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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 2018_03 genome PDB chains (SCOP 1.75)
Domains 4,857 15,215 40
Proteins 4,643 14,867 40

Functional annotation
General category Processes_EC
Detailed category Immune response

Function annotation of SCOP domain superfamilies

Disease Ontology (DO)

(show details)
DO termFDR (all)SDDO levelAnnotation (direct or inherited)
Disease Ontology (DO)nervous system disease0.1163Least InformativeInherited
Disease Ontology (DO)organ system cancer0.562Least InformativeInherited
Disease Ontology (DO)connective tissue disease0.0000000002609Moderately InformativeDirect
Disease Ontology (DO)artery disease0.00008665Moderately InformativeDirect
Disease Ontology (DO)urinary system disease0.0003473Moderately InformativeDirect
Disease Ontology (DO)disease of metabolism0.005568Moderately InformativeInherited
Disease Ontology (DO)hematologic cancer0.006983Moderately InformativeInherited
Disease Ontology (DO)hematopoietic system disease0.009461Moderately InformativeInherited
Disease Ontology (DO)endocrine system disease0.02535Moderately InformativeInherited
Disease Ontology (DO)sensory system disease0.2085Moderately InformativeInherited
Disease Ontology (DO)hypersensitivity reaction type II disease0.2813Moderately InformativeInherited
Disease Ontology (DO)neurodegenerative disease0.4172Moderately InformativeInherited
Disease Ontology (DO)skin disease0.7795Moderately InformativeInherited
Disease Ontology (DO)atherosclerosis0.000001714InformativeDirect
Disease Ontology (DO)hemorrhagic disease0.000001923InformativeDirect
Disease Ontology (DO)arthritis0.000002127InformativeDirect
Disease Ontology (DO)myeloid neoplasm0.00002651InformativeDirect
Disease Ontology (DO)multiple sclerosis0.00005089InformativeDirect
Disease Ontology (DO)intrinsic cardiomyopathy0.0003222InformativeDirect
Disease Ontology (DO)alopecia0.0005424InformativeDirect
Disease Ontology (DO)bullous skin disease0.03592InformativeInherited
Disease Ontology (DO)pancreas disease0.05729InformativeInherited
Disease Ontology (DO)primary immunodeficiency disease0.09354InformativeInherited
Disease Ontology (DO)lysosomal storage disease0.1054InformativeInherited
Disease Ontology (DO)lymphoma0.1299InformativeInherited
Disease Ontology (DO)coronary artery disease0.1617InformativeInherited
Disease Ontology (DO)rheumatic disease0.1977InformativeInherited
Disease Ontology (DO)collagen disease0.238InformativeInherited
Disease Ontology (DO)glucose metabolism disease1InformativeInherited
Disease Ontology (DO)rheumatoid arthritis0.0000000943Highly InformativeDirect
Disease Ontology (DO)pemphigus0.00001678Highly InformativeDirect
Disease Ontology (DO)primary open angle glaucoma0.00002611Highly InformativeDirect
Disease Ontology (DO)dilated cardiomyopathy0.0000324Highly InformativeDirect
Disease Ontology (DO)agammaglobulinemia0.0002363Highly InformativeDirect
Disease Ontology (DO)Burkitt lymphoma0.0002895Highly InformativeDirect
Disease Ontology (DO)thrombocytopenia0.0006343Highly InformativeDirect
Disease Ontology (DO)meningitis0.000826Highly InformativeDirect
Disease Ontology (DO)endocrine pancreas disease0.03964Highly InformativeInherited

Document: DO annotation of SCOP domains

Human Phenotype (HP)

(show details)
HP termFDR (all)SDHP levelAnnotation (direct or inherited)
Phenotypic Abnormality (PA)Abnormality of metabolism/homeostasis0.2181Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the genitourinary system0.9622Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of immune system physiology0.002721Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of blood and blood-forming tissues0.2491Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the urinary system physiology0.3889Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the upper urinary tract0.5348Moderately InformativeInherited
Phenotypic Abnormality (PA)Complement deficiency0.00003567InformativeDirect
Phenotypic Abnormality (PA)Abnormal leukocyte morphology0.07557InformativeInherited
Phenotypic Abnormality (PA)Abnormal renal physiology0.17InformativeInherited
Phenotypic Abnormality (PA)Abnormal renal morphology0.343InformativeInherited
Phenotypic Abnormality (PA)Increased inflammatory response1InformativeInherited
Phenotypic Abnormality (PA)Autoimmunity0.0002905Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormality of renal glomerulus morphology0.007207Highly InformativeInherited
Phenotypic Abnormality (PA)Abnormal immunoglobulin level0.9572Highly InformativeInherited

Document: HP annotation of SCOP domains

Mouse Phenotype (MP)

(show details)
MP termFDR (all)SDMP levelAnnotation (direct or inherited)
Mammalian Phenotype (MP)hematopoietic system phenotype0.01544Least InformativeInherited
Mammalian Phenotype (MP)immune system phenotype0.01822Least InformativeInherited
Mammalian Phenotype (MP)abnormal immune system organ morphology0.01573Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal eye morphology0.03808Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal immune serum protein physiology0.04824Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal professional antigen presenting cell physiology0.2016Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal inflammatory response0.3729Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal leukocyte physiology0.5985Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal gland morphology0.8964Moderately InformativeInherited
Mammalian Phenotype (MP)autoimmune response0.000002853InformativeDirect
Mammalian Phenotype (MP)abnormal Peyer's patch morphology0.0000841InformativeDirect
Mammalian Phenotype (MP)abnormal lymph node morphology0.0002201InformativeDirect
Mammalian Phenotype (MP)joint inflammation0.004131InformativeInherited
Mammalian Phenotype (MP)abnormal spleen morphology0.01126InformativeInherited
Mammalian Phenotype (MP)abnormal interferon secretion0.01379InformativeInherited
Mammalian Phenotype (MP)abnormal humoral immune response0.01713InformativeInherited
Mammalian Phenotype (MP)abnormal retinal neuronal layer morphology0.01738InformativeInherited
Mammalian Phenotype (MP)abnormal thymus morphology0.02536InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin secretion0.1785InformativeInherited
Mammalian Phenotype (MP)abnormal lymph organ size0.2898InformativeInherited
Mammalian Phenotype (MP)abnormal IgG2a level0.0000005937Highly InformativeDirect
Mammalian Phenotype (MP)abnormal mesenteric lymph node morphology0.000005152Highly InformativeDirect
Mammalian Phenotype (MP)abnormal spleen germinal center morphology0.00003737Highly InformativeDirect
Mammalian Phenotype (MP)lymph node hypoplasia0.000044Highly InformativeDirect
Mammalian Phenotype (MP)arthritis0.00007562Highly InformativeDirect
Mammalian Phenotype (MP)decreased interleukin-10 secretion0.000113Highly InformativeDirect
Mammalian Phenotype (MP)abnormal lymph node B cell domain morphology0.0001322Highly InformativeDirect
Mammalian Phenotype (MP)thin retinal outer nuclear layer0.0006775Highly InformativeDirect
Mammalian Phenotype (MP)abnormal thymus epithelium morphology0.0006974Highly InformativeDirect
Mammalian Phenotype (MP)thin retinal inner nuclear layer0.0007622Highly InformativeDirect
Mammalian Phenotype (MP)abnormal response to transplant0.0008881Highly InformativeDirect
Mammalian Phenotype (MP)abnormal thymus medulla morphology0.00171Highly InformativeInherited
Mammalian Phenotype (MP)abnormal peripheral lymph node morphology0.01318Highly InformativeInherited
Mammalian Phenotype (MP)abnormal Peyer's patch size0.3787Highly InformativeInherited

Document: MP annotation of SCOP domains

Zebrafish Anatomy (ZA)

(show details) Document: ZA annotation of SCOP domains

Xenopus Anatomy (XA)

(show details) Document: XA annotation of SCOP domains

InterPro annotation
Cross references IPR008983 SSF49842 Protein matches

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 · Disease Ontology (DO) · Human Phenotype (HP) · Mouse Phenotype (MP) · Zebrafish Anatomy (ZA) · Xenopus Anatomy (XA) ]

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 · Disease Ontology (DO) · Human Phenotype (HP) · Mouse Phenotype (MP) · Zebrafish Anatomy (ZA) · Xenopus Anatomy (XA) · Internal database links ]