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=Purpose of Gene Product to GO Term relations=
Gene Product to GO Term relations serve to specify how directly a gene product is related to the GO term to which it is annotated. Different relations are possible for the different GO aspects, as described below.
= Gene Product to GO Term relations =
== Molecular Function ==
* '''if a gene product is directly responsible for a reaction:'''
** [[enables]]
* '''if multiple gene products participate in a reaction:'''
** [[contributes to]]
== Biological Process ==
* '''if a gene product plays a direct role in a process:'''
** [[involved in]]
* '''if the activity of a gene product is occurs before or is required for a process:'''
**[[acts upstream of]]
**[[acts upstream of, positive effect]]
**[[acts upstream of, negative effect]]
* '''if the relation between the activity of a gene product and a process is unknown:'''
**[[acts upstream of or within]]
**[[acts upstream of or within, positive effect]]
**[[acts upstream of or within, negative effect]]
== Cellular Component ==
[[is active in]]
[[located in]]
[[part of (GP2Term)]]
[[colocalizes with]]
= GO-CAM Relations =
= GO-CAM Relations =


== Molecular Function to Biological Process  ==
GO-CAM models use contextual (e.g. occurs in) and causal (e.g. directly positively regulates) relations. For more details and specific examples of usage, click on the link to the specific relation page below.
[[part of]]
 
[[causally upstream of or within, positive effect]]
 
[[causally upstream of or within, negative effect]]
 
[[causally upstream of, positive effect]]
 
[[causally upstream of negative effect]]
 
 
== Biological Process to Molecular Function ==
 
[[causally upstream of, positive effect]]
 
[[causally upstream of negative effect]]
 
[[positively regulates]]
 
[[negatively regulates]]
 
== Molecular Function or Biological Process to Cellular Component, Cell Type, Anatomical Structure or Organism ==
 
[[Annotation Extension Relation:occurs_in | occurs_in]]
 
== Biological Process to Temporal Phase ==
 
[[happens during]]
 
== Molecular Function or Biological Process to Inputs and Outputs ==
 
[[Annotation Extension Relation:has input|has input]]
 
[[Annotation Extension Relation:has output|has output]]
 
== Biological Process to Biological Process ==
 
= Annotation Extension Relations =
*[http://wiki.geneontology.org/index.php/Annotation_usage_examples_for_each_annotation_extension_relation Annotation Extension Relations]


= Gene Product to GO term Relations =
== GO-CAM: Contextual Relations ==
The valid gp2term relations are in the Relations Ontology under the subset <code>valid_for_go_gp2term</code>.
Contextual relations are used to provide information that qualifies where, e.g. cellular components, anatomical entities, and when, e.g. biological phases, activities and processes occur.  Contextual relations can also provide information on specific targets of activities or processes, e.g. small molecules and gene products.


{| class="wikitable"
{| class="wikitable"
!colspan="2" |Gene Product-to-GO Term Relations
!Ontology Terms to Link
! Usage
! Relation
!Usage
|-
|-
|rowspan="2"|Molecular Function
|rowspan="1"|Molecular Function to Gene Product
|[[enables]]
|[[enabled by]]
|Links a gene product and the Molecular Function that a gene product executes.
|Links a Molecular Function to the gene, gene product, or protein-containing complex that executes the activity.
|-
|-
|[[contributes to]]  
|rowspan="1"|Molecular Function to Biological Process
|Links a gene product and the Molecular Function that a gene product executes as part of a complex, in which a Molecular Function cannot be ascribed to an individual subunit or a small set of subunits of a complex. Only the subunits required for the Molecular Function are annotated to the Molecular Function term,  with 'contributes to'.  
|[https://wiki.geneontology.org/Part_of_relation part of]
|Links a Molecular Function to a Biological Process when the Molecular Function is an integral part of the Biological Process.
|-
|-
|rowspan="10"|Biological Process
|rowspan="1"|Molecular Function to Anatomical Entity
|[[involved in]]
|[[occurs in]]
| Links a gene product and a Biological Process in which the gene product's Molecular Function plays an integral role.
|Links a Molecular Function to the anatomical entity, e.g. a GO cellular component or a cell or tissue type, where it occurs.
|-
|-
|[[regulates]]
|rowspan="2"|Molecular Function to Inputs and Outputs
| TO BE CONFIRMED - not in P2GO but in ShEx
|[[has input]]
|Links a Molecular Function to a specific molecular target acted upon.
|-
|-
|[[positively regulates]]
|[[has output]]
| TO BE CONFIRMED - not in P2GO but in ShEx
|Links a Molecular Function to the specific molecular output produced by the reaction or process.
|-
|-
|[[negatively regulates]]
|rowspan="1"|Molecular Function to Temporal Phase
| TO BE CONFIRMED - not in P2GO but in ShEx
|[[happens during]]
|Links a Molecular Function to a biological phase or stage, e.g. [http://amigo.geneontology.org/amigo/term/GO:0000279 M phase] or [https://ontobee.org/ontology/WBls?iri=http://purl.obolibrary.org/obo/WBls_0000106 L1 larval stage] ''when'' it occurs.
|-
|-
|[[acts upstream of or within]]
|rowspan="1"|Biological Process to Biological Process
| Links a gene product and a Biological Process for which the evidence is not sufficient to determine the mechanism relating the gene product's activity to a biological process. This is the most general gp2term relation for Biological Process.
|[[part of]]
|Links a Biological Process to another Biological Process, e.g. MAPK cascade part of a receptor signaling pathway or a receptor signaling pathway part of a development process, of which it is an integral part.
|-
|-
|[[acts upstream of or within, positive effect]]
|rowspan="1"|Biological Process to Anatomical Entity
| Links a gene product and a Biological Process for which the evidence is not sufficient to determine the mechanism relating the gene product's activity to a biological process, but it has been shown that the activity of the gene product has a positive effect on the process.
|[[occurs in]]
|Links a Biological Process to the anatomical entity, e.g. a GO cellular component or a cell or tissue type, where it occurs.
|-
|-
|[[acts upstream of or within, negative effect]]
|rowspan="2"|Biological Process to Inputs and Outputs
| Links a gene product and a Biological Process for which the evidence is not sufficient to determine the mechanism relating the gene product's activity to a biological process, but it has been shown that the activity of the gene product has a negative effect on the process.
|[[has input]]
|Links a Biological Process to a specific molecular target acted upon.
|-
|-
|[[acts upstream of]]
|[[has output]]
| Links a gene product and a Biological Process for which the evidence is sufficient to determine the mechanism relating a gene product's activity to a biological process and that activity occurs ''before'' that biological process, is not an integral part of the process, nor does it regulate the process.  
|Links a Biological Process to the specific molecular output produced by the reaction or process.
|-
|-
|[[acts upstream of, positive effect]]
|rowspan="1"|Biological Process to Temporal Phase
| Links a gene product and a Biological Process for which the evidence is sufficient to determine the mechanism relating a gene product's activity to a biological process and that activity occurs ''before'' that biological process, is not an integral part of the process, nor does it regulate the process, and is required for the process to occur.  
|[[happens during]]
|Links a Biological Process to a biological phase or stage, e.g. [http://amigo.geneontology.org/amigo/term/GO:0000279 M phase] or [https://ontobee.org/ontology/WBls?iri=http://purl.obolibrary.org/obo/WBls_0000106 L1 larval stage] ''when'' it occurs.
|-
|-
|[[acts upstream of, negative effect]]
|rowspan="1"|Anatomical Entity to Anatomical Entity
| Links a gene product and a Biological Process for which the evidence is sufficient to determine the mechanism relating a gene product's activity to a biological process and that activity occurs ''before'' that biological process, is not an integral part of the process, nor does it regulate the process, and prevents the process from occuring.  
|[https://wiki.geneontology.org/Part_of_relation part of]
|Links anatomical entities to one another to refine the location of the entity, e.g. a [http://amigo.geneontology.org/amigo/term/GO:0005634 nucleus] may be part of an [https://ontobee.org/ontology/UBERON?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FCL_0002563 intestinal epithelial cell].  
|-
|-
|rowspan="4"|Cellular Component
|rowspan="1"|Protein Containing Complex to Gene Product
|[[is active in]]
|has part
|Links a gene product and the cellular component in which it is active. Note that this excludes 'protein-containing complex' (GO:0032991) and children; those are linked using 'part of'.
|Links protein containing complexes to the genes or gene products that are members of that complex.  
|-
|-
|[[part of]]
|For protein complex members, links a gene product and the protein-containing complex (GO:0032991 and children). Non-members should be annotated to 'protein-containing complex binding (GO:0044877)' or a child.
|-
|[[located in]]
|Links a gene product and the cellular component in which a gene product has been detected. If there is data about the localization of the activity, this should be captured using 'is active in'. Note that this excludes 'protein-containing complex' (GO:0032991) and children; those are linked using 'part of'.
|-
|[[colocalizes with]]
|Being deprecated. Was used for transient or dynamic localizations.
|}
|}


= Relations Tables - GO-CAM (work in progress) =
== GO-CAM: Causal Relations ==
 
Causal relations are used to link activities to one another, and small molecules to activities, to indicate how an upstream activity or small molecule affects execution of a downstream activity. Curators should strive to use causal relations that indicate the mechanism by which activities influence one another; if the mechanism is not known, a 'causally upstream of' relation may be used until a more informative causal relation can be included in the model.
 
<span style="color:red">In Google doc for now: https://docs.google.com/spreadsheets/d/1vkBVTyUg1tjipUtYGan5Ob0vE14H_j6O-PuTH9619eg/edit#gid=0</span>
 


{| class="wikitable"
{| class="wikitable"
!colspan="9"| Molecular Function
!Ontology Pair
! Relation
!Usage
|-
|rowspan="9"|Molecular Function to Molecular Function
|[[causally upstream of, negative effect]]
|Links two activities when the upstream activity has a negative causal effect (decreasing or inhibiting) on the downstream activity but the mechanism is not known.
|-
|[[causally upstream of, positive effect]]
|Links two activities when the upstream activity has a positive causal effect (increasing or activating) on the downstream activity but the mechanism is not known.
|-
|[[provides input for]] 
|Links two successive activities when the product (output) of the upstream activity is the substrate (input) for the downstream activity, and the product is a macromolecule (i.e. DNA, RNA, protein).
|-
|[[removes input for]]
|Links two activities when the upstream activity has a negative causal effect (decreasing or inhibiting) on the downstream activity and the two activities act on or modify the same molecular target at the same site(s).
|-
|-
!rowspan="2"| Link
|[[constitutively upstream of]]
!rowspan="2"| Curation Statement
|Links two activities when the upstream activity is required for the downstream activity, but does not regulate the downstream activity.
!rowspan="2"| Allowed values (range)
!colspan="2"| GO-CAM
!colspan="4"| GPAD Output
|-
|-
!rowspan="1"| GO-CAM relation
|[[directly negatively regulates]]
!rowspan="1"| GO-CAM statement
|Links two activities when the upstream activity has a negative causal effect (decreasing or inhibiting) on an immediately downstream activity. Immediately means there is no intervening activity. The mechanism by which the upstream activity controls the downstream activity must be known.
!rowspan="1"| GPAD relation (gene product-to-term)
!rowspan="1"| GPAD example (gene product-to-term)
!rowspan="1"| GPAD annotation extension relation (see note below)
!rowspan="1"| GPAD example (annotation extension)  
|-
|-
|'''MF''' to '''Annotated Entity'''
|[[directly positively regulates]]
|The molecular activity described by the GO MF is ''[[enabled by]]'' the annotated entity.
|Links two activities when the upstream activity has a positive causal effect (increasing or activating) on an immediately downstream activity. Immediately means there is no intervening activity. The mechanism by which the upstream activity controls the downstream activity must be known.
| genes, gene products, protein-containing complexes
|[[enabled by]]
|protein kinase activity ''[[enabled by]]'' PLK1
|[[enables]]
| PLK1 ''[[enables]]'' protein kinase activity
|n/a
|n/a
|-
|-
| '''MF''' to '''Location'''
|[[indirectly negatively regulates]]
|The molecular activity described by the GO MF  ''[[Annotation Extension Relation:occurs_in | occurs_in]]'' a physical location.
|Links two activities when the upstream activity has a negative regulatory effect (decreasing or inhibiting) on the downstream activity via a larger process (e.g. proteasome-mediated protein degradation) that is reused in many contexts and the curator does not want to reproduce that process in the GO-CAM. The mechanism by which the upstream activity controls the downstream activity must be known.
| GO cellular component, cells, higher anatomical structures (e.g. tissues), organisms
|[[Annotation Extension Relation:occurs_in | occurs_in]]
|protein kinase activity ''[[enabled by]]'' PLK1 ''[[Annotation Extension Relation:occurs_in | occurs_in]]'' cytosol
|[[part of]]
| PLK1 ''[[part of]]'' cytosol
| [[Annotation Extension Relation:occurs_in | occurs_in]]
|PLK1 ''[[enables]]'' protein kinase activity  
AE: ''[[Annotation Extension Relation:occurs_in | occurs_in]]'' cytosol
|-
|-
|'''MF''' to '''Input'''
|[[indirectly positively regulates]]
|The molecular activity described by the GO MF ''[[has input]]'' one or more entities whose state is changed (bound, transported, modified, consumed, or destroyed) by the activity.
|Links two activities when the upstream activity has a positive regulatory effect (increasing or activating) on the downstream activity via a larger process (e.g. transcription) that is reused in many contexts and the curator does not want to reproduce that process in the GO-CAM. The mechanism by which the upstream activity controls the downstream activity must be known.
| genes, gene products, protein-containing complexes, chemicals
|[[has input]]
|protein kinase activity ''[[enabled by]]'' PLK1 ''[[has input]]'' KAT7
|[[enables]]
| PLK1 ''[[enables]]'' protein kinase activity
|[[has input]]
|''[[has input]]'' KAT7
|-
|-
|'''MF''' to '''Output'''
|rowspan="2"| Molecular Function to Small Molecule
|The molecular activity described by the GO MF ''[[has output]]'' one or more entities whose state was changed (bound, transported, modified, consumed, or destroyed) by the activity.
|[[Has small molecular activator |has small molecular activator]]
| genes, gene products, protein-containing complexes, chemicals
| Links a small molecule (ChEBI) to a Molecular Function or Biological Process the small molecule activates.  
|[[has output]]
|protein kinase activity ''[[enabled by]]'' PLK1 ''[[has output]]'' phosphorylated KAT7
|[[enables]]
| PLK1 ''[[enables]]'' protein kinase activity
|[[has output]]
|''[[has output]]'' phosphorylated KAT7
|-
|-
|'''MF''' to '''Temporal Phase'''
|[[Has small molecular inhibitor |has small molecular inhibitor]]
|The molecular activity described by the GO MF ''[[happens during]]'' a specific temporal or developmental stage.
| Links a small molecule (ChEBI) to a Molecular Function or Biological Process small molecule inhibits.  
| biological phases (e.g. cell cycle phases), developmental stages (e.g. larval stage)
|[[happens during]]
|protein kinase activity ''[[enabled by]]'' PLK1 ''[[happens during]]'' S phase
|[[enables]]
| PLK1 ''[[enables]]'' protein kinase activity
|[[happens during]]
|''[[happens during]]'' S phase
|-
|-
|'''MF''' providing an input for another '''MF'''
|rowspan="2"| Small Molecule to Molecular Function
|The molecular activity described by an upstream GO MF that ''[[directly provides input for]]'' for a downstream MF. The two activities act consecutively.  The intended use is to connect catalytic activities that are part of a metabolic pathway.
|[[is small molecule activator of]]
|GO molecular function
|Links a small molecule and an activity, when the small molecule activates the activity.
|[[directly provides input for]]
|6-phosphofructokinase activity ''[[enabled by]]'' PFK
''[[directly provides input for]]'' fructose bisphosphate aldolase activity
''[[enabled by]]'' ALDOA
|''[[enables]]''
|PFK ''[[enables]]'' 6-phosphofructose kinase activity
|''[[directly provides input for]]''
|''[[directly provides input for]]'' fructose bisphosphate aldolase activity
|-
|-
|'''MF''' part of a '''BP'''
|[[is small molecule inhibitor of]]
|The molecular activity enabled by a gene product is an integral ''[[part of]]'' the BP. 
|Links a small molecule and an activity, when the small molecule inhibits the activity.
|GO molecular function
|[[part of]]
|6-phosphofructokinase activity ''[[enabled by]]'' PFK ''[[part of]]'' glycolytic process through fructose-6-phosphate
|''[[involved in]]''
|PFK ''[[involved in]]'' glycolytic process through fructose-6-phosphate
|
|
|-
|-
|}
|}


*<span style="color:red">Annotation Extensions are only output in the GPAD file if the evidence for the primary annotation and the annotation extension is the same.</span>
= Standard Annotation Relations =
Standard GO annotations link gene products to GO terms.  A different set of RO relations, sometimes referred to as 'gp2term' relations, is used for standard annotations.  Standard GO annotation relations may be: 1) asserted manually, 2) asserted as part of a computational annotation pipeline, or 3) derived from a GO-CAM model.  Standard annotation relations are included in the GAF and GPAD annotation file formats.
 
== Standard Annotation: Gene Product to Term (gp2term) Relations ==
For each GO aspect there exists a default (i.e. least specific) gp2term relation that can be correctly [https://github.com/geneontology/go-site/blob/master/metadata/rules/gorule-0000061.md applied] to standard annotations if no gp2term relation is asserted. The default relation for each aspect is indicated below in '''bold'''.


{| class="wikitable"
{| class="wikitable"
!colspan="4"| Biological Process
!GO Aspect
!Gene Product-to-GO Term Relation
!Usage
|-
|rowspan="2"|Molecular Function
|'''[[enables]]'''
|Links a gene product to a Molecular Function it executes.
|-
|-
!Linked entities
|[[contributes to]]
!Usage
|Links a gene product to a Molecular Function executed by a macromolecular complex, in which the Molecular Function cannot be ascribed to an individual subunit of that complex. Only the complex subunits required for the Molecular Function are annotated to the Molecular Function term with 'contributes to'.
!Types of objects (range)
|-
!GO-CAM / GP2Term relation in GPAD output
|rowspan="7"|Biological Process
|[[involved in]]
|Links a gene product and a Biological Process in which the gene product's Molecular Function plays an integral role, i.e. is 'part of' the process.
|-
|-
|'''BP''' to '''Gene Product'''
|'''[[acts upstream of or within | <span style="color:grey">acts upstream of or within</span>]]'''
|Indicate that a gene product's activity (MF) plays an inherent role in some Biological Process.  
|<span style="color:grey">Links a gene product and a Biological Process when the mechanism relating the gene product's activity to the Biological Process is not known. This is the most general gene product to GO term relation for Biological Process.  ''Curators should always strive to use one of the more specific child relations that capture the directionality of the effect, either positive or negative. /span>''
|ChEBI information biomacromolecule (genes and gene products)
|[[part of]] <span style="color:red">was missing from other table</span>
|-
|-
|'''BP''' to '''Gene Product'''
|[[acts upstream of or within, positive effect]]
|Indicate that a gene product's activity (MF) directly regulates the rate or occurrence of some Biological Process.  
|Links a gene product and a Biological Process when the mechanism relating the gene product's activity to the Biological Process is not known, but the activity of the gene product has a positive effect on the process.
|ChEBI information biomacromolecule  (genes and gene products)
|[[regulates]] <span style="color:red">was missing from other table</span>
|-
|-
!colspan="4"| Legacy Biological Process  
|[[acts upstream of or within, negative effect]]
|Links a gene product and a Biological Process when the mechanism relating the gene product's activity to the Biological Process is not known, but the activity of the gene product has a negative effect on the process.
|-
|-
!colspan="4"| Relations to capture annotations derived from weak evidence. We aim to replace these annotations as more knowledge is accumulated.
|[[acts upstream of | <span style="color:grey">acts upstream of </span>]]
|<span style="color:grey">Links a gene product and a Biological Process when the mechanism relating a gene product's activity to a Biological Process is known and the activity occurs before the Biological Process but does not regulate it. ''Curators should always strive to use one of the more specific child relations that capture the directionality of the effect, either positive or negative. </span>''
|-
|-
|'''BP''' to '''Gene Product'''
|[[acts upstream of, positive effect]]
|Indicate that the mechanism relating a gene product's activity to a biological process is unknown, and the gene product's activity has an unknown effect on the process.
|Links a gene product and a Biological Process when the mechanism relating a gene product's activity to a Biological Process is known and the activity occurs before the Biological Process, is required for the process to occur, but does not regulate it.  
|ChEBI information biomacromolecule  (genes and gene products)
|[[acts upstream of or within]]
|-
|-
|'''BP''' to '''Gene Product'''
|[[acts upstream of, negative effect]]
|Indicate that the mechanism relating a gene product's activity to a biological process is unknown, but the gene product's activity has a positive or activating effect on the process.
|Links a gene product and a Biological Process when the mechanism relating a gene product's activity to a Biological Process is known and the activity occurs before the Biological Process, prevents or reduces the process, but does not regulate the process.  
|ChEBI information biomacromolecule  (genes and gene products)
|[[acts upstream of or within, positive effect]]
|-
|-
|'''BP''' to '''Gene Product'''
|rowspan="4"|Cellular Component
|Indicate that the mechanism relating a gene product's activity to a biological process is unknown, but the gene product's activity has a negative or inhibitory effect on the process.
|[[is active in]]
|ChEBI information biomacromolecule  (genes and gene products)
|Links a gene product and a Cellular Component, specifically a [http://amigo.geneontology.org/amigo/term/GO:0110165 cellular anatomical anatomy] or [http://amigo.geneontology.org/amigo/term/GO:0044423 virion component], in which it enables its Molecular Function. Note that 'located in' is not used for relating gene products to a [http://amigo.geneontology.org/amigo/term/GO:0032991 protein-containing complex]; those associations use 'part of'.
|[[acts upstream of or within, negative effect]]
|-
|-
|'''BP''' to '''Gene Product'''
|'''[[located in]]'''
|Indicate that the experimental evidence is sufficient to determine the mechanism relating a gene product's activity (MF) to a biological process and that activity occurs before that biological process, is not an integral part of the process, nor does it regulate the process.
|Links a gene product and the Cellular Component, specifically a [http://amigo.geneontology.org/amigo/term/GO:0110165 cellular anatomical anatomy] or [http://amigo.geneontology.org/amigo/term/GO:0044423 virion component], in which a gene product has been detectedNote that 'is active in' is not used for relating gene products to a [http://amigo.geneontology.org/amigo/term/GO:0032991 protein-containing complex]; those associations use 'part of'.
| ChEBI information biomacromolecule (genes and gene products)
|[[acts upstream of]]
|-
|-
|'''BP''' to '''Gene Product'''
|'''[https://wiki.geneontology.org/Part_of_relation#Relating_Gene_Products_to_Protein-containing_Complexes part of]'''
|Indicate that a gene product's activity (MF) is: 1) executed before the beginning of the process, 2) is not part of the process, and 3) is required for the process to occur.  
|Links a gene product and a [http://amigo.geneontology.org/amigo/term/GO:0032991 protein-containing complex].
|ChEBI information biomacromolecule  (genes and gene products)
|[[acts upstream of, positive effect]]  
|-
|-
| '''BP''' to '''Gene Product'''
|[[colocalizes with]]
| Indicate that a gene product's activity (MF) is: 1) executed before the beginning of the process, 2) is not part of the process, and 3) does not directly negatively regulate the process.
|Being deprecated. Was used for transient or dynamic localizations.
| ChEBI information biomacromolecule  (genes and gene products)
|[[acts upstream of, negative effect]]  
|}
|}
== Standard Annotation: Annotation Extension Relations ==
* Annotation extensions provide context for standard annotations to MF, BP, and CC terms.
* Note that currently this table only lists MF to BP annotation extension relations; additional annotation extension relations will be added soon
Molecular Function to Biological Process relations can also be used in standard annotations to relate activities to processes using one of the relations below.


{| class="wikitable"
{| class="wikitable"
!colspan="4"| Cellular component
!Ontology Pair
!Allowed Relation
!Usage
|-
|rowspan="8"|Molecular Function to Biological Process
|[https://wiki.geneontology.org/Part_of_relation part of]
|Links a Molecular Function to a Biological Process when the Molecular Function is an integral part of the Biological Process.
|-
|[[causally upstream of or within |<span style="color:grey">causally upstream of or within</span>]]
|<span style="color:grey">Links an activity and a Biological Process when the mechanism relating the activity to the Biological Process is not known. This is the most general Molecular Function to Biological Process relations.  ''Although this relation is used in the MOD imports into Noctua for new annotation, curators should always strive to use one of the more specific child relations that capture the directionality of the effect, either positive or negative.''</span>
|-
|[[causally upstream of or within, negative effect]]
|Links an activity and a Biological Process when the mechanism relating the activity to the Biological Process is not known, but the activity has a positive effect on the process.
|-
|-
!colspan="1" | GO-CAM relations
|[[causally upstream of or within, positive effect]]
!colspan="1" | Usage
|Links an activity and a Biological Process when the mechanism relating the activity to the Biological Process is not known, but the activity has a negative effect on the process.
!colspan="1" | Example
!colspan="1" | Corresponding Gene Product to GO Term relation in GPAD output
|-
|-
|[[is active in]]
|[[causally upstream of |<span style="color:grey">causally upstream of</span>]]
|The Cellular Component in which the gene or gene product enables its Molecular Function.
|<span style="color:grey">Links an activity and a Biological Process when the mechanism relating the activity to the Biological Process is known and the activity occurs before the Biological Process, but does not regulate it. ''Curators should always strive to use one of the more specific child relations that capture the directionality of the effect, either positive or negative.''</span>
|PLK1 ''is active'' in nucleus
|-
|[[is active in]]
|[[causally upstream of, negative effect]]
|Links an activity and a Biological Process when the mechanism relating an activity to a Biological Process is known and the activity occurs before the Biological Process, reduces or prevents the process from occurring, but does not regulate it.
|-
|-
|[[part of]]
|[[causally upstream of, positive effect]]
|(a) Relates a cellular component to some cellular component, cell or anatomical structure that it is part of. (b) It may also be used to relate a molecular function or biological process to a biological process or developmental stage of which it is a part.
|Links an activity and a Biological Process when the mechanism relating an activity to a Biological Process is known and the activity occurs before the Biological Process, is required for the process to occur, but does not regulate it.
|Represented as an AE: TLR4 ''[[is active]]'' perinuclear region of cytoplasm ''[[part of]]'' CL:0000451 (dendritic cell)
|Annotation Extension:[[part of]]
|-
|-
|[[located in]]
|[[happens during]]
|Gene product detected in a cellular location, but not shown to be active there.
|Links an activity and a biological phase, such as a cell cycle phase or a developmental stage, when the activity is executed during that phase.
|PLK1 ''[[located in]]'' in nucleus
|[[located in]]
|-
|-
|[[colocalizes with]]
| Represents transient or peripheral associations. 
|PLK1 ''[[colocalizes with]]'' in nucleus
|[[colocalizes with]]
|}
|}


==[[Deprecated relations]]== 
= Review Status =
Last reviewed: September 5th, 2023


== Link to RO documentation==
Reviewed by: Pascale Gaudet, Kimberly Van Auken
https://github.com/oborel/obo-relations/wiki/ROGuide#interaction-relations


[[Category: Relations]]
[[Category: Relations]]

Latest revision as of 08:59, 13 March 2024

GO-CAM Relations

GO-CAM models use contextual (e.g. occurs in) and causal (e.g. directly positively regulates) relations. For more details and specific examples of usage, click on the link to the specific relation page below.

GO-CAM: Contextual Relations

Contextual relations are used to provide information that qualifies where, e.g. cellular components, anatomical entities, and when, e.g. biological phases, activities and processes occur. Contextual relations can also provide information on specific targets of activities or processes, e.g. small molecules and gene products.

Ontology Terms to Link Relation Usage
Molecular Function to Gene Product enabled by Links a Molecular Function to the gene, gene product, or protein-containing complex that executes the activity.
Molecular Function to Biological Process part of Links a Molecular Function to a Biological Process when the Molecular Function is an integral part of the Biological Process.
Molecular Function to Anatomical Entity occurs in Links a Molecular Function to the anatomical entity, e.g. a GO cellular component or a cell or tissue type, where it occurs.
Molecular Function to Inputs and Outputs has input Links a Molecular Function to a specific molecular target acted upon.
has output Links a Molecular Function to the specific molecular output produced by the reaction or process.
Molecular Function to Temporal Phase happens during Links a Molecular Function to a biological phase or stage, e.g. M phase or L1 larval stage when it occurs.
Biological Process to Biological Process part of Links a Biological Process to another Biological Process, e.g. MAPK cascade part of a receptor signaling pathway or a receptor signaling pathway part of a development process, of which it is an integral part.
Biological Process to Anatomical Entity occurs in Links a Biological Process to the anatomical entity, e.g. a GO cellular component or a cell or tissue type, where it occurs.
Biological Process to Inputs and Outputs has input Links a Biological Process to a specific molecular target acted upon.
has output Links a Biological Process to the specific molecular output produced by the reaction or process.
Biological Process to Temporal Phase happens during Links a Biological Process to a biological phase or stage, e.g. M phase or L1 larval stage when it occurs.
Anatomical Entity to Anatomical Entity part of Links anatomical entities to one another to refine the location of the entity, e.g. a nucleus may be part of an intestinal epithelial cell.
Protein Containing Complex to Gene Product has part Links protein containing complexes to the genes or gene products that are members of that complex.

GO-CAM: Causal Relations

Causal relations are used to link activities to one another, and small molecules to activities, to indicate how an upstream activity or small molecule affects execution of a downstream activity. Curators should strive to use causal relations that indicate the mechanism by which activities influence one another; if the mechanism is not known, a 'causally upstream of' relation may be used until a more informative causal relation can be included in the model.

Ontology Pair Relation Usage
Molecular Function to Molecular Function causally upstream of, negative effect Links two activities when the upstream activity has a negative causal effect (decreasing or inhibiting) on the downstream activity but the mechanism is not known.
causally upstream of, positive effect Links two activities when the upstream activity has a positive causal effect (increasing or activating) on the downstream activity but the mechanism is not known.
provides input for Links two successive activities when the product (output) of the upstream activity is the substrate (input) for the downstream activity, and the product is a macromolecule (i.e. DNA, RNA, protein).
removes input for Links two activities when the upstream activity has a negative causal effect (decreasing or inhibiting) on the downstream activity and the two activities act on or modify the same molecular target at the same site(s).
constitutively upstream of Links two activities when the upstream activity is required for the downstream activity, but does not regulate the downstream activity.
directly negatively regulates Links two activities when the upstream activity has a negative causal effect (decreasing or inhibiting) on an immediately downstream activity. Immediately means there is no intervening activity. The mechanism by which the upstream activity controls the downstream activity must be known.
directly positively regulates Links two activities when the upstream activity has a positive causal effect (increasing or activating) on an immediately downstream activity. Immediately means there is no intervening activity. The mechanism by which the upstream activity controls the downstream activity must be known.
indirectly negatively regulates Links two activities when the upstream activity has a negative regulatory effect (decreasing or inhibiting) on the downstream activity via a larger process (e.g. proteasome-mediated protein degradation) that is reused in many contexts and the curator does not want to reproduce that process in the GO-CAM. The mechanism by which the upstream activity controls the downstream activity must be known.
indirectly positively regulates Links two activities when the upstream activity has a positive regulatory effect (increasing or activating) on the downstream activity via a larger process (e.g. transcription) that is reused in many contexts and the curator does not want to reproduce that process in the GO-CAM. The mechanism by which the upstream activity controls the downstream activity must be known.
Molecular Function to Small Molecule has small molecular activator  Links a small molecule (ChEBI) to a Molecular Function or Biological Process the small molecule activates.
has small molecular inhibitor  Links a small molecule (ChEBI) to a Molecular Function or Biological Process small molecule inhibits.
Small Molecule to Molecular Function is small molecule activator of Links a small molecule and an activity, when the small molecule activates the activity.
is small molecule inhibitor of Links a small molecule and an activity, when the small molecule inhibits the activity.

Standard Annotation Relations

Standard GO annotations link gene products to GO terms. A different set of RO relations, sometimes referred to as 'gp2term' relations, is used for standard annotations. Standard GO annotation relations may be: 1) asserted manually, 2) asserted as part of a computational annotation pipeline, or 3) derived from a GO-CAM model. Standard annotation relations are included in the GAF and GPAD annotation file formats.

Standard Annotation: Gene Product to Term (gp2term) Relations

For each GO aspect there exists a default (i.e. least specific) gp2term relation that can be correctly applied to standard annotations if no gp2term relation is asserted. The default relation for each aspect is indicated below in bold.

GO Aspect Gene Product-to-GO Term Relation Usage
Molecular Function enables Links a gene product to a Molecular Function it executes.
contributes to Links a gene product to a Molecular Function executed by a macromolecular complex, in which the Molecular Function cannot be ascribed to an individual subunit of that complex. Only the complex subunits required for the Molecular Function are annotated to the Molecular Function term with 'contributes to'.
Biological Process involved in Links a gene product and a Biological Process in which the gene product's Molecular Function plays an integral role, i.e. is 'part of' the process.
acts upstream of or within Links a gene product and a Biological Process when the mechanism relating the gene product's activity to the Biological Process is not known. This is the most general gene product to GO term relation for Biological Process. Curators should always strive to use one of the more specific child relations that capture the directionality of the effect, either positive or negative. /span>
acts upstream of or within, positive effect Links a gene product and a Biological Process when the mechanism relating the gene product's activity to the Biological Process is not known, but the activity of the gene product has a positive effect on the process.
acts upstream of or within, negative effect Links a gene product and a Biological Process when the mechanism relating the gene product's activity to the Biological Process is not known, but the activity of the gene product has a negative effect on the process.
acts upstream of Links a gene product and a Biological Process when the mechanism relating a gene product's activity to a Biological Process is known and the activity occurs before the Biological Process but does not regulate it. Curators should always strive to use one of the more specific child relations that capture the directionality of the effect, either positive or negative.
acts upstream of, positive effect Links a gene product and a Biological Process when the mechanism relating a gene product's activity to a Biological Process is known and the activity occurs before the Biological Process, is required for the process to occur, but does not regulate it.
acts upstream of, negative effect Links a gene product and a Biological Process when the mechanism relating a gene product's activity to a Biological Process is known and the activity occurs before the Biological Process, prevents or reduces the process, but does not regulate the process.
Cellular Component is active in Links a gene product and a Cellular Component, specifically a cellular anatomical anatomy or virion component, in which it enables its Molecular Function. Note that 'located in' is not used for relating gene products to a protein-containing complex; those associations use 'part of'.
located in Links a gene product and the Cellular Component, specifically a cellular anatomical anatomy or virion component, in which a gene product has been detected. Note that 'is active in' is not used for relating gene products to a protein-containing complex; those associations use 'part of'.
part of Links a gene product and a protein-containing complex.
colocalizes with Being deprecated. Was used for transient or dynamic localizations.

Standard Annotation: Annotation Extension Relations

  • Annotation extensions provide context for standard annotations to MF, BP, and CC terms.
  • Note that currently this table only lists MF to BP annotation extension relations; additional annotation extension relations will be added soon

Molecular Function to Biological Process relations can also be used in standard annotations to relate activities to processes using one of the relations below.

Ontology Pair Allowed Relation Usage
Molecular Function to Biological Process part of Links a Molecular Function to a Biological Process when the Molecular Function is an integral part of the Biological Process.
causally upstream of or within Links an activity and a Biological Process when the mechanism relating the activity to the Biological Process is not known. This is the most general Molecular Function to Biological Process relations. Although this relation is used in the MOD imports into Noctua for new annotation, curators should always strive to use one of the more specific child relations that capture the directionality of the effect, either positive or negative.
causally upstream of or within, negative effect Links an activity and a Biological Process when the mechanism relating the activity to the Biological Process is not known, but the activity has a positive effect on the process.
causally upstream of or within, positive effect Links an activity and a Biological Process when the mechanism relating the activity to the Biological Process is not known, but the activity has a negative effect on the process.
causally upstream of Links an activity and a Biological Process when the mechanism relating the activity to the Biological Process is known and the activity occurs before the Biological Process, but does not regulate it. Curators should always strive to use one of the more specific child relations that capture the directionality of the effect, either positive or negative.
causally upstream of, negative effect Links an activity and a Biological Process when the mechanism relating an activity to a Biological Process is known and the activity occurs before the Biological Process, reduces or prevents the process from occurring, but does not regulate it.
causally upstream of, positive effect Links an activity and a Biological Process when the mechanism relating an activity to a Biological Process is known and the activity occurs before the Biological Process, is required for the process to occur, but does not regulate it.
happens during Links an activity and a biological phase, such as a cell cycle phase or a developmental stage, when the activity is executed during that phase.

Review Status

Last reviewed: September 5th, 2023

Reviewed by: Pascale Gaudet, Kimberly Van Auken