PICALM encodes CALM, a ubiquitously expressed ANTH-domain clathrin adaptor that binds phosphatidylinositol phosphates, clathrin, AP-2, and selected cargo proteins to promote clathrin-coated pit maturation and clathrin-mediated endocytosis. It localizes mainly to cytosolic membrane interfaces including plasma membrane clathrin-coated pits, clathrin-coated vesicles, Golgi/endosomal compartments, and synaptic vesicle-related membranes. PICALM helps determine clathrin-coated vesicle size and membrane curvature, and it sorts small R-SNAREs such as VAMP2, VAMP3, and VAMP8 between the plasma membrane and endosomes. Cargo- and tissue-specific consequences include transferrin receptor/iron uptake, AMPA receptor trafficking, gamma-secretase and APP-related trafficking, amyloid-beta transcytosis across brain endothelium, and association with tau pathology.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0072583 clathrin-dependent endocytosis | IBA GO_REF:0000033 | ACCEPT | Summary: This endocytosis/receptor-internalization term captures the core PICALM role in clathrin-mediated internalization and coated-vesicle maturation. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0005546 phosphatidylinositol-4,5-bisphosphate binding | IBA GO_REF:0000033 | ACCEPT | Summary: PICALM/CALM uses its ANTH domain to bind phosphoinositides/PIP2 at clathrin-coated membrane sites, anchoring its endocytic adaptor and curvature functions. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0006900 vesicle budding from membrane | IBA GO_REF:0000033 | ACCEPT | Summary: This vesicle/coated-pit term is consistent with PICALM acting at clathrin-coated pits and clathrin-coated vesicle intermediates. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0098894 extrinsic component of presynaptic endocytic zone membrane | IBA GO_REF:0000033 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005905 clathrin-coated pit | IBA GO_REF:0000033 | ACCEPT | Summary: This vesicle/coated-pit term is consistent with PICALM acting at clathrin-coated pits and clathrin-coated vesicle intermediates. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0000149 SNARE binding | IBA GO_REF:0000033 | ACCEPT | Summary: PICALM directly binds small R-SNAREs such as VAMP2, VAMP3, and VAMP8 and mediates their endocytosis. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0030136 clathrin-coated vesicle | IBA GO_REF:0000033 | ACCEPT | Summary: This vesicle/coated-pit term is consistent with PICALM acting at clathrin-coated pits and clathrin-coated vesicle intermediates. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005545 1-phosphatidylinositol binding | IBA GO_REF:0000033 | ACCEPT | Summary: PICALM/CALM uses its ANTH domain to bind phosphoinositides/PIP2 at clathrin-coated membrane sites, anchoring its endocytic adaptor and curvature functions. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0008021 synaptic vesicle | IBA GO_REF:0000033 | ACCEPT | Summary: This synaptic-vesicle/presynaptic term is consistent with PICALM/AP180-family SNARE sorting and synaptic vesicle trafficking biology. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0032050 clathrin heavy chain binding | IBA GO_REF:0000033 | ACCEPT | Summary: Direct clathrin/clathrin-heavy-chain binding is central to PICALM recruitment and clathrin-coated pit/vesicle assembly. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0005543 phospholipid binding | IEA GO_REF:0000002 | ACCEPT | Summary: PICALM/CALM uses its ANTH domain to bind phosphoinositides/PIP2 at clathrin-coated membrane sites, anchoring its endocytic adaptor and curvature functions. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0005545 1-phosphatidylinositol binding | IEA GO_REF:0000002 | ACCEPT | Summary: PICALM/CALM uses its ANTH domain to bind phosphoinositides/PIP2 at clathrin-coated membrane sites, anchoring its endocytic adaptor and curvature functions. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear localization and transcriptional effects are context-specific, mainly from nuclear shuttling or leukemia-fusion/interactor biology, and are not the principal PICALM function. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005905 clathrin-coated pit | IEA GO_REF:0000044 | ACCEPT | Summary: This vesicle/coated-pit term is consistent with PICALM acting at clathrin-coated pits and clathrin-coated vesicle intermediates. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0006897 endocytosis | IEA GO_REF:0000117 | ACCEPT | Summary: This endocytosis/receptor-internalization term captures the core PICALM role in clathrin-mediated internalization and coated-vesicle maturation. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0012505 endomembrane system | IEA GO_REF:0000117 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0016020 membrane | IEA GO_REF:0000117 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0030136 clathrin-coated vesicle | IEA GO_REF:0000120 | ACCEPT | Summary: This vesicle/coated-pit term is consistent with PICALM acting at clathrin-coated pits and clathrin-coated vesicle intermediates. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0030276 clathrin binding | IEA GO_REF:0000002 | ACCEPT | Summary: Direct clathrin/clathrin-heavy-chain binding is central to PICALM recruitment and clathrin-coated pit/vesicle assembly. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0031982 vesicle | IEA GO_REF:0000117 | ACCEPT | Summary: This vesicle/coated-pit term is consistent with PICALM acting at clathrin-coated pits and clathrin-coated vesicle intermediates. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0048259 regulation of receptor-mediated endocytosis | IEA GO_REF:0000117 | ACCEPT | Summary: This endocytosis/receptor-internalization term captures the core PICALM role in clathrin-mediated internalization and coated-vesicle maturation. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0048268 clathrin coat assembly | IEA GO_REF:0000002 | ACCEPT | Summary: PICALM is required for orderly clathrin coat and coated-bud formation at the plasma membrane. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0072583 clathrin-dependent endocytosis | IEA GO_REF:0000002 | ACCEPT | Summary: This endocytosis/receptor-internalization term captures the core PICALM role in clathrin-mediated internalization and coated-vesicle maturation. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0005515 protein binding | IPI PMID:22829078 FHL2 interacts with CALM and is highly expressed in acute er... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for PICALM because specific clathrin, clathrin heavy chain, SNARE, phosphoinositide, and cargo-adaptor annotations are available. Reason: This is less informative or less direct than the specific PICALM functions supported by the evidence; prefer clathrin, clathrin heavy chain, SNARE, phosphoinositide, and cargo-trafficking annotations where applicable. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for PICALM because specific clathrin, clathrin heavy chain, SNARE, phosphoinositide, and cargo-adaptor annotations are available. Reason: This is less informative or less direct than the specific PICALM functions supported by the evidence; prefer clathrin, clathrin heavy chain, SNARE, phosphoinositide, and cargo-trafficking annotations where applicable. |
| GO:0005515 protein binding | IPI PMID:35044719 Proteome-scale mapping of binding sites in the unstructured ... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for PICALM because specific clathrin, clathrin heavy chain, SNARE, phosphoinositide, and cargo-adaptor annotations are available. Reason: This is less informative or less direct than the specific PICALM functions supported by the evidence; prefer clathrin, clathrin heavy chain, SNARE, phosphoinositide, and cargo-trafficking annotations where applicable. |
| GO:0005794 Golgi apparatus | EXP PMID:10436022 Clathrin assembly lymphoid myeloid leukemia (CALM) protein: ... | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0046579 positive regulation of Ras protein signal transduction | IMP PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | KEEP AS NON CORE | Summary: This annotation is supported or plausible for a specific cellular or disease context, but it is not the primary PICALM clathrin/SNARE adaptor function. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:1902991 regulation of amyloid precursor protein catabolic process | IMP PMID:24577224 Decreased CALM expression reduces AΞ²42 to total AΞ² ratio thr... | KEEP AS NON CORE | Summary: The gamma-secretase/APP processing annotation is supported as a cargo-specific consequence of CALM-dependent clathrin-mediated endocytosis, not as a separate catalytic activity. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:1902993 positive regulation of amyloid precursor protein catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This annotation is supported or plausible for a specific cellular or disease context, but it is not the primary PICALM clathrin/SNARE adaptor function. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0048268 clathrin coat assembly | IDA PMID:16262731 Effect of clathrin assembly lymphoid myeloid leukemia protei... | ACCEPT | Summary: PICALM is required for orderly clathrin coat and coated-bud formation at the plasma membrane. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0006879 intracellular iron ion homeostasis | IMP PMID:22952941 The PICALM protein plays a key role in iron homeostasis and ... | KEEP AS NON CORE | Summary: The iron-homeostasis and linked expression/proliferation phenotypes are supported, but they arise downstream of transferrin receptor endocytosis rather than defining the primary molecular role. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0060586 multicellular organismal-level iron ion homeostasis | IMP PMID:22952941 The PICALM protein plays a key role in iron homeostasis and ... | KEEP AS NON CORE | Summary: The iron-homeostasis and linked expression/proliferation phenotypes are supported, but they arise downstream of transferrin receptor endocytosis rather than defining the primary molecular role. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0150093 amyloid-beta clearance by transcytosis | ISS PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | KEEP AS NON CORE | Summary: The BBB/endothelial amyloid-beta clearance evidence is strong and Alzheimer-relevant, but it is a cargo- and tissue-specific consequence of PICALM-mediated endocytic/transcytotic trafficking. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0030132 clathrin coat of coated pit | IDA PMID:10436022 Clathrin assembly lymphoid myeloid leukemia (CALM) protein: ... | ACCEPT | Summary: PICALM is required for orderly clathrin coat and coated-bud formation at the plasma membrane. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0030132 clathrin coat of coated pit | IDA PMID:16262731 Effect of clathrin assembly lymphoid myeloid leukemia protei... | ACCEPT | Summary: PICALM is required for orderly clathrin coat and coated-bud formation at the plasma membrane. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0031267 small GTPase binding | IPI PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | KEEP AS NON CORE | Summary: The BBB/endothelial amyloid-beta clearance evidence is strong and Alzheimer-relevant, but it is a cargo- and tissue-specific consequence of PICALM-mediated endocytic/transcytotic trafficking. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0050750 low-density lipoprotein particle receptor binding | IPI PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | KEEP AS NON CORE | Summary: The BBB/endothelial amyloid-beta clearance evidence is strong and Alzheimer-relevant, but it is a cargo- and tissue-specific consequence of PICALM-mediated endocytic/transcytotic trafficking. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0000149 SNARE binding | IDA PMID:22118466 The molecular basis for the endocytosis of small R-SNAREs by... | ACCEPT | Summary: PICALM directly binds small R-SNAREs such as VAMP2, VAMP3, and VAMP8 and mediates their endocytosis. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0005515 protein binding | IPI PMID:22118466 The molecular basis for the endocytosis of small R-SNAREs by... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for PICALM because specific clathrin, clathrin heavy chain, SNARE, phosphoinositide, and cargo-adaptor annotations are available. Reason: This is less informative or less direct than the specific PICALM functions supported by the evidence; prefer clathrin, clathrin heavy chain, SNARE, phosphoinositide, and cargo-trafficking annotations where applicable. |
| GO:0006897 endocytosis | IDA PMID:22118466 The molecular basis for the endocytosis of small R-SNAREs by... | ACCEPT | Summary: This endocytosis/receptor-internalization term captures the core PICALM role in clathrin-mediated internalization and coated-vesicle maturation. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0005515 protein binding | IPI PMID:16262731 Effect of clathrin assembly lymphoid myeloid leukemia protei... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for PICALM because specific clathrin, clathrin heavy chain, SNARE, phosphoinositide, and cargo-adaptor annotations are available. Reason: This is less informative or less direct than the specific PICALM functions supported by the evidence; prefer clathrin, clathrin heavy chain, SNARE, phosphoinositide, and cargo-trafficking annotations where applicable. |
| GO:0005886 plasma membrane | IDA PMID:16262731 Effect of clathrin assembly lymphoid myeloid leukemia protei... | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0072583 clathrin-dependent endocytosis | IMP PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | ACCEPT | Summary: This endocytosis/receptor-internalization term captures the core PICALM role in clathrin-mediated internalization and coated-vesicle maturation. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0150093 amyloid-beta clearance by transcytosis | IGI PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | KEEP AS NON CORE | Summary: The BBB/endothelial amyloid-beta clearance evidence is strong and Alzheimer-relevant, but it is a cargo- and tissue-specific consequence of PICALM-mediated endocytic/transcytotic trafficking. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0001540 amyloid-beta binding | IC GO_REF:0000111 | MARK AS OVER ANNOTATED | Summary: Amyloid-beta binding is not directly established for PICALM in the cited inference; the cached BBB study supports PICALM-dependent A-beta/LRP1 trafficking and direct LRP1-tail binding rather than direct amyloid-beta binding. Reason: This is less informative or less direct than the specific PICALM functions supported by the evidence; prefer clathrin, clathrin heavy chain, SNARE, phosphoinositide, and cargo-trafficking annotations where applicable. |
| GO:0006900 vesicle budding from membrane | IMP PMID:25898166 CALM regulates clathrin-coated vesicle size and maturation b... | ACCEPT | Summary: This vesicle/coated-pit term is consistent with PICALM acting at clathrin-coated pits and clathrin-coated vesicle intermediates. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0048156 tau protein binding | IPI PMID:23589030 Clathrin adaptor CALM/PICALM is associated with neurofibrill... | KEEP AS NON CORE | Summary: The tau/neurofibrillary-tangle evidence is Alzheimer-relevant, but it reflects pathology-associated localization or binding rather than the main clathrin/SNARE adaptor role. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | MARK AS OVER ANNOTATED | Summary: The high-throughput cadherin-binding annotation is peripheral to PICALM endocytic adaptor biology and is less informative than the supported clathrin/SNARE/phosphoinositide binding terms. Reason: This is less informative or less direct than the specific PICALM functions supported by the evidence; prefer clathrin, clathrin heavy chain, SNARE, phosphoinositide, and cargo-trafficking annotations where applicable. |
| GO:0031623 receptor internalization | IMP PMID:25898166 CALM regulates clathrin-coated vesicle size and maturation b... | ACCEPT | Summary: This endocytosis/receptor-internalization term captures the core PICALM role in clathrin-mediated internalization and coated-vesicle maturation. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0005546 phosphatidylinositol-4,5-bisphosphate binding | ISS PMID:25898166 CALM regulates clathrin-coated vesicle size and maturation b... | ACCEPT | Summary: PICALM/CALM uses its ANTH domain to bind phosphoinositides/PIP2 at clathrin-coated membrane sites, anchoring its endocytic adaptor and curvature functions. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0005905 clathrin-coated pit | IMP PMID:25898166 CALM regulates clathrin-coated vesicle size and maturation b... | ACCEPT | Summary: This vesicle/coated-pit term is consistent with PICALM acting at clathrin-coated pits and clathrin-coated vesicle intermediates. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0016020 membrane | ISS PMID:25898166 CALM regulates clathrin-coated vesicle size and maturation b... | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0030136 clathrin-coated vesicle | IMP PMID:25898166 CALM regulates clathrin-coated vesicle size and maturation b... | ACCEPT | Summary: This vesicle/coated-pit term is consistent with PICALM acting at clathrin-coated pits and clathrin-coated vesicle intermediates. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0045334 clathrin-coated endocytic vesicle | NAS PMID:25898166 CALM regulates clathrin-coated vesicle size and maturation b... | ACCEPT | Summary: This vesicle/coated-pit term is consistent with PICALM acting at clathrin-coated pits and clathrin-coated vesicle intermediates. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0097494 regulation of vesicle size | IMP PMID:25898166 CALM regulates clathrin-coated vesicle size and maturation b... | ACCEPT | Summary: PICALM regulates clathrin-coated vesicle size, maturation, and membrane curvature through its PIP2-bound ANTH/amphipathic-helix module. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0097753 membrane bending | IMP PMID:25898166 CALM regulates clathrin-coated vesicle size and maturation b... | ACCEPT | Summary: PICALM regulates clathrin-coated vesicle size, maturation, and membrane curvature through its PIP2-bound ANTH/amphipathic-helix module. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0007611 learning or memory | ISS PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | KEEP AS NON CORE | Summary: This annotation is supported or plausible for a specific cellular or disease context, but it is not the primary PICALM clathrin/SNARE adaptor function. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:1902003 regulation of amyloid-beta formation | ISS NOT PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | ACCEPT | Summary: This is a NOT annotation for regulation of amyloid-beta formation; it should be retained because the cited disease-model evidence supports amyloid-beta clearance/transcytosis rather than amyloid-beta production by PICALM. Reason: The NOT annotation is consistent with evidence that the referenced study separated PICALM-dependent amyloid-beta clearance from amyloid-beta production/formation. |
| GO:1903077 negative regulation of protein localization to plasma membrane | IMP PMID:21221849 CALM, a clathrin assembly protein, influences cell surface G... | KEEP AS NON CORE | Summary: The GluR2/postsynaptic trafficking evidence is plausible but cargo-specific and not the main PICALM clathrin coat/SNARE sorting function. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:2000009 negative regulation of protein localization to cell surface | IMP PMID:21221849 CALM, a clathrin assembly protein, influences cell surface G... | KEEP AS NON CORE | Summary: The GluR2/postsynaptic trafficking evidence is plausible but cargo-specific and not the main PICALM clathrin coat/SNARE sorting function. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0005769 early endosome | IDA PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | ACCEPT | Summary: This endosomal/cargo-trafficking term is consistent with PICALM-mediated sorting of endocytic cargo between plasma membrane and endosomal compartments. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0070381 endosome to plasma membrane transport vesicle | IDA PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | ACCEPT | Summary: This endosomal/cargo-trafficking term is consistent with PICALM-mediated sorting of endocytic cargo between plasma membrane and endosomal compartments. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0009986 cell surface | IDA PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8867613 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8867754 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8867756 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868071 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868072 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868230 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868236 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868648 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868651 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868658 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868659 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868660 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8869438 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8871193 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8871194 | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0016188 synaptic vesicle maturation | ISS GO_REF:0000024 | ACCEPT | Summary: This synaptic-vesicle/presynaptic term is consistent with PICALM/AP180-family SNARE sorting and synaptic vesicle trafficking biology. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0031982 vesicle | ISS GO_REF:0000024 | ACCEPT | Summary: This vesicle/coated-pit term is consistent with PICALM acting at clathrin-coated pits and clathrin-coated vesicle intermediates. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0005515 protein binding | IPI PMID:23382074 A high-confidence interaction map identifies SIRT1 as a medi... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for PICALM because specific clathrin, clathrin heavy chain, SNARE, phosphoinositide, and cargo-adaptor annotations are available. Reason: This is less informative or less direct than the specific PICALM functions supported by the evidence; prefer clathrin, clathrin heavy chain, SNARE, phosphoinositide, and cargo-trafficking annotations where applicable. |
| GO:1902004 positive regulation of amyloid-beta formation | IMP PMID:24577224 Decreased CALM expression reduces AΞ²42 to total AΞ² ratio thr... | KEEP AS NON CORE | Summary: The gamma-secretase/APP processing annotation is supported as a cargo-specific consequence of CALM-dependent clathrin-mediated endocytosis, not as a separate catalytic activity. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0010629 negative regulation of gene expression | IMP PMID:22952941 The PICALM protein plays a key role in iron homeostasis and ... | KEEP AS NON CORE | Summary: The iron-homeostasis and linked expression/proliferation phenotypes are supported, but they arise downstream of transferrin receptor endocytosis rather than defining the primary molecular role. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0072583 clathrin-dependent endocytosis | IMP PMID:22952941 The PICALM protein plays a key role in iron homeostasis and ... | ACCEPT | Summary: This endocytosis/receptor-internalization term captures the core PICALM role in clathrin-mediated internalization and coated-vesicle maturation. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0035459 vesicle cargo loading | IMP PMID:24577224 Decreased CALM expression reduces AΞ²42 to total AΞ² ratio thr... | ACCEPT | Summary: This endosomal/cargo-trafficking term is consistent with PICALM-mediated sorting of endocytic cargo between plasma membrane and endosomal compartments. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0043025 neuronal cell body | IDA PMID:23589030 Clathrin adaptor CALM/PICALM is associated with neurofibrill... | KEEP AS NON CORE | Summary: The tau/neurofibrillary-tangle evidence is Alzheimer-relevant, but it reflects pathology-associated localization or binding rather than the main clathrin/SNARE adaptor role. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0072583 clathrin-dependent endocytosis | IMP PMID:24577224 Decreased CALM expression reduces AΞ²42 to total AΞ² ratio thr... | ACCEPT | Summary: This endocytosis/receptor-internalization term captures the core PICALM role in clathrin-mediated internalization and coated-vesicle maturation. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0097418 neurofibrillary tangle | IMP PMID:23589030 Clathrin adaptor CALM/PICALM is associated with neurofibrill... | KEEP AS NON CORE | Summary: The tau/neurofibrillary-tangle evidence is Alzheimer-relevant, but it reflects pathology-associated localization or binding rather than the main clathrin/SNARE adaptor role. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0031623 receptor internalization | IMP PMID:14985334 Analysis of clathrin-mediated endocytosis of epidermal growt... | ACCEPT | Summary: This endocytosis/receptor-internalization term captures the core PICALM role in clathrin-mediated internalization and coated-vesicle maturation. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0005515 protein binding | IPI PMID:16491119 The novel CALM interactor CATS influences the subcellular lo... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not informative for PICALM because specific clathrin, clathrin heavy chain, SNARE, phosphoinositide, and cargo-adaptor annotations are available. Reason: This is less informative or less direct than the specific PICALM functions supported by the evidence; prefer clathrin, clathrin heavy chain, SNARE, phosphoinositide, and cargo-trafficking annotations where applicable. |
| GO:0005634 nucleus | IDA PMID:16491119 The novel CALM interactor CATS influences the subcellular lo... | KEEP AS NON CORE | Summary: Nuclear localization and transcriptional effects are context-specific, mainly from nuclear shuttling or leukemia-fusion/interactor biology, and are not the principal PICALM function. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:11425879 Nucleocytoplasmic shuttling of endocytic proteins. | KEEP AS NON CORE | Summary: Nuclear localization and transcriptional effects are context-specific, mainly from nuclear shuttling or leukemia-fusion/interactor biology, and are not the principal PICALM function. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0032050 clathrin heavy chain binding | IDA PMID:10436022 Clathrin assembly lymphoid myeloid leukemia (CALM) protein: ... | ACCEPT | Summary: Direct clathrin/clathrin-heavy-chain binding is central to PICALM recruitment and clathrin-coated pit/vesicle assembly. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0032880 regulation of protein localization | IDA PMID:10436022 Clathrin assembly lymphoid myeloid leukemia (CALM) protein: ... | ACCEPT | Summary: This localization/process is consistent with PICALM acting at cytosolic membrane interfaces for clathrin-mediated endocytosis and vesicle trafficking. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0048261 negative regulation of receptor-mediated endocytosis | IDA PMID:10436022 Clathrin assembly lymphoid myeloid leukemia (CALM) protein: ... | MARK AS OVER ANNOTATED | Summary: The negative regulation term reflects dominant-negative overexpression effects on receptor endocytosis, whereas loss-of-function and rescue studies support a normal positive/core role in clathrin-mediated internalization. Reason: The annotation is not simply wrong, but it over-emphasizes an overexpression phenotype and can misrepresent normal PICALM biology; receptor-mediated endocytosis and clathrin-dependent endocytosis capture the core process better. |
| GO:0016197 endosomal transport | IMP PMID:16262731 Effect of clathrin assembly lymphoid myeloid leukemia protei... | ACCEPT | Summary: This endosomal/cargo-trafficking term is consistent with PICALM-mediated sorting of endocytic cargo between plasma membrane and endosomal compartments. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0030276 clathrin binding | IDA PMID:16262731 Effect of clathrin assembly lymphoid myeloid leukemia protei... | ACCEPT | Summary: Direct clathrin/clathrin-heavy-chain binding is central to PICALM recruitment and clathrin-coated pit/vesicle assembly. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0048268 clathrin coat assembly | IMP PMID:16262731 Effect of clathrin assembly lymphoid myeloid leukemia protei... | ACCEPT | Summary: PICALM is required for orderly clathrin coat and coated-bud formation at the plasma membrane. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0030100 regulation of endocytosis | IMP PMID:18182011 Evidence for CALM in directing VAMP2 trafficking. | ACCEPT | Summary: This endocytosis/receptor-internalization term captures the core PICALM role in clathrin-mediated internalization and coated-vesicle maturation. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0042734 presynaptic membrane | ISS GO_REF:0000024 | ACCEPT | Summary: This synaptic-vesicle/presynaptic term is consistent with PICALM/AP180-family SNARE sorting and synaptic vesicle trafficking biology. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0045211 postsynaptic membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The GluR2/postsynaptic trafficking evidence is plausible but cargo-specific and not the main PICALM clathrin coat/SNARE sorting function. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0048471 perinuclear region of cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This annotation is supported or plausible for a specific cellular or disease context, but it is not the primary PICALM clathrin/SNARE adaptor function. Reason: Retain as non-core because the annotation is supported or plausible but represents a cargo-specific, disease-model, endothelial, iron-homeostasis, nuclear/leukemia, or downstream phenotype rather than the primary clathrin/SNARE adaptor function. |
| GO:0005545 1-phosphatidylinositol binding | ISS GO_REF:0000024 | ACCEPT | Summary: PICALM/CALM uses its ANTH domain to bind phosphoinositides/PIP2 at clathrin-coated membrane sites, anchoring its endocytic adaptor and curvature functions. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0005905 clathrin-coated pit | IDA PMID:10436022 Clathrin assembly lymphoid myeloid leukemia (CALM) protein: ... | ACCEPT | Summary: This vesicle/coated-pit term is consistent with PICALM acting at clathrin-coated pits and clathrin-coated vesicle intermediates. Reason: This location is consistent with PICALM/CALM recruitment to cytosolic membrane interfaces used for clathrin-mediated endocytosis, clathrin-coated vesicle formation, SNARE sorting, and endosomal/synaptic vesicle trafficking. |
| GO:0006898 receptor-mediated endocytosis | IDA PMID:10436022 Clathrin assembly lymphoid myeloid leukemia (CALM) protein: ... | ACCEPT | Summary: This endocytosis/receptor-internalization term captures the core PICALM role in clathrin-mediated internalization and coated-vesicle maturation. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0030276 clathrin binding | IDA PMID:10436022 Clathrin assembly lymphoid myeloid leukemia (CALM) protein: ... | ACCEPT | Summary: Direct clathrin/clathrin-heavy-chain binding is central to PICALM recruitment and clathrin-coated pit/vesicle assembly. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0016192 vesicle-mediated transport | TAS PMID:8643484 The t(10;11)(p13;q14) in the U937 cell line results in the f... | ACCEPT | Summary: This vesicle/coated-pit term is consistent with PICALM acting at clathrin-coated pits and clathrin-coated vesicle intermediates. Reason: This term aligns with the core PICALM/CALM role as a phosphoinositide-binding clathrin adaptor that organizes clathrin-coated pits/vesicles, controls vesicle curvature and maturation, and sorts endocytic cargo including small R-SNAREs. |
| GO:0065003 protein-containing complex assembly | TAS PMID:8643484 The t(10;11)(p13;q14) in the U937 cell line results in the f... | MODIFY | Summary: The generic protein-containing complex assembly annotation is too broad for PICALM; the supported complex-assembly role is clathrin coat assembly. Reason: The source publication identifies CALM as a clathrin assembly protein family member, and later direct evidence supports clathrin coat formation; use the specific clathrin coat assembly term instead of a generic complex-assembly term. Proposed replacements: clathrin coat assembly |
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Download this section (compressed HTML)Q: Should amyloid-beta/LRP1 transcytosis annotations be represented as cargo-specific receptor internalization/transcytosis rather than direct amyloid-beta binding by PICALM?
Suggested experts: Alzheimer BBB trafficking experts, GO endocytosis curators
Q: Which PICALM isoforms or tissue contexts should be distinguished for neuronal SNARE sorting, endothelial amyloid-beta clearance, erythroid transferrin receptor uptake, and nuclear/leukemia-associated localization?
Suggested experts: PICALM/CALM domain experts, GO isoform annotation curators
Experiment: Rescue PICALM-null human neurons, endothelial cells, and erythroid precursors with endogenous-level wild-type, PIP2-binding-defective, clathrin-binding-defective, and SNARE-binding-defective PICALM variants, then quantify clathrin-coated pit maturation, VAMP cargo sorting, LRP1/amyloid-beta transcytosis, and transferrin receptor uptake.
Hypothesis: PIP2/membrane-curvature, clathrin, and SNARE-binding modules make separable contributions to shared endocytic adaptor function and tissue-specific cargo phenotypes.
Type: endogenous-rescue separation-of-function trafficking assay
Experiment: Test whether PICALM directly binds amyloid-beta or instead binds LRP1/cargo complexes during endothelial transcytosis using purified components, LRP1-tail mutants, and live-cell cargo uptake assays.
Hypothesis: PICALM promotes amyloid-beta clearance primarily by recognizing LRP1/cargo endocytic machinery rather than by direct amyloid-beta binding.
Type: cargo-binding and endothelial transcytosis mechanism assay
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