PICK1 encodes Protein interacting with C kinase 1, a PDZ/BAR-domain scaffold that couples cargo-protein binding to membrane binding and curvature-dependent trafficking. Its best-supported core role is regulation of membrane protein trafficking, especially AMPA receptor GluA2/GluA3 internalization/recycling and synaptic receptor organization, through PDZ-mediated partner selection, PKC-associated signaling, and BAR-domain membrane remodeling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0043113 receptor clustering | IBA GO_REF:0000033 | ACCEPT | Summary: Receptor clustering is supported by PICK1 PDZ/BAR-dependent organization of synaptic receptor complexes. Reason: receptor clustering is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0006886 intracellular protein transport | IBA GO_REF:0000033 | ACCEPT | Summary: Intracellular protein transport is central to PICK1 regulation of AMPAR and other membrane-protein trafficking. Reason: intracellular protein transport is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** |
| GO:0043005 neuron projection | IBA GO_REF:0000033 | ACCEPT | Summary: Neuron projection localization is consistent with PICK1 function in pre- and postsynaptic neuronal compartments. Reason: neuron projection is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md PICK1 is described as enriched in brain and localized to **pre- and postsynaptic compartments**, consistent with its role in regulating synaptic receptor trafficking |
| GO:0005543 phospholipid binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phospholipid binding is supported by the BAR/N-BAR membrane-binding module. Reason: phospholipid binding is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **BAR / N‑BAR domain (membrane remodeling module):** BAR domains are classically crescent-shaped, lipid-binding modules involved in membrane curvature during trafficking. file:human/PICK1/PICK1-deep-research-falcon.md **PICK1 is a dual-domain scaffolding/adaptor protein** that couples (i) **PDZ-domain–mediated binding** to C-terminal motifs on cargo proteins with (ii) **BAR/N‑BAR–mediated lipid/membrane binding and remodeling**, enabling regulation of membrane protein trafficking and compartmentalization |
| GO:0008021 synaptic vesicle | IBA GO_REF:0000033 | ACCEPT | Summary: Synaptic vesicle localization is consistent with synaptic trafficking functions of PICK1. Reason: synaptic vesicle is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md PICK1 is described as enriched in brain and localized to **pre- and postsynaptic compartments**, consistent with its role in regulating synaptic receptor trafficking |
| GO:0014069 postsynaptic density | IBA GO_REF:0000033 | ACCEPT | Summary: Postsynaptic density localization is supported by PICK1 action at postsynaptic AMPAR complexes. Reason: postsynaptic density is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md PICK1 is described as enriched in brain and localized to **pre- and postsynaptic compartments**, consistent with its role in regulating synaptic receptor trafficking file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** |
| GO:0032588 trans-Golgi network membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: trans-Golgi network membrane is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: trans-Golgi network membrane is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0097062 dendritic spine maintenance | IBA GO_REF:0000033 | ACCEPT | Summary: Dendritic spine maintenance is supported by PICK1 roles in AMPAR trafficking and synaptic plasticity. Reason: dendritic spine maintenance is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md PICK1 is described as enriched in brain and localized to **pre- and postsynaptic compartments**, consistent with its role in regulating synaptic receptor trafficking |
| GO:0002092 positive regulation of receptor internalization | IBA GO_REF:0000033 | ACCEPT | Summary: Positive regulation of receptor internalization is a core PICK1-supported process for AMPAR GluA2 trafficking. Reason: positive regulation of receptor internalization is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md In vivo evidence from mouse hippocampus (kainic acid model) supports a mechanistic switch in which **GluA2 Ser880 phosphorylation** promotes dissociation from GRIP1 and association with PICK1, driving AMPAR endocytosis/internalization; PP2A-mediated dephosphorylation reverses this and disfavors PICK1 association file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** |
| GO:0005080 protein kinase C binding | IBA GO_REF:0000033 | ACCEPT | Summary: Protein kinase C binding is supported by PICK1 identity as a PKC-alpha-binding protein. Reason: protein kinase C binding is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md PICK1 was originally cloned/recognized as a **PKCα-binding protein**, a point reiterated in 2023 work on synaptic receptor regulation |
| GO:0034315 regulation of Arp2/3 complex-mediated actin nucleation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: regulation of Arp2/3 complex-mediated actin nucleation is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: regulation of Arp2/3 complex-mediated actin nucleation is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0003779 actin binding | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: actin binding is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: actin binding is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: cytoplasm is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: cytoplasm is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md A 2024 Molecular Biology of the Cell study reports that in nonpolarized cells PICK1 is typically **cytosolic**, but under **sodium arsenite** stress it relocalizes to **perinuclear aggresomes**, identifying PICK1 as a stress-responsive organizer of protein sequestration/aggregation compartments |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: cytoskeleton is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: cytoskeleton is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0014069 postsynaptic density | IEA GO_REF:0000044 | ACCEPT | Summary: Postsynaptic density localization is supported by PICK1 action at postsynaptic AMPAR complexes. Reason: postsynaptic density is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md PICK1 is described as enriched in brain and localized to **pre- and postsynaptic compartments**, consistent with its role in regulating synaptic receptor trafficking file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** |
| GO:0016020 membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: membrane is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: membrane is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0019904 protein domain specific binding | IEA GO_REF:0000002 | ACCEPT | Summary: Protein domain specific binding is supported by PICK1 PDZ-domain recognition of receptor/cargo C-terminal motifs. Reason: protein domain specific binding is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0043005 neuron projection | IEA GO_REF:0000043 | ACCEPT | Summary: Neuron projection localization is consistent with PICK1 function in pre- and postsynaptic neuronal compartments. Reason: neuron projection is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md PICK1 is described as enriched in brain and localized to **pre- and postsynaptic compartments**, consistent with its role in regulating synaptic receptor trafficking |
| GO:0045202 synapse | IEA GO_REF:0000120 | ACCEPT | Summary: Synapse localization is supported by PICK1 enrichment in pre- and postsynaptic compartments. Reason: synapse is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md PICK1 is described as enriched in brain and localized to **pre- and postsynaptic compartments**, consistent with its role in regulating synaptic receptor trafficking |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: Metal ion binding is not the functionally informative annotation for PICK1 compared with PDZ/BAR scaffold and membrane-remodeling activities. Reason: metal ion binding is less informative than the specific PICK1 scaffold mechanism. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PICK1 is a dual-domain scaffolding/adaptor protein** that couples (i) **PDZ-domain–mediated binding** to C-terminal motifs on cargo proteins with (ii) **BAR/N‑BAR–mediated lipid/membrane binding and remodeling**, enabling regulation of membrane protein trafficking and compartmentalization |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: perinuclear region of cytoplasm is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: perinuclear region of cytoplasm is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md A 2024 Molecular Biology of the Cell study reports that in nonpolarized cells PICK1 is typically **cytosolic**, but under **sodium arsenite** stress it relocalizes to **perinuclear aggresomes**, identifying PICK1 as a stress-responsive organizer of protein sequestration/aggregation compartments |
| GO:0005515 protein binding | IPI PMID:11343649 Functional interaction between monoamine plasma membrane tra... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PICK1; PDZ-domain binding, PKC binding, receptor binding, and identical protein binding are more informative. Reason: protein binding is less informative than the specific PICK1 scaffold mechanism. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PICK1 is a dual-domain scaffolding/adaptor protein** that couples (i) **PDZ-domain–mediated binding** to C-terminal motifs on cargo proteins with (ii) **BAR/N‑BAR–mediated lipid/membrane binding and remodeling**, enabling regulation of membrane protein trafficking and compartmentalization file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0005515 protein binding | IPI PMID:11802773 Interaction of the synaptic protein PICK1 (protein interacti... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PICK1; PDZ-domain binding, PKC binding, receptor binding, and identical protein binding are more informative. Reason: protein binding is less informative than the specific PICK1 scaffold mechanism. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PICK1 is a dual-domain scaffolding/adaptor protein** that couples (i) **PDZ-domain–mediated binding** to C-terminal motifs on cargo proteins with (ii) **BAR/N‑BAR–mediated lipid/membrane binding and remodeling**, enabling regulation of membrane protein trafficking and compartmentalization file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0005515 protein binding | IPI PMID:16713569 A protein-protein interaction network for human inherited at... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PICK1; PDZ-domain binding, PKC binding, receptor binding, and identical protein binding are more informative. Reason: protein binding is less informative than the specific PICK1 scaffold mechanism. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PICK1 is a dual-domain scaffolding/adaptor protein** that couples (i) **PDZ-domain–mediated binding** to C-terminal motifs on cargo proteins with (ii) **BAR/N‑BAR–mediated lipid/membrane binding and remodeling**, enabling regulation of membrane protein trafficking and compartmentalization file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0005515 protein binding | IPI PMID:21653829 Protein interactome reveals converging molecular pathways am... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PICK1; PDZ-domain binding, PKC binding, receptor binding, and identical protein binding are more informative. Reason: protein binding is less informative than the specific PICK1 scaffold mechanism. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PICK1 is a dual-domain scaffolding/adaptor protein** that couples (i) **PDZ-domain–mediated binding** to C-terminal motifs on cargo proteins with (ii) **BAR/N‑BAR–mediated lipid/membrane binding and remodeling**, enabling regulation of membrane protein trafficking and compartmentalization file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0005515 protein binding | IPI PMID:26787460 Proteomic peptide phage display uncovers novel interactions ... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PICK1; PDZ-domain binding, PKC binding, receptor binding, and identical protein binding are more informative. Reason: protein binding is less informative than the specific PICK1 scaffold mechanism. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PICK1 is a dual-domain scaffolding/adaptor protein** that couples (i) **PDZ-domain–mediated binding** to C-terminal motifs on cargo proteins with (ii) **BAR/N‑BAR–mediated lipid/membrane binding and remodeling**, enabling regulation of membrane protein trafficking and compartmentalization file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PICK1; PDZ-domain binding, PKC binding, receptor binding, and identical protein binding are more informative. Reason: protein binding is less informative than the specific PICK1 scaffold mechanism. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PICK1 is a dual-domain scaffolding/adaptor protein** that couples (i) **PDZ-domain–mediated binding** to C-terminal motifs on cargo proteins with (ii) **BAR/N‑BAR–mediated lipid/membrane binding and remodeling**, enabling regulation of membrane protein trafficking and compartmentalization file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0005515 protein binding | IPI PMID:31413325 HENA, heterogeneous network-based data set for Alzheimer's d... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PICK1; PDZ-domain binding, PKC binding, receptor binding, and identical protein binding are more informative. Reason: protein binding is less informative than the specific PICK1 scaffold mechanism. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PICK1 is a dual-domain scaffolding/adaptor protein** that couples (i) **PDZ-domain–mediated binding** to C-terminal motifs on cargo proteins with (ii) **BAR/N‑BAR–mediated lipid/membrane binding and remodeling**, enabling regulation of membrane protein trafficking and compartmentalization file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PICK1; PDZ-domain binding, PKC binding, receptor binding, and identical protein binding are more informative. Reason: protein binding is less informative than the specific PICK1 scaffold mechanism. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PICK1 is a dual-domain scaffolding/adaptor protein** that couples (i) **PDZ-domain–mediated binding** to C-terminal motifs on cargo proteins with (ii) **BAR/N‑BAR–mediated lipid/membrane binding and remodeling**, enabling regulation of membrane protein trafficking and compartmentalization file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PICK1; PDZ-domain binding, PKC binding, receptor binding, and identical protein binding are more informative. Reason: protein binding is less informative than the specific PICK1 scaffold mechanism. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PICK1 is a dual-domain scaffolding/adaptor protein** that couples (i) **PDZ-domain–mediated binding** to C-terminal motifs on cargo proteins with (ii) **BAR/N‑BAR–mediated lipid/membrane binding and remodeling**, enabling regulation of membrane protein trafficking and compartmentalization file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PICK1; PDZ-domain binding, PKC binding, receptor binding, and identical protein binding are more informative. Reason: protein binding is less informative than the specific PICK1 scaffold mechanism. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PICK1 is a dual-domain scaffolding/adaptor protein** that couples (i) **PDZ-domain–mediated binding** to C-terminal motifs on cargo proteins with (ii) **BAR/N‑BAR–mediated lipid/membrane binding and remodeling**, enabling regulation of membrane protein trafficking and compartmentalization file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PICK1; PDZ-domain binding, PKC binding, receptor binding, and identical protein binding are more informative. Reason: protein binding is less informative than the specific PICK1 scaffold mechanism. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PICK1 is a dual-domain scaffolding/adaptor protein** that couples (i) **PDZ-domain–mediated binding** to C-terminal motifs on cargo proteins with (ii) **BAR/N‑BAR–mediated lipid/membrane binding and remodeling**, enabling regulation of membrane protein trafficking and compartmentalization file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0005515 protein binding | IPI PMID:37207277 Using brain cell-type-specific protein interactomes to inter... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PICK1; PDZ-domain binding, PKC binding, receptor binding, and identical protein binding are more informative. Reason: protein binding is less informative than the specific PICK1 scaffold mechanism. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PICK1 is a dual-domain scaffolding/adaptor protein** that couples (i) **PDZ-domain–mediated binding** to C-terminal motifs on cargo proteins with (ii) **BAR/N‑BAR–mediated lipid/membrane binding and remodeling**, enabling regulation of membrane protein trafficking and compartmentalization file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0042802 identical protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | ACCEPT | Summary: Identical protein binding is supported by BAR-domain homodimerization and higher-order PICK1 assembly. Reason: identical protein binding is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **BAR / N‑BAR domain (membrane remodeling module):** BAR domains are classically crescent-shaped, lipid-binding modules involved in membrane curvature during trafficking. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: cytosol is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: cytosol is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md A 2024 Molecular Biology of the Cell study reports that in nonpolarized cells PICK1 is typically **cytosolic**, but under **sodium arsenite** stress it relocalizes to **perinuclear aggresomes**, identifying PICK1 as a stress-responsive organizer of protein sequestration/aggregation compartments |
| GO:0005515 protein binding | IPI PMID:16314870 Serine racemase binds to PICK1: potential relevance to schiz... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for PICK1; PDZ-domain binding, PKC binding, receptor binding, and identical protein binding are more informative. Reason: protein binding is less informative than the specific PICK1 scaffold mechanism. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PICK1 is a dual-domain scaffolding/adaptor protein** that couples (i) **PDZ-domain–mediated binding** to C-terminal motifs on cargo proteins with (ii) **BAR/N‑BAR–mediated lipid/membrane binding and remodeling**, enabling regulation of membrane protein trafficking and compartmentalization file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0050796 regulation of insulin secretion | IMP PMID:29768204 An Amphipathic Helix Directs Cellular Membrane Curvature Sen... | KEEP AS NON CORE | Summary: regulation of insulin secretion is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: regulation of insulin secretion is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0140090 membrane curvature sensor activity | IDA PMID:29768204 An Amphipathic Helix Directs Cellular Membrane Curvature Sen... | ACCEPT | Summary: Membrane curvature sensor activity is supported by PICK1 BAR/N-BAR membrane-remodeling function. Reason: membrane curvature sensor activity is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **BAR / N‑BAR domain (membrane remodeling module):** BAR domains are classically crescent-shaped, lipid-binding modules involved in membrane curvature during trafficking. file:human/PICK1/PICK1-deep-research-falcon.md **PICK1 is a dual-domain scaffolding/adaptor protein** that couples (i) **PDZ-domain–mediated binding** to C-terminal motifs on cargo proteins with (ii) **BAR/N‑BAR–mediated lipid/membrane binding and remodeling**, enabling regulation of membrane protein trafficking and compartmentalization |
| GO:0001664 G protein-coupled receptor binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: G protein-coupled receptor binding is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: G protein-coupled receptor binding is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0019904 protein domain specific binding | ISS GO_REF:0000024 | ACCEPT | Summary: Protein domain specific binding is supported by PICK1 PDZ-domain recognition of receptor/cargo C-terminal motifs. Reason: protein domain specific binding is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0042802 identical protein binding | ISS GO_REF:0000024 | ACCEPT | Summary: Identical protein binding is supported by BAR-domain homodimerization and higher-order PICK1 assembly. Reason: identical protein binding is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **BAR / N‑BAR domain (membrane remodeling module):** BAR domains are classically crescent-shaped, lipid-binding modules involved in membrane curvature during trafficking. |
| GO:0002092 positive regulation of receptor internalization | ISS GO_REF:0000024 | ACCEPT | Summary: Positive regulation of receptor internalization is a core PICK1-supported process for AMPAR GluA2 trafficking. Reason: positive regulation of receptor internalization is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md In vivo evidence from mouse hippocampus (kainic acid model) supports a mechanistic switch in which **GluA2 Ser880 phosphorylation** promotes dissociation from GRIP1 and association with PICK1, driving AMPAR endocytosis/internalization; PP2A-mediated dephosphorylation reverses this and disfavors PICK1 association file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** |
| GO:0021782 glial cell development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: glial cell development is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: glial cell development is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0034316 negative regulation of Arp2/3 complex-mediated actin nucleation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: negative regulation of Arp2/3 complex-mediated actin nucleation is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: negative regulation of Arp2/3 complex-mediated actin nucleation is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0036294 cellular response to decreased oxygen levels | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: cellular response to decreased oxygen levels is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: cellular response to decreased oxygen levels is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0042149 cellular response to glucose starvation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: cellular response to glucose starvation is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: cellular response to glucose starvation is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0043005 neuron projection | ISS GO_REF:0000024 | ACCEPT | Summary: Neuron projection localization is consistent with PICK1 function in pre- and postsynaptic neuronal compartments. Reason: neuron projection is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md PICK1 is described as enriched in brain and localized to **pre- and postsynaptic compartments**, consistent with its role in regulating synaptic receptor trafficking |
| GO:0051015 actin filament binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: actin filament binding is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: actin filament binding is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0060292 long-term synaptic depression | ISS GO_REF:0000024 | ACCEPT | Summary: Long-term synaptic depression is supported as a synaptic plasticity context for PICK1-mediated AMPAR internalization. Reason: long-term synaptic depression is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md In vivo evidence from mouse hippocampus (kainic acid model) supports a mechanistic switch in which **GluA2 Ser880 phosphorylation** promotes dissociation from GRIP1 and association with PICK1, driving AMPAR endocytosis/internalization; PP2A-mediated dephosphorylation reverses this and disfavors PICK1 association file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0071933 Arp2/3 complex binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Arp2/3 complex binding is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: Arp2/3 complex binding is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0097061 dendritic spine organization | ISS GO_REF:0000024 | ACCEPT | Summary: Dendritic spine organization is supported through PICK1-dependent AMPAR trafficking and synaptic plasticity. Reason: dendritic spine organization is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md PICK1 is described as enriched in brain and localized to **pre- and postsynaptic compartments**, consistent with its role in regulating synaptic receptor trafficking |
| GO:0097062 dendritic spine maintenance | ISS GO_REF:0000024 | ACCEPT | Summary: Dendritic spine maintenance is supported by PICK1 roles in AMPAR trafficking and synaptic plasticity. Reason: dendritic spine maintenance is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md PICK1 is described as enriched in brain and localized to **pre- and postsynaptic compartments**, consistent with its role in regulating synaptic receptor trafficking |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-416639 | ACCEPT | Summary: Plasma membrane localization is supported by PICK1 roles in surface receptor internalization and trafficking. Reason: plasma membrane is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md In vivo evidence from mouse hippocampus (kainic acid model) supports a mechanistic switch in which **GluA2 Ser880 phosphorylation** promotes dissociation from GRIP1 and association with PICK1, driving AMPAR endocytosis/internalization; PP2A-mediated dephosphorylation reverses this and disfavors PICK1 association file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-416985 | ACCEPT | Summary: Plasma membrane localization is supported by PICK1 roles in surface receptor internalization and trafficking. Reason: plasma membrane is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md In vivo evidence from mouse hippocampus (kainic acid model) supports a mechanistic switch in which **GluA2 Ser880 phosphorylation** promotes dissociation from GRIP1 and association with PICK1, driving AMPAR endocytosis/internalization; PP2A-mediated dephosphorylation reverses this and disfavors PICK1 association file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-421007 | ACCEPT | Summary: Plasma membrane localization is supported by PICK1 roles in surface receptor internalization and trafficking. Reason: plasma membrane is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md In vivo evidence from mouse hippocampus (kainic acid model) supports a mechanistic switch in which **GluA2 Ser880 phosphorylation** promotes dissociation from GRIP1 and association with PICK1, driving AMPAR endocytosis/internalization; PP2A-mediated dephosphorylation reverses this and disfavors PICK1 association file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** |
| GO:0030666 endocytic vesicle membrane | TAS Reactome:R-HSA-416639 | ACCEPT | Summary: Endocytic vesicle membrane localization is consistent with PICK1-mediated receptor internalization/recycling. Reason: endocytic vesicle membrane is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md In vivo evidence from mouse hippocampus (kainic acid model) supports a mechanistic switch in which **GluA2 Ser880 phosphorylation** promotes dissociation from GRIP1 and association with PICK1, driving AMPAR endocytosis/internalization; PP2A-mediated dephosphorylation reverses this and disfavors PICK1 association file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** |
| GO:0030666 endocytic vesicle membrane | TAS Reactome:R-HSA-421007 | ACCEPT | Summary: Endocytic vesicle membrane localization is consistent with PICK1-mediated receptor internalization/recycling. Reason: endocytic vesicle membrane is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md In vivo evidence from mouse hippocampus (kainic acid model) supports a mechanistic switch in which **GluA2 Ser880 phosphorylation** promotes dissociation from GRIP1 and association with PICK1, driving AMPAR endocytosis/internalization; PP2A-mediated dephosphorylation reverses this and disfavors PICK1 association file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** |
| GO:0005737 cytoplasm | IDA PMID:16314870 Serine racemase binds to PICK1: potential relevance to schiz... | KEEP AS NON CORE | Summary: cytoplasm is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: cytoplasm is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md A 2024 Molecular Biology of the Cell study reports that in nonpolarized cells PICK1 is typically **cytosolic**, but under **sodium arsenite** stress it relocalizes to **perinuclear aggresomes**, identifying PICK1 as a stress-responsive organizer of protein sequestration/aggregation compartments |
| GO:0005102 signaling receptor binding | ISS GO_REF:0000024 | ACCEPT | Summary: Signaling receptor binding is supported by PICK1 PDZ-domain interactions with receptor cargo such as AMPAR subunits. Reason: signaling receptor binding is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** |
| GO:0043113 receptor clustering | ISS GO_REF:0000024 | ACCEPT | Summary: Receptor clustering is supported by PICK1 PDZ/BAR-dependent organization of synaptic receptor complexes. Reason: receptor clustering is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md **PDZ domain (protein interaction module):** In AMPAR biology, authoritative review evidence states that the **GluA2 C-terminus** contains a PDZ ligand that binds directly to **PICK1** (and GRIP1), and that PICK1 binds GluA2 via its PDZ domain |
| GO:0045202 synapse | ISS GO_REF:0000024 | ACCEPT | Summary: Synapse localization is supported by PICK1 enrichment in pre- and postsynaptic compartments. Reason: synapse is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md PICK1 is described as enriched in brain and localized to **pre- and postsynaptic compartments**, consistent with its role in regulating synaptic receptor trafficking |
| GO:0005080 protein kinase C binding | ISS GO_REF:0000024 | ACCEPT | Summary: Protein kinase C binding is supported by PICK1 identity as a PKC-alpha-binding protein. Reason: protein kinase C binding is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md PICK1 was originally cloned/recognized as a **PKCα-binding protein**, a point reiterated in 2023 work on synaptic receptor regulation |
| GO:0048471 perinuclear region of cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: perinuclear region of cytoplasm is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: perinuclear region of cytoplasm is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md A 2024 Molecular Biology of the Cell study reports that in nonpolarized cells PICK1 is typically **cytosolic**, but under **sodium arsenite** stress it relocalizes to **perinuclear aggresomes**, identifying PICK1 as a stress-responsive organizer of protein sequestration/aggregation compartments |
| GO:0005794 Golgi apparatus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Golgi apparatus is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: Golgi apparatus is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0006468 protein phosphorylation | ISS GO_REF:0000024 | REMOVE | Summary: PICK1 controls phosphorylation-dependent receptor partner switching as a scaffold, but it does not catalyze protein phosphorylation. Reason: PICK1 is a phosphorylation-dependent scaffold/trafficking regulator, not a kinase. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md In vivo evidence from mouse hippocampus (kainic acid model) supports a mechanistic switch in which **GluA2 Ser880 phosphorylation** promotes dissociation from GRIP1 and association with PICK1, driving AMPAR endocytosis/internalization; PP2A-mediated dephosphorylation reverses this and disfavors PICK1 association |
| GO:0005737 cytoplasm | IDA PMID:11343649 Functional interaction between monoamine plasma membrane tra... | KEEP AS NON CORE | Summary: cytoplasm is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: cytoplasm is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md A 2024 Molecular Biology of the Cell study reports that in nonpolarized cells PICK1 is typically **cytosolic**, but under **sodium arsenite** stress it relocalizes to **perinuclear aggresomes**, identifying PICK1 as a stress-responsive organizer of protein sequestration/aggregation compartments |
| GO:0005886 plasma membrane | IDA PMID:11343649 Functional interaction between monoamine plasma membrane tra... | ACCEPT | Summary: Plasma membrane localization is supported by PICK1 roles in surface receptor internalization and trafficking. Reason: plasma membrane is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md In vivo evidence from mouse hippocampus (kainic acid model) supports a mechanistic switch in which **GluA2 Ser880 phosphorylation** promotes dissociation from GRIP1 and association with PICK1, driving AMPAR endocytosis/internalization; PP2A-mediated dephosphorylation reverses this and disfavors PICK1 association file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** |
| GO:0015844 monoamine transport | IDA PMID:11343649 Functional interaction between monoamine plasma membrane tra... | KEEP AS NON CORE | Summary: monoamine transport is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: monoamine transport is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0042734 presynaptic membrane | IDA PMID:11343649 Functional interaction between monoamine plasma membrane tra... | KEEP AS NON CORE | Summary: presynaptic membrane is plausible as a context-specific PICK1 localization, binding, or downstream process, but it is secondary to the core PDZ/BAR receptor-trafficking function. Reason: presynaptic membrane is secondary to PICK1 membrane protein trafficking and synaptic receptor organization. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md Human **PICK1 (Q9NRD5)** is best annotated as a **PDZ/BAR scaffolding and membrane-remodeling protein** that controls **membrane protein trafficking**, with the strongest 2023–2024 evidence supporting roles in **AMPAR (GluA2/3) internalization/recycling and synaptic plasticity** through phosphorylation-dependent partner switching and regulated complex formation. |
| GO:0045161 neuronal ion channel clustering | TAS PMID:11343649 Functional interaction between monoamine plasma membrane tra... | ACCEPT | Summary: Neuronal ion channel clustering is consistent with PICK1 synaptic receptor clustering and trafficking roles. Reason: neuronal ion channel clustering is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function. Supporting Evidence: file:human/PICK1/PICK1-deep-research-falcon.md Across the recent literature, PICK1’s primary molecular role is best described as a **PDZ/BAR scaffold that regulates the trafficking and surface availability of membrane proteins—especially AMPA-type glutamate receptors—by coordinating protein complex assembly with membrane remodeling and endocytic/recycling processes** file:human/PICK1/PICK1-deep-research-falcon.md PICK1 is described as enriched in brain and localized to **pre- and postsynaptic compartments**, consistent with its role in regulating synaptic receptor trafficking |
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