SERCA (Ca-P60A, CG3725) is the single sarco/endoplasmic reticulum Ca2+-ATPase of Drosophila melanogaster, a P2A-type P-type ATPase with ten transmembrane helices, cytoplasmic actuator, phosphorylation (catalytic Asp351) and nucleotide-binding domains. It couples ATP hydrolysis to the transport of Ca2+ from the cytosol into the lumen of the endoplasmic reticulum and, in muscle, the sarcoplasmic reticulum, thereby lowering cytosolic Ca2+ and filling the intracellular Ca2+ stores released through ryanodine and InsP3 receptors. Its activity is tuned by binding partners including the sarcolamban micropeptides SclA/SclB in muscle, Seipin in fat body and THADA, which acts as an uncoupler. Through store filling and Ca2+ clearance SERCA is required for muscle relaxation and cardiac function, neurotransmitter release at neuromuscular and photoreceptor synapses, fat storage and organismal energy balance, and ER-dependent maturation of the Notch receptor; null loss is lethal.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000166 nucleotide binding | IEA GO_REF:0000002 | TOO GENERAL | Summary: Nucleotide binding is true (SERCA binds ATP in its N domain) but uninformative; ATP binding and P-type calcium transporter activity in this review already entail it. Reason: InterPro IPR023299 (P-type ATPase cytoplasmic N domain) maps to generic nucleotide binding. The more specific ATP binding row and the core P-type calcium transporter activity are both retained, so this parent adds nothing. Supporting Evidence: file:DROME/SERCA/SERCA-uniprot.txt This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. |
| GO:0005388 P-type calcium transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function. Inherited from the PANTHER SERCA clade node (PTN002450634) seeded by experimentally characterised SERCAs (human ATP2A1/2/3, rodent orthologs, C. elegans sca-1) and supported by direct activity assays on fly SERCA. Reason: Drosophila SERCA is the sole fly member of the SERCA (P2A) clade, with 67-71% identity to mammalian SERCAs, conserved phospho-Asp and Ca2+-binding residues, and Ca2+-dependent thapsigargin-sensitive ATPase activity measured in fly extracts. The fly SERCA itself appears in WITH/FROM because its own experimental annotations were used to place the node; this is expected, not circular. Supporting Evidence: PMID:2148477 It shows 67-71% amino acid identity and an apparently identical hydropathy profile with the mammalian sarco/endoplasmic reticulum-type Ca2(+)-ATPases. PMID:28399403 An SERCA activity assay that quantifies Ca2+-dependent ATP hydrolysis (Gehrig et al., 2012) revealed that loss of THADA leads to significantly elevated calcium-dependent SERCA activity both in flies file:DROME/SERCA/SERCA-uniprot.txt TIGR01116; ATPase-IIA1_Ca |
| GO:0005388 P-type calcium transporter activity | IDA PMID:24807223 Seipin promotes adipose tissue fat storage through the ER Ca... | ACCEPT | Summary: Direct evidence: dSERCA Ca2+-ATPase activity measured in Drosophila and shown to be modulated by Seipin. Reason: Only the abstract is cached, but it states that dSeipin affects dSERCA activity, consistent with a curator-read activity assay; the annotation agrees with all other evidence for the core function, so it is accepted. Supporting Evidence: PMID:24807223 SERCA, an endoplasmic reticulum (ER) calcium pump, is solely responsible for transporting cytosolic calcium into the ER lumen. PMID:24807223 dSeipin affects dSERCA activity and modulates intracellular calcium homeostasis. |
| GO:0005388 P-type calcium transporter activity | IEA GO_REF:0000120 | ACCEPT | Summary: Correct electronic assignment of the core activity from IPR005782 (P-type ATPase IIA), RHEA:18105 and EC 7.2.2.10. Reason: The UniProt catalytic activity (RHEA:18105) and P2A family membership agree with the experimental data. Supporting Evidence: file:DROME/SERCA/SERCA-uniprot.txt Reaction=Ca(2+)(in) + ATP + H2O = Ca(2+)(out) + ADP + phosphate + H(+); file:DROME/SERCA/SERCA-uniprot.txt Belongs to the cation transport ATPase (P-type) (TC 3.A.3) |
| GO:0005388 P-type calcium transporter activity | IMP PMID:33892078 Oxidative modification impairs SERCA activity in Drosophila ... | ACCEPT | Summary: SERCA enzymatic activity measured in fly PD-model (DJ-1beta mutant) extracts is reduced, correlating with oxidative carbonylation of SERCA; supports the core pump activity. Reason: Abstract-only, but it reports SERCA enzymatic activity in Drosophila and its pharmacological rescue by the SERCA activator CDN1163; consistent with the core function, so the curator annotation is accepted. Supporting Evidence: PMID:33892078 Our results showed that SERCA enzymatic activity is significantly reduced in DJ-1Ξ² mutant flies |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: ATP binding is true: ATP is the substrate that phosphorylates the catalytic Asp in the P domain. It is a component of the pump mechanism rather than a separate function. Reason: InterPro IPR001757 (P-type ATPase) mapping. Correct but subsidiary to P-type calcium transporter activity. Supporting Evidence: file:DROME/SERCA/SERCA-uniprot.txt This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000117 | ACCEPT | Summary: ER location is correct; SERCA is an integral ER/SR membrane pump. The sub-compartment (ER membrane) is carried by other rows. Reason: Root organelle term (policy: keep the organelle row). The ARBA prediction is not itself evidence, but the organelle claim is independently established by direct localisation in fat body, salivary gland and muscle, and by SERCA use as an ER marker. Supporting Evidence: PMID:28399403 SERCA, which is widely used as an ER marker, co-localizes with THADA in all tissues tested such as the fat body and salivary gland (Figure 2D). file:DROME/SERCA/SERCA-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005783 endoplasmic reticulum | ISS PMID:2148477 Molecular cloning and chromosomal localization of a sarco/en... | ACCEPT | Summary: ER location by similarity to mammalian SERCA; correct and confirmed by direct fly data. Reason: Root organelle term kept. The cloning paper infers organellar membrane targeting from similarity to mammalian SERCAs; fly SERCA is used as an ER marker in later work. ER membrane is captured separately. Supporting Evidence: PMID:2148477 It shows 67-71% amino acid identity and an apparently identical hydropathy profile with the mammalian sarco/endoplasmic reticulum-type Ca2(+)-ATPases. PMID:28399403 SERCA, which is widely used as an ER marker, co-localizes with THADA in all tissues tested such as the fat body and salivary gland (Figure 2D). |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:23970561 Conserved regulation of cardiac calcium uptake by peptides e... | ACCEPT | Summary: ER membrane localisation from the sarcolamban study (colocalisation with SclA/SclB). Reason: UniProt cites this paper for ER membrane and SR membrane localisation with colocalisation at diads. SERCA is a 10-TM integral membrane pump, so membrane is the correct sub-compartment. Supporting Evidence: file:DROME/SERCA/SERCA-uniprot.txt Endoplasmic reticulum membrane file:DROME/SERCA/SERCA-uniprot.txt Interacts with SclA and SclB. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:24807223 Seipin promotes adipose tissue fat storage through the ER Ca... | ACCEPT | Summary: ER membrane is where the pump is active. Reason: Abstract-only but consistent with all other localisation evidence; is_active_in is appropriate for a membrane pump acting at the ER membrane. Supporting Evidence: PMID:24807223 SERCA, an endoplasmic reticulum (ER) calcium pump, is solely responsible for transporting cytosolic calcium into the ER lumen. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:28399403 THADA Regulates the Organismal Balance between Energy Storag... | ACCEPT | Summary: SERCA immunostaining marks the ER network in fat body and salivary gland. Reason: Full text read: SERCA staining is used as the ER marker that colocalises with GFP-KDEL reticular ER and with THADA. Supporting Evidence: PMID:28399403 SERCA, which is widely used as an ER marker, co-localizes with THADA in all tissues tested such as the fat body and salivary gland (Figure 2D). |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Correct mapping of the UniProt subcellular location (ER membrane, multi-pass). Reason: The UniProt location is curated from experimental evidence (PMID:23970561). Supporting Evidence: file:DROME/SERCA/SERCA-uniprot.txt Endoplasmic reticulum membrane |
| GO:0006816 calcium ion transport | IEA GO_REF:0000002 | MODIFY | Summary: Calcium ion transport is correct but general; the specific process SERCA performs is calcium ion transport from cytosol to ER, which the gene already carries by IDA/IMP. Reason: Correct-but-general term; refine to its is_a descendant GO:1903515. Proposed replacements: calcium ion transport from cytosol to endoplasmic reticulum Supporting Evidence: PMID:24807223 SERCA, an endoplasmic reticulum (ER) calcium pump, is solely responsible for transporting cytosolic calcium into the ER lumen. PMID:15520268 SERCA, a sarco-endoplasmic reticulum calcium ATPase, being the main agent for calcium uptake into the ER, plays a central role in this process. |
| GO:0006874 intracellular calcium ion homeostasis | IBA GO_REF:0000033 | ACCEPT | Summary: SERCA directly sets intracellular Ca2+ levels by removing cytosolic Ca2+ into the ER/SR store; inherited from the SERCA clade node and confirmed experimentally in flies. Reason: Pumping cytosolic Ca2+ into the ER is itself a component of intracellular Ca2+ homeostasis; fly mutants show altered Ca2+ handling in muscle, fat body and heart. Supporting Evidence: PMID:24807223 dSeipin affects dSERCA activity and modulates intracellular calcium homeostasis. PMID:15520268 At motor nerve terminals, SERCA inhibition retards calcium sequestration and reduces the amplitude of evoked excitatory junctional currents. |
| GO:0006874 intracellular calcium ion homeostasis | IGI PMID:24098595 Disruption of sarcoendoplasmic reticulum calcium ATPase func... | ACCEPT | Summary: Genetic interaction with the ryanodine receptor (RyR, FBgn0011286): a RyR mutation suppresses the cardiac phenotype of SERCA kum170, consistent with SERCA balancing SR Ca2+ release. Reason: Full text read. The rescue by reduced SR Ca2+ release indicates that the cardiac phenotype reflects disturbed Ca2+ homeostasis. Supporting Evidence: PMID:24098595 the co-expression of a calcium release channel mutation with CaP60A (kum170) is sufficient to rescue the cardiac phenotype but not paralysis. |
| GO:0006874 intracellular calcium ion homeostasis | IMP PMID:15520268 Analysis of conditional paralytic mutants in Drosophila sarc... | ACCEPT | Summary: Conditional SERCA mutants show retarded Ca2+ sequestration at motor terminals and prolonged contraction. Reason: Abstract states SERCA is the main agent of ER Ca2+ uptake and that its inhibition slows Ca2+ sequestration. Supporting Evidence: PMID:15520268 SERCA, a sarco-endoplasmic reticulum calcium ATPase, being the main agent for calcium uptake into the ER, plays a central role in this process. PMID:15520268 At motor nerve terminals, SERCA inhibition retards calcium sequestration and reduces the amplitude of evoked excitatory junctional currents. |
| GO:0006874 intracellular calcium ion homeostasis | IMP PMID:16899722 Compensation of inositol 1,4,5-trisphosphate receptor functi... | ACCEPT | Summary: Reducing SERCA activity raises cytosolic Ca2+ and compensates reduced InsP3R-mediated release in flight-circuit neurons. Reason: Abstract states that reduced Ca2+ uptake into stores compensates InsP3R deficits, i.e. SERCA activity sets cytosolic Ca2+ levels. Supporting Evidence: PMID:16899722 Decreased Ca2+ release in aminergic neurons during development of the flight circuit can be compensated by reducing Ca2+ uptake from the cytosol to intracellular stores. |
| GO:0007274 neuromuscular synaptic transmission | IMP PMID:15520268 Analysis of conditional paralytic mutants in Drosophila sarc... | KEEP AS NON CORE | Summary: SERCA mutants reduce evoked junctional currents at the NMJ; store-derived Ca2+ contributes to quantal content. A real but downstream physiological role. Reason: SERCA fills the presynaptic ER Ca2+ store that contributes to release; the pump does not itself mediate transmission, so this is non-core. Supporting Evidence: PMID:15520268 At motor nerve terminals, SERCA inhibition retards calcium sequestration and reduces the amplitude of evoked excitatory junctional currents. |
| GO:0007629 flight behavior | IGI PMID:16899722 Compensation of inositol 1,4,5-trisphosphate receptor functi... | KEEP AS NON CORE | Summary: Genetic modifier of InsP3R (itpr) flight defects; reduced SERCA partly compensates flight-circuit development. Reason: Organismal behaviour downstream of cytosolic Ca2+ levels in aminergic neurons; supported as a genetic interaction but peripheral to the pump function. Supporting Evidence: PMID:16899722 Decreased Ca2+ release in aminergic neurons during development of the flight circuit can be compensated by reducing Ca2+ uptake from the cytosol to intracellular stores. |
| GO:0012505 endomembrane system | HDA PMID:19317464 Mapping organelle proteins and protein complexes in Drosophi... | MODIFY | Summary: LOPIT organelle proteomics places SERCA in the endomembrane fraction; correct but general. The specific location is ER membrane, already carried by the gene. Reason: Correct-but-general term; endomembrane system is an ancestor (part_of) of ER membrane, which is supported by direct localisation and by the 10-TM topology. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:19317464 Here, we apply LOPIT, a mass-spectrometry based technique that simultaneously maps proteins to specific subcellular compartments, to Drosophila embryos. file:DROME/SERCA/SERCA-uniprot.txt Endoplasmic reticulum membrane |
| GO:0016020 membrane | IBA GO_REF:0000033 | MODIFY | Summary: Membrane is correct but generic; the node (PTN001943383) spans P-type ATPases located in different membranes. For SERCA the specific active location is the ER/SR membrane. Reason: Refine to ER membrane (and SR membrane in muscle), both carried by the gene from experimental rows. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN001943383 SUPPORTS TRANSFER Deep P-type ATPase node whose members sit in plasma, Golgi, ER and vacuolar membranes; membrane is the only common location. Inheritance is sound; granularity is refined with target evidence. Proposed replacements: endoplasmic reticulum membrane sarcoplasmic reticulum membrane Supporting Evidence: file:DROME/SERCA/SERCA-uniprot.txt Endoplasmic reticulum membrane file:DROME/SERCA/SERCA-uniprot.txt Sarcoplasmic reticulum membrane |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Membrane from InterPro P-type ATPase signatures; correct but generic. Refine to ER membrane. Reason: Correct-but-general term; ER membrane already carried by the gene. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:DROME/SERCA/SERCA-uniprot.txt Endoplasmic reticulum membrane |
| GO:0016529 sarcoplasmic reticulum | IDA PMID:15520268 Analysis of conditional paralytic mutants in Drosophila sarc... | MODIFY | Summary: SR localisation in muscle is correct; for an integral 10-TM pump the specific location is SR membrane, which the gene already carries. Reason: Correct-but-general (SR membrane is part_of SR). SR is a specialised ER and not one of the root organelle terms covered by the organelle policy. Abstract-only for this paper; SR membrane is independently supported by UniProt (PMID:23970561). Proposed replacements: sarcoplasmic reticulum membrane Supporting Evidence: file:DROME/SERCA/SERCA-uniprot.txt Sarcoplasmic reticulum membrane PMID:15520268 Conditional paralysis of SERCA mutants is also marked by prolonged neural activity-driven muscle contraction, thus reflecting the phylogenetically conserved role of SERCA in terminating contraction. |
| GO:0016529 sarcoplasmic reticulum | ISS PMID:2148477 Molecular cloning and chromosomal localization of a sarco/en... | MODIFY | Summary: SR location by similarity; correct but general. Refine to SR membrane. Reason: Correct-but-general term; SR membrane is carried by the gene from EXP evidence. Proposed replacements: sarcoplasmic reticulum membrane Supporting Evidence: PMID:2148477 It shows 67-71% amino acid identity and an apparently identical hydropathy profile with the mammalian sarco/endoplasmic reticulum-type Ca2(+)-ATPases. file:DROME/SERCA/SERCA-uniprot.txt Sarcoplasmic reticulum membrane |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: SERCA hydrolyses ATP (measured as Ca2+-dependent ATPase activity in flies); the hydrolysis is normally coupled to Ca2+ transport but can be partly uncoupled, producing heat. Reason: ATP hydrolysis is the chemical step of the P-type transport cycle and is measured directly in fly SERCA assays. It is retained as a non-core MF beside the core transporter activity, which already describes the coupled reaction. Supporting Evidence: PMID:28399403 An SERCA activity assay that quantifies Ca2+-dependent ATP hydrolysis (Gehrig et al., 2012) revealed that loss of THADA leads to significantly elevated calcium-dependent SERCA activity both in flies PMID:28399403 SERCA uses the energy derived from ATP hydrolysis in part to translocate calcium from the cytosol into the ER, and in part to produce heat via a futile cycle (Reis et al., 2001). |
| GO:0030322 stabilization of membrane potential | IGI PMID:16899722 Compensation of inositol 1,4,5-trisphosphate receptor functi... | UNDECIDED | Summary: Stabilization of membrane potential from genetic interactions with Gq, PLC21C and itpr in the flight circuit; the cached abstract does not mention membrane potential and the full text could not be read. Reason: The abstract describes compensation of InsP3R Ca2+ release by reduced SERCA activity in flight-circuit development, not membrane potential. The curator may have used electrophysiology in the full text (not available via PMC here). Cannot verify; left undecided rather than removed. Supporting Evidence: PMID:16899722 Decreased Ca2+ release in aminergic neurons during development of the flight circuit can be compensated by reducing Ca2+ uptake from the cytosol to intracellular stores. |
| GO:0030707 follicle cell of egg chamber development | IMP PMID:26205122 A large-scale in vivo RNAi screen to identify genes involved... | MARK AS OVER ANNOTATED | Summary: Ca-P60A was a hit in a follicle-cell RNAi screen for Notch-dependent differentiation; the effect is an indirect consequence of impaired Notch receptor trafficking. Reason: Full text read. The authors attribute the phenotype to SERCA-dependent Notch receptor trafficking. SERCA does not perform a step of follicle cell development; the annotation captures a pleiotropic downstream effect of ER Ca2+ loss on Notch maturation. Supporting Evidence: PMID:26205122 Ca-P60A positively regulates calcium-transporting ATPase activity for proper intracellular trafficking of the Notch receptor47. PMID:26205122 Ca-P60A and Hsc70-4 regulate proper intracellular trafficking of the Notch receptor4751. |
| GO:0033017 sarcoplasmic reticulum membrane | EXP PMID:23970561 Conserved regulation of cardiac calcium uptake by peptides e... | ACCEPT | Summary: SR membrane localisation with sarcolamban peptides at diads in muscle. Reason: Curated by UniProt from this paper; consistent with SERCA function in muscle relaxation. Supporting Evidence: file:DROME/SERCA/SERCA-uniprot.txt Sarcoplasmic reticulum membrane file:DROME/SERCA/SERCA-uniprot.txt Interacts with SclA and SclB. |
| GO:0033017 sarcoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Correct mapping of the UniProt subcellular location (SR membrane). Reason: UniProt location is experimentally supported (PMID:23970561). Supporting Evidence: file:DROME/SERCA/SERCA-uniprot.txt Sarcoplasmic reticulum membrane |
| GO:0036335 intestinal stem cell homeostasis | IMP PMID:23434461 Complementary genomic screens identify SERCA as a therapeuti... | MARK AS OVER ANNOTATED | Summary: Ca-P60A knockdown in midgut progenitors phenocopies Notch inhibition (expanded stem and enteroendocrine pools); indirect, via defective Notch maturation. Reason: Full text read. The midgut assay was used as a readout of Notch inhibition; SERCA loss acts by impairing Notch receptor processing/trafficking rather than by participating in stem cell homeostasis. Supporting Evidence: PMID:23434461 If thapsigargin inhibits Notch signaling through effects on calcium channels, then genetic modulation of SERCA should produce similar phenotypes. PMID:23434461 Of note, loss-of-function mutations in a Drosophila SERCA homolog, Ca-P60A, have been reported to produce Notch loss-of-function phenotypes in this model organism by altering Notch trafficking (Periz and Fortini, 1999). |
| GO:0045202 synapse | IEA GO_REF:0000108 | REMOVE | Summary: Location inferred by an inter-ontology rule from the BP row neuromuscular synaptic transmission; a process phenotype does not establish where SERCA is located. Reason: SERCA is an ER/SR membrane pump. Its presence in presynaptic ER at terminals is plausible but there is no direct localisation evidence at synapses; the row was generated from GO:0007274 (IMP), not from a localisation assay. Recorded as an upstream source defect of the inference rule. Supporting Evidence: file:DROME/SERCA/SERCA-uniprot.txt Endoplasmic reticulum membrane PMID:15520268 At motor nerve terminals, SERCA inhibition retards calcium sequestration and reduces the amplitude of evoked excitatory junctional currents. |
| GO:0048863 stem cell differentiation | IMP PMID:23434461 Complementary genomic screens identify SERCA as a therapeuti... | MARK AS OVER ANNOTATED | Summary: Stem cell differentiation phenotype in the midgut is an indirect consequence of reduced Notch signalling after SERCA knockdown. Reason: Full text read. SERCA knockdown is used to inhibit Notch; SERCA does no work in stem cell differentiation itself. Supporting Evidence: PMID:23434461 If thapsigargin inhibits Notch signaling through effects on calcium channels, then genetic modulation of SERCA should produce similar phenotypes. PMID:23434461 Of note, loss-of-function mutations in a Drosophila SERCA homolog, Ca-P60A, have been reported to produce Notch loss-of-function phenotypes in this model organism by altering Notch trafficking (Periz and Fortini, 1999). |
| GO:0060047 heart contraction | IMP PMID:24098595 Disruption of sarcoendoplasmic reticulum calcium ATPase func... | KEEP AS NON CORE | Summary: Cardiac-specific SERCA disruption causes dilation and contractile dysfunction; SERCA SR Ca2+ reuptake is part of the contraction-relaxation cycle. Reason: Full text read. SERCA removes Ca2+ from the cytosol after each beat; heart contraction is a true physiological role but downstream of the core pump activity. Supporting Evidence: PMID:24098595 In contrast to prior work, we show that disruption of CaP60A in a cardiac specific manner results in cardiac dilation and dysfunction rather than alteration in heart rate. PMID:23970561 Here, we describe two peptides of less than 30 amino acids regulating calcium transport, and hence influencing regular muscle contraction, in the Drosophila heart. |
| GO:0070588 calcium ion transmembrane transport | IBA GO_REF:0000033 | MODIFY | Summary: Calcium ion transmembrane transport is correct; SERCA specifically moves Ca2+ from cytosol into the ER lumen, which the gene carries by IDA/IMP. Reason: Refine to the is_a descendant GO:1903515. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002450634 SUPPORTS TRANSFER SERCA clade node seeded by experimentally characterised SERCAs; transfer is sound and refined with fly-specific evidence for direction (cytosol to ER). Proposed replacements: calcium ion transport from cytosol to endoplasmic reticulum Supporting Evidence: PMID:24807223 SERCA, an endoplasmic reticulum (ER) calcium pump, is solely responsible for transporting cytosolic calcium into the ER lumen. PMID:15520268 SERCA, a sarco-endoplasmic reticulum calcium ATPase, being the main agent for calcium uptake into the ER, plays a central role in this process. |
| GO:1903515 calcium ion transport from cytosol to endoplasmic reticulum | IDA PMID:24807223 Seipin promotes adipose tissue fat storage through the ER Ca... | ACCEPT | Summary: Core process: SERCA pumps cytosolic Ca2+ into the ER lumen; Seipin modulates this. Reason: Defines the core function; consistent with all fly and orthologous evidence. Supporting Evidence: PMID:24807223 SERCA, an endoplasmic reticulum (ER) calcium pump, is solely responsible for transporting cytosolic calcium into the ER lumen. PMID:24807223 dSeipin affects dSERCA activity and modulates intracellular calcium homeostasis. |
| GO:1903515 calcium ion transport from cytosol to endoplasmic reticulum | IMP PMID:28399403 THADA Regulates the Organismal Balance between Energy Storag... | ACCEPT | Summary: SERCA activity assays and ER Ca2+ measurements in THADA mutants and SERCA knockdown flies support SERCA-dependent ER Ca2+ uptake. Reason: Full text read; SERCA-dependent pumping into the ER is measured (activity assay, thapsigargin-releasable store). Supporting Evidence: PMID:28399403 Together with the SERCA activity assay, these data indicate improved pumping of calcium into the ER in THADA mutants, suggesting that THADA acts either as an SERCA inhibitor or SERCA uncoupler. PMID:28399403 An SERCA activity assay that quantifies Ca2+-dependent ATP hydrolysis (Gehrig et al., 2012) revealed that loss of THADA leads to significantly elevated calcium-dependent SERCA activity both in flies |
| GO:1990845 adaptive thermogenesis | IMP PMID:28399403 THADA Regulates the Organismal Balance between Energy Storag... | KEEP AS NON CORE | Summary: Uncoupled SERCA ATP hydrolysis is a recognised source of heat; in flies the evidence is via THADA, an uncoupler whose loss reduces heat production, and SERCA knockdown rescues THADA-mutant obesity. Reason: SERCA itself performs the heat-generating futile hydrolysis, so it does work in thermogenesis; however the fly thermogenic phenotypes were measured in THADA mutants and are mild. Kept as a non-core physiological role. Supporting Evidence: PMID:28399403 SERCA uses the energy derived from ATP hydrolysis in part to translocate calcium from the cytosol into the ER, and in part to produce heat via a futile cycle (Reis et al., 2001). PMID:28399403 The thermogenic phenotypes in THADA knockout flies are relatively mild, perhaps reflecting the ectothermic nature of flies. |
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Download this section (compressed HTML)Q: Does the GO_REF:0000108 rule that infers located_in synapse from neuromuscular synaptic transmission need an exclusion for integral ER/SR membrane proteins such as SERCA?
Q: Does PMID:16899722 contain electrophysiological evidence that justifies stabilization of membrane potential (GO:0030322) for SERCA, or should the row be re-termed?
Q: How do the SERCA regulators SclA/SclB, Seipin and THADA differ in mechanism (inhibition of Ca2+ affinity versus uncoupling), and are they tissue-restricted?
Experiment: Measure Ca2+ transport and ATP hydrolysis stoichiometry of purified or microsomal Drosophila SERCA with and without THADA, SclA/SclB or Seipin to distinguish inhibition from uncoupling, and test heat production in SERCA hypomorphs by microcalorimetry.
Type: biochemical assay
Experiment: Localise endogenously tagged SERCA at the larval NMJ and photoreceptor terminals with presynaptic ER markers to establish whether a presynaptic ER pool exists.
Type: imaging
Sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) encodes an endoplasmic reticulum (ER) calcium pump with roles in ER calcium homeostasis and lipid storage.
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