CALCA

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005615 extracellular space	IBA GO_REF:0000033	ACCEPT	Summary: Calcitonin is a secreted peptide hormone released from thyroid parafollicular C cells into the bloodstream where it acts on osteoclasts to inhibit bone resorption. This localization is well-supported by phylogenetic inference and consistent with the UniProt annotation indicating calcitonin is secreted. The IBA annotation from phylogenetic analysis is appropriate for this conserved localization. Reason: Calcitonin is a secreted hormone that acts in the extracellular space. UniProt explicitly annotates SUBCELLULAR LOCATION as Secreted. Serum calcitonin levels have been measured clinically (PMID:18057382) confirming its presence in extracellular fluids. The IBA annotation correctly reflects this core localization. Supporting Evidence: PMID:18057382 Reference range of serum calcitonin levels in humans: influence of calcitonin assays, sex, age, and cigarette smoking.
GO:0051480 regulation of cytosolic calcium ion concentration	IBA GO_REF:0000033	ACCEPT	Summary: Calcitonin is a calciotropic hormone whose primary physiological function involves regulating calcium homeostasis. It causes a rapid drop in blood calcium and phosphate levels by promoting incorporation into bones and inhibiting bone resorption. The IBA annotation appropriately captures this core biological process at the right level of specificity. Reason: Regulation of calcium ion concentration is a core function of calcitonin. UniProt describes calcitonin as a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood. Katacalcin is also described as a potent plasma calcium-lowering peptide (PMID:6132180). This is the defining biological process for calcitonin family peptides. Supporting Evidence: UniProt:P01258 Calcitonin is a peptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones.
GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: Calcitonin signals through the calcitonin receptor (CALCR), a class B GPCR that couples to Gs to activate adenylate cyclase and raise cAMP levels. This is a well-established and primary signaling mechanism for calcitonin action. The IBA annotation appropriately captures this core signaling pathway. Reason: Adenylate cyclase activation via Gs-coupled GPCR signaling is the primary signaling mechanism for calcitonin. Studies show calcitonin stimulates a cAMP response in osteoclasts and other cells (PMID:11014233, PMID:8078488). The deep research review confirms CGRP receptors primarily couple to Gs to raise cAMP/PKA. This is a core molecular function of the calcitonin family. Supporting Evidence: PMID:8078488 Calcitonin stimulates a cAMP response in both T47D and transfected baby hamster kidney cells. PMID:11014233 CT-sensitive adenylate cyclase responsiveness returned to the control levels by 96 h after removal of CT.
GO:0031716 calcitonin receptor binding	IBA GO_REF:0000033	ACCEPT	Summary: Calcitonin receptor binding is the primary molecular function of calcitonin. The peptide hormone binds to the calcitonin receptor (CALCR) to mediate its biological effects. This is supported by extensive biochemical and structural evidence including cryo-EM structures of calcitonin bound to receptor complexes (PMID:35324283). The IBA annotation correctly identifies this core molecular function. Reason: Calcitonin receptor binding is the defining molecular function of calcitonin. Structural studies have determined the structure of calcitonin bound to CTR and AMYR complexes (PMID:35324283). Ligand binding studies show calcitonin has high affinity for the calcitonin receptor (PMID:8078488). Supporting Evidence: PMID:35324283 We determined the structure and dynamics of active AMYRs with amylin, AMY1R with salmon CT (sCT), AMY2R with sCT or human CT (hCT), and CTR with amylin, sCT, or hCT. PMID:8078488 Like the endogenous T47D receptor, the recombinant receptor has an equally high affinity for salmon and porcine calcitonin but a 3-4-fold lower affinity for human calcitonin.
GO:0005179 hormone activity	IEA GO_REF:0000120	ACCEPT	Summary: Calcitonin is a well-established peptide hormone secreted by thyroid parafollicular C cells. It acts as a calciotropic hormone regulating calcium and phosphate homeostasis. The IEA annotation based on InterPro domain mapping is correct and consistent with experimental evidence. Reason: Hormone activity is a core molecular function of calcitonin. UniProt annotation explicitly describes calcitonin as a peptide hormone. This IEA annotation is redundant with the IDA annotation for the same term but is acceptable.
GO:0005576 extracellular region	IEA GO_REF:0000120	ACCEPT	Summary: Calcitonin is a secreted peptide hormone that is released into the extracellular space. The IEA annotation based on domain/subcellular location mapping is correct. This term is broader than GO:0005615 (extracellular space) which is also annotated. Reason: Extracellular region is the correct localization for a secreted hormone. UniProt explicitly annotates SUBCELLULAR LOCATION as Secreted. Multiple annotations for this term exist (IEA, TAS, IBA) and all are consistent with the core function of calcitonin as a circulating hormone.
GO:0048018 receptor ligand activity	IEA GO_REF:0000117	ACCEPT	Summary: Calcitonin functions as a receptor ligand, binding to and activating the calcitonin receptor (CALCR). This general term is appropriate but less specific than the more informative annotation GO:0031716 (calcitonin receptor binding). Reason: Receptor ligand activity is correct for calcitonin. However, GO:0031716 (calcitonin receptor binding) is a more specific and informative term. This IEA annotation is acceptable as a broader annotation but the IBA for calcitonin receptor binding is preferred for curation purposes.
GO:0097646 calcitonin family receptor signaling pathway	IEA GO_REF:0000117	ACCEPT	Summary: Calcitonin is the ligand that initiates the calcitonin receptor signaling pathway by binding to CALCR and activating downstream Gs-coupled cAMP signaling. This IEA annotation correctly identifies involvement in this core signaling pathway. Reason: Calcitonin family receptor signaling pathway is a core biological process for calcitonin. The deep research confirms that calcitonin signals through CALCR to activate Gs and raise cAMP/PKA. This IEA annotation is consistent with the IDA annotation for the same term.
GO:0005515 protein binding	IPI PMID:17689535 The interaction between endogenous calcineurin and the plasm...	REMOVE	Summary: This annotation is based on a publication studying PMCA-calcineurin interactions in breast cancer cells. Reviewing the paper, this appears to study calcineurin (PPP3CA) and PMCA interactions, not CALCA (calcitonin). The gene symbol confusion likely arose from similarity between CALCA and calcineurin abbreviations. Reason: The publication PMID:17689535 studies the interaction between calcineurin and plasma membrane calcium-dependent ATPase (PMCA) isoforms. Calcineurin is PPP3CA/PPP3CB, not CALCA (calcitonin). This appears to be an erroneous annotation based on gene symbol confusion. The paper abstract states that PMCA2 and PMCA4 interact with calcineurin, not calcitonin. Supporting Evidence: PMID:17689535 we demonstrate that endogenous human PMCA2 and -4 both interact with the signal transduction phosphatase, calcineurin, whereas, no interaction was detected with PMCA1.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: This annotation derives from a high-throughput yeast two-hybrid study mapping the human binary protein interactome. The interaction with ANKRD11 (X5D778) requires further validation. Protein binding is an uninformative term that does not specify the functional relationship. Reason: High-throughput interaction studies can generate false positives. The term protein binding is too general to be informative about calcitonin function. The primary function of calcitonin as a secreted hormone binding to CALCR is better captured by the calcitonin receptor binding annotation. This annotation should be retained but noted as non-core. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome.
GO:0042802 identical protein binding	IPI PMID:23395606 Identification of a novel 'aggregation-prone'/'amyloidogenic...	KEEP AS NON CORE	Summary: Human calcitonin is known to self-aggregate and form amyloid fibrils, which is the basis for this annotation. The study identified amyloidogenic determinant peptides in calcitonin that mediate self-assembly. This is a real biochemical property of calcitonin but represents pathological aggregation rather than a core physiological function. Reason: Calcitonin self-association and amyloid fibril formation is well-documented and relevant to medullary thyroid carcinoma pathology. However, this aggregation-prone behavior is not a core physiological function. The primary function is hormone activity via calcitonin receptor binding. This annotation should be retained as it documents a real biochemical property with clinical implications. Supporting Evidence: PMID:23395606 Calcitonin is a 32-residue polypeptide hormone, which takes part in calcium metabolism in bones. It may form amyloid fibrils. Amyloid fibrils are related with serious diseases known as amyloidoses. The amyloid form of calcitonin takes part in medullary thyroid carcinoma.
GO:0005615 extracellular space	IEA GO_REF:0000120	ACCEPT	Summary: This IEA annotation for extracellular space is redundant with the IBA and IDA annotations for the same term. Calcitonin is a secreted hormone found in serum. Keeping multiple evidence codes for well-supported localizations is acceptable. Reason: Extracellular space localization is correct for calcitonin. Serum calcitonin levels have been measured clinically (PMID:18057382). This IEA annotation is redundant with IBA and IDA annotations for the same term but is acceptable.
GO:0030424 axon	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: This annotation is transferred from rat ortholog based on Ensembl Compara. While the CALCA gene produces alpha-CGRP through alternative splicing which is expressed in sensory neurons, the calcitonin isoform (P01258) itself is primarily expressed in thyroid C cells. This localization may be more relevant to alpha-CGRP (P06881) than to calcitonin. Reason: Axonal localization is relevant for the alternatively spliced alpha-CGRP isoform expressed in sensory neurons, not the calcitonin peptide hormone. The deep research notes that alpha-CGRP is expressed in peripheral sensory neurons including trigeminal and dorsal root ganglia. However, this annotation applies to the P01258 entry which is the calcitonin precursor, not alpha-CGRP. Keep as non-core with the caveat that this may be more relevant to the CGRP splice variant.
GO:0042311 vasodilation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Vasodilation is a well-established function of alpha-CGRP, which is produced from the CALCA gene by alternative splicing. CGRP is described in the deep research as a potent vasodilatory neuropeptide. However, calcitonin itself (the peptide from this UniProt entry) is not primarily a vasodilator - that function is specific to CGRP. Reason: Vasodilation is a core function of alpha-CGRP (P06881) produced by alternative splicing of the CALCA gene, not of calcitonin (P01258) itself. The deep research describes CGRP as acting at vascular smooth muscle as a potent vasodilator. This annotation likely derives from ortholog transfer that does not distinguish between splice variants. Keep as non-core to acknowledge the gene-level function while noting it is not the primary function of the calcitonin peptide.
GO:0043025 neuronal cell body	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Neuronal cell body localization is more relevant to the alpha-CGRP splice variant that is expressed in sensory neurons (trigeminal ganglia, dorsal root ganglia), not to calcitonin which is secreted from thyroid C cells. This annotation derives from ortholog transfer. Reason: The deep research describes alpha-CGRP as expressed in peripheral sensory neurons including trigeminal and DRG neurons. Calcitonin (the product of this UniProt entry) is secreted from thyroid C cells, not neurons. Keep as non-core to acknowledge that the CALCA gene product (as CGRP) is found in neurons while noting this is not the calcitonin peptide function.
GO:0045776 negative regulation of blood pressure	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Blood pressure lowering is a consequence of vasodilation, which is a function of alpha-CGRP rather than calcitonin itself. CGRP causes vasodilation and thus reduces blood pressure. This annotation derives from ortholog transfer and reflects the gene-level function. Reason: Negative regulation of blood pressure is secondary to the vasodilatory activity of alpha-CGRP produced from the CALCA gene. Calcitonin (P01258) itself is not known for blood pressure regulation. Keep as non-core to acknowledge this is a gene-level function via the CGRP splice variant.
GO:0045986 negative regulation of smooth muscle contraction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Relaxation of smooth muscle (vasodilation) is a function of alpha-CGRP acting on vascular smooth muscle cells. This is not a primary function of calcitonin. The annotation derives from ortholog transfer. Reason: Smooth muscle relaxation leading to vasodilation is a function of alpha-CGRP, not calcitonin. The deep research describes CGRP as acting at vascular smooth muscle. Keep as non-core to reflect gene-level function via the CGRP splice variant.
GO:0071356 cellular response to tumor necrosis factor	IEA GO_REF:0000107	UNDECIDED	Summary: This annotation suggests calcitonin or CGRP is involved in TNF response. While procalcitonin (the calcitonin prohormone) is induced during sepsis and inflammation, this annotation appears to conflate response to TNF with calcitonin expression regulation. Reason: The relationship between CALCA gene products and TNF response is unclear. Procalcitonin is a sepsis biomarker induced during systemic inflammation, but this does not mean calcitonin mediates cellular responses to TNF. This annotation from ortholog transfer requires further evidence to evaluate. The original reference for the rat ortholog annotation is not available for review.
GO:0098686 hippocampal mossy fiber to CA3 synapse	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: This highly specific synaptic localization annotation likely derives from rat ortholog transfer. CGRP is expressed in sensory neurons and has been detected in various CNS regions. However, this specific localization to hippocampal mossy fiber synapses is overly specific for the UniProt calcitonin entry. Reason: This annotation is too specific without clear supporting evidence for human calcitonin. While CGRP has CNS expression, hippocampal mossy fiber synapse localization is a very specific claim. The calcitonin peptide (P01258) is primarily a thyroid-derived hormone acting on bone. This annotation should be marked as over-annotation.
GO:0098992 neuronal dense core vesicle	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Neuropeptides like CGRP are stored in and released from dense core vesicles in neurons. This annotation is relevant to alpha-CGRP expressed in sensory neurons but not to calcitonin secreted from thyroid C cells. Thyroid C cells are neuroendocrine cells that may also use dense core vesicles, but this annotation specifies neuronal vesicles. Reason: Dense core vesicle localization is relevant to neuropeptide secretion. CGRP is released from sensory neurons via dense core vesicles. While calcitonin from C cells may also be secreted via secretory granules, the annotation specifically refers to neuronal dense core vesicles. Keep as non-core to acknowledge CGRP function.
GO:1990090 cellular response to nerve growth factor stimulus	IEA GO_REF:0000107	UNDECIDED	Summary: This annotation suggests CALCA expression is regulated by NGF or that CALCA products mediate responses to NGF. CGRP expression in sensory neurons may be regulated by NGF signaling. This annotation derives from ortholog transfer. Reason: The relationship between CALCA/CGRP and NGF response in sensory neurons is plausible but the original evidence is not available for review. NGF is known to regulate neuropeptide expression in sensory neurons. Without access to the original rat evidence, cannot confirm if this applies to the calcitonin peptide (P01258) or is specific to CGRP.
GO:0005576 extracellular region	TAS Reactome:R-HSA-379044	ACCEPT	Summary: This Reactome annotation for extracellular region derives from the pathway reaction showing calcitonin acting as an extracellular ligand for Gs-activating GPCRs. Calcitonin is a secreted hormone that acts in the extracellular space. Reason: Extracellular region is the correct localization for calcitonin. This TAS annotation from Reactome pathway curation is consistent with the IBA and IDA annotations for extracellular space. Calcitonin acts as an extracellular ligand for CALCR.
GO:0005576 extracellular region	TAS Reactome:R-HSA-419843	ACCEPT	Summary: This Reactome annotation derives from the reaction CALCA(83-119) binds CALCR, showing calcitonin as an extracellular ligand binding to the calcitonin receptor. Correctly places calcitonin in the extracellular compartment. Reason: Extracellular region is correct for calcitonin which binds CALCR as an extracellular ligand. The Reactome reference specifically models calcitonin-receptor binding.
GO:0005576 extracellular region	TAS Reactome:R-HSA-744886	ACCEPT	Summary: This Reactome annotation from the Ligand:GPCR:Gs complex dissociation pathway places calcitonin in the extracellular region as expected for a secreted hormone ligand. Reason: Extracellular region is the correct localization for calcitonin. Redundant with other extracellular annotations but consistent with pathway modeling.
GO:0005576 extracellular region	TAS Reactome:R-HSA-744887	ACCEPT	Summary: This Reactome annotation from the GPCR-Gs binding pathway correctly places calcitonin as an extracellular ligand. Reason: Extracellular region is correct. Redundant with other annotations for this localization but acceptable for pathway context.
GO:0005576 extracellular region	TAS Reactome:R-HSA-9702354	ACCEPT	Summary: This Reactome annotation from the reaction CALCA(83-119) binds CALCA antibodies places calcitonin in the extracellular region where it can be bound by therapeutic antibodies. Reason: Extracellular region is correct. Calcitonin is a circulating hormone that can be targeted by antibodies in the extracellular space.
GO:0005576 extracellular region	TAS Reactome:R-HSA-976734	ACCEPT	Summary: This annotation from the amyloid fibril pathway places calcitonin in the extracellular region where amyloid deposits can form. Calcitonin amyloid is found in medullary thyroid carcinoma. Reason: Extracellular region is correct. Calcitonin amyloid deposits form extracellularly in pathological conditions.
GO:0005576 extracellular region	TAS Reactome:R-HSA-977136	ACCEPT	Summary: This annotation from the amyloid fibril formation pathway correctly places calcitonin in the extracellular region where amyloid precursor proteins can aggregate. Reason: Extracellular region is correct for calcitonin. This Reactome pathway models amyloid formation from extracellular calcitonin.
GO:0005179 hormone activity	IDA PMID:35324283 A structural basis for amylin receptor phenotype.	ACCEPT	Summary: Hormone activity is a core molecular function of calcitonin. The structural study PMID:35324283 demonstrates calcitonin binding to and activating its receptor complexes (CTR and AMYR2), which is the mechanistic basis for its hormone activity. Reason: Calcitonin is a well-established peptide hormone. The cryo-EM structures show calcitonin binding to CTR and AMYR complexes in active conformations, directly demonstrating its ability to act as a hormone ligand. Supporting Evidence: PMID:35324283 We determined the structure and dynamics of active AMYRs with amylin, AMY1R with salmon CT (sCT), AMY2R with sCT or human CT (hCT), and CTR with amylin, sCT, or hCT.
GO:0097646 calcitonin family receptor signaling pathway	IDA PMID:35324283 A structural basis for amylin receptor phenotype.	ACCEPT	Summary: Calcitonin is the prototypical ligand of the calcitonin receptor signaling pathway. The structural study demonstrates calcitonin bound to CTR in active G protein-coupled conformations, directly supporting its role in this signaling pathway. Reason: Calcitonin family receptor signaling pathway is a core biological process for calcitonin. The cryo-EM structures in PMID:35324283 show calcitonin bound to CTR-G protein complexes, providing direct structural evidence for calcitonin activating this pathway. Supporting Evidence: PMID:35324283 We determined the structure and dynamics of active AMYRs with amylin, AMY1R with salmon CT (sCT), AMY2R with sCT or human CT (hCT), and CTR with amylin, sCT, or hCT.
GO:0150060 amylin receptor 2 signaling pathway	IDA PMID:35324283 A structural basis for amylin receptor phenotype.	ACCEPT	Summary: UniProt explicitly states that calcitonin function is mediated by the CALCR-RAMP2 (AMYR2) receptor complex, and the structural study shows calcitonin bound to AMY2R. Calcitonin can signal through amylin receptor 2 in addition to CTR. Reason: The structural study PMID:35324283 directly demonstrates calcitonin bound to AMY2R (CTR+RAMP2) in active conformations. UniProt annotation also notes that calcitonin function is mediated by CALCR-RAMP2 complex. This is a legitimate signaling pathway for calcitonin. Supporting Evidence: PMID:35324283 Amylin receptors (AMYRs) are heterodimers of the calcitonin (CT) receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs), AMY1R, AMY2R, and AMY3R.
GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway	IDA PMID:11014233 Calcitonin receptor regulation and responsiveness to calcito...	ACCEPT	Summary: The study demonstrates that calcitonin treatment activates adenylate cyclase in human osteoclast-like cells. Calcitonin-sensitive adenylate cyclase responsiveness was measured to track receptor function and desensitization. Reason: Adenylate cyclase activation is a core signaling mechanism for calcitonin. The study directly measures CT-sensitive adenylate cyclase responsiveness in human osteoclasts, providing experimental evidence for this pathway. Supporting Evidence: PMID:11014233 The reduced specific binding, CTR messenger RNA levels, and CT-sensitive adenylate cyclase responsiveness returned to the control levels by 96 h after removal of CT.
GO:0002548 monocyte chemotaxis	IDA PMID:15248232 Expression and function of RANK in human monocyte chemotaxis...	REMOVE	Summary: This publication studies RANKL-induced monocyte chemotaxis, not calcitonin. The study demonstrates that RANKL stimulates monocyte migration via RANK. Calcitonin is not directly studied in this paper; this appears to be an erroneous annotation. Reason: PMID:15248232 studies RANKL (TNFSF11) and its receptor RANK (TNFRSF11A), not calcitonin (CALCA). The abstract clearly states that RANKL stimulates monocyte chemotaxis via RANK. There is no evidence in this paper for calcitonin involvement in monocyte chemotaxis. This annotation should be removed as it appears to be incorrectly attributed to CALCA. Supporting Evidence: PMID:15248232 RANKL significantly stimulated monocyte chemotaxis via activation of phosphatidylinositol 3-kinase, phosphodiesterase, and Src kinase.
GO:0005615 extracellular space	IDA PMID:18057382 Reference range of serum calcitonin levels in humans: influe...	ACCEPT	Summary: This study measures serum calcitonin levels using immunoassays, directly demonstrating that calcitonin is present in the extracellular space (serum/blood). This is direct experimental evidence for extracellular localization. Reason: The study measured serum calcitonin concentrations in healthy subjects using multiple immunoassays, providing direct experimental evidence that calcitonin is secreted into and present in the extracellular space (blood/serum). Supporting Evidence: PMID:18057382 The objective of this study was to re-evaluate the adult C(T) reference values determined by five different immunoassays and by introducing criteria for selecting control subjects.
GO:0007204 positive regulation of cytosolic calcium ion concentration	IDA PMID:17983652 Calcitonin promotes outgrowth of trophoblast cells on endome...	ACCEPT	Summary: The study shows that calcitonin treatment causes rapid increases in cytosolic calcium levels in endometrial epithelial cells. This calcium mobilization is part of the signaling mechanism by which calcitonin promotes trophoblast outgrowth. Reason: The study directly demonstrates that calcitonin exposure causes rapid increase in cytosolic calcium in endometrial epithelial cells. This is direct experimental evidence for calcitonin-induced calcium mobilization. Note this is distinct from the IBA annotation for GO:0051480 (regulation of cytosolic calcium ion concentration) which is about systemic calcium homeostasis. Supporting Evidence: PMID:17983652 Cytosolic calcium (Ca(2+)) levels in EEC increased rapidly upon exposure to calcitonin, and blockade of Ca(2+) release by BAPTA-AM effectively prevented the promoting effect of calcitonin on trophoblast expansion on EEC.
GO:0007566 embryo implantation	IDA PMID:17983652 Calcitonin promotes outgrowth of trophoblast cells on endome...	KEEP AS NON CORE	Summary: The study demonstrates that calcitonin promotes trophoblast cell outgrowth on endometrial epithelial cells, suggesting a role in facilitating embryo implantation. However, this is an in vitro cell culture study and embryo implantation is a complex organismal process. Reason: While the study provides evidence that calcitonin facilitates trophoblast-endometrial interaction in vitro, embryo implantation is not a core function of calcitonin. The primary function of calcitonin is calcium homeostasis and bone resorption inhibition. The role in implantation is a secondary/pleiotropic effect. Keep as non-core. Supporting Evidence: PMID:17983652 calcitonin promotes trophoblastic displacement of EEC through calcium mobilization and PKC activation, thereby facilitating embryo implantation.
GO:0032147 activation of protein kinase activity	IDA PMID:17983652 Calcitonin promotes outgrowth of trophoblast cells on endome...	ACCEPT	Summary: The study shows that calcitonin activates protein kinase C (PKC) in endometrial epithelial cells as part of its signaling mechanism. PKC activation is downstream of calcium mobilization induced by calcitonin. Reason: PKC activation is part of the calcitonin signaling mechanism demonstrated in this study. This is consistent with the broader understanding of calcitonin receptor signaling through both adenylate cyclase and PKC pathways. Supporting Evidence: PMID:17983652 The Ca(2+)-dependent protein kinase C (PKC) was also activated in EEC after calcitonin treatment, and the PKC inhibitors staurosporine and calphostin C could completely abolish calcitonin-induced augmentation of trophoblast expansion on EEC.
GO:0045779 negative regulation of bone resorption	IDA PMID:17241109 Regulation and enzymatic basis of bone resorption by human o...	ACCEPT	Summary: Inhibition of bone resorption is a core physiological function of calcitonin. The study directly demonstrates that calcitonin dose-dependently inhibits bone resorption by human osteoclasts in vitro. This is the classical pharmacological action of calcitonin. Reason: Negative regulation of bone resorption is a core function of calcitonin. The study uses a functional assay measuring CTX-I release (collagen degradation product) and shows calcitonin dose-dependently inhibits resorption. This is consistent with the deep research noting that calcitonin rapidly inhibits osteoclast activity. Supporting Evidence: PMID:17241109 CT (calcitonin) dose-dependently inhibited bone resorption, whereas PTH (parathyroid hormone), IL (interleukin)-1, TNF-alpha (tumour necrosis factor-alpha), IL-6, IL-8, VEGF (vascular endothelial growth factor), MCP-1 (monocyte chemoattractant protein-1), MIP-1gamma (macrophage inflammatory protein-1gamma), IFN (interferon)-gamma and dibutyryl cGMP had no significant effect.
GO:0031716 calcitonin receptor binding	IPI PMID:8078488 Cloning and characterization of an abundant subtype of the h...	ACCEPT	Summary: This study cloned and characterized the human calcitonin receptor and demonstrated calcitonin binding to the recombinant receptor with high affinity. Binding studies directly demonstrate the physical interaction between calcitonin and its receptor. Reason: Calcitonin receptor binding is a core molecular function. The study directly measures calcitonin binding to cloned human CTR and demonstrates high affinity binding. This is experimental evidence for the primary ligand-receptor interaction. Supporting Evidence: PMID:8078488 Like the endogenous T47D receptor, the recombinant receptor has an equally high affinity for salmon and porcine calcitonin but a 3-4-fold lower affinity for human calcitonin.
GO:0031716 calcitonin receptor binding	IPI PMID:8940110 The deletion of 14 amino acids in the seventh transmembrane ...	ACCEPT	Summary: This study characterized calcitonin binding to different CTR isoforms including a novel splice variant. Binding studies with salmon and human calcitonin demonstrate the physical interaction with receptor isoforms. Reason: The study directly measures calcitonin binding to CTR isoforms, demonstrating the ligand-receptor interaction. This is experimental evidence supporting calcitonin receptor binding as a core molecular function. Supporting Evidence: PMID:8940110 Deletion of the residues in the seventh transmembrane domain in CTRDeltae13 reduced the binding affinity for salmon and human calcitonin by more than 10-fold and approximately 2-fold, respectively, resulting in a receptor that failed to discriminate between the two forms of calcitonin.
GO:0045892 negative regulation of DNA-templated transcription	IDA PMID:11014233 Calcitonin receptor regulation and responsiveness to calcito...	KEEP AS NON CORE	Summary: The study shows that calcitonin treatment reduces CTR mRNA expression levels in osteoclasts, indicating negative regulation of transcription. This is part of the receptor down-regulation mechanism. Reason: The study demonstrates that calcitonin treatment reduces calcitonin receptor (CTR) mRNA levels, which is a form of negative transcriptional regulation. However, this is a secondary effect related to receptor desensitization rather than a primary function of calcitonin. Keep as non-core. Supporting Evidence: PMID:11014233 Treatment with sCT reduced CTR messenger RNA expression, suggesting that CTR down-regulation is, at least partly, attributable to an inhibition of de novo CTR synthesis.

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

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