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DEATH domain superfamily

SCOP classification
Root:   SCOP hierarchy in SUPERFAMILY [ 0] (11)
Class:   All alpha proteins [ 46456] (284)
Fold:   DEATH domain [ 47985]
Superfamily:   DEATH domain [ 47986] (4)
Families:   DEATH domain, DD [ 81312] (8)
  DEATH effector domain, DED [ 81388] (2)
  Caspase recruitment domain, CARD [ 81313] (5)
  Pyrin domain, PYD [ 101298] (2)


Superfamily statistics
Genomes (147) Uniprot 2018_03 genome PDB chains (SCOP 1.75)
Domains 9,260 0 25
Proteins 8,457 0 25


Functional annotation
General category Processes_IC
Detailed category Cell cycle, Apoptosis

Document:
Function annotation of SCOP domain superfamilies

Enzyme Commission (EC)

(show details)
EC termFDR (all)SDEO levelAnnotation (direct or inherited)
Enzyme Commission (EC)Acting on peptide bonds (peptide hydrolases)0Least InformativeDirect
Enzyme Commission (EC)Protein-serine/threonine kinases0Moderately InformativeDirect
Enzyme Commission (EC)Cysteine endopeptidases0Moderately InformativeDirect

Document: EC annotation of SCOP domains

Disease Ontology (DO)

(show details)
DO termFDR (all)SDDO levelAnnotation (direct or inherited)
Disease Ontology (DO)disease by infectious agent0.00000007443Moderately InformativeDirect
Disease Ontology (DO)connective tissue disease0.002191Moderately InformativeInherited
Disease Ontology (DO)gastrointestinal system disease0.01184Moderately InformativeInherited
Disease Ontology (DO)syndrome0.05146Moderately InformativeInherited
Disease Ontology (DO)hypersensitivity reaction type II disease0.9769Moderately InformativeInherited
Disease Ontology (DO)inflammatory bowel disease0.000001371InformativeDirect
Disease Ontology (DO)arthropathy0.0168InformativeInherited
Disease Ontology (DO)hypersensitivity reaction type IV disease0.03921InformativeInherited
Disease Ontology (DO)viral infectious disease1InformativeInherited
Disease Ontology (DO)irritable bowel syndrome0.000008894Highly InformativeDirect
Disease Ontology (DO)spondyloarthropathy0.00001098Highly InformativeDirect

Document: DO annotation of SCOP domains

Human Phenotype (HP)

(show details)
HP termFDR (all)SDHP levelAnnotation (direct or inherited)
Phenotypic Abnormality (PA)Abnormality of the integument0.009921Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of metabolism/homeostasis0.03406Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the digestive system0.1836Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the cardiovascular system0.3437Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the head0.3523Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the skeletal system0.8753Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of nervous system morphology0.8839Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the eye0.8901Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the genitourinary system0.9485Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of blood and blood-forming tissues0.0001994Moderately InformativeDirect
Phenotypic Abnormality (PA)Abnormality of immune system physiology0.01231Moderately InformativeInherited
Phenotypic Abnormality (PA)Neoplasm0.01276Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the abdominal organs0.01422Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the vasculature0.04372Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the respiratory system0.04542Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal fundus morphology0.4232Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of cardiovascular system morphology0.4507Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the oral cavity0.4526Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of digestive system physiology0.617Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal eye physiology0.6207Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal joint morphology0.6402Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of skin morphology0.9031Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal reproductive system morphology0.9735Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal spleen morphology0.000001725InformativeDirect
Phenotypic Abnormality (PA)CNS infection0.00009045InformativeDirect
Phenotypic Abnormality (PA)Visceromegaly0.0001137InformativeDirect
Phenotypic Abnormality (PA)Abnormal lung morphology0.00184InformativeInherited
Phenotypic Abnormality (PA)Constitutional symptom0.00297InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the uvea0.007732InformativeInherited
Phenotypic Abnormality (PA)Abnormal leukocyte morphology0.02169InformativeInherited
Phenotypic Abnormality (PA)Abnormality of oral mucosa0.03164InformativeInherited
Phenotypic Abnormality (PA)Autoimmunity0.08628InformativeInherited
Phenotypic Abnormality (PA)Localized skin lesion0.1493InformativeInherited
Phenotypic Abnormality (PA)Abdominal symptom0.1587InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the optic nerve0.2729InformativeInherited
Phenotypic Abnormality (PA)Abnormality of circulating protein level0.4723InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the testis0.7724InformativeInherited
Phenotypic Abnormality (PA)Increased inflammatory response1InformativeInherited
Phenotypic Abnormality (PA)Lymphadenopathy0.00000000001021Highly InformativeDirect
Phenotypic Abnormality (PA)Vasculitis0.00000005826Highly InformativeDirect
Phenotypic Abnormality (PA)Uveitis0.00000006738Highly InformativeDirect
Phenotypic Abnormality (PA)Splenomegaly0.0000002141Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormality of skin physiology0.0000002512Highly InformativeDirect
Phenotypic Abnormality (PA)Lymphoma0.00001666Highly InformativeDirect
Phenotypic Abnormality (PA)Anemia0.00002008Highly InformativeDirect
Phenotypic Abnormality (PA)Optic neuritis0.00006595Highly InformativeDirect
Phenotypic Abnormality (PA)Recurrent aphthous stomatitis0.0001177Highly InformativeDirect
Phenotypic Abnormality (PA)Elevated C-reactive protein level0.0001177Highly InformativeDirect
Phenotypic Abnormality (PA)Pulmonary infiltrates0.0001702Highly InformativeDirect
Phenotypic Abnormality (PA)Pericarditis0.0001943Highly InformativeDirect
Phenotypic Abnormality (PA)Abdominal pain0.0003393Highly InformativeDirect
Phenotypic Abnormality (PA)Papule0.0006761Highly InformativeDirect
Phenotypic Abnormality (PA)Autoimmune thrombocytopenia0.0008935Highly InformativeDirect

Document: HP annotation of SCOP domains

Mouse Phenotype (MP)

(show details)
MP termFDR (all)SDMP levelAnnotation (direct or inherited)
Mammalian Phenotype (MP)hematopoietic system phenotype0.000000002927Least InformativeDirect
Mammalian Phenotype (MP)immune system phenotype0.0000000288Least InformativeDirect
Mammalian Phenotype (MP)cellular phenotype0.000001748Least InformativeDirect
Mammalian Phenotype (MP)mortality/aging0.08315Least InformativeInherited
Mammalian Phenotype (MP)abnormal homeostasis0.4614Least InformativeInherited
Mammalian Phenotype (MP)altered susceptibility to infection0.000000000005929Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal protein level0.000000411Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal immune serum protein physiology0.000004604Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal induced morbidity/mortality0.00001771Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal cell death0.0009775Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal immune system organ morphology0.01005Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal professional antigen presenting cell physiology0.01549Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal hematopoietic cell number0.02024Moderately InformativeInherited
Mammalian Phenotype (MP)liver/biliary system phenotype0.0333Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal leukocyte physiology0.04289Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal blood cell morphology/development0.1104Moderately InformativeInherited
Mammalian Phenotype (MP)respiratory system phenotype0.1193Moderately InformativeInherited
Mammalian Phenotype (MP)hearing/vestibular/ear phenotype0.2692Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal mononuclear cell morphology0.3454Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal inflammatory response0.3874Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal blood cell morphology0.5293Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal myeloid cell morphology0.6814Moderately InformativeInherited
Mammalian Phenotype (MP)autoimmune response0.000001933InformativeDirect
Mammalian Phenotype (MP)abnormal phagocyte morphology0.000006542InformativeDirect
Mammalian Phenotype (MP)abnormal macrophage physiology0.00007851InformativeDirect
Mammalian Phenotype (MP)abnormal circulating cytokine level0.0001274InformativeDirect
Mammalian Phenotype (MP)abnormal liver physiology0.0007444InformativeDirect
Mammalian Phenotype (MP)abnormal intestine physiology0.003024InformativeInherited
Mammalian Phenotype (MP)abnormal spleen morphology0.006411InformativeInherited
Mammalian Phenotype (MP)abnormal lymph node morphology0.01686InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin secretion0.02463InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin level0.0613InformativeInherited
Mammalian Phenotype (MP)abnormal mature B cell morphology0.1324InformativeInherited
Mammalian Phenotype (MP)abnormal interferon secretion0.1742InformativeInherited
Mammalian Phenotype (MP)abnormal hearing physiology0.2023InformativeInherited
Mammalian Phenotype (MP)abnormal respiratory function0.272InformativeInherited
Mammalian Phenotype (MP)abnormal interferon level0.3801InformativeInherited
Mammalian Phenotype (MP)abnormal Peyer's patch morphology0.835InformativeInherited
Mammalian Phenotype (MP)abnormal lymph organ size0.8476InformativeInherited
Mammalian Phenotype (MP)decreased T cell number0.9255InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin-1 beta secretion0.000000000006367Highly InformativeDirect
Mammalian Phenotype (MP)abnormal Peyer's patch size0.000000008807Highly InformativeDirect
Mammalian Phenotype (MP)enlarged lymph nodes0.0000003015Highly InformativeDirect
Mammalian Phenotype (MP)decreased interferon-alpha secretion0.000002049Highly InformativeDirect
Mammalian Phenotype (MP)abnormal spleen germinal center morphology0.00002105Highly InformativeDirect
Mammalian Phenotype (MP)abnormal gut flora balance0.00002707Highly InformativeDirect
Mammalian Phenotype (MP)abnormal airway responsiveness0.00006559Highly InformativeDirect
Mammalian Phenotype (MP)decreased apoptosis0.00007433Highly InformativeDirect
Mammalian Phenotype (MP)abnormal B-1 B cell number0.00008135Highly InformativeDirect
Mammalian Phenotype (MP)abnormal circulating interleukin-18 level0.000256Highly InformativeDirect
Mammalian Phenotype (MP)abnormal macrophage apoptosis0.0003307Highly InformativeDirect
Mammalian Phenotype (MP)abnormal acute inflammation0.000595Highly InformativeDirect
Mammalian Phenotype (MP)decreased inflammatory response0.0009603Highly InformativeDirect
Mammalian Phenotype (MP)abnormal interleukin-6 secretion0.05399Highly InformativeInherited

Document: MP annotation of SCOP domains

Worm Phenotype (WP)

(show details)
WP termFDR (all)SDWP levelAnnotation (direct or inherited)
Worm Phenotype (WP)organism environmental stimulus response variant0.0001605Least InformativeDirect
Worm Phenotype (WP)cell physiology variant0.002867Least InformativeInherited
Worm Phenotype (WP)organism metabolism processing variant0.007256Least InformativeInherited
Worm Phenotype (WP)apoptosis variant0.0004964Moderately InformativeDirect
Worm Phenotype (WP)protein expression variant0.106Moderately InformativeInherited
Worm Phenotype (WP)pattern protein expression variant0.0004733InformativeDirect

Document: WP annotation of SCOP domains

Fly Phenotype (FP)

(show details) Document: FP annotation of SCOP domains

Fly Anatomy (FA)

(show details) Document: FA 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

Enzyme Commission (EC)

(show details)
EC termFDR (all)SDEC levelAnnotation (direct or inherited)
Enzyme Commission (EC)Hydrolases0.0000003309Least InformativeDirect
Enzyme Commission (EC)Transferring phosphorus-containing groups0.0001719Least InformativeDirect
Enzyme Commission (EC)Protein-serine/threonine kinases0Moderately InformativeDirect
Enzyme Commission (EC)Acting on peptide bonds (peptidases)0Moderately InformativeDirect
Enzyme Commission (EC)Acyltransferases0.06538Moderately InformativeInherited
Enzyme Commission (EC)Non-specific serine/threonine protein kinase0InformativeDirect
Enzyme Commission (EC)Cysteine endopeptidases0InformativeDirect
Enzyme Commission (EC)RING-type E3 ubiquitin transferase0.000001506InformativeDirect
Enzyme Commission (EC)Protein-tyrosine kinases0.0004717InformativeDirect
Enzyme Commission (EC)Non-specific protein-tyrosine kinase0.0000007929Highly InformativeDirect

Document: EC annotation of SCOP domains

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Biological processApoptosis0Moderately InformativeDirect
Biological processImmunity0Moderately InformativeDirect
Biological processDifferentiation0.00004735Moderately InformativeDirect
Biological processHost-virus interaction0.00004929Moderately InformativeDirect
Biological processInflammatory response0InformativeDirect
Biological processInnate immunity2.452e-16InformativeDirect
Biological processBiological rhythms0.00000002462InformativeDirect
Cellular componentNucleus0.000000000003473Least InformativeDirect
Cellular componentCytoplasm0.000000000006444Least InformativeDirect
Cellular componentMembrane0.00000571Least InformativeDirect
Cellular componentCell junction0.0000006705Moderately InformativeDirect
Cellular componentCytoskeleton0.00003133Moderately InformativeDirect
Cellular componentCell projection0.00005839Moderately InformativeDirect
Cellular componentSynapse0.00000000002682InformativeDirect
Cellular componentLysosome0.0009904InformativeDirect
Cellular componentSarcoplasmic reticulum0.00000003742Highly InformativeDirect
Coding sequence diversityPolymorphism0.000322Moderately InformativeDirect
DiseaseAmyloidosis0.00000006084Highly InformativeDirect
DomainRepeat0Least InformativeDirect
DomainTransmembrane1Least InformativeInherited
DomainANK repeat0InformativeDirect
DomainLeucine-rich repeat0InformativeDirect
DomainImmunoglobulin domain0.000000001258InformativeDirect
Molecular functionNucleotide-binding0.04304Least InformativeInherited
Post-translational modificationHydrolase1Least InformativeInherited
Post-translational modificationTransferase1Least InformativeInherited
Post-translational modificationDevelopmental protein0Moderately InformativeDirect
Post-translational modificationReceptor0Moderately InformativeDirect
Post-translational modificationProtease0.00000000001228Moderately InformativeDirect
Post-translational modificationActivator0.000002142Moderately InformativeDirect
Post-translational modificationKinase0.1682Moderately InformativeInherited
Post-translational modificationThiol protease0InformativeDirect
Post-translational modificationCalmodulin-binding0.000000000004784InformativeDirect
Post-translational modificationSerine/threonine-protein kinase0.000000003458InformativeDirect
Post-translational modificationPhosphoprotein0.00000000000001046Least InformativeDirect
Post-translational modificationUbl conjugation0.00000001169Moderately InformativeDirect
Post-translational modificationZymogen0.0000000001006InformativeDirect

Document: KW annotation of SCOP domains

InterPro annotation
Cross references IPR011029 SSF47986 Protein matches
Abstract

The death domain (DD) is a conserved region of about 80 residues found on death receptors, and which is required for death signalling, as well as a variety of non-apoptotic functions [PubMed11828422, PubMed12655292]. Proteins containing this domain include the low affinity neurotrophin receptor p73, Fas, FADD (Fas-associated death domain protein), TNF-1 (tumour necrosis factor receptor-1), Pelle protein kinase, and the Tube adaptor protein [PubMed15226512].

The induction of apoptosis also relies on the presence of a second domain, called the death effector domain. The death effector domain (DED) occurs in proteins that regulate programmed cell death, including both pro- and anti-apoptotic proteins; many of these proteins are also involved in controlling cellular activation and proliferation pathways [PubMed12719729]. Proteins containing this domain include FADD (DED N-terminal, DD C-terminal), PEA-15 (phosphoproteins enriched in astrocytes 15kDa), caspases and FLIP.

The induction of apoptosis results in the activation of caspases, a family of aspartyl-specific cysteine proteases that are the main executioners of apoptosis. For example, the DED of FADD recruits two DED-containing caspases, caspase-8 and caspase-10, to form the death-inducing signal complex, which initiates apoptosis. Proteins containing the caspase recruitment domain (CARD) are involved in the recruitment and activation of caspases during apoptosis [PubMed12101092]. Other CARD proteins participate in NF-kappaB signalling pathways associated with innate or adaptive immune responses. Proteins containing CARD include Raidd, APAF-1 (apoptotic protease activating factor 1), procaspase 9 and iceberg (inhibitor of interleukin-1-beta generation).

The DD shows strong structural similarity to both DED and CARD. They all display a 6-helical closed bundle fold, with greek key topology and an internal psuedo two-fold symmetry. However, despite their overall similarity in topology, each domain forms specialised interactions, typically only with members of its own subfamily, for example DED with DED.


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 · Enzyme Commission (EC) · Disease Ontology (DO) · Human Phenotype (HP) · Mouse Phenotype (MP) · Worm Phenotype (WP) · Fly Phenotype (FP) · Fly Anatomy (FA) · Zebrafish Anatomy (ZA) · Xenopus Anatomy (XA) · Enzyme Commission (EC) · 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 18 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 DEATH domain 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 18 hidden Markov models representing the DEATH domain 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 · Enzyme Commission (EC) · Disease Ontology (DO) · Human Phenotype (HP) · Mouse Phenotype (MP) · Worm Phenotype (WP) · Fly Phenotype (FP) · Fly Anatomy (FA) · Zebrafish Anatomy (ZA) · Xenopus Anatomy (XA) · Enzyme Commission (EC) · UniProtKB KeyWords (KW) · Internal database links ]