||Content and format
||The accession number is the unique identifier for each entry. Its format is "NX" in capital letters followed by nine digits (e.g. NX000012345).
||Contains the name of a reaction. Reaction names have different arrows indicating their type:
- -> semantic activation
- -/ semantic inhibition
- <-> semantic interaction
||The effect field contains the NetPro interaction verb. An interaction verb defines the type of relationship between two entities (molecules) A and B. Since version 1.3, the controlled vocabulary for verbs has been redefined and few changes have been incorporated in the pre-existing list to enable the data to be presented in a way more relevant to the author's discretion in the abstract.
The verbs are now classified into:
INTERACION VERBS (OR PRIMARY VERBS)
SUB-INTERACTION VERBS (OR SECONDARY VERBS)
The following table shows the (sub-)interaction verbs used in NetPro:
|Reduce (chemical reduction)|
Interaction verbs are used as stand-alone verbs except for the four verbs "Decreases, Increases, Regulates, Inhibits" which are supported by a sub-interaction verb.
Each interaction has either a Primary verb or a Primary (Decreases, Increases, Regulates, Inhibits) + Secondary verb.
The version is updated also taking into consideration the "nature of interaction" i.e Direct/Indirect: For example, though the verbs bind and associate mean the same, in the database "Bind" and "Associate" are used to bifurcate molecules that show physical interactions from those that don't show physical interaction. Bind has been used to mark a physical binding and hence nature is Direct, whereas Associate has been used to show non-physical interactions or when the interaction between two molecules is not sure, hence nature Indirect.
The reactions from NetPro are depicted as indirect if
the interaction nature is indirect. Else, if the interaction nature is
direct, then they are depicted as semantic.
Interaction nature is the nature of the link between two molecules that are related by an interaction verb. This slot defines whether the effect of one molecule on another is a direct or an indirect event.
- A physical association between two entities specifies a 'direct' interaction.
- During post transitional modification when it is known that molecule A is directly involved in the event. Example: kinases, phospatases etc.
- When abstract talks about binding event between the molecules and the same molecules are involved in another interaction. Example:
- EGF activates EGFR by direct binding.
- NFKB1 activates COX2 promoter by direct binding to NFKappaB binding site.
- P38 kinase phosphorylates ATF6 (this is a direct event).
- Casp3 cleaves Grap2 (this is a direct event).
- If cellular stimulation using one molecule affects the status of a second molecule, and if we are not sure whether there is a direct association between these two entities. Example:
- Stimulation of cells with IL6 increases expression of COX2. In this case, IL6 does not directly mediate increase in COX2 expression. (This is an indirect event).
- EGF induces phosphorylation of EGFR. Here, EGF promotes autophosphorylation of EGFR (This is an indirect event).
- TGF beta1 activates p38 kinase. Here, TGF beta1 doesn't physically interact with p38 kinase (This is an indirect event).
- Sometimes for interaction where the verbs are Interact, Complex formation, Associate or Bind, the nature of interaction is taken as 'indirect', if the abstract mentions so and if more than 2 molecules are a part of the complex/immunoprecipitate. Example:
- The transmembrane adapter LAT coprecipitates with SLP-76 and PLCgamma2, as well as with a number of other adapter proteins, some of which have not been previously described in platelets, including Cbl, Grb2, Gads, and SKAP-HOM. Interaction /association between LAT and SLP-76 is an indirect event.
This field contains different categories of annotations to the reaction:
It is the statement/s taken from the abstract that is used to curate information about the interaction.
Pathway/sub-pathway ontologies in NetPro have been developed in-house, compliant with GO ontology. The context of the abstract is used as a guideline in determining the pathway combination to which the interaction can be mapped. Generally, for an indirect interaction the pathway through which Molecule A affects Molecule B is captured, if it can be deciphered. For an interaction of direct nature it could be the pathway/process that leads to the interaction. Sometimes the biological process to which the interacting molecules contribute to, is also captured in this field.
For example: Morphogenesis:Ossification/osteogenesis The Main pathway always precedes a sub-pathway. In case a sub-pathway is not found in the CV, main pathway is taken to make data comprehensive.
Example:Modification-dependent protein catabolism:Ubiquitin-dependent protein catabolism
Multiple Pathways could be present in an interaction separated by a semicolon.
Example:Modification-dependent protein catabolism:Ubiquitin-dependent protein catabolism; Transmembrane receptor protein tyrosine kinase signaling pathway:Epidermal growth factor receptor signaling pathway; Cell differentiation:Epidermal cell differentiation
Disease entry shows disease information mined from the literature. A controlled vocabulary derived from MeSH or OMIM is used to capture disease records. In case a disease could not be mapped to any public database, the same description as used by the authors is captured.
Following fields are comprehended under Disease.
Disease conditions are associated for an interaction in 3 different categories:
- disease, disease name pertaining to the interaction. Even if one of the molecules (A or B) is involved in a disease, the name of the disease is captured in the interaction field.
- expression, A field for capturing any altered expression pattern of the molecules (A or B) in the disease condition.
- mutation, Mutation/s in Molecules A or B in the disease condition
- significance, Any other significance of the molecules (A or B) in the disease condition. For example if the molecule can be of therapeutic value, the information is captured in this field.
Positive regulator/ Negative regulator/ Regulator
Information regarding any protein/small molecule/condition/post-translational modification/ biological process that influences the interaction between the two molecules is recorded in these fields, depending on whether it is positive influence, negative influence or simply influence. Also, if, in any disease state, there is an enhancement or suppression in the specific interaction, the disease is recorded in these fields, which means that there is a quantitative effect of the interaction during the disease state. In addition, if there is a time or temperature dependent increase or decrease in the influence on molecule B, this is also recorded in these fields. Eg., Long time treatment, Low concentration.
Information regarding molecules which act as coactivators/corepressors or defined as coregulators by the authors in affecting transcriptional activity of Molecule A.
In interactions with verb as ‘bind’ or ‘associate’, information in this field refer to the domains/motifs or residues involved in the physical association of the two molecules. In other interaction records which depict influence of one molecule on the other, entries in this field correspond to region/s of Molecule A that affect Molecule B or region/s of Molecule B that gets affected.
Format of entry: Domain/motif/site/residue information followed by molecule name in brackets; Domain/motif/residue (Molecule A/B).
Contains information about the effect of the interaction, which is generally a change in a biological process.
Contains information regarding any specific property of the molecules A or B involved in the interaction, like post-translational modification/s or isoform information etc. Eg. Thr298 phosphorylated EGFR.
Entries in this field substantiates the location entry, which gives information on where the interaction takes place. The in vivo or in vitro condition under which the experiment was carried out is captured in this field.
For Eg. Streptozocin/Alloxan induced diabetes, UV treated PC12 cells, Diabetic patient.
Contains information about the interaction other than that can be filled in the above fields.
||Location positive and experiment(s)
Location comprehends the data regarding the site of occurrence of the interaction whenever given in the literature. To make this field granularized, information is filled in four fields given below.
species, Age, strain or genotype of the experimental system is also recorded in this field. Eg. Wistar rat (Young), Igf1r-/- mouse
organ, Eg. Liver, Heart
cell, Eg. Hepatocytes, PC5 cells
subcellular, Subcellular location is generally captured for translocation/secretion related interactions; prefix 'From/To’ is denoted to bring out the direction of movement. Eg. Cytoplasm to nucleus.
Experimental method is the visualization method mentioned in a study to validate an interaction. A controlled vocabulary for Experimental methods has been developed in-house which is referred to populate this field whenever data is available from literature.
||All molecules/genes which the reaction consumes, receives a signal from or is an interaction for.
||All the molecules/genes which the reaction produces or signals to.
||[consecutive entry reference number].
A list of the papers from which the information in this entry was extracted.
||Medline database hyperlink
||The PMID number in
||List of authors.
||Title of the paper.