Annotation Extension Relation:has input

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Definition

Identifies an entity affected (bound, transported, modified, consumed or destroyed) by the gene product's participation in a molecular function or biological process.

Comment

More details on the limited use of has_input with biological process annotations

If you know that the target is bound by the annotated gene product then consider using this child relationship

For Molecular Function GO terms such as endopeptidase activity use the relationship 'has_direct_input' substrate (possibly has_substrate if this relationship is made available). The substrate included in the annotation extension should be known to bind the protein annotated.

The endopeptidase, in the example above, would also have the Biological Process GO term annotation (eg proteolysis with the annotation extension relationship 'has_input' substrate.

For Molecular Function GO terms such as endopeptidase inhibitor activity use the relationship 'has_direct_input' endopeptidase, the protein included in the annotation extension should be known to bind the annotated inhibitor.


If the annotation associated with the gene product is a regulation of Biological Process then consider using the child relationship

eg: negative regulation of proteolysis with the annotation extension relationship 'has_regulation_target' target of proteolysis, with the substrate of the endopeptidase that is regulated by the inhibitor included in the annotation extension field


If the annotation associated with the gene product is a regulation of Molecular Function (eg if the gene product is an enzyme regulator) then consider using the child relationship

eg: negative regulation of endopeptidase activity, with the annotation relationship 'has_input' endopeptidase, the endopeptidase that is inhibited by (in this case) the endopeptidase inhibitor is included in the annotation extension field

Therefore the endopeptidase inhibitor would have two Biological Process GO term annotations and one Molecular Function annotation eg:

Folded/unfolded Gene Name (col 2) GO ID (col 5) Reference (col 6) Evidence (col 7) Annotation Extension (col 16) Parent terms of new folded GO term
Unfolded Endopeptidase A GO:0004175 endopeptidase activity PMID:1234567 IDA has_direct_input(substrate of endopeptidase A)
Folded Endopeptidase A GO:0004175 endopeptidase activity PMID:1234567 IDA No new GO term created

Synonyms

has_target (EXACT)

localizes (NARROW)

Child terms

If you know that the target is bound by the annotated gene product then consider using this child relationship

Scope of use

Domain

BFO:0000007 ! process (Biological Process or Molecular Function)

Range

ENTITY_UNION:0000005 ! chemical, gene product, or complex


Annotation Extension Usage Examples

Enhancing Molecular Function and Biological Process Annotations

Specifying the chemical that was applied and induced a 'response to chemicals'

GOC policy is not to use the annotation extension field to capture the input to the process (eg a chemical/protein), instead new GO terms are requested (using Term Genie).


Cellular response to drug

Statement from paper: incubation of cells with low concentrations of phenformin and depletion of Ppm1E increased AMPK phosphorylation

So one of the annotations would be:


DB (Col 2) Object (Col 3) GO ID (Col 5) Reference (Col 6) Evidence (Col 7) Extension (Col 16)
Q8WY54 PPM1E GO:0035690 cellular response to drug PMID:20801214 IDA has_input(CHEBI:6801 metformin)

Specifying the protein which is a target of a Biological Process

Proteolysis targets

Statement from paper: MICA shedding by tumor cells was inhibited by silencing of the related ADAM10 and ADAM17 proteases.

No direct binding of MICA to ADAM10 and ADAM17 was shown therefore the relationship 'has_direct_input' was not applied.

So one of the annotations would be:

DB (Col 2) Object (Col 3) GO ID (Col 5) Reference (Col 6) Evidence (Col 7) Extension (Col 16)
O14672 ADAM10 GO:0006509 membrane protein ectodomain proteolysis PMID:18676862 IMP has_input(UNIPROT:Q29983 MICA)

Using examples (from above) to demonstrate Folding_and_Unfolding using the relationship has_input

Specifying the protein which is a target of a Biological Process

Proteolysis targets

Statement from paper: MICA shedding by tumor cells was inhibited by silencing of the related ADAM10 and ADAM17 proteases

Folded/unfolded Gene Name (col 2) GO ID (col 5) Reference (col 6) Evidence (col 7) Annotation Extension (col 16) Parent terms of new folded GO term
Unfolded O14672 ADAM10 GO:0006509 membrane protein ectodomain proteolysis PMID:18676862 IMP has_input(UNIPROT:Q29983 MICA)
Folded O14672 ADAM10 GO:0006509 membrane protein ectodomain proteolysis PMID:18676862 IMP No new GO term created

OWL class expression: GO:0006509 membrane protein ecodomain proteolysis AND has_input SOME UNIPROT:Q29983 MICA

No new term will be created in this example because this is outside of the scope of GO, although tools using GO could use the relationship to create the following:

Folded/unfolded Gene Name (col 2) GO ID (col 5) Reference (col 6) Evidence (col 7) Annotation Extension (col 16) Parent terms of new folded GO term
Unfolded O14672 ADAM10 GO:0006509 membrane protein ectodomain proteolysis PMID:18676862 IMP has_input(UNIPROT:Q29983 MICA)
Folded O14672 ADAM10 New GO term membrane protein ectodomain proteolysis of MICA PMID:18676862 IMP GO:0006509 membrane protein ectodomain proteolysis

OWL class expression: GO:0006509 membrane protein ecodomain proteolysis AND has_input SOME UNIPROT:Q29983 MICA

Specifying the gene which is a target of a transcription factor

gene transcription targets This example is still under discussion.

Statement example:

DNA binding transcription factor A binds the promoter of Polo2 and increases transcription of Polo2

Folded/unfolded Gene Name (col 2) GO ID (col 5) Reference (col 6) Evidence (col 7) Annotation Extension (col 16) Parent terms of new folded GO term
Unfolded Pxxx transcription factor A GO:0001228 RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription PMID:xxx IDA has_regulation_target(UNIPROT:Qxxx Polo2)
Folded Pxxx transcription factor A GO:0001228 RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription PMID:xxx IDA No new GO term created
Unfolded Pxxx transcription factor A GO:0044212 transcription regulatory region DNA binding PMID:xxx IDA has_direct_input(UNIPROT:Qxxx Polo2) (could include a feature ID to specify the specific motif eg a SO ID or Ensembl ID for the gene ID)
Folded Pxxx transcription factor A GO:0044212 transcription regulatory region DNA binding PMID:xxx IDA No new GO term created

No new term will be created in this example because this is outside of the scope of GO, although tools using GO could use the relationship to create the following:

Folded/unfolded Gene Name (col 2) GO ID (col 5) Reference (col 6) Evidence (col 7) Annotation Extension (col 16) Parent terms of new folded GO term
Unfolded Pxxx transcription factor A GO:0001228 RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription PMID:xxx IDA has_input(UNIPROT:Qxxx Polo2)
Folded Pxxx transcription factor A New GO term RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription of Polo2 PMID:xxx IDA GO:0001228 RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription



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