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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 disease0.002212Moderately InformativeInherited
Disease Ontology (DO)gastrointestinal system disease0.01189Moderately InformativeInherited
Disease Ontology (DO)syndrome0.05167Moderately InformativeInherited
Disease Ontology (DO)hypersensitivity reaction type II disease0.9764Moderately InformativeInherited
Disease Ontology (DO)inflammatory bowel disease0.00000139InformativeDirect
Disease Ontology (DO)arthropathy0.01774InformativeInherited
Disease Ontology (DO)hypersensitivity reaction type IV disease0.03932InformativeInherited
Disease Ontology (DO)viral infectious disease1InformativeInherited
Disease Ontology (DO)irritable bowel syndrome0.000009017Highly InformativeDirect
Disease Ontology (DO)spondyloarthropathy0.0000123Highly 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 integument0.002664Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of metabolism/homeostasis0.02622Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the cardiovascular system0.07037Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the digestive system0.1556Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the head0.4167Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the skeletal system0.8254Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the eye0.9549Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of nervous system morphology0.9691Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the genitourinary system0.9788Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of blood and blood-forming tissues0.000285Moderately InformativeDirect
Phenotypic Abnormality (PA)Abnormality of immune system physiology0.01504Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the vasculature0.01774Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the abdominal organs0.01833Moderately InformativeInherited
Phenotypic Abnormality (PA)Neoplasm0.02134Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of the respiratory system0.03578Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal joint morphology0.5731Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of digestive system physiology0.6303Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal eye morphology0.7412Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal eye physiology0.7772Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of cardiovascular system morphology0.855Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal circulating metabolite concentration0.9326Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal reproductive system morphology0.9853Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormal oral cavity morphology1Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of skin morphology1Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of skin physiology0.00000001818InformativeDirect
Phenotypic Abnormality (PA)Abnormality of temperature regulation0.0000005055InformativeDirect
Phenotypic Abnormality (PA)Abnormal spleen morphology0.000001517InformativeDirect
Phenotypic Abnormality (PA)Unusual CNS infection0.00008385InformativeDirect
Phenotypic Abnormality (PA)Visceromegaly0.0001071InformativeDirect
Phenotypic Abnormality (PA)Abnormality of the lymph nodes0.0001296InformativeDirect
Phenotypic Abnormality (PA)Abnormal lung morphology0.0009316InformativeDirect
Phenotypic Abnormality (PA)Abnormal cellular physiology0.005869InformativeInherited
Phenotypic Abnormality (PA)Constitutional symptom0.006694InformativeInherited
Phenotypic Abnormality (PA)Abnormal uvea morphology0.01192InformativeInherited
Phenotypic Abnormality (PA)Vascular skin abnormality0.03073InformativeInherited
Phenotypic Abnormality (PA)Abnormal oral mucosa morphology0.0363InformativeInherited
Phenotypic Abnormality (PA)Abnormal immune system morphology0.05694InformativeInherited
Phenotypic Abnormality (PA)Localized skin lesion0.1354InformativeInherited
Phenotypic Abnormality (PA)Abdominal symptom0.1389InformativeInherited
Phenotypic Abnormality (PA)Abnormal testis morphology0.7843InformativeInherited
Phenotypic Abnormality (PA)Increased inflammatory response1InformativeInherited
Phenotypic Abnormality (PA)Lymphadenopathy0.0000000000009373Highly InformativeDirect
Phenotypic Abnormality (PA)Uveitis0.00000004398Highly InformativeDirect
Phenotypic Abnormality (PA)Vasculitis0.00000004499Highly InformativeDirect
Phenotypic Abnormality (PA)Splenomegaly0.0000001772Highly InformativeDirect
Phenotypic Abnormality (PA)Retrobulbar optic neuritis0.0000004737Highly InformativeDirect
Phenotypic Abnormality (PA)Lymphoma0.00002167Highly InformativeDirect
Phenotypic Abnormality (PA)Anemia0.00005452Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormal erythrocyte sedimentation rate0.00006783Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormal C-reactive protein level0.0001066Highly InformativeDirect
Phenotypic Abnormality (PA)Recurrent aphthous stomatitis0.0001269Highly InformativeDirect
Phenotypic Abnormality (PA)Pericarditis0.0002056Highly InformativeDirect
Phenotypic Abnormality (PA)Pulmonary infiltrates0.0002634Highly InformativeDirect
Phenotypic Abnormality (PA)Inflammatory abnormality of the skin0.0003119Highly InformativeDirect
Phenotypic Abnormality (PA)Abdominal pain0.000444Highly InformativeDirect
Phenotypic Abnormality (PA)Papule0.0007761Highly InformativeDirect
Phenotypic Abnormality (PA)Arthritis0.0009508Highly InformativeDirect
Phenotypic Abnormality (PA)Abnormal leukocyte morphology0.0362Highly InformativeInherited
Phenotypic Abnormality (PA)Autoimmunity0.1053Highly InformativeInherited
Phenotypic Abnormality (PA)Abnormal platelet count0.9264Highly 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 phenotype0.00000000283Least InformativeDirect
Mammalian Phenotype (MP)immune system phenotype0.00000002825Least InformativeDirect
Mammalian Phenotype (MP)cellular phenotype0.000001696Least InformativeDirect
Mammalian Phenotype (MP)mortality/aging0.08324Least InformativeInherited
Mammalian Phenotype (MP)abnormal homeostasis0.4619Least InformativeInherited
Mammalian Phenotype (MP)abnormal protein level0.0000004164Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal immune serum protein physiology0.000004688Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal induced morbidity/mortality0.00001746Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal cell death0.0009793Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal immune system organ morphology0.01006Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal professional antigen presenting cell physiology0.01552Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal hematopoietic cell number0.02026Moderately InformativeInherited
Mammalian Phenotype (MP)liver/biliary system phenotype0.03334Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal leukocyte physiology0.04294Moderately 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 response0.3862Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal blood cell morphology0.5294Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal myeloid cell morphology0.6815Moderately InformativeInherited
Mammalian Phenotype (MP)autoimmune response0.000001914InformativeDirect
Mammalian Phenotype (MP)abnormal phagocyte morphology0.000006457InformativeDirect
Mammalian Phenotype (MP)abnormal macrophage physiology0.00007862InformativeDirect
Mammalian Phenotype (MP)abnormal circulating cytokine level0.0001316InformativeDirect
Mammalian Phenotype (MP)abnormal liver physiology0.0007421InformativeDirect
Mammalian Phenotype (MP)abnormal intestine physiology0.00303InformativeInherited
Mammalian Phenotype (MP)abnormal spleen morphology0.006422InformativeInherited
Mammalian Phenotype (MP)abnormal lymph node morphology0.01689InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin secretion0.02467InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin level0.05943InformativeInherited
Mammalian Phenotype (MP)abnormal mature B cell morphology0.1325InformativeInherited
Mammalian Phenotype (MP)abnormal interferon secretion0.1743InformativeInherited
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 morphology0.835InformativeInherited
Mammalian Phenotype (MP)abnormal lymph organ size0.8476InformativeInherited
Mammalian Phenotype (MP)decreased T cell number0.9257InformativeInherited
Mammalian Phenotype (MP)abnormal interleukin-1 beta secretion0.000000000006313Highly InformativeDirect
Mammalian Phenotype (MP)abnormal Peyer's patch size0.000000008763Highly InformativeDirect
Mammalian Phenotype (MP)enlarged lymph nodes0.0000002991Highly InformativeDirect
Mammalian Phenotype (MP)decreased interferon-alpha secretion0.000002042Highly InformativeDirect
Mammalian Phenotype (MP)abnormal spleen germinal center morphology0.00002097Highly InformativeDirect
Mammalian Phenotype (MP)abnormal gut flora balance0.00002708Highly InformativeDirect
Mammalian Phenotype (MP)abnormal airway responsiveness0.00006539Highly InformativeDirect
Mammalian Phenotype (MP)decreased apoptosis0.00007452Highly InformativeDirect
Mammalian Phenotype (MP)abnormal B-1 B cell number0.00008094Highly InformativeDirect
Mammalian Phenotype (MP)abnormal circulating interleukin-18 level0.0002567Highly InformativeDirect
Mammalian Phenotype (MP)abnormal macrophage apoptosis0.0003314Highly InformativeDirect
Mammalian Phenotype (MP)abnormal acute inflammation0.0005966Highly InformativeDirect
Mammalian Phenotype (MP)decreased inflammatory response0.0009606Highly InformativeDirect
Mammalian Phenotype (MP)abnormal interleukin-6 secretion0.05405Highly 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 variant0.0001868Least InformativeDirect
Worm Phenotype (WP)cell physiology variant0.002874Least InformativeInherited
Worm Phenotype (WP)cell development variant0.04737Least InformativeInherited
Worm Phenotype (WP)apoptosis variant0.0004823Moderately InformativeDirect
Worm Phenotype (WP)neuronal cell fate specification variant0.000007034Highly 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 structure0.09124Least InformativeInherited
Zebrafish Anatomy (ZA)compound organ0.5404Least InformativeInherited
Zebrafish Anatomy (ZA)cardiovascular system0.04265Moderately 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)Hydrolases0.0000001256Least InformativeDirect
Enzyme Commission (EC)Transferring phosphorus-containing groups0.00006115Least InformativeDirect
Enzyme Commission (EC)Protein-serine/threonine kinases0Moderately InformativeDirect
Enzyme Commission (EC)Acting on peptide bonds (peptidases)0Moderately InformativeDirect
Enzyme Commission (EC)Aminoacyltransferases0.00004232Moderately InformativeDirect
Enzyme Commission (EC)Non-specific serine/threonine protein kinase0InformativeDirect
Enzyme Commission (EC)Cysteine endopeptidases0InformativeDirect
Enzyme Commission (EC)RING-type E3 ubiquitin transferase0.000001603InformativeDirect
Enzyme Commission (EC)Protein-tyrosine kinases0.0005819InformativeDirect
Enzyme Commission (EC)Non-specific protein-tyrosine kinase0.0000007831Highly 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 ]