CHM encodes Rab escort protein 1 (REP1), a soluble Rab-binding protein that couples Rab geranylgeranylation to membrane delivery. REP1 presents Rab substrates to the RABGGTA–RABGGTB catalytic machinery, remains associated with prenylated Rab products and delivers them to intracellular membranes. It also inhibits GDP release from Rab proteins in biochemical assays. Its defining work is substrate recognition and escort rather than autonomous geranylgeranyl-transfer chemistry. A cytosolic pool supports this trafficking cycle; nuclear localization has also been reported, with its functional significance unresolved. Loss of REP1 causes choroideremia, linking defective Rab processing and trafficking to retinal degeneration.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004663 Rab geranylgeranyltransferase activity | TAS PMID:8380507 Retinal degeneration in choroideremia: deficiency of rab ger... | MARK AS OVER ANNOTATED | Summary: Retain the prenyltransferase contribution but flag the autonomous enables relation. Reason: REP1 is the Rab-binding accessory component of the Rab geranylgeranyltransferase machinery. The catalytic heterodimer performs geranylgeranyl transfer; REP1 presents substrate and escorts the prenylated product. Original PMID:8380507 is accessible at abstract level, while the recovered full reconstitution in PMID:7957092 and human REP1 experiments in PMID:18532927 establish this distinction. The preserved enables relation overstates autonomous catalytic activity. A curator change to contributes_to is appropriate; the core records the genuine complex contribution without altering this source object or inventing a replacement-qualifier field. Supporting Evidence: PMID:7957092 accessory component file:human/CHM/CHM-source-evidence.json The seeded enables GO:0004663 assertion is preserved. REP1 supplies substrate presentation and escort work, whereas the RABGGTA–RABGGTB catalytic component transfers geranylgeranyl groups; complex contribution is distinct from independent catalysis. |
| GO:0005092 GDP-dissociation inhibitor activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine GDP-release inhibition to the measured Rab-specific activity. Reason: The family/domain inference is not rejected because REP1 differs from conventional RabGDI. Figure 7 of the full primary measures time- and concentration-dependent inhibition of Rab5 GDP release by REP1, including both prenylated and unprenylated Rab5, with BSA and RabGDI comparisons. GO:0005093 is the verified Rab-specific child of GO:0005092. No GTPase hydrolysis or GDP/GTP exchange catalysis is inferred. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: InterPro:IPR018203 SUPPORTS TRANSFER The original family-domain source is compatible with the measured GDP-inhibitory activity. The proposed change specifies the experimentally demonstrated Rab substrate class rather than rejecting the family assignment. Proposed replacements: Rab GDP-dissociation inhibitor activity Supporting Evidence: PMID:7957092 inhibit the release of GDP GO_REF:0000002 file:human/CHM/CHM-source-evidence.json Original Fig. 7 measures REP1-dependent retention of Rab5-bound GDP; the BSA control does not reproduce it. REP1 inhibits GDP release from unprenylated Rab5 as well as the modified protein, unlike the conventional RabGDI comparator. |
| GO:0005515 protein binding | IPI PMID:21905166 Comprehensive mutation analysis (20 families) of the choroid... | KEEP AS NON CORE | Summary: Retain the source-specific RABGGTA association. Reason: The original human mutation-study abstract reports that H507R disrupts REP1 association with Rab geranylgeranyltransferase. The full body and exact construct panel were not recovered. The curated Q92696 pair is retained with independent REP1–RGGT biochemical support; neither an uninspected wild-type construct nor a purified binary interface is invented. RABGGTA is the alpha component of the prenyltransferase machinery; partner association alone does not assign transfer chemistry, enzyme activation or a new bridging activity to REP1. Supporting Evidence: file:human/CHM/CHM-source-evidence.json Original row 2 retains P24386 with Q92696 under PMID:21905166. The original human mutation-study abstract reports that H507R disrupts REP1 association with Rab geranylgeranyltransferase. The full body and exact construct panel were not recovered. The curated Q92696 pair is retained with independent REP1–RGGT biochemical support; neither an uninspected wild-type construct nor a purified binary interface is invented. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: Retain the source-specific RABGGTA association. Reason: The exact original IntAct record is a positive anti-tag co-immunoprecipitation/AP–MS association in human HEK293T cells, with a C-terminal tandem tag. Original pipeline Methods distinguish complex recovery from a purified binary interface. RABGGTA is the alpha component of the prenyltransferase machinery; partner association alone does not assign transfer chemistry, enzyme activation or a new bridging activity to REP1. Supporting Evidence: file:human/CHM/CHM-source-evidence.json Original row 3 retains P24386 with Q92696 under PMID:28514442. The exact original IntAct record is a positive anti-tag co-immunoprecipitation/AP–MS association in human HEK293T cells, with a C-terminal tandem tag. Original pipeline Methods distinguish complex recovery from a purified binary interface. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Retain the source-specific RABGGTA association. Reason: Two exact positive IntAct records retain the CHM–Q92696 pair in human HCT116 and HEK293T contexts, using anti-tag co-immunoprecipitation and a C-terminal tandem tag. The selected cache is flagged full but contains Introduction/Discussion only; literal records supply the bounded assay context. RABGGTA is the alpha component of the prenyltransferase machinery; partner association alone does not assign transfer chemistry, enzyme activation or a new bridging activity to REP1. Supporting Evidence: file:human/CHM/CHM-source-evidence.json Original row 4 retains P24386 with Q92696 under PMID:33961781. Two exact positive IntAct records retain the CHM–Q92696 pair in human HCT116 and HEK293T contexts, using anti-tag co-immunoprecipitation and a C-terminal tandem tag. The selected cache is flagged full but contains Introduction/Discussion only; literal records supply the bounded assay context. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | KEEP AS NON CORE | Summary: Retain the source-specific RABGGTA association. Reason: The authentic official OpenCell interaction table contains reciprocal CHM–RABGGTA associations (CSV lines4370/18935). Prey groups are Q92696/H0YLH3/H0YKP6 and P24386/P24386-2 respectively, so the measurements do not resolve every product independently. Library metadata line245 identifies CHM/P24386, ENST00000357749 and an N-terminal endogenous tag. The recovered main text establishes HEK293T affinity-MS context; this is complex association rather than purified binary contact. RABGGTA association does not assign transfer chemistry, enzyme activation or a new bridging activity to REP1. Supporting Evidence: file:human/CHM/CHM-source-evidence.json Original row5 retains P24386 with Q92696 under PMID:35271311. The authentic official OpenCell interaction table contains reciprocal CHM–RABGGTA associations (CSV lines4370/18935). Prey groups are Q92696/H0YLH3/H0YKP6 and P24386/P24386-2 respectively, so the measurements do not resolve every product independently. Library metadata line245 identifies CHM/P24386, ENST00000357749 and an N-terminal endogenous tag. The recovered main text establishes HEK293T affinity-MS context; this is complex association rather than purified binary contact. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Retain the source-specific RABGGTA association. Reason: The authentic source U2OS AP–MS network has CHM node555838 and RABGGTA node565884 connected by edge605342. RABGGTA is the tagged bait and CHM the prey in the network attributes. The source uses C-terminal HA–FLAG ORFeome baits and quality-controlled affinity-MS; this is a positive complex association, not a separate proof of purified binary contact. RABGGTA is the alpha component of the prenyltransferase machinery; partner association alone does not assign transfer chemistry, enzyme activation or a new bridging activity to REP1. Supporting Evidence: file:human/CHM/CHM-source-evidence.json Original row 6 retains P24386 with Q92696 under PMID:40205054. The authentic source U2OS AP–MS network has CHM node555838 and RABGGTA node565884 connected by edge605342. RABGGTA is the tagged bait and CHM the prey in the network attributes. The source uses C-terminal HA–FLAG ORFeome baits and quality-controlled affinity-MS; this is a positive complex association, not a separate proof of purified binary contact. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the curated nuclear assertion with limited mechanistic scope. Reason: The PTN000209558 propagation and CHML/P26374 donor are preserved. The current P26374 nucleus record repeats the same IBA/PTN propagation rather than an independent experimental nuclear assay. Target HPA reports CHM nucleoplasm as well as cytosol. Inspected HPA003231 A431/U2OS images corroborate a nuclear pool, although the individual antibody subassay is rated uncertain. These localization observations do not independently reconstruct the ancestral active-in placement or identify a particular nuclear molecular activity. Retain the curated assertion outside the core and leave the nuclear role unresolved. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000209558 UNRESOLVED The authenticated ancestral source is preserved. Historical PAINT tree/node placement was not independently reconstructed; current target and donor evidence corroborate applicability, not exact ancestral placement. Target self-evidence is legitimate. Supporting Evidence: GO_REF:0000033 GO_REF:0000052 file:human/CHM/CHM-source-evidence.json HPA CHM/P24386 has aggregate nucleoplasm-plus-cytosol localization; the HPA003231 human-cell subassay is individually uncertain. The live CHML/P26374 nucleus record repeats the same curated IBA propagation. Target HPA corroborates a nuclear pool, not a reconstructed PAINT node or a defined nuclear reaction. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Retain cytosol as a core site of escort activity. Reason: Cytosolic REP1/Rab complexes, endogenous human fractionation and HPA support the original active-in relation. PTN000209443 and its exact donor fields remain unchanged; target self-evidence is legitimate, and neither donor count nor current target evidence is presented as a historical PAINT reconstruction. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000209443 UNRESOLVED The authenticated ancestral source is preserved. Historical PAINT tree/node placement was not independently reconstructed; current target and donor evidence corroborate applicability, not exact ancestral placement. Target self-evidence is legitimate. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Retain HPA cytosolic localization. Reason: The original HPA003231 A431 and U2OS images were inspected and show green target signal outside the blue nuclear region, consistent with the literal cytosol label. The individual antibody subassay is uncertain, while independent cytosolic fractionation and escort reconstitution support this compartment. Nuclear staining is a separate reported pool, not an objection to cytosolic activity. Supporting Evidence: GO_REF:0000052 file:human/CHM/CHM-source-evidence.json HPA003231 images 57_G5_1 in A431 and 56_G5_1 in U2OS were visually inspected. Literal HPA labels include cytosol and nucleoplasm; independent biochemical fractionation corroborates the cytosolic escort pool. |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: Retain cytosolic location inferred from the subcellular vocabulary. Reason: The exact SL-0091 mapping is consistent with endogenous cytosolic REP1 and soluble Rab–REP1 complexes. This does not imply that every molecule remains cytosolic or that transient membrane delivery makes REP1 a permanent membrane component. |
| GO:0005829 cytosol | IMP PMID:7957092 Rab escort protein-1 is a multifunctional protein that accom... | ACCEPT | Summary: Retain the soluble cytosolic escort pool. Reason: The full source demonstrates soluble REP1–Rab complexes and cytosolic REP1 detection. During MDCK membrane delivery, Rab becomes membrane associated while REP1 remains predominantly soluble. Human A431 Rab localization and rat NRK co-immunoprecipitation are separate assays; Rab localization is not substituted for permanent REP1 membrane residence. Supporting Evidence: |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6801109 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The original event explicitly uses CHM entity6801097 in the cytosol as an input, although the RGGT-bound output is assigned to the plasma membrane. Only the original CHM cytosol assertion is retained. Supporting Evidence: Reactome:R-HSA-6801109 file:human/CHM/CHM-source-evidence.json R-HSA-6801109 (CHM binds RGGT): The original event explicitly uses CHM entity6801097 in the cytosol as an input, although the RGGT-bound output is assigned to the plasma membrane. Only the original CHM cytosol assertion is retained. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8870465 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event uses a cytosolic CHMs-containing prenylation assembly. The CHMs set8870446 explicitly includes CHM entity6801097 (UniProt P24386) and CHML; the set is not evidence that both escorts act simultaneously in every reaction. Supporting Evidence: Reactome:R-HSA-8870465 file:human/CHM/CHM-source-evidence.json R-HSA-8870465 (RGGT binds the RAB-binding subunit): The event uses a cytosolic CHMs-containing prenylation assembly. The CHMs set8870446 explicitly includes CHM entity6801097 (UniProt P24386) and CHML; the set is not evidence that both escorts act simultaneously in every reaction. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8870466 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event uses a cytosolic CHMs-containing prenylation assembly. The CHMs set8870446 explicitly includes CHM entity6801097 (UniProt P24386) and CHML; the set is not evidence that both escorts act simultaneously in every reaction. Supporting Evidence: Reactome:R-HSA-8870466 file:human/CHM/CHM-source-evidence.json R-HSA-8870466 (RGGT:CHM binds RABs): The event uses a cytosolic CHMs-containing prenylation assembly. The CHMs set8870446 explicitly includes CHM entity6801097 (UniProt P24386) and CHML; the set is not evidence that both escorts act simultaneously in every reaction. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8870469 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event uses a cytosolic CHMs-containing prenylation assembly. The CHMs set8870446 explicitly includes CHM entity6801097 (UniProt P24386) and CHML; the set is not evidence that both escorts act simultaneously in every reaction. Supporting Evidence: Reactome:R-HSA-8870469 file:human/CHM/CHM-source-evidence.json R-HSA-8870469 (RGGT geranylgeranylates RAB proteins): The event uses a cytosolic CHMs-containing prenylation assembly. The CHMs set8870446 explicitly includes CHM entity6801097 (UniProt P24386) and CHML; the set is not evidence that both escorts act simultaneously in every reaction. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8875318 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8875318 file:human/CHM/CHM-source-evidence.json R-HSA-8875318 (RAB3 GEFs exchange GTP for GDP on RAB3A): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8875320 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8875320 file:human/CHM/CHM-source-evidence.json R-HSA-8875320 (RAB5 GEFs exchange GTP for GDP on RAB5): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8876188 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8876188 file:human/CHM/CHM-source-evidence.json R-HSA-8876188 (DENND4s exchange GTP for GDP on RAB10): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8876190 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8876190 file:human/CHM/CHM-source-evidence.json R-HSA-8876190 (RAB8 GEFs exchange GTP for GDP on RAB8): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8876191 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8876191 file:human/CHM/CHM-source-evidence.json R-HSA-8876191 (RAB9 GEFs exchange GTP for GDP on RAB9): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8876193 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8876193 file:human/CHM/CHM-source-evidence.json R-HSA-8876193 (RIC1-RGP1 exchanges GTP for GDP on RAB6): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8876454 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8876454 file:human/CHM/CHM-source-evidence.json R-HSA-8876454 (DENND3 exchanges GTP for GDP on RAB12): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8876615 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8876615 file:human/CHM/CHM-source-evidence.json R-HSA-8876615 (RAB13 GEFs exchange GTP for GDP on RAB13): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8876616 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8876616 file:human/CHM/CHM-source-evidence.json R-HSA-8876616 (DENND6A,B exchange GTP for GDP on RAB14): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8876837 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8876837 file:human/CHM/CHM-source-evidence.json R-HSA-8876837 (RAB21 GEFs exchange GTP for GDP on RAB21): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8877308 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8877308 file:human/CHM/CHM-source-evidence.json R-HSA-8877308 (MADD exchanges GTP for GDP on RAB27): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8877311 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8877311 file:human/CHM/CHM-source-evidence.json R-HSA-8877311 (RAB31 GEFs exchange GTP for GDP on RAB31): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8877451 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8877451 file:human/CHM/CHM-source-evidence.json R-HSA-8877451 (MON1:CCZ1 exchanges GTP for GDP on RAB7): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8877475 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8877475 file:human/CHM/CHM-source-evidence.json R-HSA-8877475 (TRAPPC complexes exchange GTP for GDP on RAB1): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8877612 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8877612 file:human/CHM/CHM-source-evidence.json R-HSA-8877612 (DENND1s exchange GTP for GDP on RAB35): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8877760 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8877760 file:human/CHM/CHM-source-evidence.json R-HSA-8877760 (HPS1:HPS4 exchange GTP for GDP on RAB32 and RAB38): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8877813 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8877813 file:human/CHM/CHM-source-evidence.json R-HSA-8877813 (DENND5A,B exchange GTP for GDP on RAB39): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8877998 | ACCEPT | Summary: Retain the compartment of the represented CHM entity. Reason: The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. Supporting Evidence: Reactome:R-HSA-8877998 file:human/CHM/CHM-source-evidence.json R-HSA-8877998 (RAB3GAP1:RAB3GAP2 exchanges GTP for GDP on RAB18): The event produces the cytosolic GDIs,CHMs set8875305, which explicitly contains CHM entity6801097 (UniProt P24386). This supports the represented compartment, not direct experimental proof for every named Rab substrate or guanine-nucleotide exchange catalysis by REP1. |
| GO:0005968 Rab-protein geranylgeranyltransferase complex | IBA GO_REF:0000033 | ACCEPT | Summary: Retain accessory membership in Rab geranylgeranyltransferase machinery. Reason: The official complex definition explicitly includes association of the catalytic alpha/beta complex with accessory Rep. The exact PTN000209558 and donor fields are retained; no historical ancestral reconstruction is claimed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000209558 UNRESOLVED The authenticated ancestral source is preserved. Historical PAINT tree/node placement was not independently reconstructed; current target and donor evidence corroborate applicability, not exact ancestral placement. Target self-evidence is legitimate. |
| GO:0005968 Rab-protein geranylgeranyltransferase complex | IDA PMID:7957092 Rab escort protein-1 is a multifunctional protein that accom... | ACCEPT | Summary: Retain accessory membership in Rab geranylgeranyltransferase machinery. Reason: The original reconstitution demonstrates REP1-dependent geranylgeranyl transfer, with REP1–Rab product complexes separable from the catalytic heterodimer. Independent human REP1 binding experiments support transient functional assembly rather than invariant stoichiometry. |
| GO:0005968 Rab-protein geranylgeranyltransferase complex | IEA GO_REF:0000120 | ACCEPT | Summary: Retain accessory membership in Rab geranylgeranyltransferase machinery. Reason: The original ARBA/IPR001738 inference agrees with the accessory complex role. This is not a transfer of catalytic chemistry from the alpha/beta component to REP1. |
| GO:0005968 Rab-protein geranylgeranyltransferase complex | TAS PMID:8380507 Retinal degeneration in choroideremia: deficiency of rab ger... | ACCEPT | Summary: Retain accessory membership in Rab geranylgeranyltransferase machinery. Reason: The accessible original abstract identifies deficient component-A activity in patient lymphoblasts with preserved component-B activity. Full original text remains unavailable; independent recovered reconstitution confirms the accessory association and supports deferring to this correct curated complex assignment. |
| GO:0006612 protein targeting to membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Rab membrane targeting is performed escort work. Reason: The isolated REP1–prenylated Rab5 complex delivers Rab5 to permeabilized MDCK membranes without RabGDI or added cytosol; the unprenylated complex does not reproduce delivery. REP1 remains predominantly soluble after release. This establishes an actual transport step rather than only a loss-of-function requirement. The curated PTN000209558 is retained without reconstructing its historical placement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000209558 UNRESOLVED The authenticated ancestral source is preserved. Historical PAINT tree/node placement was not independently reconstructed; current target and donor evidence corroborate applicability, not exact ancestral placement. Target self-evidence is legitimate. Supporting Evidence: |
| GO:0006612 protein targeting to membrane | IMP PMID:7957092 Rab escort protein-1 is a multifunctional protein that accom... | ACCEPT | Summary: Rab membrane targeting is performed escort work. Reason: The isolated REP1–prenylated Rab5 complex delivers Rab5 to permeabilized MDCK membranes without RabGDI or added cytosol; the unprenylated complex does not reproduce delivery. REP1 remains predominantly soluble after release. This establishes an actual transport step rather than only a loss-of-function requirement. The original IMP/source fields remain exact alongside the reconstitution evidence. Supporting Evidence: |
| GO:0006886 intracellular protein transport | IEA GO_REF:0000002 | ACCEPT | Summary: Retain intracellular protein transport as the broader escort process. Reason: Direct binding and delivery of prenylated Rab proteins to intracellular membranes is intracellular protein transport. The source IPR001738 inference is corroborated by the recovered reconstitution, without claiming an ATP-driven transmembrane pump. |
| GO:0007264 small GTPase-mediated signal transduction | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Retain the broader small-GTPase signaling context. Reason: REP1 makes Rab proteins membrane competent through substrate presentation, prenylation support and delivery, and inhibits Rab GDP release in vitro. This supports the broad signaling context while its defining molecular work is Rab escort. REP1 is not assigned intrinsic GTPase, GAP or guanine-nucleotide exchange catalysis from the domain label or downstream membrane exchange. |
| GO:0007601 visual perception | TAS PMID:7981670 Cloning and characterization of the human choroideremia gene... | KEEP AS NON CORE | Summary: Retain the vision-related disease context outside the molecular core. Reason: The authentic original abstract identifies the complete human CHM gene and patient rearrangement context; full text was not recovered. The established choroideremia phenotype supports the broad curated visual-perception association. This is not an assertion that REP1 directly senses light or catalyzes phototransduction, and the disease outcome is kept separate from the escort mechanism. |
| GO:0016192 vesicle-mediated transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the broader vesicular-trafficking context. Reason: The exact PTN000209443 propagation is retained. REP1 prepares and delivers Rab regulators of vesicle traffic, and the recovered source links delivered Rab5 to endosome fusion. That is broader biological context for the performed Rab transport step, not direct membrane-fusion catalysis by REP1 or a reconstruction of the ancestral node. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000209443 UNRESOLVED The authenticated ancestral source is preserved. Historical PAINT tree/node placement was not independently reconstructed; current target and donor evidence corroborate applicability, not exact ancestral placement. Target self-evidence is legitimate. |
| GO:0018344 protein geranylgeranylation | IDA PMID:7957092 Rab escort protein-1 is a multifunctional protein that accom... | ACCEPT | Summary: Retain participation in protein geranylgeranylation. Reason: REP1 directly presents Rab substrate to the catalytic heterodimer and supports the prenylation reaction. Unlike an inert substrate or a necessity-only phenotype, the escort performs accessory work required by the step. This process participation is compatible with flagging an autonomous enables-prenyltransferase relation. Figure 9 distinguishes REP1 accessory activity from RabGDI, which does not substitute. |
| GO:0018344 protein geranylgeranylation | TAS PMID:8380507 Retinal degeneration in choroideremia: deficiency of rab ger... | ACCEPT | Summary: Retain participation in protein geranylgeranylation. Reason: REP1 directly presents Rab substrate to the catalytic heterodimer and supports the prenylation reaction. Unlike an inert substrate or a necessity-only phenotype, the escort performs accessory work required by the step. This process participation is compatible with flagging an autonomous enables-prenyltransferase relation. The original 1993 paper is abstract-only in the available access; full independent reconstitution and human REP1 mutagenesis corroborate the conserved mechanism. |
| GO:0031267 small GTPase binding | IDA PMID:7957092 Rab escort protein-1 is a multifunctional protein that accom... | MODIFY | Summary: Refine binding to the demonstrated Rab protein-transport activity. Reason: The same full source goes beyond association: a purified REP1–prenylated Rab5 complex delivers Rab5 to membranes, with isolated-complex, unprenylated-Rab and soluble-REP1 controls. GO:0140318 requires direct binding and delivery to a cellular location, which this assay establishes. This is a lateral functional refinement of the preserved IDA assertion, not a new process annotation or an ATP-driven membrane pump. Specific IPI partner assertions remain separately retained. Proposed replacements: protein transporter activity Supporting Evidence: PMID:7957092 binding of rab proteins to the membrane file:human/CHM/CHM-source-evidence.json Original Figs. 2–3 and 10 measure membrane delivery by an isolated REP1–prenylated Rab5 complex. The transport readout, unprenylated control and release of soluble REP1 establish protein delivery beyond simple binding. |
| GO:0031267 small GTPase binding | IEA GO_REF:0000117 | ACCEPT | Summary: Retain small-GTPase recognition as part of the escort mechanism. Reason: The original ARBA assertion is corroborated by biochemical REP1–Rab complex isolation, Rab-binding experiments and membrane delivery. The broad binding term does not assign all small GTPases as equivalent substrates or replace source-specific Rab partner evidence. |
| GO:0031267 small GTPase binding | IPI PMID:7957092 Rab escort protein-1 is a multifunctional protein that accom... | ACCEPT | Summary: Retain the original Rab5A interaction. Reason: The preserved P20339 partner is supported by original REP1–Rab5 complex assays; Methods include human His-Rab5a and distinct canine Rab5 preparations. The original partner tag is not generalized to all Rab5 isoforms or every assay, and the current IntAct-query absence is not negative evidence. Supporting Evidence: file:human/CHM/CHM-source-evidence.json Original Methods distinguish human His-Rab5a made in E. coli from canine Rab5 made in Sf9. REP1–Rab5 complex isolation, GDP-release and membrane-delivery assays are positive; the seeded P20339 partner remains unchanged. |
| GO:0031267 small GTPase binding | IPI PMID:7957092 Rab escort protein-1 is a multifunctional protein that accom... | ACCEPT | Summary: Retain the original Rab1A interaction with the assay-species boundary. Reason: Original Methods identify the recombinant Rab1a preparation as canine, while the seeded human partner P62822 is retained. The source supports conserved REP1–Rab1 association and prenylation, not a claim that every assay used human Rab1A. Independent human REP1 reconstitution supplies additional target context; it does not retroactively rewrite the original partner field. Supporting Evidence: file:human/CHM/CHM-source-evidence.json Original Methods specify canine His-Rab1a. The human P62822 partner assertion is preserved with this transfer boundary rather than silently relabeling the experimental protein or treating species scope as proof that the association is false. |
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Download this section (compressed HTML)Q: Should the original enables Rab geranylgeranyltransferase activity assertion be changed by curators to contributes_to, preserving REP1 accessory work while distinguishing the catalytic heterodimer?
Q: What molecular activity is carried out by the reported nuclear REP1 pool, and what assay supports the ancestral active-in assignment beyond localization?
Q: Is the recorded 110-residue P24386-2 product expressed as a stable endogenous protein, and does it have a function distinct from the established full-length REP1 escort activity?
Q: Which endogenous Rab clients depend preferentially on REP1 rather than REP2 in retinal cells, and how much in-vivo Rab recycling is performed by REP1 after initial prenylation?
Experiment: First test the P24386-2-specific splice junction and translation using junction-specific RNA measurements and protein detection directed at its unique RSTLLL terminus, with full-length REP1 and negative controls. If an endogenous short protein is detected, establish its abundance, stability and localization before testing interactions or a possible cellular function; comparable Rab escort activity is not assumed.
Hypothesis: The recorded P24386-2 transcript may produce a stable short protein with a function distinct from full-length REP1.
Experiment: Validate endogenous nuclear localization using orthogonal antibodies and a functional endogenous tag, then perturb nuclear access without disrupting Rab/RGGT binding and measure nuclear interactors and specific biochemical outputs.
Hypothesis: Nuclear REP1 has a separable activity from cytosolic Rab escort.
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