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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 0 40
Proteins 4,643 0 40


Functional annotation
General category Processes_EC
Detailed category Immune response

Document:
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/homeostasis0.2132Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the genitourinary system0.9571Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of immune system physiology0.002312Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of blood and blood-forming tissues0.2272Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the urinary system0.7874Moderately InformativeInherited
Phenotypic Abnormality (PA)Complement deficiency0.00003727InformativeDirect
Phenotypic Abnormality (PA)Autoimmunity0.0003397InformativeDirect
Phenotypic Abnormality (PA)Abnormality of cell physiology0.04053InformativeInherited
Phenotypic Abnormality (PA)Abnormal leukocyte morphology0.07828InformativeInherited
Phenotypic Abnormality (PA)Abnormal renal physiology0.1673InformativeInherited
Phenotypic Abnormality (PA)Abnormal renal morphology0.3383InformativeInherited
Phenotypic Abnormality (PA)Increased inflammatory response1InformativeInherited
Phenotypic Abnormality (PA)Abnormality of renal glomerulus morphology0.007151Highly InformativeInherited
Phenotypic Abnormality (PA)Abnormal immunoglobulin level0.9516Highly 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 phenotype0.01549Least InformativeInherited
Mammalian Phenotype (MP)immune system phenotype0.01828Least InformativeInherited
Mammalian Phenotype (MP)abnormal immune system organ morphology0.01572Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal eye morphology0.03797Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal immune serum protein physiology0.04822Moderately 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 physiology0.5986Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal gland morphology0.8964Moderately InformativeInherited
Mammalian Phenotype (MP)autoimmune response0.000002859InformativeDirect
Mammalian Phenotype (MP)abnormal Peyer's patch morphology0.00008421InformativeDirect
Mammalian Phenotype (MP)abnormal lymph node morphology0.0002202InformativeDirect
Mammalian Phenotype (MP)joint inflammation0.004131InformativeInherited
Mammalian Phenotype (MP)abnormal spleen morphology0.01127InformativeInherited
Mammalian Phenotype (MP)abnormal interferon secretion0.01379InformativeInherited
Mammalian Phenotype (MP)abnormal humoral immune response0.01713InformativeInherited
Mammalian Phenotype (MP)abnormal retinal neuronal layer morphology0.01739InformativeInherited
Mammalian Phenotype (MP)abnormal thymus morphology0.02536InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin secretion0.1784InformativeInherited
Mammalian Phenotype (MP)abnormal lymph organ size0.2898InformativeInherited
Mammalian Phenotype (MP)abnormal IgG2a level0.000000595Highly InformativeDirect
Mammalian Phenotype (MP)abnormal mesenteric lymph node morphology0.000005159Highly InformativeDirect
Mammalian Phenotype (MP)abnormal spleen germinal center morphology0.0000374Highly InformativeDirect
Mammalian Phenotype (MP)lymph node hypoplasia0.00004408Highly InformativeDirect
Mammalian Phenotype (MP)arthritis0.00007574Highly InformativeDirect
Mammalian Phenotype (MP)decreased interleukin-10 secretion0.0001131Highly InformativeDirect
Mammalian Phenotype (MP)abnormal lymph node B cell domain morphology0.0001324Highly InformativeDirect
Mammalian Phenotype (MP)thin retinal outer nuclear layer0.0006786Highly InformativeDirect
Mammalian Phenotype (MP)abnormal thymus epithelium morphology0.0006977Highly InformativeDirect
Mammalian Phenotype (MP)thin retinal inner nuclear layer0.0007629Highly InformativeDirect
Mammalian Phenotype (MP)abnormal response to transplant0.0008894Highly InformativeDirect
Mammalian Phenotype (MP)abnormal thymus medulla morphology0.001711Highly 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

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Biological processImmunity0Moderately InformativeDirect
Biological processApoptosis0.0000000002185Moderately InformativeDirect
Biological processDifferentiation0.0000001699Moderately InformativeDirect
Biological processAngiogenesis0.000000000000008998InformativeDirect
Biological processCell adhesion0.000000009315InformativeDirect
Biological processInnate immunity0.04814InformativeInherited
Biological processComplement pathway0.000000000003068Highly InformativeDirect
Cellular componentMembrane0Least InformativeDirect
Cellular componentSecreted0Moderately InformativeDirect
Cellular componentCell junction0.000674Moderately InformativeDirect
Cellular componentCell membrane0.0006926Moderately InformativeDirect
Cellular componentSynapse0.000000274InformativeDirect
Cellular componentLysosome0.0000006112InformativeDirect
DiseaseDisease mutation0.0009282Least InformativeDirect
DomainSignal0.0000000000000319Least InformativeDirect
DomainTransmembrane0.0004102Least InformativeDirect
DomainSignal-anchor0InformativeDirect
DomainCollagen0Highly InformativeDirect
Post-translational modificationCytokine0Highly InformativeDirect
Post-translational modificationHormone0.000000000000003965Highly 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 · Disease Ontology (DO) · Human Phenotype (HP) · Mouse Phenotype (MP) · Zebrafish Anatomy (ZA) · Xenopus Anatomy (XA) · 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 · Disease Ontology (DO) · Human Phenotype (HP) · Mouse Phenotype (MP) · Zebrafish Anatomy (ZA) · Xenopus Anatomy (XA) · UniProtKB KeyWords (KW) · Internal database links ]