ABCC8 encodes sulfonylurea receptor 1 (SUR1), an ABC-family membrane protein that regulates ATP-sensitive potassium channels. Four SUR1 subunits associate with four KCNJ11/Kir6.2 pore subunits at the plasma membrane, particularly in pancreatic beta cells and neuroendocrine tissues. SUR1 binds adenine nucleotides and sulfonylurea drugs, contributes to channel assembly and surface expression, and couples metabolic signals to channel gating. Its nucleotide-binding domains possess ATPase activity, whereas potassium passes through Kir6.2 rather than a SUR1 transport pore. In beta cells, channel opening restrains calcium-dependent insulin release; glucose-driven channel closure permits secretion. Loss-of-function variants cause congenital hyperinsulinism, while activating variants can cause neonatal diabetes. Injury-associated SUR1 signaling also contributes to neurovascular dysfunction in experimental models.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001678 intracellular glucose homeostasis | IEA GO_REF:0000107 | UNDECIDED | Summary: Intracellular glucose homeostasis is not resolved by the donor drug-response evidence. Reason: The rat Q09429 annotation traces to PMID:23828271, a glibenclamide-analogue study in streptozotocin-treated rats. Its accessible abstract concerns systemic glucose and lipid endpoints, not a demonstrated ABCC8-specific intracellular glucose-homeostasis step. Full text was not accessible, so preserve uncertainty instead of calling the original experimental curation wrong. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q09429 UNRESOLVED The rat Q09429 annotation traces to PMID:23828271, a glibenclamide-analogue study in streptozotocin-treated rats. Its accessible abstract concerns systemic glucose and lipid endpoints, not a demonstrated ABCC8-specific intracellular glucose-homeostasis step. Full text was not accessible, so preserve uncertainty instead of calling the original experimental curation wrong. ensembl:ENSRNOP00000028696 UNRESOLVED Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0005267 potassium channel activity | IMP PMID:24814349 Monoallelic ABCC8 mutations are a common cause of diazoxide-... | MODIFY | Summary: SUR1 regulates the potassium-conducting Kir6.2 pore. Reason: PMID:24814349 measures trafficking and MgADP/diazoxide responses of human SUR1 mutants, demonstrating loss of channel regulation despite normal surface delivery in several cases. The human complex structure (PMID:29286281) places the ion pathway in Kir6.2 and SUR1 around it. Use potassium channel regulator activity for the SUR1-specific molecular role; this refinement does not dispute the measured channel phenotype. Proposed replacements: potassium channel regulator activity Supporting Evidence: PMID:24814349 Seven of the 8 mutants reaching the plasma membrane had dramatically reduced response to MgADP or to diazoxide (<10% of wild-type response). |
| GO:0005267 potassium channel activity | IMP PMID:25720052 Alternating hypoglycemia and hyperglycemia in a toddler with... | MODIFY | Summary: SUR1 regulates the potassium-conducting Kir6.2 pore. Reason: PMID:25720052 reports that the R1419H SUR1 variant fails to form functional KATP channels in expression, flux and electrophysiological assays. The human complex structure (PMID:29286281) places the ion pathway in Kir6.2 and SUR1 around it. Use potassium channel regulator activity for the SUR1-specific molecular role; this refinement does not dispute the measured channel phenotype. Proposed replacements: potassium channel regulator activity |
| GO:0005267 potassium channel activity | IMP PMID:26181369 Molecular determinants of ATP-sensitive potassium channel Mg... | MODIFY | Summary: SUR1 regulates the potassium-conducting Kir6.2 pore. Reason: PMID:26181369 measures how SUR1 nucleotide-domain substitutions change MgATPase activity and gating in reconstituted channels. The human complex structure (PMID:29286281) places the ion pathway in Kir6.2 and SUR1 around it. Use potassium channel regulator activity for the SUR1-specific molecular role; this refinement does not dispute the measured channel phenotype. Proposed replacements: potassium channel regulator activity |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: SUR1 directly binds ATP in its ABC nucleotide-binding domains. Reason: Human SUR1 nucleotide occupancy is directly resolved in PMID:29286281, with ATP at its degenerate nucleotide site and ADP at the consensus site. The conserved ABC nucleotide-binding architecture supports the inferred row; direct human target evidence corroborates the family/domain transfer. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:B2RUS7 SOURCE WEAK OR INFERRED Mouse Abcc8 identity verified. The current source record has no experimental entries; its negative-insulin-secretion row is itself inferred from rat Q09429. Direct human evidence supports the accepted target function/location independently. ensembl:ENSMUSP00000033123 SUPPORTS TRANSFER Mouse Abcc8 protein identifier paired with UniProtKB:B2RUS7; the mouse source chain and any transfer from rat are assessed in that donor entry. This identifier supplies no additional experiment. InterPro:IPR000388 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. The mapped function is corroborated by the cited primary SUR1 evidence. InterPro:IPR000844 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. The mapped function is corroborated by the cited primary SUR1 evidence. InterPro:IPR003439 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. The mapped function is corroborated by the cited primary SUR1 evidence. InterPro:IPR011527 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. The mapped function is corroborated by the cited primary SUR1 evidence. InterPro:IPR017871 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. The mapped function is corroborated by the cited primary SUR1 evidence. InterPro:IPR036640 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. The mapped function is corroborated by the cited primary SUR1 evidence. Supporting Evidence: PMID:29286281 These structures support the role of SUR1 as an ADP sensor |
| GO:0005524 ATP binding | TAS Reactome:R-HSA-265682 | ACCEPT | Summary: SUR1 directly binds ATP in its ABC nucleotide-binding domains. Reason: Human SUR1 nucleotide occupancy is directly resolved in PMID:29286281, with ATP at its degenerate nucleotide site and ADP at the consensus site. The conserved ABC nucleotide-binding architecture supports the inferred row. Reactome:R-HSA-265682 emphasizes inhibitory ATP binding to Kir6.2; independent structural evidence establishes ATP binding to SUR1 itself, so these two sites must not be conflated. |
| GO:0005886 plasma membrane | EXP PMID:24814349 Monoallelic ABCC8 mutations are a common cause of diazoxide-... | ACCEPT | Summary: Mature SUR1-containing KATP channels function at the plasma membrane. Reason: PMID:24814349 supports the membrane channel context. Human ABCC8 surface-trafficking assays in PMID:24814349 and functional human SUR1/Kir6.2 reconstitution in PMID:29286281 establish this as the principal functional location. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Mature SUR1-containing KATP channels function at the plasma membrane. Reason: GO_REF:0000033 supports the membrane channel context. Human ABCC8 surface-trafficking assays in PMID:24814349 and functional human SUR1/Kir6.2 reconstitution in PMID:29286281 establish this as the principal functional location. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002795584 SUPPORTS TRANSFER PAINT placement of the inherited plasma-membrane location is compatible with direct human SUR1 surface-expression data. The target among experimental descendants is expected, not circular. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Mature SUR1-containing KATP channels function at the plasma membrane. Reason: GO_REF:0000120 supports the membrane channel context. Human ABCC8 surface-trafficking assays in PMID:24814349 and functional human SUR1/Kir6.2 reconstitution in PMID:29286281 establish this as the principal functional location. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:B2RUS7 SOURCE WEAK OR INFERRED Mouse Abcc8 identity verified. The current source record has no experimental entries; its negative-insulin-secretion row is itself inferred from rat Q09429. Direct human evidence supports the accepted target function/location independently. ensembl:ENSMUSP00000033123 SUPPORTS TRANSFER Mouse Abcc8 protein identifier paired with UniProtKB:B2RUS7; the mouse source chain and any transfer from rat are assessed in that donor entry. This identifier supplies no additional experiment. UniProtKB-SubCell:SL-0039 SUPPORTS TRANSFER GO_REF:0000120 supports the membrane channel context. Human ABCC8 surface-trafficking assays in PMID:24814349 and functional human SUR1/Kir6.2 reconstitution in PMID:29286281 establish this as the principal functional location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1296024 | ACCEPT | Summary: Mature SUR1-containing KATP channels function at the plasma membrane. Reason: Reactome:R-HSA-1296024 supports the membrane channel context. Human ABCC8 surface-trafficking assays in PMID:24814349 and functional human SUR1/Kir6.2 reconstitution in PMID:29286281 establish this as the principal functional location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-265682 | ACCEPT | Summary: Mature SUR1-containing KATP channels function at the plasma membrane. Reason: Reactome:R-HSA-265682 supports the membrane channel context. Human ABCC8 surface-trafficking assays in PMID:24814349 and functional human SUR1/Kir6.2 reconstitution in PMID:29286281 establish this as the principal functional location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5683113 | ACCEPT | Summary: Mature SUR1-containing KATP channels function at the plasma membrane. Reason: Reactome:R-HSA-5683113 supports the membrane channel context. Human ABCC8 surface-trafficking assays in PMID:24814349 and functional human SUR1/Kir6.2 reconstitution in PMID:29286281 establish this as the principal functional location. The mutant loss-of-function event does not require every pathogenic variant to reach the membrane; it is the native functional complex that resides there. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5683209 | ACCEPT | Summary: Mature SUR1-containing KATP channels function at the plasma membrane. Reason: Reactome:R-HSA-5683209 supports the membrane channel context. Human ABCC8 surface-trafficking assays in PMID:24814349 and functional human SUR1/Kir6.2 reconstitution in PMID:29286281 establish this as the principal functional location. Activating variants change gating at the membrane without making that location mutation-specific. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9650858 | ACCEPT | Summary: Mature SUR1-containing KATP channels function at the plasma membrane. Reason: Reactome:R-HSA-9650858 supports the membrane channel context. Human ABCC8 surface-trafficking assays in PMID:24814349 and functional human SUR1/Kir6.2 reconstitution in PMID:29286281 establish this as the principal functional location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9652580 | ACCEPT | Summary: Mature SUR1-containing KATP channels function at the plasma membrane. Reason: Reactome:R-HSA-9652580 supports the membrane channel context. Human ABCC8 surface-trafficking assays in PMID:24814349 and functional human SUR1/Kir6.2 reconstitution in PMID:29286281 establish this as the principal functional location. |
| GO:0006813 potassium ion transport | IEA GO_REF:0000002 | ACCEPT | Summary: SUR1 participates in potassium transport as the regulatory KATP subunit. Reason: PMID:7502040 reconstitutes inward-rectifying, ATP-sensitive K+ channels from Kir6.2 and SUR. PMID:29286281 resolves human SUR1 coupled to the Kir6.2 pore. ABCC8 directly regulates this transport machinery; acceptance of the process does not assign the ion-conducting pore or an ATP-driven pump to SUR1. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR000388 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. The mapped function is corroborated by the cited primary SUR1 evidence. InterPro:IPR000844 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. The mapped function is corroborated by the cited primary SUR1 evidence. |
| GO:0006813 potassium ion transport | TAS PMID:7502040 Reconstitution of IKATP: an inward rectifier subunit plus th... | ACCEPT | Summary: SUR1 participates in potassium transport as the regulatory KATP subunit. Reason: PMID:7502040 reconstitutes inward-rectifying, ATP-sensitive K+ channels from Kir6.2 and SUR. PMID:29286281 resolves human SUR1 coupled to the Kir6.2 pore. ABCC8 directly regulates this transport machinery; acceptance of the process does not assign the ion-conducting pore or an ATP-driven pump to SUR1. |
| GO:0007565 female pregnancy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SUR1 is implicated in pregnancy-dependent uterine excitability. Reason: Rat donor Q09429 traces to PMID:21527399, which reports gestation-dependent SUR1 expression and pharmacological relaxation of uterine tissue. This is a tissue and developmental context of channel regulation, not the principal molecular function or proof of an indispensable human pregnancy mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q09429 SUPPORTS TRANSFER Rat donor Q09429 traces to PMID:21527399, which reports gestation-dependent SUR1 expression and pharmacological relaxation of uterine tissue. This is a tissue and developmental context of channel regulation, not the principal molecular function or proof of an indispensable human pregnancy mechanism. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0007613 memory | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Memory retention after subarachnoid hemorrhage is a contextual downstream phenotype. Reason: The rat source PMID:24114458 includes a day-12 Morris-water-maze memory probe after training. In bilateral entorhinal hemorrhage, glibenclamide-treated animals retained performance comparable to uninjured controls, whereas vehicle-treated animals performed at chance. Unilateral injury did not impair this probe. Retain the context-specific memory association as non-core: these injury/protection results do not establish a direct memory-encoding mechanism for ABCC8 or identify the injury-associated SUR1–TRPM4 channel with pancreatic KATP. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q09429 SUPPORTS TRANSFER Rat Abcc8 donor evidence is PMID:24114458: the day-12 memory probe distinguishes retention after bilateral injury from the absence of a unilateral-injury deficit. The contextual pharmacological result is retained as non-core, not as a direct memory-encoding function. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. Supporting Evidence: PMID:24114458 Both the memory probe on day 12 and the test of rapid learning on day 19 showed that they swam in the correct quadrant no more than a quarter of the time, as expected from chance alone |
| GO:0008281 sulfonylurea receptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: SUR1 provides the sulfonylurea-sensitive regulatory site of KATP. Reason: The SUR1-family InterPro assignment agrees with functional sulfonylurea inhibition in reconstituted channels (PMID:7502040), the glibenclamide-bound channel structure (PMID:28092267), and conformationally sensitive ligand binding in PMID:30587573. The receptor term denotes drug-responsive signaling through the associated channel, not a solute transporter. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR000388 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. The mapped function is corroborated by the cited primary SUR1 evidence. InterPro:IPR000844 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. The mapped function is corroborated by the cited primary SUR1 evidence. |
| GO:0008282 inward rectifying potassium channel | IDA PMID:20610380 Ankyrin-B regulates Kir6.2 membrane expression and function ... | ACCEPT | Summary: SUR1 is a regulatory component of the heteromeric inward-rectifying KATP channel. Reason: Cached human KATP structures in PMID:29286281 resolve the SUR1–Kir6.2 interface and place SUR1 in the heteromeric inward-rectifying channel complex. The externally read original Results and Figure 3 of PMID:20610380 corroborate SUR1/Kir6.2 co-immunoprecipitation in cotransfected HEK293 cells. Its local cache is abstract-only. Ankyrin-B association with SUR requires Kir6.2; direct ankyrin-B/SUR1 binding is not inferred. Supporting Evidence: PMID:29286281 A lasso extension forms an interface between SUR1 and Kir6.2 adjacent to the ATP site in the propeller form and is disrupted in the quatrefoil form. |
| GO:0008282 inward rectifying potassium channel | IEA GO_REF:0000120 | ACCEPT | Summary: SUR1 is a regulatory component of the heteromeric inward-rectifying KATP channel. Reason: GO:0008282 explicitly includes Kir6.x pore subunits and SURx regulatory subunits. The ARBA/rat-source complex-membership inference is corroborated by the human structure in PMID:29286281, which contains four SUR1 and four Kir6.2 subunits. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00092363 SUPPORTS TRANSFER Rule-based assertion corroborated by direct human SUR1/Kir6.2 complex and insulin-secretion evidence, not independent experimental support. UniProtKB:Q09429 SUPPORTS TRANSFER GO:0008282 explicitly includes Kir6.x pore subunits and SURx regulatory subunits. The human complex in PMID:29286281 contains four of each. This establishes the core complex membership independently of the cardiac focus of PMID:20610380; that paper is abstract-only in the cache, so no unsupported claim about its individual constructs is made. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0008282 inward rectifying potassium channel | IPI PMID:29286281 Molecular structure of human KATP in complex with ATP and AD... | ACCEPT | Summary: SUR1 is a regulatory component of the heteromeric inward-rectifying KATP channel. Reason: The cited human structure in PMID:29286281 resolves four SUR1 subunits associated with the Kir6.2 tetramer. This directly supports membership in GO:0008282, whose definition explicitly includes the regulatory SURx subunits as well as the Kir6.x pore. |
| GO:0008542 visual learning | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Water-maze learning after hemorrhage supports a contextual, non-core learning association. Reason: The rat donor annotation to visual learning derives from PMID:24114458 Morris-water-maze platform acquisition and search-strategy experiments, distinct from its day-12 memory-retention probe. Glibenclamide improved incremental learning after bilateral injury and rapid learning after unilateral injury; it did not significantly rescue the day-19 rapid-learning deficit after bilateral injury. Retain the curated learning association with these injury and task limits, without claiming a direct visual-processing function or general enhancement of learning by ABCC8. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q09429 SUPPORTS TRANSFER Rat Abcc8 donor evidence is PMID:24114458 water-maze acquisition/search performance. The task-specific effects differ between unilateral and bilateral hemorrhage; no direct visual-processing mechanism is established. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. Supporting Evidence: PMID:24114458 rats with bilateral entorhinal SAH administered glibenclamide performed better, with incremental learning on days 7 to 11 |
| GO:0009268 response to pH | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Extracellular pH and zinc modulate SUR1-containing channels in the donor assay. Reason: Rat Q09429 traces to PMID:15613469, whose abstract describes pH-dependent zinc activation and mutational mapping in SUR1-containing channels, contrasted with SUR2A. Retain a contextual modulation response; do not assert that this is the principal physiological ligand or that human residue equivalence was directly assayed. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q09429 SUPPORTS TRANSFER Rat Q09429 traces to PMID:15613469, whose abstract describes pH-dependent zinc activation and mutational mapping in SUR1-containing channels, contrasted with SUR2A. Retain a contextual modulation response; do not assert that this is the principal physiological ligand or that human residue equivalence was directly assayed. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The xenobiotic response is an expression response in a rat cell model. Reason: PMID:17174476 reports reduced SUR1 mRNA after risperidone treatment of rat PC12 cells, without a corresponding rat-brain change in the described exposure. Retain this narrow response context; it is not evidence that SUR1 exports xenobiotics. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q09429 SUPPORTS TRANSFER PMID:17174476 reports reduced SUR1 mRNA after risperidone treatment of rat PC12 cells, without a corresponding rat-brain change in the described exposure. Retain this narrow response context; it is not evidence that SUR1 exports xenobiotics. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0010043 response to zinc ion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Extracellular pH and zinc modulate SUR1-containing channels in the donor assay. Reason: Rat Q09429 traces to PMID:15613469, whose abstract describes pH-dependent zinc activation and mutational mapping in SUR1-containing channels, contrasted with SUR2A. Retain a contextual modulation response; do not assert that this is the principal physiological ligand or that human residue equivalence was directly assayed. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q09429 SUPPORTS TRANSFER Rat Q09429 traces to PMID:15613469, whose abstract describes pH-dependent zinc activation and mutational mapping in SUR1-containing channels, contrasted with SUR2A. Retain a contextual modulation response; do not assert that this is the principal physiological ligand or that human residue equivalence was directly assayed. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0010989 negative regulation of low-density lipoprotein particle clearance | IEA GO_REF:0000107 | UNDECIDED | Summary: Direct negative regulation of LDL clearance is not established by accessible donor evidence. Reason: The Q09429 source PMID:23828271 reports blood-lipid changes following glibenclamide-analogue treatment in diabetic rats. The accessible abstract does not resolve an ABCC8-specific LDL-clearance mechanism or distinguish clearance from lipid production. Full text could not be obtained; do not infer a lipid transporter function from these endpoints. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q09429 UNRESOLVED The Q09429 source PMID:23828271 reports blood-lipid changes following glibenclamide-analogue treatment in diabetic rats. The accessible abstract does not resolve an ABCC8-specific LDL-clearance mechanism or distinguish clearance from lipid production. Full text could not be obtained; do not infer a lipid transporter function from these endpoints. ensembl:ENSRNOP00000028696 UNRESOLVED Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0015272 ATP-activated inward rectifier potassium channel activity | NAS PMID:28842488 Conserved functional consequences of disease-associated muta... | ACCEPT | Summary: SUR1 contributes to ATP-sensitive inward-rectifying KATP channel activity. Reason: The seeded contributes_to qualifier is essential: Kir6.2 forms the pore while SUR1 regulates it. PMID:28842488 studies SUR-coassembled channels by flux and patch clamp; independent human structural and electrophysiological evidence in PMID:29286281 substantiates the contribution. The live GO:0015272 definition concerns ATP-sensitive inward rectification despite its ATP-activated label; do not reject this annotation on label wording alone. |
| GO:0015272 ATP-activated inward rectifier potassium channel activity | TAS Reactome:R-HSA-5683209 | MODIFY | Summary: Activating SUR1 variants alter regulation of a separate potassium pore. Reason: Reactome:R-HSA-5683209 describes gain-of-function ABCC8 variants that keep the Kir6.2-containing channel open and suppress insulin secretion. The SUR1-specific activity is potassium channel regulation; the seeded contributes_to annotation is separately retained for the complex-level activity. The replacement preserves the regulatory mechanism rather than assigning pore formation to the ABC subunit. Proposed replacements: potassium channel regulator activity |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Plasma membrane is the informative functional membrane location. Reason: The InterPro membrane-domain inference is correct but broad. Direct human surface-expression and functional-channel assays in PMID:24814349 and PMID:29286281 establish the plasma membrane. This specificity improvement does not deny ER transit during assembly. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR000388 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. Direct target evidence permits refinement to plasma membrane. InterPro:IPR000844 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. Direct target evidence permits refinement to plasma membrane. InterPro:IPR011527 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. Direct target evidence permits refinement to plasma membrane. InterPro:IPR036640 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. Direct target evidence permits refinement to plasma membrane. Proposed replacements: plasma membrane |
| GO:0016525 negative regulation of angiogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SUR1 inhibition affects angiogenesis during post-stroke repair. Reason: Rat Q09429 traces to PMID:23149556: acute glibenclamide treatment increases migration of doublecortin-positive cells, subsequent neuronal generation and hippocampal angiogenesis. Retain the existing negative-regulation inference as a contextual injury phenotype, with the limitation that a drug intervention and tissue repair endpoints do not establish a cell-autonomous developmental activity of human SUR1. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q09429 SUPPORTS TRANSFER Rat Q09429 traces to PMID:23149556: acute glibenclamide treatment increases migration of doublecortin-positive cells, subsequent neuronal generation and hippocampal angiogenesis. Retain the existing negative-regulation inference as a contextual injury phenotype, with the limitation that a drug intervention and tissue repair endpoints do not establish a cell-autonomous developmental activity of human SUR1. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: SUR1 has intrinsic MgATPase activity within its regulatory nucleotide cycle. Reason: PMID:26181369 directly measures ATP hydrolysis by recombinant SUR1 nucleotide-domain constructs and relates variants to channel responses. PMID:29286281 also measures ATPase activity of the purified human channel complex. Catalysis supports nucleotide-dependent regulation, not stoichiometric ATP-driven K+ translocation. PMID:30587573 shows that ATP binding without hydrolysis can promote opening in specifically sensitized channel constructs. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR003439 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. The mapped function is corroborated by the cited primary SUR1 evidence. InterPro:IPR017871 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. The mapped function is corroborated by the cited primary SUR1 evidence. Supporting Evidence: PMID:26181369 sulfonylurea receptor 1 (SUR1) S1369A diabetes risk variant increases MgATPase activity |
| GO:0019829 ATPase-coupled monoatomic cation transmembrane transporter activity | IDA PMID:26181369 Molecular determinants of ATP-sensitive potassium channel Mg... | MODIFY | Summary: The cited experiment establishes ATPase activity and channel regulation, not a cation pump. Reason: The full text of PMID:26181369 uses direct biochemical MgATPase assays together with patch clamp, including human SUR1 constructs. GO:0019829 requires cation translocation coupled to ATP hydrolysis as a pump reaction. The channel pore conducts K+ through Kir6.2, while SUR1 nucleotide-domain activity regulates gating. Replace with the directly measured ATPase activity; this is a term-scope correction, not rejection of the experiment. Proposed replacements: ATP hydrolysis activity Supporting Evidence: PMID:26181369 sulfonylurea receptor 1 (SUR1) S1369A diabetes risk variant increases MgATPase activity |
| GO:0019829 ATPase-coupled monoatomic cation transmembrane transporter activity | ISS GO_REF:0000024 | MODIFY | Summary: Hamster SUR1 genetic channel assays support a regulator, not an ATP-driven cation pump. Reason: The hamster donor accession carries an IGI annotation to PMID:28842488, which studies SUR/Kir channel gating using flux and patch clamp. Its full text was not accessible here, but independent human structures distinguish the SUR1 regulator from the Kir6.2 ion pathway. ATP-sensitive channel gating does not satisfy the ATP-coupled cation-pump definition of GO:0019829. Use the established SUR1-specific regulator activity without alleging a wrong-gene citation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:A0A1S4NYG1 SOURCE WEAK OR INFERRED The hamster donor accession carries an IGI annotation to PMID:28842488, which studies SUR/Kir channel gating using flux and patch clamp. Its full text was not accessible here, but independent human structures distinguish the SUR1 regulator from the Kir6.2 ion pathway. ATP-sensitive channel gating does not satisfy the ATP-coupled cation-pump definition of GO:0019829. Use the established SUR1-specific regulator activity without alleging a wrong-gene citation. Proposed replacements: potassium channel regulator activity |
| GO:0019829 ATPase-coupled monoatomic cation transmembrane transporter activity | ISS GO_REF:0000024 | MODIFY | Summary: Hamster SUR1 genetic channel assays support a regulator, not an ATP-driven cation pump. Reason: The hamster donor accession carries an IGI annotation to PMID:28842488, which studies SUR/Kir channel gating using flux and patch clamp. Its full text was not accessible here, but independent human structures distinguish the SUR1 regulator from the Kir6.2 ion pathway. ATP-sensitive channel gating does not satisfy the ATP-coupled cation-pump definition of GO:0019829. Use the established SUR1-specific regulator activity without alleging a wrong-gene citation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:A0A1U7R319 SOURCE WEAK OR INFERRED The hamster donor accession carries an IGI annotation to PMID:28842488, which studies SUR/Kir channel gating using flux and patch clamp. Its full text was not accessible here, but independent human structures distinguish the SUR1 regulator from the Kir6.2 ion pathway. ATP-sensitive channel gating does not satisfy the ATP-coupled cation-pump definition of GO:0019829. Use the established SUR1-specific regulator activity without alleging a wrong-gene citation. Proposed replacements: potassium channel regulator activity |
| GO:0030672 synaptic vesicle membrane | IEA GO_REF:0000107 | UNDECIDED | Summary: The precise presynaptic or synaptic-vesicle location needs source verification. Reason: Rat Q09429 traces to PMID:14645230. The accessible abstract describes syntaxin-1A binding to SUR1 nucleotide-binding folds and inhibition of KATP activity in islet/insulinoma-related experiments. That summary does not resolve the specific synaptic location; the full text was not accessible. A syntaxin interaction alone is insufficient to confirm or refute the curator-assigned compartment. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q09429 UNRESOLVED Rat Q09429 traces to PMID:14645230. The accessible abstract describes syntaxin-1A binding to SUR1 nucleotide-binding folds and inhibition of KATP activity in islet/insulinoma-related experiments. That summary does not resolve the specific synaptic location; the full text was not accessible. A syntaxin interaction alone is insufficient to confirm or refute the curator-assigned compartment. ensembl:ENSRNOP00000028696 UNRESOLVED Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0031004 potassium ion-transporting ATPase complex | ISS GO_REF:0000024 | MODIFY | Summary: SUR1 belongs to the KATP channel complex, not a potassium-importing ATPase complex. Reason: Live GO:0031004 defines an ATP-hydrolysis-coupled K+ uptake complex, exemplified by bacterial Kdp. Rat Q09429 carries an inferred source citing PMID:28842488; its SUR/Kir channel is mechanistically different. GO:0008282 explicitly comprises Kir6.x pore and SURx regulatory subunits and is directly demonstrated for human SUR1 in PMID:29286281. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q09429 SOURCE WEAK OR INFERRED Live GO:0031004 defines an ATP-hydrolysis-coupled K+ uptake complex, exemplified by bacterial Kdp. Rat Q09429 carries an inferred source citing PMID:28842488; its SUR/Kir channel is mechanistically different. GO:0008282 explicitly comprises Kir6.x pore and SURx regulatory subunits and is directly demonstrated for human SUR1 in PMID:29286281. Proposed replacements: inward rectifying potassium channel |
| GO:0032496 response to lipopolysaccharide | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Endotoxemia changes Abcc8 expression in rat tissues. Reason: PMID:17285300 measures ABC-transporter transcription after lipopolysaccharide exposure and reports renal Abcc8 downregulation. This supports a contextual response-to-LPS annotation. It does not show that SUR1 binds, transports or detoxifies LPS. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q09429 SUPPORTS TRANSFER PMID:17285300 measures ABC-transporter transcription after lipopolysaccharide exposure and reports renal Abcc8 downregulation. This supports a contextual response-to-LPS annotation. It does not show that SUR1 binds, transports or detoxifies LPS. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0032760 positive regulation of tumor necrosis factor production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SUR1-dependent injury signaling promotes inflammatory TNF expression. Reason: In the rat subarachnoid-hemorrhage study PMID:18854840, glibenclamide reduces TNF upregulation along with barrier disruption. PMID:24114458 adds SUR1 antisense evidence. Retain this injury-associated regulatory effect, not a direct TNF biosynthetic activity or constitutive core process. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q09429 SUPPORTS TRANSFER In the rat subarachnoid-hemorrhage study PMID:18854840, glibenclamide reduces TNF upregulation along with barrier disruption. PMID:24114458 adds SUR1 antisense evidence. Retain this injury-associated regulatory effect, not a direct TNF biosynthetic activity or constitutive core process. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0032868 response to insulin | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SUR1 expression responds in the insulin-induced hypoglycemia context. Reason: Rat Q09429 traces to PMID:18084728, which examines hypothalamic SUR1 expression under insulin-induced hypoglycemia with hormonal and metabolic modifiers. Preserve this contextual response; insulin secretion regulation by pancreatic SUR1 is a different, core process. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q09429 SUPPORTS TRANSFER Rat Q09429 traces to PMID:18084728, which examines hypothalamic SUR1 expression under insulin-induced hypoglycemia with hormonal and metabolic modifiers. Preserve this contextual response; insulin secretion regulation by pancreatic SUR1 is a different, core process. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse GO-CAMs recover the conditional positive insulin-secretion evidence. Reason: The cached mouse GO-CAM 62f58d8800002184 assigns MGI:MGI:1352629 to GO:0035774 with IMP evidence from PMID:16924481. Its PubMed abstract reports reduced glucose-stimulated secretion after complete SUR1 loss, whereas heterozygous loss increases secretion. Retain the conserved physiological association as non-core with dosage dependence; it does not mean that acute opening of KATP channels stimulates insulin release. The donor was missed by the initial UniProt-only search, not absent from curated mouse evidence. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:B2RUS7 SUPPORTS TRANSFER Mouse Abcc8 is MGI:MGI:1352629; cached GO-CAM 62f58d8800002184 records IMP PMID:16924481 with MGI:MGI:2388392. Positive secretion support concerns complete-loss physiology, not an acute channel-opening response. ensembl:ENSMUSP00000033123 SUPPORTS TRANSFER Mouse Abcc8 protein identifier paired with UniProtKB:B2RUS7; the mouse source chain and any transfer from rat are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0042383 sarcolemma | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SUR1 has a reported cardiac sarcolemmal location in rodents. Reason: PMID:15647111 uses antibody controls and immunolocalization in mouse and rat myocardium, reporting SUR1 at the ventricular sarcolemmal surface. Retain this tissue-specific location without claiming that SUR1 is the principal ventricular KATP isoform in all contexts or replacing its pancreatic plasma-membrane role. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q09429 SUPPORTS TRANSFER PMID:15647111 uses antibody controls and immunolocalization in mouse and rat myocardium, reporting SUR1 at the ventricular sarcolemmal surface. Retain this tissue-specific location without claiming that SUR1 is the principal ventricular KATP isoform in all contexts or replacing its pancreatic plasma-membrane role. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. Supporting Evidence: PMID:15647111 Both Kir6.1 and SUR1 subunits were found to express strongly at the sarcolemma. |
| GO:0042734 presynaptic membrane | IEA GO_REF:0000107 | UNDECIDED | Summary: The precise presynaptic or synaptic-vesicle location needs source verification. Reason: Rat Q09429 traces to PMID:14645230. The accessible abstract describes syntaxin-1A binding to SUR1 nucleotide-binding folds and inhibition of KATP activity in islet/insulinoma-related experiments. That summary does not resolve the specific synaptic location; the full text was not accessible. A syntaxin interaction alone is insufficient to confirm or refute the curator-assigned compartment. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q09429 UNRESOLVED Rat Q09429 traces to PMID:14645230. The accessible abstract describes syntaxin-1A binding to SUR1 nucleotide-binding folds and inhibition of KATP activity in islet/insulinoma-related experiments. That summary does not resolve the specific synaptic location; the full text was not accessible. A syntaxin interaction alone is insufficient to confirm or refute the curator-assigned compartment. ensembl:ENSRNOP00000028696 UNRESOLVED Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0043268 positive regulation of potassium ion transport | IEA GO_REF:0000107 | ACCEPT | Summary: SUR1 Mg-nucleotide sensing promotes KATP channel activity. Reason: The rat-source study PMID:15962003 reports SUR1-dependent MgATP stimulation, lost with SUR1 nucleotide-domain mutations. Human functional and structural work in PMID:29286281 supports the same regulatory role. SUR1 directly performs channel regulation, so participation in positive regulation of potassium transport is mechanistically supported. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q09429 SUPPORTS TRANSFER The rat-source study PMID:15962003 reports SUR1-dependent MgATP stimulation, lost with SUR1 nucleotide-domain mutations. Human functional and structural work in PMID:29286281 supports the same regulatory role. SUR1 directly performs channel regulation, so participation in positive regulation of potassium transport is mechanistically supported. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0043531 ADP binding | IEA GO_REF:0000107 | ACCEPT | Summary: SUR1 directly binds ADP as a metabolic signal. Reason: The mouse B2RUS7 donor term was not recovered in the current record, but the human SUR1 consensus nucleotide site contains ADP in PMID:29286281. Direct target evidence establishes the activity irrespective of the stale inferred source chain. Propagation Review Root cause: SOURCE STALE OR MISSING Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:B2RUS7 SOURCE STALE OR MISSING The mouse B2RUS7 donor term was not recovered in the current record, but the human SUR1 consensus nucleotide site contains ADP in PMID:29286281. Direct target evidence establishes the activity irrespective of the stale inferred source chain. ensembl:ENSMUSP00000033123 SOURCE STALE OR MISSING Mouse Abcc8 protein identifier paired with UniProtKB:B2RUS7; the mouse source chain and any transfer from rat are assessed in that donor entry. This identifier supplies no additional experiment. Supporting Evidence: PMID:29286281 These structures support the role of SUR1 as an ADP sensor |
| GO:0044325 transmembrane transporter binding | IPI PMID:20610380 Ankyrin-B regulates Kir6.2 membrane expression and function ... | ACCEPT | Summary: SUR1 associates with the Kir6.2 transporter subunit. Reason: Cached human KATP structures in PMID:29286281 resolve an interface between SUR1 and the Kir6.2 pore, supporting the specific transmembrane-transporter binding function. The externally read original Results and Figure 3 of PMID:20610380 corroborate SUR1/Kir6.2 co-immunoprecipitation in cotransfected HEK293 cells. The public primary Methods identify human Kir6.2 and human SUR1 constructs (https://pmc.ncbi.nlm.nih.gov/articles/PMC2937900/, KATP Constructs and Results Figure 3). Its local cache is abstract-only. Ankyrin-B association with SUR requires Kir6.2; direct ankyrin-B/SUR1 binding is not inferred. Supporting Evidence: PMID:29286281 A lasso extension forms an interface between SUR1 and Kir6.2 adjacent to the ATP site in the propeller form and is disrupted in the quatrefoil form. |
| GO:0046676 negative regulation of insulin secretion | IEA GO_REF:0000120 | ACCEPT | Summary: Functional SUR1-containing KATP channels restrain insulin secretion. Reason: The rat Q09429 source PMID:15163199 shows channel-opener-mediated inhibition of insulin secretion. The mouse donor currently carries a transfer from rat rather than independent experimental evidence. Human loss-of-function ABCC8 variants cause excessive secretion and impaired channel activation (PMID:24814349), corroborating the core negative regulatory role. Channel closure as glucose rises releases this restraint. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:B2RUS7 SOURCE WEAK OR INFERRED Mouse Abcc8 identity verified. The current source record has no experimental entries; its negative-insulin-secretion row is itself inferred from rat Q09429. Direct human evidence supports the accepted target function/location independently. ensembl:ENSMUSP00000033123 SUPPORTS TRANSFER Mouse Abcc8 protein identifier paired with UniProtKB:B2RUS7; the mouse source chain and any transfer from rat are assessed in that donor entry. This identifier supplies no additional experiment. UniProtKB:Q09429 SUPPORTS TRANSFER The rat Q09429 source PMID:15163199 shows channel-opener-mediated inhibition of insulin secretion. The mouse donor currently carries a transfer from rat rather than independent experimental evidence. Human loss-of-function ABCC8 variants cause excessive secretion and impaired channel activation (PMID:24814349), corroborating the core negative regulatory role. Channel closure as glucose rises releases this restraint. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0050768 negative regulation of neurogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SUR1 inhibition affects neurogenesis during post-stroke repair. Reason: Rat Q09429 traces to PMID:23149556: acute glibenclamide treatment increases migration of doublecortin-positive cells, subsequent neuronal generation and hippocampal angiogenesis. Retain the existing negative-regulation inference as a contextual injury phenotype, with the limitation that a drug intervention and tissue repair endpoints do not establish a cell-autonomous developmental activity of human SUR1. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q09429 SUPPORTS TRANSFER Rat Q09429 traces to PMID:23149556: acute glibenclamide treatment increases migration of doublecortin-positive cells, subsequent neuronal generation and hippocampal angiogenesis. Retain the existing negative-regulation inference as a contextual injury phenotype, with the limitation that a drug intervention and tissue repair endpoints do not establish a cell-autonomous developmental activity of human SUR1. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0050796 regulation of insulin secretion | IEA GO_REF:0000117 | ACCEPT | Summary: SUR1 couples metabolic nucleotide signals to insulin secretion. Reason: The ARBA/pathway assignment agrees with reconstituted human channels and ABCC8 disease-variant assays (PMID:29286281; PMID:24814349). SUR1 regulates the K+ conductance that controls beta-cell membrane potential and hence voltage-gated calcium entry and insulin release. It participates through channel regulation, not insulin biosynthesis or granule proteolysis. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00091593 SUPPORTS TRANSFER Rule-based assertion corroborated by direct human SUR1/Kir6.2 complex and insulin-secretion evidence, not independent experimental support. |
| GO:0050796 regulation of insulin secretion | TAS Reactome:R-HSA-422356 | ACCEPT | Summary: SUR1 couples metabolic nucleotide signals to insulin secretion. Reason: The ARBA/pathway assignment agrees with reconstituted human channels and ABCC8 disease-variant assays (PMID:29286281; PMID:24814349). SUR1 regulates the K+ conductance that controls beta-cell membrane potential and hence voltage-gated calcium entry and insulin release. It participates through channel regulation, not insulin biosynthesis or granule proteolysis. |
| GO:0055085 transmembrane transport | IBA GO_REF:0000033 | MODIFY | Summary: The supported transmembrane-transport role is regulation of potassium passage through KATP. Reason: SUR1 directly contributes to the Kir6.2-containing transport complex. The broad transmembrane-transport annotation can therefore be retained in substance but refined to potassium ion transmembrane transport (PMID:29286281; PMID:7502040). The ABC-like fold must not be read as evidence that SUR1 translocates an independent solute. For PAINT, this refines process scope rather than rejecting inherited membrane-transport participation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000657997 SUPPORTS TRANSFER The inherited participation in transmembrane transport is retained; the target directly regulates a K+ channel and supports refinement to potassium transport. Proposed replacements: potassium ion transmembrane transport |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: The supported transmembrane-transport role is regulation of potassium passage through KATP. Reason: SUR1 directly contributes to the Kir6.2-containing transport complex. The broad transmembrane-transport annotation can therefore be retained in substance but refined to potassium ion transmembrane transport (PMID:29286281; PMID:7502040). The ABC-like fold must not be read as evidence that SUR1 translocates an independent solute. InterPro:IPR011527 supplies the broad family/domain mapping; direct human evidence supplies the specific transported ion and regulatory role. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR011527 SUPPORTS TRANSFER Domain/family mapping supports SUR1 membrane/nucleotide architecture. Direct target evidence specifies participation in potassium-channel transport. Proposed replacements: potassium ion transmembrane transport |
| GO:0055085 transmembrane transport | ISS GO_REF:0000024 | MODIFY | Summary: The supported transmembrane-transport role is regulation of potassium passage through KATP. Reason: SUR1 directly contributes to the Kir6.2-containing transport complex. The broad transmembrane-transport annotation can therefore be retained in substance but refined to potassium ion transmembrane transport (PMID:29286281; PMID:7502040). The ABC-like fold must not be read as evidence that SUR1 translocates an independent solute. The UniProtKB:A0A1S4NYG1 hamster donor carries an IGI annotation to PMID:28842488 from SUR/Kir flux and patch-clamp experiments; this supports channel-associated K+ transport, not a separate SUR1 solute pump. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:A0A1S4NYG1 SUPPORTS TRANSFER SUR1 directly contributes to the Kir6.2-containing transport complex. The broad transmembrane-transport annotation can therefore be retained in substance but refined to potassium ion transmembrane transport (PMID:29286281; PMID:7502040). The ABC-like fold must not be read as evidence that SUR1 translocates an independent solute. The UniProtKB:A0A1S4NYG1 hamster donor carries an IGI annotation to PMID:28842488 from SUR/Kir flux and patch-clamp experiments; this supports channel-associated K+ transport, not a separate SUR1 solute pump. Proposed replacements: potassium ion transmembrane transport |
| GO:0055085 transmembrane transport | ISS GO_REF:0000024 | MODIFY | Summary: The supported transmembrane-transport role is regulation of potassium passage through KATP. Reason: SUR1 directly contributes to the Kir6.2-containing transport complex. The broad transmembrane-transport annotation can therefore be retained in substance but refined to potassium ion transmembrane transport (PMID:29286281; PMID:7502040). The ABC-like fold must not be read as evidence that SUR1 translocates an independent solute. The UniProtKB:A0A1U7R319 hamster donor carries an IGI annotation to PMID:28842488 from SUR/Kir flux and patch-clamp experiments; this supports channel-associated K+ transport, not a separate SUR1 solute pump. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:A0A1U7R319 SUPPORTS TRANSFER SUR1 directly contributes to the Kir6.2-containing transport complex. The broad transmembrane-transport annotation can therefore be retained in substance but refined to potassium ion transmembrane transport (PMID:29286281; PMID:7502040). The ABC-like fold must not be read as evidence that SUR1 translocates an independent solute. The UniProtKB:A0A1U7R319 hamster donor carries an IGI annotation to PMID:28842488 from SUR/Kir flux and patch-clamp experiments; this supports channel-associated K+ transport, not a separate SUR1 solute pump. Proposed replacements: potassium ion transmembrane transport |
| GO:0060253 negative regulation of glial cell proliferation | IEA GO_REF:0000107 | UNDECIDED | Summary: The specific negative glial-proliferation inference is not resolved by accessible evidence. Reason: The rat Q09429 source PMID:23149556 describes glibenclamide-associated repair and reactive microglial SUR1/Kir6.2 expression, but the abstract does not establish the particular glial-proliferation experiment. Full text was not accessible. Keep uncertainty rather than interpreting expression, migration or overall repair as proof of this exact regulatory process. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q09429 UNRESOLVED The rat Q09429 source PMID:23149556 describes glibenclamide-associated repair and reactive microglial SUR1/Kir6.2 expression, but the abstract does not establish the particular glial-proliferation experiment. Full text was not accessible. Keep uncertainty rather than interpreting expression, migration or overall repair as proof of this exact regulatory process. ensembl:ENSRNOP00000028696 UNRESOLVED Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0061855 negative regulation of neuroblast migration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SUR1 inhibition affects neuroblast migration during post-stroke repair. Reason: Rat Q09429 traces to PMID:23149556: acute glibenclamide treatment increases migration of doublecortin-positive cells, subsequent neuronal generation and hippocampal angiogenesis. Retain the existing negative-regulation inference as a contextual injury phenotype, with the limitation that a drug intervention and tissue repair endpoints do not establish a cell-autonomous developmental activity of human SUR1. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q09429 SUPPORTS TRANSFER Rat Q09429 traces to PMID:23149556: acute glibenclamide treatment increases migration of doublecortin-positive cells, subsequent neuronal generation and hippocampal angiogenesis. Retain the existing negative-regulation inference as a contextual injury phenotype, with the limitation that a drug intervention and tissue repair endpoints do not establish a cell-autonomous developmental activity of human SUR1. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:0071805 potassium ion transmembrane transport | NAS PMID:28842488 Conserved functional consequences of disease-associated muta... | ACCEPT | Summary: SUR1 directly regulates the KATP complex that carries transmembrane potassium flux. Reason: PMID:28842488 measures flux and electrophysiology of SUR-coassembled Kir channels. Human SUR1/Kir6.2 reconstitution and structure (PMID:29286281) establish the same transport machinery. The BP is appropriate for the regulatory subunit; K+ conduction is executed by the associated Kir6.2 pore. |
| GO:0140359 ABC-type transporter activity | IBA GO_REF:0000033 | MODIFY | Summary: SUR1 is an ABC-family channel regulator rather than an established primary active transporter. Reason: GO:0140359 describes ATP-driven substrate translocation by a primary active ABC transporter. Human SUR1 structures and electrophysiology (PMID:29286281; PMID:34815345) resolve a separate Kir6.2 ion pathway and regulatory SUR1 nucleotide domains. SUR1 retains ATP binding and ATPase activity, but no independent transported solute is demonstrated. This target-specific functional specialization makes primary-active-transporter propagation inappropriate; replace with potassium channel regulator activity, without asserting loss of ATPase catalytic residues. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE ROLE CONFLATION Sources checked: PANTHER:PTN009085477 SUPPORTS SOURCE BUT NOT TARGET Challenge the active-transporter activity at this ancestral-node transfer specifically for the SUR regulatory lineage: direct human structural and functional data show regulation of a separate pore, not a SUR1 solute-pump mechanism. This does not deny the ATPase fold or use donor count as evidence. Proposed replacements: potassium channel regulator activity Supporting Evidence: PMID:29286281 These structures support the role of SUR1 as an ADP sensor |
| GO:0140359 ABC-type transporter activity | IEA GO_REF:0000002 | MODIFY | Summary: SUR1 is an ABC-family channel regulator rather than an established primary active transporter. Reason: GO:0140359 describes ATP-driven substrate translocation by a primary active ABC transporter. Human SUR1 structures and electrophysiology (PMID:29286281; PMID:34815345) resolve a separate Kir6.2 ion pathway and regulatory SUR1 nucleotide domains. SUR1 retains ATP binding and ATPase activity, but no independent transported solute is demonstrated. This target-specific functional specialization makes primary-active-transporter propagation inappropriate; replace with potassium channel regulator activity, without asserting loss of ATPase catalytic residues. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE ROLE CONFLATION Sources checked: InterPro:IPR011527 SUPPORTS SOURCE BUT NOT TARGET Domain/family mapping supports SUR1 membrane/nucleotide architecture. ABC homology does not establish solute translocation in this regulatory subfamily. Proposed replacements: potassium channel regulator activity |
| GO:1900721 positive regulation of uterine smooth muscle relaxation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SUR1-containing channels contribute to uterine smooth-muscle relaxation in a rat context. Reason: PMID:25891870 studies beta2-agonist relaxation of pregnant rat uterine rings and modulation by KATP agents; effects vary with gestational stage. Together with SUR1 expression in PMID:21527399, this supports a tissue-specific regulatory role. Pharmacological subunit specificity and direct human transfer remain more limited than the canonical beta-cell mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q09429 SUPPORTS TRANSFER PMID:25891870 studies beta2-agonist relaxation of pregnant rat uterine rings and modulation by KATP agents; effects vary with gestational stage. Together with SUR1 expression in PMID:21527399, this supports a tissue-specific regulatory role. Pharmacological subunit specificity and direct human transfer remain more limited than the canonical beta-cell mechanism. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:1905075 positive regulation of tight junction disassembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SUR1-associated injury signaling contributes to tight-junction disruption. Reason: The rat source PMID:23633925 reports reduced blood-tumor barrier permeability and ZO-1 disruption with glyburide. Accessible full-text work in PMID:18854840 likewise links SUR1 inhibition to preserved endothelial junctional ZO-1 after hemorrhage. Retain this pathological signaling context, without assigning junction-disassembly enzymatic machinery to SUR1. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q09429 SUPPORTS TRANSFER The rat source PMID:23633925 reports reduced blood-tumor barrier permeability and ZO-1 disruption with glyburide. Accessible full-text work in PMID:18854840 likewise links SUR1 inhibition to preserved endothelial junctional ZO-1 after hemorrhage. Retain this pathological signaling context, without assigning junction-disassembly enzymatic machinery to SUR1. ensembl:ENSRNOP00000028696 SUPPORTS TRANSFER Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. |
| GO:1905604 negative regulation of blood-brain barrier permeability | IEA GO_REF:0000107 | MODIFY | Summary: The traced injury evidence supports increased, not decreased, barrier permeability. Reason: The Q09429 source PMID:18854840 reports that inhibiting SUR1 reduces IgG extravasation and restores junctional ZO-1 after rat subarachnoid hemorrhage. PMID:24114458 independently reports the same direction with SUR1 antisense. Thus the transferred negative sign is opposite to the source intervention logic: intact injury-induced SUR1 signaling promotes permeability. Replace with positive regulation, restricted in interpretation to the injury context; this is a source-side sign correction, not a claim of normal human barrier maintenance. Propagation Review Root cause: SOURCE BAD Failure modes: REGULATORY SIGN INVERSION Sources checked: UniProtKB:Q09429 SOURCE BAD The Q09429 source PMID:18854840 reports that inhibiting SUR1 reduces IgG extravasation and restores junctional ZO-1 after rat subarachnoid hemorrhage. PMID:24114458 independently reports the same direction with SUR1 antisense. Thus the transferred negative sign is opposite to the source intervention logic: intact injury-induced SUR1 signaling promotes permeability. Replace with positive regulation, restricted in interpretation to the injury context; this is a source-side sign correction, not a claim of normal human barrier maintenance. ensembl:ENSRNOP00000028696 SOURCE BAD Rat Abcc8 protein identifier paired with UniProtKB:Q09429; the source-specific experimental chain and its limitations are assessed in that donor entry. This identifier supplies no additional experiment. Proposed replacements: positive regulation of blood-brain barrier permeability Supporting Evidence: PMID:18854840 inhibiting SUR1 using low-dose glibenclamide after SAH resulted in a significant reduction in IgG extravasation PMID:24114458 inhibiting Sur1 using antisense or the selective Sur1 inhibitor glibenclamide reduced SAH-induced immunoglobulin G extravasation |
| GO:1990573 potassium ion import across plasma membrane | ISS GO_REF:0000114 | MODIFY | Summary: Direction-independent potassium transport is supported, but this donor does not establish physiological human K+ import. Reason: The live ComplexPortal CPX-185 record identifies a rat Kir6.2–SUR2B complex (4xAbcc9:4xKcnj11), not SUR1. Its K+ influx annotation is a homologous-complex source, whose direction-specific tissue claim should not automatically transfer to human ABCC8. Inward rectification does not itself imply net physiological influx; beta-cell KATP carries outward current under its normal electrochemical conditions. The conserved supported role is potassium ion transmembrane transport via channel regulation (PMID:29286281; Reactome:R-HSA-1296024). Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH GRANULARITY MISMATCH Sources checked: ComplexPortal:CPX-185 SUPPORTS SOURCE BUT NOT TARGET The live ComplexPortal CPX-185 record identifies a rat Kir6.2–SUR2B complex (4xAbcc9:4xKcnj11), not SUR1. Its K+ influx annotation is a homologous-complex source, whose direction-specific tissue claim should not automatically transfer to human ABCC8. Inward rectification does not itself imply net physiological influx; beta-cell KATP carries outward current under its normal electrochemical conditions. The conserved supported role is potassium ion transmembrane transport via channel regulation (PMID:29286281; Reactome:R-HSA-1296024). Proposed replacements: potassium ion transmembrane transport |
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Download this section (compressed HTML)Q: Which experiments support the rat-source presynaptic and synaptic-vesicle membrane locations, intracellular glucose homeostasis, LDL clearance and glial proliferation, and do these roles transfer to human SUR1?
Q: Under which native injury conditions does human SUR1 form a functional TRPM4-associated channel, given differing heterologous-system results in PMID:22291026 and PMID:23255597?
Q: Should GO:0015272 terminology and its ATP pore-block wording be clarified to distinguish SUR1 nucleotide activation from inhibitory ATP binding to Kir6.2?
Experiment: Measure SUR1 nucleotide occupancy, hydrolysis and Kir6.2 single-channel gating simultaneously in purified human complexes and beta-cell models, using binding-competent and catalysis-altered controls, to separate nucleotide sensing from obligatory hydrolytic coupling.
Experiment: Compare endogenous SUR1 complex composition and currents in injured human neurovascular cells with genetically rescued ABCC8 and TRPM4 perturbations, controlling for KCNJ11-containing KATP and drug off-target effects.
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