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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 integument0.002067Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of metabolism/homeostasis0.003983Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the cardiovascular system0.04114Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the digestive system0.1428Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the head0.3371Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of skeletal morphology0.712Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of nervous system physiology0.8962Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the eye0.8968Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the genitourinary system0.9514Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of nervous system morphology0.9993Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of immune system physiology0.00000001969Moderately InformativeDirect
Phenotypic Abnormality (PA)Abnormality of blood and blood-forming tissues0.0003295Moderately InformativeDirect
Phenotypic Abnormality (PA)Abnormality of the vasculature0.01225Moderately InformativeInherited
Phenotypic Abnormality (PA)Neoplasm0.01835Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the respiratory system0.01975Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the abdominal organs0.01989Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal ocular adnexa morphology0.07209Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal joint morphology0.1236Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of digestive system physiology0.2454Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the gastrointestinal tract0.5157Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal posterior eye segment morphology0.543Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal eye physiology0.6266Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal anterior eye segment morphology0.8214Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of cardiovascular system morphology0.8822Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal reproductive system morphology0.8977Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal circulating metabolite concentration0.9155Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal oral cavity morphology1Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of skin morphology1Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of temperature regulation0.0000005286InformativeDirect
Phenotypic Abnormality (PA)Abnormality of B cell physiology0.0000008678InformativeDirect
Phenotypic Abnormality (PA)Abnormal spleen morphology0.000001222InformativeDirect
Phenotypic Abnormality (PA)Inflammatory abnormality of the eye0.000006018InformativeDirect
Phenotypic Abnormality (PA)Abnormal cellular immune system morphology0.000007717InformativeDirect
Phenotypic Abnormality (PA)Abnormal lung morphology0.00004582InformativeDirect
Phenotypic Abnormality (PA)Unusual CNS infection0.0001319InformativeDirect
Phenotypic Abnormality (PA)Abnormal uvea morphology0.001438InformativeInherited
Phenotypic Abnormality (PA)Generalized abnormality of skin0.002551InformativeInherited
Phenotypic Abnormality (PA)Constitutional symptom0.004982InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the vasculature of the eye0.006977InformativeInherited
Phenotypic Abnormality (PA)Stomatitis0.01378InformativeInherited
Phenotypic Abnormality (PA)Localized skin lesion0.128InformativeInherited
Phenotypic Abnormality (PA)Abnormal cornea morphology0.2968InformativeInherited
Phenotypic Abnormality (PA)Abnormal intestine morphology0.3234InformativeInherited
Phenotypic Abnormality (PA)Visceromegaly0.4143InformativeInherited
Phenotypic Abnormality (PA)Functional abnormality of the gastrointestinal tract0.5464InformativeInherited
Phenotypic Abnormality (PA)Abnormal testis morphology0.6778InformativeInherited
Phenotypic Abnormality (PA)Lymphadenopathy0.00000000000001846Highly InformativeDirect
Phenotypic Abnormality (PA)Uveitis0.0000000002442Highly InformativeDirect
Phenotypic Abnormality (PA)Splenomegaly0.00000004111Highly InformativeDirect
Phenotypic Abnormality (PA)Vasculitis0.00000007703Highly InformativeDirect
Phenotypic Abnormality (PA)Retrobulbar optic neuritis0.000000442Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormal erythrocyte sedimentation rate0.0000009092Highly InformativeDirect
Phenotypic Abnormality (PA)Recurrent aphthous stomatitis0.000001633Highly InformativeDirect
Phenotypic Abnormality (PA)Lymphoma0.000004813Highly InformativeDirect
Phenotypic Abnormality (PA)Abdominal pain0.0000105Highly InformativeDirect
Phenotypic Abnormality (PA)Inflammatory abnormality of the skin0.00006422Highly InformativeDirect
Phenotypic Abnormality (PA)Inflammation of the large intestine0.00009949Highly InformativeDirect
Phenotypic Abnormality (PA)Pulmonary infiltrates0.0001085Highly InformativeDirect
Phenotypic Abnormality (PA)Keratoconjunctivitis sicca0.0002626Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormal granulocyte morphology0.0004698Highly InformativeDirect
Phenotypic Abnormality (PA)Headache0.0005041Highly InformativeDirect
Phenotypic Abnormality (PA)Papule0.0007147Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormal circulating protein level0.5328Highly 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 phenotype0.000000002872Least InformativeDirect
Mammalian Phenotype (MP)immune system phenotype0.00000002865Least InformativeDirect
Mammalian Phenotype (MP)cellular phenotype0.000001678Least InformativeDirect
Mammalian Phenotype (MP)mortality/aging0.08357Least InformativeInherited
Mammalian Phenotype (MP)abnormal homeostasis0.4616Least InformativeInherited
Mammalian Phenotype (MP)abnormal protein level0.000000412Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal immune serum protein physiology0.000004539Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal induced morbidity/mortality0.00001738Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal cell death0.0009666Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal immune system organ morphology0.009838Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal professional antigen presenting cell physiology0.01516Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal hematopoietic cell number0.02006Moderately InformativeInherited
Mammalian Phenotype (MP)liver/biliary system phenotype0.03332Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal leukocyte physiology0.04295Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal blood cell morphology/development0.1101Moderately InformativeInherited
Mammalian Phenotype (MP)respiratory system phenotype0.1187Moderately InformativeInherited
Mammalian Phenotype (MP)hearing/vestibular/ear phenotype0.2697Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal mononuclear cell morphology0.3428Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal inflammatory response0.3862Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal blood cell morphology0.5299Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal myeloid cell morphology0.6823Moderately InformativeInherited
Mammalian Phenotype (MP)autoimmune response0.000001919InformativeDirect
Mammalian Phenotype (MP)abnormal phagocyte morphology0.000006459InformativeDirect
Mammalian Phenotype (MP)abnormal macrophage physiology0.00007859InformativeDirect
Mammalian Phenotype (MP)abnormal circulating cytokine level0.0001334InformativeDirect
Mammalian Phenotype (MP)abnormal liver physiology0.0007392InformativeDirect
Mammalian Phenotype (MP)abnormal intestine physiology0.003019InformativeInherited
Mammalian Phenotype (MP)abnormal spleen morphology0.006284InformativeInherited
Mammalian Phenotype (MP)abnormal lymph node morphology0.01701InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin secretion0.02467InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin level0.05945InformativeInherited
Mammalian Phenotype (MP)abnormal mature B cell morphology0.1317InformativeInherited
Mammalian Phenotype (MP)abnormal interferon secretion0.1742InformativeInherited
Mammalian Phenotype (MP)abnormal hearing physiology0.2033InformativeInherited
Mammalian Phenotype (MP)abnormal respiratory function0.2721InformativeInherited
Mammalian Phenotype (MP)abnormal interferon level0.3775InformativeInherited
Mammalian Phenotype (MP)abnormal Peyer's patch morphology0.8349InformativeInherited
Mammalian Phenotype (MP)abnormal lymph organ size0.8471InformativeInherited
Mammalian Phenotype (MP)decreased T cell number0.9256InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin-1 beta secretion0.000000000006311Highly InformativeDirect
Mammalian Phenotype (MP)abnormal Peyer's patch size0.000000008753Highly InformativeDirect
Mammalian Phenotype (MP)enlarged lymph nodes0.0000002999Highly InformativeDirect
Mammalian Phenotype (MP)decreased interferon-alpha secretion0.000002047Highly InformativeDirect
Mammalian Phenotype (MP)abnormal spleen germinal center morphology0.00001965Highly InformativeDirect
Mammalian Phenotype (MP)abnormal gut flora balance0.00002703Highly InformativeDirect
Mammalian Phenotype (MP)abnormal airway responsiveness0.00006534Highly InformativeDirect
Mammalian Phenotype (MP)decreased apoptosis0.00007544Highly InformativeDirect
Mammalian Phenotype (MP)abnormal B-1 B cell number0.00007616Highly InformativeDirect
Mammalian Phenotype (MP)abnormal circulating interleukin-18 level0.0002567Highly InformativeDirect
Mammalian Phenotype (MP)abnormal macrophage apoptosis0.0003323Highly InformativeDirect
Mammalian Phenotype (MP)abnormal acute inflammation0.000595Highly InformativeDirect
Mammalian Phenotype (MP)decreased inflammatory response0.0009567Highly InformativeDirect
Mammalian Phenotype (MP)abnormal interleukin-6 secretion0.05404Highly 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 variant0.0002151Least InformativeDirect
Worm Phenotype (WP)blast cell physiology variant0.004081Least InformativeInherited
Worm Phenotype (WP)cell physiology variant0.004089Least InformativeInherited
Worm Phenotype (WP)cell development variant0.05349Least InformativeInherited
Worm Phenotype (WP)apoptosis variant0.0005101Moderately InformativeDirect
Worm Phenotype (WP)cell fate specification variant0.003045InformativeInherited
Worm Phenotype (WP)neuronal cell fate specification variant0.000007455Highly 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 structure0.1021Least InformativeInherited
Zebrafish Anatomy (ZA)compound organ0.5713Least InformativeInherited
Zebrafish Anatomy (ZA)cardiovascular system0.04117Moderately InformativeInherited

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 ]