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Phenotype Ontology
Like Gene Ontology (GO), phenotypy ontology classifies and organizes gene-mutant/null phenotypic information from the very general at the top to more specific terms in the directed acyclic graph (DAG) by viewing an individual term as a node and its relations to parental terms (allowing for multiple parents) as directed edges. To navigate this hierarchy, we display all parental phenotypic terms to the current phenotypic term of interest ordered by their shortest distances to the current term. Also, only direct children phenotypic terms of the current phenotypic term are listed. Phenotype ontologies we have incorporated are as follows:

• Disease Ontology (DO) Ontology (DO)
  DO semantically integrates disease and medical vocabularies through extensive cross mapping of DO terms to MeSH, ICD, NCI thesaurus, SNOMED and OMIM.
  
• Human Phenotype (HP) Ontology (HP)
  HP captures phenotypic abnormalities that are described in OMIM, along with the corresponding disease-causing genes. It includes three complementary biological concepts: Mode_of_Inheritance (MI), ONset_and_clinical_course (ON), and Phenotypic_Abnormality (PA).
  
• Mouse Phenotype (MP) Ontology (MP)
  MP describes phenotypes of the mouse after a specific gene is genetically disrupted. Using it, Mouse Genome Informatics (MGI) provides high-coverate gene-level phenotypes for the mouse.
  
• Worm Phenotype (WP) Ontology (WP)
  WP classifies and organizes phenotype descriptions for C. elegans and other nematodes. Using it, WormBase provides primary resource for phenotype annotations for C. elegans.
  
• Yeast Phenotype (YP) Ontology (YP)
  Based on YP which is the major contributor to the Ascomycete phenotype ontology, Saccharomyces Genome Database (SGD) provides single mutant phenotypes for every gene in the yeast genome.
  
• Fly Phenotype (FP) Ontology (FP)
  FP refers to FlyBase controlled vocabulary. Specifically, a structured controlled vocabulary is used for the annotation of alleles (for their mutagen etc) in FlyBase.
  
• Fly Anatomy (FA) Ontology (FA)
  FA is a structured controlled vocabulary of the anatomy of Drosophila melanogaster, used for the description of phenotypes and where a gene is expressed.
  
• Zebrafish Anatomy (ZA) Ontology (ZA)
  ZA displays anatomical terms of the zebrafish using standard anatomical nomenclature, together with affected genes.
  
• Xenopus Anatomy (XA) Ontology (XA)
  XA represents the lineage of tissues and the timing of development for frogs (Xenopus laevis and Xenopus tropicalis). It is used to annotate Xenopus gene expression patterns and mutant and morphant phenotypes.
  
• Arabidopsis Plant Ontology (AP) Ontology (AP)
  As a major contributor to Plant Ontology which describes plant anatomical and morphological structures (AN) and growth and developmental stages (DE), the Arabidopsis Information Resource (TAIR) provides arabidopsis plant ontology annotations for the model higher plant Arabidopsis thaliana.
  
• Enzyme Commission (EC) Ontology (EC)
  Each enzyme is allocated a four-digit EC number, the first three digits of which define the reaction catalysed and the fourth of which is a unique identifier (serial number). Each enzyme is also assigned a systematic name that uniquely defines the reaction catalysed.
  
• DrugBank ATC (DB) Ontology (DB)
  In the Anatomical Therapeutic Chemical (ATC) classification system, drugs are classified in groups at five different levels according to the organ or system (1st level, anatomical main group) on which they act and their therapeutic (2nd level, therapeutic subgroup), pharmacological (3rd level, pharmacological subgroup) and chemical properties (4th level, chemical subgroup; 5th level, chemical substance). Only drugs in DrugBank are considered.
  
• UniProtKB KeyWords (KW) Ontology (KW)
  Keywords in UniProtKB are controlled vocabulary, providing a summary of the entry content and are used to index UniProtKB/Swiss-Prot entries based on 10 categories (the category "Technical term" being excluded here). Each keyword is attributed manually to UniProtKB/Swiss-Prot entries and automatically to UniProtKB/TrEMBL entries (according to specific annotation rules).
  
• UniProtKB UniPathway (UP) Ontology (UP)
  UP is a fully manually curated resource for the representation and annotation of metabolic pathways, being used as controlled vocabulary for pathway annotation in UniProtKB.
  

Structural Domain Phenotype Ontology and its Annotations
Structural Classification of Proteins (SCOP) classifies evolutionary-related domains into Superfamily level and Family level. Using the phenotype ontologies above, we have generated the domain-centric phenotype annotations, and further identified those phenotype terms which are the most informative to annotate SCOP domains. Promisingly, domain-centric phenotypic annotations can serve as an alternative starting point to explore genotype-phenotype relationships. We provide several relevant files for the download, including the annotation and the corresponding ontology for each phenotype ontology.

• Structural Domain Disease Ontology (DO) Ontology (SDDO) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2DO.txt, and the corresponding ontology:SDDO.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Human Phenotype (HP) Ontology (SDHP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2HP.txt, and the corresponding ontology:SDHP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Mouse Phenotype (MP) Ontology (SDMP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2MP.txt, and the corresponding ontology:SDMP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Worm Phenotype (WP) Ontology (SDWP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2WP.txt, and the corresponding ontology:SDWP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Yeast Phenotype (YP) Ontology (SDYP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2YP.txt, and the corresponding ontology:SDYP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Fly Phenotype (FP) Ontology (SDFP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2FP.txt, and the corresponding ontology:SDFP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Fly Anatomy (FA) Ontology (SDFA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2FA.txt, and the corresponding ontology:SDFA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Zebrafish Anatomy (ZA) Ontology (SDZA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2ZA.txt, and the corresponding ontology:SDZA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Xenopus Anatomy (XA) Ontology (SDXA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2XA.txt, and the corresponding ontology:SDXA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Arabidopsis Plant Ontology (AP) Ontology (SDAP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2AP.txt, and the corresponding ontology:SDAP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Enzyme Commission (EC) Ontology (SDEC) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2EC.txt, and the corresponding ontology:SDEC.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain DrugBank ATC (DB) Ontology (SDDB) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2DB.txt, and the corresponding ontology:SDDB.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain UniProtKB KeyWords (KW) Ontology (SDKW) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2KW.txt, and the corresponding ontology:SDKW.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain UniProtKB UniPathway (UP) Ontology (SDUP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2UP.txt, and the corresponding ontology:SDUP.txt) and mysql tables (Domain2PO.sql.gz).
  

Supra-domain Phenotype Ontology and its Annotations
Although domain-centric annotations hold great promise in describing phenotypic nature of independent domains, most domains themselves may not just work alone. In multi-domain proteins, they may be combined together to form distinct domain architectures. The recombination of the existing domains is considered as one of major driving forces for phenotypic diversificaation. As an extension, we have also generated supra-domain phenotype ontology and its annotations. Compared to domain-centric phenotype ontology and annotations (SCOP domains at the Superfamily level and Family level), this version focuses on supra-domains and individual SCOP domains ONLY at the Superfamily level. Besides, in terms of individual superfamilies, their annotations from the domain-centric version may be different from those from supra-domains version. Depending on your focus, the former should be used for the consideration of both the Superfamily level and Family level, otherwise the latter should be used if you are interested in domain combinations. Also, we provide several relevant files for the download, including the annotation and the corresponding ontology for each phenotype ontology.

• Supra-domain Domain Disease Ontology (DO) Ontology (SPDO) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2DO.txt, and the corresponding ontology:SPDO.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Human Phenotype (HP) Ontology (SPHO) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2HP.txt, and the corresponding ontology:SPHO.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Mouse Phenotype (MP) Ontology (SPMP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2MP.txt, and the corresponding ontology:SPMP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Worm Phenotype (WP) Ontology (SPWP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2WP.txt, and the corresponding ontology:SPWP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Yeast Phenotype (YP) Ontology (SPYP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2YP.txt, and the corresponding ontology:SPYP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Fly Phenotype (FP) Ontology (SPFP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2FP.txt, and the corresponding ontology:SPFP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Fly Anatomy (FA) Ontology (SPFA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2FA.txt, and the corresponding ontology:SPFA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Zebrafish Anatomy (ZA) Ontology (SPZA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2ZA.txt, and the corresponding ontology:SPZA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Xenopus Anatomy (XA) Ontology (SPXA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2XA.txt, and the corresponding ontology:SPXA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Arabidopsis Plant Ontology (AP) Ontology (SPAP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2AP.txt, and the corresponding ontology:SPAP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Enzyme Commission (EC) Ontology (SPEC) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2EC.txt, and the corresponding ontology:SPEC.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain DrugBank ATC (DB) Ontology (SPDB) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2DB.txt, and the corresponding ontology:SPDB.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain UniProtKB KeyWords (KW) Ontology (SPKW) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2KW.txt, and the corresponding ontology:SPKW.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain UniProtKB UniPathway (UP) Ontology (SPUP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2UP.txt, and the corresponding ontology:SPUP.txt) and mysql tables (SP2PO.sql.gz).
  

Superfamily domains annotated to this XA term (SDXA level: Moderately Informative)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
SCP-like	0	DIRECT
PAH2 domain	0	DIRECT
Succinyl-CoA synthetase domains	0	DIRECT
Thiolase-like	0	DIRECT
Mannose 6-phosphate receptor domain	0	DIRECT
F1F0 ATP synthase subunit C	0	DIRECT
4Fe-4S ferredoxins	0	DIRECT
Aminomethyltransferase beta-barrel domain	0	DIRECT
Lipovitellin-phosvitin complex; beta-sheet shell regions	0	DIRECT
Moesin tail domain	0	DIRECT
Fibrinogen coiled-coil and central regions	0	DIRECT
NAP-like	0	DIRECT
Isocitrate/Isopropylmalate dehydrogenase-like	0	DIRECT
Amidase signature (AS) enzymes	0	DIRECT
MAPEG domain-like	0	DIRECT
N-acetylmuramoyl-L-alanine amidase-like	0	DIRECT
Guanido kinase N-terminal domain	0	DIRECT
Subunits of heterodimeric actin filament capping protein Capz	0	DIRECT
ACP-like	0	DIRECT
C-terminal domain of alpha and beta subunits of F1 ATP synthase	0	DIRECT
Peripheral subunit-binding domain of 2-oxo acid dehydrogenase complex	0	DIRECT
PLP-binding barrel	0	DIRECT
Apolipoprotein A-I	0	DIRECT
Surp module (SWAP domain)	0	DIRECT
Glutamine synthetase/guanido kinase	0	DIRECT
TGS-like	0	DIRECT
Vasodilator-stimulated phosphoprotein, VASP, tetramerisation domain	0	DIRECT
AraD/HMP-PK domain-like	0	DIRECT
TK C-terminal domain-like	0	DIRECT
BSD domain-like	0	DIRECT
Hedgehog/DD-peptidase	0	DIRECT
Alanine racemase C-terminal domain-like	0	DIRECT
Lipovitellin-phosvitin complex, superhelical domain	0	DIRECT
Delta-sleep-inducing peptide immunoreactive peptide	0	DIRECT
eIF1-like	0	DIRECT
NAD(P)-binding Rossmann-fold domains	0.001248	INHERITED FROM: intestine
ALDH-like	0.001669	INHERITED FROM: intestine
PLP-dependent transferases	0.007435	INHERITED FROM: intestine
RNA-binding domain, RBD	0.02085	INHERITED FROM: intestine
Thiamin diphosphate-binding fold (THDP-binding)	0.03656	INHERITED FROM: pancreas
Trypsin-like serine proteases	0.04481	INHERITED FROM: pancreas
Translation proteins SH3-like domain	0.05217	INHERITED FROM: pancreas
Translational machinery components	0.0736	INHERITED FROM: pancreas
Leukotriene A4 hydrolase N-terminal domain	0.07419	INHERITED FROM: pancreas
SMAD MH1 domain	0.1448	INHERITED FROM: heart || endocardium
SMAD/FHA domain	0.147	INHERITED FROM: endocardium
WD40 repeat-like	0.1477	INHERITED FROM: intestine
Actin-like ATPase domain	0.1848	INHERITED FROM: pancreas
MHC antigen-recognition domain	0.2717	INHERITED FROM: pancreas
Zn-binding ribosomal proteins	0.3012	INHERITED FROM: pancreas
HMG-box	0.3183	INHERITED FROM: endocardial tube || endocardium
EGF/Laminin	0.4629	INHERITED FROM: heart
"Winged helix" DNA-binding domain	0.4725	INHERITED FROM: stomach
p53-like transcription factors	0.7418	INHERITED FROM: heart || myocardium
Troponin coil-coiled subunits	0.773	INHERITED FROM: heart
Snake toxin-like	0.8214	INHERITED FROM: heart
Homeodomain-like	1	INHERITED FROM: heart || small intestine || stomach || large intestine
EF-hand	1	INHERITED FROM: cardiac atrium || right atrium || left atrium || cardiac ventricle
Tropomyosin	1	INHERITED FROM: cardiac atrium || outflow tract || left atrium || myocardium
Cystine-knot cytokines	1	INHERITED FROM: heart
Growth factor receptor domain	1	INHERITED FROM: heart
HLH, helix-loop-helix DNA-binding domain	1	INHERITED FROM: heart || stomach
Frizzled cysteine-rich domain	1	INHERITED FROM: gall bladder || small intestine || stomach

Family domains annotated to this XA term (SDXA level: Moderately Informative)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
Thiolase-related	0	DIRECT
Hedgehog (development protein), N-terminal signaling domain	0	DIRECT
Ferritin	0	DIRECT
Branched-chain alpha-keto acid dehydrogenase beta-subunit, C-terminal-domain	0	DIRECT
IP3 receptor type 1 binding core, domain 2	0	DIRECT
Pumilio repeat	0	DIRECT
Neurolysin-like	0	DIRECT
eIF1-like	0	DIRECT
Fibronectin type II module	0	DIRECT
Glyoxalase II (hydroxyacylglutathione hydrolase)	0	DIRECT
Arginase-like amidino hydrolases	0	DIRECT
Protein-L-isoaspartyl O-methyltransferase	0	DIRECT
RuBisCo LSMT catalytic domain	0	DIRECT
HCDH C-domain-like	0	DIRECT
Glucose 6-phosphate dehydrogenase-like	0	DIRECT
Mannose 6-phosphate receptor domain	0	DIRECT
Crotonase-like	0	DIRECT
HAT/Suf repeat	0	DIRECT
gamma-adaptin C-terminal appendage domain-like	0	DIRECT
Guanido kinase catalytic domain	0	DIRECT
Group II chaperonin (CCT, TRIC), intermediate domain	0	DIRECT
F1F0 ATP synthase subunit C	0	DIRECT
UDPGT-like	0	DIRECT
DNA ligase	0	DIRECT
Fibronectin type I module	0	DIRECT
Alpha-adaptin ear subdomain-like	0	DIRECT
GABARAP-like	0	DIRECT
Aminomethyltransferase beta-barrel domain	0	DIRECT
PDI-like	0	DIRECT
D-aminoacid oxidase-like	0	DIRECT
Guanido kinase N-terminal domain	0	DIRECT
MSP-like	0	DIRECT
Vasodilator-stimulated phosphoprotein, VASP, tetramerisation domain	0	DIRECT
Delta-sleep-inducing peptide immunoreactive peptide	0	DIRECT
Variant RING domain	0	DIRECT
Sterol carrier protein, SCP	0	DIRECT
Alanine racemase-like, N-terminal domain	0	DIRECT
Hypoxia-inducible factor HIF ihhibitor (FIH1)	0	DIRECT
Peripheral subunit-binding domain of 2-oxo acid dehydrogenase complex	0	DIRECT
Dimeric isocitrate & isopropylmalate dehydrogenases	0	DIRECT
Branched-chain alpha-keto acid dehydrogenase PP module	0	DIRECT
Lipovitellin-phosvitin complex, superhelical domain	0	DIRECT
Moesin tail domain	0	DIRECT
CAT-like	0	DIRECT
Apolipoprotein A-I	0	DIRECT
Eukaryotic ODC-like	0	DIRECT
NAP-like	0	DIRECT
PAH2 domain	0	DIRECT
alpha-catenin/vinculin	0	DIRECT
Amidase signature (AS) enzymes	0	DIRECT
MAPEG domain	0	DIRECT
Fibrinogen coiled-coil and central regions	0	DIRECT
Lipovitellin-phosvitin complex; beta-sheet shell regions	0	DIRECT
Threonyl-tRNA synthetase (ThrRS), second 'additional' domain	0	DIRECT
C-terminal domain of alpha and beta subunits of F1 ATP synthase	0	DIRECT
Chromo barrel domain	0	DIRECT
BSD domain	0	DIRECT
Malic enzyme N-domain	0	DIRECT
Phosphoribosylpyrophosphate synthetase-like	0	DIRECT
N-acetylmuramoyl-L-alanine amidase-like	0	DIRECT
Steroid-binding domain	0	DIRECT
S-adenosylhomocystein hydrolase	0	DIRECT
Noncollagenous (NC1) domain of collagen IV	0	DIRECT
Transferrin	0	DIRECT
Anticodon-binding domain of Class II aaRS	0	DIRECT
Surp module (SWAP domain)	0	DIRECT
Succinyl-CoA synthetase domains	0	DIRECT
AraD-like aldolase/epimerase	0	DIRECT
Clathrin adaptor appendage, alpha and beta chain-specific domain	0	DIRECT
ALDH-like	0.001524	INHERITED FROM: intestine
Canonical RBD	0.002096	INHERITED FROM: intestine
GABA-aminotransferase-like	0.002183	INHERITED FROM: intestine
Leukotriene A4 hydrolase N-terminal domain	0.01253	INHERITED FROM: pancreas
Class I aldolase	0.03816	INHERITED FROM: heart
Eukaryotic proteases	0.04088	INHERITED FROM: pancreas
Actin/HSP70	0.08928	INHERITED FROM: pancreas || heart
SMAD domain	0.09838	INHERITED FROM: heart || endocardium
Leukotriene A4 hydrolase catalytic domain	0.09838	INHERITED FROM: pancreas
Complement components	0.1373	INHERITED FROM: liver
SMAD MH1 domain	0.1373	INHERITED FROM: heart || endocardium
Erythroid transcription factor GATA-1	0.1946	INHERITED FROM: heart || myocardium
MHC antigen-recognition domain	0.2607	INHERITED FROM: pancreas
WD40-repeat	0.2757	INHERITED FROM: intestine
HMG-box	0.3352	INHERITED FROM: endocardial tube || endocardium
LIM domain	0.349	INHERITED FROM: heart
Lectin leg-like	0.3537	INHERITED FROM: pancreas
Translational machinery components	0.6611	INHERITED FROM: pancreas
Calmodulin-like	0.812	INHERITED FROM: cardiac atrium || right atrium || left atrium || cardiac ventricle
T-box	0.8822	INHERITED FROM: heart || myocardium
Forkhead DNA-binding domain	0.9748	INHERITED FROM: myocardium || stomach
Frizzled cysteine-rich domain	0.9899	INHERITED FROM: gall bladder || small intestine || stomach
Homeodomain	1	INHERITED FROM: heart || small intestine || stomach || large intestine
Transforming growth factor (TGF)-beta	1	INHERITED FROM: heart
HLH, helix-loop-helix DNA-binding domain	1	INHERITED FROM: heart || stomach
Growth factor receptor domain	1	INHERITED FROM: heart
Tropomyosin	1	INHERITED FROM: cardiac atrium || outflow tract || left atrium || myocardium

Trees by TreeVector

A presence/absence matrix is generated using protein domain architecture data for all genomes in SUPERFAMILY. The PAUP software is used to produce a single, large tree topology using heuristic parsimony methods. Genome combinations, or specific clades, can be displayed as if individual trees had been produced. However, this data is extracted from the single large tree. This produces a higher quality topology than if the trees had been produced on their own, and allows the trees to be displayed instantly.

Supra-domains annotated to this XA term (SPXA level: Moderately Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Single)	FDR (all)	Annotation (direct or inherited)
SCP-like	0	DIRECT
Hedgehog/DD-peptidase	0	DIRECT
PLP-binding barrel	0	DIRECT
Surp module (SWAP domain)	0	DIRECT
F1F0 ATP synthase subunit C	0	DIRECT
Thiolase-like	0	DIRECT
4Fe-4S ferredoxins	0	DIRECT
N-acetylmuramoyl-L-alanine amidase-like	0	DIRECT
Mannose 6-phosphate receptor domain	0	DIRECT
Succinyl-CoA synthetase domains	0	DIRECT
Aminomethyltransferase beta-barrel domain	0	DIRECT
TK C-terminal domain-like	0	DIRECT
Lipovitellin-phosvitin complex; beta-sheet shell regions	0	DIRECT
Moesin tail domain	0	DIRECT
eIF1-like	0	DIRECT
Fibrinogen coiled-coil and central regions	0	DIRECT
Apolipoprotein A-I	0	DIRECT
Subunits of heterodimeric actin filament capping protein Capz	0	DIRECT
Guanido kinase N-terminal domain	0	DIRECT
TGS-like	0	DIRECT
Isocitrate/Isopropylmalate dehydrogenase-like	0	DIRECT
Peripheral subunit-binding domain of 2-oxo acid dehydrogenase complex	0	DIRECT
BSD domain-like	0	DIRECT
C-terminal domain of alpha and beta subunits of F1 ATP synthase	0	DIRECT
NAP-like	0	DIRECT
Lipovitellin-phosvitin complex, superhelical domain	0	DIRECT
Glutamine synthetase/guanido kinase	0	DIRECT
Vasodilator-stimulated phosphoprotein, VASP, tetramerisation domain	0	DIRECT
PAH2 domain	0	DIRECT
MAPEG domain-like	0	DIRECT
Amidase signature (AS) enzymes	0	DIRECT
AraD/HMP-PK domain-like	0	DIRECT
ACP-like	0	DIRECT
Alanine racemase C-terminal domain-like	0	DIRECT
Delta-sleep-inducing peptide immunoreactive peptide	0	DIRECT
NAD(P)-binding Rossmann-fold domains	0.0009503	DIRECT
ALDH-like	0.001275	INHERITED FROM: intestine
PLP-dependent transferases	0.005805	INHERITED FROM: intestine
RNA-binding domain, RBD	0.01655	INHERITED FROM: intestine
Thiamin diphosphate-binding fold (THDP-binding)	0.02965	INHERITED FROM: pancreas
Trypsin-like serine proteases	0.03665	INHERITED FROM: pancreas
Translation proteins SH3-like domain	0.04289	INHERITED FROM: pancreas
Translational machinery components	0.06126	INHERITED FROM: pancreas
Leukotriene A4 hydrolase N-terminal domain	0.06178	INHERITED FROM: pancreas
Orange domain-like	0.08843	INHERITED FROM: heart
SMAD MH1 domain	0.1255	INHERITED FROM: heart || endocardium
SMAD/FHA domain	0.1276	INHERITED FROM: heart || endocardium
WD40 repeat-like	0.1283	INHERITED FROM: intestine
Actin-like ATPase domain	0.1623	INHERITED FROM: heart || pancreas
Alpha-macroglobulin receptor domain	0.1759	INHERITED FROM: liver
MHC antigen-recognition domain	0.2442	INHERITED FROM: pancreas
Zn-binding ribosomal proteins	0.2727	INHERITED FROM: pancreas
HMG-box	0.289	INHERITED FROM: endocardium || endocardial tube
EGF/Laminin	0.429	INHERITED FROM: heart
"Winged helix" DNA-binding domain	0.4383	INHERITED FROM: stomach
p53-like transcription factors	0.7071	INHERITED FROM: heart || myocardium
Troponin coil-coiled subunits	0.7393	INHERITED FROM: heart
Snake toxin-like	0.7906	INHERITED FROM: heart
Frizzled cysteine-rich domain	0.9768	INHERITED FROM: stomach || gall bladder || small intestine
Growth factor receptor domain	0.9872	INHERITED FROM: heart
Cystine-knot cytokines	1	INHERITED FROM: heart
HLH, helix-loop-helix DNA-binding domain	1	INHERITED FROM: stomach || heart
EF-hand	1	INHERITED FROM: cardiac ventricle || right atrium || left atrium || cardiac atrium
Tropomyosin	1	INHERITED FROM: outflow tract || left atrium || myocardium || cardiac atrium
Homeodomain-like	1	INHERITED FROM: stomach || heart || small intestine || large intestine
Immunoglobulin	1	INHERITED FROM: spleen

Supra-domains annotated to this XA term (SPXA level: Moderately Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Duplex) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
57184,49899 57184 - Growth factor receptor domain 49899 - Concanavalin A-like lectins/glucanases	0	DIRECT
54534,47473 54534 - FKBP-like 47473 - EF-hand	0	DIRECT
54403,54403 54403 - Cystatin/monellin 54403 - Cystatin/monellin	0	DIRECT
51419,50621 51419 - PLP-binding barrel 50621 - Alanine racemase C-terminal domain-like	0	DIRECT
55550,50729 55550 - SH2 domain 50729 - PH domain-like	0	DIRECT
49899,52540 49899 - Concanavalin A-like lectins/glucanases 52540 - P-loop containing nucleoside triphosphate hydrolases	0	DIRECT
52518,52922 52518 - Thiamin diphosphate-binding fold (THDP-binding) 52922 - TK C-terminal domain-like	0	DIRECT
51230,47005 51230 - Single hybrid motif 47005 - Peripheral subunit-binding domain of 2-oxo acid dehydrogenase complex	0	DIRECT
57196,50494 57196 - EGF/Laminin 50494 - Trypsin-like serine proteases	0	DIRECT
48592,54849 48592 - GroEL equatorial domain-like 54849 - GroEL-intermediate domain like	0	DIRECT
103025,101790 103025 - Folate-binding domain 101790 - Aminomethyltransferase beta-barrel domain	0	DIRECT
52540,47917 52540 - P-loop containing nucleoside triphosphate hydrolases 47917 - C-terminal domain of alpha and beta subunits of F1 ATP synthase	0	DIRECT
56059,52210 56059 - Glutathione synthetase ATP-binding domain-like 52210 - Succinyl-CoA synthetase domains	0	DIRECT
56968,48431 56968 - Lipovitellin-phosvitin complex; beta-sheet shell regions 48431 - Lipovitellin-phosvitin complex, superhelical domain	0	DIRECT
47005,52777 47005 - Peripheral subunit-binding domain of 2-oxo acid dehydrogenase complex 52777 - CoA-dependent acyltransferases	0	DIRECT
81995,81811 81995 - beta-sandwich domain of Sec23/24 81811 - Helical domain of Sec23/24	0	DIRECT
53901,53901 53901 - Thiolase-like 53901 - Thiolase-like	0	DIRECT
82895,57424 82895 - TSP-1 type 1 repeat 57424 - LDL receptor-like module	0	DIRECT
53300,81995 53300 - vWA-like 81995 - beta-sandwich domain of Sec23/24	0	DIRECT
47095,47095 47095 - HMG-box 47095 - HMG-box	0	DIRECT
48034,55931 48034 - Guanido kinase N-terminal domain 55931 - Glutamine synthetase/guanido kinase	0	DIRECT
57424,57184 57424 - LDL receptor-like module 57184 - Growth factor receptor domain	0	DIRECT
54534,54534 54534 - FKBP-like 54534 - FKBP-like	0	DIRECT
81271,55186 81271 - TGS-like 55186 - ThrRS/AlaRS common domain	0	DIRECT
48371,46785 48371 - ARM repeat 46785 - "Winged helix" DNA-binding domain	0	DIRECT
53850,53850 53850 - Periplasmic binding protein-like II 53850 - Periplasmic binding protein-like II	0	DIRECT
57603,57440 57603 - FnI-like domain 57440 - Kringle-like	0	DIRECT
54160,57850 54160 - Chromo domain-like 57850 - RING/U-box	0	DIRECT
50729,55550 50729 - PH domain-like 55550 - SH2 domain	0	DIRECT
55486,48371 55486 - Metalloproteases ("zincins"), catalytic domain 48371 - ARM repeat	0	DIRECT
57630,57196 57630 - GLA-domain 57196 - EGF/Laminin	0	DIRECT
57924,57924 57924 - Inhibitor of apoptosis (IAP) repeat 57924 - Inhibitor of apoptosis (IAP) repeat	0	DIRECT
54236,50729 54236 - Ubiquitin-like 50729 - PH domain-like	0	DIRECT
54928,54928 54928 - RNA-binding domain, RBD 54928 - RNA-binding domain, RBD	0.0002503	DIRECT
63737,55486 63737 - Leukotriene A4 hydrolase N-terminal domain 55486 - Metalloproteases ("zincins"), catalytic domain	0.06178	INHERITED FROM: pancreas
47459,158457 47459 - HLH, helix-loop-helix DNA-binding domain 158457 - Orange domain-like	0.08843	INHERITED FROM: heart
53067,53067 53067 - Actin-like ATPase domain 53067 - Actin-like ATPase domain	0.1152	INHERITED FROM: heart || pancreas
103657,50729 103657 - BAR/IMD domain-like 50729 - PH domain-like	0.1966	INHERITED FROM: pancreas
54791,54791 54791 - Eukaryotic type KH-domain (KH-domain type I) 54791 - Eukaryotic type KH-domain (KH-domain type I)	0.2283	INHERITED FROM: pancreas
52518,52518 52518 - Thiamin diphosphate-binding fold (THDP-binding) 52518 - Thiamin diphosphate-binding fold (THDP-binding)	0.2442	INHERITED FROM: pancreas
50494,50494 50494 - Trypsin-like serine proteases 50494 - Trypsin-like serine proteases	0.2442	INHERITED FROM: pancreas
57196,57184 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.3351	INHERITED FROM: heart
57716,57716 57716 - Glucocorticoid receptor-like (DNA-binding domain) 57716 - Glucocorticoid receptor-like (DNA-binding domain)	0.3859	INHERITED FROM: heart
57196,57196 57196 - EGF/Laminin 57196 - EGF/Laminin	0.4429	INHERITED FROM: heart
57184,57184 57184 - Growth factor receptor domain 57184 - Growth factor receptor domain	0.8417	INHERITED FROM: heart

Supra-domains annotated to this XA term (SPXA level: Moderately Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Triple) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
50729,55550,56112 50729 - PH domain-like 55550 - SH2 domain 56112 - Protein kinase-like (PK-like)	0	DIRECT
54791,54791,54791 54791 - Eukaryotic type KH-domain (KH-domain type I) 54791 - Eukaryotic type KH-domain (KH-domain type I) 54791 - Eukaryotic type KH-domain (KH-domain type I)	0	DIRECT
63737,55486,48371 63737 - Leukotriene A4 hydrolase N-terminal domain 55486 - Metalloproteases ("zincins"), catalytic domain 48371 - ARM repeat	0	DIRECT
57424,57424,57184 57424 - LDL receptor-like module 57424 - LDL receptor-like module 57184 - Growth factor receptor domain	0	DIRECT
53300,81995,81811 53300 - vWA-like 81995 - beta-sandwich domain of Sec23/24 81811 - Helical domain of Sec23/24	0	DIRECT
48592,54849,52029 48592 - GroEL equatorial domain-like 54849 - GroEL-intermediate domain like 52029 - GroEL apical domain-like	0	DIRECT
57196,49854,57535 57196 - EGF/Laminin 49854 - Spermadhesin, CUB domain 57535 - Complement control module/SCR domain	0	DIRECT
56436,56436,56436 56436 - C-type lectin-like 56436 - C-type lectin-like 56436 - C-type lectin-like	0	DIRECT
57630,57196,57196 57630 - GLA-domain 57196 - EGF/Laminin 57196 - EGF/Laminin	0	DIRECT
81995,81811,82754 81995 - beta-sandwich domain of Sec23/24 81811 - Helical domain of Sec23/24 82754 - C-terminal, gelsolin-like domain of Sec23/24	0	DIRECT
52058,52058,52058 52058 - L domain-like 52058 - L domain-like 52058 - L domain-like	0	DIRECT
50249,50249,50249 50249 - Nucleic acid-binding proteins 50249 - Nucleic acid-binding proteins 50249 - Nucleic acid-binding proteins	0	DIRECT
54160,57850,57845 54160 - Chromo domain-like 57850 - RING/U-box 57845 - B-box zinc-binding domain	0	DIRECT
52833,52833,52833 52833 - Thioredoxin-like 52833 - Thioredoxin-like 52833 - Thioredoxin-like	0	DIRECT
51230,47005,52777 51230 - Single hybrid motif 47005 - Peripheral subunit-binding domain of 2-oxo acid dehydrogenase complex 52777 - CoA-dependent acyltransferases	0	DIRECT
57424,57184,63825 57424 - LDL receptor-like module 57184 - Growth factor receptor domain 63825 - YWTD domain	0	DIRECT
55550,56112,56112 55550 - SH2 domain 56112 - Protein kinase-like (PK-like) 56112 - Protein kinase-like (PK-like)	0	DIRECT
57716,57716,57716 57716 - Glucocorticoid receptor-like (DNA-binding domain) 57716 - Glucocorticoid receptor-like (DNA-binding domain) 57716 - Glucocorticoid receptor-like (DNA-binding domain)	0.2282	INHERITED FROM: heart
57196,57184,57184 57196 - EGF/Laminin 57184 - Growth factor receptor domain 57184 - Growth factor receptor domain	0.2442	INHERITED FROM: heart
57196,57196,57184 57196 - EGF/Laminin 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.5402	INHERITED FROM: heart
57184,57196,57196 57184 - Growth factor receptor domain 57196 - EGF/Laminin 57196 - EGF/Laminin	0.9658	INHERITED FROM: heart

Trees by TreeVector

A presence/absence matrix is generated using protein domains and supradomains for all genomes in SUPERFAMILY. The RAxML software is used to produce a single, large tree topology using heuristic parsimony methods. Genome combinations, or specific clades, can be displayed as if individual trees had been produced. However, this data is extracted from the single large tree. This produces a higher quality topology than if the trees had been produced on their own, and allows the trees to be displayed instantly.