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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 integument0.00245Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of metabolism/homeostasis0.004234Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the cardiovascular system0.04388Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the digestive system0.1466Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the head0.2528Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of skeletal morphology0.6103Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the eye0.9026Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of nervous system physiology0.9062Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the genitourinary system0.9542Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of nervous system morphology1Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of immune system physiology0.00000002262Moderately InformativeDirect
Phenotypic Abnormality (PA)Abnormality of blood and blood-forming tissues0.00008817Moderately InformativeDirect
Phenotypic Abnormality (PA)Abnormality of the vasculature0.0143Moderately InformativeInherited
Phenotypic Abnormality (PA)Neoplasm0.01864Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the abdominal organs0.02066Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the respiratory system0.02221Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal ocular adnexa morphology0.07909Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal joint morphology0.1245Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of digestive system physiology0.2551Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the gastrointestinal tract0.5336Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal posterior eye segment morphology0.5494Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal eye physiology0.6468Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal anterior eye segment morphology0.82Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of cardiovascular system morphology0.8818Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal reproductive system morphology0.9062Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal circulating metabolite concentration0.9165Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal oral cavity morphology1Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of skin morphology1Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of temperature regulation0.0000001437InformativeDirect
Phenotypic Abnormality (PA)Abnormality of the lymphatic system0.000001766InformativeDirect
Phenotypic Abnormality (PA)Inflammatory abnormality of the eye0.000005257InformativeDirect
Phenotypic Abnormality (PA)Abnormal lung morphology0.00005129InformativeDirect
Phenotypic Abnormality (PA)Unusual CNS infection0.0001234InformativeDirect
Phenotypic Abnormality (PA)Abnormal uvea morphology0.001353InformativeInherited
Phenotypic Abnormality (PA)Abnormal oral mucosa morphology0.001645InformativeInherited
Phenotypic Abnormality (PA)Generalized abnormality of skin0.002395InformativeInherited
Phenotypic Abnormality (PA)Constitutional symptom0.005177InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the vasculature of the eye0.006795InformativeInherited
Phenotypic Abnormality (PA)Abnormal cellular physiology0.007418InformativeInherited
Phenotypic Abnormality (PA)Abnormal leukocyte morphology0.01692InformativeInherited
Phenotypic Abnormality (PA)Localized skin lesion0.1297InformativeInherited
Phenotypic Abnormality (PA)Abnormal cornea morphology0.2986InformativeInherited
Phenotypic Abnormality (PA)Abnormal intestine morphology0.3159InformativeInherited
Phenotypic Abnormality (PA)Visceromegaly0.3989InformativeInherited
Phenotypic Abnormality (PA)Functional abnormality of the gastrointestinal tract0.5669InformativeInherited
Phenotypic Abnormality (PA)Abnormal testis morphology0.6863InformativeInherited
Phenotypic Abnormality (PA)Uveitis0.0000000002313Highly InformativeDirect
Phenotypic Abnormality (PA)Splenomegaly0.00000004945Highly InformativeDirect
Phenotypic Abnormality (PA)Vasculitis0.00000006328Highly InformativeDirect
Phenotypic Abnormality (PA)Retrobulbar optic neuritis0.0000004202Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormal erythrocyte sedimentation rate0.0000008227Highly InformativeDirect
Phenotypic Abnormality (PA)Recurrent aphthous stomatitis0.00000154Highly InformativeDirect
Phenotypic Abnormality (PA)Lymphoma0.00000683Highly InformativeDirect
Phenotypic Abnormality (PA)Abdominal pain0.000009291Highly InformativeDirect
Phenotypic Abnormality (PA)Arthritis0.00001116Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormality of the lymph nodes0.00002426Highly InformativeDirect
Phenotypic Abnormality (PA)Inflammatory abnormality of the skin0.00006337Highly InformativeDirect
Phenotypic Abnormality (PA)Inflammation of the large intestine0.0001189Highly InformativeDirect
Phenotypic Abnormality (PA)Pulmonary infiltrates0.0001344Highly InformativeDirect
Phenotypic Abnormality (PA)Keratoconjunctivitis sicca0.0002523Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormal pericardium morphology0.0003206Highly InformativeDirect
Phenotypic Abnormality (PA)Headache0.0006023Highly InformativeDirect
Phenotypic Abnormality (PA)Papule0.0006261Highly InformativeDirect
Phenotypic Abnormality (PA)Arthropathy0.005882Highly InformativeInherited
Phenotypic Abnormality (PA)Abnormal circulating protein level0.53Highly 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 phenotype0.000000002829Least InformativeDirect
Mammalian Phenotype (MP)immune system phenotype0.00000002827Least InformativeDirect
Mammalian Phenotype (MP)cellular phenotype0.00000168Least InformativeDirect
Mammalian Phenotype (MP)mortality/aging0.08356Least InformativeInherited
Mammalian Phenotype (MP)abnormal homeostasis0.4616Least InformativeInherited
Mammalian Phenotype (MP)abnormal protein level0.000000412Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal immune serum protein physiology0.000004466Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal induced morbidity/mortality0.00001738Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal cell death0.0009662Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal immune system organ morphology0.009917Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal professional antigen presenting cell physiology0.01505Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal hematopoietic cell number0.02001Moderately InformativeInherited
Mammalian Phenotype (MP)liver/biliary system phenotype0.03332Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal leukocyte physiology0.04285Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal blood cell morphology/development0.1105Moderately InformativeInherited
Mammalian Phenotype (MP)respiratory system phenotype0.1187Moderately InformativeInherited
Mammalian Phenotype (MP)hearing/vestibular/ear phenotype0.2697Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal mononuclear cell morphology0.3454Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal inflammatory response0.3874Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal blood cell morphology0.5317Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal myeloid cell morphology0.6836Moderately InformativeInherited
Mammalian Phenotype (MP)autoimmune response0.000001919InformativeDirect
Mammalian Phenotype (MP)abnormal phagocyte morphology0.000006459InformativeDirect
Mammalian Phenotype (MP)abnormal macrophage physiology0.00007973InformativeDirect
Mammalian Phenotype (MP)abnormal circulating cytokine level0.0001334InformativeDirect
Mammalian Phenotype (MP)abnormal liver physiology0.0007398InformativeDirect
Mammalian Phenotype (MP)abnormal intestine physiology0.003019InformativeInherited
Mammalian Phenotype (MP)abnormal spleen morphology0.006318InformativeInherited
Mammalian Phenotype (MP)abnormal lymph node morphology0.01701InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin secretion0.02543InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin level0.05947InformativeInherited
Mammalian Phenotype (MP)abnormal mature B cell morphology0.1329InformativeInherited
Mammalian Phenotype (MP)abnormal interferon secretion0.1721InformativeInherited
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 size0.847InformativeInherited
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 size0.000000008746Highly InformativeDirect
Mammalian Phenotype (MP)enlarged lymph nodes0.0000002997Highly InformativeDirect
Mammalian Phenotype (MP)decreased interferon-alpha secretion0.000002046Highly 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 responsiveness0.00006531Highly 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 inflammation0.0005951Highly InformativeDirect
Mammalian Phenotype (MP)decreased inflammatory response0.0009565Highly 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 variant0.0003925Least InformativeDirect
Worm Phenotype (WP)cell physiology variant0.004783Least InformativeInherited
Worm Phenotype (WP)cell development variant0.05108Least InformativeInherited
Worm Phenotype (WP)apoptosis variant0.0005442Moderately InformativeDirect
Worm Phenotype (WP)cell fate specification variant0.003537InformativeInherited
Worm Phenotype (WP)neuronal cell fate specification variant0.000008239Highly 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 structure0.1019Least InformativeInherited
Zebrafish Anatomy (ZA)cavitated compound organ0.9142Least InformativeInherited
Zebrafish Anatomy (ZA)cardiovascular system0.04083Moderately 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)Hydrolases0.00000009788Least InformativeDirect
Enzyme Commission (EC)Transferring phosphorus-containing groups0.00005897Least InformativeDirect
Enzyme Commission (EC)Protein-serine/threonine kinases0Moderately InformativeDirect
Enzyme Commission (EC)Acting on peptide bonds (peptidases)0Moderately InformativeDirect
Enzyme Commission (EC)Aminoacyltransferases0.00004284Moderately InformativeDirect
Enzyme Commission (EC)Non-specific serine/threonine protein kinase0InformativeDirect
Enzyme Commission (EC)Cysteine endopeptidases0InformativeDirect
Enzyme Commission (EC)RING-type E3 ubiquitin transferase0.000001649InformativeDirect
Enzyme Commission (EC)Protein-tyrosine kinases0.0005915InformativeDirect
Enzyme Commission (EC)Non-specific protein-tyrosine kinase0.0000007771Highly 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 ]