Pathway Studio ResNet Database Description and Workflow Examples

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Jun 10, 2015

1. Entities: Definitions and Annotation

a. Entity Types and Definition

Entity Type

Definition

Cell Process

Basic processes occurring within and carried out by the cell. Cell processes may contain proteins as property = child concepts.

Clinical Parameter

Parameters measured in clinical

Complex

Several polypeptides that form a complex via physical interactions.

Disease

Health conditions and diseases

Functional Class

Classes of proteins, such as enzyme families. Functional classes contain proteins as property = child concepts.

Protein

Genes and gene products defined by Entrez Gene, including proteins, miRNAs, pseudogenes and non-coding RNAs

Small Molecule

ResNet Mammal: Naturally occurring metabolites and small molecules found in cells;

ResNet Mammal + ChemEffect® adds drugs (including biologically active peptides and antibody drugs), environmental chemicals and non-naturally occurring small molecules.

Treatment

Non-chemical treatments and environmental conditions

b. Entity Annotations

Complex

Property Name

Property Type

Source

Description

Name

short string

GO Cellular Component with manual curation

The display name for a complex.

Alias

short string

manual curation from multiple sources

Other identifiers assigned to the complex.

MedScanID

short string

MedScan

Internal Elsevier’s identifier

GO ID

short string

http://geneontology.org/

The Gene Ontology project provides a controlled vocabulary of terms for describing gene product characteristics.

KEGG ID

short string

http://www.genome.jp/kegg/

KEGG is a database resource for understanding high-level functions and utilities of the biological system, such as the cell, the organism and the ecosystem, from molecular-level information, especially large-scale molecular datasets generated by genome sequencing and other high-throughput experimental technologies.

Functional Class

Property Name

Property Type

Source

Description

Name

short string

http://www.expasy.org/

The display name for the functional class

Alias

short string

Manual curation from multiple sources

Other identifiers assigned to the functional class

MedScanID

short string

MedScan

Internal Elsevier’s identifier

GO ID

short string

http://geneontology.org/

The Gene Ontology project provides a controlled vocabulary of terms for describing gene product characteristics.

Cell

dictionary

http://geneontology.org/

Gene Ontology – Cellular Component. Not all cellular

Localization

processes have localization assignment.

Mol Function

dictionary

http://geneontology.org/

Functional classes with associated activities: ligand, phosphatases, protein kinases, receptor and transcription factor are annotated as such in the Mol Function property.

Description

short string

manually curated from multiple sources

Full names of the functional class.

EC Number

short string

Enzyme Commission Number

The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze.

Protein

Property Name

Property Type

Source

Description

Name

short string

Entrez official gene symbol

http://www.ncbi.nlm.nih.gov/gquery/

Display symbol for a gene

Alias

short string

Entrez with manual curation

Other identifiers assigned to the protein.

MedScanID

short string

MedScan dictionary – Elsevier

Internal Elsevier’s identifier

GO ID

short string

http://geneontology.org/

The Gene Ontology project provides a controlled vocabulary of terms for describing gene product characteristics.

Cell Localization

dictionary

http://geneontology.org/

Gene Ontology – Cellular Component. The Gene Ontology project provides a controlled vocabulary of terms for describing gene product characteristics. Cellular Process entities are derived from Gene

Organism

dictionary

http://www.ncbi.nlm.nih.gov/taxonomy

The Entrez Taxonomy database displays the species names (and higher-level classification) of all of the organisms that are represented in the Entrez sequence databases (or any of the other Entrez databases that are indexed by taxonomy).

Primary Cell Localization

dictionary

http://geneontology.org

Gene Ontology – Cellular Component. The Gene Ontology project provides a controlled vocabulary of terms for describing gene product characteristics. Cellular Process entities are derived from Gene

Notes

long Text

Summary of gene/gene product function provided by RefSeq

Description

short string

Official full name from Entrez

Full name for the gene

EC Number

short string

The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze.

Ensembl ID

short string

http://www.ensembl.org/

GenBank ID

short string

http://www.ncbi.nlm.nih.gov/

Homologene ID

short string

http://www.ncbi.nlm.nih.gov/homologene

An automated system for constructing putative homology groups from the complete gene sets of a wide range of eukaryotic species.

Hugo ID

short string

http://www.genenames.org/

HUGO Gene Nomenclature Committee is a curated online repository of HGNC-approved gene nomenclature, gene families and associated resources including links to genomic, proteomic and phenotypic information.

Human chromosome position

short string

http://www.ncbi.nlm.nih.gov/gene

Gene cytoband location

KEGG ID

short string

http://www.genome.jp/kegg/

KEGG is a database resource for understanding high-level functions and utilities of the biological system,

such as the cell, the organism and the ecosystem, from molecular-level information, especially large-scale molecular datasets generated by genome sequencing and other high-throughput experimental technologies.

LocusLink ID

short string

http://www.ncbi.nlm.nih.gov/LocusLink

Old NCBI identifier that has transitioned to Entrez IDs.

MGI ID

short string

http://www.informatics.jax.org/

Mouse Genome Informatics identifier for genes.

Mouse chromosome position

short string

http://www.ncbi.nlm.nih.gov/gene

Gene cytoband location

OMIM ID

short string

http://omim.org/

Online Mendelian Inheritance in Man® is an Online Catalog of Human Genes and Genetic Disorders. OMIM focuses on the relationship between phenotype and genotype.

PIR ID

short string

http://pir.georgetown.edu/pirwww/index.shtml

Integrated Protein Informatics Resources for Genomic, Proteomic and Systems Biology Research

RGD ID

short string

http://rgd.mcw.edu/wg/home

Rat Genome Database gene identifiers.

Rat chromosome position

short string

http://www.ncbi.nlm.nih.gov/gene

Gene cytoband location

Swiss-Prot Accession

short string

http://www.uniprot.org/

The Universal Protein Resource (UniProt) is a comprehensive resource for protein sequence and annotation data.

Swiss-Prot ID

short string

Unigene ID

short string

http://www.ncbi.nlm.nih.gov/unigene

UniGene computationally identifies transcripts from the same locus; analyzes expression by tissue, age, and health status; and reports related proteins (protEST).and clone resources.

miRBase ID

short string

http://www.mirbase.org/

miRBase is a database of published miRNA sequences and annotation.

Small Molecule

Property Name

Property Type

Source

Description

Name

short string

PubChem compounds and manual curation from multiple sources

Display name for the small molecule

Alias

short string

PubChem compounds and manual curation from multiple sources

Other identifiers assigned to the small molecule.

MedScanID

short string

MedScan dictionary – Elsevier

Internal Elsevier’s identifier

Molecular Weight

Numerical

https://pubchem.ncbi.nlm.nih.gov/

Molecular weight of a small molecule

Rotatable Bond Count

Numerical

https://pubchem.ncbi.nlm.nih.gov/

Number of rotatable bonds in the molecule. Rotatable bonds are defined as single bonds between heavy atoms. It doesn't include ring bonds, those connected to a heavy atom that is attached to only hydrogens or amide bonds.

CAS ID

short string

https://www.cas.org/content/chemical-substances/faqs

A CAS Registry Number, is a unique numerical identifier assigned by Chemical Abstracts Service (CAS) to every chemical substance described in the open scientific literature.

ChEBI ID

short string

http://www.ebi.ac.uk/chebi/init.do

ChEBI stands for 'Chemical Entities of Biological Interest'. It is a freely available database of 'small molecular entities', developed at the EBI. The term 'molecular entity' encompasses any constitutionally or isotopically distinct atom, molecule, ion, ion pair,

radical, radical ion, complex, conformer, etc., identifiable as a separately distinguishable entity.

HMDB ID

short string

http://www.hmdb.ca/

The Human Metabolome Database (HMDB) is an electronic database containing detailed information about small molecule metabolites found in the human body.

IUPAC Name

short string

http://www.iupac.org/

Name assigned according to the IUPAC nomenclature of organic chemistry,

InChIKey

short string

http://www.iupac.org/

The IUPAC International Chemical Identifier (InChITM) is a non-proprietary identifier for chemical substances that can be used in printed and electronic data sources thus enabling easier linking of diverse data compilations.

KEGG ID

short string

http://www.genome.jp/kegg/

KEGG is a database resource for understanding high-level functions and utilities of the biological system, such as the cell, the organism and the ecosystem, from molecular-level information, especially large-scale molecular datasets generated by genome sequencing and other high-throughput experimental technologies.

Molecular Formula

short string

https://pubchem.ncbi.nlm.nih.gov/

Molecular formula of a small molecule

PharmaPendium Name

short string

https://www.pharmapendium.com /#/home

The name of the drug as it appears in Pharmapendium. Elsevier’s PharmaPendium offers dedicated data modules that provide insights and information on the critical focused areas of drug development, drug safety, ADME and drug-drug interactions.

PubChem CID

short string

https://pubchem.ncbi.nlm.nih.gov/

The PubChem Compound Database contains validated chemical depiction information provided to describe substances in PubChem Substance. Structures stored within PubChem Compounds are pre-clustered and cross-referenced by identity and similarity groups. A compound identifier (CID) is the permanent identifer for a unique chemical structure. Each stereoisomer of a compound has its own CID. It is also possible for different tautomeric forms of the same compound to have different CID's.

PubChem SID

short string

http://pubchem.ncbi.nlm.nih.gov/

The PubChem Compound Database contains validated chemical depiction information provided to describe substances in PubChem Substance. Structures stored within PubChem Compounds are pre-clustered and cross-referenced by identity and similarity groups. A substance identifier (SID) is the permanent identifier for a depositor-supplied molecule. Each SID corresponds to a unique external registry ID provided by a PubChem data source.

Reaxys ID

short string

https://www.reaxys.com

Elsevier’s Reaxys and Reaxys Medicinal Chemistry combine comprehensive databases of chemistry data and literature with powerful search interfaces. They return relevant extracted data and citations in optimal formats for chemistry research. Both can seamlessly integrate into an existing environment of tools and systems, saving time and reducing the risk of inconsistencies.

XLogP

Numerical

https://pubchem.ncbi.nlm.nih.gov/

A partition coefficient or distribution coefficient that is a measure of differential solubility of a compound in two solvents.

XLogP-AA

short string

https://pubchem.ncbi.nlm.nih.gov/

A partition coefficient or distribution coefficient that is a measure of differential solubility of a compound in two solvents.

Cell Process

Property Name

Property Type

Source

Description

Name

short string

Manual curation from GO http://geneontology.org/

Display name for the cell process

Alias

short string

Manual curation from multiple sources

Other identifiers assigned to the cell process.

MedScanID

short string

MedScan dictionary – Elsevier

Internal Elsevier’s identifier

GO ID

short string

http://geneontology.org/

The Gene Ontology project provides a controlled vocabulary of terms for describing gene product characteristics. Cellular Process entities are derived from Gene Ontology with additional manual curation.

Cell localization

dictionary

http://geneontology.org/

Gene Ontology – Cellular Component. The Gene Ontology project provides a controlled vocabulary of terms for describing gene product characteristics. Cellular Process entities are derived from Gene Ontology with additional manual curation.

Description

short string

manually curated

Full name for the cell process

Treatment

Property Name

Property Type

Source

Description

Name

short string

Manually curated from multiple sources

Display name for the treatment

Alias

short string

Manually curated from multiple sources

Other identifiers assigned to the treatment.

MedScanID

short string

MedScan dictionary – Elsevier

Internal Elsevier’s identifier

Clinical Parameters

Property Name

Property Type

Source

Description

Name

short string

Manually curated from multiple sources

Display name for the clinical parameter

Alias

short string

Manually curated from multiple sources

Other identifiers assigned to the clinical parameter

MedScan

short string

MedScan dictionary – Elsevier

ID assigned in the MedScan dictionary (text mining tool)

Disease

Property Name

Property Type

Source

Description

Name

short string

MeSH with manual curation, OphaNet with manual curation

http://www.ncbi.nlm.nih.gov/mesh

http://www.orpha.net/consor/cgi-bin/index.php

Display name for the disease

Alias

short string

MeSH with manual curation, OphaNet with manual curation

http://www.ncbi.nlm.nih.gov/mesh

http://www.orpha.net/conso

Other identifiers assigned to the disease.

r/cgi-bin/index.php

MedScanID

short string

MedScan dictionary – Elsevier

Internal Elsevier’s identifier

MeSH heading

short string

https://www.nlm.nih.gov/mesh/

MeSH (Medical Subject Headings) is the National Library of Medicine controlled vocabulary thesaurus used for indexing articles for PubMed.

Additional Annotation for Entities

Property Name

Description

ObjectType

For entities, the object types are each entity type (protein, small molecule, etc.)

For relations, the object types are each relation type (expression, binding, etc.)

ChildConcepts

Concepts (proteins) mapped to a concept. For example, functional classes include all the proteins associated with the functional class as “child concepts.”

ParentConcepts

The ontological parent of a protein, which can be a functional class, or cellular process

URN

Elsevier internal identifier

2. Relations: Definitions and Annotations

The following relation types are included in the Mammal+ChemEffect+DiseaseFx Database.

a. Relation Types and Definitions

Type

Filtering Field Name

Sub-Categories

Definition

Binding

-

-

Direct physical interaction between two molecules. This relation type has no Direction and no Effect

Biomarker

BiomarkerType

diagnostic, prognostic

Molecule was reported as a biomarker for a disease (Disease  Protein/ Complex/Functional class/small molecule). This relation type has no Effect.

ChemicalReaction

-

-

Enzyme catalyzes reaction involving small molecule

ClinicalTrial

Phase

N/A, Phase 0, Phase 1, Phase1/Phase2, Phase2, Phase2/Phase3, Phase 3, Phase4

Disease/cell process relation representing clinical trials conducted for a drug against a disease (from clinicaltrials.gov) (Small molecule  Disease, CellProcess). This relation type has no Effect

Food and Drug Administration (FDA) categories for describing the clinical trial of a drug based on the study's characteristics. There are five phases:

Phase 0: Exploratory study involving very limited human exposure to the drug, with no therapeutic or diagnostic goals.

Phase 1: Studies that are usually conducted with healthy volunteers and that emphasize safety.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition. Safety continues to be evaluated, and short-term adverse events are studied.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing. These studies gather additional information about a drug's safety, efficacy, or optimal use.

DirectRegulation

-

-

Regulator influences target activity by direct physical interaction (excluding promoter binding interactions)

Expression

-

-

Regulator changes protein abundance by affecting levels of transcript or protein stability

FunctionalAssociation

-

-

Disease is associated to cell process, clinical parameter or another disease. This relation type has no Direction and no Effect.

GeneticChange

ChangeType

gene deletion, mutation, gene

amplification, epigenic methylation

Genetic changes associated with a disease (Disease  Protein/ Complex/Functional class)

miRNAEffect

-

-

The inhibitory effect of a miRNA on its mRNA target. These relations have two sources: 1) literature, 2) Public databases: miRanda (human, mouse, rat), PicTar(human) and TargetScan (human, mouse, rat).

This information is provided in the field “source.”

MolSynthesis

-

-

Regulator changes the concentrations of the

target (usually a small molecule target)

MolTransport

-

-

Regulator changes the localization of the target

(molecular translocation, export, import etc.)

PromoterBinding

-

-

Regulator binds to the promoter of a gene

ProtModification

Mechanism

acetylation,

cleavage, deacetylation,

demethylation,

dephosphorylation, direct

interaction, methylation,

phosphorylation,

posttrascriptional inhibition,

proteolysis, ubiquitination

Regulator changes the modification of the target

molecule, usually by a direct interaction

QuantitativeChange

QuantitativeType

expression,

abundance, activity

Changes in abundance/activity/expression of a gene/protein/small molecule associated with a disease (Disease  Protein/ Complex/Functional class)

Regulation

-

-

Regulator changes the activity of the target by an unknown

mechanism (direct or indirect). This is a less specific relation type than others provided

StateChange

Change Type

alternative

splicing, phosphorylation

Changes in a protein’s posttranslational modification status or alternative splicing events associated with a disease (Disease  Protein/ Complex/Functional class)

b. Relation Annotations

Most of the annotations for relations share common annotations fields. Below is a list of shared annotations for all relation types except Clinical Trials. Relations are assigned effect (positive, negative, or unknown) and directionality except Binding and Functional Association. Biomarker is assigned directionality but has no assigned effect.

Property Name

Property Type

Source

Description

CellType

dictionary

Elsevier’s Natural Language Processing (NLP) tool

Contains cell name recognized by Elsevier NLP in the supporting sentence or in the text upstream from the sentence

Organ

dictionary

Elsevier’s Natural Language Processing (NLP) tool

Contains organ name recognized by Elsevier NLP in the supporting sentence or in the text upstream from the sentence

Organism

dictionary

Elsevier’s Natural Language Processing (NLP) tool

Contains organism name recognized by Elsevier NLP in the supporting sentence or in the text upstream from the sentence

Tissue

dictionary

Elsevier’s Natural Language Processing (NLP) tool

Contains tissue recognized by Elsevier NLP in the supporting sentence or in the text upstream from the sentence

CellLineName

short string

Elsevier’s Natural

Contains cell line name recognized by Elsevier NLP in the

Language Processing (NLP) tool

supporting sentence or in the text upstream from the sentence

Effect

dictionary

Elsevier’s Natural Language Processing (NLP) tool

Relations are assigned effect (positive, negative, or unknown) except binding, functional association and biomarker.

TextMods

long text

Elsevier’s Natural Language Processing (NLP) tool

The “TextMods” property for a reference indicates a substitution has been made in the original text resulting in the display of the full entity name in place of the abbreviation appearing in the original text.

Title

long text

Elsevier’s Natural Language Processing (NLP) tool

Article title

msrc

long text

Elsevier’s Natural Language Processing (NLP) tool

Display name in UI: Sentence. Contains sentence recognized by Elsevier NLP supporting the relation

PubYear

numerical

Elsevier’s Natural Language Processing (NLP) tool

Publication year of the article with the sentence

Authors

short string

Elsevier’s Natural Language Processing (NLP) tool

Article author

DOI

short string

Elsevier’s Natural Language Processing (NLP) tool

Document Object Identifier

EMBASE

short string

Elsevier’s Natural Language Processing (NLP) tool

Embase article identifier

ESSN

short string

Elsevier’s Natural Language Processing (NLP) tool

Electronic ISSN number

ISSN

short string

Elsevier’s Natural Language Processing (NLP) tool

International Standard Serial Number

Journal

short string

Elsevier’s Natural Language Processing (NLP) tool

Journal name for a journal not included in PubMed

MedlineTA

short string

Elsevier’s Natural Language Processing (NLP) tool

Journal name for journals from Pubmed

PII

short string

Elsevier’s Natural Language Processing (NLP) tool

Publisher Item Identifier

PMID

short string

Elsevier’s Natural Language Processing (NLP) tool

Pubmed abstract identifier

PUI

short string

Elsevier’s Natural Language

Publisher Item Identifier from Embase

Processing (NLP) tool

PubVersion

short string

Elsevier’s Natural Language Processing (NLP) tool

Version number of article

TextRef

short string

Elsevier’s Natural Language Processing (NLP) tool

Information in the TextRef field indicates if the relation was identified in an abstract, title, body of a paper or when no location can be identified. For example:

#title:1 means the “first sentence of the article’s title’

#abs:9 meand the ‘9th sentence of the article’s abstract’

#body:21 means the ‘21st sentence of the article’s body’

#cont:21 means the ‘21st sentence of the article’s extracted text with no identifiable parts

mref

short string

Elsevier’s Natural Language Processing (NLP) tool

Display name in UI: MedLine reference. Contains Pubmed abstract identifier (PMID)

Clinical Trials

Clinical Trials data is obtained directly from ClinicalTrials.gov (it is not literature extracted using MedScan).

Property Name

Property Type

Source

Description

Phase

dictionary

clinicaltrials.gov

Food and Drug Administration (FDA) categories for describing the clinical trial of a drug based on the study's characteristics, such as the objective and number of participants. There are five phases:

Phase 0: Exploratory study involving very limited human exposure to the drug, with no therapeutic or diagnostic goals (for example, screening studies, microdose studies)

Phase 1: Studies that are usually conducted with healthy volunteers and that emphasize safety. The goal is to find out what the drug's most frequent and serious adverse events are and, often, how the drug is metabolized and excreted.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition). For example, participants receiving the drug may be compared with similar participants receiving a different treatment, usually an inactive substance (called a placebo) or a different drug. Safety continues to be evaluated, and short-term adverse events are studied.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing. These including postmarket requirement and commitment studies that are required of or agreed to by the sponsor. These studies gather additional information about a drug's safety, efficacy, or

optimal use.

msrc

long text

text extraction

Display name in UI: Sentence. Contains sentence recognized by Elsevier NLP supporting the relation

TrialStatus

dictionary

clinicaltrials.gov

The status of the trial: Active not recruiting, approved for marketing, available, completed, enrolling by invitation, no longer available, not yet recruiting, recruiting, suspended temporarily not available, terminated, withdrawn, withheld

Condition

long text

clinicaltrials.gov

A disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues such as lifespan, quality of life, and health risks.

Intervention

long text

clinicaltrials.gov

A process or action that is the focus of a clinical study. This can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches such as surveys, education, and interviews.

Title

long text

clinicaltrials.gov

The title given to the specific study.

Collaborator

short string

clinicaltrials.gov

A collaborator is an organization other than the sponsor that provides support for a clinical study. This may include funding, design, implementation, data analysis, or reporting.

Company

short string

clinicaltrials.gov

The company sponsoring the trial.

NCT ID

short string

clinicaltrials.gov

ClinicalTrials.gov identifier

Start

short string

clinicaltrials.gov

The start date of the study.

TextRef

short string

MedScan Reader

TextRef for clinical trials includes the NCT identifier

mref

short string

Elsevier’s Natural Language Processing (NLP) tool

Display name in UI: MedLine reference. Contains Pubmed abstract identifier (PMID)

Additional Annotation for Relations

Property Name

Description

Effect

The described effect of a relation (positive, negative, unknown) on a target.

In/Out

Indicator of the directionality of the relation (in or out from the entity). In the

RelationNumberOfReferences

The number of sentences from which the relation has been extracted.

URN

Elsevier internal identifier

3. Additional Database Information

a. Groups and Pathways

Groups in ResNet consist simply of a list of entities. Ontologies are presented as groups.

Pathways in ResNet include both entities and relations. The Elsevier curated pathway collection includes over 1300 pathways. A complete list of the pathways included in the ResNet database is provided at the end of this document (see Appendix).

b. Ontologies

Two ontologies are included in ResNet: Gene Ontology (cellular component, molecular function, and biological process) and Pathway Studio Ontology.

Gene Ontology:

The Gene Ontology IDs, from the Gene Ontology Consortium, for each protein and cellular process are listed in their annotation fields. Please visit http://geneontology.org/ for more information.

Pathway Studio Ontology:

Pathway Studio Ontology was designed from a different prospective than 'the Gene Ontology' (GO) provided by the Gene Ontology Consortium. Whereas GO is a multi-level hierarchy with multiple, often overlapping, functional descriptions of genes, Pathway Studio Ontology consists of a non-overlapping core set of cell-level molecular function groups. To complement the molecular function groups, Elsevier has defined the cellular process groups that represent the most basic and well-established cellular processes. Elsevier experts have manually assigned proteins to these groups based on protein primary function. The result is a well-designed organization of proteins that reflect the current knowledge of their primary function(s) in the cell. Organism-level biological processes can be represented by combination of basic cellular processes and molecular function groups. ResNet Mammal, Pathway Studio Ontology includes 8,666 genes and 1006 miRNAs, organized in 519 groups, with 11,788 'assignments'. Cellular Processes:

Biochemical Pathways:

41 groups

1573 proteins

Metabolite/Ion Transport:

42 groups

1053 proteins

Structural Processes:

(DNA replication, translation, actin polymerization, endocytosis)

63 groups

3814 proteins

Molecular Functions:

Ligands:

42 groups

448 proteins

Receptors:

68 groups

930 proteins

Signaling Proteins:

155 groups

766proteins

miRNAs:

10 groups

2154 miRNAs

Transcription Factors:

94 groups

1,822 proteins

Disease Regulation:

Oncogenes:

1 group

271 proteins

Tumor Suppressors:

1 group

92 proteins

APPENDIX: WORKFLOW EXAMPLES

The examples below include the biological question, the relation types and the entity types selected, and considerations for each workflow.

Question

Wizard Selections

Considerations

Gene/Protein Expression

1

What proteins (transcription factors) bind to the promoter of a gene(s)?

initial selection: protein directionality: upstream entity type: protein relation type: promoterbinding

Finds transcription factors for genes (directly binding to promoters)

2

What known miRNAs regulate expression of a gene(s)?

initial selection: protein directionality: upstream entity type: protein relation type: miRNAEffect

Finds miRNA targets.

3

What proteins are involved in the expression of a gene(s), either directly or indirectly?

initial selection: protein directionality: upstream entity type: protein relation type: promoterbinding or expression

Finds both direct expression regulators (promoterbinding) and proteins with possibly an indirect effect on expression (expression)

Physical Interaction with Proteins

4

What proteins bind to a protein?

initial selection: protein directionality: (all) entity type: protein relation type: binding or directregulation

Identifies protein binding partners (no additional regulatory event known) Binding relations have no directionality (DirectRegulation is regulation through a direct physical interaction and can also be considered here.)

5

What small molecules bind to a protein?

initial selection: protein directionality: (all) entity type: small molecules relation type: binding or directregulation

Identifies small molecules that bind to a protein (no additional regulatory event known) (DirectRegulation is regulation through a direct physical interaction and can also be considered here.)

Question

Wizard Selections

Considerations

6

What proteins regulate a protein through a direct physical interaction?

initial selection: protein directionality: upstream entity type: protein relation type: directregulation

Finds proteins that regulate the activity of a target protein through a direct physical interaction Can also consider "protmodification" relations

7

What small molecules regulate a protein through direct physical interactions?

initial selection: protein directionality: upstream entity type: small molecule relation type: directregulation

Finds small molecules that regulate the activity of a protein through a direct physical interaction (Drugs/non-naturally occurring small molecules included in ChemEffect data)

Protein Modification(s)

8

What protein(s) acetylate/deacetylate a protein?

initial selection: protein directionality: upstream entity type: protein relation type: protmodification mechanism: acetylation or deacetylation

Identifies proteins involved in acetylation/deacetylation of target protein(s).

9

What protein(s) cleave a protein?

initial selection: protein directionality: upstream entity type: protein relation type: protmodification mechanism: cleavage

Identifies proteins involved in the proteolytic cleavage of target protein(s).

10

What proteins(s) methylate/demethylate a protein?

initial selection: protein directionality: upstream entity type: protein relation type: protmodification mechanism: methylation or demethylation

Identifies proteins involved in the methylation/demethylation of target protein(s).

11

What protein(s) phosphorylate/dephosphorylate a protein?

initial selection: protein directionality: upstream entity type: protein relation type: protmodification mechanism: phosphorylation or

dephosphorylation

Identifies protein(s) involved in the phosphorylation/

dephosphorylation of target protein(s).

Question

Wizard Selections

Considerations

12

What protein(s) ubiquitinate a protein?

initial selection: protein directionality: upstream entity type: protein relation type: protmodification mechanism: ubiquitination

Identifies proteins involved in the ubiquitination of target protein(s).

Protein /Small Molecule Transport

13

What protein mediates the translocation of a protein or small molecule?

initial selection: protein or small molecule directionality: upstream entity type: protein relation type: moltransport

Identifies proteins involved in the translocation of a protein or small molecule target.

14

What small molecule mediates the translocation of a protein

initial selection: protein directionality: upstream entity type: small molecule relation type: moltransport

Identifies small molecules involved in the translocation of a protein target.

Question

Wizard Selections

Considerations

Proteins/Small molecules involved in chemical interactions

15

What enzymes are involved in a chemical reaction with a small molecule?

initial selection: small molecule directionality: all entity type(s): proteins, functional classes relation type: chemical reaction

Identifies functional classes and proteins that catalyze chemical reactions of small molecules. Most metabolism enzymes in the metabolism pathways are represented by functional classes.

Protein/Small Molecule associations and changes in Diseases and Cell Processes

16

What proteins are known to be associated with a disease or cellular process?

initial selection: disease or cell process directionality: upstream entity type: protein relation type: regulation

Identifies proteins known to be associated with a specific disease or cellular process. (More specific data relating proteins to diseases is available in DiseaseFx data including statechange, genetic change and quantitativechange.)

17

What small molecules are associated with a disease or cellular process?

initial selection: disease or cell process directionality: upstream entity type: small molecules relation type: regulation

Identifies small molecules that are associated with diseases or cellular processes. Small molecule association with diseases and cell processes through regulation relations are found in the ChemEffect® Database. In addition, more information about small molecules associated with diseases can be found in the DiseaseFx database through quantitivechange and biomarker relations.

18

What proteins are known to change in expression, activity or abundance in a disease?

initial selection: disease directionality: downstream entity type: protein relation type: quantitativechange quantitativeType: expression or abundance or activity

Identifies proteins that are changed in activity abundance or expression in a disease. Quantitativechange relations are found only in DiseaseFx data

19

What small molecules are known to change in abundance in a disease?

initial selection: disease directionality: downstream entity type: small molecules relation type: quantitativechange quantitativetype: abundance

Identifies small molecules that are changed in abundance in a disease. Quantitativechange relations are found in DiseaseFx data

Question

Wizard Selections

Considerations

20

What proteins with genetic mutations are associated with a disease?

initial selection: disease directionality: downstream entity type: protein relation type: geneticchange

Identifies proteins with genetic changes (gene deletions, amplifications, mutations, epigenic changes, or methylation) associated with a disease. Geneticchange relations are found in DiseaseFx data.

21

What proteins or small molecules are diagnostic for a disease?

initial selection: disease directionality: downstream entity type: protein relation type: biomarker biomarkertype: diagnostic

Identifies proteins/small molecules know to be diagnostic for a disease. Biomarker relations are found in DiseaseFx data.

22

What proteins or small molecules are prognostic for a disease?

initial selection: disease directionality: downstream entity type: protein relation type: biomarker biomarkertype: prognostic

Identifies proteins/small molecules known to be prognostic for a disease. Biomarker relations are found in DiseaseFx data.

23

What protein phosphorylation/dephosphorylation events are associated with a disease?

initial selection: disease directionality: downstream entity type: protein relation type: statechange

changetype: phosphorylation or dephosphorylation

Identifies post translational protein phosphorylation/dephosphorylation events associated with a disease. Statechange relations are found in DiseaseFx data.

24

What protein/gene splice variants are associated with a disease?

initial selection: disease directionality: downstream entity type: protein relation type: statechange changetype: alternative splicing

Identifies alternate gene splicing events/splice variants associated with a disease. Statechange relations are found only in DiseaseFx data.

Question

Wizard Selections

Considerations

Small Molecule concentrations

25

What proteins regulate the synthesis or catabolism of a small molecule?

initial selection: small molecule directionality: upstream entity type(s): protein relation type(s): molsynthesis

Identifies proteins that regulat the concentrations of small molecules through metabolic events

Clinical Trials

26

What small molecules/drugs have been tested in clinical trials for a disease?

initial selection: small molecules directionality: downstream entity type(s): disease or cell process relation type: clinicaltrials

Identifies small molecules/drugs that have been involved in clinical trials. Drugs are included in ChemEffect Data. Clinicaltrials relations are included in DiseaseFx data. Monoclonal antibodies are represented as small molecules on the ChemEffect database.

Functional Associations between Diseases and Cell Processes

27

What cellular processes are associated with a disease?

initial selection: disease directionality: (all) entity type: cellular process relation type: functional class

Identifies associations between cellular processes and diseases (no directionality in the relations). Functionalassociation relations are found in DiseaseFx data.

APPENDIX: LIST OF CURATED PATHWAYS IN RESNET MAMMAL+CHEMEFFCT+DISEASEFX

Cell Process Pathways

Apoptosis

Apoptosis

Cleavage of Lamina in Apoptosis

Cell Division

Centriole Duplication and Separation

Chromosome Condensation

Kinetochore Assembly

Nuclear Envelope

Sister Chromatid Cohesion

Spindle Assembly

Cellular Contacts

Adherens Junction Assembly (Cadherins)

Adherens Junction Assembly (Nectin)

Desmosome Assembly

Extracellular Matrix Turnover

Focal Junction Assembly

Gap Junction Assembly

Hemidesmosome Assembly

Tight Junction Assembly (Claudins)

Tight Junction Assembly (JAMs)

Tight Junction Assembly (Occludin)

Chromatin Remodeling

CHRAC Chromatin Remodeling

INO80 Chromatin Remodeling

NURD Chromatin Remodeling

NURF Chromatin Remodeling

SRCAP Chromatin Remodeling

SWI/SNF BRG1/BAF Chromatin Remodeling

SWI/SNF BRG1/PBAF Chromatin Remodeling

SWI/SNF BRM/BAF Chromatin Remodeling

TRRAP/TIP60 Chromatin Remodeling

Complement Activation

Alternative Complement Pathway

Classical Complement Pathway

Lectin-Induced Complement Pathway

Cytoskeleton Assembly

Actin Cytoskeleton Assembly

Actomyosin-Based Movement

Intermediate Filament Polymerization

Microtubule Cytoskeleton Assembly

DNA Repair

Direct DNA Repair

Double Strand DNA Homologous Repair

Double Strand DNA Non-Homologous Repair

Single-Strand Base Excision DNA Repair

Single-Strand Mismatch DNA Repair

Single-Strand Nucleotide Excision DNA Repair

Histone Modification

Histone Acetylation

Histone and DNA Methylation

Histone Phosphorylation

Histone Sumoylation

Histone Ubiquitylation

Mitochondrial

Mitochondrial DNA Replication and Transcription

Mitochondrial Fusion and Fission

Mitochondrial Protein Transport

Transcription

mRNA Transcription and Processing

rRNA Transcription and Processing

tRNA Transcription and Processing

Vesicular Transport

Co-Translational ER Protein Import

Endosomal Recycling

ER-Associated Degradation

Exocytosis

Golgi to Endosome Transport

Peroxisome Protein Import and Peroxisome Division

Secretory Pathway: Golgi Transport

Transcytosis

Cell Cycle

Circadian Clock

Coagulation Cascade

DNA Replication

mRNA Degradation

Presentation of Endogenous Peptide Antigen

Protein Folding

Protein Nuclear Import and Export

RNA Gene Silencing

Telomere Maintenance

Translation

Ubiquitin-Dependent Protein Degradation

Cell Signaling

Actin Cytoskeleton Regulation

Adherens Junction Regulation

Adipocytokine Signaling

Apoptosis Regulation

Axon Guidance

B Cell Activation

Cell Cycle Regulation

Focal Adhesion Regulation

Gap Junction Regulation

Gonadotrope Cell Activation

Guanylate Cyclase Pathway

Hedgehog Pathway

Insulin Action

Mast Cell Activation

Melanogenesis

NK Cell Activation

Notch Pathway

Skeletal Myogenesis Control

T Cell Activation

Tight Junction Regulation

Translation Control

Disease Collections

Acute Myeloid Leukemia

Acute Myeloid Leukemia Overview

Block of Apoptosis in Acute Myeloid Leukemia

Block of Differentiation in Acute Myeloid Leukemia

FLT3 and KIT Signaling to MLL Pathway in Acute Myeloid Leukemia (M5)

Proteins Involved in Pathogenesis of Acute Myeloid Leukemia

RARA Signaling Pathway in Acute Myeloid Leukemia (M3)

Alzheimer's Disease

Alzheimer's Disease Overview

Amyloid beta and APP Intracellular Transport in Alzheimer's Disease

Amyloid beta Formation

APP and Glutamate Signaling-Related Neuronal Dysfunction in Alzheimer's Disease

APP Processing

Ca2+ Toxicity in Alzheimer's Disease

Complement Activation in Alzheimer's Disease

Mechanism of Amyloid beta Clearance

Metals and Amyloid beta Toxicity

Microglia Activation in Alzheimer's Disease

Mitochondria Enlargement and Apoptosis in Alzheimer's Disease

Mitochondrial Respiratory Chain Dysfunction in Alzheimer's Disease

Multiple Functions of Estrogen in Mitochondria in Alzheimer's Disease

Neurofibrillary Tangle Formation in Alzheimer's Disease

Overview of Mitochondrial Dysfunction in Alzheimer's Disease

Proteins Involved in Pathogenesis of Alzheimer's Disease

Traffic and Degradation of Extracellular Amyloid beta in Alzheimer's Disease

Tricarboxylic Acid Cycle Involvement in Alzheimer's Disease

Amyotrophic Lateral Sclerosis

Dysregulation of Endosomal Trafficking in Amyotrophic Lateral Sclerosis

Dysregulation of RNA and DNA Metabolism in Amyotrophic Lateral Sclerosis

Glutamate-Mediated Excitotoxicity in Amyotrophic Lateral Sclerosis

Impairment of Microglia Inhibition by Motor Neuron in Amyotrophic Lateral Sclerosis

Neuroinflammation in Amyotrophic Lateral Sclerosis

Oxidative Stress in Amyotrophic Lateral Sclerosis

Proteins Involved in Pathogenesis of Amyotrophic Lateral Sclerosis

SOD1 Mutation in Amyotrophic Lateral Sclerosis

Atherosclerosis

Activation and Proliferation of Th1 Cells in Atherosclerosis

Arterial Calcification in Atherosclerosis

Chemokines and their Receptors in Atherogenic Cell Recruitment

Proteins Involved in Pathogenesis of Atherosclerosis

RAGE/AGER and S100 Proteins in Cardiovascular Injury in Atherosclerosis

Role of Dendritic Cells in Atherosclerosis

Role of Low-density Lipoproteins and Chemokines in Atherogenesis

Role of Scavenger Receptor OLR1 in Inflammation-Related Endothelial Dysfunction in Atherosclerosis

Atopic Dermatitis

Acute Phase of Atopic Dermatitis

Atopic Dermatitis Overview

Corneodesmosomes in Atopic Dermatitis

Epidermal Barrier Dysfunction in Atopic Dermatitis

Mast Cells in Atopic Dermatitis

Onset of Atopic Dermatitis

Proteins Involved in Pathogenesis of Atopic Dermatitis

B-cell Acute Lymphoblastic Leukemia

B-cell Acute Lymphoblastic Leukemia Overview

B-cell Chronic Lymphocytic Leukemia

B-cell Chronic Lymphocytic Leukemia Overview

Proteins Involved in Pathogenesis of B-cell Chronic Lymphocytic Leukemia

Breast Cancer

Basal Breast Cancer

Breast Cancer Related to ERBB/VEGFR/Akt Signaling Pathway

Breast Cancer Related to ESR1 Signaling Pathway

Breast Cancer Related to IGF1R/Akt Signaling Pathway

Breast Cancer Related to NOTCH1 Signaling Pathway

Breast Cancer Related to WNT Signaling Pathway

ESR1/ERBB-positive Luminal Breast Cancer

Proteins Involved in Pathogenesis of Breast Cancer Related to ERBB2/VEGFR/Akt Signaling Pathway

Proteins Involved in Pathogenesis of Breast Cancer Related to ESR1 Signaling Pathway

Proteins Involved in Pathogenesis of Breast Cancer Related to IGF1R/Akt Signaling Pathway

Proteins Involved in Pathogenesis of Breast Cancer Related to NOTCH Signaling Pathway

Proteins Involved in Pathogenesis of Breast Cancer Related to WNT Signaling Pathway

Cataract

Age-Related Cataract

Ca2+ Toxicity in Lens Cells

Cancer Overview

Congenital Cataract

Diabetes-Induced Cataract

Mutations in EPHA2 Cause Cataract

Steroid-Induced Cataract

Chronic Myeloid Leukemia

Proteins Involved in Pathogenesis of Cataract

Proteins Involved in Pathogenesis of Chronic Myeloid Leukemia

Colorectal Cancer

Chronic Myeloid Leukemia Overview

Mechanism of Cetuximab Resistance in Colorectal Cancer

Metastatic Colorectal Cancer Overview

Congenital Hypothyroidism

Congenital Secondary (Central) Hypothyroidism

FOXE1 Targets Possibly Involved in Thyroid Dysgenesis

GLIS3 Targets Possibly Involved in Thyroid Dysgenesis

Iodine Metabolism Related Thyroid Dyshormonogenesis

NKX2-1 Targets Possibly Involved in Thyroid Dysgenesis

Nuclear EGFR

PAX8 Targets Possibly Involved in Thyroid Dysgenesis

Proteins Involved in Pathogenesis of Congenital Hypothyroidism

Proteins Involved in Thyroid Dysgenesis

Thyroglobulin Related Thyroid Dyshormonogenesis

Crohn's Disease

B-cell Activation in Crohn's Disease

Congenital Hypothyroidism Due to Thyroid-Stimulating Hormone Resistance

Crohn's Disease Overview

Dendritic Cell Function in Crohn's Disease

Macrophage Function in Crohn's Disease

Paneth Cell Function in Crohn's Disease

Susceptibility Genes for Crohn's Disease and Ulcerative Colitis

Th1 Cell Activation in Crohn's Disease

Th17 Cell Activation in Crohn's Disease

Cystic Fibrosis

CFTR Expression in Epithelial Cells (Class I Mutations)

CFTR Up-regulates the Oxidative Stress in Airway Epithelium in Cystic Fibrosis

CFTR-Related Ion-Channel Dysfunction in Cystic Fibrosis Airway Epithelium (Class III Mutations)

Class II Mutations Cause CFTR Misfolding and Degradation in Cystic Fibrosis

Mucin Production in Goblet Airway Epithelial Cells in Cystic Fibrosis

Proteins Involved in Pathogenesis of Cystic Fibrosis

Proteins Involved in Pathogenesis of Inflammatory Bowel Diseases

The Role of CFTR in Sperm Capacitation and Acrosome Reaction

Diffuse Large-B-cell Lymphoma

Diffuse Large-B-cell Lymphoma Overview

Diffuse Large-B-cell Lymphoma, ABC Subtype

Diffuse Large-B-cell Lymphoma, GCB Subtype

Diffuse Large-B-cell Lymphoma, PMBL Subtype

Pancreatic Beta-cell Death in Diabetes Mellitus Type 2

Endometrial Cancer

Proteins Involved in Pathogenesis of Diffuse Large-B-cell Lymphoma

Proteins Involved in Pathogenesis of Endometrial Cancer

Type I Endometrial Cancer (Endometrioid Endometrial Cancer)

Type II Endometrial Cancer (Clear-cell Endometrial Cancer and Papillary Serous Endometrial Cancer)

Epileptiform Disorders

ADK Downregulation after Acute Seizures in Epilepsy

ADK Upregulation in Chronic Epilepsy

Astrocyte Dysfunction and GABA Signaling Deficiency in Epilepsy

Effects of BDNF Upregulation Induced by Seizures

Endometrial Cancer Overview

Epilepsies Associated with Blood-Brain Barrier Disruption

Glutamate, D-serine, and ATP Release from Astrocytes

Induction of Apoptosis and Immediate Early Gene Activation in Hippocampal Neurons Following Seizures

Inherited Channelopathies Associated with Epilepsy

mTOR Hyperactivation after Status Epilepticus

Proposed Mechanisms of Antiepileptic Effects of a Ketogenic Diet

Proteins Involved in Pathogenesis of Epilepsy

Role of HMGB1 and IL1B in Neuronal Hyperexcitation in Epilepsy

Familial Hemiplegic Migraine

Activation of eNOS (NOS3) via Prostaglandin E2 and Histamine in Familial Hemiplegic Migraine

Activation of nNOS (NOS1) and iNOS (NOS2) via Glutamate in Familial Hemiplegic Migraine

Activation of Prostaglandin E2 Synthesis via Glutamate in Familial Hemiplegic Migraine

Effect of NO on Vasodilation and Triptans on Vasoconstriction in Familial Hemiplegic Migraine

Glutamate Overdose and Aura Effect in Familial Hemiplegic Migraine Type 1

Glutamate Overdose and Aura Effect in Familial Hemiplegic Migraine Type 2

Role of HMGB1 and IL1B in Neuroinflammation in Epilepsy

Follicular Lymphoma

Follicular Lymphoma Overview

Glutamate Overdose and Aura Effect in Familial Hemiplegic Migraine Type 3

Proteins Involved in Pathogenesis of Follicular Lymphoma

Glioblastoma

Classical Subtype of Glioblastoma

Mesenchymal Subtype of Glioblastoma

Neural Subtype of Glioblastoma

Primary Glioblastoma

Proneural Subtype of Glioblastoma

Proteins Involved in Pathogenesis of Glioblastoma

Secondary Glioblastoma

Glioma

Activation of Glioma Stem Cell Program

Astrocytoma

Ependymoma

Glioma Invasion Signaling

Proteins Involved in Pathogenesis of Astrocytoma

Proteins Involved in Pathogenesis of Ependymoma

Proteins Involved in Pathogenesis of Glioma

Proteins Involved in Pathogenesis of Oligodendroglioma

Gout

Impaired Osteoblast Function in Gout

Impaired Renal Uric Acid Excretion in Gout

Increased Uric Acid Synthesis in Gout

Neutrophil Recruitment in Sinovium in Gout

Osteoclast Activation in Gout

Proteins Involved in Pathogenesis of Gout

The Action of Monocytes in Gout

Hashimoto's Thyroiditis

Apoptosis in Hashimoto's Thyroiditis

Hashimoto's Thyroiditis Overview

Immune Response Activation in Hashimoto's Thyroiditis

Proteins Involved in Pathogenesis of Hashimoto's Thyroiditis

Triggers of Hashimoto's Thyroiditis

Hepatocellular Carcinoma

Growth Factor Signaling in Hepatocellular Carcinoma

Hepatocellular Carcinoma Overview

NOTCH Signaling in Hepatocellular Carcinoma

Proteins Involved in Pathogenesis of Hepatocellular Carcinoma

TP53 Signaling in Hepatocellular Carcinoma

Vascularization in Hepatocellular Carcinoma

WNT/beta-Catenin Signaling in Hepatocellular Carcinoma

Hereditary Syndromes Associated with Breast and/or Ovarian Cancer

Cowden Syndrome

Hereditary Breast and Ovarian Cancer Syndrome

Li-Fraumeni Syndrome

Hirschsprung Disease

Impairment of EDN, NRG, NRTN, and GDNF/RET Signaling in Hirschsprung Disease

Mutation in KIF1-Binding Protein (KIAA1279) Gene in Hirschsprung Disease

Mutations in Neurogenic Transcription Factor Genes in Hirschsprung Disease

Proteins Involved in Pathogenesis of Hirschsprung Disease

Syndromic Forms of Hirschsprung Disease

HIV Type 1 Infection

Block of Apoptosis in Infected Cells in HIV Type 1 Infection

Block of CD4+ T-cell Signaling in HIV Type 1 Infection

CCR5 Signaling in Macrophages in HIV Type 1 Infection

CD4+ T-cell Death in HIV Type 1 Infection

Impairment of CD8+ T-cell Action in HIV Type 1 Infection

Macrophage Survival through CCR5 and CXCR4 Mediated Signaling in HIV Type 1 Infection

Proteins Involved in Pathogenesis of HIV Type 1 Infection

Reduction of Th17 cell Numbers in HIV Type 1 Infection

Hodgkin Lymphoma

Effects of Hodgkin and Reed-Sternberg Cells on Microenvironment Cells

Hodgkin Lymphoma Overview

Proteins Involved in Pathogenesis of Hodgkin Lymphoma

Reprogramming of Hodgkin and Reed-Sternberg Cells

Hyper IgM Syndrome

Hyper IgM Syndrome Overview

Hyperthyroidism

Cardiovascular Effects of Hyperthyroidism

Common Genomic Effects of Thyroid Hormones

Common Non-genomic Effects of Thyroid Hormones

Effects of Hyperthyroidism on Bone Remodeling

Graves Ophthalmopathy

Immune System Activation in Graves Disease Overview

Proteins Involved in Pathogenesis of Graves Disease

Thyroid Dysfunction in Graves Disease

Thyroid Hormones in Adipose Tissue Metabolism

Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy Overview

Mechanisms of Cardiomyocyte Hypertrophy in Hypertrophic Cardiomyopathy

Proteins Involved in Pathogenesis of Hypertrophic Cardiomyopathy

Sarcomere Disorganization and Intracellular Calcium Overload in Hypertrophic Cardiomyopathy

Insulin Related Pathology

Diabetes Complications

Airway Epithelial Cell Dysfunction in Cystic Fibrosis (Overview)

Proliferative Diabetic Retinopathy

Role of Advanced Glycation End Products Pathway in Diabetic Microangiopathy

Role of Hexosamine Pathway in Diabetic Microangiopathy

Role of Polyol Pathway in Diabetic Microangiopathy

Role of Protein Kinase C in Diabetic Microangiopathy

Diabetes Mellitus Type 1

CD8+ T-cell Response to Self-Determinants in Diabetes Mellitus Type 1

Pancreatic Beta-cell Destruction in Diabetes Mellitus Type 1

Peripheral Tissue Microangiopathy in Insulin Resistance

Proteins Involved in Pathogenesis of Diabetes Mellitus Type 1

Diabetes Mellitus Type 2

Impaired Peripheral Tolerance to Autoantigens in Diabetes Mellitus Type 1

Proteins Involved in Pathogenesis of Diabetes Mellitus Type 2

Insulin Receptor Signaling

Glycolysis

Insulin Influence on Glycogenesis

Insulin Influence on Lipogenesis

Insulin Influence on Protein Synthesis

Insulin Secretion

Insulin Resistance

Adipose Tissue Inflammation Provokes Insulin Resistance

Impaired Adiponectin Synthesis in Insulin Resistance

Insulin Resistance in Hepatocytes

Obesity Induced Insulin Resistance in Myocytes

Proteins Involved in Pathogenesis of Insulin Resistance

Role of Adiponectin in Insulin Resistance Prevention

Mantle Cell Lymphoma

Canonical WNT Signaling in Mantle Cell Lymphoma

Deregulation of Apoptosis in Mantle Cell Lymphoma

Deregulation of Cell Cycle and DNA Repair in Mantle Cell Lymphoma

Hedgehog Signaling in Mantle Cell Lymphoma

Mantle Cell Lymphoma Overview

Medulloblastoma Overview

Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma Overview

PI3K/AKT/MTOR, NF-kB and BCR Signaling Deregulation in Mantle Cell Lymphoma

Proteins Involved in Pathogenesis of Mantle Cell Lymphoma

Proteins Involved in Pathogenesis of Marginal Zone Lymphoma

Proteins Involved in Pathogenesis of Medulloblastoma

Splenic Marginal Zone Lymphoma Overview

Melanoma

Block of Apoptosis in Melanoma

Dedifferentiation and Metastatic Progression of Melanoma

Deregulation of Cell Cycle in Melanoma

Melanoma Overview

MicroRNAs in Melanoma

MITF as a Regulator of Melanoma Cell Development

Proteins Involved in Pathogenesis of Melanoma

WNT Signaling in Melanoma

Multiple Myeloma

IL-6/IGF-1/VEGFA in Multiple Myeloma

Multiple Myeloma Overview

Notch Pathway in Multiple Myeloma Plasma Cells

Osteoclast Activation in Multiple Myeloma

Proteins Involved in Pathogenesis of Multiple Myeloma

TNFR to NF-kB Alternative Pathway in Multiple Myeloma Plasma Cells

TNFR to NF-kB Classical Pathway in Multiple Myeloma Plasma Cells

WNT Inhibition by DKK1 in Osteoblast in Multiple Myeloma

Muscular Dystrophies

Ca2+ Overload in Duchenne Muscular Dystrophy

Contraction-Induced IL6 Up-regulation in Skeletal Muscles

Duchenne Muscular Dystrophy Overview

Dystrophin Glycoprotein Complex Signaling in Duchenne Muscular Dystrophy

IGF1 in Muscle Hypertrophy

IL6 in Insulin Resistance

IL6 Promotes Inflammation

Myostatin-IGF1 Crosstalk in Skeletal Muscles

Role of Myostatin in Skeletal Muscles

Myocardial Ischemia

Changes of Homeostasis in Myocardial Ischemia

Myocardial Infarction

Myocardial Ischemia/Reperfusion Injury

Myocardial Remodeling in Myocardial Ischemia

Preconditioning Ischemia

Proteins Involved in Pathogenesis of Myocardial Ischemia

Renin-Angiotensin-Aldosterone System in Myocardial Ischemia

Neuroblastoma

ALK-Associated Neuroblastoma

Growth Factor Signaling in Neuroblastoma

Neuroblastoma Overview

Non-Hereditary Genetic Rearrangements in Neuroblastoma

PHOX2B-Associated Neuroblastoma

Proteins Involved in Pathogenesis of Neuroblastoma

Sonic Hedgehog Signaling in Neuroblastoma

Non-autoimmune Hypothyroidism

Central Hypothyroidism Overview

Hypothyroidism Influence on Hypothalamic Release of Thyrotropin-Releasing Hormone

Overt Hypothyroidism Influence on Thyroid-Stimulating Hormone Secretion

Primary Overt Hypothyroidism Overview

Proteins Involved in Pathogenesis of Hypothyroidism

Proteins Involved in Pathogenesis of Thyroid Hormone Resistance

Tertiary Hypothyroidism Overview

Osteoarthritis

Chondrocyte Apoptosis in Osteoarthritis

IL1B-Induced Arthralgia in Osteoarthritis

Impaired TGFB2 Signaling in Osteoarthritis

Osteoarthritis Overview

Proteins Involved in Pathogenesis of Osteoarthritis

TNF and IL1B Induce Metalloproteinase Synthesis

Ovarian Cancer

Clear Cell Ovarian Carcinoma

Endometrioid Ovarian Carcinoma

High-grade Serous Ovarian Carcinoma

Low-grade Serous Ovarian Carcinoma

Mucinous Ovarian Carcinoma

Ovarian Cancer Overview

Proteins Involved in Pathogenesis of Clear Cell Ovarian Carcinoma

Proteins Involved in Pathogenesis of Endometrioid Ovarian Carcinoma

Proteins Involved in Pathogenesis of High-grade Serous Ovarian Carcinoma

Proteins Involved in Pathogenesis of Low-grade Serous Ovarian Carcinoma

Proteins Involved in Pathogenesis of Mucinous Ovarian Carcinoma

Proteins Overexpressed in Ovarian Cancer

Pancreatic Neoplasms

Block of DNA Repair and Chromatin Remodeling in Pancreatic Cancer

Growth Factor Signaling in Pancreatic Cancer

Pancreatic Ductal Carcinoma

Pancreatic Neuroendocrine Tumors

Proteins Involved in Pathogenesis of Pancreatic Cancer

STK11 Signaling in Pancreatic Cancer

TGFBR Signaling in Pancreatic Cancer

TP53 Signaling in Pancreatic Cancer

Parkinson's Disease

Dopamine Metabolism in Parkinson's Disease

Glutamate in Parkinson's Disease

Microglia Activation in Parkinson's Disease

Neurotoxin-Induced Parkinson's Disease

Proteins Involved in Pathogenesis of Parkinson's Disease

Young Onset PARK2, PINK1, and UCHL1 Induced Parkinson's Disease

Young Onset PARK7 and LRRK2 Induced Parkinson's Disease

Young Onset SNCA Induced Parkinson's Disease

Peutz-Jeghers Syndrome

Peutz-Jeghers Syndrome Overview

Proteins Involved in Pathogenesis of Peutz-Jeghers Syndrome

Polycystic Ovary Syndrome

Block of Ovulation in Polycystic Ovary Syndrome

FSH Action in Polycystic Ovary Syndrome

Impaired SHBG and IGFBP1 Synthesis in Polycystic Ovary Syndrome

Impaired Steroidogenesis in Polycystic Ovary Syndrome

Polycystic Ovary Syndrome Overview

Proteins Involved in Pathogenesis of Polycystic Ovary Syndrome

Prostate Cancer

Androgen Receptor and Cell Cycle

Androgen Receptor Coregulator ARA55 (TGFB1I1) in Prostate Cancer

Androgen Receptor to Akt Signaling in Prostate Cancer

Androgen Receptor to Beta-2-Microglobulin Signaling in Prostate Cancer

Androgen Receptor to c-Met Signaling in Prostate Cancer

Androgen Receptor to FKBP5 Signaling in Prostate Cancer

Androgen Receptor to GJB1 Signaling in Prostate Cancer

Androgen Receptor to NKX-3.1 Signaling in Prostate Cancer

Androgen Receptor to Prostate Specific Antigen Signaling in Prostate Cancer

Androgen Receptor to Protein Kinase C-delta Signaling in Prostate Cancer

Androgen Receptor to SGK1 Signaling in Prostate Cancer

Beta-Catenin to Androgen Receptor Signaling in Prostate Cancer

Dihydrotestosterone Biosynthesis

Fatty Acid Synthase Signaling in Prostate Cancer

FOXA2 Signaling in Prostate Cancer

FOXM1 Signaling in Prostate Cancer

Kruppel-like Factor 6 Signaling in Prostate Cancer

Prostate Cancer Overview

Proteins Involved in Pathogenesis of Prostate Cancer

RNase L Signaling in Prostate Cancer

Psoriasis

Dendritic Cells in Psoriasis

Differentiation of Psoriatic T-cells

IFN-gamma/TNF-alpha Mediated anti-Apoptotic Effect in Psoriatic Keratinocytes

Interleukin-17 Signaling in Psoriatic Keratinocytes

Interleukin-22 Induced Keratinocyte Proliferation in Psoriasis

Proteins Involved in Pathogenesis of Psoriasis

Pulmonary Hypertension

BMP2 Activates Canonical WNT Signaling in Pulmonary Artery Endothelial Cells

BMP2 Activates Non-Canonical WNT Signaling in Pulmonary Artery Endothelial Cells

BMP2 Activates WNT Signaling in Pulmonary Artery Smooth Muscle Cells

Endothelial Cell Dysfunction in Pulmonary Arterial Hypertension

Hemolysis-Associated Arterial Pulmonary Hypertension

Impairment of BMP and TGF-beta Signaling in Familial and Idiopathic Pulmonary Arterial Hypertension

Proteins Involved in Pathogenesis of Hypoxia-Induced Pulmonary Hypertension

Proteins Involved in Pathogenesis of Pulmonary Hypertension

Smooth Muscle Cell Dysfunction in Pulmonary Arterial Hypertension

Raynaud Disease

Cold Stress and Adrenoceptor Alpha 2C Signaling in Raynaud Disease

NO and ADMA Signaling in Raynaud Disease

Proteins Involved in Pathogenesis of Raynaud Disease

Regulation of Vascular Reactivity in Raynaud Disease

Rheumatoid Arthritis

Block of Synovial Fibroblast Apoptosis in Rheumatoid Arthritis

Cytokine-Dependent Synovial Fibroblast Activation in Rheumatoid Arthritis

Osteoclast Activation in Rheumatoid Arthritis

Proteins Involved in Pathogenesis of Rheumatoid Arthritis

PTPN22 Involvement in Rheumatoid Arthritis

Synovial Fibroblast Proliferation in Rheumatoid Arthritis

TLR2-Induced Synovial Fibroblast Activation in Rheumatoid Arthritis

Systemic Lupus Erythematosus

B-cell Activation in Systemic Lupus Erythematosus

Defective Clearance of Apoptotic Keratinocytes in Systemic Lupus Erythematosus

Dendritic Cell Activation in Systemic Lupus Erythematosus

Neutrophil and Macrophage Function in Systemic Lupus Erythematosus

Proteins Involved in Pathogenesis of Systemic Lupus Erythematosus

Th0 Cell Aberrant Activation in Systemic Lupus Erythematosus

Th1 Cell Function in Systemic Lupus Erythematosus

Th17 Cell Function in Systemic Lupus Erythematosus

Th2 Cell Function in Systemic Lupus Erythematosus

The Complement System Defects in Systemic Lupus Erythematosus

Systemic Scleroderma

B-cells Function in Systemic Scleroderma

FAS Mediated Apoptosis in Systemic Scleroderma

Mechanism of Skin Fibrosis in Systemic Scleroderma

Model Autocrine Cytokine/Chemokine Loops in Systemic Scleroderma Fibroblasts 1

Proteins Involved in Pathogenesis of Systemic Scleroderma

Role of Th2 cells in Systemic Scleroderma

T-cell Acute Lymphoblastic Leukemia

Genetic Rearrangements Involved in T-cell Acute Lymphoblastic Leukemia Development

Proteins Involved in Pathogenesis of T-cell Acute Lymphoblastic Leukemia

T-cell Acute Lymphoblastic Leukemia Overview

Vasospasm

Contraction due Vasospasm

Hemoglobin Reduction and Leukocyte Adhesion Initiate Vasospasm

Necrosis of Neurons Caused by Energy Deficiency in Late Vasospasm

NO Synthesis in Early Vasospasm

Proteins Involved in Pathogenesis of Vasospasm

WHIM Syndrome

WHIM Syndrom Overview

Expression Targets Pathways

B-cell Receptors Expression Targets

CD19 Expression Targets

CD21 Expression Targets

CD81 Expression Targets

Gamma Globulins Expression Targets

Cell Adhesion Molecules Expression Targets

CTGF/AP-1/CREB/MYC Expression Targets

CTGF/FOXO3A Expression Target

CTGF/NCOR2 Expression Target

Fibrinogen Expression Targets

Fibronectin Expression Targets

ICAM1 Expression Targets

NCAM1 Expression Targets

PECAM1 Expression Targets

Cytokines Expression Targets

Chemokines Expression Targets

CCL11 Expression Targets

CCL15 Expression Targets

CCL16 Expression Targets

CCL2 Expression Targets

CCL3 Expression Targets

CCL3L1 Expression Target

CCL4 Expression Targets

CCL5 Expression Targets

CCL7 Expression Target

CCL8 Expression Targets

CXCL12 Expression Targets

IL8 Expression Targets

Colony Stimulating Factors Expression Targets

CSF2/NF-kB Expression Targets

CSF2/STAT Expression Targets

CSF3 Expression Targets

Erythropoietin Expression Targets

Erythropoietin/AP-1/MYC/CREB Expression Targets

Erythropoietin/ELK-SRF Expression Targets

Erythropoietin/FOXO3A Expression Targets

Erythropoietin/NF-kB Expression Targets

Erythropoietin/STAT Expression Targets

Growth Hormones Expression Targets

CSH1-GHR Expression Targets

CSH1-PRLR Expression Targets

FLT3LG/AP-1/CREB/CREBBP Expression Targets

GAS6/AP-1/CREB Expression Targets

GH1-GHR/NF-kB/ELK-SRF/MYC Expression Targets

GH1-GHR/STAT Expression Targets

GH1-PRLR Expression Targets

GH2-GHR Expression Target

PGF/AP-1/CREB/CREBBP/MYC Expression Targets

Interferons Expression Targets

IFNA1-IFNR Expression Targets

IFNB1-IFNR Expression Targets

IFNG-IFNR Expression Targets

IFNW1-IFNR Expression Target

Interleukins Expression Targets

IL10 Expression Targets

IL11 Expression Targets

IL12B Expression Targets

IL13 Expression Targets

IL15 Expression Targets

IL2 Expression Targets

IL21 Expression Targets

IL22 Expression Targets

IL3 Expression Targets

IL31 Expression Targets

IL4 Expression Targets

IL5 Expression Targets

IL6 Expression Targets

IL7 Expression Targets

IL9 Expression Targets

Leptin Expression Targets

Leptin/ELK-SRF Expression Targets

Leptin/STAT Expression Targets

Oncostatin M Expression Targets

OSM-IL6ST/LIFR Expression Targets

OSM-OSMR Expression Targets

Prolactin Expression Targets

PRL-GHR/NF-kB/ELK-SRF/MYC Expression Targets

PRL-GHR/STAT Expression Targets

PRL-PRLR Expression Targets

Thrombopoietin Expression Targets

Thrombopoietin/AP-1/CREB/CREBBP/MYC Expression Targets

Thrombopoietin/FOXO3A Expression Target

Thrombopoietin/SP1 Expression Targets

Thrombopoietin/SPI1 Expression Targets

Thrombopoietin/STAT Expression Targets

CLCF1 Expression Targets

CNTF Expression Targets

CTF1 Expression Targets

LIF Expression Targets

Delta/Notch Expression Targets

ADAM17 Expression Targets

DLL1 Expression Targets

DLL3 Expression Targets

DLL4 Expression Targets

JAG1 Expression Targets

NOTCH Expression Targets

GPCR Ligands Expression Targets

Signaling via Gi

Acetylcholine Expression Targets

Dopamine/Gi Expression Targets

Dronabinol/Anandamide Expression Targets

LPA Expression Targets

NPY Expression Targets

SST Expression Targets

Signaling via Gq

Adenosine Expression Targets

AVP/Gq -> CREB/ELK-SRF/AP-1/EGR Expression Targets

AVP/Gq -> MEF/MYOD/NFATC/MYOG Expression Targets

AVP/Gq -> STAT Expression Targets

CCK Expression Targets

EDN1 Expression Targets

EDN3 Expression Targets

Epinephrine/Gq Expression Targets

F2 -> AP-1/CREB/ELK-SRF/SP1 Expression Targets

F2 -> STAT1/NF-kB Expression Targets

GAST Expression Targets

Glutamate/Gq Expression Targets

GNRH1 Expression Targets

GNRH2 Expression Targets

IFNA1/Gq Expression Targets

Morphine Expression Targets

Noreadrenaline/Gq Expression Targets

NTS Expression Targets

OXT Expression Targets

PAF/Gq -> AP-1/ATF1/CREB/ERK-SRF Expression Targets

PAF/Gq -> NF-kB Expression Targets

PLG -> AP-1/CREB/ELK-SRF/SP1 Expression Targets

PLG -> STAT1/NF-kB Expression Targets

POMC Expression Targets

Prostaglandin F Expression Targets

Serotonin/Gq Expression Targets

Thromboxane A2 Expression Targets

Signaling via Gq/i

CXCL1 Expression Targets

CXCL2 Expression Targets

CXCL3 Expression Targets

CXCL5 Expression Targets

CXCL6 Expression Targets

S1P Expression Targets

Signaling via Gq/s

ADCYAP1 Expression Targets

AGT/CREB Expression Targets

AGT/ELK-SRF Expression Targets

AGT/STAT Expression Targets

AGT/TP53 Expression Targets

Epinephrine/Gs Expression Targets

Noradrenaline/Gs Expression Targets

PGE1 Expression Targets

TAC1 Expression Targets

VIP Expression Targets

Signaling via Gs

AVP/Gs -> CREB/ELK-SRF/AP-1/EGR Expression Targets

AVP/Gs -> MEF/MYOD/NFATC/MYOG Expression Targets

AVP/Gs -> STAT Expression Targets

Dopamine/Gs Expression Targets

FSHR Expression Targets

GCG Expression Targets

Serotonin/Gs Expression Targets

Neurotrophins Expression Targets

BDNF Expression Targets

NGF/AP-1/TP53/MYC Expression Targets

NGF/CREB/CEBPB/MEF2A Expression Targets

NGF/FOXO/MYCN/ELK-SRF Expression Targets

NGF/SMAD3/NF-kB Expression Targets

NTF3 Expression Targets

NTF4 Expression Targets

NK-cell Receptors Expression Targets

CD247 Expression Targets

FCGR3A Expression Targets

RAGE Ligands Expression Targets

HMGB1 Expression Targets

S100A Expression Targets

S100B Expression Targets

S100P Expression Target

TTR Expression Targets

Receptor Tyrosine Kinases Expression Targets

Growth Factors Expression Targets

EGFR Ligands Expression Targets

AREG Expression Targets

AREG/AP-1 Expression Targets

AREG/CREB/CREBBP Expression Targets

AREG/CTNN Expression Targets

AREG/FOXO3A Expression Target

AREG/HIF1A Expression Targets

AREG/NCOR2 Expression Targets

AREG/NFATC Expression Target

AREG/SMAD1 Expression Target

AREG/STAT Expression Targets

BTC Expression Targets

BTC/AP-1/ATF/CREB Expression Targets

BTC/CTNN Expression Targets

BTC/EP300/ETS/ETV/SP1 Expression Targets

BTC/NFATC Expression Targets

BTC/STAT Expression Targets

EGF Expression Targets

EGF/AP-1/ATF Expression Targets

EGF/CREB/CREBBP/ELK-SRF/MYC Expression Targets

EGF/CTNN Expression Targets

EGF/FOXO3A Expression Targets

EGF/HIF1A Expression Targets

EGF/MEF/MYOD/NFATC Expression Targets

EGF/NCOR2 Expression Target

EGF/STAT Expression Targets

EGF/TP53 Expression Targets

EREG Expression Targets

EREG/AP-1/ATF Expression Targets

EREG/CREB Expression Target

EREG/CTNNB/CTNND Expression Target

EREG/EP300/SP1 Expression Targets

EREG/FOXO3A Expression Target

EREG/HIF1A Expression Target

EREG/STAT Expression Targets

HBEGF Expression Targets

HBEGF/AP-1/ATF Expression Targets

HBEGF/CREB/MYC Expression Targets

HBEGF/EP300/ETS/ETV/SP1 Expression Targets

HBEGF/FOXO3A Expression Target

HBEGF/HIF1A Expression Targets

HBEGF/MEF/MYOD Expression Target

HBEGF/STAT Expression Targets

HBEGF/TP53 Expression Targets

TGFA Expression Targets

TGFA/AP-1/ATF Expression Targets

TGFA/CREB/CREBBP/ELK-SRF/MYC Expression Targets

TGFA/CTNNB/CTNND Expression Targets

TGFA/FOXO3A Expression Targets

TGFA/HIF1A Expression Targets

TGFA/MEF/MYOD/NFATC Expression Targets

TGFA/STAT Expression Targets

TGFA/TP53 Expression Targets

FGF Expression Targets

FGF1 Expression Targets

FGF1/AP-1/CREB/ELK-SRF/MYC Expression Targets

FGF1/NCOR2 Expression Target

FGF1/RUNX Expression Targets

FGF1/STAT Expression Targets

FGF10 Expression Targets

FGF10/AP-1/CREB/CREBBP/MYC Expression Targets

FGF10/FOXO3A Expression Target

FGF10/STAT Expression Targets

FGF18 Expression Targets

FGF18/AP-1/CREB Expression Targets

FGF18/STAT Expression Targets

FGF2 Expression Targets

FGF2/AP-1/CREB/CREBBP/ELK-SRF/MYC Expression Targets

FGF2/FOXO3A Expression Targets

FGF2/NCOR2 Expression Targets

FGF2/RUNX Expression Targets

FGF2/STAT Expression Targets

FGF23 Expression Targets

FGF23/NCOR2 Expression Targets

FGF4 Expression Targets

FGF4/AP-1/MYC Expression Targets

FGF7 Expression Targets

FGF7/AP-1/CREB/CREBBP/MYC Expression Targets

FGF7/FOXO3A Expression Target

FGF7/RUNX Expression Targets

FGF8 Expression Targets

FGF8/AP-1/CREB/MYC Expression Targets

FGF8/RUNX Expression Targets

FGF8/STAT Expression Targets

FGF9 Expression Targets

FGF9/AP-1/CREB/MYC Expression Targets

FGF9/RUNX Expression Targets

FGF9/STAT Expression Targets

HGF Expression Targets

HGF/AP-1/CREB/ELK-SRF/MYC Expression Targets

HGF/FOXO3A Expression Targets

HGF/STAT Expression Targets

Insulin/IGF Expression Targets

IGF1 Expression Targets

IGF1/CEBPA/FOXO1A Expression Targets

IGF1/ELK-SRF/HIF1A/MYC/SREBF Expression Targets

IGF1/MEF/MYOD/MYOG Expression Targets

IGF1/STAT Expression Targets

IGF2 Expression Targets

IGF2/CEBPA/FOXO1A Expression Targets

IGF2/HIF1A/MYC Expression Targets

IGF2/MEF/MYOD Expression Targets

IGF2/STAT Expression Targets

Insulin Expression Targets

Insulin/CEBPA/CTNNB/FOXA/FOXO Expression Targets

Insulin/ELK-SRF/HIF1A/MYC/SREBF Expression Targets

Insulin/MEF/MYOD Expression Targets

Insulin/STAT Expression Targets

PDGFR Ligands Expression Targets

CSF1 Expression Targets

CSF1/AP-1/CREB/CREBBP/MYC Expression Targets

CSF1/FOXO3A Expression Targets

CSF1/STAT Expression Targets

KITLG Expression Targets

KITLG/AP-1/CREB/CREBBP/MYC Expression Targets

KITLG/STAT Expression Targets

PDGFB Expression Targets

PDGFB/AP-1/CREB/MYC Expression Target

PDGFB/FOXO3A Expression Target

PDGFB/STAT Expression Target

PDGFC Expression Targets

PDGFC/CREB Expression Target

PDGFC/STAT Expression Target

PDGFD Expression Targets

PDGFD/AP-1 Expression Targets

PDGFD/STAT Expression Targets

PDGF/AP-1/CREB/CREBBP/MYC Expression Targets

PDGF/FOXO3A Expression Targets

PDGF/STAT Expression Targets

VEGF Expression Targets

FIGF Expression Targets

FIGF/AP-1 Expression Target

FIGF/NCOR2 Expression Target

VEGFA Expression Targets

VEGFA/AP-1/CREBBP/MYC Expression Targets

VEGFA/ATF/CREB/ELK-SRF Expression Targets

VEGFA/CTNNB/CTNND Expression Targets

VEGFA/FOXO3A Expression Targets

VEGFA/NCOR2 Expression Target

VEGFA/NFATC Expression Targets

VEGFA/STAT Expression Targets

VEGFC Expression Targets

VEGFC/ATF Expression Target

VEGFC/CTNNB Expression Target

EGFR Ligands Expression Targets

Growth Factors Expression Targets

NRG1/AP-1/ATF Expression Targets

NRG1/Catenin Expression Targets

NRG1/CREB/CREBBP/ELK-SRF/MYC Expression Targets

NRG1/EP300/ETS/ETV/SP1 Expression Targets

NRG1/FOXO3A Expression Targets

NRG1/HIF1A Expression Target

NRG1/MEF/MYOD Expression Targets

NRG1/STAT Expression Targets

NRG1/TP53 Expression Target

ANGPT1/CREB/CREBBP Expression Targets

ANGPT1/STAT Expression Targets

ANGPT2/AP-1/CREBBP/MYC Expression Targets

ANGPT2/STAT Expression Targets

Collagen/NF-kB Expression Targets

EFNA1/STAT Expression Target

EphrinR Expression Targets

GDNF/HSF1 Expression Targets

MDK/PTN Expression Targets

PAF Expression Targets

RPTP Expression Targets

PTPRC/BCL6 Expression Targets

PTPRC/STAT6 Expression Targets

PTPRJ Expression Targets

T-cell Receptors Expression Targets

CD22/72/279 Expression Targets

CD22/NF-kB Expression Targets

CD22/STAT Expression Targets

CD72/AP-1 Expression Targets

CD72/CREB/CREBBP Expression Targets

CD72/NFATC Expression Targets

CD72/NF-kB Expression Targets

CD72/STAT Expression Target

PDCD1/AP-1 Expression Targets

PDCD1/ATF/CREB/CREBBP Expression Targets

PDCD1/NFATC Expression Targets

PDCD1/NF-kB Expression Targets

PDCD1/STAT Expression Targets

CD8 Expression Targets

CD8/AP-1 Expression Targets

CD8/ATF/CREB/CREBBP Expression Targets

CD8/NFATC Expression Targets

CD8/NF-kB Expression Targets

CD8/STAT Expression Targets

CD80 Expression Targets

CD80/AP-1 Expression Targets

CD80/ATF/CREB/CREBBP Expression Targets

CD80/NFATC Expression Targets

CD80/NF-kB Expression Targets

CD80/STAT Expression Targets

CD86 Expression Targets

CD86/AP-1 Expression Targets

CD86/ATF/CREB/CREBBP Expression Targets

CD86/NFATC Expression Targets

CD86/NF-kB Expression Targets

CD86/STAT Expression Targets

IL16 Expression Targets

IL16/AP-1 Expression Targets

IL16/ATF/CREB/CREBBP Expression Target

IL16/NF-kB Expression Targets

IL16/STAT Expression Targets

CD2 Expression Targets

TCR/AP-1 Expression Targets

TCR/CREB/CREBBP/ATF Expression Targets

TCR/NFAT Expression Targets

TCR/NF-kB Expression Targets

TCR/STAT Expression Targets

TGFB Superfamily Expression Targets

BMP Expression Targets

BMP15-BMPR2 Expression Targets

BMP2-BMPR2 Expression Targets

BMP4-BMPR2 Expression Targets

BMP6-ACVR2A Expression Targets

BMP7-ACVR2 Expression Targets

BMP7-BMPR2/ACVR2 Expression Targets

INHB Expression Targets

INHBA-ACVR2/ACVR1 Expression Targets

INHBA-ACVR2/BMPR Expression Targets

INHBB-ACVR2 Expression Target

Other ACVR/BMPR Ligands Expression Targets

AMH-AMHR2 Expression Targets

GDF5-BMPR2/ACVR2 Expression Targets

MSTN-ACVR2/ACVR1 Expression Targets

MSTN-ACVR2/BMPR Expression Targets

NODAL-ACVR2B Expression Targets

TDGF1-ACVR2B Expression Targets

TGFB Expression Targets

TGFB1-ACVRL1 Expression Targets

TGFB1-TGFBR1 Expression Targets

TGFB1-TGFBR1/AP-1 Expression Targets

TGFB1-TGFBR2 Expression Targets

TGFB2-TGFBR1 Expression Targets

TGFB2-TGFBR2 Expression Targets

TGFB3-TGFBR1 Expression Targets

TGFB3-TGFBR2 Expression Targets

TNF Family Expression Targets

CD40LG/ATF2/AP-1/TP53/E2F Expression Targets

CD40LG/NF-kB/ELK-SRF/CREB/NFATC Expression Targets

CD40LG/STAT Expression Targets

EDA Expression Targets

FASLG Expression Targets

LTA Expression Targets

TNF/AP-1 Expression Targets

TNF/CREB Expression Targets

TNF/ELK-SRF Expression Targets

TNF/NF-kB Expression Targets

TNF/STAT Expression Targets

TNF/TP53/ATF Expression Targets

TNFSF10 Expression Targets

TNFSF13 Expression Targets

TNFSF13B Expression Targets

TNFSF14 Expression Targets

Toll-like Receptors Expression Targets

IL1A Expression Targets

IL1B Expression Targets

IL1B/NO Expression Targets

IL1B/PGE2 Expression Targets

TLR1/2/6 Expression Targets

TLR3 Expression Targets

TLR4/AP-1 Expression Targets

TLR4/AP-1/EGR1/HIF1A Expression Targets

TLR4/NF-kB/IRF Expression Targets

TLR5 Expression Targets

TLR7 Expression Targets

TLR9 Expression Targets

Urokinase Expression Targets

PLAU/ELK-SRF/AP-1 Expression Targets

PLAU/STAT1 Expression Targets

WNT Expression Targets

Canonical WNT Signaling Expression Targets

WNT1 Expression Targets

WNT2 Expression Targets

WNT3A Expression Targets

WNT4 Expression Targets

WNT5A Expression Targets

WNT7A Expression Targets

WNT7B Expression Targets

WNT9A Expression Targets

WNT9B Expression Targets

Immunological Pathways

Antigen Processing

MHC1-Mediated Antigen Presentation

MHC2-Mediated Antigen Presentation

B-cell Activation

T-cell-Dependent B-cell Activation

T-cell-Independent B-cell Activation

Natural Killer Cell Receptors Signaling

Leukocyte Adhesion to Endothelial Cell

Natural Killer Cell Activation through C-type Lectin-like Receptors

Natural Killer Cell Activation through ITAM-Containing Receptors

Natural Killer Cell Activation through ITSM-Containing Receptors

Natural Killer Cell Inhibitory Receptor Signaling

Production of Immunoglobulins

Activation of Immunoglobulin Class-Switch Recombination

Immunoglobulin Class-Switch Recombination via Alternative End-Joining

Immunoglobulin Class-Switch Recombination via Classical Non-Homologous End-Joining

Natural Killer Cell Activation through Integrins and non-ITAM-Containing Receptors

V(D)J Recombination

V(D)J Recombination Activation

Receptors of Antigen Recognition in Innate Immune System

Antiviral Signaling through Pattern Recognition Receptors

DCIR1 (CLEC4A) Signaling

Dectin-1 (CLEC7A) Signaling

Dectin-2 (CLEC6A), Mincle (CLEC4E), and BDCA2 (CLEC4C) Signaling

Mannose Receptor Signaling

NOD-like Receptors in Pathogen Recognition

TLR4 Signaling in Leukocytes

Toll-like Receptors Act through MYD88 Signaling

Toll-like Receptors Act through MYD88-TIRAP Signaling

Transcriptional Activation of Immunoglobulin Genes

Self Tolerance

CD8+ T-cell Activation

Central T-cell Tolerance

DC-SIGN (CD209) Signaling

Model of T-cell Maturation

Natural Killer Cell Activation

Peripheral T-cell Tolerance Overview

T-cell Positive Selection and Neglect-Induced Death

T-cell Activation and Differentiation

Cell Death Mediated by Cytotoxic Cells

Regulatory T-cell Differentiation

T-cell Receptor Signaling

Th1 Cell Differentiation

Th17 Cell Differentiation

Th2 Cell Differentiation

Metabolic Pathways

Alanine metabolism

Alpha oxidation of phytanic acid

Amino sugars synthesis

Arachidonic acid metabolism

Ascorbate biosyntesis

Aspartate metabolism

Bile acid metabolism (alternative pathway)

Bile acids metabolism

Biosynthesis of cholesterol

Biotin metabolism

Branched chain amino acids metabolism

Caffeine metabolism

Capecitabine and Fluorafur metabolism

Cholesterol catabolism

D-amino acid metabolism

Ethanol metabolism

Fatty acid biosynthesis

Fatty acid oxidation

Folate biosynthesis

Galactose metabolism

Ganglioside-type glycosphingolipid biosynthesis

Globoside-type glycosphingolipid biosynthesis

Glu/Gln/Pro metabolsm

Glucose metabolism

Glutathione metabolism

Glycogen metabolism

Glycosylphosphatidylinositol(GPI)-anchor biosynthesis

Glyoxylate and glycerate metabolism

Heme biosynthesis

Heme oxidation

Histidine metabolism

Inositol phosphate metabolism

Irinotecan metabolism

Ketonogenesis

Lacto- and neolacto-type glycosphingolipid biosynthesis

Lipoyl-protein complex biosynthesis I

Lipoyl-protein complex biosynthesis II

L-sugars oxidation

Lysine metabolsm

Malonate, propanoate and beta-alanine metabolism

Mannose metabolism

Metabolism of estrogens and androgens

Metabolism of glucocorticoids and mineralcorticoids

Metabolism of glycerophospholipids and ether lipids

Metabolism of triacylglycerols

Methionine metabolism

Mevalonate pathway

N-Glycan biosynthesis

Nicotinate and nicotinamide metabolism

Omega-3-fatty acid metabolism

Omega-6-fatty acid metabolism

Organophosphorus compounds degradation

Pentose-phosphate shunt

Phenylalanine and Tyrosine metabolism

Polysaccharide degradation

Pterine biosynthesis

Purine metabolism

Pyrimidine metabolism

Pyruvate metabolism

Respiratory chain and oxidative phosphorylation

Riboflavin metabolism

ROS metabolism

Selencompound biosynthesis

Ser/Gly/Thr/Cys metabolism

Serine and Glycine metabolism

Sphingolipid metabolism

Sulfur metabolism

Tricarboxylic acid cycle

Tryptophan metabolism

Ubiquinoine biosynthesis

Ubiquinoine biosynthesis in humans

Ubiquinoine biosynthesis in rats

Urea cycle and arginine metabolism

Vitamin A (retinol) metabolism and visual cycle

Vitamin B1(thiamine) metabolism

Vitamin B5 (pantothenate) metabolism and biosynthesis of CoA and holo-ACP

Vitamin B6 (pyridoxine) metabolism

Vitamin K metabolism

Nociception Pathways

Neuronal Signaling

Adrenergic receptors

ADRA1 -> ion channels

ADRA2A -> hyperpolarization

ADRA2A -> neurotransmitter release

ADRA2C/ADRB2 -> synaptic endocytosis

ADRB1 -> ion channels

ATP receptors

P2RXs -> synaptic transmission

P2RY1/2/4/6 -> potassium channels

P2RY11/13/14 -> IL8/10 production

P2RY2/12/13/14 -> N-type calcium channel

Bradykinin receptors

BDKRB1/2 -> ion channels

Cannabinoid receptors

CNR1/2 -> membrane transport

Cholecystokinin B receptor

CCKBR -> neurotransmitter uptake

Dopamine receptors

DRD1/3 -> potassium uptake

DRD2 -> TRPC1 transcription

DRD2/4 -> membrane transport

DRD3 -> dopamine uptake

Ephrin receptors

EPHB -> NMDA receptor activation

GABA receptors

GABA(A)R -> membrane hyperpolarization

GABA(B)R -> postsynaptic inhibition

Galanin receptors

GALR1/2/3 -> neurotransmitter metabolism

GFs signaling

GFs/TNF -> ion channels

Glutamate receptors

AMPA receptors -> calcium influx

GRM1/5 (postsynaptic) -> ion channels

GRM2-4/6-8 (presynaptic) -> glutamate release attenuation

NMDA receptor -> synaptic excitation

NMDA receptors -> Ca2+/CREB activation/PGE2 synthesis

Glycine receptor

GlyR -> synaptic inhibition

Histamine receptor

HRH1/2 -> membrane polarization

HRH1/3 -> synaptic transmission

Muscarinic receptors

CHRM1/2/3/5 -> ion channels

Neuropeptide Y receptor

NPY1R -> CRH/POMC production

Neurotrophin receptors

NTRK1/2/3 -> acetylcholine production

Nicotinic receptors

CHRNA3-B4/A4-B2/A7 -> ion transport

CHRNA7 -> NOS1 production

Opioid receptors

OPRD/OPRM -> ion channels

OPRK -> pain perception

OPRL1 -> ion channels

Serotonin receptors

HTR1 -> membrane transport

HTR2 -> membrane transport

HTR3A -> cation transport

HTR4/6/7 -> cation channels

Substance P receptor

TACR1 -> membrane transport

Trace amine receptor

TAAR1 -> neurotransmitter uptake

Neurotransmitter Release Cycles

Acetylcholine release cycle

Dopamine release cycle

Epinephrine/Norepinephrine release cycle

GABA release cycle

Glutamate release cycle

Serotonin release cycle

Reference Nociception Pathways

Regulation of calcium flux

Regulation of potassium flux

Regulation of sodium flux

Summarized nociception-related expression targets

Summarized vascular motility pathway

Tissue Signaling

Non-transcriptionally Regulated Processes

Adenosine receptors

ADORA1/2A -> exocytosis

ADORA2A/B -> vasodilation

ADORA3 -> mast cell degranulation

Adrenergic receptors

ADRA1 -> prostaglandin generation

ADRA1 -> vasoconstriction

ADRA2C/ADRB2 -> vasoconstriction

ADRB1 -> prostaglandin generation

ADRB1/3 -> vasodilation

Bradykinin receptors

BDKRB1/2 -> prostaglandin generation

BDKRB1/2 -> vasodilation

Calcitonin receptor-like receptor

CGRP -> calcium influx

Cannabinoid receptors

CNR1/2 -> vascular motility

Endothelin receptors

EDNRA/B -> vascular motility

Histamine receptors

HRH1/2 -> vascular motility

Leptin signaling

Leptin -> NO production/vasodilation

Muscarinic receptors

CHRM1/2/3 -> vascular motility

Prostaglandin receptors

PTGER2/3 -> inflammation-related expression targets

PTGIR -> IL6 production

Serotonin receptors

HTR1 -> vascular motility

HTR4/6/7 -> vasodilation

Transcriptionally Regulated Processes

Adrenergic receptors

ADRA1A -> IL6 production

Bradykinin receptors

BDKRB1/2 -> interleukins production

Cannabinoid receptors

CNR1/2 -> IL1B/2/4/6/10 production

Chemokine receptor 1

Nociception-related CCR1 expression targets

Corticotropin releasing hormone receptor

CRH -> synthesis of corticosteroids

Dopamine receptors

Nociception-related DRD1/5 expression targets

Nociception-related DRD2 expression targets

Galanin receptors

GALR1/2/3 -> POMC/NPY production

Histamine receptor

HRH2/4 -> IL6/10 production

Interleukin signaling

Nociception-related IL1B expression targets

Nociception-related IL6 expression targets

Leptin signaling

Leptin -> CD25/IL6/IL10 production

Muscarinic receptors

CHRM1 -> IL2 production

Neurotensin receptor

Nociception-related NTSR1 expression targets

Nicotinic receptors

CHRNA7 -> IL8 production

Prostaglandin receptors

PTGDR -> vasodilation

PTGER1/4 -> vascular motility

PTGER2/3 -> vascular motility

PTGFR -> vasoconstriction

PTGIR -> vasodilation

Serotonin receptors

HTR1 -> IL6 production

HTR5 -> TNF production

HTR7 -> IL6 production

Substance P receptor

TACR1 -> TNF/IL6/IL8 production

Signaling Pathways

Receptor Signaling

Advanced Glycosylation End Product-specific Receptor

AGER -> CREB/SP1 signaling

AGER -> NF-kB signaling

B-cell Receptors

B-cell receptor -> AP-1 signaling

B-cell receptor -> NFATC signaling

B-cell receptor -> NF-kB signaling

CD19 -> AP-1/ELK-SRF signaling

CD19 -> NF-kB signaling

Cytokine Receptors

CNTFR -> STAT3 signaling

CSF2R -> NF-kB signaling

CSF2R -> STAT signaling

CSF3R -> STAT signaling

ErythropoietinR -> AP-1/CREB/MYC signaling

ErythropoietinR -> ELK-SRF/FOS signaling

ErythropoietinR -> FOXO3A signaling

ErythropoietinR -> NF-kB signaling

ErythropoietinR -> STAT signaling

GHR -> ELK-SRF/MYC signaling

GHR -> NF-kB signaling

GHR -> STAT signaling

IFNAR -> STAT signaling

IFNGR -> STAT signaling

LeptinR -> ELK-SRF signaling

LeptinR -> STAT signaling

LIFR -> STAT5A signaling

OncostatinR -> STAT3 signaling

ProlactinR -> STAT signaling

ThrombopoietinR -> AP-1/CREB/ELK-SRF/MYC signaling

ThrombopoietinR -> SP1 signaling

ThrombopoietinR -> SPI1 signaling

ThrombopoietinR -> STAT signaling

Frizzled Receptor family

FrizzledR -> CTNNB signaling

FrizzledR -> JUN/PAX2 signaling

G-protein-coupled Receptors

Gi-coupled Receptors

CannabinoidR -> AP-1/EGR signaling

CCR1 -> STAT signaling

CCR2/5 -> STAT signaling

CCR5 -> TP53 signaling

CholinergicRm -> CREB/ELK-SRF signaling

CXCR4 -> STAT signaling

DopamineR2 -> AP-1/CREB/ELK-SRF signaling

DopamineR2 -> NF-kB signaling

EDG2 -> ELK-SRF signaling

NeuropeptideYR -> ATF/CREB signaling

SerotoninR1 -> FOS signaling

SomatostatinR -> ATF1/TP53 signaling

G-protein-coupled Receptors

ThrombinR -> AP-1/CREB/ELK-SRF/SP1 signaling

ThrombinR -> NF-kB signaling

ThrombinR -> STAT1 signaling

ThromboxaneR -> CREB signaling

Gq/i-coupled Receptors

EDG3/5 -> AP-1/ELK-SRF signaling

EndothelinRb -> AP-1/CREB/ELK-SRF signaling

IL8R -> CREB/EGR signaling

Gq/s-coupled Receptors

AdrenergicRb -> CREB signaling

AdrenergicRb -> STAT3 signaling

AngiotensinR -> CREB/ELK-SRF/TP53 signaling

AngiotensinR -> STAT signaling

EndothelinRa -> AP-1/CREB signaling

ProstaglandinIR -> ATF1/ELK-SRF/CREB signaling

TachykininR -> ELK-SRF signaling

VIPR -> CREB/CEBP signaling

Gq-coupled Receptors

AdenosineR -> AP-1 signaling

AdenosineR -> NF-kB signaling

AdrenergicRa -> ELK-SRF signaling

AdrenergicRa -> STAT1 signaling

AdrenergicRa -> STAT3 signaling

BradykininR -> STAT3 signaling

CholecystokininR -> ELK-SRF signaling

CholecystokininR -> STAT signaling

GNRHR -> ELK-SRF signaling

GRM1/5 -> CREB signaling

NeurotensinR -> ELK-SRF/AP-1/EGR signaling

OpioidR -> CREB/ELK-SRF/STAT3 signaling

OxytocinR -> ELK-SRF/GATA/AP-1 signaling

ProstaglandinFR -> ATF1/ELK-SRF/CREB signaling

PTAFR -> AP-1/ATF1/CREB/ERK-SRF signaling

PTAFR -> NF-kB signaling

PTAFR -> STAT3 signaling

SerotoninR2 -> ELK-SRF/GATA4 signaling

SerotoninR2 -> STAT3 signaling

VasopressinR1 -> CREB/ELK-SRF/AP-1/EGR signaling

VasopressinR1 -> MEF/MYOD/NFATC/MYOG signaling

VasopressinR1 -> STAT signaling

Gs-coupled Receptors

DopamineR1 -> CREB/ELK-SRF signaling

FSHR -> CREB/ELK-SRF/GATA4 signaling

FSHR -> FOXO1A signaling

GlucagonR -> CREB/ELK-SRF/SP1 signaling

SerotoninR4/6/7 -> NR3C signaling

VasopressinR2 -> CREB/ELK-SRF/AP-1/EGR signaling

VasopressinR2 -> MEF/MYOD/NFATC/MYOG signaling

VasopressinR2 -> STAT signaling

Integrins and Cell Adhesion Receptors

FibronectinR -> AP-1/ELK-SRF/SREBF signaling

FibronectinR -> CTNNB signaling

FibronectinR -> ICAP-1A/MYC signaling

FibronectinR -> NF-kB signaling

ICAM1 -> AP-1/CREB/ELK-SRF signaling

ICAM2 -> CTNNB/FOXO/STAT3 signaling

MacrophageR -> CEBPB/NF-kB signaling

NCAM1 -> CREB/ELK-SRF/MYC signaling

PECAM -> CTNNB1 signaling

PECAM -> SP1 signaling

PECAM -> STAT signaling

SELE -> ELK-SRF signaling

Sialophorin -> CTNNB/MYC/TP53 signaling

Interleukin Receptors

IL10R -> STAT signaling

IL11R -> STAT3 signaling

IL12R -> NF-kB/NFATC signaling

IL12R -> STAT signaling

IL13R -> STAT signaling

IL13R -> STAT6 signaling

IL15R -> NF-kB/NFATC signaling

IL15R -> STAT signaling

IL21R -> STAT signaling

IL22R -> STAT3 signaling

IL2R -> ELK-SRF/MYC signaling

IL2R -> STAT signaling

IL31R -> STAT signaling

IL3R -> STAT signaling

IL4R -> ELK-SRF/HMGY signaling

IL4R -> STAT signaling

IL5R -> SOX4 signaling

IL5R -> STAT signaling

IL6R -> CEBP/ELK-SRF signaling

IL6R -> STAT signaling

IL6ST -> STAT5B signaling

IL7R -> FOXO/NF-kB signaling

IL7R -> STAT signaling

IL9R -> STAT signaling

NK-cell Receptors

FcIgER -> ELK-SRF signaling

FcIgER -> NFATC1 signaling

Notch Receptors

Notch -> EP300/ASCL signaling

Notch -> LEF1 signaling

Notch -> MEF/MYOD signaling

Notch -> NF-kB signaling

Notch -> RBPJ/HES/HEY signaling

Notch -> SMAD3 signaling

Notch -> TCF3 signaling

Protein Tyrosine Phosphatase Receptors

PTPRC -> BCL6 signaling

PTPRC -> STAT6 signaling

PTPRF -> CTNNB signaling

PTPRJ -> CTNND signaling

PTPRU -> CTNNB signaling

Receptor Tyrosine Kinases

Growth Factor Receptors

HGFR

HGFR -> AP-1/CREB/MYC signaling

HGFR -> FOXO3A signaling

HGFR -> STAT signaling

EGFR family

EGFR -> AP-1/ATF2 signaling

EGFR -> AP-1/CREB/ELK-SRF/MYC signaling

EGFR -> CTNND signaling

EGFR -> NCOR2 signaling

EGFR -> SMAD1 signaling

EGFR -> ZNF259 signaling

EGFR/ERBB -> STAT signaling

EGFR/ERBB2 -> CTNNB signaling

EGFR/ERBB2 -> HIF1A signaling

EGFR/ERBB2 -> TP53 signaling

EGFR/ERBB3 -> MEF/MYOD/NFATC/MYOG signaling

ERBB2/3 -> EP300/ETS/ETV/SP1 signaling

FGFR family

FGFR -> AP-1/CREB/CREBBP/ELK-SRF/MYC signaling

FGFR -> RUNX2 signaling

FGFR1 -> STAT signaling

FGFR3 -> STAT signaling

PDGFR family

CSF1R -> STAT signaling

KIT -> MITF signaling

KIT -> STAT signaling

PDGFR -> AP-1/MYC signaling

PDGFR -> FOXO3A signaling

PDGFR -> STAT signaling

VEGFR family

VEGFR -> AP-1/CREB/MYC signaling

VEGFR -> ATF/CREB/ELK-SRF signaling

VEGFR -> CTNNB signaling

VEGFR -> CTNND signaling

VEGFR -> FOXO3A signaling

VEGFR -> NFATC signaling

VEGFR -> STAT signaling

Insulin Receptors

IGF1R -> CEBPA/FOXO1A signaling

IGF1R -> ELK-SRF/HIF1A/MYC/SREBF signaling

IGF1R -> MEF/MYOD/MYOG signaling

IGF1R -> STAT signaling

InsulinR -> CTNNB/FOXA/FOXO signaling

InsulinR -> ELK-SRF/SREBF signaling

InsulinR -> STAT signaling

ALK -> STAT signaling

AngiopoietinR -> AP-1 signaling

AngiopoietinR -> FOXO signaling

AngiopoietinR -> STAT signaling

DDR1 -> NF-kB signaling

EphrinR -> actin signaling

EphrinR -> STAT signaling

GDNF -> HSF1 signaling

NTRK -> AP-1/CREB/ELK-SRF/MYC/SMAD3/TP53 signaling

NTRK -> FOXO/MYCN signaling

T-cell Receptors

CD2 -> NFATC1 signaling

CD2 -> STAT signaling

T-cell receptor -> AP-1 signaling

T-cell receptor -> ATF/CREB signaling

T-cell receptor -> CREBBP signaling

T-cell receptor -> NFATC signaling

T-cell receptor -> NF-kB signaling

T-cell receptor -> STAT signaling

TGFBR family

ActivinR -> SMAD2/3 signaling

ActivinR/BMPR -> SMAD1/5/9 signaling

TGFBR -> AP-1 signaling

TGFBR -> ATF/GADD/MAX/TP53 signaling

TGFBR -> CREB/ELK-SRF signaling

TGFBR -> MEF/MYOD/MYOG signaling

TGFBR -> SMAD1/5/9 signaling

TGFBR/BMPR -> SMAD2/3 signaling

TNFR family

EctodysplasinR -> AP-1 signaling

EctodysplasinR -> LEF1 signaling

EctodysplasinR -> NF-kB signaling

NGFR -> AP-1/CEBPB/CREB/ELK-SRF/TP53 signaling

NGFR -> MEF signaling

NGFR -> NF-kB signaling

TNFR -> AP-1/ATF/TP53 signaling

TNFR -> CREB/ELK-SRF signaling

TNFR -> NF-kB signaling

TNFRSF1A -> AP-1/ATF/TP53 signaling

TNFRSF1A -> CREB/ELK-SRF signaling

TNFRSF1A -> STAT signaling

TNFRSF5 -> STAT signaling

TNFRSF5/13B -> NFATC1 signaling

TNFRSF5/6 -> RB1/E2F signaling

TNFRSF6 -> DDIT3 signaling

TNFRSF6 -> FOXO3A signaling

TNFRSF6 -> HSF1 signaling

Toll-like Receptors

IL1R -> NF-kB signaling

IL1R -> STAT3 signaling

TLR -> AP-1 signaling

TLR1/2/6 -> NF-kB signaling

TLR3 -> IRF signaling

TLR3 -> NF-kB signaling

TLR4 -> IRF signaling

TLR4/5/7/9 -> NF-kB signaling

Urokinase Receptor

UrokinaseR -> ELK-SRF signaling

UrokinaseR -> STAT signaling

CD38 -> NF-kB signaling

CholinergicRn -> CREB signaling

EphrinB -> JUN signaling

Atlas of Signaling

Toxicity Pathways

Drug Toxicity Pathways

Acetaminophen-Induced Hepatotoxicity

Clozapine-Induced Granulocytopenia

Cocaine-Induced Hepatotoxicity

Cyclosporine-Induced Nephrotoxicity

Dexamethasone-Induced Diabetes

Dexamethasone-Induced Neurotoxicity

Dexamethasone-Induced Osteoporosis

Doxorubicin-Induced Cardiotoxicity

Ethanol-Induced Hepatotoxicity

Ritonavir-Induced Cardiovascular Dysfunction

Ritonavir-Induced Diabetes

Tamoxifen-Induced Endometrial Cancer

Valdecoxib-Induced Ischemic Disease

General Mechanisms of Toxicity

Cytosolic Calcium Overload

ER Stress (Unfolded Protein Response)

Glutamate-Mediated Excitotoxicity

Hypoxia-Induced Mitochondrial Damage

Protein Oxidation and Nitration Products as Disease Biomarkers

ROS and RNS in the Regulation of Vasoconstriction and Vasodilation

ROS in Angiotensin-Mediated Cardiovascular Remodeling and Hypertrophy

ROS in Neutrophil-Mediated Cell Damage

ROS in Triggering Vascular Inflammation