Phospholamban is a 52-residue single-pass transmembrane phosphoprotein of the cardiac sarcoplasmic reticulum (SR) and the founding member of the regulin family of SERCA-regulating micropeptides. Monomeric unphosphorylated PLN binds the transmembrane groove of the SERCA2a Ca2+-ATPase (M2/M4/M6/M9) and lowers the pump's apparent Ca2+ affinity, slowing Ca2+ re-uptake into the SR and thereby limiting cardiac relaxation and contractility. Phosphorylation of Ser16 by PKA and Thr17 by CaMKII during beta-adrenergic stimulation relieves inhibition and shifts PLN into a homopentameric reservoir held together by a transmembrane leucine/isoleucine zipper. PLN also inhibits SERCA3, forms hetero-oligomers with sarcolipin, DWORF and other regulins, and binds HAX1. Loss of PLN in mice enhances basal contractility, and human mutations (R9C, R14del) cause dilated or arrhythmogenic cardiomyopathy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001675 acrosome assembly | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Mouse-derived transfer: PLN cleaved by SPPL2C in elongated spermatids, affecting Ca2+ homeostasis. Reason: The mouse data (UniProt: 'Controls intracellular Ca(2+) levels in elongated spermatids', by similarity to P61014) make PLN a substrate of SPPL2C whose clearance affects Ca2+; this is an indirect role, not participation in acrosome assembly, and nothing is known for human testis. |
| GO:0001675 acrosome assembly | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Mouse-derived transfer: PLN cleaved by SPPL2C in elongated spermatids, affecting Ca2+ homeostasis. Reason: The mouse data (UniProt: 'Controls intracellular Ca(2+) levels in elongated spermatids', by similarity to P61014) make PLN a substrate of SPPL2C whose clearance affects Ca2+; this is an indirect role, not participation in acrosome assembly, and nothing is known for human testis. |
| GO:0002026 regulation of the force of heart contraction | IC PMID:19708671 Effects of phospholamban transmembrane mutants on the calciu... | ACCEPT | Summary: PLN sets basal cardiac contractility via SERCA2a inhibition; inferred by curator from ATPase inhibitor activity. Reason: Well established physiological role: PLN-null hearts show enhanced contractility and phosphorylation relief of PLN underlies beta-adrenergic inotropy. Supporting Evidence: PMID:8062415 These findings indicate that phospholamban acts as a critical repressor of basal myocardial contractility PMID:22679139 Cyclic AMP-dependent phosphorylation of PLN reverses its inhibitory effect on the Ca2+ pump. |
| GO:0004857 enzyme inhibitor activity | ISS PMID:12032137 Sarcolipin inhibits polymerization of phospholamban to induc... | MODIFY | Summary: ISS from rabbit PLN (P61015), SERCA inhibition in HEK-293 co-expression. Reason: Correct but too general. The enzyme PLN inhibits is the SERCA Ca2+-ATPase; ATPase inhibitor activity is the precise term already carried by IBA and IDA. Proposed replacements: ATPase inhibitor activity Supporting Evidence: PMID:12032137 NF-SLN binds directly to PLN and that NF-SLN inhibits the formation of PLN pentamers. PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. |
| GO:0005515 protein binding | IPI PMID:15598648 Myotonic dystrophy protein kinase phosphorylates phospholamb... | REMOVE | Summary: Co-IP of PLN with DMPK; DMPK phosphorylates PLN. Reason: PLN is the kinase substrate here. Bare protein binding adds no information about PLN's own activity (the substrate relationship belongs on DMPK). Removal does not imply the interaction is false. Supporting Evidence: PMID:15598648 DMPK expression in cardiac myocytes is highly enriched in the sarcoplasmic reticulum (SR) where it colocalizes with the ryanodine receptor and phospholamban (PLN) |
| GO:0005515 protein binding | IPI PMID:24722188 Protein interaction network of alternatively spliced isoform... | REMOVE | Summary: High-throughput binary interaction screen (PMID:24722188) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:24722188 Protein interaction network of alternatively spliced isoform... | REMOVE | Summary: High-throughput binary interaction screen (PMID:24722188) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput binary interaction screen (PMID:25416956) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: High-throughput binary interaction screen (PMID:25910212) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: High-throughput binary interaction screen (PMID:25910212) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: High-throughput binary interaction screen (PMID:25910212) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: High-throughput binary interaction screen (PMID:25910212) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:28890335 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates ... | MODIFY | Summary: IPI with ATP2A2/SERCA2. The paper describes PLN as part of the SERCA inhibitory complex that VMP1 prevents from forming. Reason: The interaction with SERCA2 is the basis of PLN's core activity. Bare protein binding is uninformative; the cited work frames the PLN-SERCA interaction as an inhibitory complex, so ATPase inhibitor activity is the informative MF. Proposed replacements: ATPase inhibitor activity Supporting Evidence: PMID:28890335 VMP1 interacts with SERCA and prevents formation of the SERCA/PLN/SLN inhibitory complex. PMID:23996003 In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. |
| GO:0005515 protein binding | IPI PMID:28890335 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates ... | REMOVE | Summary: IPI with VMP1, which competes with PLN/SLN for SERCA. Reason: Bare protein binding is uninformative. The PLN-VMP1 interaction is reported in the context of VMP1 preventing the SERCA/PLN/SLN inhibitory complex; no distinct PLN molecular function follows from it. Removal does not imply the interaction is false. Supporting Evidence: PMID:28890335 VMP1 interacts with SERCA and prevents formation of the SERCA/PLN/SLN inhibitory complex. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: High-throughput binary interaction screen (PMID:31515488) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interaction screen (PMID:32296183) reporting PLN binding a partner with no known role in SERCA regulation. Reason: Generic protein binding from a high-throughput Y2H-type screen is uninformative. PLN is a hydrophobic single-pass TM peptide; most partners in these screens (EDA, BCL2L13, LDLRAD1, TMEM and SLC proteins) are unrelated membrane proteins without a demonstrated physiological link. Removal does not mean the interactions are false. |
| GO:0005739 mitochondrion | HDA PMID:20833797 Phosphoproteome analysis of functional mitochondria isolated... | UNDECIDED | Summary: HDA: detected in phosphoproteome of mitochondria isolated from human skeletal muscle. Reason: Organelle proteomics from muscle is prone to SR co-purification; the paper does not discuss PLN specifically, and no mitochondrial function is known for PLN. Cannot adjudicate from the cached data; not core. |
| GO:0005783 endoplasmic reticulum | ISS GO_REF:0000024 | ACCEPT | Summary: ER localization by similarity to rabbit PLN expressed in HEK-293 cells. Reason: PLN is an ER/SR membrane protein; in non-muscle cells it localizes to the ER. Supporting Evidence: PMID:17241641 HAX-1 redistributed and co-localized with PLN at the endoplasmic reticulum. |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:17241641 Phospholamban interacts with HAX-1, a mitochondrial protein ... | ACCEPT | Summary: ER membrane. Reason: PLN is a single-pass ER/SR membrane protein; co-localizes with HAX1 at the ER of HEK-293 cells. Supporting Evidence: PMID:17241641 HAX-1 redistributed and co-localized with PLN at the endoplasmic reticulum. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: ER membrane. Reason: PLN is a single-pass ER/SR membrane protein; co-localizes with HAX1 at the ER of HEK-293 cells. Supporting Evidence: PMID:17241641 HAX-1 redistributed and co-localized with PLN at the endoplasmic reticulum. |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: ER membrane. Reason: PLN is a single-pass ER/SR membrane protein; co-localizes with HAX1 at the ER of HEK-293 cells. Supporting Evidence: PMID:17241641 HAX-1 redistributed and co-localized with PLN at the endoplasmic reticulum. |
| GO:0006816 calcium ion transport | IEA GO_REF:0000107 | MODIFY | Summary: IEA from rat: calcium ion transport. Reason: PLN does not itself transport Ca2+ (the pentamer channel reported in vesicles does not conduct Ca2+); it negatively regulates SERCA-mediated Ca2+ import into the SR. Proposed replacements: negative regulation of calcium ion import into sarcoplasmic reticulum Supporting Evidence: PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. PMID:26673394 highlight a preference for Cs(+) over K(+) and do not conduct Ca(2+). |
| GO:0006874 intracellular calcium ion homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Intracellular calcium ion homeostasis, transferred from mouse. Reason: Downstream consequence of SERCA2a regulation; true but less specific than the SR Ca2+ import regulation terms. Supporting Evidence: PMID:23996003 In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. |
| GO:0006874 intracellular calcium ion homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Intracellular calcium ion homeostasis, transferred from mouse. Reason: Downstream consequence of SERCA2a regulation; true but less specific than the SR Ca2+ import regulation terms. Supporting Evidence: PMID:23996003 In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. |
| GO:0007283 spermatogenesis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Spermatogenesis IEA from mouse. Reason: Based on mouse spermatid SPPL2C-processing data in which PLN is a substrate; not a demonstrated role of PLN in spermatogenesis, and untested in human. |
| GO:0008015 blood circulation | NAS PMID:8406504 Chromosome mapping of five human cardiac and skeletal muscle... | MARK AS OVER ANNOTATED | Summary: NAS from a chromosome mapping paper. Reason: The cited paper only maps PLN to 6q22.1; 'blood circulation' is a very broad statement that is better captured by the specific cardiac contractility/relaxation terms. |
| GO:0008016 regulation of heart contraction | IMP PMID:16432188 A mutation in the human phospholamban gene, deleting arginin... | ACCEPT | Summary: IMP: human R14del mutation causes DCM; transgenic mice recapitulate; SERCA superinhibition. Reason: PLN regulates heart contraction through SERCA2a; mutant evidence is consistent. Supporting Evidence: PMID:16432188 Coexpression of the normal and mutant-PLN in HEK-293 cells resulted in sarcoplasmic reticulum Ca(2+)-ATPase superinhibition. |
| GO:0008542 visual learning | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: visual learning transferred from mouse (thalamic reticular nucleus behavioural phenotype). Reason: Behavioural phenotype of mouse Pln perturbation (UniProt: 'In the thalamic reticular nucleus of the brain, plays a role in the regulation of sleep patterns and executive functioning', by similarity). This is a distal organismal consequence of SERCA regulation in neurons, not a process PLN executes; untested in human. |
| GO:0008542 visual learning | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: visual learning transferred from mouse (thalamic reticular nucleus behavioural phenotype). Reason: Behavioural phenotype of mouse Pln perturbation (UniProt: 'In the thalamic reticular nucleus of the brain, plays a role in the regulation of sleep patterns and executive functioning', by similarity). This is a distal organismal consequence of SERCA regulation in neurons, not a process PLN executes; untested in human. |
| GO:0010043 response to zinc ion | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to zinc ion (IEA), transferred from rat Pln, from a study of zinc-induced relaxation in isolated cardiomyocytes (PMID:23812383). Reason: The row is transferred from rat Pln, annotated by direct assay in a study of the cellular mechanisms of zinc-induced relaxation in isolated cardiomyocytes (PMID:23812383), so it rests on an experiment in which phospholamban was examined as a candidate mechanism rather than on expression profiling alone. A change in the state of phospholamban after zinc exposure shows that it is affected by the treatment, not that it carries out a response to zinc, and only the abstract is available. The term over-reads the observation and is marked as an over-annotation rather than removed. |
| GO:0010459 negative regulation of heart rate | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA negative regulation of heart rate from PANTHER regulin node. Reason: PLN knockout mice show enhanced contractility without changes in heart rate, so heart rate is not a direct PLN output. The node assertion appears seeded from the human IMP row (R14del cardiomyopathy with arrhythmia), which is a disease consequence rather than heart-rate regulation. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN002722410 SOURCE WEAK OR INFERRED Regulin node; correct for SERCA inhibition but heart-rate regulation is not supported by the PLN-null mouse, which has unchanged heart rate. UniProtKB:P26678 · PLN SOURCE WEAK OR INFERRED Human IMP from R14del cardiomyopathy (PMID:16432188); arrhythmia in DCM is not regulation of heart rate. Supporting Evidence: PMID:8062415 exhibited enhanced myocardial performance without changes in heart rate |
| GO:0010459 negative regulation of heart rate | IMP PMID:16432188 A mutation in the human phospholamban gene, deleting arginin... | MARK AS OVER ANNOTATED | Summary: IMP from the R14del cardiomyopathy paper. Reason: Not removed because the full text is unavailable, but the abstract reports episodic ventricular arrhythmias in carriers, a disease outcome, not regulation of heart rate; the PLN-null mouse shows no change in heart rate. Full text not available to see the curator's basis. Supporting Evidence: PMID:16432188 Coexpression of the normal and mutant-PLN in HEK-293 cells resulted in sarcoplasmic reticulum Ca(2+)-ATPase superinhibition. PMID:8062415 exhibited enhanced myocardial performance without changes in heart rate |
| GO:0016020 membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Membrane. Reason: PLN is an integral single-pass membrane protein of the SR/ER. Supporting Evidence: PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. |
| GO:0016020 membrane | IDA PMID:19708671 Effects of phospholamban transmembrane mutants on the calciu... | ACCEPT | Summary: Membrane. Reason: PLN is an integral single-pass membrane protein of the SR/ER. Supporting Evidence: PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Membrane. Reason: PLN is an integral single-pass membrane protein of the SR/ER. Supporting Evidence: PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. |
| GO:0016020 membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Membrane. Reason: PLN is an integral single-pass membrane protein of the SR/ER. Supporting Evidence: PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. |
| GO:0016529 sarcoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: Sarcoplasmic reticulum. Reason: PLN resides in the cardiac SR membrane. Supporting Evidence: PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. |
| GO:0016529 sarcoplasmic reticulum | IEA GO_REF:0000120 | ACCEPT | Summary: Sarcoplasmic reticulum. Reason: PLN resides in the cardiac SR membrane. Supporting Evidence: PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Mitochondrial membrane via UniProt SubCell (by similarity to bovine A4IFH6). Reason: Mitochondrial localization rests on similarity to a bovine record and proteomic detection; PLN function and established localization are in SR/ER. Unlike the HDA mitochondrion row (left UNDECIDED because the experimental dataset itself cannot be re-examined from the cache), this row is an electronic transfer whose source adds no human data, so it can be judged on the established SR/ER localization alone. |
| GO:0031982 vesicle | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Vesicle IEA from rat. Reason: Likely reflects SR microsomal vesicle preparations rather than a vesicular compartment in cells. |
| GO:0032868 response to insulin | IEA GO_REF:0000107 | REMOVE | Summary: response to insulin IEA from rat. Reason: Response-to terms transferred from rat expression-change experiments. A change in PLN level in response to a stimulus does not show that PLN functions in that response; no human evidence. |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | MODIFY | Summary: Protein-containing complex IEA. Reason: Too general; PLN forms the homopentameric phospholamban complex. Proposed replacements: phospholamban complex Supporting Evidence: PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. |
| GO:0033017 sarcoplasmic reticulum membrane | EXP PMID:12804600 Ca2+ -dependent interaction of S100A1 with the sarcoplasmic ... | ACCEPT | Summary: Sarcoplasmic reticulum membrane. Reason: Principal location of PLN, where it regulates SERCA2a. Supporting Evidence: PMID:12804600 we showed that all three proteins co-localize at the level of the SR in primary mouse cardiomyocytes and confirmed these results by immunoelectron microscopy in human biopsies. PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. |
| GO:0033017 sarcoplasmic reticulum membrane | EXP PMID:15598648 Myotonic dystrophy protein kinase phosphorylates phospholamb... | ACCEPT | Summary: Sarcoplasmic reticulum membrane. Reason: Principal location of PLN, where it regulates SERCA2a. Supporting Evidence: PMID:15598648 DMPK expression in cardiac myocytes is highly enriched in the sarcoplasmic reticulum (SR) where it colocalizes with the ryanodine receptor and phospholamban (PLN) PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. |
| GO:0033017 sarcoplasmic reticulum membrane | EXP PMID:22427649 Hydrophobic imbalance in the cytoplasmic domain of phosphola... | ACCEPT | Summary: Sarcoplasmic reticulum membrane. Reason: Principal location of PLN, where it regulates SERCA2a. Supporting Evidence: PMID:22427649 we made a series of amino acid substitutions in the cytoplasmic domain of PLN and tested their ability to inhibit SERCA. PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. |
| GO:0033017 sarcoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Sarcoplasmic reticulum membrane. Reason: Principal location of PLN, where it regulates SERCA2a. Supporting Evidence: PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. |
| GO:0033017 sarcoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Sarcoplasmic reticulum membrane. Reason: Principal location of PLN, where it regulates SERCA2a. Supporting Evidence: PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. |
| GO:0033017 sarcoplasmic reticulum membrane | TAS Reactome:R-HSA-5578777 | ACCEPT | Summary: Sarcoplasmic reticulum membrane. Reason: Principal location of PLN, where it regulates SERCA2a. Supporting Evidence: PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. |
| GO:0033017 sarcoplasmic reticulum membrane | TAS Reactome:R-HSA-5617182 | ACCEPT | Summary: Sarcoplasmic reticulum membrane. Reason: Principal location of PLN, where it regulates SERCA2a. Supporting Evidence: PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. |
| GO:0033574 response to testosterone | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to testosterone (IEA), transferred from rat Pln, from a study of testosterone regulation of SERCA activity in orchidectomized rats (PMID:23203968). Reason: The row is transferred from rat Pln, annotated by direct assay in a study showing that testosterone regulates cardiac contractile activation by modulating SERCA activity in orchidectomized rats (PMID:23203968), so it rests on an experiment in which phospholamban was examined as part of the SERCA regulatory system. A change in the state of phospholamban with testosterone status shows that it is affected by the hormone, not that it carries out a response to testosterone, and only the abstract is available. The term over-reads the observation and is marked as an over-annotation rather than removed. |
| GO:0042030 ATPase inhibitor activity | IBA GO_REF:0000033 | ACCEPT | Summary: ATPase inhibitor activity: PLN binds SERCA2a and lowers its apparent Ca2+ affinity. Reason: Core molecular function. Reconstitution, structure and genetic data show that monomeric PLN binds the SERCA transmembrane groove and inhibits Ca2+ binding; inhibition is reversed by phosphorylation. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002722410 SUPPORTS TRANSFER Regulin node; SERCA inhibition is the defining activity of PLN and its orthologs. UniProtKB:P26678 · PLN SUPPORTS TRANSFER Human PLN's own IDA (PMID:19708671) is among the descendant evidence; expected, not circular. Supporting Evidence: PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. PMID:23996003 In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. PMID:23996003 The two high affinity Ca 2+ -binding sites (sites I and II) of SERCA, which are formed between transmembrane helices M4, M5, M6, and M8 near the cytoplasmic membrane interface ( 26 ), are both severely disrupted by PLB4 binding. PMID:22679139 Cyclic AMP-dependent phosphorylation of PLN reverses its inhibitory effect on the Ca2+ pump. |
| GO:0042030 ATPase inhibitor activity | IDA PMID:19708671 Effects of phospholamban transmembrane mutants on the calciu... | ACCEPT | Summary: ATPase inhibitor activity: PLN binds SERCA2a and lowers its apparent Ca2+ affinity. Reason: Core molecular function. Reconstitution, structure and genetic data show that monomeric PLN binds the SERCA transmembrane groove and inhibits Ca2+ binding; inhibition is reversed by phosphorylation. Supporting Evidence: PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. PMID:23996003 In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. PMID:23996003 The two high affinity Ca 2+ -binding sites (sites I and II) of SERCA, which are formed between transmembrane helices M4, M5, M6, and M8 near the cytoplasmic membrane interface ( 26 ), are both severely disrupted by PLB4 binding. PMID:22679139 Cyclic AMP-dependent phosphorylation of PLN reverses its inhibitory effect on the Ca2+ pump. |
| GO:0042030 ATPase inhibitor activity | IEA GO_REF:0000120 | ACCEPT | Summary: ATPase inhibitor activity: PLN binds SERCA2a and lowers its apparent Ca2+ affinity. Reason: Core molecular function. Reconstitution, structure and genetic data show that monomeric PLN binds the SERCA transmembrane groove and inhibits Ca2+ binding; inhibition is reversed by phosphorylation. Supporting Evidence: PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. PMID:23996003 In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. PMID:23996003 The two high affinity Ca 2+ -binding sites (sites I and II) of SERCA, which are formed between transmembrane helices M4, M5, M6, and M8 near the cytoplasmic membrane interface ( 26 ), are both severely disrupted by PLB4 binding. PMID:22679139 Cyclic AMP-dependent phosphorylation of PLN reverses its inhibitory effect on the Ca2+ pump. |
| GO:0042030 ATPase inhibitor activity | ISS GO_REF:0000024 | ACCEPT | Summary: ATPase inhibitor activity: PLN binds SERCA2a and lowers its apparent Ca2+ affinity. Reason: Core molecular function. Reconstitution, structure and genetic data show that monomeric PLN binds the SERCA transmembrane groove and inhibits Ca2+ binding; inhibition is reversed by phosphorylation. Supporting Evidence: PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. PMID:23996003 In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. PMID:23996003 The two high affinity Ca 2+ -binding sites (sites I and II) of SERCA, which are formed between transmembrane helices M4, M5, M6, and M8 near the cytoplasmic membrane interface ( 26 ), are both severely disrupted by PLB4 binding. PMID:22679139 Cyclic AMP-dependent phosphorylation of PLN reverses its inhibitory effect on the Ca2+ pump. |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Identical protein binding (homopentamer). Reason: PLN self-associates into a homopentamer that acts as an inactive reservoir; real but secondary to SERCA inhibition. Supporting Evidence: PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. PMID:22679139 Phosphorylation of PLN monomers promotes association into inactive pentamers. |
| GO:0042802 identical protein binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Identical protein binding (homopentamer). Reason: PLN self-associates into a homopentamer that acts as an inactive reservoir; real but secondary to SERCA inhibition. Supporting Evidence: PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. PMID:22679139 Phosphorylation of PLN monomers promotes association into inactive pentamers. |
| GO:0042803 protein homodimerization activity | IEA GO_REF:0000107 | MODIFY | Summary: Protein homodimerization activity transferred from mouse. Reason: PLN forms homopentamers, not dimers; identical protein binding is the appropriate term. Proposed replacements: identical protein binding Supporting Evidence: PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. PMID:16043693 The unusual bellflower-like assembly is held together by leucine/isoleucine zipper motifs along the membrane-spanning helices. |
| GO:0042803 protein homodimerization activity | ISS GO_REF:0000024 | MODIFY | Summary: Protein homodimerization activity transferred from mouse. Reason: PLN forms homopentamers, not dimers; identical protein binding is the appropriate term. Proposed replacements: identical protein binding Supporting Evidence: PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. PMID:16043693 The unusual bellflower-like assembly is held together by leucine/isoleucine zipper motifs along the membrane-spanning helices. |
| GO:0044325 transmembrane transporter binding | IPI PMID:19708671 Effects of phospholamban transmembrane mutants on the calciu... | KEEP AS NON CORE | Summary: IPI with SERCA1a (P04191) in co-reconstituted proteoliposomes. Reason: Binding to SERCA is real and informative, but the functional term ATPase inhibitor activity better describes the consequence. Supporting Evidence: PMID:19708671 Regulation of the SERCA calcium pump by phospholamban (PLB) is largely due to interactions between their respective transmembrane domains. |
| GO:0045475 locomotor rhythm | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: locomotor rhythm transferred from mouse (thalamic reticular nucleus behavioural phenotype). Reason: Behavioural phenotype of mouse Pln perturbation (UniProt: 'In the thalamic reticular nucleus of the brain, plays a role in the regulation of sleep patterns and executive functioning', by similarity). This is a distal organismal consequence of SERCA regulation in neurons, not a process PLN executes; untested in human. |
| GO:0045475 locomotor rhythm | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: locomotor rhythm transferred from mouse (thalamic reticular nucleus behavioural phenotype). Reason: Behavioural phenotype of mouse Pln perturbation (UniProt: 'In the thalamic reticular nucleus of the brain, plays a role in the regulation of sleep patterns and executive functioning', by similarity). This is a distal organismal consequence of SERCA regulation in neurons, not a process PLN executes; untested in human. |
| GO:0048471 perinuclear region of cytoplasm | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Perinuclear region of cytoplasm, ISS from rabbit PLN in HEK-293. Reason: Perinuclear signal in transfected non-muscle cells reflects the ER/nuclear envelope; ER membrane captures it. |
| GO:0050802 circadian sleep/wake cycle, sleep | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: circadian sleep/wake cycle, sleep transferred from mouse (thalamic reticular nucleus behavioural phenotype). Reason: Behavioural phenotype of mouse Pln perturbation (UniProt: 'In the thalamic reticular nucleus of the brain, plays a role in the regulation of sleep patterns and executive functioning', by similarity). This is a distal organismal consequence of SERCA regulation in neurons, not a process PLN executes; untested in human. |
| GO:0050802 circadian sleep/wake cycle, sleep | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: circadian sleep/wake cycle, sleep transferred from mouse (thalamic reticular nucleus behavioural phenotype). Reason: Behavioural phenotype of mouse Pln perturbation (UniProt: 'In the thalamic reticular nucleus of the brain, plays a role in the regulation of sleep patterns and executive functioning', by similarity). This is a distal organismal consequence of SERCA regulation in neurons, not a process PLN executes; untested in human. |
| GO:0051117 ATPase binding | ISS PMID:12032137 Sarcolipin inhibits polymerization of phospholamban to induc... | KEEP AS NON CORE | Summary: ATPase binding (SERCA), ISS from rabbit. Reason: Binding to SERCA is real; the informative functional term is ATPase inhibitor activity. Supporting Evidence: PMID:12032137 NF-SLN binds directly to PLN and that NF-SLN inhibits the formation of PLN pentamers. |
| GO:0051480 regulation of cytosolic calcium ion concentration | IDA PMID:19708671 Effects of phospholamban transmembrane mutants on the calciu... | KEEP AS NON CORE | Summary: Regulation of cytosolic Ca2+ concentration, IDA from reconstitution. Reason: Consequence of SERCA inhibition; true physiologically, though the cited assay was in proteoliposomes. Supporting Evidence: PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. |
| GO:0051924 regulation of calcium ion transport | IDA PMID:22427649 Hydrophobic imbalance in the cytoplasmic domain of phosphola... | MODIFY | Summary: Regulation of calcium ion transport. Reason: Correct direction is negative and the specific target is SERCA-mediated Ca2+ import into the SR. Proposed replacements: negative regulation of calcium ion import into sarcoplasmic reticulum Supporting Evidence: PMID:22427649 we made a series of amino acid substitutions in the cytoplasmic domain of PLN and tested their ability to inhibit SERCA. |
| GO:0051924 regulation of calcium ion transport | IDA PMID:26673394 Phospholamban spontaneously reconstitutes into giant unilame... | MODIFY | Summary: IDA from GUV channel study. Reason: The cached abstract reports a cation-selective pentamer channel that does not conduct Ca2+ in giant vesicles; the curator's basis is not visible without full text, but PLN regulation of Ca2+ transport is clearly correct. As for the other rows, the precise term is negative regulation of SR Ca2+ import. Proposed replacements: negative regulation of calcium ion import into sarcoplasmic reticulum Supporting Evidence: PMID:26673394 highlight a preference for Cs(+) over K(+) and do not conduct Ca(2+). PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. |
| GO:0051924 regulation of calcium ion transport | ISS GO_REF:0000024 | MODIFY | Summary: Regulation of calcium ion transport. Reason: Correct direction is negative and the specific target is SERCA-mediated Ca2+ import into the SR. Proposed replacements: negative regulation of calcium ion import into sarcoplasmic reticulum Supporting Evidence: PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. |
| GO:0051926 negative regulation of calcium ion transport | IDA PMID:19708671 Effects of phospholamban transmembrane mutants on the calciu... | ACCEPT | Summary: Negative regulation of calcium ion transport. Reason: PLN inhibits SERCA Ca2+ transport. Supporting Evidence: PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. |
| GO:0055119 relaxation of cardiac muscle | TAS PMID:22679139 Modulation of cardiac contractility by the phospholamban/SER... | MODIFY | Summary: Relaxation of cardiac muscle, TAS from review. Reason: PLN regulates rather than executes relaxation: by limiting SERCA2a Ca2+ re-uptake it slows relaxation, and phosphorylation relief accelerates it. Proposed replacements: regulation of relaxation of cardiac muscle Supporting Evidence: PMID:22679139 Cyclic AMP-dependent phosphorylation of PLN reverses its inhibitory effect on the Ca2+ pump. PMID:8062415 These findings indicate that phospholamban acts as a critical repressor of basal myocardial contractility |
| GO:0086004 regulation of cardiac muscle cell contraction | IC PMID:19708671 Effects of phospholamban transmembrane mutants on the calciu... | ACCEPT | Summary: Regulation of cardiac muscle cell contraction, IC from SERCA inhibition. Reason: Follows directly from SERCA2a inhibition, supported by knockout physiology. Supporting Evidence: PMID:8062415 These findings indicate that phospholamban acts as a critical repressor of basal myocardial contractility |
| GO:0086004 regulation of cardiac muscle cell contraction | IDA PMID:26673394 Phospholamban spontaneously reconstitutes into giant unilame... | ACCEPT | Summary: IDA from GUV channel study. Reason: The cached abstract describes only vesicle reconstitution and patch clamp, not cardiomyocyte contraction; the full text is not available, so we defer to the curator because the process is clearly correct for PLN (knockout physiology). Supporting Evidence: PMID:26673394 highlight a preference for Cs(+) over K(+) and do not conduct Ca(2+). PMID:8062415 These findings indicate that phospholamban acts as a critical repressor of basal myocardial contractility |
| GO:0086036 regulation of cardiac muscle cell membrane potential | IC PMID:19708671 Effects of phospholamban transmembrane mutants on the calciu... | MARK AS OVER ANNOTATED | Summary: Regulation of cardiac muscle cell membrane potential, IC. Reason: Membrane potential effects are indirect consequences of altered Ca2+ handling; PLN does not regulate membrane potential through its own activity. |
| GO:0090281 negative regulation of calcium ion import | ISS PMID:12032137 Sarcolipin inhibits polymerization of phospholamban to induc... | ACCEPT | Summary: Negative regulation of calcium ion import, ISS from rabbit. Reason: Correct; parent of the more specific SR import term. Supporting Evidence: PMID:12032137 NF-SLN binds directly to PLN and that NF-SLN inhibits the formation of PLN pentamers. |
| GO:0090534 calcium ion-transporting ATPase complex | IDA PMID:19708671 Effects of phospholamban transmembrane mutants on the calciu... | KEEP AS NON CORE | Summary: Calcium ion-transporting ATPase complex, IDA. Reason: PLN forms a regulatory complex with SERCA as a monomer; acceptable but the PLN-SERCA complex is a transient regulatory association. Supporting Evidence: PMID:19708671 Regulation of the SERCA calcium pump by phospholamban (PLB) is largely due to interactions between their respective transmembrane domains. |
| GO:0141110 transporter inhibitor activity | IDA PMID:19708671 Effects of phospholamban transmembrane mutants on the calciu... | ACCEPT | Summary: Transporter inhibitor activity, IDA from reconstitution. Reason: SERCA is an ATPase-coupled Ca2+ transporter; PLN reduces its Ca2+ transport. This term is a valid parallel to ATPase inhibitor activity. Supporting Evidence: PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. PMID:19708671 Regulation of the SERCA calcium pump by phospholamban (PLB) is largely due to interactions between their respective transmembrane domains. |
| GO:1901894 regulation of ATPase-coupled calcium transmembrane transporter activity | IDA PMID:22427649 Hydrophobic imbalance in the cytoplasmic domain of phosphola... | ACCEPT | Summary: regulation of ATPase-coupled calcium transmembrane transporter activity Reason: PLN inhibits SERCA Ca2+ transport activity; core process. Supporting Evidence: PMID:22427649 we made a series of amino acid substitutions in the cytoplasmic domain of PLN and tested their ability to inhibit SERCA. PMID:23996003 In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. |
| GO:1901895 negative regulation of ATPase-coupled calcium transmembrane transporter activity | IDA PMID:26673394 Phospholamban spontaneously reconstitutes into giant unilame... | ACCEPT | Summary: negative regulation of ATPase-coupled calcium transmembrane transporter activity Reason: PLN inhibits SERCA Ca2+ transport activity; core process. The cited GUV paper's abstract does not show SERCA assays, but the function is clearly correct for PLN. Supporting Evidence: PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. PMID:23996003 In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. |
| GO:1901895 negative regulation of ATPase-coupled calcium transmembrane transporter activity | IDA PMID:28890335 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates ... | ACCEPT | Summary: negative regulation of ATPase-coupled calcium transmembrane transporter activity Reason: PLN inhibits SERCA Ca2+ transport activity; core process. Supporting Evidence: PMID:28890335 VMP1 interacts with SERCA and prevents formation of the SERCA/PLN/SLN inhibitory complex. PMID:23996003 In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. |
| GO:1901897 regulation of relaxation of cardiac muscle | IC PMID:19708671 Effects of phospholamban transmembrane mutants on the calciu... | ACCEPT | Summary: Regulation of relaxation of cardiac muscle, IC. Reason: PLN slows SR Ca2+ re-uptake and hence relaxation; phosphorylation relief accelerates relaxation. Supporting Evidence: PMID:8062415 These findings indicate that phospholamban acts as a critical repressor of basal myocardial contractility PMID:22679139 Cyclic AMP-dependent phosphorylation of PLN reverses its inhibitory effect on the Ca2+ pump. |
| GO:1902081 negative regulation of calcium ion import into sarcoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: Negative regulation of calcium ion import into sarcoplasmic reticulum. Reason: Core process: PLN inhibits SERCA2a-mediated Ca2+ uptake into the SR. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002722410 SUPPORTS TRANSFER Regulin node; SR Ca2+ import inhibition via SERCA is the conserved PLN role. Supporting Evidence: PMID:23996003 In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. |
| GO:1902081 negative regulation of calcium ion import into sarcoplasmic reticulum | IDA PMID:19708671 Effects of phospholamban transmembrane mutants on the calciu... | ACCEPT | Summary: Negative regulation of calcium ion import into sarcoplasmic reticulum. Reason: Core process: PLN inhibits SERCA2a-mediated Ca2+ uptake into the SR. Supporting Evidence: PMID:23996003 In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. |
| GO:1902081 negative regulation of calcium ion import into sarcoplasmic reticulum | IEA GO_REF:0000107 | ACCEPT | Summary: Negative regulation of calcium ion import into sarcoplasmic reticulum. Reason: Core process: PLN inhibits SERCA2a-mediated Ca2+ uptake into the SR. Supporting Evidence: PMID:23996003 In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. |
| GO:1902081 negative regulation of calcium ion import into sarcoplasmic reticulum | ISS GO_REF:0000024 | ACCEPT | Summary: Negative regulation of calcium ion import into sarcoplasmic reticulum. Reason: Core process: PLN inhibits SERCA2a-mediated Ca2+ uptake into the SR. Supporting Evidence: PMID:23996003 In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. |
| GO:1902081 negative regulation of calcium ion import into sarcoplasmic reticulum | ISS GO_REF:0000024 | ACCEPT | Summary: Negative regulation of calcium ion import into sarcoplasmic reticulum. Reason: Core process: PLN inhibits SERCA2a-mediated Ca2+ uptake into the SR. Supporting Evidence: PMID:23996003 In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. |
| GO:1902081 negative regulation of calcium ion import into sarcoplasmic reticulum | ISS PMID:12032137 Sarcolipin inhibits polymerization of phospholamban to induc... | ACCEPT | Summary: Negative regulation of calcium ion import into sarcoplasmic reticulum. Reason: Core process: PLN inhibits SERCA2a-mediated Ca2+ uptake into the SR. Supporting Evidence: PMID:23996003 In cardiac muscle, SERCA is regulated by phospholamban (PLB), a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates contractile strength. PMID:19708671 Only three steps in the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium ion, a subsequent conformational change in SERCA, and binding of the second calcium ion. |
| GO:1990629 phospholamban complex | IPI PMID:16043693 The structure of phospholamban pentamer reveals a channel-li... | ACCEPT | Summary: Phospholamban complex (homopentamer), IPI from NMR structure. Reason: Solution NMR structure of the human PLN homopentamer. Supporting Evidence: PMID:16043693 Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. PMID:16043693 The unusual bellflower-like assembly is held together by leucine/isoleucine zipper motifs along the membrane-spanning helices. |
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Download this section (compressed HTML)Q: Should SERCA-inhibiting regulins (PLN, SLN, MRLN, ERLN) be annotated consistently to ATPase inhibitor activity (GO:0042030), transporter inhibitor activity (GO:0141110), or both? PLN currently carries both by IDA from the same paper, while DWORF carries transporter activator activity (GO:0141109). A single convention, possibly a dedicated 'calcium-transporting ATPase inhibitor activity' child, would make the family comparable.
Q: Does the PLN pentamer's cation channel activity observed in giant vesicles occur in native SR membranes, and does it have a physiological role?
Q: Is PLN present in mitochondrial membranes in human muscle, or is the proteomic detection SR carry-over?
Experiment: Compare SR vesicle K+/Cs+ permeability and single-channel recordings from wild-type versus monomeric (pentamer-disrupting TM zipper mutant) PLN knock-in cardiomyocytes.
Hypothesis: The PLN pentamer forms a functional cation channel in native SR membranes.
Type: electrophysiology
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