moderately Informative Inherited
Biological Process (BP) macromolecule localization 0.001427 Moderately Informative Inherited
Biological Process (BP) single-organism catabolic process 0.001466 Moderately Informative Inherited
Biological Process (BP) response to oxygen-containing compound 0.001872 Moderately Informative Inherited
Biological Process (BP) multi-organism process 0.6478 Moderately Informative Inherited
Biological Process (BP) cellular response to stress 1 Moderately Informative Inherited
Biological Process (BP) regulation of cellular component organization 0.01154 Moderately Informative Inherited
Biological Process (BP) regulation of cellular biosynthetic process 0.003011 Moderately Informative Inherited
Biological Process (BP) regulation of gene expression 0.02283 Moderately Informative Inherited
Biological Process (BP) cell differentiation 0.1932 Moderately Informative Inherited
Biological Process (BP) negative regulation of metabolic process 1 Moderately Informative Inherited
Biological Process (BP) response to biotic stimulus 0.6211 Moderately Informative Inherited
Biological Process (BP) regulation of biological quality 0.9546 Moderately Informative Inherited
Biological Process (BP) anatomical structure morphogenesis 1 Moderately Informative Inherited
Biological Process (BP) response to endogenous stimulus 1 Moderately Informative Inherited
Biological Process (BP) cellular protein modification process 0.8659 Moderately Informative Inherited
Biological Process (BP) lipid metabolic process 0.05011 Moderately Informative Inherited
Biological Process (BP) negative regulation of cellular process 0.5165 Moderately Informative Inherited
Biological Process (BP) positive regulation of cellular process 0.1066 Moderately Informative Inherited
Biological Process (BP) response to external stimulus 1 Moderately Informative Inherited
Biological Process (BP) cellular catabolic process 0.339 Moderately Informative Inherited
Biological Process (BP) organic substance catabolic process 0.6177 Moderately Informative Inherited
Biological Process (BP) carbohydrate metabolic process 0.002424 Moderately Informative Inherited
Biological Process (BP) regulation of multicellular organismal process 0.7373 Moderately Informative Inherited
Biological Process (BP) positive regulation of metabolic process 0.182 Moderately Informative Inherited
Biological Process (BP) negative regulation of cellular component organization 0 Informative Direct
Biological Process (BP) regulation of cytokine production 0 Informative Direct
Biological Process (BP) regulation of apoptotic process 0 Informative Direct
Biological Process (BP) regulation of phosphorylation 0 Informative Direct
Biological Process (BP) regulation of transferase activity 0 Informative Direct
Biological Process (BP) positive regulation of immune system process 0 Informative Direct
Biological Process (BP) immune response 0 Informative Direct
Biological Process (BP) cell death 0 Informative Direct
Biological Process (BP) positive regulation of cellular protein metabolic process 0 Informative Direct
Biological Process (BP) protein oligomerization 0.0000000000215 Informative Direct
Biological Process (BP) monosaccharide metabolic process 0.00000000008227 Informative Direct
Biological Process (BP) positive regulation of phosphate metabolic process 0.00000000008291 Informative Direct
Biological Process (BP) response to bacterium 0.0000000001426 Informative Direct
Biological Process (BP) immune effector process 0.0000000003278 Informative Direct
Biological Process (BP) lipid catabolic process 0.000000003598 Informative Direct
Biological Process (BP) regulation of protein modification process 0.000000007293 Informative Direct
Biological Process (BP) regulation of immune response 0.00000005148 Informative Direct
Biological Process (BP) cell activation 0.00000005981 Informative Direct
Biological Process (BP) fatty acid metabolic process 0.00000009993 Informative Direct
Biological Process (BP) negative regulation of transport 0.0000001403 Informative Direct
Biological Process (BP) regulation of cell proliferation 0.0000002907 Informative Direct
Biological Process (BP) regulation of intracellular signal transduction 0.0000003393 Informative Direct
Biological Process (BP) carboxylic acid catabolic process 0.000001579 Informative Direct
Biological Process (BP) single-organism cellular localization 0.000009463 Informative Direct
Biological Process (BP) response to nitrogen compound 0.00001281 Informative Direct
Biological Process (BP) single-organism membrane organization 0.00001392 Informative Direct
Biological Process (BP) positive regulation of catalytic activity 0.00001503 Informative Direct
Biological Process (BP) regulation of lipid metabolic process 0.00002764 Informative Direct
Biological Process (BP) regulation of peptide transport 0.0001399 Informative Direct
Biological Process (BP) regulation of system process 0.0002297 Informative Direct
Biological Process (BP) regulation of protein localization 0.0003016 Informative Direct
Biological Process (BP) positive regulation of signal transduction 0.0003174 Informative Direct
Biological Process (BP) positive regulation of cellular component organization 0.0004725 Informative Direct
Biological Process (BP) regulation of proteolysis 1 Informative Inherited
Biological Process (BP) regulation of hydrolase activity 1 Informative Inherited
Biological Process (BP) regulation of cell differentiation 0.1566 Informative Inherited
Biological Process (BP) regulation of cellular localization 0.01254 Informative Inherited
Biological Process (BP) cell surface receptor signaling pathway 1 Informative Inherited
Biological Process (BP) positive regulation of developmental process 0.5284 Informative Inherited
Biological Process (BP) positive regulation of multicellular organismal process 0.008709 Informative Inherited
Biological Process (BP) negative regulation of multicellular organismal process 0.01764 Informative Inherited
Biological Process (BP) cellular response to oxygen-containing compound 0.08319 Informative Inherited
Biological Process (BP) cellular response to hormone stimulus 0.006952 Informative Inherited
Biological Process (BP) response to oxidative stress 0.002175 Informative Inherited
Biological Process (BP) regulation of anatomical structure morphogenesis 0.003613 Informative Inherited
Biological Process (BP) phosphorylation 0.02076 Informative Inherited
Biological Process (BP) negative regulation of molecular function 1 Informative Inherited
Biological Process (BP) negative regulation of cell communication 0.1006 Informative Inherited
Biological Process (BP) regulation of defense response 0.9745 Informative Inherited
Biological Process (BP) regulation of response to external stimulus 0.3708 Informative Inherited
Biological Process (BP) negative regulation of cellular biosynthetic process 0.5774 Informative Inherited
Biological Process (BP) negative regulation of macromolecule biosynthetic process 0.7761 Informative Inherited
Biological Process (BP) negative regulation of signaling 0.04233 Informative Inherited
Biological Process (BP) animal organ morphogenesis 0.5363 Informative Inherited
Biological Process (BP) negative regulation of cellular protein metabolic process 0.5588 Informative Inherited
Biological Process (BP) regulation of cellular component movement 0.001006 Informative Inherited
Biological Process (BP) regulation of locomotion 0.02214 Informative Inherited
Biological Process (BP) positive regulation of transport 0.004479 Informative Inherited
Biological Process (BP) negative regulation of response to stimulus 0.8908 Informative Inherited
Biological Process (BP) response to wounding 0.008325 Informative Inherited
Biological Process (BP) system process 0.0265 Informative Inherited
Biological Process (BP) intracellular signal transduction 1 Informative Inherited
Biological Process (BP) positive regulation of sequence-specific DNA binding transcription factor activity 0 Highly Informative Direct
Biological Process (BP) regulation of MAP kinase activity 0 Highly Informative Direct
Biological Process (BP) positive regulation of cytokine production 0 Highly Informative Direct
Biological Process (BP) negative regulation of carbohydrate metabolic process 0 Highly Informative Direct
Biological Process (BP) positive regulation of apoptotic process 0 Highly Informative Direct
Biological Process (BP) cytokine-mediated signaling pathway 0 Highly Informative Direct
Biological Process (BP) regulation of protein complex disassembly 0 Highly Informative Direct
Biological Process (BP) positive regulation of protein serine/threonine kinase activity 0 Highly Informative Direct
Biological Process (BP) glucose metabolic process 0.000000000000003734 Highly Informative Direct
Biological Process (BP) inflammatory response 0.00000000000004085 Highly Informative Direct
Biological Process (BP) regulation of lipid localization 0.0000000000001663 Highly Informative Direct
Biological Process (BP) lipid modification 0.0000000000002859 Highly Informative Direct
Biological Process (BP) regulation of cellular response to stress 0.0000000000003704 Highly Informative Direct
Biological Process (BP) regulation of carbohydrate biosynthetic process 0.0000000000006035 Highly Informative Direct
Biological Process (BP) protein localization to membrane 0.000000000009004 Highly Informative Direct
Biological Process (BP) cell proliferation 0.00000000002305 Highly Informative Direct
Biological Process (BP) negative regulation of establishment of protein localization 0.0000000002278 Highly Informative Direct
Biological Process (BP) regulation of blood pressure 0.0000000002406 Highly Informative Direct
Biological Process (BP) endomembrane system organization 0.0000000002886 Highly Informative Direct
Biological Process (BP) positive regulation of leukocyte proliferation 0.0000000005107 Highly Informative Direct
Biological Process (BP) fatty acid catabolic process 0.0000000005234 Highly Informative Direct
Biological Process (BP) coagulation 0.000000002322 Highly Informative Direct
Biological Process (BP) response to carbohydrate 0.000000009475 Highly Informative Direct
Biological Process (BP) regulation of cellular ketone metabolic process 0.000000009718 Highly Informative Direct
Biological Process (BP) regulation of cellular carbohydrate metabolic process 0.00000001231 Highly Informative Direct
Biological Process (BP) negative regulation of defense response 0.00000001535 Highly Informative Direct
Biological Process (BP) regulation of smooth muscle cell proliferation 0.0000001255 Highly Informative Direct
Biological Process (BP) positive regulation of lipid metabolic process 0.0000001804 Highly Informative Direct
Biological Process (BP) negative regulation of response to external stimulus 0.0000001804 Highly Informative Direct
Biological Process (BP) negative regulation of intracellular transport 0.00000021 Highly Informative Direct
Biological Process (BP) MAPK cascade 0.000000259 Highly Informative Direct
Biological Process (BP) negative regulation of locomotion 0.0000002875 Highly Informative Direct
Biological Process (BP) kidney development 0.0000003867 Highly Informative Direct
Biological Process (BP) carbohydrate homeostasis 0.0000004273 Highly Informative Direct
Biological Process (BP) negative regulation of cellular component movement 0.0000005639 Highly Informative Direct
Biological Process (BP) regulation of intracellular protein transport 0.000002306 Highly Informative Direct
Biological Process (BP) wound healing 0.000003591 Highly Informative Direct
Biological Process (BP) regulation of vesicle-mediated transport 0.000003707 Highly Informative Direct
Biological Process (BP) regulation of hemopoiesis 0.000009203 Highly Informative Direct
Biological Process (BP) positive regulation of cell adhesion 0.00001618 Highly Informative Direct
Biological Process (BP) response to drug 0.00001895 Highly Informative Direct
Biological Process (BP) response to peptide hormone 0.00003539 Highly Informative Direct
Biological Process (BP) hemostasis 0.0000519 Highly Informative Direct
Biological Process (BP) negative regulation of cytokine production 0.00005624 Highly Informative Direct
Biological Process (BP) regulation of DNA metabolic process 0.00007932 Highly Informative Direct
Biological Process (BP) protein homotrimerization 0.0001105 Highly Informative Direct
Biological Process (BP) positive regulation of cell development 0.000139 Highly Informative Direct
Biological Process (BP) positive regulation of MAPK cascade 0.0002429 Highly Informative Direct
Biological Process (BP) response to molecule of bacterial origin 0.0003703 Highly Informative Direct
Biological Process (BP) lymphocyte activation 0.0005688 Highly Informative Direct
Biological Process (BP) cellular response to organonitrogen compound 0.0009135 Highly Informative Direct
Biological Process (BP) regulation of apoptotic signaling pathway 0.09444 Highly Informative Inherited
Biological Process (BP) regulation of binding 0.007684 Highly Informative Inherited
Biological Process (BP) apoptotic process 1 Highly Informative Inherited
Biological Process (BP) negative regulation of protein modification process 0.3364 Highly Informative Inherited
Biological Process (BP) negative regulation of phosphate metabolic process 0.7091 Highly Informative Inherited
Biological Process (BP) regulation of lymphocyte proliferation 0.001366 Highly Informative Inherited
Biological Process (BP) positive regulation of lymphocyte activation 0.002323 Highly Informative Inherited
Biological Process (BP) negative regulation of cell proliferation 0.01003 Highly Informative Inherited
Biological Process (BP) negative regulation of intracellular signal transduction 0.3893 Highly Informative Inherited
Biological Process (BP) regulation of nucleocytoplasmic transport 1 Highly Informative Inherited
Biological Process (BP) positive regulation of protein transport 0.5617 Highly Informative Inherited
Biological Process (BP) positive regulation of cellular protein localization 0.7947 Highly Informative Inherited
Biological Process (BP) positive regulation of intracellular transport 0.9294 Highly Informative Inherited
Biological Process (BP) regulation of protein import 0.717 Highly Informative Inherited
Biological Process (BP) regulation of protein localization to nucleus 1 Highly Informative Inherited
Biological Process (BP) negative regulation of immune system process 0.00468 Highly Informative Inherited
Biological Process (BP) positive regulation of proteolysis 1 Highly Informative Inherited
Biological Process (BP) positive regulation of hydrolase activity 1 Highly Informative Inherited
Biological Process (BP) regulation of cysteine-type endopeptidase activity 0.002437 Highly Informative Inherited
Biological Process (BP) positive regulation of immune effector process 1 Highly Informative Inherited
Biological Process (BP) regulation of leukocyte mediated immunity 0.353 Highly Informative Inherited
Biological Process (BP) positive regulation of adaptive immune response based on somatic recombination of immune receptors b 0.07978 Highly Informative Inherited
Biological Process (BP) regulation of production of molecular mediator of immune response 0.09302 Highly Informative Inherited
Molecular Function (MF) binding 0.1388 Least Informative Inherited
Molecular Function (MF) structural molecule activity 0.2252 Moderately Informative Inherited
Molecular Function (MF) oxidoreductase activity 1 Moderately Informative Inherited
Molecular Function (MF) receptor binding 0 Informative Direct
Molecular Function (MF) cytokine receptor binding 0.00001157 Highly Informative Direct
Molecular Function (MF) peroxidase activity 0.00008951 Highly Informative Direct
Cellular Component (CC) cytoplasmic part 1 Least Informative Inherited
Cellular Component (CC) extracellular region part 0 Moderately Informative Direct
Cellular Component (CC) cell surface 0 Informative Direct
Cellular Component (CC) perinuclear region of cytoplasm 0.000003635 Highly Informative Direct

Document: GO annotation of SCOP domains

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Biological processImmunity0Moderately InformativeDirect
Biological processApoptosis0.000000000241Moderately InformativeDirect
Biological processDifferentiation0.0000001484Moderately InformativeDirect
Biological processAngiogenesis0.000000000000007769InformativeDirect
Biological processCell adhesion0.00000000953InformativeDirect
Biological processInnate immunity0.04467InformativeInherited
Biological processComplement pathway0.000000000009948Highly InformativeDirect
Cellular componentMembrane0Least InformativeDirect
Cellular componentSecreted0Moderately InformativeDirect
Cellular componentCell junction0.0005446Moderately InformativeDirect
Cellular componentCell membrane0.0005521Moderately InformativeDirect
Cellular componentSynapse0.0000001985InformativeDirect
Cellular componentLysosome0.0000005813InformativeDirect
DiseaseDisease mutation0.0007722Least InformativeDirect
DomainSignal0.0000000000000324Least InformativeDirect
DomainTransmembrane0.0004033Least InformativeDirect
DomainSignal-anchor0InformativeDirect
DomainCollagen0Highly InformativeDirect
Post-translational modificationCytokine0Highly InformativeDirect
Post-translational modificationHormone0.000000000000004136Highly InformativeDirect
Post-translational modificationGlycoprotein0Least InformativeDirect
Post-translational modificationDisulfide bond0Least InformativeDirect
Post-translational modificationHydroxylation0InformativeDirect
Post-translational modificationMyristate0InformativeDirect

Document: KW annotation of SCOP domains

InterPro annotation
Cross references IPR008983 SSF49842 Protein matches
Abstract

The tumour necrosis factor (TNF)-like domains are found in both TNF and C1q protein families. Structurally these domains self-associate to make a compact bell-shaped homotrimer, each monomer being composed of an anti-parallel beta-sheet sandwich with a jellyroll topology. Both TNF and C1q family members can be expressed as soluble plasma proteins or as type II membrane-bound proteins.

TNF family members bind extracellularly to cysteine-rich receptors, thereby inducing a clustering of the receptors, which subsequently triggers the intracellular apoptotic cascade. The TNF proteins are important mediators in inflammation, immune responses and cytotoxicity through their interaction with the TNF-R55 and the TNF-R75 cell-surface receptors [PubMed9442056]. Other TNF family members include the CD40 ligand (C-terminal TNF-like domain) which is involved in the immune response via the CD40 receptor [PubMed8589998], TRAIL which selectively induces apoptosis in tumour cells via DR4 and DR5 receptors [PubMed10651627], the RANK ligand which triggers osteoclastogenesis via the RANK receptor [PubMed11733492], and TALL-1 (soluble domain) which is involved in the immune response via the TACI, BCMA, and BAFF-R receptors [PubMed11862220].

C1q proteins also contain TNF-like domains. C1q family members include the serum protein ACRP30 (C-terminal TNF-like domain) which may be involved in energy homeostasis and obesity, and X-NC1 (C-terminal TNF-like domain) which is crucial for collagen X assembly in bone tissue [PubMed11839302].


InterPro database


PDBeMotif information about ligands, sequence and structure motifs
Cross references PDB entries
Ligand binding statistics
Nucleic-acid binding statistics
Occurrence of secondary structure elements
Occurrence of small 3D structural motifs

PDBeMotif resource

Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Gene Ontology (high-coverage) · UniProtKB KeyWords (KW) ]

Internal database links

Browse genome assignments for this superfamily. The SUPERFAMILY hidden Markov model library has been used to carry out SCOP domain assignments to all genomes at the superfamily level.


Alignments of sequences to 19 models in this superfamily are available by clicking on the 'Alignments' icon above. PDB sequences less than 40% identical are shown by default, but any other sequence(s) may be aligned. Select PDB sequences, genome sequences, or paste in or upload your own sequences.


Browse and view proteins in genomes which have different domain combinations including a TNF-like domain.


Examine the distribution of domain superfamilies, or families, across the major taxonomic kingdoms or genomes within a kingdom. This gives an immediate impression of how superfamilies, or families, are restricted to certain kingdoms of life.


Explore domain occurrence network where nodes represent genomes and edges are domain architectures (shared between genomes) containing the superfamily of interest.

There are 19 hidden Markov models representing the TNF-like superfamily. Information on how the models are built, and plots showing hydrophobicity, match emmission probabilities and insertion/deletion probabilities can be inspected.


Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Gene Ontology (high-coverage) · UniProtKB KeyWords (KW) · Internal database links ]