LPAR1 is a class-A seven-transmembrane G protein-coupled receptor that binds extracellular lysophosphatidic acid at the plasma membrane and converts ligand occupancy into heterotrimeric G-protein signaling. Integrated human evidence supports coupling to Gi/Go, Gq/11, and G12/13; direct recombinant-human studies particularly establish a pertussis-toxin-sensitive Gi route to phospholipase-C-dependent inositol-phosphate production and cytosolic calcium elevation. Gi signaling also inhibits adenylyl cyclase, lowering cAMP and PKA activity, while Gq- and G12/13-linked branches connect the receptor to calcium and Rho-family cytoskeletal responses. LPAR1 is delivered to the cell surface through regulated biosynthetic trafficking and undergoes agonist-induced internalization to endosomes; RalA and GRK2 regulate signaling output and desensitization. Downstream LPAR1-dependent migration, actin remodeling, ciliogenesis inhibition, chemotaxis, and nervous-system development are tissue-, disease-, or organism-specific outcomes of this receptor mechanism rather than separate core molecular activities. UniProt records two splice products, Q92633-1 and Q92633-2; Q92633-2 replaces the first 15 residues, but no direct study has established isoform-specific ligand binding, coupling, trafficking, or tissue function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Marked as over-annotated because cytoplasm with an is_active_in qualifier misstates the functional compartment of an integral plasma-membrane and endosomal receptor. Reason: LPAR1 has cytoplasm-facing domains, but the intact receptor is active in the plasma membrane and traffics through endosomal membranes; those topological facts do not make cytoplasm an active compartment for the receptor. The broad family transfer therefore overstates localization and is less accurate than the direct plasma-membrane and endosome annotations. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: MGI:MGI:104615 SUPPORTS SOURCE BUT NOT TARGET The donor may support cytoplasmic signaling context, but is_active_in cytoplasm is unsafe for intact human LPAR1. PANTHER:PTN002733616 SUPPORTS SOURCE BUT NOT TARGET This family node also propagates signaling terms that do not fit LPAR1; it does not establish cytoplasm as the receptor's active compartment. UniProtKB:F1STP7 SUPPORTS SOURCE BUT NOT TARGET Source context does not justify is_active_in cytoplasm for intact human LPAR1. UniProtKB:O95977 SUPPORTS SOURCE BUT NOT TARGET Source context does not justify is_active_in cytoplasm for intact human LPAR1. UniProtKB:P34972 SUPPORTS SOURCE BUT NOT TARGET Source context does not justify is_active_in cytoplasm for intact human LPAR1. UniProtKB:Q92633 SUPPORTS SOURCE BUT NOT TARGET Self-support does not override the membrane topology of the intact receptor. UniProtKB:Q9HBW0 SUPPORTS SOURCE BUT NOT TARGET Source context does not justify is_active_in cytoplasm for intact human LPAR1. ZFIN:ZDB-GENE-030502-2 SUPPORTS SOURCE BUT NOT TARGET Source context does not justify is_active_in cytoplasm for intact human LPAR1. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: plasma membrane. Reason: The plasma membrane is the core site at which this seven-transmembrane receptor binds extracellular LPA and activates heterotrimeric G proteins. IBA, electronic, Reactome, and multiple direct human localization rows provide convergent support. Propagation Review Root cause: NO FAILURE CORE Sources checked: MGI:MGI:104615 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. MGI:MGI:108429 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. MGI:MGI:1096355 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. MGI:MGI:1858422 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. PANTHER:PTN002733616 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. RGD:2369 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. RGD:619713 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. RGD:620563 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. UniProtKB:F1STP7 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. UniProtKB:O95136 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. UniProtKB:P21453 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. UniProtKB:P21554 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. UniProtKB:P32245 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. UniProtKB:P33032 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. UniProtKB:P34972 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. UniProtKB:Q01718 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. UniProtKB:Q01726 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. UniProtKB:Q92633 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. UniProtKB:Q99500 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. UniProtKB:Q9UBY5 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. ZFIN:ZDB-GENE-030502-1 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. ZFIN:ZDB-GENE-030502-2 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. |
| GO:0022008 neurogenesis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: neurogenesis. Reason: Neurogenesis is supported by rodent Lpar1 genetics or orthology and is biologically plausible for the conserved receptor. It is nevertheless an organismal/developmental outcome of LPA signaling rather than the receptor's defining molecular activity, and the inferred human annotation is therefore retained as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002733659 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. RGD:620563 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway | IBA GO_REF:0000033 | REMOVE | Summary: Removed because adenylate cyclase-activating G protein-coupled receptor signaling pathway conflicts with the established LPAR1 G-protein coupling profile. Reason: Removed as an unsafe family-level IBA transfer. Human LPAR1 is established to couple to Gi/Go, Gq/11, and G12/13, and direct human evidence records inhibition—not activation—of adenylyl cyclase and reduced cAMP. The IBA donor set spans other GPCR subfamilies and does not establish Gs coupling for LPAR1, so this conflicts with the receptor-specific signaling profile rather than representing an additional core branch. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: MGI:MGI:1333809 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; the donor-side annotation may be valid, but activating adenylyl cyclase is not supported for LPAR1. PANTHER:PTN002733616 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; the donor-side annotation may be valid, but activating adenylyl cyclase is not supported for LPAR1. UniProtKB:F1STP7 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; the donor-side annotation may be valid, but activating adenylyl cyclase is not supported for LPAR1. UniProtKB:P32245 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; the donor-side annotation may be valid, but activating adenylyl cyclase is not supported for LPAR1. UniProtKB:P33032 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; the donor-side annotation may be valid, but activating adenylyl cyclase is not supported for LPAR1. UniProtKB:P41968 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; the donor-side annotation may be valid, but activating adenylyl cyclase is not supported for LPAR1. UniProtKB:Q01718 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; the donor-side annotation may be valid, but activating adenylyl cyclase is not supported for LPAR1. UniProtKB:Q01726 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; the donor-side annotation may be valid, but activating adenylyl cyclase is not supported for LPAR1. ZFIN:ZDB-GENE-021223-2 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; the donor-side annotation may be valid, but activating adenylyl cyclase is not supported for LPAR1. ZFIN:ZDB-GENE-030502-2 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; the donor-side annotation may be valid, but activating adenylyl cyclase is not supported for LPAR1. |
| GO:0070915 lysophosphatidic acid receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: lysophosphatidic acid receptor activity. Reason: This is the defining molecular activity of LPAR1. Human cloning, ligand binding, receptor activation, and structural studies establish a plasma-membrane GPCR selectively activated by lysophosphatidic acid; the inferred and direct rows are mutually corroborating. Propagation Review Root cause: NO FAILURE CORE Sources checked: MGI:MGI:108429 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. PANTHER:PTN002733659 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. UniProtKB:Q92633 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. ZFIN:ZDB-GENE-030616-499 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. |
| GO:0004930 G protein-coupled receptor activity | IEA GO_REF:0000002 | MODIFY | Summary: Modified because G protein-coupled receptor activity is valid in essence but less informative than the established LPAR1-specific term or partner class. Reason: The GPCR-family assignment is correct but unnecessarily broad for this well-characterized receptor. Direct human ligand-response studies and the existing specific annotations establish lysophosphatidic acid receptor activity, so GO:0070915 preserves the valid receptor claim while adding the known ligand specificity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR000276 SUPPORTS TRANSFER Exact WITH/FROM source; it supports the original broad assignment, while direct LPAR1 evidence supports a more informative term. Proposed replacements: lysophosphatidic acid receptor activity |
| GO:0005768 endosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: endosome. Reason: Human imaging shows ligand-induced LPAR1 internalization to endosomes. This localization is valid but represents receptor trafficking/desensitization after activation rather than the defining site of ligand recognition and G-protein activation. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0101 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: plasma membrane. Reason: The plasma membrane is the core site at which this seven-transmembrane receptor binds extracellular LPA and activates heterotrimeric G proteins. IBA, electronic, Reactome, and multiple direct human localization rows provide convergent support. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P61793 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. ensembl:ENSMUSP00000052581 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. UniProtKB-SubCell:SL-0039 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. |
| GO:0007186 G protein-coupled receptor signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: G protein-coupled receptor signaling pathway. Reason: LPAR1 is a ligand-activated heterotrimeric-G-protein-coupled receptor. This broad signaling process is directly demonstrated in human cells and remains a valid core parent of its Gi-, Gq-, and G12/13-dependent signaling branches. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00029021 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. InterPro:IPR000276 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. InterPro:IPR002277 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. InterPro:IPR004065 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. |
| GO:0007204 positive regulation of cytosolic calcium ion concentration | IEA GO_REF:0000117 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: positive regulation of cytosolic calcium ion concentration. Reason: LPA stimulation through human LPAR1 increases cytosolic calcium through a directly demonstrated pertussis-toxin-sensitive Gi-to-PLC/IP3 route. Broader evidence also supports parallel Gq coupling, but the direct human calcium experiment is not attributed to Gq alone. The electronic and TAS rows represent a core second-messenger response. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028136 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. |
| GO:0008289 lipid binding | IEA GO_REF:0000117 | MODIFY | Summary: Modified because lipid binding is valid in essence but less informative than the established LPAR1-specific term or partner class. Reason: Lipid binding is directionally correct but too broad. LPAR1 directly binds lysophosphatidic acid and transduces its signal, and GO:0035727 states that demonstrated ligand interaction without suggesting generic binding to unrelated lipids or phospholipids. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: ARBA:ARBA00027537 SUPPORTS TRANSFER Exact WITH/FROM source; it supports the original broad assignment, while direct LPAR1 evidence supports a more informative term. Proposed replacements: lysophosphatidic acid binding |
| GO:0009986 cell surface | IEA GO_REF:0000044 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: cell surface. Reason: Direct human localization and UniProt mapping place unstimulated LPAR1 at the cell surface, where ligand is encountered. Ligand-induced internalization does not negate this core steady-state functional location. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0310 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Modified because membrane is valid in essence but less informative than the established LPAR1-specific term or partner class. Reason: The InterPro-derived membrane assignment is valid but loses the biologically established compartment. LPAR1 is a seven-transmembrane receptor directly localized to the plasma membrane and cell surface, with ligand-induced endosomal internalization; GO:0005886 is therefore the appropriate specific steady-state functional location. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR000276 SUPPORTS TRANSFER Exact WITH/FROM source; it supports the original broad assignment, while direct LPAR1 evidence supports a more informative term. InterPro:IPR002277 SUPPORTS TRANSFER Exact WITH/FROM source; it supports the original broad assignment, while direct LPAR1 evidence supports a more informative term. InterPro:IPR004065 SUPPORTS TRANSFER Exact WITH/FROM source; it supports the original broad assignment, while direct LPAR1 evidence supports a more informative term. InterPro:IPR017452 SUPPORTS TRANSFER Exact WITH/FROM source; it supports the original broad assignment, while direct LPAR1 evidence supports a more informative term. Proposed replacements: plasma membrane |
| GO:0070915 lysophosphatidic acid receptor activity | IEA GO_REF:0000120 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: lysophosphatidic acid receptor activity. Reason: This is the defining molecular activity of LPAR1. Human cloning, ligand binding, receptor activation, and structural studies establish a plasma-membrane GPCR selectively activated by lysophosphatidic acid; the inferred and direct rows are mutually corroborating. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P61793 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. ensembl:ENSMUSP00000052581 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. InterPro:IPR002277 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. InterPro:IPR004065 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Modified because protein binding is valid in essence but less informative than the established LPAR1-specific term or partner class. Reason: The source quantitatively maps interactions between LPAR1's C-terminal PDZ-binding motif and twenty PDZ-domain proteins. Generic protein binding discards the experimentally defined binding module, whereas GO:0030165 captures the shared molecular feature across the normalized partner set. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36577757 LPA receptor 1 (LPAR1) is a novel interaction partner of Fil... | MODIFY | Summary: Modified because protein binding is valid in essence but less informative than the established LPAR1-specific term or partner class. Reason: The study identifies filamin A (P21333) as the LPAR1 partner and tests the interaction mechanistically. GO:0031005 records the informative partner class; generic protein binding adds no useful functional content. Proposed replacements: filamin binding |
| GO:0005515 protein binding | IPI PMID:39083597 Multiplexed mapping of the interactome of GPCRs with recepto... | MARK AS OVER ANNOTATED | Summary: Marked as over-annotated because generic protein binding does not establish a defining LPAR1 activity. Reason: The RAMP interactome study provides experimental evidence for plasma-membrane interactions with RAMP1, RAMP2, and RAMP3, and the occurs_in extension is retained. However, GO:0005515 is uninformative and the screen does not yet establish how these contacts alter LPAR1 ligand specificity, trafficking, or signaling. The annotation is retained with curator deference but should not be treated as a defining molecular function. |
| GO:0001965 G-protein alpha-subunit binding | IEA GO_REF:0000107 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: G-protein alpha-subunit binding. Reason: G-alpha-subunit engagement is a proximal, defining part of LPAR1 signaling. Orthology-based support is consistent with direct human evidence for coupling to Gi/Go, Gq/11, and G12/13, so the inferred molecular function is biologically sound and core. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. |
| GO:0005543 phospholipid binding | IEA GO_REF:0000107 | MODIFY | Summary: Modified because phospholipid binding is valid in essence but less informative than the established LPAR1-specific term or partner class. Reason: Phospholipid binding is directionally correct but too broad. LPAR1 directly binds lysophosphatidic acid and transduces its signal, and GO:0035727 states that demonstrated ligand interaction without suggesting generic binding to unrelated lipids or phospholipids. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; it supports the original broad assignment, while direct LPAR1 evidence supports a more informative term. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; it supports the original broad assignment, while direct LPAR1 evidence supports a more informative term. Proposed replacements: lysophosphatidic acid binding |
| GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway. Reason: LPAR1 coupling to Gi/Go inhibits adenylyl cyclase and lowers cellular cAMP. The mouse/rat inferences agree with direct human receptor signaling evidence, making this a core proximal second-messenger branch rather than a downstream phenotype. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P61793 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. ensembl:ENSMUSP00000052581 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. |
| GO:0008360 regulation of cell shape | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: regulation of cell shape. Reason: Regulation of cell shape is a documented or orthology-supported downstream consequence of LPAR1 signaling in a specific cellular, developmental, inflammatory, or disease context. It is retained because the source evidence is biologically coherent, but it is not the core ligand-binding/G-protein-coupling activity of the receptor. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61793 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSMUSP00000052581 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0010977 negative regulation of neuron projection development | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: negative regulation of neuron projection development. Reason: Negative regulation of neuron projection development is supported by rodent Lpar1 genetics or orthology and is biologically plausible for the conserved receptor. It is nevertheless an organismal/developmental outcome of LPA signaling rather than the receptor's defining molecular activity, and the inferred human annotation is therefore retained as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61793 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSMUSP00000052581 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0014003 oligodendrocyte development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: oligodendrocyte development. Reason: Oligodendrocyte development is supported by rodent Lpar1 genetics or orthology and is biologically plausible for the conserved receptor. It is nevertheless an organismal/developmental outcome of LPA signaling rather than the receptor's defining molecular activity, and the inferred human annotation is therefore retained as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0021549 cerebellum development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: cerebellum development. Reason: Cerebellum development is supported by rodent Lpar1 genetics or orthology and is biologically plausible for the conserved receptor. It is nevertheless an organismal/developmental outcome of LPA signaling rather than the receptor's defining molecular activity, and the inferred human annotation is therefore retained as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0021554 optic nerve development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: optic nerve development. Reason: Optic nerve development is supported by rodent Lpar1 genetics or orthology and is biologically plausible for the conserved receptor. It is nevertheless an organismal/developmental outcome of LPA signaling rather than the receptor's defining molecular activity, and the inferred human annotation is therefore retained as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0022008 neurogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: neurogenesis. Reason: Neurogenesis is supported by rodent Lpar1 genetics or orthology and is biologically plausible for the conserved receptor. It is nevertheless an organismal/developmental outcome of LPA signaling rather than the receptor's defining molecular activity, and the inferred human annotation is therefore retained as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0022038 corpus callosum development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: corpus callosum development. Reason: Corpus callosum development is supported by rodent Lpar1 genetics or orthology and is biologically plausible for the conserved receptor. It is nevertheless an organismal/developmental outcome of LPA signaling rather than the receptor's defining molecular activity, and the inferred human annotation is therefore retained as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0030165 PDZ domain binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: PDZ domain binding. Reason: The C-terminal PDZ-binding motif and direct human PDZ-fragment interaction map support this activity. It organizes receptor-associated scaffolds and trafficking but is accessory to the defining LPA receptor activity, so it is non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61793 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSMUSP00000052581 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0042552 myelination | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: myelination. Reason: Myelination is supported by rodent Lpar1 genetics or orthology and is biologically plausible for the conserved receptor. It is nevertheless an organismal/developmental outcome of LPA signaling rather than the receptor's defining molecular activity, and the inferred human annotation is therefore retained as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0042734 presynaptic membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: presynaptic membrane. Reason: Presynaptic membrane is a neuron-specific localization transferred from rat Lpar1. The orthologous receptor and conserved neuronal biology make the transfer defensible, but this specialized synaptic compartment is context-dependent and does not replace the general plasma-membrane core location. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: neuronal cell body. Reason: Neuronal cell body is a neuron-specific localization transferred from rat Lpar1. The orthologous receptor and conserved neuronal biology make the transfer defensible, but this specialized synaptic compartment is context-dependent and does not replace the general plasma-membrane core location. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0043065 positive regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: positive regulation of apoptotic process. Reason: Positive regulation of apoptotic process is a documented or orthology-supported downstream consequence of LPAR1 signaling in a specific cellular, developmental, inflammatory, or disease context. It is retained because the source evidence is biologically coherent, but it is not the core ligand-binding/G-protein-coupling activity of the receptor. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0043197 dendritic spine | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: dendritic spine. Reason: Dendritic spine is a neuron-specific localization transferred from rat Lpar1. The orthologous receptor and conserved neuronal biology make the transfer defensible, but this specialized synaptic compartment is context-dependent and does not replace the general plasma-membrane core location. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0043198 dendritic shaft | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: dendritic shaft. Reason: Dendritic shaft is a neuron-specific localization transferred from rat Lpar1. The orthologous receptor and conserved neuronal biology make the transfer defensible, but this specialized synaptic compartment is context-dependent and does not replace the general plasma-membrane core location. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0045211 postsynaptic membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: postsynaptic membrane. Reason: Postsynaptic membrane is a neuron-specific localization transferred from rat Lpar1. The orthologous receptor and conserved neuronal biology make the transfer defensible, but this specialized synaptic compartment is context-dependent and does not replace the general plasma-membrane core location. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0051496 positive regulation of stress fiber assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: positive regulation of stress fiber assembly. Reason: Positive regulation of stress fiber assembly is a documented or orthology-supported downstream consequence of LPAR1 signaling in a specific cellular, developmental, inflammatory, or disease context. It is retained because the source evidence is biologically coherent, but it is not the core ligand-binding/G-protein-coupling activity of the receptor. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61793 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSMUSP00000052581 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0060999 positive regulation of dendritic spine development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: positive regulation of dendritic spine development. Reason: Positive regulation of dendritic spine development is supported by rodent Lpar1 genetics or orthology and is biologically plausible for the conserved receptor. It is nevertheless an organismal/developmental outcome of LPA signaling rather than the receptor's defining molecular activity, and the inferred human annotation is therefore retained as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0071453 cellular response to oxygen levels | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: cellular response to oxygen levels. Reason: Cellular response to oxygen levels is a documented or orthology-supported downstream consequence of LPAR1 signaling in a specific cellular, developmental, inflammatory, or disease context. It is retained because the source evidence is biologically coherent, but it is not the core ligand-binding/G-protein-coupling activity of the receptor. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0071673 positive regulation of smooth muscle cell chemotaxis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: positive regulation of smooth muscle cell chemotaxis. Reason: Positive regulation of smooth muscle cell chemotaxis is a documented or orthology-supported downstream consequence of LPAR1 signaling in a specific cellular, developmental, inflammatory, or disease context. It is retained because the source evidence is biologically coherent, but it is not the core ligand-binding/G-protein-coupling activity of the receptor. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0098693 regulation of synaptic vesicle cycle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: regulation of synaptic vesicle cycle. Reason: Regulation of synaptic vesicle cycle is a documented or orthology-supported downstream consequence of LPAR1 signaling in a specific cellular, developmental, inflammatory, or disease context. It is retained because the source evidence is biologically coherent, but it is not the core ligand-binding/G-protein-coupling activity of the receptor. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: glutamatergic synapse. Reason: Glutamatergic synapse is a neuron-specific localization transferred from rat Lpar1. The orthologous receptor and conserved neuronal biology make the transfer defensible, but this specialized synaptic compartment is context-dependent and does not replace the general plasma-membrane core location. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0098982 GABA-ergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: GABA-ergic synapse. Reason: Gaba-ergic synapse is a neuron-specific localization transferred from rat Lpar1. The orthologous receptor and conserved neuronal biology make the transfer defensible, but this specialized synaptic compartment is context-dependent and does not replace the general plasma-membrane core location. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0099149 regulation of postsynaptic neurotransmitter receptor internalization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: regulation of postsynaptic neurotransmitter receptor internalization. Reason: Regulation of postsynaptic neurotransmitter receptor internalization is a documented or orthology-supported downstream consequence of LPAR1 signaling in a specific cellular, developmental, inflammatory, or disease context. It is retained because the source evidence is biologically coherent, but it is not the core ligand-binding/G-protein-coupling activity of the receptor. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0141162 negative regulation of cAMP/PKA signal transduction | IEA GO_REF:0000107 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: negative regulation of cAMP/PKA signal transduction. Reason: Negative regulation of cAMP/PKA signaling is the downstream consequence of the receptor's established Gi/Go-mediated inhibition of adenylyl cyclase. The rat-derived inference is conserved and mechanistically proximal to core LPAR1 signaling. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. |
| GO:1904566 cellular response to 1-oleoyl-sn-glycerol 3-phosphate | IEA GO_REF:0000107 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: cellular response to 1-oleoyl-sn-glycerol 3-phosphate. Reason: The named chemical is a lysophosphatidic-acid species, so cellular response to it directly captures the ligand-triggered role of LPAR1. Orthology support is consistent with direct human LPA-response experiments and is retained as core. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P61794 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. ensembl:ENSRNOP00000043652 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. |
| GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway | IMP PMID:19733258 Lysophosphatidic acid mediates migration of human mesenchyma... | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: phospholipase C-activating G protein-coupled receptor signaling pathway. Reason: Human receptor-signaling studies support a pertussis-toxin-sensitive Gi-to-PLC route and a distinct RalA-linked PLC branch downstream of LPAR1; integrated evidence also supports parallel Gq coupling. This is a proximal core signaling branch, while the mesenchymal-stem-cell migration outcome is reviewed separately as non-core. |
| GO:0007186 G protein-coupled receptor signaling pathway | IDA PMID:19306925 Dual regulation of lysophosphatidic acid (LPA1) receptor sig... | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: G protein-coupled receptor signaling pathway. Reason: LPAR1 is a ligand-activated heterotrimeric-G-protein-coupled receptor. This broad signaling process is directly demonstrated in human cells and remains a valid core parent of its Gi-, Gq-, and G12/13-dependent signaling branches. |
| GO:0005886 plasma membrane | EXP PMID:25025571 Molecular regulation of lysophosphatidic acid receptor 1 tra... | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: plasma membrane. Reason: The plasma membrane is the core site at which this seven-transmembrane receptor binds extracellular LPA and activates heterotrimeric G proteins. IBA, electronic, Reactome, and multiple direct human localization rows provide convergent support. |
| GO:0005886 plasma membrane | EXP PMID:26091040 Crystal Structure of Antagonist Bound Human Lysophosphatidic... | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: plasma membrane. Reason: The plasma membrane is the core site at which this seven-transmembrane receptor binds extracellular LPA and activates heterotrimeric G proteins. IBA, electronic, Reactome, and multiple direct human localization rows provide convergent support. |
| GO:0009986 cell surface | EXP PMID:25025571 Molecular regulation of lysophosphatidic acid receptor 1 tra... | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: cell surface. Reason: Direct human localization and UniProt mapping place unstimulated LPAR1 at the cell surface, where ligand is encountered. Ligand-induced internalization does not negate this core steady-state functional location. |
| GO:1902018 negative regulation of cilium assembly | IDA PMID:31204173 Akt Regulates a Rab11-Effector Switch Required for Ciliogene... | KEEP AS NON CORE | Summary: Retained as a direct but contextual cellular consequence of LPAR1 signaling: inhibition of cilium assembly. Reason: PMID:31204173 directly shows that serum LPA acting through LPAR1 activates PI3K/Akt, disrupts the Rab11a-Rabin8 interaction, and inhibits ciliogenesis independently of cell-cycle effects. This is a mechanistically supported downstream cellular outcome, but it is not the receptor's defining ligand-binding or G-protein-coupling activity. |
| GO:0005768 endosome | IDA PMID:19306925 Dual regulation of lysophosphatidic acid (LPA1) receptor sig... | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: endosome. Reason: Human imaging shows ligand-induced LPAR1 internalization to endosomes. This localization is valid but represents receptor trafficking/desensitization after activation rather than the defining site of ligand recognition and G-protein activation. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: plasma membrane. Reason: The plasma membrane is the core site at which this seven-transmembrane receptor binds extracellular LPA and activates heterotrimeric G proteins. IBA, electronic, Reactome, and multiple direct human localization rows provide convergent support. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P61793 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. |
| GO:0005886 plasma membrane | IDA PMID:19306925 Dual regulation of lysophosphatidic acid (LPA1) receptor sig... | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: plasma membrane. Reason: The plasma membrane is the core site at which this seven-transmembrane receptor binds extracellular LPA and activates heterotrimeric G proteins. IBA, electronic, Reactome, and multiple direct human localization rows provide convergent support. |
| GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway. Reason: LPAR1 coupling to Gi/Go inhibits adenylyl cyclase and lowers cellular cAMP. The mouse/rat inferences agree with direct human receptor signaling evidence, making this a core proximal second-messenger branch rather than a downstream phenotype. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P61793 SUPPORTS TRANSFER Exact WITH/FROM source; its propagated assignment agrees with established human LPAR1 biology. |
| GO:0008360 regulation of cell shape | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: regulation of cell shape. Reason: Regulation of cell shape is a documented or orthology-supported downstream consequence of LPAR1 signaling in a specific cellular, developmental, inflammatory, or disease context. It is retained because the source evidence is biologically coherent, but it is not the core ligand-binding/G-protein-coupling activity of the receptor. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61793 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0010977 negative regulation of neuron projection development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: negative regulation of neuron projection development. Reason: Negative regulation of neuron projection development is supported by rodent Lpar1 genetics or orthology and is biologically plausible for the conserved receptor. It is nevertheless an organismal/developmental outcome of LPA signaling rather than the receptor's defining molecular activity, and the inferred human annotation is therefore retained as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61793 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0035025 positive regulation of Rho protein signal transduction | ISS GO_REF:0000024 | ACCEPT | Summary: Accepted as a proximal core branch of LPAR1 signaling through G12/13 to Rho. Reason: LPAR1 couples to G12/13 and promotes Rho activation; the founding Lpar1 study also separates pertussis-toxin-insensitive cell rounding from Gi activation. Rho activation is therefore a proximal receptor-signaling branch, distinct from the more downstream stress-fiber, migration, and developmental phenotypes. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P61793 SUPPORTS TRANSFER The mouse ortholog transfer agrees with the established human LPAR1 G12/13-to-Rho signaling branch. |
| GO:0043410 positive regulation of MAPK cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: positive regulation of MAPK cascade. Reason: Positive regulation of mapk cascade is a documented or orthology-supported downstream consequence of LPAR1 signaling in a specific cellular, developmental, inflammatory, or disease context. It is retained because the source evidence is biologically coherent, but it is not the core ligand-binding/G-protein-coupling activity of the receptor. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61793 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0051496 positive regulation of stress fiber assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: positive regulation of stress fiber assembly. Reason: Positive regulation of stress fiber assembly is a documented or orthology-supported downstream consequence of LPAR1 signaling in a specific cellular, developmental, inflammatory, or disease context. It is retained because the source evidence is biologically coherent, but it is not the core ligand-binding/G-protein-coupling activity of the receptor. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P61793 SUPPORTS TRANSFER Exact WITH/FROM source; transfer is biologically defensible but the term is contextual or secondary for human LPAR1. |
| GO:0060326 cell chemotaxis | IMP PMID:19733258 Lysophosphatidic acid mediates migration of human mesenchyma... | KEEP AS NON CORE | Summary: Retained as a direct but context-specific human mesenchymal-stem-cell migration phenotype. Reason: PMID:19733258 shows that LPA-LPAR1 drives rheumatoid-arthritis synovial-fluid-induced human bone-marrow mesenchymal stem-cell migration through CaMKII, with receptor-specific RNA-silencing support. This directly supports chemotaxis in that cellular context, but the migration phenotype is downstream of the receptor's core ligand-binding and proximal signaling activities. |
| GO:0070915 lysophosphatidic acid receptor activity | IDA PMID:19306925 Dual regulation of lysophosphatidic acid (LPA1) receptor sig... | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: lysophosphatidic acid receptor activity. Reason: This is the defining molecular activity of LPAR1. Human cloning, ligand binding, receptor activation, and structural studies establish a plasma-membrane GPCR selectively activated by lysophosphatidic acid; the inferred and direct rows are mutually corroborating. |
| GO:0035727 lysophosphatidic acid binding | IDA PMID:9070858 Molecular cloning of the human Edg2 protein and its identifi... | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: lysophosphatidic acid binding. Reason: Direct human experiments identify lysophosphatidic acid as the ligand for the cloned receptor. Ligand binding is integral to the receptor mechanism and is appropriately retained as core. |
| GO:0070915 lysophosphatidic acid receptor activity | IMP PMID:9070858 Molecular cloning of the human Edg2 protein and its identifi... | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: lysophosphatidic acid receptor activity. Reason: This is the defining molecular activity of LPAR1. Human cloning, ligand binding, receptor activation, and structural studies establish a plasma-membrane GPCR selectively activated by lysophosphatidic acid; the inferred and direct rows are mutually corroborating. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-379048 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: plasma membrane. Reason: The plasma membrane is the core site at which this seven-transmembrane receptor binds extracellular LPA and activates heterotrimeric G proteins. IBA, electronic, Reactome, and multiple direct human localization rows provide convergent support. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-380073 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: plasma membrane. Reason: The plasma membrane is the core site at which this seven-transmembrane receptor binds extracellular LPA and activates heterotrimeric G proteins. IBA, electronic, Reactome, and multiple direct human localization rows provide convergent support. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-419389 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: plasma membrane. Reason: The plasma membrane is the core site at which this seven-transmembrane receptor binds extracellular LPA and activates heterotrimeric G proteins. IBA, electronic, Reactome, and multiple direct human localization rows provide convergent support. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-749448 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: plasma membrane. Reason: The plasma membrane is the core site at which this seven-transmembrane receptor binds extracellular LPA and activates heterotrimeric G proteins. IBA, electronic, Reactome, and multiple direct human localization rows provide convergent support. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-749452 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: plasma membrane. Reason: The plasma membrane is the core site at which this seven-transmembrane receptor binds extracellular LPA and activates heterotrimeric G proteins. IBA, electronic, Reactome, and multiple direct human localization rows provide convergent support. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-749454 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: plasma membrane. Reason: The plasma membrane is the core site at which this seven-transmembrane receptor binds extracellular LPA and activates heterotrimeric G proteins. IBA, electronic, Reactome, and multiple direct human localization rows provide convergent support. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-749456 | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: plasma membrane. Reason: The plasma membrane is the core site at which this seven-transmembrane receptor binds extracellular LPA and activates heterotrimeric G proteins. IBA, electronic, Reactome, and multiple direct human localization rows provide convergent support. |
| GO:0005515 protein binding | IPI PMID:19306925 Dual regulation of lysophosphatidic acid (LPA1) receptor sig... | MODIFY | Summary: Modified because protein binding is valid in essence but less informative than the established LPAR1-specific term or partner class. Reason: The two normalized partners are the small GTPase RALA and G-protein-coupled receptor kinase 2. The paper directly studies both interactions in receptor trafficking/signaling, so GO:0031267 and GO:0019901 retain the distinct informative binding activities hidden by generic protein binding. Proposed replacements: small GTPase binding protein kinase binding |
| GO:0009986 cell surface | IDA PMID:19306925 Dual regulation of lysophosphatidic acid (LPA1) receptor sig... | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: cell surface. Reason: Direct human localization and UniProt mapping place unstimulated LPAR1 at the cell surface, where ligand is encountered. Ligand-induced internalization does not negate this core steady-state functional location. |
| GO:0030139 endocytic vesicle | IDA PMID:19306925 Dual regulation of lysophosphatidic acid (LPA1) receptor sig... | KEEP AS NON CORE | Summary: Retained as a valid but contextual or downstream aspect of LPAR1 biology: endocytic vesicle. Reason: The receptor colocalizes with RALA in endocytic vesicles after LPA treatment. The qualifier correctly limits the claim to colocalization, and the trafficking state is retained as contextual rather than core. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IEP PMID:12761501 Large-scale identification and characterization of human gen... | UNDECIDED | Summary: The accessible abstract does not expose the LPAR1-specific evidence for this experimental NF-kappaB-response annotation. Reason: The IEP annotation indicates that the curator had experimental expression-pattern evidence, but the cached PMID:12761501 record is abstract-only and does not name LPAR1. Without the relevant full-text result, the gene-specific support cannot be independently assessed. Curator deference precludes removal, while the inaccessible evidence precludes accepting or retaining the downstream process as established. |
| GO:0004930 G protein-coupled receptor activity | TAS PMID:8922387 Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic a... | MODIFY | Summary: Modified because G protein-coupled receptor activity is valid in essence but less informative than the established LPAR1-specific term or partner class. Reason: The GPCR-family assignment is correct but unnecessarily broad for this well-characterized receptor. Direct human ligand-response studies and the existing specific annotations establish lysophosphatidic acid receptor activity, so GO:0070915 preserves the valid receptor claim while adding the known ligand specificity. Proposed replacements: lysophosphatidic acid receptor activity |
| GO:0005886 plasma membrane | TAS PMID:9070858 Molecular cloning of the human Edg2 protein and its identifi... | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: plasma membrane. Reason: The plasma membrane is the core site at which this seven-transmembrane receptor binds extracellular LPA and activates heterotrimeric G proteins. IBA, electronic, Reactome, and multiple direct human localization rows provide convergent support. |
| GO:0007186 G protein-coupled receptor signaling pathway | TAS PMID:8922387 Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic a... | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: G protein-coupled receptor signaling pathway. Reason: LPAR1 is a ligand-activated heterotrimeric-G-protein-coupled receptor. This broad signaling process is directly demonstrated in human cells and remains a valid core parent of its Gi-, Gq-, and G12/13-dependent signaling branches. |
| GO:0007204 positive regulation of cytosolic calcium ion concentration | TAS PMID:9804623 Recombinant human G protein-coupled lysophosphatidic acid re... | ACCEPT | Summary: Accepted as a core component of LPAR1 ligand recognition, membrane localization, or proximal G-protein signaling: positive regulation of cytosolic calcium ion concentration. Reason: LPA stimulation through human LPAR1 increases cytosolic calcium through a directly demonstrated pertussis-toxin-sensitive Gi-to-PLC/IP3 route. Broader evidence also supports parallel Gq coupling, but the direct human calcium experiment is not attributed to Gq alone. The electronic and TAS rows represent a core second-messenger response. |
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Download this section (compressed HTML)Q: Do Q92633-1 and Q92633-2 differ in maturation, plasma-membrane delivery, LPA affinity, G-protein coupling, or tissue distribution?
Q: What are the relative Gi/Go, Gq/11, G12/13, and beta-arrestin coupling efficacies of endogenous human LPAR1 in physiologically relevant cell types?
Q: Do RAMP1-3 alter LPAR1 ligand pharmacology, surface residence, coupling bias, or desensitization in cells that naturally coexpress the proteins?
Q: Which PDZ-domain scaffolds bind full-length endogenous LPAR1 strongly enough to control receptor trafficking or signaling?
Experiment: Express Q92633-1 and Q92633-2 from matched genomic landing sites and, where possible, tag endogenous isoforms selectively. Quantify glycosylation, total and surface abundance, LPA-binding affinity, G-protein and beta-arrestin recruitment, internalization, and recycling under identical conditions.
Hypothesis: The alternative LPAR1 N termini produce isoform-specific differences in receptor maturation and signaling.
Type: isoform-resolved receptor pharmacology and trafficking
Experiment: Use CRISPR-tagged endogenous LPAR1 in neuronal, mesenchymal, epithelial, and fibroblast models with multiplexed conformational or BRET biosensors for Gi/o, Gq/11, G12/13, beta-arrestin, cAMP, IP3, calcium, and Rho. Resolve ligand-dose and time-course responses with selective G-alpha knockouts and rescue.
Hypothesis: Native LPAR1 coupling is cell-context dependent, with Gi/o dominating the PLC/calcium response in some human cells and Gq/11 or G12/13 dominating in others.
Type: endogenous multiplexed GPCR coupling analysis
Experiment: In human cells with endogenous LPAR1 and RAMP expression, knock out each RAMP singly and in combination, restore wild-type or interaction-defective RAMPs, and measure LPA affinity, surface residence, internalization, recycling, G-protein bias, and beta-arrestin recruitment.
Hypothesis: RAMP proteins create distinct LPAR1 trafficking or signaling states rather than serving only as detectable membrane contacts.
Type: RAMP genetic epistasis and receptor pharmacology
Experiment: Compare endogenous proximity labeling and affinity purification for wild-type LPAR1 and a precise PDZ-binding-motif mutant before and after LPA stimulation. Validate motif-dependent partners individually and test their requirement for surface delivery, endocytosis, recycling, and signaling resensitization.
Hypothesis: A restricted subset of PDZ proteins binds the intact LPAR1 C-terminal motif in cells and controls agonist-induced receptor trafficking.
Type: endogenous receptor-scaffold interactome and functional validation
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: Functional differences between Q92633-1 and Q92633-2 have not been established.
OPEN BIOLOGY
What is known: Two alternatively spliced products are recorded, and isoform 2 replaces the first 15 residues, but none of the audited ligand-binding, signaling, trafficking, localization, or phenotype studies compares the isoforms.
Significance: The altered N terminus could affect receptor maturation, surface delivery, or ligand access, so assuming identical biology may conceal a regulatory product distinction.
What would resolve it: Compare endogenous or equivalently expressed tagged isoforms for glycosylation, surface abundance, LPA affinity, G-protein coupling, internalization, and tissue-specific expression.
Provenance (the field's own admissions):
Gap: The quantitative contributions of Gi/Go, Gq/11, and G12/13 to native human LPAR1 signaling remain incompletely resolved across cell types and ligand concentrations.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: Direct recombinant-human evidence strongly supports pertussis-toxin-sensitive Gi-dependent PLC/calcium signaling, while integrated pathway and UniProt records support the broader coupling repertoire; these sources do not provide matched quantitative coupling measurements in native cells.
Significance: Branch-specific coupling determines whether LPAR1 primarily alters cAMP, calcium, Rho signaling, or a combination in each physiological setting.
What would resolve it: Measure endogenous receptor coupling with parallel Gi/o, Gq/11, G12/13, beta-arrestin, cAMP, IP3, calcium, and Rho biosensors under matched ligand-dose and time-course conditions.
Gap: The physiological effects of LPAR1 interactions with RAMP1, RAMP2, and RAMP3 are unknown.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: A systematic plasma-membrane interactome detects all three RAMP contacts, but the accessible evidence does not establish an LPAR1-specific change in ligand affinity, surface delivery, internalization, G-protein preference, or beta-arrestin recruitment.
Significance: RAMP-dependent modulation could explain cell-type differences in LPAR1 pharmacology and signaling without constituting a universal stable complex.
What would resolve it: Test each RAMP by endogenous knockout and add-back in coexpressing human cells, quantifying receptor surface abundance, LPA binding, coupling bias, internalization, and desensitization.
Gap: Which PDZ-domain interactions occur with full-length endogenous LPAR1 and materially regulate receptor trafficking or signaling is unresolved.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: The LPAR1 C-terminal motif binds a broad panel of isolated PDZ domains with measured affinities, but fragment binding alone does not establish every full-length interaction in a shared physiological compartment.
Significance: Identifying the load-bearing scaffolds would distinguish receptor-specific trafficking control from a promiscuous motif-level interactome.
What would resolve it: Combine endogenous LPAR1 proximity labeling and coimmunoprecipitation with C-terminal motif mutants, then test validated partners for effects on surface delivery, endocytosis, recycling, and branch-specific signaling.
Provenance (the field's own admissions):
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