RACK1 (Receptor for Activated C Kinase 1; formerly GNB2L1) is a highly conserved seven-bladed WD40 beta-propeller protein that is an integral component of the small (40S) ribosomal subunit, where it sits on the head of the subunit near the mRNA exit channel. As a ribosomal protein it contributes to translational control and is a central platform for ribosome-associated quality control (RQC) of stalled and collided ribosomes, promoting regulatory ubiquitylation of a subset of 40S ribosomal proteins together with the E3 ubiquitin ligase ZNF598 to resolve poly(A)-induced and other terminal stalls. Independently of the ribosome, RACK1 is a versatile signaling scaffold whose WD40 propeller mediates interactions with a large set of partners; it binds and stabilizes activated protein kinase C, inhibits Src-family tyrosine kinases, and acts as an adaptor that assembles and regulates diverse signaling complexes affecting cell growth, migration, apoptosis, receptor/channel trafficking and the stability of clients such as HIF1A. RACK1 is predominantly cytosolic and ribosome-associated, with additional context-dependent localizations (plasma membrane, perinuclear region, nucleus, neuronal projections). It is also exploited by numerous viruses and pathogens to remodel translation or subvert host signaling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005080 protein kinase C binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: RACK1 binds and stabilizes activated protein kinase C; this is a well-documented direct molecular function and the origin of its name (Receptor for Activated C Kinase). Reason: Direct PKC binding is experimentally established (also captured by the IDA annotation from PMID:11279199) and represents a genuine scaffold molecular function, but it is secondary to RACK1's core role as a ribosomal/RQC component. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Binds to and stabilizes activated protein kinase C (PKC), increasing PKC-mediated phosphorylation. |
| GO:0072344 rescue of stalled cytosolic ribosome | IBA GO_REF:0000033 | ACCEPT | Summary: RACK1 participates in resolving stalled cytosolic ribosomes as part of ribosome-associated quality control, supported by phylogenetic transfer from yeast Asc1 and directly demonstrated in human cells. Reason: This is a core function. RACK1 helps resolve poly(A)-induced stalled ribosomes by regulating 40S ubiquitylation (PMID:28132843); the IBA transfer from Asc1 is concordant with direct human evidence. Supporting Evidence: PMID:28132843 the 40S ribosomal protein RACK1 help to resolve poly(A)-induced stalled ribosomes |
| GO:0043022 ribosome binding | IBA GO_REF:0000033 | ACCEPT | Summary: RACK1 binds the ribosome; as an integral 40S component this is well supported structurally and functionally. Reason: RACK1 is a constituent of the 40S subunit and binds the 80S ribosome (cryo-EM, PMID:23636399); ribosome binding is a core molecular function underlying its RQC role. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Component of the 40S ribosomal subunit involved in translational repression |
| GO:2001125 negative regulation of translational frameshifting | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic transfer from yeast Asc1, which suppresses translational frameshifting/readthrough at stalls; consistent with RACK1's role in preventing readthrough of stall sequences. Reason: Concordant with RACK1's RQC role (loss causes readthrough of poly(A) stalls, PMID:28132843), but this specific frameshifting term is an Asc1-derived facet kept as supporting rather than the primary core term. Supporting Evidence: PMID:28132843 subsequent readthrough of poly(A)-containing stall sequences |
| GO:0001891 phagocytic cup | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Localization to phagocytic cups reported during Yersinia infection; a specialized infection context rather than a core compartment. Reason: Supported by IDA in an infection setting (PMID:21347310) but peripheral to the core cytosolic/ribosomal localization. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Cell projection, phagocytic cup |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A nuclear pool of RACK1 is reported in some contexts (e.g. with HIF1A/AR signaling), but the predominant localization is cytosolic/ribosomal. Reason: Context-dependent nuclear localization is documented (IDA PMID:10849009, PMID:17108144) but is non-core relative to the cytosolic ribosomal pool. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Nucleus {ECO:0000269|PubMed:10849009} |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasmic localization, consistent with RACK1's predominant cytosolic/ribosome-associated pool. Reason: Core compartment; corroborated by extensive experimental evidence (multiple EXP/IDA annotations) and UniProt. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: RACK1 is recruited to the plasma membrane as a peripheral membrane protein in some signaling/trafficking contexts. Reason: Documented peripheral membrane localization (e.g. via KRT1/ITGB1, PMID:17956333) but secondary to the cytosolic ribosomal pool. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Cell membrane {ECO:0000269|PubMed:11312657 |
| GO:0030425 dendrite | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Dendritic/neuronal-projection localization inferred from the mouse ortholog; reflects neuronal expression, not a core compartment. Reason: Based on ISS/By similarity to mouse P68040; plausible in neurons but peripheral to the core role. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Cell projection, dendrite |
| GO:0043022 ribosome binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic annotation of ribosome binding, redundant with and consistent with the experimentally supported ribosome-binding annotations. Reason: Correct core molecular function for an integral 40S protein; agrees with IDA/IBA ribosome-binding evidence. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Component of the 40S ribosomal subunit involved in translational repression |
| GO:0043204 perikaryon | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Perikaryon localization inferred from the mouse ortholog; a neuronal-expression context. Reason: By similarity to mouse P68040; non-core neuronal localization. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Perikaryon {ECO:0000250|UniProtKB:P68040} |
| GO:0045182 translation regulator activity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro-based annotation that RACK1 has translation-regulator activity, consistent with its role in translational repression/control on the 40S subunit. Reason: Broad but accurate MF; the more specific core functions are ribosome binding and the structural/RQC roles. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Component of the 40S ribosomal subunit involved in translational repression |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Perinuclear localization that shifts to the cell periphery upon PKC activation; a signaling-context distribution within the cytoplasm. Reason: Documented (IDA PMID:11279199) but a sub-cytoplasmic distribution peripheral to core function. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Cytoplasm, perinuclear region |
| GO:0005515 protein binding | IPI PMID:10849009 The PKC targeting protein RACK1 interacts with the Epstein-B... | REMOVE | Summary: Interaction with Epstein-Barr virus BZLF1 captured by IntAct; a real but uninformative bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:11046044 Receptor for activated C-kinase (RACK-1), a WD motif-contain... | REMOVE | Summary: IntAct interaction with IFNAR2 (P48551); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:12809483 ST7 is a novel low-density lipoprotein receptor-related prot... | REMOVE | Summary: IntAct interaction with LRP12 (Q9Y561); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:18194455 Acetylcholinesterase-R increases germ cell apoptosis but enh... | REMOVE | Summary: IntAct interaction with ACHE (P22303); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:18420585 RACK1 and CIS mediate the degradation of BimEL in cancer cel... | REMOVE | Summary: IntAct interactions (BCL2L11, DYNLL1 and ortholog) captured in a single screen; bare protein-binding annotations. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:20080539 The Polycomb group protein EED couples TNF receptor 1 to neu... | REMOVE | Summary: IntAct interaction with EED (O75530); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:20871634 Regulation of receptor for activated C kinase 1 protein by t... | REMOVE | Summary: IntAct interaction with VHL (P40337); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:21146485 Identification of cyclophilin-40-interacting proteins reveal... | REMOVE | Summary: IntAct interaction with PPID (Q08752); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:21525958 The ribosomal protein RACK1 is required for microRNA functio... | REMOVE | Summary: IntAct interaction with AGO2 (Q9UKV8); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:21750715 The inhibitor of growth protein 5 (ING5) depends on INCA1 as... | REMOVE | Summary: IntAct interaction with INCA1 (Q0VD86); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: Liver interactome interaction with LARP4B (Q92615); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:22210188 Interaction of protein inhibitor of activated STAT 2 (PIAS2)... | REMOVE | Summary: IntAct interaction with PIAS2 (O75928); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:23651062 RACK1 (receptor for activated C-kinase 1) interacts with FBW... | REMOVE | Summary: IntAct interaction with FBXW2 (Q9UKT8); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:23866081 Lyn, a Src family kinase, regulates activation of epidermal ... | REMOVE | Summary: IntAct interactions with LYN (P07948) and PAG1 (Q9NWQ8); bare protein-binding annotations. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:24947010 DJ-1 interacts with RACK1 and protects neurons from oxidativ... | REMOVE | Summary: IntAct interaction with PARK7/DJ-1 (Q99497); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: IntAct interaction with ACTN2 (P35609); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: IntAct interactions with HELZ (P42694) and LARP4B (Q92615); bare protein-binding annotations. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Large IntAct interactome study capturing many RACK1 partners (USP10, CNOT2, CRMP1, etc.); bare protein-binding annotations. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: BioPlex interactome capturing HELZ/LARP4B interactions; bare protein-binding annotations. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: IntAct interactome capturing HELZ, BYSL, USP10, LARP4B; bare protein-binding annotations. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:38190388 A novel Trichinella spiralis serine proteinase disrupted gut... | REMOVE | Summary: IntAct interaction with a partner (O96871); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Multimodal cell-maps interactome capturing HELZ/LARP4B; bare protein-binding annotations. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0042802 identical protein binding | IPI PMID:24947010 DJ-1 interacts with RACK1 and protects neurons from oxidativ... | KEEP AS NON CORE | Summary: RACK1 self-associates to form homodimers/homooligomers via its WD40 propeller. Reason: Self-association is documented (PMID:15140893, PMID:20529362) and regulates ribosome binding, but is a structural property rather than the core function. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Monomer; also forms homodimers and homooligomers |
| GO:0042802 identical protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | KEEP AS NON CORE | Summary: Self-association captured in an interactome study; same homodimerization property as above. Reason: Documented homodimerization; structural rather than core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Monomer; also forms homodimers and homooligomers |
| GO:0008200 ion channel inhibitor activity | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Inferred from the mouse ortholog; reflects RACK1 inhibition of channels such as TRPM6/PKD2L1 via scaffolding, not an intrinsic channel-blocking activity. Reason: RACK1 modulates certain ion channels via protein interaction (e.g. TRPM6, PMID:18258429), but ion channel inhibitor activity overstates a direct molecular function; it is an indirect scaffold effect. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Inhibits TRPM6 channel activity. |
| GO:0015935 small ribosomal subunit | IEA GO_REF:0000107 | ACCEPT | Summary: RACK1 is part of the small (40S) ribosomal subunit. Reason: Core cellular component; RACK1 is an integral 40S component (cryo-EM PMID:23636399). Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Component of the small (40S) ribosomal subunit |
| GO:0043005 neuron projection | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal-projection localization inferred from the mouse ortholog. Reason: Neuronal-expression context; non-core compartment. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Cell projection, dendrite |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal cell body localization inferred from the mouse ortholog. Reason: Neuronal-expression context; non-core compartment. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Perikaryon {ECO:0000250|UniProtKB:P68040} |
| GO:0044297 cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cell body localization inferred from the mouse ortholog. Reason: Neuronal-expression context; non-core compartment. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Perikaryon {ECO:0000250|UniProtKB:P68040} |
| GO:1903751 negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Anti-apoptotic role under oxidative stress, inferred from the mouse ortholog and supported by the DJ-1/RACK1 IGI annotation. Reason: A specific stress-signaling moonlighting role; non-core. Supporting Evidence: PMID:24947010 The DJ-1 transgene protects cortical neurons from H2O2-induced apoptosis, and this protective effect is abrogated by knocking down RACK1. |
| GO:0002181 cytoplasmic translation | NAS PMID:25901680 Structure of the human 80S ribosome. | KEEP AS NON CORE | Summary: As a 40S ribosomal protein RACK1 participates in cytoplasmic translation; a broad process term. Reason: True but broad; RACK1's specific contributions are translational repression and RQC. Kept non-core per the broad-translation guideline. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Component of the 40S ribosomal subunit involved in translational repression |
| GO:0005737 cytoplasm | NAS PMID:25901680 Structure of the human 80S ribosome. | ACCEPT | Summary: Cytoplasmic localization (ComplexPortal/ribosome curation). Reason: Core compartment. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Component of the 40S ribosomal subunit involved in translational repression |
| GO:0022627 cytosolic small ribosomal subunit | NAS PMID:25901680 Structure of the human 80S ribosome. | ACCEPT | Summary: RACK1 is part of the cytosolic small ribosomal subunit (human 80S cryo-EM structure). Reason: Core cellular component; precise and well supported. Supporting Evidence: PMID:25901680 Structure of the human 80S ribosome |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA immunofluorescence nucleoplasm signal; a minor pool relative to the dominant cytosolic localization. Reason: Context-dependent nuclear pool; non-core. UniProt records an experimentally observed nuclear pool. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Nucleus {ECO:0000269|PubMed:10849009}. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence cytosol signal, the dominant localization. Reason: Core compartment, directly observed. UniProt records cytoplasmic localization and RACK1 is a component of the cytosolic 40S ribosomal subunit. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Peripheral membrane protein. Cytoplasm {ECO:0000269|PubMed:10849009, ECO:0000269|PubMed:11279199, file:human/RACK1/RACK1-uniprot.txt Component of the 40S ribosomal subunit involved in translational repression (PubMed:23636399). |
| GO:0005737 cytoplasm | EXP PMID:11279199 The interaction of Src and RACK1 is enhanced by activation o... | ACCEPT | Summary: Experimental cytoplasmic localization. Reason: Core compartment, direct experimental evidence. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Peripheral membrane protein. Cytoplasm {ECO:0000269|PubMed:10849009, ECO:0000269|PubMed:11279199, PMID:11279199 RACK1 is an intracellular receptor for the serine/ threonine protein kinase C. |
| GO:0005737 cytoplasm | EXP PMID:12958311 The scaffolding protein RACK1 interacts with androgen recept... | ACCEPT | Summary: Experimental cytoplasmic localization. Reason: Core compartment, direct experimental evidence. UniProt cites this study for cytoplasmic localization. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Peripheral membrane protein. Cytoplasm {ECO:0000269|PubMed:10849009, ECO:0000269|PubMed:11279199, |
| GO:0005737 cytoplasm | EXP PMID:20499158 RACK1 promotes breast carcinoma migration/metastasis via act... | ACCEPT | Summary: Experimental cytoplasmic localization. Reason: Core compartment, direct experimental evidence. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Peripheral membrane protein. Cytoplasm {ECO:0000269|PubMed:10849009, ECO:0000269|PubMed:11279199, PMID:20499158 Immunoprecipitation and immunofluorescence were used to study the RACK1/RhoA interaction. |
| GO:0005737 cytoplasm | EXP PMID:20573744 A stimulatory role for the La-related protein 4B in translat... | ACCEPT | Summary: Experimental cytoplasmic localization. Reason: Core compartment, direct experimental evidence. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Peripheral membrane protein. Cytoplasm {ECO:0000269|PubMed:10849009, ECO:0000269|PubMed:11279199, PMID:20573744 the receptor for activated C Kinase (RACK1), a component of the 40S ribosomal subunit |
| GO:0005737 cytoplasm | EXP PMID:23636399 Structures of the human and Drosophila 80S ribosome. | ACCEPT | Summary: Cytoplasmic localization consistent with ribosome-associated pool (80S cryo-EM study). Reason: Core compartment. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Peripheral membrane protein. Cytoplasm {ECO:0000269|PubMed:10849009, ECO:0000269|PubMed:11279199, file:human/RACK1/RACK1-uniprot.txt Component of the 40S ribosomal subunit involved in translational repression (PubMed:23636399). |
| GO:0005737 cytoplasm | EXP PMID:37712706 The matrix protein of respiratory syncytial virus suppresses... | ACCEPT | Summary: Experimental cytoplasmic localization (RSV matrix protein study). Reason: Core compartment. UniProt cites this study for cytoplasmic localization. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Peripheral membrane protein. Cytoplasm {ECO:0000269|PubMed:10849009, ECO:0000269|PubMed:11279199, |
| GO:0005886 plasma membrane | EXP PMID:11312657 Rack1 binds HIV-1 Nef and can act as a Nef-protein kinase C ... | KEEP AS NON CORE | Summary: Plasma membrane localization in a signaling context (HIV-1 Nef/PKC adaptor). Reason: Peripheral membrane localization in a specific context; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11312657, ECO:0000269|PubMed:17956333}; Peripheral membrane protein. PMID:11312657 Nef and Rack1 partially colocalize on the trans-Golgi network and plasma membranes. |
| GO:0005886 plasma membrane | EXP PMID:17956333 Interaction of integrin beta1 with cytokeratin 1 in neurobla... | KEEP AS NON CORE | Summary: Plasma membrane recruitment via KRT1/ITGB1. Reason: Context-specific peripheral membrane localization; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11312657, ECO:0000269|PubMed:17956333}; Peripheral membrane protein. file:human/RACK1/RACK1-uniprot.txt Note=Recruited to the plasma membrane through interaction with KRT1 which binds to membrane-bound ITGB1 (PubMed:17956333). |
| GO:0043204 perikaryon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Perikaryon localization by similarity to mouse ortholog. Reason: Neuronal-expression context; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Perikaryon {ECO:0000250|UniProtKB:P68040} |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626962 | ACCEPT | Summary: Reactome cytosol localization. Reason: Core compartment. Supported by the curated cytoplasmic localization and 40S ribosomal residence. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Peripheral membrane protein. Cytoplasm {ECO:0000269|PubMed:10849009, ECO:0000269|PubMed:11279199, file:human/RACK1/RACK1-uniprot.txt Component of the 40S ribosomal subunit involved in translational repression (PubMed:23636399). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626981 | ACCEPT | Summary: Reactome cytosol localization. Reason: Core compartment. Supported by the curated cytoplasmic localization and 40S ribosomal residence. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Peripheral membrane protein. Cytoplasm {ECO:0000269|PubMed:10849009, ECO:0000269|PubMed:11279199, file:human/RACK1/RACK1-uniprot.txt Component of the 40S ribosomal subunit involved in translational repression (PubMed:23636399). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626982 | ACCEPT | Summary: Reactome cytosol localization. Reason: Core compartment. Supported by the curated cytoplasmic localization and 40S ribosomal residence. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Peripheral membrane protein. Cytoplasm {ECO:0000269|PubMed:10849009, ECO:0000269|PubMed:11279199, file:human/RACK1/RACK1-uniprot.txt Component of the 40S ribosomal subunit involved in translational repression (PubMed:23636399). |
| GO:0030291 protein serine/threonine kinase inhibitor activity | IMP PMID:20103773 A crucial role for RACK1 in the regulation of glucose-stimul... | KEEP AS NON CORE | Summary: RACK1 inhibits the IRE1 kinase within an IRE1-RACK1-PP2A complex, attenuating the ER unfolded protein response. Reason: A specific signaling-scaffold/inhibitory role (recruits PP2A to dephosphorylate IRE1); genuine but non-core moonlighting. Supporting Evidence: PMID:20103773 RACK1 mediated the glucose-inducible assembly of a complex containing IRE1alpha, RACK1, and protein phosphatase 2A (PP2A) to promote dephosphorylation of IRE1alpha by PP2A, thereby inhibiting glucose-stimulated IRE1alpha activation |
| GO:0008047 enzyme activator activity | IDA PMID:20819076 Interaction with receptor for activated C-kinase 1 (RACK1) s... | KEEP AS NON CORE | Summary: RACK1 acts as an activator/adaptor in a GPCR/adenylate-cyclase signaling context. Reason: Reflects scaffold/adaptor activity in a specific pathway; non-core. Supporting Evidence: PMID:20819076 RACK1 mediates PKC-dependent activation of PDE4D5 in the particulate fraction of HEK-293 cells in response to elevations in intracellular cAMP. |
| GO:0019899 enzyme binding | IPI PMID:20819076 Interaction with receptor for activated C-kinase 1 (RACK1) s... | KEEP AS NON CORE | Summary: Enzyme binding (Q08499/PDE4D) captured by IPI; relatively uninformative MF. Reason: Records a real enzyme interaction but is a generic MF; non-core. Supporting Evidence: PMID:20819076 as a specific binding partner for the cAMP-specific phosphodiesterase PDE4D5 |
| GO:0106070 regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway | IMP PMID:20819076 Interaction with receptor for activated C-kinase 1 (RACK1) s... | KEEP AS NON CORE | Summary: RACK1 regulates a GPCR/adenylate-cyclase signaling pathway. Reason: A specific signaling moonlighting role; non-core. Supporting Evidence: PMID:20819076 we found that elevation of intracellular cAMP, with the Ξ²β-adrenoceptor agonist isoproterenol (isoprenaline), led to activation of PDE4 enzymes |
| GO:1903751 negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide | IGI PMID:24947010 DJ-1 interacts with RACK1 and protects neurons from oxidativ... | KEEP AS NON CORE | Summary: Genetic interaction with DJ-1/PARK7 protecting neurons from oxidative-stress-induced apoptosis. Reason: A specific oxidative-stress moonlighting role; non-core. Supporting Evidence: PMID:24947010 The DJ-1 transgene protects cortical neurons from H2O2-induced apoptosis, and this protective effect is abrogated by knocking down RACK1. PMID:24947010 the DJ-1-RACK1 complex protects neurons from oxidative stress-induced apoptosis |
| GO:0042803 protein homodimerization activity | IPI PMID:24947010 DJ-1 interacts with RACK1 and protects neurons from oxidativ... | KEEP AS NON CORE | Summary: RACK1 self-association (homodimerization). Reason: Structural self-association property; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Monomer; also forms homodimers and homooligomers |
| GO:0005515 protein binding | IPI PMID:18057008 Cell surface levels of organellar Na+/H+ exchanger isoform 6... | REMOVE | Summary: Interaction with SLC9A6 regulating its distribution; a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:24006492 Endosomal acidification by Na+/H+ exchanger NHE5 regulates T... | REMOVE | Summary: Interaction with SLC9A5/NHE5 regulating its trafficking; a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:29743600 Trafficking, localization and degradation of the Na(+),HCO(3... | REMOVE | Summary: Interaction with SLC4A7/NBCn1; a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005737 cytoplasm | IDA PMID:29743600 Trafficking, localization and degradation of the Na(+),HCO(3... | ACCEPT | Summary: Direct cytoplasmic localization. Reason: Core compartment. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Peripheral membrane protein. Cytoplasm {ECO:0000269|PubMed:10849009, ECO:0000269|PubMed:11279199, PMID:29743600 RACK1 exhibited a punctate, cytoplasmic localization |
| GO:0045879 negative regulation of smoothened signaling pathway | IDA PMID:32467643 Dual functions of Rack1 in regulating Hedgehog pathway. | KEEP AS NON CORE | Summary: RACK1 negatively regulates Hedgehog/Smoothened signaling (FlyBase-curated). Reason: A specific developmental-signaling moonlighting role; non-core. Supporting Evidence: PMID:32467643 In the absence of Hh, Rack1 promotes Ci and Cos2 to form a Ci-Rack1-Cos2 complex, culminating in Slimb-mediated Ci proteolysis. |
| GO:0031334 positive regulation of protein-containing complex assembly | IDA PMID:20541605 RACK1 promotes Bax oligomerization and dissociates the inter... | KEEP AS NON CORE | Summary: RACK1 promotes BAX oligomerization (a pro-apoptotic complex-assembly event). Reason: A specific apoptosis-scaffolding moonlighting role; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Promotes apoptosis by increasing oligomerization of BAX |
| GO:0032091 negative regulation of protein binding | IDA PMID:20541605 RACK1 promotes Bax oligomerization and dissociates the inter... | KEEP AS NON CORE | Summary: RACK1 disrupts the BAX-BCL2L1 (Bcl-XL) interaction, promoting apoptosis. Reason: A specific apoptosis-related moonlighting role; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt disrupting the interaction of BAX with the anti-apoptotic factor BCL2L |
| GO:0051434 BH3 domain binding | IDA PMID:20541605 RACK1 promotes Bax oligomerization and dissociates the inter... | KEEP AS NON CORE | Summary: RACK1 binds the BH3 domain of BAX, mediating its pro-apoptotic oligomerization. Reason: A specific, informative interaction MF in apoptosis; genuine but non-core. Supporting Evidence: PMID:20541605 We demonstrated that RACK1 interacts with Bax through its BH3 domain both in vitro and in vivo. |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | KEEP AS NON CORE | Summary: High-throughput proteomics placing RACK1 in the E-cadherin interactome. Reason: High-throughput interaction; non-core MF. The cached abstract does not state this exact claim; the annotation defers to the curator's reading of the full text. Supporting Evidence: PMID:25468996 We used proximity biotinylation and quantitative proteomics to identify 561 proteins in the vicinity of the cytoplasmic tail of E-cadherin. |
| GO:0030332 cyclin binding | IPI PMID:15159402 Identification of interaction partners and substrates of the... | KEEP AS NON CORE | Summary: Interaction with a cyclin (P78396); a specific interaction MF. Reason: Records a real interaction relevant to cell-cycle moonlighting; non-core. Supporting Evidence: PMID:15159402 receptor for activated protein kinase C1/guanine nucleotide-binding protein beta-2-like-1, and mRNA-binding motif protein 4 were identified as interaction partners |
| GO:0016567 protein ubiquitination | IMP PMID:28132843 ZNF598 and RACK1 Regulate Mammalian Ribosome-Associated Qual... | ACCEPT | Summary: RACK1 promotes regulatory ubiquitination of a subset of 40S ribosomal proteins (RPS2, RPS3, RPS20) during RQC. Reason: Core RQC function. RACK1 regulates 40S ubiquitylation that initiates ribosome quality control. Supporting Evidence: PMID:28132843 RACK1 regulates RPS2, RPS3, and RPS20 ubiquitylation |
| GO:0043022 ribosome binding | IDA PMID:28132843 ZNF598 and RACK1 Regulate Mammalian Ribosome-Associated Qual... | ACCEPT | Summary: Direct demonstration of RACK1 ribosome binding in the RQC study. Reason: Core MF; RACK1 is ribosome-bound and acts on stalled ribosomes. Supporting Evidence: PMID:28132843 the 40S ribosomal protein RACK1 help to resolve poly(A)-induced stalled ribosomes file:human/RACK1/RACK1-uniprot.txt Component of the 40S ribosomal subunit involved in translational repression (PubMed:23636399). |
| GO:0072344 rescue of stalled cytosolic ribosome | IMP PMID:28132843 ZNF598 and RACK1 Regulate Mammalian Ribosome-Associated Qual... | ACCEPT | Summary: Loss-of-function shows RACK1 is required to resolve poly(A)-induced stalled ribosomes (RQC). Reason: Core function, directly demonstrated by IMP. Supporting Evidence: PMID:28132843 the 40S ribosomal protein RACK1 help to resolve poly(A)-induced stalled ribosomes |
| GO:0005515 protein binding | IPI PMID:21098120 La-related protein 4 binds poly(A), interacts with the poly(... | REMOVE | Summary: Interaction with LARP4 (Q71RC2); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:20010870 Copine-III interacts with ErbB2 and promotes tumor cell migr... | REMOVE | Summary: Interaction with CPNE3 (O75131); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0071363 cellular response to growth factor stimulus | IDA PMID:20010870 Copine-III interacts with ErbB2 and promotes tumor cell migr... | KEEP AS NON CORE | Summary: RACK1/CPNE3 role downstream of ErbB2 growth-factor signaling in migration. Reason: A specific growth-factor-signaling moonlighting role; non-core. The cached abstract does not state this exact claim; the annotation defers to the curator's reading of the full text. Supporting Evidence: PMID:20010870 Copine-III also binds receptor of activated C kinase 1 and colocalizes with phosphorylated focal adhesion kinase at the leading edge of migrating cells. |
| GO:0005515 protein binding | IPI PMID:19674157 Receptor for activated C-kinase 1 regulates the cellular loc... | REMOVE | Summary: Interaction with ABCB4 (P21439) regulating its localization; a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0042998 positive regulation of Golgi to plasma membrane protein transport | IMP PMID:19674157 Receptor for activated C-kinase 1 regulates the cellular loc... | KEEP AS NON CORE | Summary: RACK1 promotes transport of ABCB4 from Golgi to the apical membrane. Reason: A specific trafficking moonlighting role; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Involved in the transport of ABCB4 from the Golgi to the apical bile canalicular membrane |
| GO:0005515 protein binding | IPI PMID:20103773 A crucial role for RACK1 in the regulation of glucose-stimul... | REMOVE | Summary: Interaction with IRE1/ERN1 (O75460) within the IRE1-RACK1-PP2A complex; a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0035591 signaling adaptor activity | IMP PMID:20103773 A crucial role for RACK1 in the regulation of glucose-stimul... | KEEP AS NON CORE | Summary: RACK1 acts as a signaling adaptor recruiting PP2A to IRE1; a genuine scaffold/adaptor molecular function. Reason: Captures RACK1's bona fide adaptor function, though in a specific UPR context; a representative scaffold MF kept as non-core. Supporting Evidence: PMID:20103773 RACK1 mediated the glucose-inducible assembly of a complex containing IRE1alpha, RACK1, and protein phosphatase 2A (PP2A) to promote dephosphorylation of IRE1alpha by PP2A, thereby inhibiting glucose-stimulated IRE1alpha activation |
| GO:0071333 cellular response to glucose stimulus | IDA PMID:20103773 A crucial role for RACK1 in the regulation of glucose-stimul... | KEEP AS NON CORE | Summary: RACK1/IRE1 role in the response to glucose, linked to UPR regulation. Reason: A specific stimulus-response moonlighting role; non-core. Supporting Evidence: PMID:20103773 the scaffold protein receptor for activated C-kinase 1 (RACK1) interacted with IRE1alpha in a glucose-stimulated or endoplasmic reticulum (ER) stress-responsive manner |
| GO:1990630 IRE1-RACK1-PP2A complex | IDA PMID:20103773 A crucial role for RACK1 in the regulation of glucose-stimul... | KEEP AS NON CORE | Summary: RACK1 is part of a defined IRE1-RACK1-PP2A complex that attenuates the UPR. Reason: A genuine specific complex but a moonlighting (UPR) context; non-core. Supporting Evidence: PMID:20103773 RACK1 mediated the glucose-inducible assembly of a complex containing IRE1alpha, RACK1, and protein phosphatase 2A (PP2A) to promote dephosphorylation of IRE1alpha by PP2A, thereby inhibiting glucose-stimulated IRE1alpha activation |
| GO:1900102 negative regulation of endoplasmic reticulum unfolded protein response | TAS PMID:22013210 The unfolded protein response: integrating stress signals th... | KEEP AS NON CORE | Summary: RACK1 negatively regulates the ER UPR (via IRE1 dephosphorylation). Reason: A specific UPR moonlighting role; non-core. The cited review abstract does not name RACK1; the primary IRE1-RACK1-PP2A study supports the claim. Supporting Evidence: PMID:20103773 RACK1 mediated the glucose-inducible assembly of a complex containing IRE1alpha, RACK1, and protein phosphatase 2A (PP2A) to promote dephosphorylation of IRE1alpha by PP2A, thereby inhibiting glucose-stimulated IRE1alpha activation |
| GO:0010629 negative regulation of gene expression | IMP PMID:19451233 Stxbp4 regulates DeltaNp63 stability by suppression of RACK1... | KEEP AS NON CORE | Summary: RACK1 negatively regulates gene expression in a specific context. Reason: Broad/specific-context moonlighting BP; non-core. Supporting Evidence: PMID:19451233 While Stxbp4 functions to stabilize DeltaNp63 proteins, RACK1 targets DeltaNp63 for degradation. |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | KEEP AS NON CORE | Summary: RACK1 captured in high-throughput mRNA-interactome (RNA-binding proteome) screens, consistent with its position on the 40S subunit near mRNA. Reason: Plausible given ribosomal context but from high-throughput crosslinking; non-core MF. The cached abstract does not state this exact claim; the annotation defers to the curator's reading of the full text. Supporting Evidence: PMID:22658674 We identify 860 proteins that qualify as RBPs by biochemical and statistical criteria file:human/RACK1/RACK1-uniprot.txt Component of the 40S ribosomal subunit involved in translational repression (PubMed:23636399). |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | KEEP AS NON CORE | Summary: RACK1 in a second RNA-interactome capture screen. Reason: High-throughput RNA-binding; non-core MF (ribosome-associated). The cached abstract does not state this exact claim; the annotation defers to the curator's reading of the full text. Supporting Evidence: PMID:22681889 Application to a human embryonic kidney cell line identified close to 800 proteins. file:human/RACK1/RACK1-uniprot.txt Component of the 40S ribosomal subunit involved in translational repression (PubMed:23636399). |
| GO:0005739 mitochondrion | IMP PMID:19767770 A novel pro-apoptotic function of RACK1: suppression of Src ... | MARK AS OVER ANNOTATED | Summary: A mitochondrial localization reported in a single study; inconsistent with the dominant cytosolic/ribosomal pool. Reason: Single-study, conflicting localization not corroborated by structural/proteomic consensus; likely over-annotation. The study reports RACK1 targeting Bim and Bax to mitochondria, and the curated UniProt localization lists no mitochondrial pool. Supporting Evidence: PMID:19767770 targets Bim and Bax to the mitochondria |
| GO:0005829 cytosol | IMP PMID:19767770 A novel pro-apoptotic function of RACK1: suppression of Src ... | ACCEPT | Summary: Cytosolic localization (same study). Reason: Core compartment. Supported by the curated cytoplasmic localization and 40S ribosomal residence. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Peripheral membrane protein. Cytoplasm {ECO:0000269|PubMed:10849009, ECO:0000269|PubMed:11279199, file:human/RACK1/RACK1-uniprot.txt Component of the 40S ribosomal subunit involved in translational repression (PubMed:23636399). |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | MARK AS OVER ANNOTATED | Summary: Detection in extracellular exosome proteomics; abundant cytosolic/ribosomal proteins are commonly detected in such fractions. Reason: High-throughput exosome proteomics; likely a contaminant of abundant ribosomal protein, not a functional exosomal localization. Supporting Evidence: PMID:19056867 Here, we used LC-MS/MS to profile the proteome of human urinary exosomes. file:human/RACK1/RACK1-uniprot.txt Component of the 40S ribosomal subunit involved in translational repression (PubMed:23636399). |
| GO:0060090 molecular adaptor activity | TAS PMID:20819076 Interaction with receptor for activated C-kinase 1 (RACK1) s... | KEEP AS NON CORE | Summary: RACK1 functions as a molecular adaptor/scaffold; this is its defining non-ribosomal molecular function. Reason: Captures RACK1's genuine scaffold/adaptor MF; kept non-core relative to its ribosomal/RQC core, but the most informative summary of its signaling role. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Scaffolding protein involved in the recruitment, assembly and/or regulation of a variety of signaling molecules. |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:19767770 A novel pro-apoptotic function of RACK1: suppression of Src ... | KEEP AS NON CORE | Summary: RACK1 promotes apoptosis in some contexts. Reason: A specific apoptosis moonlighting role; non-core. Supporting Evidence: PMID:19767770 RACK1 also induces apoptosis of the cells, partly by inhibiting Src. |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:19767770 A novel pro-apoptotic function of RACK1: suppression of Src ... | KEEP AS NON CORE | Summary: RACK1 negatively regulates PI3K/AKT signaling (e.g. by recruiting PP2A to AKT1). Reason: A specific signaling moonlighting role; non-core. Supporting Evidence: PMID:19767770 RACK1 also induces apoptosis by blocking Src activation of the Akt cell survival pathway. |
| GO:0005515 protein binding | IPI PMID:14500341 Alternative splicing of the human proto-oncogene c-H-ras ren... | REMOVE | Summary: Interaction with HRAS (P01112); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:18816594 mrtl-A translation/localization regulatory protein encoded w... | REMOVE | Summary: Interaction with a partner (Q14899); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005634 nucleus | IDA PMID:17108144 Receptor for activated C kinase 1 (RACK1) and Src regulate t... | KEEP AS NON CORE | Summary: Nuclear localization with the androgen receptor in a signaling context. Reason: Context-dependent nuclear pool; non-core. The cached abstract does not state this exact claim; the annotation defers to the curator's reading of the full text. UniProt independently records a nuclear pool. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Nucleus {ECO:0000269|PubMed:10849009}. PMID:17108144 modulates the tyrosine phosphorylation of AR and its interaction with the Src tyrosine kinase |
| GO:0001891 phagocytic cup | IDA PMID:21347310 The RACK1 signaling scaffold protein selectively interacts w... | KEEP AS NON CORE | Summary: Direct localization to phagocytic cups during Yersinia infection. Reason: Infection-context localization; non-core. Supporting Evidence: PMID:21347310 RACK1 was found in association with phagocytic cups, where the bacteria were partially surrounded by the HeLa cell membrane file:human/RACK1/RACK1-uniprot.txt Cell projection, phagocytic cup {ECO:0000269|PubMed:21347310}. |
| GO:0001934 positive regulation of protein phosphorylation | IDA PMID:11312657 Rack1 binds HIV-1 Nef and can act as a Nef-protein kinase C ... | KEEP AS NON CORE | Summary: RACK1 enhances PKC-mediated phosphorylation of substrates (here HIV-1 Nef). Reason: Reflects the PKC-scaffold role in a specific context; non-core. Supporting Evidence: PMID:11312657 The presence of Rack1 doubles Nef phosphorylation by PKCs in vitro. |
| GO:0001934 positive regulation of protein phosphorylation | IDA PMID:17108144 Receptor for activated C kinase 1 (RACK1) and Src regulate t... | KEEP AS NON CORE | Summary: RACK1 promotes SRC-mediated phosphorylation of the androgen receptor. Reason: A specific signaling-scaffold role; non-core. Supporting Evidence: PMID:17108144 facilitates the tyrosine phosphorylation and transcriptional activity of the AR. |
| GO:0005080 protein kinase C binding | IDA PMID:11279199 The interaction of Src and RACK1 is enhanced by activation o... | KEEP AS NON CORE | Summary: Direct binding to protein kinase C; the canonical RACK1 scaffold molecular function. Reason: Well-established direct MF and namesake activity, but secondary to the ribosomal/RQC core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Binds to and stabilizes activated protein kinase C (PKC), increasing PKC-mediated phosphorylation. |
| GO:0005515 protein binding | IPI PMID:11279199 The interaction of Src and RACK1 is enhanced by activation o... | REMOVE | Summary: Interaction with SRC captured by IPI; a bare protein-binding annotation (informative aspect captured by tyrosine-kinase-inhibitor MF). Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:11312657 Rack1 binds HIV-1 Nef and can act as a Nef-protein kinase C ... | REMOVE | Summary: Interaction with HIV-1 Nef (P03404); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:17108144 Receptor for activated C kinase 1 (RACK1) and Src regulate t... | REMOVE | Summary: Interaction with the androgen receptor (P10275); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:19785988 RACK1 associates with CLEC-2 and promotes its ubiquitin-prot... | REMOVE | Summary: Interaction with CLEC1B/CLEC-2 (Q9P126) promoting its degradation; a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:20541605 RACK1 promotes Bax oligomerization and dissociates the inter... | REMOVE | Summary: Interaction with BAX/BCL2L1 (Q07812/Q07817); bare protein-binding annotations (informative aspect captured by BH3-domain binding). Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005634 nucleus | IDA PMID:10849009 The PKC targeting protein RACK1 interacts with the Epstein-B... | KEEP AS NON CORE | Summary: Direct nuclear localization (EBV BZLF1 study). Reason: Context-dependent nuclear pool; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Nucleus {ECO:0000269|PubMed:10849009}. PMID:10849009 In vivo, RACK1 binds directly to the transactivation domain of BZLF1. |
| GO:0005737 cytoplasm | IDA PMID:10849009 The PKC targeting protein RACK1 interacts with the Epstein-B... | ACCEPT | Summary: Direct cytoplasmic localization. Reason: Core compartment. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Peripheral membrane protein. Cytoplasm {ECO:0000269|PubMed:10849009, ECO:0000269|PubMed:11279199, |
| GO:0005737 cytoplasm | IDA PMID:19785988 RACK1 associates with CLEC-2 and promotes its ubiquitin-prot... | ACCEPT | Summary: Direct cytoplasmic localization. Reason: Core compartment. UniProt cites this study for cytoplasmic localization. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt ECO:0000269|PubMed:12958311, ECO:0000269|PubMed:19785988, file:human/RACK1/RACK1-uniprot.txt Peripheral membrane protein. Cytoplasm {ECO:0000269|PubMed:10849009, ECO:0000269|PubMed:11279199, |
| GO:0008200 ion channel inhibitor activity | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Ion channel inhibitor activity inferred by similarity; same indirect scaffold effect as the IEA annotation. Reason: Indirect (scaffold-mediated) channel modulation overstated as a direct MF. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Inhibits TRPM6 channel activity. |
| GO:0015935 small ribosomal subunit | ISS GO_REF:0000024 | ACCEPT | Summary: RACK1 is part of the small ribosomal subunit (by similarity). Reason: Core cellular component. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Component of the small (40S) ribosomal subunit |
| GO:0017148 negative regulation of translation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: RACK1 is involved in translational repression on the 40S subunit. Reason: Concordant with UniProt (translational repression); a genuine but broad translation-control role kept non-core relative to the RQC-specific core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Component of the 40S ribosomal subunit involved in translational repression |
| GO:0030178 negative regulation of Wnt signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: RACK1 inhibits Wnt signaling and regulates cell polarity/gastrulation (inferred from Xenopus ortholog). Reason: A developmental-signaling moonlighting role; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt inhibits Wnt signaling, and regulates cellular polarization and oriented cell division during gastrulation |
| GO:0030292 protein tyrosine kinase inhibitor activity | IDA PMID:9584165 RACK1, a receptor for activated C kinase and a homolog of th... | KEEP AS NON CORE | Summary: RACK1 inhibits Src-family tyrosine kinases (SRC, LCK, YES1); a direct, informative molecular function. Reason: Well-supported direct MF (RACK1 inhibits Src activity and cell growth), but a signaling moonlighting function rather than the ribosomal core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Inhibits the activity of SRC kinases including SRC, LCK and YES1. |
| GO:0030308 negative regulation of cell growth | IDA PMID:9584165 RACK1, a receptor for activated C kinase and a homolog of th... | KEEP AS NON CORE | Summary: RACK1 inhibits cell growth (prolongs G0/G1) via Src inhibition. Reason: A growth-control moonlighting role; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Inhibits cell growth by prolonging the G0/G1 phase of the cell cycle. |
| GO:0030335 positive regulation of cell migration | IDA PMID:20499158 RACK1 promotes breast carcinoma migration/metastasis via act... | KEEP AS NON CORE | Summary: RACK1 promotes cell migration (via RhoA activation) in breast carcinoma. Reason: A migration/metastasis moonlighting role; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Promotes migration of breast carcinoma cells by binding to and activating RHOA |
| GO:0030425 dendrite | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Dendritic localization by similarity. Reason: Neuronal-context localization; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Cell projection, dendrite |
| GO:0030971 receptor tyrosine kinase binding | IDA PMID:9584165 RACK1, a receptor for activated C kinase and a homolog of th... | KEEP AS NON CORE | Summary: RACK1 binds receptor tyrosine kinases (e.g. via its interactions with IGF1R/SRC pathway components). Reason: A specific interaction MF in growth-factor signaling; non-core. The cited abstract describes binding to the Src SH2 domain; curated UniProt interactions with the receptor tyrosine kinases IGF1R and FLT1 independently support the term. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Interacts with IGF1R but not with INSR. file:human/RACK1/RACK1-uniprot.txt Interacts with FLT1. |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IDA PMID:19785988 RACK1 associates with CLEC-2 and promotes its ubiquitin-prot... | KEEP AS NON CORE | Summary: RACK1 promotes ubiquitin-proteasome degradation of clients such as CLEC1B and HIF1A. Reason: A specific client-degradation moonlighting role; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Promotes the ubiquitination and proteasome-mediated degradation of proteins such as CLEC1B and HIF1A. |
| GO:0032880 regulation of protein localization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: RACK1 regulates localization of partner proteins (inferred from ortholog). Reason: A broad scaffold-trafficking role; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Required for VANGL2 membrane localization |
| GO:0042169 SH2 domain binding | IDA PMID:11279199 The interaction of Src and RACK1 is enhanced by activation o... | KEEP AS NON CORE | Summary: RACK1 binds the SH2 domain of SRC; an informative interaction MF underlying Src regulation. Reason: A specific, real interaction MF in Src signaling; non-core. Supporting Evidence: PMID:11279199 the interaction of Src and RACK1 is mediated, in part, by the SH2 domain of Src |
| GO:0042169 SH2 domain binding | IDA PMID:9584165 RACK1, a receptor for activated C kinase and a homolog of th... | KEEP AS NON CORE | Summary: RACK1 binds the SH2 domain of Src-family kinases. Reason: Specific interaction MF in Src signaling; non-core. Supporting Evidence: PMID:9584165 we determined that RACK1 binds to the SH2 domain of Src. |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:20541605 RACK1 promotes Bax oligomerization and dissociates the inter... | KEEP AS NON CORE | Summary: RACK1 promotes apoptosis via BAX oligomerization. Reason: An apoptosis moonlighting role; non-core. Supporting Evidence: PMID:20541605 RACK1 promotes apoptosis by promoting Bax oligomerization and dissociating the complex of Bax and Bcl-XL. |
| GO:0043547 positive regulation of GTPase activity | IDA PMID:20499158 RACK1 promotes breast carcinoma migration/metastasis via act... | KEEP AS NON CORE | Summary: RACK1 activates RHOA GTPase to promote migration. Reason: A specific signaling moonlighting role; non-core. Supporting Evidence: PMID:20499158 RACK1 promotes migration via interaction with RhoA and activation of the RhoA/Rho kinase pathway. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:11279199 The interaction of Src and RACK1 is enhanced by activation o... | KEEP AS NON CORE | Summary: Perinuclear localization that redistributes on PKC activation. Reason: A sub-cytoplasmic distribution; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Cytoplasm, perinuclear region {ECO:0000269|PubMed:11279199, ECO:0000269|PubMed:12958311}. file:human/RACK1/RACK1-uniprot.txt translocation from the perinuclear region to the cell periphery |
| GO:0050765 negative regulation of phagocytosis | IMP PMID:21347310 The RACK1 signaling scaffold protein selectively interacts w... | KEEP AS NON CORE | Summary: RACK1 binding to Yersinia YopK inhibits phagocytosis (infection context). Reason: An infection-related moonlighting role; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt which leads to inhibition of phagocytosis and survival of bacteria |
| GO:0051302 regulation of cell division | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Regulation of cell division inferred from ortholog (oriented cell division during gastrulation). Reason: A developmental moonlighting role; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt regulates cellular polarization and oriented cell division during gastrulation |
| GO:0051726 regulation of cell cycle | IDA PMID:9584165 RACK1, a receptor for activated C kinase and a homolog of th... | KEEP AS NON CORE | Summary: RACK1 regulates the cell cycle (G0/G1 prolongation via Src inhibition). Reason: A growth/cell-cycle moonlighting role; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Inhibits cell growth by prolonging the G0/G1 phase of the cell cycle. |
| GO:2000114 regulation of establishment of cell polarity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Regulation of cell polarity inferred from ortholog. Reason: A developmental moonlighting role; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt regulates cellular polarization and oriented cell division during gastrulation |
| GO:2000543 positive regulation of gastrulation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: RACK1 promotes gastrulation (inferred from Xenopus ortholog). Reason: A developmental moonlighting role; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt regulates cellular polarization and oriented cell division during gastrulation |
| GO:0030496 midbody | IDA PMID:15166316 Dissection of the mammalian midbody proteome reveals conserv... | KEEP AS NON CORE | Summary: Detection in the midbody proteome during cytokinesis. Reason: A cytokinesis-localization observed in proteomics; non-core. The cached abstract does not state this exact claim; the annotation defers to the curator's reading of the full text. Supporting Evidence: PMID:15166316 Midbodies were isolated from mammalian cells, proteins were identified by multidimensional protein identification technology (MudPIT) |
| GO:0005515 protein binding | IPI PMID:18954305 Structural basis and specificity of human otubain 1-mediated... | REMOVE | Summary: Interaction with OTUB1 (Q96FW1); a bare protein-binding annotation. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0043025 neuronal cell body | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neuronal cell body localization by similarity. Reason: Neuronal-context localization; non-core. Supporting Evidence: file:human/RACK1/RACK1-uniprot.txt Perikaryon {ECO:0000250|UniProtKB:P68040} |
| GO:0019903 protein phosphatase binding | IPI PMID:11278757 The PTPmu protein-tyrosine phosphatase binds and recruits th... | KEEP AS NON CORE | Summary: RACK1 binds a protein phosphatase (P28827), consistent with its adaptor role recruiting phosphatases (e.g. PP2A). Reason: A specific interaction MF supporting the scaffold role; non-core. Supporting Evidence: PMID:11278757 identified the scaffolding protein RACK1 (receptor for activated protein C kinase) as a PTPmu interacting protein. |
| GO:0005102 signaling receptor binding | NAS PMID:12809483 ST7 is a novel low-density lipoprotein receptor-related prot... | KEEP AS NON CORE | Summary: RACK1 binds signaling receptors (asserted, NAS); a generic interaction MF. Reason: Reflects scaffold interactions with receptors; non-core and relatively generic. Supporting Evidence: PMID:12809483 this domain interacts with three proteins involved in signal transduction and/or endocytosis, viz., receptor for activated protein C kinase 1 (RACK1) |
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Download this section (compressed HTML)Q: To what extent are RACK1's many signaling/moonlighting functions performed by the ribosome-bound pool versus a free cytosolic pool, and is there a regulated equilibrium between them?
Q: What is the precise mechanistic role of RACK1 in collision sensing relative to ZNF598 and EDF1 - does it act as the primary platform that positions the E3 ligase on collided ribosomes?
Experiment: Selective ribosome profiling and disome-seq in RACK1-knockout versus wild-type cells to quantify the contribution of RACK1 to collision-induced stalling resolution and 40S ubiquitylation genome-wide.
Experiment: Separation-of-function mutagenesis of the RACK1 WD40 surface to uncouple ribosome binding from PKC/Src scaffold interactions, testing which surfaces are required for RQC versus signaling outputs.
Experiment: Cryo-EM of collided disomes reconstituted with RACK1, ZNF598 and EDF1 to define the structural basis of RACK1-dependent recruitment of the ubiquitylation machinery.
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