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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 24,966 25
Proteins 8,457 22,625 25

Functional annotation
General category Processes_IC
Detailed category Cell cycle, Apoptosis

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 metabolism/homeostasis0.0354Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the digestive system0.1936Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the cardiovascular system0.3599Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the head0.3655Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the skeletal system0.8887Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of nervous system morphology0.8921Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the eye0.8949Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the genitourinary system0.9527Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of blood and blood-forming tissues0.000288Moderately InformativeDirect
Phenotypic Abnormality (PA)Abnormality of immune system physiology0.0129Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the abdominal organs0.01334Moderately InformativeInherited
Phenotypic Abnormality (PA)Neoplasm0.01374Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the vasculature0.04378Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the respiratory system0.04882Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of cardiovascular system morphology0.4628Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal oral cavity morphology0.4807Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of digestive system physiology0.6316Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal eye physiology0.6319Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal globe morphology0.6482Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal joint morphology0.6563Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of skin morphology0.9027Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal reproductive system morphology0.9747Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal spleen morphology0.000001801InformativeDirect
Phenotypic Abnormality (PA)CNS infection0.00008966InformativeDirect
Phenotypic Abnormality (PA)Visceromegaly0.0001127InformativeDirect
Phenotypic Abnormality (PA)Abnormal lung morphology0.001978InformativeInherited
Phenotypic Abnormality (PA)Constitutional symptom0.003679InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the uvea0.007614InformativeInherited
Phenotypic Abnormality (PA)Abnormal leukocyte morphology0.01779InformativeInherited
Phenotypic Abnormality (PA)Abnormal oral mucosa morphology0.03146InformativeInherited
Phenotypic Abnormality (PA)Localized skin lesion0.1481InformativeInherited
Phenotypic Abnormality (PA)Abdominal symptom0.1663InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the testis0.7745InformativeInherited
Phenotypic Abnormality (PA)Increased inflammatory response1InformativeInherited
Phenotypic Abnormality (PA)Lymphadenopathy0.00000000001084Highly InformativeDirect
Phenotypic Abnormality (PA)Uveitis0.00000004985Highly InformativeDirect
Phenotypic Abnormality (PA)Vasculitis0.0000000566Highly InformativeDirect
Phenotypic Abnormality (PA)Splenomegaly0.0000002274Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormality of skin physiology0.0000002803Highly InformativeDirect
Phenotypic Abnormality (PA)Lymphoma0.00001988Highly InformativeDirect
Phenotypic Abnormality (PA)Anemia0.0000397Highly InformativeDirect
Phenotypic Abnormality (PA)Optic neuritis0.0000632Highly InformativeDirect
Phenotypic Abnormality (PA)Elevated C-reactive protein level0.00009838Highly InformativeDirect
Phenotypic Abnormality (PA)Recurrent aphthous stomatitis0.0001178Highly InformativeDirect
Phenotypic Abnormality (PA)Pulmonary infiltrates0.0001629Highly InformativeDirect
Phenotypic Abnormality (PA)Pericarditis0.0001949Highly InformativeDirect
Phenotypic Abnormality (PA)Abdominal pain0.0003127Highly InformativeDirect
Phenotypic Abnormality (PA)Papule0.0006833Highly 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 phenotype0.000000002911Least InformativeDirect
Mammalian Phenotype (MP)immune system phenotype0.00000002865Least InformativeDirect
Mammalian Phenotype (MP)cellular phenotype0.00000174Least InformativeDirect
Mammalian Phenotype (MP)mortality/aging0.083Least InformativeInherited
Mammalian Phenotype (MP)abnormal homeostasis0.4617Least InformativeInherited
Mammalian Phenotype (MP)altered susceptibility to infection0.000000000005906Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal protein level0.000000408Moderately 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 death0.0009778Moderately 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 phenotype0.03327Moderately 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 phenotype0.2691Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal mononuclear cell morphology0.3453Moderately 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 response0.00000193InformativeDirect
Mammalian Phenotype (MP)abnormal phagocyte morphology0.000006528InformativeDirect
Mammalian Phenotype (MP)abnormal macrophage physiology0.00007852InformativeDirect
Mammalian Phenotype (MP)abnormal circulating cytokine level0.0001274InformativeDirect
Mammalian Phenotype (MP)abnormal liver physiology0.0007437InformativeDirect
Mammalian Phenotype (MP)abnormal intestine physiology0.003024InformativeInherited
Mammalian Phenotype (MP)abnormal spleen morphology0.006412InformativeInherited
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 physiology0.2022InformativeInherited
Mammalian Phenotype (MP)abnormal respiratory function0.2719InformativeInherited
Mammalian Phenotype (MP)abnormal interferon level0.3801InformativeInherited
Mammalian Phenotype (MP)abnormal Peyer's patch morphology0.8349InformativeInherited
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 size0.000000008797Highly InformativeDirect
Mammalian Phenotype (MP)enlarged lymph nodes0.0000003011Highly InformativeDirect
Mammalian Phenotype (MP)decreased interferon-alpha secretion0.000002047Highly InformativeDirect
Mammalian Phenotype (MP)abnormal spleen germinal center morphology0.00002104Highly InformativeDirect
Mammalian Phenotype (MP)abnormal gut flora balance0.00002706Highly InformativeDirect
Mammalian Phenotype (MP)abnormal airway responsiveness0.00006554Highly InformativeDirect
Mammalian Phenotype (MP)decreased apoptosis0.00007431Highly InformativeDirect
Mammalian Phenotype (MP)abnormal B-1 B cell number0.00008127Highly InformativeDirect
Mammalian Phenotype (MP)abnormal circulating interleukin-18 level0.000256Highly InformativeDirect
Mammalian Phenotype (MP)abnormal macrophage apoptosis0.0003307Highly InformativeDirect
Mammalian Phenotype (MP)abnormal acute inflammation0.0005949Highly InformativeDirect
Mammalian Phenotype (MP)decreased inflammatory response0.0009605Highly InformativeDirect
Mammalian Phenotype (MP)abnormal interleukin-6 secretion0.05398Highly 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 variant0.000163Least InformativeDirect
Worm Phenotype (WP)cell physiology variant0.002927Least InformativeInherited
Worm Phenotype (WP)organism metabolism processing variant0.007384Least InformativeInherited
Worm Phenotype (WP)apoptosis variant0.0004989Moderately InformativeDirect
Worm Phenotype (WP)protein expression variant0.1059Moderately InformativeInherited
Worm Phenotype (WP)pattern protein expression variant0.0004722InformativeDirect

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)Hydrolases0.0000003642Least InformativeDirect
Enzyme Commission (EC)Transferring phosphorus-containing groups0.0001692Least InformativeDirect
Enzyme Commission (EC)Protein-serine/threonine kinases0Moderately InformativeDirect
Enzyme Commission (EC)Acting on peptide bonds (peptidases)0Moderately InformativeDirect
Enzyme Commission (EC)Acyltransferases0.06338Moderately InformativeInherited
Enzyme Commission (EC)Non-specific serine/threonine protein kinase0InformativeDirect
Enzyme Commission (EC)Cysteine endopeptidases0InformativeDirect
Enzyme Commission (EC)RING-type E3 ubiquitin transferase0.00000124InformativeDirect
Enzyme Commission (EC)Protein-tyrosine kinases0.0004656InformativeDirect
Enzyme Commission (EC)Non-specific protein-tyrosine kinase0.0000007623Highly InformativeDirect

Document: EC annotation of SCOP domains

InterPro annotation
Cross references IPR011029 SSF47986 Protein matches

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) ]

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) · Internal database links ]