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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

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 agent0.00000007772Moderately InformativeDirect
Disease Ontology (DO)connective tissue disease0.002211Moderately InformativeInherited
Disease Ontology (DO)gastrointestinal system disease0.01189Moderately InformativeInherited
Disease Ontology (DO)syndrome0.05173Moderately InformativeInherited
Disease Ontology (DO)hypersensitivity reaction type II disease0.9763Moderately InformativeInherited
Disease Ontology (DO)inflammatory bowel disease0.00000139InformativeDirect
Disease Ontology (DO)arthropathy0.01772InformativeInherited
Disease Ontology (DO)hypersensitivity reaction type IV disease0.03931InformativeInherited
Disease Ontology (DO)viral infectious disease1InformativeInherited
Disease Ontology (DO)irritable bowel syndrome0.00000903Highly InformativeDirect
Disease Ontology (DO)spondyloarthropathy0.00001232Highly 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 integument0.003836Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of metabolism/homeostasis0.03216Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the cardiovascular system0.09442Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the digestive system0.2202Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the head0.3725Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of skeletal morphology0.7429Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the eye0.9307Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of nervous system physiology0.967Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of nervous system morphology0.9838Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the genitourinary system0.9915Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of immune system physiology0.00000002952Moderately InformativeDirect
Phenotypic Abnormality (PA)Abnormality of blood and blood-forming tissues0.0006332Moderately InformativeDirect
Phenotypic Abnormality (PA)Abnormality of the abdominal organs0.004705Moderately InformativeInherited
Phenotypic Abnormality (PA)Neoplasm0.0124Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the vasculature0.01826Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal respiratory system morphology0.03557Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal joint morphology0.3668Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of digestive system physiology0.5095Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the gastrointestinal tract0.6515Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal eye morphology0.6635Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal eye physiology0.7004Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of cardiovascular system morphology0.8583Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal circulating metabolite concentration0.9463Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal reproductive system morphology0.9543Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal oral cavity morphology1Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of skin morphology1Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of skin physiology0.000000001349InformativeDirect
Phenotypic Abnormality (PA)Abnormal spleen morphology0.0000003338InformativeDirect
Phenotypic Abnormality (PA)Abnormality of temperature regulation0.000001474InformativeDirect
Phenotypic Abnormality (PA)Inflammatory abnormality of the eye0.000003023InformativeDirect
Phenotypic Abnormality (PA)Visceromegaly0.00003125InformativeDirect
Phenotypic Abnormality (PA)Unusual CNS infection0.0001015InformativeDirect
Phenotypic Abnormality (PA)Abnormal cellular immune system morphology0.0001351InformativeDirect
Phenotypic Abnormality (PA)Abnormal lung morphology0.0004616InformativeDirect
Phenotypic Abnormality (PA)Abnormal uvea morphology0.001154InformativeInherited
Phenotypic Abnormality (PA)Abnormal cellular physiology0.006213InformativeInherited
Phenotypic Abnormality (PA)Abnormal oral mucosa morphology0.01792InformativeInherited
Phenotypic Abnormality (PA)Localized skin lesion0.1289InformativeInherited
Phenotypic Abnormality (PA)Abdominal symptom0.3127InformativeInherited
Phenotypic Abnormality (PA)Abnormal intestine morphology0.3667InformativeInherited
Phenotypic Abnormality (PA)Functional abnormality of the gastrointestinal tract0.538InformativeInherited
Phenotypic Abnormality (PA)Abnormal testis morphology0.8121InformativeInherited
Phenotypic Abnormality (PA)Lymphadenopathy0.000000000004017Highly InformativeDirect
Phenotypic Abnormality (PA)Uveitis0.0000000002053Highly InformativeDirect
Phenotypic Abnormality (PA)Vasculitis0.00000003935Highly InformativeDirect
Phenotypic Abnormality (PA)Retrobulbar optic neuritis0.0000004381Highly InformativeDirect
Phenotypic Abnormality (PA)Lymphoma0.000002734Highly InformativeDirect
Phenotypic Abnormality (PA)Recurrent aphthous stomatitis0.0000174Highly InformativeDirect
Phenotypic Abnormality (PA)Pulmonary infiltrates0.00005134Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormal erythrocyte sedimentation rate0.00005673Highly InformativeDirect
Phenotypic Abnormality (PA)Anemia0.0001428Highly InformativeDirect
Phenotypic Abnormality (PA)Inflammatory abnormality of the skin0.0001475Highly InformativeDirect
Phenotypic Abnormality (PA)Pericarditis0.0002283Highly InformativeDirect
Phenotypic Abnormality (PA)Inflammation of the large intestine0.0005658Highly InformativeDirect
Phenotypic Abnormality (PA)Papule0.0007934Highly InformativeDirect
Phenotypic Abnormality (PA)Headache0.0008655Highly InformativeDirect
Phenotypic Abnormality (PA)Pain0.04805Highly InformativeInherited
Phenotypic Abnormality (PA)Abnormal circulating protein level0.4047Highly InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the stomach0.6643Highly 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 phenotype0.000000002859Least InformativeDirect
Mammalian Phenotype (MP)immune system phenotype0.00000002853Least InformativeDirect
Mammalian Phenotype (MP)cellular phenotype0.000001694Least InformativeDirect
Mammalian Phenotype (MP)mortality/aging0.08361Least InformativeInherited
Mammalian Phenotype (MP)abnormal homeostasis0.4616Least InformativeInherited
Mammalian Phenotype (MP)abnormal protein level0.0000004119Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal immune serum protein physiology0.000004538Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal induced morbidity/mortality0.00001746Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal cell death0.0009676Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal immune system organ morphology0.009912Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal professional antigen presenting cell physiology0.01515Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal hematopoietic cell number0.02027Moderately InformativeInherited
Mammalian Phenotype (MP)liver/biliary system phenotype0.0334Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal leukocyte physiology0.04298Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal blood cell morphology/development0.1105Moderately InformativeInherited
Mammalian Phenotype (MP)respiratory system phenotype0.1189Moderately InformativeInherited
Mammalian Phenotype (MP)hearing/vestibular/ear phenotype0.2699Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal mononuclear cell morphology0.3454Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal inflammatory response0.3862Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal blood cell morphology0.5294Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal myeloid cell morphology0.6816Moderately InformativeInherited
Mammalian Phenotype (MP)autoimmune response0.000001924InformativeDirect
Mammalian Phenotype (MP)abnormal phagocyte morphology0.000006486InformativeDirect
Mammalian Phenotype (MP)abnormal macrophage physiology0.00007865InformativeDirect
Mammalian Phenotype (MP)abnormal circulating cytokine level0.0001334InformativeDirect
Mammalian Phenotype (MP)abnormal liver physiology0.0007406InformativeDirect
Mammalian Phenotype (MP)abnormal intestine physiology0.003022InformativeInherited
Mammalian Phenotype (MP)abnormal spleen morphology0.006315InformativeInherited
Mammalian Phenotype (MP)abnormal lymph node morphology0.017InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin secretion0.02466InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin level0.05947InformativeInherited
Mammalian Phenotype (MP)abnormal mature B cell morphology0.1317InformativeInherited
Mammalian Phenotype (MP)abnormal interferon secretion0.1742InformativeInherited
Mammalian Phenotype (MP)abnormal hearing physiology0.2034InformativeInherited
Mammalian Phenotype (MP)abnormal respiratory function0.272InformativeInherited
Mammalian Phenotype (MP)abnormal interferon level0.3775InformativeInherited
Mammalian Phenotype (MP)abnormal Peyer's patch morphology0.8349InformativeInherited
Mammalian Phenotype (MP)abnormal lymph organ size0.847InformativeInherited
Mammalian Phenotype (MP)decreased T cell number0.9256InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin-1 beta secretion0.000000000006327Highly InformativeDirect
Mammalian Phenotype (MP)abnormal Peyer's patch size0.000000008771Highly InformativeDirect
Mammalian Phenotype (MP)enlarged lymph nodes0.0000003008Highly InformativeDirect
Mammalian Phenotype (MP)decreased interferon-alpha secretion0.000002048Highly InformativeDirect
Mammalian Phenotype (MP)abnormal spleen germinal center morphology0.0000197Highly InformativeDirect
Mammalian Phenotype (MP)abnormal gut flora balance0.00002708Highly InformativeDirect
Mammalian Phenotype (MP)abnormal airway responsiveness0.00006551Highly InformativeDirect
Mammalian Phenotype (MP)decreased apoptosis0.00007545Highly InformativeDirect
Mammalian Phenotype (MP)abnormal B-1 B cell number0.00007635Highly InformativeDirect
Mammalian Phenotype (MP)abnormal circulating interleukin-18 level0.0002565Highly InformativeDirect
Mammalian Phenotype (MP)abnormal macrophage apoptosis0.0003322Highly InformativeDirect
Mammalian Phenotype (MP)abnormal acute inflammation0.0005956Highly InformativeDirect
Mammalian Phenotype (MP)decreased inflammatory response0.0009577Highly InformativeDirect
Mammalian Phenotype (MP)abnormal interleukin-6 secretion0.05406Highly 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 variant0.0001968Least InformativeDirect
Worm Phenotype (WP)blast cell physiology variant0.003687Least InformativeInherited
Worm Phenotype (WP)cell physiology variant0.003694Least InformativeInherited
Worm Phenotype (WP)cell development variant0.05282Least InformativeInherited
Worm Phenotype (WP)apoptosis variant0.0004963Moderately InformativeDirect
Worm Phenotype (WP)neuronal cell fate specification variant0.000007293Highly InformativeDirect

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)
ZA termFDR (all)SDZA levelAnnotation (direct or inherited)
Zebrafish Anatomy (ZA)multi-tissue structure0.1031Least InformativeInherited
Zebrafish Anatomy (ZA)compound organ0.5743Least InformativeInherited
Zebrafish Anatomy (ZA)cardiovascular system0.04169Moderately InformativeInherited
Zebrafish Anatomy (ZA)blood vasculature0.000962InformativeDirect

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)Hydrolases0.0000001097Least InformativeDirect
Enzyme Commission (EC)Transferring phosphorus-containing groups0.00006072Least InformativeDirect
Enzyme Commission (EC)Protein-serine/threonine kinases0Moderately InformativeDirect
Enzyme Commission (EC)Acting on peptide bonds (peptidases)0Moderately InformativeDirect
Enzyme Commission (EC)Aminoacyltransferases0.00004223Moderately InformativeDirect
Enzyme Commission (EC)Non-specific serine/threonine protein kinase0InformativeDirect
Enzyme Commission (EC)Cysteine endopeptidases0InformativeDirect
Enzyme Commission (EC)RING-type E3 ubiquitin transferase0.000001604InformativeDirect
Enzyme Commission (EC)Protein-tyrosine kinases0.0005894InformativeDirect
Enzyme Commission (EC)Non-specific protein-tyrosine kinase0.0000007816Highly InformativeDirect

Document: EC 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) ]

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 24 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 24 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 ]