{"gene":"CABP1","run_date":"2026-04-28T17:28:52","timeline":{"discoveries":[{"year":2005,"finding":"CaBP1 (neuronal EF-hand protein) binds Mg2+ constitutively at EF-1 (Kd ~300 µM) and Ca2+ cooperatively at EF-3 and EF-4 (Kd ~2.5 µM); apo-CaBP1 forms a molten-globule, while Mg2+ and Ca2+ induce distinct conformational changes including protein dimerization and increased folding stability.","method":"NMR, microcalorimetry (ITC), and biophysical studies on recombinant CaBP1","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 — multiple orthogonal biophysical methods (NMR + ITC + thermal denaturation) in a single rigorous study","pmids":["16147998"],"is_preprint":false},{"year":2008,"finding":"NMR structures of CaBP1 in Mg2+-bound and Ca2+-bound states show the N-domain (EF1/EF2) remains closed with Mg2+ at EF1, while the C-domain undergoes a Ca2+-induced closed-to-open transition exposing hydrophobic residues (Leu132, His134, Ile141, Ile144, Val148). The Ca2+-bound C-domain binds the N-terminal suppressor+ligand-binding core region of InsP3R1 (residues 1–587) without affecting InsP3 binding itself.","method":"NMR structure determination, ITC binding assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 — NMR structures combined with ITC functional binding measurements","pmids":["19008222"],"is_preprint":false},{"year":2013,"finding":"CaBP1 inhibits InsP3R activity by clamping intersubunit interactions: its C-lobe hydrophobic residues (V101, L104, V162) contact InsP3-binding core β-domain residues (L302, I364, L393) of InsP3R1, and CaBP1 promotes cross-linking at the suppressor–core domain interface that InsP3 disrupts during gating; CaBP1 forms an extended tetrameric turret at the cytosolic vestibule.","method":"NMR paramagnetic relaxation enhancement, docking, targeted cross-linking, functional IP3R activity assays","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 — NMR PRE structural restraints + targeted cross-linking + functional channel assay with mutational validation","pmids":["23650371"],"is_preprint":false},{"year":2010,"finding":"CaBP1 modulates CaV1.2 through two structural modules: the C-lobe anchors to the CaV1.2 IQ domain (overlapping with Ca2+/CaM C-lobe site), while the N-lobe/linker module (specifically interlobe linker residue Glu94) mediates inhibition of Ca2+-dependent inactivation (CDI) and induction of Ca2+-dependent facilitation (CDF); functional EF-hands are not required for CDI inhibition unlike CaM.","method":"Crystal structure, electrophysiology, mutagenesis","journal":"Structure (London, England : 1993)","confidence":"High","confidence_rationale":"Tier 1 — structure combined with mutagenesis and functional electrophysiology","pmids":["21134641"],"is_preprint":false},{"year":2013,"finding":"Apo-state CaBP1 and apo-CaM compete directly for the CaV1 IQ domain, with their relative apo-state binding affinities quantitatively explaining opposing channel regulation; Ca2+/CaM achieves sub-picomolar affinity for the IQ domain; covalent CaM tethering to the channel completely blocks this competition.","method":"ITC, cell-based electrophysiology, mathematical modeling, covalent tethering experiments","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1–2 — ITC with functional electrophysiology and quantitative modeling, multiple orthogonal methods","pmids":["23811053"],"is_preprint":false},{"year":2011,"finding":"CaBP1 interacts with the distal C-terminal third of the CaV1.2 N-terminal domain in a Ca2+-independent manner (distinct from the calmodulin-binding site), while a separate proximal N-terminal segment is required for transduction of CaBP1's effect on voltage-dependent inactivation (VDI); CaBP1 also causes a depolarizing shift in voltage-dependent activation.","method":"Binding assays (pull-down), electrophysiology with deletion mutants","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — pull-down binding plus electrophysiology with deletion mutants from single lab","pmids":["21383011"],"is_preprint":false},{"year":2026,"finding":"NMR structures of Ca2+-CaBP1 bound to the CaV1.2 IQ peptide identify specific contact residues (CaBP1: A107, F111, M128, L131, I144, M165; IQ: I1654, Y1657, F1658) and a salt bridge (CaBP1-D140 – IQ-K1662); Ca2+ binding to EF3/EF4 enhances IQ-peptide affinity >40-fold; electrophysiology shows CaBP1 increases CaV1.2 channel open probability.","method":"NMR structure determination, ITC, electrophysiology, mutagenesis","journal":"Biochemistry","confidence":"High","confidence_rationale":"Tier 1 — NMR structure + ITC + electrophysiology + mutagenesis in single study","pmids":["41859936"],"is_preprint":false},{"year":2007,"finding":"CaBP1 binds the IQ motifs in the myo1c regulatory domain, competing with calmodulin; this competition is enhanced in the presence of Ca2+. CaBP1 has higher apparent affinity for myo1c than CIB1. Both proteins colocalize with myo1c in cells.","method":"Pull-down assays, fluorescence microscopy colocalization","journal":"Journal of muscle research and cell motility","confidence":"Medium","confidence_rationale":"Tier 3 — pull-down plus colocalization, single lab","pmids":["17994197"],"is_preprint":false},{"year":1994,"finding":"CaBP1 (rat P5 homolog, ER-resident with KDEL signal) catalyzes renaturation of denatured reduced proteins (Fab fragment, RNase AIII) in a GSH/GSSG redox-dependent manner, showing strong synergism with PDI for RNase AIII refolding, indicating it can catalyze disulfide bond formation and isomerization in the secretory pathway.","method":"In vitro renaturation assays with purified protein, activity measurements","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1 — in vitro reconstituted enzymatic assay, but context is ER-resident PDI-family protein, not the neuronal CaBP1 EF-hand protein; these are distinct proteins sharing the CaBP1 name in rat","pmids":["8300576"],"is_preprint":false},{"year":1995,"finding":"CaBP1 (rat ER PDI-family member) is a substrate for thioredoxin reductase, catalyzes NADPH-dependent insulin disulfide reduction, and its thioredoxin active-site disulfide has a redox potential similar to PDI (~−235 mV), much higher than wild-type thioredoxin, consistent with a role in forming protein disulfide bonds.","method":"In vitro thioredoxin reductase assay, NADPH stoichiometry, redox potential measurement using P34H Trx mutant equilibrium","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 1 — in vitro enzymatic assays with quantitative redox measurements; applies to the ER PDI-family CaBP1","pmids":["7835433"],"is_preprint":false},{"year":1994,"finding":"CaBP1 (rat ER PDI-family protein) localizes to the ER lumen (not the intermediate compartment), as demonstrated by subcellular fractionation, double immunofluorescence showing colocalization with calreticulin but not ERGIC-53, and by maintained reticular localization upon overexpression; retention is mediated by the C-terminal KDEL signal.","method":"Subcellular fractionation, indirect immunofluorescence, laser scanning microscopy, VSV tsO45 trafficking assay","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal localization methods; applies to ER PDI-family CaBP1","pmids":["7876340"],"is_preprint":false},{"year":1997,"finding":"CaBP1 (ER PDI-family) is phosphorylated by protein kinase CK2 at serine 427 (N-terminal site) and at C-terminal serines/threonines by endogenous CK2-type kinase; phosphorylation was also detected in intact hepatocytes.","method":"32P-labeling, purification, proteolytic peptide sequencing, CK2 in vitro kinase assay","journal":"Journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 1-2 — in vitro kinase assay with site identification by peptide sequencing, confirmed in intact cells; applies to ER PDI-family CaBP1","pmids":["9058200"],"is_preprint":false},{"year":2018,"finding":"CaBP1 regulates CaV1 (L-type) channels in cochlear spiral ganglion neurons in vivo: CaBP1-knockout SGNs show greater Ca2+-dependent inactivation of CaV1 currents, impaired activity-dependent neurite growth repression unresponsive to CaV1 antagonists, and reduced CaV1-mediated CREB phosphorylation.","method":"Whole-cell patch clamp in CaBP1-KO neurons, neurite growth assays, CREB phosphorylation measurements","journal":"Molecular and cellular neurosciences","confidence":"Medium","confidence_rationale":"Tier 2 — clean KO with defined cellular phenotypes and pathway placement, single lab","pmids":["29548764"],"is_preprint":false},{"year":2024,"finding":"CaBP1 and CaBP2 cooperatively suppress both voltage- and Ca2+-dependent inactivation of IHC CaV1.3 channels; double-KO mice show strongly enhanced inactivation, slowed recovery from inactivation, and impaired sustained exocytosis; transgenic CaBP2 rescue restores IHC synaptic function and hearing.","method":"Double-KO mouse electrophysiology (whole-cell patch clamp), exocytosis measurements, in vivo auditory nerve recordings, transgenic rescue","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 — double-KO with multiple functional readouts (electrophysiology, exocytosis, in vivo recordings) and transgenic rescue","pmids":["39718549"],"is_preprint":false},{"year":2006,"finding":"L-CaBP1 binds Ca2+-dependently to several partners from bovine brain including ARF1, Ca2+-dependent activator protein for secretion 1, cyclic nucleotide phosphodiesterase, vacuolar ATPase, AP1 and AP2 complexes, and type I TGF-β receptor, with some interactions specific to CaBP1 and not shared with other NCS proteins.","method":"GST pull-down from bovine brain cytosol and membrane extracts, MALDI-MS, Western blotting","journal":"Proteomics","confidence":"Low","confidence_rationale":"Tier 3 — single pull-down/MS screen without follow-up functional validation","pmids":["16470652"],"is_preprint":false}],"current_model":"Neuronal CaBP1, a calmodulin-like EF-hand protein, constitutively binds Mg2+ at EF1 and cooperatively binds Ca2+ at EF3/EF4, switching between structurally distinct states that regulate voltage-gated Ca2+ channels (CaV1.2/1.3) by competitively displacing calmodulin from the IQ domain—blocking Ca2+-dependent inactivation and promoting facilitation through its C-lobe anchor and N-lobe/linker module—and inhibits InsP3R gating by clamping intersubunit conformational changes via hydrophobic contacts between its Ca2+-exposed C-lobe and the InsP3-binding core β-domain."},"narrative":{"teleology":[{"year":2005,"claim":"Establishing how CaBP1 senses divalent cations resolved the question of which EF-hands are functional and showed that Mg²⁺ and Ca²⁺ drive the protein into structurally distinct states — a prerequisite for understanding how ion occupancy controls target selection.","evidence":"NMR, ITC, and thermal denaturation on recombinant CaBP1","pmids":["16147998"],"confidence":"High","gaps":["No structural detail on how Mg²⁺-induced dimerization affects target binding","EF-hand mutations not tested in cellular context"]},{"year":2008,"claim":"Determining the NMR structures of Mg²⁺-bound and Ca²⁺-bound CaBP1 revealed that the Ca²⁺-loaded C-lobe opens to expose hydrophobic residues that bind the InsP3R1 suppressor–ligand-binding core without blocking InsP3 binding, establishing the structural basis for CaBP1–InsP3R interaction.","evidence":"NMR structure determination and ITC binding to InsP3R1 fragments","pmids":["19008222"],"confidence":"High","gaps":["Full-length InsP3R context not addressed","Effect on InsP3R gating not yet measured in this study"]},{"year":2010,"claim":"Crystallography and electrophysiology defined a two-module mechanism for CaBP1 regulation of CaV1.2: the C-lobe anchors to the IQ domain while the N-lobe/linker module (Glu94) mediates suppression of Ca²⁺-dependent inactivation and induction of facilitation, establishing that functional EF-hands are dispensable for CDI inhibition.","evidence":"Crystal structure of CaBP1–CaV1.2 IQ complex, mutagenesis, whole-cell patch clamp","pmids":["21134641"],"confidence":"High","gaps":["Mechanism of facilitation induction by N-lobe/linker not resolved at atomic detail","Role of CaBP1 dimerization in channel regulation unclear"]},{"year":2011,"claim":"Identification of a Ca²⁺-independent CaBP1 binding site on the CaV1.2 N-terminal domain, distinct from the IQ-domain site, showed that CaBP1 engages the channel at a second locus that influences voltage-dependent inactivation and activation gating.","evidence":"Pull-down with deletion mutants, electrophysiology","pmids":["21383011"],"confidence":"Medium","gaps":["No structure of N-terminal domain complex","Relative contribution of N-terminal versus IQ-domain interaction in intact channel not quantified"]},{"year":2013,"claim":"Two complementary studies resolved the competitive mechanism at the CaV1 IQ domain and the inhibitory mechanism at InsP3R1: apo-CaBP1/apo-CaM competition for the IQ domain quantitatively explains opposing channel regulation, while CaBP1's C-lobe hydrophobic contacts with InsP3R β-domain residues clamp intersubunit movements to inhibit gating.","evidence":"ITC and covalent CaM-tethering electrophysiology for CaV1 competition; NMR PRE, docking, cross-linking, and functional InsP3R assays for InsP3R mechanism","pmids":["23811053","23650371"],"confidence":"High","gaps":["Full tetrameric InsP3R architecture of CaBP1 complex not validated by cryo-EM","Kinetics of CaBP1–CaM exchange on the channel in situ unknown"]},{"year":2018,"claim":"CaBP1-knockout cochlear spiral ganglion neurons confirmed that CaBP1 suppresses CaV1 Ca²⁺-dependent inactivation in vivo and showed downstream consequences: impaired CaV1-mediated CREB phosphorylation and loss of activity-dependent neurite growth repression.","evidence":"Whole-cell patch clamp, neurite growth assays, CREB phosphorylation in CaBP1-KO neurons","pmids":["29548764"],"confidence":"Medium","gaps":["Single neuron type studied","Contribution of CaBP1 versus CaBP2 not disambiguated in this system"]},{"year":2024,"claim":"Double-knockout of CaBP1 and CaBP2 in mice demonstrated cooperative and partially redundant suppression of CaV1.3 inactivation in inner hair cells, with loss causing impaired sustained exocytosis and deafness that is rescued by transgenic CaBP2, establishing a physiological requirement for CaBP-family regulation of CaV1.3 in hearing.","evidence":"Double-KO mouse electrophysiology, capacitance measurements, auditory nerve recordings, transgenic rescue","pmids":["39718549"],"confidence":"High","gaps":["Specific structural determinants of CaBP1 versus CaBP2 functional differences on CaV1.3 not resolved","Whether CaBP1 alone is sufficient for hearing rescue not tested"]},{"year":2026,"claim":"Atomic-resolution NMR structures of Ca²⁺-CaBP1 bound to the CaV1.2 IQ peptide identified specific intermolecular contacts and a salt bridge, showed that Ca²⁺ binding to EF3/EF4 enhances IQ affinity >40-fold, and linked CaBP1 binding to increased channel open probability — completing the structural picture of C-lobe–IQ engagement.","evidence":"NMR structure, ITC, electrophysiology, mutagenesis","pmids":["41859936"],"confidence":"High","gaps":["Structure captured on isolated IQ peptide, not full-length channel","Mechanism by which CaBP1 increases open probability versus blocking inactivation not delineated"]},{"year":null,"claim":"It remains unknown how CaBP1 partitions between CaV channels and InsP3Rs within a single neuron, whether its dimerization state is regulated in vivo, and whether it has physiologically relevant targets beyond ion channels.","evidence":"","pmids":[],"confidence":"Low","gaps":["No in vivo imaging or quantification of CaBP1 target partitioning","Dimerization regulation unexplored in cellular context","Proteomics hits (ARF1, CAPS1, AP complexes) lack functional validation"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[3,4,6,12,13]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[7]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,1,2]}],"pathway":[{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[12,13]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[3,4,6,12,13]}],"complexes":[],"partners":["CACNA1C","CACNA1D","ITPR1","MYO1C","CABP2"],"other_free_text":[]},"mechanistic_narrative":"CaBP1 is a neuronal calmodulin-related EF-hand calcium sensor that tunes the activity of voltage-gated calcium channels and inositol 1,4,5-trisphosphate receptors by competing with calmodulin for shared binding determinants. CaBP1 constitutively binds Mg²⁺ at EF-1 and cooperatively binds Ca²⁺ at EF-3/EF-4, with each ion inducing distinct conformational states: the Ca²⁺-loaded C-lobe opens to expose hydrophobic residues that anchor to the IQ domain of CaV1.2/CaV1.3 channels, blocking Ca²⁺-dependent inactivation and promoting facilitation through its N-lobe/linker module, while the same C-lobe surface contacts the InsP3-binding core β-domain of InsP3R1 to clamp intersubunit conformational changes and inhibit channel gating [PMID:16147998, PMID:19008222, PMID:21134641, PMID:23650371, PMID:41859936]. Apo-CaBP1 and apo-calmodulin compete directly for the CaV1 IQ domain, with their relative affinities governing opposing modes of channel regulation [PMID:23811053]. In vivo, CaBP1 suppresses CaV1 inactivation in cochlear neurons to sustain CaV1-dependent CREB signaling and neurite growth regulation, and cooperates with CaBP2 to maintain sustained exocytosis at inner hair cell synapses required for normal hearing [PMID:29548764, PMID:39718549]."},"prefetch_data":{"uniprot":{"accession":"Q9NZU7","full_name":"Calcium-binding protein 1","aliases":["Calbrain","Caldendrin"],"length_aa":370,"mass_kda":39.8,"function":"Modulates calcium-dependent activity of inositol 1,4,5-triphosphate receptors (ITPRs) (PubMed:14570872). Inhibits agonist-induced intracellular calcium signaling (PubMed:15980432). Enhances inactivation and does not support calcium-dependent facilitation of voltage-dependent P/Q-type calcium channels (PubMed:11865310). Causes calcium-dependent facilitation and inhibits inactivation of L-type calcium channels by binding to the same sites as calmodulin in the C-terminal domain of CACNA1C, but has an opposite effect on channel function (PubMed:15140941). Suppresses the calcium-dependent inactivation of CACNA1D (By similarity). Inhibits TRPC5 channels (PubMed:15895247). Prevents NMDA receptor-induced cellular degeneration. Required for the normal transfer of light signals through the retina (By similarity)","subcellular_location":"Cytoplasm, cell cortex; Cell membrane","url":"https://www.uniprot.org/uniprotkb/Q9NZU7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CABP1","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CABP1","total_profiled":1310},"omim":[{"mim_id":"618759","title":"CALCIUM-BINDING PROTEIN 7; CABP7","url":"https://www.omim.org/entry/618759"},{"mim_id":"607315","title":"CALCIUM-BINDING PROTEIN 5; CABP5","url":"https://www.omim.org/entry/607315"},{"mim_id":"607314","title":"CALCIUM-BINDING PROTEIN 2; CABP2","url":"https://www.omim.org/entry/607314"},{"mim_id":"605563","title":"CALCIUM-BINDING PROTEIN 1; CABP1","url":"https://www.omim.org/entry/605563"},{"mim_id":"602293","title":"CALCIUM- AND INTEGRIN-BINDING PROTEIN 1; CIB1","url":"https://www.omim.org/entry/602293"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"brain","ntpm":419.6}],"url":"https://www.proteinatlas.org/search/CABP1"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q9NZU7","domains":[{"cath_id":"1.10.238.10","chopping":"220-298","consensus_level":"medium","plddt":76.1135,"start":220,"end":298},{"cath_id":"1.10.238.10","chopping":"299-370","consensus_level":"medium","plddt":79.3607,"start":299,"end":370}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NZU7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NZU7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NZU7-F1-predicted_aligned_error_v6.png","plddt_mean":58.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CABP1","jax_strain_url":"https://www.jax.org/strain/search?query=CABP1"},"sequence":{"accession":"Q9NZU7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NZU7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NZU7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NZU7"}},"corpus_meta":[{"pmid":"8300576","id":"PMC_8300576","title":"Effects of CaBP2, the rat analog of ERp72, and of CaBP1 on the refolding of denatured reduced proteins. Comparison with protein disulfide isomerase.","date":"1994","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/8300576","citation_count":77,"is_preprint":false},{"pmid":"7835433","id":"PMC_7835433","title":"Two resident ER-proteins, CaBP1 and CaBP2, with thioredoxin domains, are substrates for thioredoxin reductase: comparison with protein disulfide isomerase.","date":"1995","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/7835433","citation_count":72,"is_preprint":false},{"pmid":"16147998","id":"PMC_16147998","title":"Structural analysis of Mg2+ and Ca2+ binding to CaBP1, a neuron-specific regulator of calcium channels.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16147998","citation_count":72,"is_preprint":false},{"pmid":"19008222","id":"PMC_19008222","title":"Structural insights into Ca2+-dependent regulation of inositol 1,4,5-trisphosphate receptors by CaBP1.","date":"2008","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19008222","citation_count":52,"is_preprint":false},{"pmid":"21134641","id":"PMC_21134641","title":"Structural basis for the differential effects of CaBP1 and calmodulin on Ca(V)1.2 calcium-dependent inactivation.","date":"2010","source":"Structure (London, England : 1993)","url":"https://pubmed.ncbi.nlm.nih.gov/21134641","citation_count":51,"is_preprint":false},{"pmid":"16470652","id":"PMC_16470652","title":"Analysis of the interacting partners of the neuronal calcium-binding proteins L-CaBP1, hippocalcin, NCS-1 and neurocalcin delta.","date":"2006","source":"Proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/16470652","citation_count":50,"is_preprint":false},{"pmid":"23811053","id":"PMC_23811053","title":"Apo states of calmodulin and CaBP1 control CaV1 voltage-gated calcium channel function through direct competition for the IQ domain.","date":"2013","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/23811053","citation_count":47,"is_preprint":false},{"pmid":"21383011","id":"PMC_21383011","title":"CaBP1 regulates voltage-dependent inactivation and activation of Ca(V)1.2 (L-type) calcium channels.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21383011","citation_count":39,"is_preprint":false},{"pmid":"23650371","id":"PMC_23650371","title":"CaBP1, a neuronal Ca2+ sensor protein, inhibits inositol trisphosphate receptors by clamping intersubunit interactions.","date":"2013","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/23650371","citation_count":37,"is_preprint":false},{"pmid":"7876340","id":"PMC_7876340","title":"CaBP1, a calcium binding protein of the thioredoxin family, is a resident KDEL protein of the ER and not of the intermediate compartment.","date":"1994","source":"Journal of cell 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transmission in inner hair cells.","date":"2024","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/39718549","citation_count":7,"is_preprint":false},{"pmid":"29548764","id":"PMC_29548764","title":"CaBP1 regulates Cav1 L-type Ca2+ channels and their coupling to neurite growth and gene transcription in mouse spiral ganglion neurons.","date":"2018","source":"Molecular and cellular neurosciences","url":"https://pubmed.ncbi.nlm.nih.gov/29548764","citation_count":7,"is_preprint":false},{"pmid":"9770267","id":"PMC_9770267","title":"A homologue of the calcium-binding disulfide isomerase CaBP1 is expressed in the developing CNS of Drosophila melanogaster.","date":"1998","source":"Developmental genetics","url":"https://pubmed.ncbi.nlm.nih.gov/9770267","citation_count":3,"is_preprint":false},{"pmid":"19636926","id":"PMC_19636926","title":"1H, 15N, and 13C chemical shift assignments of calcium-bound calcium-binding protein 1 (CaBP1).","date":"2008","source":"Biomolecular NMR 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assignments","url":"https://pubmed.ncbi.nlm.nih.gov/36064846","citation_count":0,"is_preprint":false},{"pmid":"41859936","id":"PMC_41859936","title":"Structural Insights into L-Type Voltage-Gated Ca2+ Channel (CaV1.2) Activation by CaBP1.","date":"2026","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/41859936","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.10.24.684426","title":"Pleckstrin homology domain-containing serine/threonine kinase plays a crucial role in the survival and phagocytosis of  <i>Entamoeba histolytica</i>","date":"2025-10-26","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.24.684426","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":13255,"output_tokens":3683,"usd":0.047505},"stage2":{"model":"claude-opus-4-6","input_tokens":7122,"output_tokens":2468,"usd":0.145965},"total_usd":0.19347,"stage1_batch_id":"msgbatch_011kfMfE81o6CTcyhVUqumuW","stage2_batch_id":"msgbatch_01DTputS6WNkH745x1nVSoBo","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"CaBP1 (neuronal EF-hand protein) binds Mg2+ constitutively at EF-1 (Kd ~300 µM) and Ca2+ cooperatively at EF-3 and EF-4 (Kd ~2.5 µM); apo-CaBP1 forms a molten-globule, while Mg2+ and Ca2+ induce distinct conformational changes including protein dimerization and increased folding stability.\",\n      \"method\": \"NMR, microcalorimetry (ITC), and biophysical studies on recombinant CaBP1\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — multiple orthogonal biophysical methods (NMR + ITC + thermal denaturation) in a single rigorous study\",\n      \"pmids\": [\"16147998\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"NMR structures of CaBP1 in Mg2+-bound and Ca2+-bound states show the N-domain (EF1/EF2) remains closed with Mg2+ at EF1, while the C-domain undergoes a Ca2+-induced closed-to-open transition exposing hydrophobic residues (Leu132, His134, Ile141, Ile144, Val148). The Ca2+-bound C-domain binds the N-terminal suppressor+ligand-binding core region of InsP3R1 (residues 1–587) without affecting InsP3 binding itself.\",\n      \"method\": \"NMR structure determination, ITC binding assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — NMR structures combined with ITC functional binding measurements\",\n      \"pmids\": [\"19008222\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CaBP1 inhibits InsP3R activity by clamping intersubunit interactions: its C-lobe hydrophobic residues (V101, L104, V162) contact InsP3-binding core β-domain residues (L302, I364, L393) of InsP3R1, and CaBP1 promotes cross-linking at the suppressor–core domain interface that InsP3 disrupts during gating; CaBP1 forms an extended tetrameric turret at the cytosolic vestibule.\",\n      \"method\": \"NMR paramagnetic relaxation enhancement, docking, targeted cross-linking, functional IP3R activity assays\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — NMR PRE structural restraints + targeted cross-linking + functional channel assay with mutational validation\",\n      \"pmids\": [\"23650371\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"CaBP1 modulates CaV1.2 through two structural modules: the C-lobe anchors to the CaV1.2 IQ domain (overlapping with Ca2+/CaM C-lobe site), while the N-lobe/linker module (specifically interlobe linker residue Glu94) mediates inhibition of Ca2+-dependent inactivation (CDI) and induction of Ca2+-dependent facilitation (CDF); functional EF-hands are not required for CDI inhibition unlike CaM.\",\n      \"method\": \"Crystal structure, electrophysiology, mutagenesis\",\n      \"journal\": \"Structure (London, England : 1993)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — structure combined with mutagenesis and functional electrophysiology\",\n      \"pmids\": [\"21134641\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Apo-state CaBP1 and apo-CaM compete directly for the CaV1 IQ domain, with their relative apo-state binding affinities quantitatively explaining opposing channel regulation; Ca2+/CaM achieves sub-picomolar affinity for the IQ domain; covalent CaM tethering to the channel completely blocks this competition.\",\n      \"method\": \"ITC, cell-based electrophysiology, mathematical modeling, covalent tethering experiments\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — ITC with functional electrophysiology and quantitative modeling, multiple orthogonal methods\",\n      \"pmids\": [\"23811053\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"CaBP1 interacts with the distal C-terminal third of the CaV1.2 N-terminal domain in a Ca2+-independent manner (distinct from the calmodulin-binding site), while a separate proximal N-terminal segment is required for transduction of CaBP1's effect on voltage-dependent inactivation (VDI); CaBP1 also causes a depolarizing shift in voltage-dependent activation.\",\n      \"method\": \"Binding assays (pull-down), electrophysiology with deletion mutants\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — pull-down binding plus electrophysiology with deletion mutants from single lab\",\n      \"pmids\": [\"21383011\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"NMR structures of Ca2+-CaBP1 bound to the CaV1.2 IQ peptide identify specific contact residues (CaBP1: A107, F111, M128, L131, I144, M165; IQ: I1654, Y1657, F1658) and a salt bridge (CaBP1-D140 – IQ-K1662); Ca2+ binding to EF3/EF4 enhances IQ-peptide affinity >40-fold; electrophysiology shows CaBP1 increases CaV1.2 channel open probability.\",\n      \"method\": \"NMR structure determination, ITC, electrophysiology, mutagenesis\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — NMR structure + ITC + electrophysiology + mutagenesis in single study\",\n      \"pmids\": [\"41859936\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"CaBP1 binds the IQ motifs in the myo1c regulatory domain, competing with calmodulin; this competition is enhanced in the presence of Ca2+. CaBP1 has higher apparent affinity for myo1c than CIB1. Both proteins colocalize with myo1c in cells.\",\n      \"method\": \"Pull-down assays, fluorescence microscopy colocalization\",\n      \"journal\": \"Journal of muscle research and cell motility\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — pull-down plus colocalization, single lab\",\n      \"pmids\": [\"17994197\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"CaBP1 (rat P5 homolog, ER-resident with KDEL signal) catalyzes renaturation of denatured reduced proteins (Fab fragment, RNase AIII) in a GSH/GSSG redox-dependent manner, showing strong synergism with PDI for RNase AIII refolding, indicating it can catalyze disulfide bond formation and isomerization in the secretory pathway.\",\n      \"method\": \"In vitro renaturation assays with purified protein, activity measurements\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — in vitro reconstituted enzymatic assay, but context is ER-resident PDI-family protein, not the neuronal CaBP1 EF-hand protein; these are distinct proteins sharing the CaBP1 name in rat\",\n      \"pmids\": [\"8300576\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"CaBP1 (rat ER PDI-family member) is a substrate for thioredoxin reductase, catalyzes NADPH-dependent insulin disulfide reduction, and its thioredoxin active-site disulfide has a redox potential similar to PDI (~−235 mV), much higher than wild-type thioredoxin, consistent with a role in forming protein disulfide bonds.\",\n      \"method\": \"In vitro thioredoxin reductase assay, NADPH stoichiometry, redox potential measurement using P34H Trx mutant equilibrium\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — in vitro enzymatic assays with quantitative redox measurements; applies to the ER PDI-family CaBP1\",\n      \"pmids\": [\"7835433\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"CaBP1 (rat ER PDI-family protein) localizes to the ER lumen (not the intermediate compartment), as demonstrated by subcellular fractionation, double immunofluorescence showing colocalization with calreticulin but not ERGIC-53, and by maintained reticular localization upon overexpression; retention is mediated by the C-terminal KDEL signal.\",\n      \"method\": \"Subcellular fractionation, indirect immunofluorescence, laser scanning microscopy, VSV tsO45 trafficking assay\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal localization methods; applies to ER PDI-family CaBP1\",\n      \"pmids\": [\"7876340\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"CaBP1 (ER PDI-family) is phosphorylated by protein kinase CK2 at serine 427 (N-terminal site) and at C-terminal serines/threonines by endogenous CK2-type kinase; phosphorylation was also detected in intact hepatocytes.\",\n      \"method\": \"32P-labeling, purification, proteolytic peptide sequencing, CK2 in vitro kinase assay\",\n      \"journal\": \"Journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 — in vitro kinase assay with site identification by peptide sequencing, confirmed in intact cells; applies to ER PDI-family CaBP1\",\n      \"pmids\": [\"9058200\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CaBP1 regulates CaV1 (L-type) channels in cochlear spiral ganglion neurons in vivo: CaBP1-knockout SGNs show greater Ca2+-dependent inactivation of CaV1 currents, impaired activity-dependent neurite growth repression unresponsive to CaV1 antagonists, and reduced CaV1-mediated CREB phosphorylation.\",\n      \"method\": \"Whole-cell patch clamp in CaBP1-KO neurons, neurite growth assays, CREB phosphorylation measurements\",\n      \"journal\": \"Molecular and cellular neurosciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined cellular phenotypes and pathway placement, single lab\",\n      \"pmids\": [\"29548764\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CaBP1 and CaBP2 cooperatively suppress both voltage- and Ca2+-dependent inactivation of IHC CaV1.3 channels; double-KO mice show strongly enhanced inactivation, slowed recovery from inactivation, and impaired sustained exocytosis; transgenic CaBP2 rescue restores IHC synaptic function and hearing.\",\n      \"method\": \"Double-KO mouse electrophysiology (whole-cell patch clamp), exocytosis measurements, in vivo auditory nerve recordings, transgenic rescue\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — double-KO with multiple functional readouts (electrophysiology, exocytosis, in vivo recordings) and transgenic rescue\",\n      \"pmids\": [\"39718549\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"L-CaBP1 binds Ca2+-dependently to several partners from bovine brain including ARF1, Ca2+-dependent activator protein for secretion 1, cyclic nucleotide phosphodiesterase, vacuolar ATPase, AP1 and AP2 complexes, and type I TGF-β receptor, with some interactions specific to CaBP1 and not shared with other NCS proteins.\",\n      \"method\": \"GST pull-down from bovine brain cytosol and membrane extracts, MALDI-MS, Western blotting\",\n      \"journal\": \"Proteomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single pull-down/MS screen without follow-up functional validation\",\n      \"pmids\": [\"16470652\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Neuronal CaBP1, a calmodulin-like EF-hand protein, constitutively binds Mg2+ at EF1 and cooperatively binds Ca2+ at EF3/EF4, switching between structurally distinct states that regulate voltage-gated Ca2+ channels (CaV1.2/1.3) by competitively displacing calmodulin from the IQ domain—blocking Ca2+-dependent inactivation and promoting facilitation through its C-lobe anchor and N-lobe/linker module—and inhibits InsP3R gating by clamping intersubunit conformational changes via hydrophobic contacts between its Ca2+-exposed C-lobe and the InsP3-binding core β-domain.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CaBP1 is a neuronal calmodulin-related EF-hand calcium sensor that tunes the activity of voltage-gated calcium channels and inositol 1,4,5-trisphosphate receptors by competing with calmodulin for shared binding determinants. CaBP1 constitutively binds Mg²⁺ at EF-1 and cooperatively binds Ca²⁺ at EF-3/EF-4, with each ion inducing distinct conformational states: the Ca²⁺-loaded C-lobe opens to expose hydrophobic residues that anchor to the IQ domain of CaV1.2/CaV1.3 channels, blocking Ca²⁺-dependent inactivation and promoting facilitation through its N-lobe/linker module, while the same C-lobe surface contacts the InsP3-binding core β-domain of InsP3R1 to clamp intersubunit conformational changes and inhibit channel gating [PMID:16147998, PMID:19008222, PMID:21134641, PMID:23650371, PMID:41859936]. Apo-CaBP1 and apo-calmodulin compete directly for the CaV1 IQ domain, with their relative affinities governing opposing modes of channel regulation [PMID:23811053]. In vivo, CaBP1 suppresses CaV1 inactivation in cochlear neurons to sustain CaV1-dependent CREB signaling and neurite growth regulation, and cooperates with CaBP2 to maintain sustained exocytosis at inner hair cell synapses required for normal hearing [PMID:29548764, PMID:39718549].\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Establishing how CaBP1 senses divalent cations resolved the question of which EF-hands are functional and showed that Mg²⁺ and Ca²⁺ drive the protein into structurally distinct states — a prerequisite for understanding how ion occupancy controls target selection.\",\n      \"evidence\": \"NMR, ITC, and thermal denaturation on recombinant CaBP1\",\n      \"pmids\": [\"16147998\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structural detail on how Mg²⁺-induced dimerization affects target binding\", \"EF-hand mutations not tested in cellular context\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Determining the NMR structures of Mg²⁺-bound and Ca²⁺-bound CaBP1 revealed that the Ca²⁺-loaded C-lobe opens to expose hydrophobic residues that bind the InsP3R1 suppressor–ligand-binding core without blocking InsP3 binding, establishing the structural basis for CaBP1–InsP3R interaction.\",\n      \"evidence\": \"NMR structure determination and ITC binding to InsP3R1 fragments\",\n      \"pmids\": [\"19008222\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full-length InsP3R context not addressed\", \"Effect on InsP3R gating not yet measured in this study\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Crystallography and electrophysiology defined a two-module mechanism for CaBP1 regulation of CaV1.2: the C-lobe anchors to the IQ domain while the N-lobe/linker module (Glu94) mediates suppression of Ca²⁺-dependent inactivation and induction of facilitation, establishing that functional EF-hands are dispensable for CDI inhibition.\",\n      \"evidence\": \"Crystal structure of CaBP1–CaV1.2 IQ complex, mutagenesis, whole-cell patch clamp\",\n      \"pmids\": [\"21134641\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of facilitation induction by N-lobe/linker not resolved at atomic detail\", \"Role of CaBP1 dimerization in channel regulation unclear\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Identification of a Ca²⁺-independent CaBP1 binding site on the CaV1.2 N-terminal domain, distinct from the IQ-domain site, showed that CaBP1 engages the channel at a second locus that influences voltage-dependent inactivation and activation gating.\",\n      \"evidence\": \"Pull-down with deletion mutants, electrophysiology\",\n      \"pmids\": [\"21383011\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure of N-terminal domain complex\", \"Relative contribution of N-terminal versus IQ-domain interaction in intact channel not quantified\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Two complementary studies resolved the competitive mechanism at the CaV1 IQ domain and the inhibitory mechanism at InsP3R1: apo-CaBP1/apo-CaM competition for the IQ domain quantitatively explains opposing channel regulation, while CaBP1's C-lobe hydrophobic contacts with InsP3R β-domain residues clamp intersubunit movements to inhibit gating.\",\n      \"evidence\": \"ITC and covalent CaM-tethering electrophysiology for CaV1 competition; NMR PRE, docking, cross-linking, and functional InsP3R assays for InsP3R mechanism\",\n      \"pmids\": [\"23811053\", \"23650371\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full tetrameric InsP3R architecture of CaBP1 complex not validated by cryo-EM\", \"Kinetics of CaBP1–CaM exchange on the channel in situ unknown\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"CaBP1-knockout cochlear spiral ganglion neurons confirmed that CaBP1 suppresses CaV1 Ca²⁺-dependent inactivation in vivo and showed downstream consequences: impaired CaV1-mediated CREB phosphorylation and loss of activity-dependent neurite growth repression.\",\n      \"evidence\": \"Whole-cell patch clamp, neurite growth assays, CREB phosphorylation in CaBP1-KO neurons\",\n      \"pmids\": [\"29548764\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single neuron type studied\", \"Contribution of CaBP1 versus CaBP2 not disambiguated in this system\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Double-knockout of CaBP1 and CaBP2 in mice demonstrated cooperative and partially redundant suppression of CaV1.3 inactivation in inner hair cells, with loss causing impaired sustained exocytosis and deafness that is rescued by transgenic CaBP2, establishing a physiological requirement for CaBP-family regulation of CaV1.3 in hearing.\",\n      \"evidence\": \"Double-KO mouse electrophysiology, capacitance measurements, auditory nerve recordings, transgenic rescue\",\n      \"pmids\": [\"39718549\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Specific structural determinants of CaBP1 versus CaBP2 functional differences on CaV1.3 not resolved\", \"Whether CaBP1 alone is sufficient for hearing rescue not tested\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Atomic-resolution NMR structures of Ca²⁺-CaBP1 bound to the CaV1.2 IQ peptide identified specific intermolecular contacts and a salt bridge, showed that Ca²⁺ binding to EF3/EF4 enhances IQ affinity >40-fold, and linked CaBP1 binding to increased channel open probability — completing the structural picture of C-lobe–IQ engagement.\",\n      \"evidence\": \"NMR structure, ITC, electrophysiology, mutagenesis\",\n      \"pmids\": [\"41859936\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structure captured on isolated IQ peptide, not full-length channel\", \"Mechanism by which CaBP1 increases open probability versus blocking inactivation not delineated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how CaBP1 partitions between CaV channels and InsP3Rs within a single neuron, whether its dimerization state is regulated in vivo, and whether it has physiologically relevant targets beyond ion channels.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No in vivo imaging or quantification of CaBP1 target partitioning\", \"Dimerization regulation unexplored in cellular context\", \"Proteomics hits (ARF1, CAPS1, AP complexes) lack functional validation\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [3, 4, 6, 12, 13]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": []},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [12, 13]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [3, 4, 6, 12, 13]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CACNA1C\", \"CACNA1D\", \"ITPR1\", \"MYO1C\", \"CABP2\"],\n    \"other_free_text\": []\n  }\n}\n```"}