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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 YP term (SDYP level: Least Informative)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
FAD-linked oxidoreductase	0	DIRECT
YjgF-like	0	DIRECT
HIT-like	0	DIRECT
Ferritin-like	0	DIRECT
F1F0 ATP synthase subunit C	0	DIRECT
S13-like H2TH domain	0	DIRECT
Nucleoporin domain	0	DIRECT
Restriction endonuclease-like	0	DIRECT
KA1-like	0	DIRECT
Radical SAM enzymes	0	DIRECT
TK C-terminal domain-like	0	DIRECT
ThrRS/AlaRS common domain	0	DIRECT
Ligand-binding domain in the NO signalling and Golgi transport	0	DIRECT
YAP1 redox domain	0	DIRECT
EPT/RTPC-like	0	DIRECT
HRDC-like	0	DIRECT
Seven-hairpin glycosidases	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
Clathrin adaptor appendage domain	0	DIRECT
Chromo domain-like	0	DIRECT
Fe,Mn superoxide dismutase (SOD), C-terminal domain	0	DIRECT
HD-domain/PDEase-like	0	DIRECT
Bromodomain	0	DIRECT
R3H domain	0	DIRECT
ValRS/IleRS/LeuRS editing domain	0	DIRECT
Cysteine alpha-hairpin motif	0	DIRECT
Tubulin C-terminal domain-like	0	DIRECT
LexA/Signal peptidase	0	DIRECT
Heat shock protein 70kD (HSP70), C-terminal subdomain	0	DIRECT
Glycoside hydrolase/deacetylase	0	DIRECT
ALDH-like	0	DIRECT
GHMP Kinase, C-terminal domain	0	DIRECT
tRNA-intron endonuclease catalytic domain-like	0	DIRECT
WW domain	0	DIRECT
PP2C-like	0	DIRECT
Aconitase iron-sulfur domain	0	DIRECT
HLH, helix-loop-helix DNA-binding domain	0	DIRECT
Endosomal sorting complex assembly domain	0	DIRECT
Phosphoenolpyruvate/pyruvate domain	0	DIRECT
Sec7 domain	0	DIRECT
HMA, heavy metal-associated domain	0	DIRECT
DNA repair protein MutS, domain I	0	DIRECT
PA domain	0	DIRECT
Cap-Gly domain	0	DIRECT
Trimeric LpxA-like enzymes	0	DIRECT
cAMP-binding domain-like	0	DIRECT
Cytochrome P450	0	DIRECT
Glutamine synthetase/guanido kinase	0	DIRECT
VPS9 domain	0	DIRECT
Ribosomal protein L14	0	DIRECT
GYF domain	0	DIRECT
SAICAR synthase-like	0	DIRECT
CRAL/TRIO N-terminal domain	0	DIRECT
Thiolase-like	0	DIRECT
EF-G C-terminal domain-like	0	DIRECT
DNA repair protein MutS, domain II	0	DIRECT
YVTN repeat-like/Quinoprotein amine dehydrogenase	0	DIRECT
Kelch motif	0	DIRECT
Ras GEF	0	DIRECT
Ribosomal protein S8	0	DIRECT
N-terminal domain of alpha and beta subunits of F1 ATP synthase	0	DIRECT
HMG-box	0	DIRECT
CRAL/TRIO domain	0	DIRECT
Tryptophan synthase beta subunit-like PLP-dependent enzymes	0	DIRECT
Zn-binding ribosomal proteins	0	DIRECT
MurD-like peptide ligases, peptide-binding domain	0	DIRECT
Prefoldin	0	DIRECT
Arginase/deacetylase	0	DIRECT
CCCH zinc finger	0	DIRECT
Actin depolymerizing proteins	0	DIRECT
Ribokinase-like	0	DIRECT
Carbon-nitrogen hydrolase	0	DIRECT
MurD-like peptide ligases, catalytic domain	0	DIRECT
Terpenoid synthases	0	DIRECT
Tricorn protease domain 2	0	DIRECT
Transferrin receptor-like dimerisation domain	0	DIRECT
FAD/NAD-linked reductases, dimerisation (C-terminal) domain	0	DIRECT
Aquaporin-like	0	DIRECT
Mss4-like	0	DIRECT
Ribosomal L11/L12e N-terminal domain	0	DIRECT
Anticodon-binding domain of a subclass of class I aminoacyl-tRNA synthetases	0	DIRECT
C-terminal domain of alpha and beta subunits of F1 ATP synthase	0	DIRECT
Methylglyoxal synthase-like	0	DIRECT
CheY-like	0	DIRECT
Supernatant protein factor (SPF), C-terminal domain	0	DIRECT
DNA-binding domain of Mlu1-box binding protein MBP1	0	DIRECT
FtsH protease domain-like	0	DIRECT
Calponin-homology domain, CH-domain	0	DIRECT
HSP40/DnaJ peptide-binding domain	0	DIRECT
4'-phosphopantetheinyl transferase	0	DIRECT
Ribosomal protein L10-like	0	DIRECT
PR-1-like	0	DIRECT
Ribosomal protein L11, C-terminal domain	0	DIRECT
POZ domain	0	DIRECT
DnaJ/Hsp40 cysteine-rich domain	0	DIRECT
Family A G protein-coupled receptor-like	0	DIRECT
Ribosomal protein L13	0	DIRECT
Cytochrome c	0	DIRECT
C-terminal autoproteolytic domain of nucleoporin nup98	0	DIRECT
CBS-domain pair	0	DIRECT
Heat shock protein 70kD (HSP70), peptide-binding domain	0	DIRECT
Mitochondrial cytochrome c oxidase subunit IV	0	DIRECT
HCP-like	0	DIRECT
alpha/beta knot	0	DIRECT
Inosine monophosphate dehydrogenase (IMPDH)	0	DIRECT
Undecaprenyl diphosphate synthase	0	DIRECT
Ribosomal protein L6	0	DIRECT
PYP-like sensor domain (PAS domain)	0	DIRECT
Zinc domain conserved in yeast copper-regulated transcription factors	0	DIRECT
Zn-dependent exopeptidases	0	DIRECT
Acetyl-CoA synthetase-like	0	DIRECT
Protein kinase-like (PK-like)	0.3258	INHERITED FROM: osmotic stress resistance || ionic stress resistance
Subtilisin-like	0.7955	INHERITED FROM: acid pH resistance

Family domains annotated to this YP term (SDYP level: Least Informative)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
MIF4G domain-like	0	DIRECT
Erythroid transcription factor GATA-1	0	DIRECT
PyrH-like	0	DIRECT
TRAPP components	0	DIRECT
Sec7 domain	0	DIRECT
FAD-linked oxidases, N-terminal domain	0	DIRECT
Heat shock protein 70kD (HSP70), peptide-binding domain	0	DIRECT
CRAL/TRIO N-terminal domain	0	DIRECT
Histone deacetylase, HDAC	0	DIRECT
GABA-aminotransferase-like	0	DIRECT
Serine carboxypeptidase-like	0	DIRECT
Bromodomain	0	DIRECT
Ferredoxin reductase FAD-binding domain-like	0	DIRECT
FAD/NAD-linked reductases, dimerisation (C-terminal) domain	0	DIRECT
Aconitase iron-sulfur domain	0	DIRECT
Cofilin-like	0	DIRECT
HCP-like	0	DIRECT
Hexokinase	0	DIRECT
RNA-polymerase beta-prime	0	DIRECT
RNB domain-like	0	DIRECT
Glycosyl hydrolases family 16	0	DIRECT
CRAL/TRIO domain	0	DIRECT
Undecaprenyl diphosphate synthase	0	DIRECT
CheY-related	0	DIRECT
Higher-molecular-weight phosphotyrosine protein phosphatases	0	DIRECT
p120GAP domain-like	0	DIRECT
ABC transporter transmembrane region	0	DIRECT
Adenosine/AMP deaminase	0	DIRECT
C-terminal domain of alpha and beta subunits of F1 ATP synthase	0	DIRECT
Pseudouridine synthase I TruA	0	DIRECT
Translational machinery components	0	DIRECT
Ribosomal protein S8	0	DIRECT
Lysophospholipase	0	DIRECT
CCCH zinc finger	0	DIRECT
HLH, helix-loop-helix DNA-binding domain	0	DIRECT
DNA gyrase/MutL, N-terminal domain	0	DIRECT
Zinc domain conserved in yeast copper-regulated transcription factors	0	DIRECT
Thiamin biosynthesis kinases	0	DIRECT
Acetyl-CoA synthetase-like	0	DIRECT
Class I aldolase	0	DIRECT
PA domain	0	DIRECT
Ribosomal protein L14e	0	DIRECT
Tetratricopeptide repeat (TPR)	0	DIRECT
DNA polymerase I	0	DIRECT
FabD-like	0	DIRECT
Ribosomal protein L14	0	DIRECT
Phosphoribosylpyrophosphate synthetase-like	0	DIRECT
Clathrin coat assembly domain	0	DIRECT
VHS domain	0	DIRECT
DNA repair protein MutS, domain I	0	DIRECT
C-terminal domain of ribosomal protein L2	0	DIRECT
Anticodon-binding domain of a subclass of class I aminoacyl-tRNA synthetases	0	DIRECT
Inosine monophosphate dehydrogenase (IMPDH)	0	DIRECT
Helical domain of Sec23/24	0	DIRECT
Tryptophan synthase beta subunit-like PLP-dependent enzymes	0	DIRECT
VPS9 domain	0	DIRECT
Aquaporin-like	0	DIRECT
Dual specificity phosphatase-like	0	DIRECT
N-terminal domain of alpha and beta subunits of F1 ATP synthase	0	DIRECT
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, kinase domain	0	DIRECT
Class I aminoacyl-tRNA synthetases (RS), catalytic domain	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, phosphatase domain	0	DIRECT
Eps15 homology domain (EH domain)	0	DIRECT
Ribosomal protein L6	0	DIRECT
Cytochrome P450	0	DIRECT
HSP40/DnaJ peptide-binding domain	0	DIRECT
FtsH protease domain-like	0	DIRECT
PR-1-like	0	DIRECT
Prefoldin	0	DIRECT
Calponin-homology domain, CH-domain	0	DIRECT
YjgF/L-PSP	0	DIRECT
UBC-related	0	DIRECT
Ribosomal protein L13	0	DIRECT
Ribosomal protein S13	0	DIRECT
Ribokinase-like	0	DIRECT
Histidine acid phosphatase	0	DIRECT
Bacteriorhodopsin-like	0	DIRECT
F1F0 ATP synthase subunit C	0	DIRECT
DNA gyrase/MutL, second domain	0	DIRECT
C-terminal autoproteolytic domain of nucleoporin nup98	0	DIRECT
ALDH-like	0	DIRECT
GHMP Kinase, N-terminal domain	0	DIRECT
HMA, heavy metal-associated domain	0	DIRECT
Clathrin adaptor core protein	0	DIRECT
Actin/HSP70	0	DIRECT
La domain	0	DIRECT
SWIRM domain	0	DIRECT
Myb/SANT domain	0	DIRECT
XPF/Rad1/Mus81 nuclease	0	DIRECT
Transferrin receptor-like dimerisation domain	0	DIRECT
Folylpolyglutamate synthetase	0	DIRECT
DnaJ/Hsp40 cysteine-rich domain	0	DIRECT
Ribosomal protein L11, C-terminal domain	0	DIRECT
ValRS/IleRS/LeuRS editing domain	0	DIRECT
Class I alpha-1;2-mannosidase, catalytic domain	0	DIRECT
PP2C-like	0	DIRECT
Thiolase-related	0	DIRECT
tRNA-intron endonuclease catalytic domain-like	0	DIRECT
WW domain	0	DIRECT
DnaQ-like 3'-5' exonuclease	0	DIRECT
Heat shock protein 70kD (HSP70), C-terminal subdomain	0	DIRECT
HMG-box	0	DIRECT
Bacterial dinuclear zinc exopeptidases	0	DIRECT
Protein serine/threonine phosphatase	0	DIRECT
Phosphoribulokinase/pantothenate kinase	0	DIRECT
ENTH domain	0	DIRECT
EF-G/eEF-2 domains III and V	0	DIRECT
GYF domain	0	DIRECT
Vacuolar sorting protein domain	0	DIRECT
SAM (sterile alpha motif) domain	0	DIRECT
CBS-domain pair	0	DIRECT
Ras GEF	0	DIRECT
Tryptophan biosynthesis enzymes	0	DIRECT
Cap-Gly domain	0	DIRECT
YAP1 redox domain	0	DIRECT
FAD-linked reductases, N-terminal domain	0	DIRECT
LeuD-like	0	DIRECT
Ribosomal L11/L12e N-terminal domain	0	DIRECT
BCR-homology GTPase activation domain (BH-domain)	0	DIRECT
DJ-1/PfpI	0	DIRECT
Ran-binding domain	0	DIRECT
Phosphate binding protein-like	0	DIRECT
Pepsin-like	0	DIRECT
Reductases	0	DIRECT
DNA-binding domain of Mlu1-box binding protein MBP1	0	DIRECT
Isoprenyl diphosphate synthases	0	DIRECT
Protein kinases, catalytic subunit	0.2623	INHERITED FROM: osmotic stress resistance
Thioltransferase	0.3172	INHERITED FROM: oxidative stress resistance
Inositol polyphosphate 5-phosphatase (IPP5)	0.5898	INHERITED FROM: osmotic stress resistance || hyperosmotic stress resistance
RecA protein-like (ATPase-domain)	0.6505	INHERITED FROM: oxidative stress resistance || alkaline pH resistance
Subtilases	0.7823	INHERITED FROM: acid pH resistance
Glutathione peroxidase-like	0.8247	INHERITED FROM: oxidative stress resistance

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 YP term (SPYP level: Least Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Single)	FDR (all)	Annotation (direct or inherited)
EPT/RTPC-like	0	DIRECT
Zn-dependent exopeptidases	0	DIRECT
Calponin-homology domain, CH-domain	0	DIRECT
SAICAR synthase-like	0	DIRECT
Ligand-binding domain in the NO signalling and Golgi transport	0	DIRECT
Acetyl-CoA synthetase-like	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
Heat shock protein 70kD (HSP70), peptide-binding domain	0	DIRECT
WW domain	0	DIRECT
ThrRS/AlaRS common domain	0	DIRECT
HIT-like	0	DIRECT
Undecaprenyl diphosphate synthase	0	DIRECT
S13-like H2TH domain	0	DIRECT
Aquaporin-like	0	DIRECT
Tubulin C-terminal domain-like	0	DIRECT
PR-1-like	0	DIRECT
Fe,Mn superoxide dismutase (SOD), C-terminal domain	0	DIRECT
PYP-like sensor domain (PAS domain)	0	DIRECT
PP2C-like	0	DIRECT
FtsH protease domain-like	0	DIRECT
Phosphoenolpyruvate/pyruvate domain	0	DIRECT
Cytochrome c	0	DIRECT
DNA-binding domain of Mlu1-box binding protein MBP1	0	DIRECT
HRDC-like	0	DIRECT
Tricorn protease domain 2	0	DIRECT
Sec7 domain	0	DIRECT
DnaJ/Hsp40 cysteine-rich domain	0	DIRECT
Cap-Gly domain	0	DIRECT
GHMP Kinase, C-terminal domain	0	DIRECT
Ribosomal protein L10-like	0	DIRECT
Carbon-nitrogen hydrolase	0	DIRECT
KA1-like	0	DIRECT
CheY-like	0	DIRECT
ALDH-like	0	DIRECT
Ribosomal L11/L12e N-terminal domain	0	DIRECT
Ribokinase-like	0	DIRECT
DNA repair protein MutS, domain II	0	DIRECT
Aconitase iron-sulfur domain	0	DIRECT
Kelch motif	0	DIRECT
LexA/Signal peptidase	0	DIRECT
MurD-like peptide ligases, catalytic domain	0	DIRECT
YAP1 redox domain	0	DIRECT
C-terminal domain of alpha and beta subunits of F1 ATP synthase	0	DIRECT
EF-G C-terminal domain-like	0	DIRECT
Seven-hairpin glycosidases	0	DIRECT
HMA, heavy metal-associated domain	0	DIRECT
Zn-binding ribosomal proteins	0	DIRECT
YjgF-like	0	DIRECT
Clathrin adaptor appendage domain	0	DIRECT
Cysteine alpha-hairpin motif	0	DIRECT
HMG-box	0	DIRECT
Zinc domain conserved in yeast copper-regulated transcription factors	0	DIRECT
C-terminal autoproteolytic domain of nucleoporin nup98	0	DIRECT
YVTN repeat-like/Quinoprotein amine dehydrogenase	0	DIRECT
CRAL/TRIO N-terminal domain	0	DIRECT
TK C-terminal domain-like	0	DIRECT
Inosine monophosphate dehydrogenase (IMPDH)	0	DIRECT
Glycoside hydrolase/deacetylase	0	DIRECT
4'-phosphopantetheinyl transferase	0	DIRECT
CCCH zinc finger	0	DIRECT
Chromo domain-like	0	DIRECT
Endosomal sorting complex assembly domain	0	DIRECT
cAMP-binding domain-like	0	DIRECT
Restriction endonuclease-like	0	DIRECT
HD-domain/PDEase-like	0	DIRECT
Ferritin-like	0	DIRECT
VPS9 domain	0	DIRECT
Ribosomal protein L6	0	DIRECT
DNA repair protein MutS, domain I	0	DIRECT
N-terminal domain of alpha and beta subunits of F1 ATP synthase	0	DIRECT
CBS-domain pair	0	DIRECT
PA domain	0	DIRECT
Cytochrome P450	0	DIRECT
Arginase/deacetylase	0	DIRECT
Mss4-like	0	DIRECT
Thiolase-like	0	DIRECT
Ras GEF	0	DIRECT
Transferrin receptor-like dimerisation domain	0	DIRECT
HCP-like	0	DIRECT
Tryptophan synthase beta subunit-like PLP-dependent enzymes	0	DIRECT
FAD/NAD-linked reductases, dimerisation (C-terminal) domain	0	DIRECT
GYF domain	0	DIRECT
Ribosomal protein L13	0	DIRECT
Terpenoid synthases	0	DIRECT
Mitochondrial cytochrome c oxidase subunit IV	0	DIRECT
Bromodomain	0	DIRECT
Nucleoporin domain	0	DIRECT
Glutamine synthetase/guanido kinase	0	DIRECT
Anticodon-binding domain of a subclass of class I aminoacyl-tRNA synthetases	0	DIRECT
Heat shock protein 70kD (HSP70), C-terminal subdomain	0	DIRECT
POZ domain	0	DIRECT
Ribosomal protein L14	0	DIRECT
HLH, helix-loop-helix DNA-binding domain	0	DIRECT
CRAL/TRIO domain	0	DIRECT
Prefoldin	0	DIRECT
Ribosomal protein L11, C-terminal domain	0	DIRECT
Ribosomal protein S8	0	DIRECT
Actin depolymerizing proteins	0	DIRECT
FAD-linked oxidoreductase	0	DIRECT
Supernatant protein factor (SPF), C-terminal domain	0	DIRECT
Trimeric LpxA-like enzymes	0	DIRECT
Radical SAM enzymes	0	DIRECT
R3H domain	0	DIRECT
ValRS/IleRS/LeuRS editing domain	0	DIRECT
Family A G protein-coupled receptor-like	0	DIRECT
HSP40/DnaJ peptide-binding domain	0	DIRECT
tRNA-intron endonuclease catalytic domain-like	0	DIRECT
Methylglyoxal synthase-like	0	DIRECT
F1F0 ATP synthase subunit C	0	DIRECT
alpha/beta knot	0	DIRECT
MurD-like peptide ligases, peptide-binding domain	0	DIRECT
C2 domain (Calcium/lipid-binding domain, CaLB)	0.174	INHERITED FROM: ionic stress resistance
Protein kinase-like (PK-like)	0.3099	INHERITED FROM: ionic stress resistance || osmotic stress resistance
Subtilisin-like	0.7869	INHERITED FROM: acid pH resistance

Supra-domains annotated to this YP term (SPYP level: Least 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)
49562,49562 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 49562 - C2 domain (Calcium/lipid-binding domain, CaLB)	0	DIRECT
50677,52374 50677 - ValRS/IleRS/LeuRS editing domain 52374 - Nucleotidylyl transferase	0	DIRECT
48371,52540 48371 - ARM repeat 52540 - P-loop containing nucleoside triphosphate hydrolases	0	DIRECT
53901,53901 53901 - Thiolase-like 53901 - Thiolase-like	0	DIRECT
90229,90229 90229 - CCCH zinc finger 90229 - CCCH zinc finger	0	DIRECT
-7,52540 -7 - CATH 52540 - P-loop containing nucleoside triphosphate hydrolases	0	DIRECT
57850,52540 57850 - RING/U-box 52540 - P-loop containing nucleoside triphosphate hydrolases	0	DIRECT
52540,140990 52540 - P-loop containing nucleoside triphosphate hydrolases 140990 - FtsH protease domain-like	0	DIRECT
46938,52087 46938 - CRAL/TRIO N-terminal domain 52087 - CRAL/TRIO domain	0	DIRECT
52490,55307 52490 - Tubulin nucleotide-binding domain-like 55307 - Tubulin C-terminal domain-like	0	DIRECT
46689,46689 46689 - Homeodomain-like 46689 - Homeodomain-like	0	DIRECT
100920,100934 100920 - Heat shock protein 70kD (HSP70), peptide-binding domain 100934 - Heat shock protein 70kD (HSP70), C-terminal subdomain	0	DIRECT
63380,52343 63380 - Riboflavin synthase domain-like 52343 - Ferredoxin reductase-like, C-terminal NADP-linked domain	0	DIRECT
56053,56053 56053 - Ribosomal protein L6 56053 - Ribosomal protein L6	0	DIRECT
54236,57829 54236 - Ubiquitin-like 57829 - Zn-binding ribosomal proteins	0	DIRECT
49493,49493 49493 - HSP40/DnaJ peptide-binding domain 49493 - HSP40/DnaJ peptide-binding domain	0	DIRECT
50615,52540 50615 - N-terminal domain of alpha and beta subunits of F1 ATP synthase 52540 - P-loop containing nucleoside triphosphate hydrolases	0	DIRECT
50249,50104 50249 - Nucleic acid-binding proteins 50104 - Translation proteins SH3-like domain	0	DIRECT
54980,54211 54980 - EF-G C-terminal domain-like 54211 - Ribosomal protein S5 domain 2-like	0	DIRECT
57756,57756 57756 - Retrovirus zinc finger-like domains 57756 - Retrovirus zinc finger-like domains	0	DIRECT
54631,51412 54631 - CBS-domain pair 51412 - Inosine monophosphate dehydrogenase (IMPDH)	0	DIRECT
46565,57938 46565 - Chaperone J-domain 57938 - DnaJ/Hsp40 cysteine-rich domain	0	DIRECT
55681,52954 55681 - Class II aaRS and biotin synthetases 52954 - Class II aaRS ABD-related	0	DIRECT
50044,50044 50044 - SH3-domain 50044 - SH3-domain	0	DIRECT
52374,47323 52374 - Nucleotidylyl transferase 47323 - Anticodon-binding domain of a subclass of class I aminoacyl-tRNA synthetases	0	DIRECT
49879,56112 49879 - SMAD/FHA domain 56112 - Protein kinase-like (PK-like)	0	DIRECT
55874,54211 55874 - ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase 54211 - Ribosomal protein S5 domain 2-like	0	DIRECT
52518,52922 52518 - Thiamin diphosphate-binding fold (THDP-binding) 52922 - TK C-terminal domain-like	0	DIRECT
54631,54631 54631 - CBS-domain pair 54631 - CBS-domain pair	0	DIRECT
50447,54980 50447 - Translation proteins 54980 - EF-G C-terminal domain-like	0	DIRECT
57938,49493 57938 - DnaJ/Hsp40 cysteine-rich domain 49493 - HSP40/DnaJ peptide-binding domain	0	DIRECT
50249,50249 50249 - Nucleic acid-binding proteins 50249 - Nucleic acid-binding proteins	0	DIRECT
54791,54791 54791 - Eukaryotic type KH-domain (KH-domain type I) 54791 - Eukaryotic type KH-domain (KH-domain type I)	0	DIRECT
53067,100920 53067 - Actin-like ATPase domain 100920 - Heat shock protein 70kD (HSP70), peptide-binding domain	0	DIRECT
48371,48371 48371 - ARM repeat 48371 - ARM repeat	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
52518,52518 52518 - Thiamin diphosphate-binding fold (THDP-binding) 52518 - Thiamin diphosphate-binding fold (THDP-binding)	0	DIRECT
54747,46906 54747 - Ribosomal L11/L12e N-terminal domain 46906 - Ribosomal protein L11, C-terminal domain	0	DIRECT
51905,55424 51905 - FAD/NAD(P)-binding domain 55424 - FAD/NAD-linked reductases, dimerisation (C-terminal) domain	0	DIRECT
53732,52016 53732 - Aconitase iron-sulfur domain 52016 - LeuD/IlvD-like	0	DIRECT
81333,81333 81333 - F1F0 ATP synthase subunit C 81333 - F1F0 ATP synthase subunit C	0	DIRECT
53098,56672 53098 - Ribonuclease H-like 56672 - DNA/RNA polymerases	0	DIRECT
103657,50729 103657 - BAR/IMD domain-like 50729 - PH domain-like	0	DIRECT
52025,53187 52025 - PA domain 53187 - Zn-dependent exopeptidases	0	DIRECT
53187,47672 53187 - Zn-dependent exopeptidases 47672 - Transferrin receptor-like dimerisation domain	0	DIRECT
46785,46785 46785 - "Winged helix" DNA-binding domain 46785 - "Winged helix" DNA-binding domain	0	DIRECT
54211,55060 54211 - Ribosomal protein S5 domain 2-like 55060 - GHMP Kinase, C-terminal domain	0	DIRECT
53150,48334 53150 - DNA repair protein MutS, domain II 48334 - DNA repair protein MutS, domain III	0	DIRECT
53623,53244 53623 - MurD-like peptide ligases, catalytic domain 53244 - MurD-like peptide ligases, peptide-binding domain	0	DIRECT
53613,48613 53613 - Ribokinase-like 48613 - Heme oxygenase-like	0	DIRECT
54211,54980 54211 - Ribosomal protein S5 domain 2-like 54980 - EF-G C-terminal domain-like	0	DIRECT
52540,90123 52540 - P-loop containing nucleoside triphosphate hydrolases 90123 - ABC transporter transmembrane region	0	DIRECT
52540,53254 52540 - P-loop containing nucleoside triphosphate hydrolases 53254 - Phosphoglycerate mutase-like	0	DIRECT

Supra-domains annotated to this YP term (SPYP level: Least 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)
50447,54980,54211 50447 - Translation proteins 54980 - EF-G C-terminal domain-like 54211 - Ribosomal protein S5 domain 2-like	0	DIRECT
53067,100920,100934 53067 - Actin-like ATPase domain 100920 - Heat shock protein 70kD (HSP70), peptide-binding domain 100934 - Heat shock protein 70kD (HSP70), C-terminal subdomain	0	DIRECT
54980,54211,54980 54980 - EF-G C-terminal domain-like 54211 - Ribosomal protein S5 domain 2-like 54980 - EF-G C-terminal domain-like	0	DIRECT
46565,57938,49493 46565 - Chaperone J-domain 57938 - DnaJ/Hsp40 cysteine-rich domain 49493 - HSP40/DnaJ peptide-binding domain	0	DIRECT
49562,49562,49562 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 49562 - C2 domain (Calcium/lipid-binding domain, CaLB)	0	DIRECT
57938,49493,49493 57938 - DnaJ/Hsp40 cysteine-rich domain 49493 - HSP40/DnaJ peptide-binding domain 49493 - HSP40/DnaJ peptide-binding domain	0	DIRECT
53150,48334,52540 53150 - DNA repair protein MutS, domain II 48334 - DNA repair protein MutS, domain III 52540 - P-loop containing nucleoside triphosphate hydrolases	0	DIRECT
48371,48371,48371 48371 - ARM repeat 48371 - ARM repeat 48371 - ARM repeat	0	DIRECT
52540,50447,54980 52540 - P-loop containing nucleoside triphosphate hydrolases 50447 - Translation proteins 54980 - EF-G C-terminal domain-like	0	DIRECT
57756,57756,57756 57756 - Retrovirus zinc finger-like domains 57756 - Retrovirus zinc finger-like domains 57756 - Retrovirus zinc finger-like domains	0	DIRECT
90123,52540,90123 90123 - ABC transporter transmembrane region 52540 - P-loop containing nucleoside triphosphate hydrolases 90123 - ABC transporter transmembrane region	0	DIRECT
52540,90123,52540 52540 - P-loop containing nucleoside triphosphate hydrolases 90123 - ABC transporter transmembrane region 52540 - P-loop containing nucleoside triphosphate hydrolases	0	DIRECT
53067,53067,100920 53067 - Actin-like ATPase domain 53067 - Actin-like ATPase domain 100920 - Heat shock protein 70kD (HSP70), peptide-binding domain	0	DIRECT
50615,52540,47917 50615 - N-terminal domain of alpha and beta subunits of F1 ATP synthase 52540 - P-loop containing nucleoside triphosphate hydrolases 47917 - C-terminal domain of alpha and beta subunits of F1 ATP synthase	0	DIRECT
48371,52540,52540 48371 - ARM repeat 52540 - P-loop containing nucleoside triphosphate hydrolases 52540 - P-loop containing nucleoside triphosphate hydrolases	0	DIRECT
52025,53187,47672 52025 - PA domain 53187 - Zn-dependent exopeptidases 47672 - Transferrin receptor-like dimerisation domain	0	DIRECT

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.