aurelian 0.3.2__py3-none-any.whl

aurelian/agents/gocam/documents/E3_ubiquitin_ligases.md

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+# E3 ubiquitin ligases
+
+An **E3 ubiquitin ligase** is a protein that recruits an E2 ubiquitin-conjugating enzyme loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 to the protein substrate.
+
+The recognition of the protein substrate can be done by the ubiquitin protein ligase itself or through a complex composed of ubiquitin ligase-substrate adaptor and ubiquitin ligase complex scaffolds.
+
+<https://en.wikipedia.org/wiki/Ubiquitin_ligase>
+
+# How to annotate E3 ubiquitin ligases
+
+## E3 ligase that promotes ubiquitination by itself
+
+The molecular activity unit for the ubiquitin ligase is:
+
+* **MF**: 'enables' ubiquitin protein ligase activity [GO:0061630](https://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0061630#term=history)
+* 'has input'the substrate protein
+* **BPs**:
+* 'part of' ubiquitination ([GO:0016567](https://www.ebi.ac.uk/QuickGO/term/GO%3A0070936))**:** if known, the **BP** should describe the type of ubiquitination (K-48, K-63…)
+
+ex: protein K48-linked ubiquitination [GO:0070936](https://www.ebi.ac.uk/QuickGO/term/GO%3A0070936); otherwise, use the parent protein ubiquitination GO:0016567 or protein polyubiquitination GO:0000209.
+
+* the ubiquitination is part\_of the biological process in which the ubiquitination is involved:
+
+e. g. : proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161](https://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0043161#term=history) or children, such as: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process ([GO:0031146](https://www.ebi.ac.uk/QuickGO/term/GO%3A0031146)) or ubiquitin-dependent protein catabolic process via the C-end degron rule pathway ([GO:0140627](https://www.ebi.ac.uk/QuickGO/term/GO%3A0140627))
+
+* and/or part of’ the BP in which the ubiquitination is involved: DNA repair, DNA damage response, lysosomal degradation, etc regulated by this mechanism (ex: negative regulation of inflammatory response, [GO:0050728](https://www.ebi.ac.uk/QuickGO/term/GO%3A0050728))
+* The causal relation to the substrate molecular activity unit is: ‘indirectly negatively regulates’.
+
+Example: [TRIM45-mediated degradation of TAB2 leading to inflammatory response inhibition (Human)](http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel%3A63f809ec00000307)
+
+![](data:image/png;base64...)
+
+## An E3-ligase complex with adaptors and scaffold protein(s)
+
+####
+
+* The molecular activity unit for the ubiquitin ligase complex scaffold, such as CUL4A and/or DDB1 is:
+* **MF**: ubiquitin ligase complex scaffold activity [GO:0160072](https://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0160072#term=history)
+* Has **input** both the ubiquitin ligase-substrate adaptor and the ubiquitin protein ligase
+* **BP**: if known, the **BP** should describe the type of ubiquitination (K-48, K-63…)
+
+ex: protein K48-linked ubiquitination [GO:0070936](https://www.ebi.ac.uk/QuickGO/term/GO%3A0070936)
+
+if not known, use a **BP** describing the biological process in which the ubiquitination is involved in.
+
+ex: proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161](https://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0043161#term=history) or children, such as: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process ([GO:0031146](https://www.ebi.ac.uk/QuickGO/term/GO%3A0031146)) or ubiquitin-dependent protein catabolic process via the C-end degron rule pathway ([GO:0140627](https://www.ebi.ac.uk/QuickGO/term/GO%3A0140627))
+
+‘Part of’ the BP regulated by this mechanism (ex: T cell activation, [GO:0042110](https://www.ebi.ac.uk/QuickGO/term/GO%3A0042110))
+
+* The causal relation between the substrate molecular activity unit is: ‘directly negatively regulates’ if it leads to degradation. (to decide for the other cases)
+* The causal relation to the ubiquitin ligase-substrate adaptor molecular activity unit is: ‘directly regulates’.
+* The molecular activity unit for the ubiquitin ligase-substrate adaptor is:
+* **MF**: ubiquitin ligase-substrate adaptor activity [GO:1990756](http://amigo.geneontology.org/amigo/term/GO%3A1990756)
+* Has **input** the substrate protein
+* **BP**: if known, the **BP** should describe the type of ubiquitination (K-48, K-63…)
+
+ex: protein K48-linked ubiquitination [GO:0070936](https://www.ebi.ac.uk/QuickGO/term/GO%3A0070936)
+
+if not known, use a **BP** describing the biological process in which the ubiquitination is involved in.
+
+ex: proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161](https://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0043161#term=history) or children, such as: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process ([GO:0031146](https://www.ebi.ac.uk/QuickGO/term/GO%3A0031146)) or ubiquitin-dependent protein catabolic process via the C-end degron rule pathway ([GO:0140627](https://www.ebi.ac.uk/QuickGO/term/GO%3A0140627))
+
+‘Part of’ the BP regulated by this mechanism (ex: T cell activation, [GO:0042110](https://www.ebi.ac.uk/QuickGO/term/GO%3A0042110))
+
+* The causal relation to the ubiquitin ligase molecular activity unit is: ‘directly provides input for’.
+* Annotation of the ubiquitin ligase is the same as [above](#_j8u1po26cp9w)
+
+Example: [DCAF12 controls MOV10 during T cell activation. (Human)](http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel%3A636d9ce800001192)
+
+![](data:image/png;base64...)
+
+#### When only substrate adaptor and substrate are known (scaffold and ligase not known)
+
+Example: [FBXL19-mediated degradation of IL1R1 via GSK3B (Human)](http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel%3A63d320cd00001588)![](data:image/png;base64...)
+
+* The molecular activity unit for the ubiquitin ligase-substrate adaptor is:
+* **MF**: ubiquitin ligase-substrate adaptor activity [GO:1990756](http://amigo.geneontology.org/amigo/term/GO%3A1990756)
+* Has **input** the substrate protein
+* **BP**: if known, the **BP** should describe the type of ubiquitination (K-48, K-63…)
+
+ex: protein K48-linked ubiquitination [GO:0070936](https://www.ebi.ac.uk/QuickGO/term/GO%3A0070936)
+
+if not known, use a **BP** describing the biological process in which the ubiquitination is involved in.
+
+ex: proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161](https://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0043161#term=history) or children, such as: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process ([GO:0031146](https://www.ebi.ac.uk/QuickGO/term/GO%3A0031146)) or ubiquitin-dependent protein catabolic process via the C-end degron rule pathway ([GO:0140627](https://www.ebi.ac.uk/QuickGO/term/GO%3A0140627))
+
+‘Part of’ the BP regulated by this mechanism (ex: T cell activation, [GO:0042110](https://www.ebi.ac.uk/QuickGO/term/GO%3A0042110))
+
+* The causal relation to the substrate molecular activity unit is: ‘indirectly regulates’ since we don’t add/have information about the E3 ligase.
+
+#### When only substrate adaptor, scaffold and substrate are known (ligase not known)
+
+Ex: [DCAF13 supports the spindle assembly and chromosome condensation during oocyte meiotic division by targeting PTEN polyubiquitination and degradation. (Human)](http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel%3A63c0ac2b00001634)
+
+![](data:image/png;base64...)
+
+* The molecular activity unit for the ubiquitin ligase complex scaffold, such as CUL4A and/or DDB1 is:
+* **MF**: ubiquitin ligase complex scaffold activity [GO:0160072](https://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0160072#term=history)
+* Has **input** both the ubiquitin ligase-substrate adaptor and the ubiquitin protein ligase
+* **BP**: if known, the **BP** should describe the type of ubiquitination (K-48, K-63…)
+
+ex: protein K48-linked ubiquitination [GO:0070936](https://www.ebi.ac.uk/QuickGO/term/GO%3A0070936)
+
+if not known, use a **BP** describing the biological process in which the ubiquitination is involved in.
+
+ex: proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161](https://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0043161#term=history) or children, such as: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process ([GO:0031146](https://www.ebi.ac.uk/QuickGO/term/GO%3A0031146)) or ubiquitin-dependent protein catabolic process via the C-end degron rule pathway ([GO:0140627](https://www.ebi.ac.uk/QuickGO/term/GO%3A0140627))
+
+‘Part of’ the BP regulated by this mechanism (ex: T cell activation, [GO:0042110](https://www.ebi.ac.uk/QuickGO/term/GO%3A0042110))
+
+* The causal relation to the ubiquitin ligase-substrate adaptor molecular activity unit is: ‘directly regulates’.
+* The molecular activity unit for the ubiquitin ligase-substrate adaptor is:
+* **MF**: ubiquitin ligase-substrate adaptor activity [GO:1990756](http://amigo.geneontology.org/amigo/term/GO%3A1990756)
+* Has **input** the substrate protein
+* **BP**: if known, the **BP** should describe the type of ubiquitination (K-48, K-63…)
+
+ex: protein K48-linked ubiquitination [GO:0070936](https://www.ebi.ac.uk/QuickGO/term/GO%3A0070936)
+
+if not known, use a **BP** describing the biological process in which the ubiquitination is involved in.
+
+ex: proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161](https://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0043161#term=history) or children, such as: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process ([GO:0031146](https://www.ebi.ac.uk/QuickGO/term/GO%3A0031146)) or ubiquitin-dependent protein catabolic process via the C-end degron rule pathway ([GO:0140627](https://www.ebi.ac.uk/QuickGO/term/GO%3A0140627))
+
+‘Part of’ the BP regulated by this mechanism (ex: T cell activation, [GO:0042110](https://www.ebi.ac.uk/QuickGO/term/GO%3A0042110))
+
+* The causal relation to the substrate molecular activity unit is: ‘indirectly regulates’ since we don’t add/have information about the E3 ligase.
+
+## Examples of larger processes in which various types of ubiquitination play a role
+
+![](data:image/png;base64...)
+
+Source: PMID:[27285106](https://pubmed.ncbi.nlm.nih.gov/27285106)
+
+**Review date:**
+
+**Reviewed by:**

aurelian/agents/gocam/documents/GO-CAM_annotation_guidelines_README.md

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+

aurelian/agents/gocam/documents/GO-CAM_modelling_guidelines_TO_DO.md

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+Moved here.
+
+https://docs.google.com/document/d/13MWyxdfcS78dYz9hg61R4ZS4ydp3OY8Y16LAb3xD3Ug/edit#

aurelian/agents/gocam/documents/How_to_annotate_complexes_in_GO-CAM.md

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+# How to annotate complexes in GO-CAM
+
+When complexes are involved in specific activities, several options are available in GO-CAM to represent them.
+
+1. **The subunit that carries the molecular activity is known:**
+
+In that case, the complex is not described and the activity(ies) is represented by the specific protein (s) carrying the activity.
+
+Ex:
+
+![](data:image/x-emf;base64...)
+
+In this example, all the proteins in the E3 ligase complex have a defined and precise activity. Therefore, they are all displayed in the model. In this case, the scaffold activity is usually represented first, *activating subsequent activities from the* complex.
+
+1. **The subunit which carries the molecular activity is not known:**
+
+If the precise subunit carrying the activity is not known, we can use the GO accession for the complex.
+
+Ex: Ragulator complex (GO:0071986): Ragulator is comprised of the membrane anchor subunit LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5.
+
+![A screenshot of a computer
+
+Description automatically generated](data:image/png;base64...)
+
+In this example LAMTOR1 activity is known (protein-membrane adaptor activity) but the protein that carries the guanyl-nucleotide exchange factor activity is not known, therefore we use the complex ID from GO in this situation.
+
+1. **If the activity is shared by several proteins**
+
+EX: Heterodimeric receptor where both activities are important for activity.

aurelian/agents/gocam/documents/How_to_annotate_molecular_adaptors.md

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+# How to annotate molecular adaptors
+
+Here we describe how to capture a molecular adaptor activity which is defined as the binding activity of a molecule that brings together two or more molecules through a selective, non-covalent, often stoichiometric interaction, permitting those molecules to function in a coordinated way.
+
+Example 1: [TYROBP acts as an adaptor between a receptor and a downstream effector](http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel%3A633b013300001197)
+
+![A screenshot of a computer
+
+Description automatically generated with medium confidence](data:image/png;base64...)
+
+The molecular activity unit for molecular adaptor may include:
+
+o **MF**: molecular adaptor activity ([GO:0060090](https://www.ebi.ac.uk/QuickGO/term/GO%3A0060090)) or one of its children
+
+o **Has input** the two (or more) molecules it brings together.
+
+o **BP**: the BP it participates in
+
+o **CC**: the place where the activity occurs.
+
+The relation with the downstream activity used is **“directly positively regulates”**
+
+Example 2: When an adaptor brings together an enzyme and its substrate
+
+![A screenshot of a computer
+
+Description automatically generated with medium confidence](data:image/png;base64...)
+
+The molecular activity is the same as above (MF, inputs, BP, CC)
+
+But in that case, the relation with the downstream activity used is “**provides input for**”

aurelian/agents/gocam/documents/How_to_annotate_sequestering_proteins.md

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+# Sequestering activity
+
+A sequestering activity is defined as the binding to a specific molecule to prevent it from interacting with other partners or to inhibit its localization to the area of the cell or complex where the target is active.
+
+# Pathway Editor
+
+The activity unit for sequestering activity is:
+
+* **MF**: molecular sequestering activity ([GO:0140313](https://www.ebi.ac.uk/QuickGO/term/GO%3A0140313)) or a child
+* **Context:**
+  + The relation between the protein that act to sequester and its target receptor is *'*has input'
+  + **BP**: the BP it inhibits
+  + **CC**: the place where the activity occurs.
+  + The causal relation between the **sequestering activity** and the activity of the protein it inhibits is 'directly positively regulates'.
+
+Example 1: [Sequestering activity of CAV1 on TLR4 signaling](http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel%3A645d887900001414)
+
+![A screenshot of a computer
+
+Description automatically generated with medium confidence](data:image/png;base64...)
+
+The molecular activity unit for molecular adaptor may include:
+
+o **MF**: molecular sequestering activity ([GO:0140313](https://www.ebi.ac.uk/QuickGO/term/GO%3A0140313)) or one of its children
+
+o
+
+The relation with the downstream activity used is **“directly negatively regulates”**
+
+Example 2: [Sequestering activity of YWHAZ on RAF1](http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel%3A63d320cd00000820)
+
+![](data:image/png;base64...)
+
+In that example, the difference in the cellular component between the two activities clearly show that the YWHAZ protein sequesters RAF1 in the cytoplasm, preventing its activity in the plasma membrane.
+
+The relation used between both activities is **“directly negatively regulates”** because there is direct interaction between both proteins.
+
+# Form Editor
+
+Review date: 2023-06-22
+
+Reviewed by: Pascale Gaudet, Patrick Masson

aurelian/agents/gocam/documents/Molecular_adaptor_activity.md

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+# Guidelines for annotating molecular adaptor activity
+
+A molecular adaptor activity is the binding activity of a molecule that brings together two or more molecules through a selective, non-covalent, often stoichiometric interaction, permitting those molecules to function in a coordinated way.
+
+# Pathway Editor
+
+The molecular activity unit for a molecular adaptor is:
+
+* **MF**: 'enables' molecular adaptor activity ([GO:0060090](https://www.ebi.ac.uk/QuickGO/term/GO%3A0060090)) or a child
+* **Context:**
+  + The relation between the adaptor activity and the two (or more) molecules it brings together is 'has input'
+  + **BP**: 'part of' the BP in which the adaptor participates
+  + **CC**: 'occurs in' the cellular location where the activity takes place.
+
+The relation between the adaptor and the proteins it adapts can be 'directly positively regulates' or 'provides input for', depending if the activity of the adaptor is regulatory.
+
+**Example 1:** [**TYROBP acts as an adaptor between a receptor and a downstream effector**](http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel%3A633b013300001197)
+
+SIGLEC1 recognizes and endocytoses virions, which leads to activation of the TYROBP molecular adaptor, which recruits PTPN11. The scaffolding activity of PTPN11 is activated by TYROBP.
+
+![A screenshot of a computer
+
+Description automatically generated with medium confidence](data:image/png;base64...)
+
+**Example 2:** [**An adaptor that brings together an enzyme and its substrate**](http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel%3A636d9ce800001192)
+
+![](data:image/png;base64...)
+
+In that case, the relation between the adaptor activity and the downstream activity is 'provides input for'.
+
+## Form Editor
+
+* **MF**: 'enables' molecular adaptor activity ([GO:0060090](https://www.ebi.ac.uk/QuickGO/term/GO%3A0060090)) or a child
+* **Context:**
+  + The relation between the adaptor activity and the two (or more) molecules it brings together is 'has input'
+  + **BP**: 'part of' the BP in which the adaptor participates
+  + **CC**: 'occurs in' the cellular location where the activity takes place.
+
+![](data:image/png;base64...)
+
+# Differences between GO-CAM and standard annotation of a molecular adaptor activity
+
+In standard annotation (captured with the Noctua Form or Protein2GO), relations between molecular functions are not captured.
+
+#
+
+# Review information
+
+Review date: 2023-07-20
+
+Reviewed by: Cristina Casals, Pascale Gaudet, Patrick Masson

aurelian/agents/gocam/documents/Molecular_carrier_activity.md

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+Guidelines for annotating molecular carrier activity
+
+#
+
+# Pathway Editor
+
+The activity unit for a molecular carrier is:
+
+* **MF**: a molecular carrier 'enables' molecular carrier activity ([GO:0140104](https://www.ebi.ac.uk/QuickGO/term/GO%3A0048018)) or a child
+* **Context:**
+  + The relation between a transported molecule and its carrier is *'*has input'. The carrier and the small molecule are linked with the 'has output' relation, so that the small molecule can be the input for the next reaction.
+  + **BP** 'part of' the process in the molecule using the small molecule participates, or 'part of' regulation of the process, if the carrier is regulators (rate-limiting for the execution of the process)
+  + **CC**: 'occurs in' the cellular location where the activity takes place.
+
+Example 1: [LPS is carried to its receptor by CD14](http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel%3A5f46c3b700001031)
+
+![](data:image/png;base64...)
+
+#
+
+# Form Editor
+
+The activity unit for a molecular carrier is:
+
+* **MF**: a molecular carrier 'enables' molecular carrier activity ([GO:0140104](https://www.ebi.ac.uk/QuickGO/term/GO%3A0048018)) or a child
+* **Context:**
+  + The relation between a transported molecule and its carrier is *'*has input'. The carrier and the small molecule are linked with the 'has output' relation, so that the small molecule can be the input for the next reaction.
+  + **BP** 'part of' the process in the molecule using the small molecule participates, or 'part of' regulation of the process, if the carrier is regulators (rate-limiting for the execution of the process)
+  + **CC**: 'occurs in' the cellular location where the activity takes place.
+
+![](data:image/png;base64...)
+
+# Differences between GO-CAM and standard annotation for a molecular carrier activity
+
+The same information is captured for the carrier activity and its context; however in the standard annotations,it is not possible to capture the order of the reactions.
+
+# Review information
+
+Review date: 2023-07-25
+
+Reviewed by: Cristina Casals, Pasclae Gaudet, Patrick Masson

aurelian/agents/gocam/documents/Protein_sequestering_activity.md

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+# Guidelines for annotating molecular sequestering activity
+
+A sequestering activity is defined as the binding to a specific molecule to prevent it from interacting with other partners or to inhibit its localization to the area of the cell or complex where the target is active.
+
+# Pathway Editor
+
+The activity unit for a molecular sequestering activity is:
+
+* **MF**: molecular sequestering activity ([GO:0140313)](https://www.ebi.ac.uk/QuickGO/term/GO%3A0140313). **The most commonly used child is protein sequestering activity (**[**GO:0140311**](https://www.ebi.ac.uk/QuickGO/term/GO%3A0140311)**).**
+* **Context:**
+  + The relation between the protein that act to sequester and its target is *'*has input'
+  + **BP**: 'part of' negative regulation of the BP in which the target protein participates .
+  + **CC**: the location where the activity occurs.
+  + The causal relation between the **sequestering activity** and the activity of the protein it inhibits is 'directly negatively regulates' because there is a direct interaction between the two proteins.
+
+**Example 1:** [**Sequestering activity of CAV1 negatively regulates TLR4 signaling**](http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel%3A645d887900001414)
+
+![A screenshot of a computer
+
+Description automatically generated with medium confidence](data:image/png;base64...)
+
+**Example 2:** [**Trans-negative regulation of Sars-CoV-2 viral entry into host cell by LRRC15.**](http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel%3A63f809ec00000027)
+
+**![](data:image/png;base64...)**
+
+#
+
+# Form Editor
+
+The activity unit for sequestering activity is:
+
+* **MF**: molecular sequestering activity ([GO:0140313](https://www.ebi.ac.uk/QuickGO/term/GO%3A0140313)) or a child
+* **Context:**
+  + The relation between the protein that act to sequester and its target receptor is *'*has input'
+  + **BP**: negative regulation of the BP in which the regulated protein participates
+  + **CC**: the location where the activity occurs.
+
+**Example 1:** [**Sequestering activity of CAV1 negatively regulates TLR4 signaling**](http://noctua.geneontology.org/workbench/noctua-form/?model_id=gomodel%3A645d887900001414)
+
+![](data:image/png;base64...)
+
+# Differences between GO-CAM and standard annotation of a sequestering activity
+
+In standard annotation (captured with the Noctua Form or Protein2GO), relations between molecular functions are not captured, so there is no relation between the sequestering activity and the activity of the protein being sequestered.
+
+# Review information
+
+Review date: 2023-07-25
+
+Reviewed by: Cristina Casals, Pascale Gaudet, Patrick Masson

aurelian/agents/gocam/documents/Signaling_receptor_activity_annotation_guidelines.md

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+Guidelines for annotating signaling receptor activity
+
+Receptor activation by a ligand is represented differently in GO-CAM depending on whether the ligand is (i) a protein (i. e., encoded by a gene) or (ii) a small molecule.
+
+# Pathway Editor
+
+##
+
+## Protein ligand-activated signaling receptor
+
+### Ligand
+
+The activity unit for a ligand of a signaling receptor is:
+
+* **MF**: a ligand 'enables' receptor ligand activity ([GO:0048018](https://www.ebi.ac.uk/QuickGO/term/GO%3A0048018)) or a child
+* **Context:**
+  + The relation between a ligand and its target receptor is *'*has input'
+  + **BP** 'part of' the process in which the ligand participates, usually a child of signal transduction ([GO:0007165](https://www.ebi.ac.uk/QuickGO/term/GO%3A0007165))
+  + **CC:**
+    - extracellular ligands:'occurs in' extracellular space ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO%3A0005886))
+    - membrane-bound ligands: 'occurs in' plasma membrane ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO%3A0005886))
+  + The causal relation between the **ligand activity** and the **receptor activity** is
+    'directly positively regulates'.
+
+### Signaling receptor
+
+The activity unit for a signaling receptor is:
+
+* **MF:** 'enables' signaling receptor activity ([GO:0038023](https://www.ebi.ac.uk/QuickGO/term/GO%3A0038023)*)* or a child*.*
+* **Context:**
+  + The input (target) of the receptor is the **effector protein it regulates**, for example a molecular adaptor, captured with the *'*has input' relation.
+  + **Note that the input (target) of the receptor is NOT its ligand**
+* **BP** 'part of' the same BP/signal transduction pathway as the ligand
+* **CC:** transmembrane receptors: 'occurs in' plasma membrane ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO%3A0005886))
+  + The causal relation between the MF of the **receptor** and the MF of its **target** is 'directly positively regulates'*.*
+
+**Example:** [**Insulin signaling model**](http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel%3A6482692800000931)
+
+![](data:image/png;base64...)
+
+##
+
+##
+
+##
+
+##
+
+## Small molecule-activated signaling receptor activity
+
+* Since small molecules are not annotated in GO, a small molecule ligand does not have a molecular function. Instead, the **ligand** and the **receptor activity** are linked by the causal relation 'is small molecule activator'*.*
+* The receptor's function, input, and contextual relations are the same as for protein ligand-activated receptors.
+* Note that it is also possible to annotate an inhibitory ligand using the relation 'is small molecule inhibitor'*.*
+* BP and CC annotations are the same as for protein ligand-activated receptor activity.
+
+**Example:** [**Activation of a GPCR by succinate**](http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel%3A648d0dc100000022)
+
+![](data:image/png;base64...)
+
+##
+
+## Special cases
+
+###
+
+### Receptor with coreceptor
+
+This is common in immune receptors. The typical sequence of events is that the ligand binds the signaling receptor, which signals to the co-receptor to activate its downstream effector (such as a protein kinase).
+
+**Example:** [**IL2 signaling pathway (Human)**](http://noctua.geneontology.org/workbench/noctua-visual-pathway-editor/?model_id=gomodel:6205c24300001663)
+
+In this case, the receptor is activated by an information biomacromolecule (i.e. a protein). Interleukin-2 ([IL2](https://www.uniprot.org/uniprot/P60568)), a cytokine, activates its receptor, interleukin-2 receptor A ([IL2RA](https://www.uniprot.org/uniprot/P01589)).
+
+IL2RA directly positively regulates (activates) [IL2RB](https://www.uniprot.org/uniprot/P14784), which phosphorylates and positively regulates [JAK1](https://www.uniprot.org/uniprotkb/P23458).
+
+The activity unit for a signaling coreceptor is:
+
+* **MF:** coreceptor activity ([GO:0015026](https://www.ebi.ac.uk/QuickGO/term/GO%3A0015026)*)*
+* **Context:**
+  + The relation between the receptor and its input (target) is the **signaling coreceptor** it regulates, captured with the *'*has input' relation
+  + **Note that the input (target) of the coreceptor is NOT the ligand**
+* **BP** 'part of' the BP in which the signaling receptor is involved, usually a child of signal transduction ([GO:0007165](https://www.ebi.ac.uk/QuickGO/term/GO%3A0007165))
+* **CC:** transmembrane receptors: 'occurs in' plasma membrane ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO%3A0005886))
+  + The causal relation between the MF of the **receptor** and the MF of its **coreceptor** is 'directly positively regulates'*.*
+
+![Diagram
+
+Description automatically generated with medium confidence](data:image/png;base64...)
+
+Note:
+
+* cytokine activity is\_a receptor ligand activity
+* interleukin-2 receptor activity is\_a signaling receptor activity
+
+###
+
+###
+
+#
+
+# Form Editor
+
+## Protein ligand-activated signaling receptor
+
+### Ligand activity
+
+The activity unit for a ligand of a signaling receptor is:
+
+* **MF**: a ligand 'enables' receptor ligand activity ([GO:0048018](https://www.ebi.ac.uk/QuickGO/term/GO%3A0048018)) or a child
+* **Context:**
+  + The relation between a ligand and its target receptor is *'*has input'
+  + **BP** 'part of' the BP in which this ligand is involved (usually a child of signal transduction ([GO:0007165](https://www.ebi.ac.uk/QuickGO/term/GO%3A0007165)))
+  + **CC:**
+    - extracellular ligands: 'occurs in' extracellular space ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO%3A0005886))
+    - membrane-bound ligands: 'occurs in' plasma membrane ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO%3A0005886))
+* The causal relation between the ***ligand* *activity*** and the ***receptor activity*** is
+  'directly positively regulates'.
+
+**Example:** [**Insulin signaling model**](http://noctua.geneontology.org/workbench/noctua-form/?model_id=gomodel%3A6482692800000931)
+
+![](data:image/png;base64...)
+
+### Signaling receptor activity
+
+The activity unit for a signaling receptor is:
+
+* **MF:** The receptor 'enables' signaling receptor activity ([GO:0038023](https://www.ebi.ac.uk/QuickGO/term/GO%3A0038023)*)* or a child*.*
+* **Context:**
+  + The input (target) of the receptor is the **effector protein it regulates**, for example a molecular adaptor, captured with the *'*has input' relation
+  + **Note that the input (target) of the receptor is NOT its ligand**
+* **BP** in which the signaling receptor is involved, usually a child of signal transduction ([GO:0007165](https://www.ebi.ac.uk/QuickGO/term/GO%3A0007165))
+* **CC:** 'occurs in' a child of cellular anatomical entity (GO:0110165). For transmembrane receptors, annotate to plasma membrane ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO%3A0005886))
+
+**Example:** [**Insulin signaling model**](http://noctua.geneontology.org/workbench/noctua-form/?model_id=gomodel%3A6482692800000931)
+
+![](data:image/png;base64...)
+
+* + The causal relation between the MF of the **receptor** and the MF of its **target** is 'directly positively regulates'*.*
+
+##
+
+## Small molecule-activated signaling receptor activity
+
+* In the Form, small molecules are not captured, so the MF for the receptor. Therefore, the MF is 'enables' signaling receptor activity ([GO:0038023](https://www.ebi.ac.uk/QuickGO/term/GO%3A0038023)*)* or a child*.*
+* BP and CC annotations are the same as for protein ligand-activated receptor activity.
+
+![](data:image/png;base64...)
+
+##
+
+## Receptor with coreceptor
+
+###
+
+**Example:** [**IL2 signaling pathway (Human)**](http://noctua.geneontology.org/workbench/noctua-form/?model_id=gomodel%3A6205c24300001663)
+
+In this case, the receptor, interleukin-2 receptor A ([IL2RA](https://www.uniprot.org/uniprot/P01589)), is activated by a protein ligand, interleukin-2 ([IL2](https://www.uniprot.org/uniprot/P60568)). IL2RA directly positively regulates (activates) the coreceptor [IL2RB](https://www.uniprot.org/uniprot/P14784), which phosphorylates and positively regulates [JAK1](https://www.uniprot.org/uniprotkb/P23458).
+
+The activity unit for a signaling coreceptor is:
+
+* **MF:** The coreceptor 'enables' coreceptor activity ([GO:0015026](https://www.ebi.ac.uk/QuickGO/term/GO%3A0015026)*)* or a child*.*
+* **Context:**
+  + The input (target) of the coreceptor is the **signaling receptor** it regulates, captured with the *'*has input' relation
+  + **Note that the input (target) of the coreceptor is NOT the ligand**
+* **BP** 'part of' the BP in which the signaling receptor is involved, usually a child of signal transduction ([GO:0007165](https://www.ebi.ac.uk/QuickGO/term/GO%3A0007165))
+* **CC:** transmembrane receptors:'occurs in' plasma membrane ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO%3A0005886))
+
+![](data:image/png;base64...)
+
+Note:
+
+* cytokine activity is\_a receptor ligand activity
+* interleukin-2 receptor activity is\_a signaling receptor activity
+
+##
+
+## Differences between GO-CAM and standard annotation of a signaling receptor and its ligand
+
+In standard annotation (captured with the Noctua Form or Protein2GO), relations between molecular functions are not captured, so there is no relation between the ligand activity and the signaling receptor activity, nor is there a relation between the signaling receptor activity and the activity of its target. Likewise for receptor activity and coreceptor activity, there is no relation between these activities captured in standard annotations.
+
+#
+
+# Review information
+
+Review date: 2023-07-20
+
+Reviewed by: Cristina Casals, Pascale Gaudet, Patrick Masson