Existing Annotations Review

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...	KEEP AS NON CORE	Summary: Interaction with Epstein-Barr virus BZLF1 captured by IntAct; a real but uninformative bare protein-binding annotation. Reason: Records a genuine (viral) interaction but "protein binding" is uninformative as a molecular function; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:10849009 UniProtKB:P03206
GO:0005515 protein binding	IPI PMID:11046044 Receptor for activated C-kinase (RACK-1), a WD motif-contain...	KEEP AS NON CORE	Summary: IntAct interaction with IFNAR2 (P48551); a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:11046044 UniProtKB:P48551
GO:0005515 protein binding	IPI PMID:12809483 ST7 is a novel low-density lipoprotein receptor-related prot...	KEEP AS NON CORE	Summary: IntAct interaction with LRP12 (Q9Y561); a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:12809483 UniProtKB:Q9Y561
GO:0005515 protein binding	IPI PMID:18194455 Acetylcholinesterase-R increases germ cell apoptosis but enh...	KEEP AS NON CORE	Summary: IntAct interaction with ACHE (P22303); a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18194455 UniProtKB:P22303
GO:0005515 protein binding	IPI PMID:18420585 RACK1 and CIS mediate the degradation of BimEL in cancer cel...	KEEP AS NON CORE	Summary: IntAct interactions (BCL2L11, DYNLL1 and ortholog) captured in a single screen; bare protein-binding annotations. Reason: Real interactions but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18420585 UniProtKB:O43521
GO:0005515 protein binding	IPI PMID:20080539 The Polycomb group protein EED couples TNF receptor 1 to neu...	KEEP AS NON CORE	Summary: IntAct interaction with EED (O75530); a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20080539 UniProtKB:O75530
GO:0005515 protein binding	IPI PMID:20871634 Regulation of receptor for activated C kinase 1 protein by t...	KEEP AS NON CORE	Summary: IntAct interaction with VHL (P40337); a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20871634 UniProtKB:P40337
GO:0005515 protein binding	IPI PMID:21146485 Identification of cyclophilin-40-interacting proteins reveal...	KEEP AS NON CORE	Summary: IntAct interaction with PPID (Q08752); a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:21146485 UniProtKB:Q08752
GO:0005515 protein binding	IPI PMID:21525958 The ribosomal protein RACK1 is required for microRNA functio...	KEEP AS NON CORE	Summary: IntAct interaction with AGO2 (Q9UKV8); a bare protein-binding annotation. Reason: Real interaction (RACK1 associates with the miRNA machinery) but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:21525958 UniProtKB:Q9UKV8
GO:0005515 protein binding	IPI PMID:21750715 The inhibitor of growth protein 5 (ING5) depends on INCA1 as...	KEEP AS NON CORE	Summary: IntAct interaction with INCA1 (Q0VD86); a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:21750715 UniProtKB:Q0VD86
GO:0005515 protein binding	IPI PMID:21988832 Toward an understanding of the protein interaction network o...	KEEP AS NON CORE	Summary: Liver interactome interaction with LARP4B (Q92615); a bare protein-binding annotation. Reason: Real interaction (RACK1 binds LARP4/LARP4B translation factors) but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:21988832 UniProtKB:Q92615
GO:0005515 protein binding	IPI PMID:22210188 Interaction of protein inhibitor of activated STAT 2 (PIAS2)...	KEEP AS NON CORE	Summary: IntAct interaction with PIAS2 (O75928); a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:22210188 UniProtKB:O75928
GO:0005515 protein binding	IPI PMID:23651062 RACK1 (receptor for activated C-kinase 1) interacts with FBW...	KEEP AS NON CORE	Summary: IntAct interaction with FBXW2 (Q9UKT8); a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:23651062 UniProtKB:Q9UKT8
GO:0005515 protein binding	IPI PMID:23866081 Lyn, a Src family kinase, regulates activation of epidermal ...	KEEP AS NON CORE	Summary: IntAct interactions with LYN (P07948) and PAG1 (Q9NWQ8); bare protein-binding annotations. Reason: Real interactions but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:23866081 UniProtKB:P07948
GO:0005515 protein binding	IPI PMID:24947010 DJ-1 interacts with RACK1 and protects neurons from oxidativ...	KEEP AS NON CORE	Summary: IntAct interaction with PARK7/DJ-1 (Q99497); a bare protein-binding annotation. Reason: Real interaction (DJ-1 binds RACK1 in oxidative-stress protection) but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:24947010 UniProtKB:Q99497
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	KEEP AS NON CORE	Summary: IntAct interaction with ACTN2 (P35609); a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25910212 UniProtKB:P35609
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	KEEP AS NON CORE	Summary: IntAct interactions with HELZ (P42694) and LARP4B (Q92615); bare protein-binding annotations. Reason: Real interactions but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:28514442 UniProtKB:P42694
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	Summary: Large IntAct interactome study capturing many RACK1 partners (USP10, CNOT2, CRMP1, etc.); bare protein-binding annotations. Reason: Real high-throughput interactions but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:Q14694
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: BioPlex interactome capturing HELZ/LARP4B interactions; bare protein-binding annotations. Reason: Real interactions but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:P42694
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	KEEP AS NON CORE	Summary: IntAct interactome capturing HELZ, BYSL, USP10, LARP4B; bare protein-binding annotations. Reason: Real interactions but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:35271311 UniProtKB:P42694
GO:0005515 protein binding	IPI PMID:38190388 A novel Trichinella spiralis serine proteinase disrupted gut...	KEEP AS NON CORE	Summary: IntAct interaction with a partner (O96871); a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:38190388 UniProtKB:O96871
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	KEEP AS NON CORE	Summary: Multimodal cell-maps interactome capturing HELZ/LARP4B; bare protein-binding annotations. Reason: Real interactions but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:40205054 UniProtKB:P42694
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: file:human/RACK1/RACK1-goa.tsv negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide
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. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005654 nucleoplasm cellular_component ECO:0000314 IDA GO_REF:0000052
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: HPA immunofluorescence cytosol signal, the dominant localization. Reason: Core compartment, directly observed. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005829 cytosol cellular_component ECO:0000314 IDA GO_REF:0000052
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-goa.tsv GO:0005737 cytoplasm cellular_component ECO:0000269 EXP PMID:11279199
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. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005737 cytoplasm cellular_component ECO:0000269 EXP PMID:12958311
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-goa.tsv GO:0005737 cytoplasm cellular_component ECO:0000269 EXP PMID:20499158
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-goa.tsv GO:0005737 cytoplasm cellular_component ECO:0000269 EXP PMID:20573744
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-goa.tsv GO:0005737 cytoplasm cellular_component ECO:0000269 EXP PMID: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. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005737 cytoplasm cellular_component ECO:0000269 EXP PMID:37712706
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-goa.tsv GO:0005886 plasma membrane cellular_component ECO:0000269 EXP PMID:11312657
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-goa.tsv GO:0005886 plasma membrane cellular_component ECO:0000269 EXP PMID: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. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-5626962
GO:0005829 cytosol	TAS Reactome:R-HSA-5626981	ACCEPT	Summary: Reactome cytosol localization. Reason: Core compartment. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-5626981
GO:0005829 cytosol	TAS Reactome:R-HSA-5626982	ACCEPT	Summary: Reactome cytosol localization. Reason: Core compartment. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-5626982
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: file:human/RACK1/RACK1-goa.tsv GO:0030291 protein serine/threonine kinase inhibitor activity molecular_function ECO:0000315 IMP PMID:20103773
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: file:human/RACK1/RACK1-goa.tsv GO:0008047 enzyme activator activity molecular_function ECO:0000314 IDA PMID:20819076
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: file:human/RACK1/RACK1-goa.tsv GO:0019899 enzyme binding molecular_function ECO:0000353 IPI PMID:20819076 UniProtKB:Q08499
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: file:human/RACK1/RACK1-goa.tsv regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway
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: file:human/RACK1/RACK1-goa.tsv negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide
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...	KEEP AS NON CORE	Summary: Interaction with SLC9A6 regulating its distribution; a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18057008 UniProtKB:Q8IVB4
GO:0005515 protein binding	IPI PMID:24006492 Endosomal acidification by Na+/H+ exchanger NHE5 regulates T...	KEEP AS NON CORE	Summary: Interaction with SLC9A5/NHE5 regulating its trafficking; a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:24006492 UniProtKB:Q14940
GO:0005515 protein binding	IPI PMID:29743600 Trafficking, localization and degradation of the Na(+),HCO(3...	KEEP AS NON CORE	Summary: Interaction with SLC4A7/NBCn1; a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:29743600 UniProtKB:Q9R1N3-2
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-goa.tsv GO:0005737 cytoplasm cellular_component ECO:0000314 IDA PMID:29743600
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: file:human/RACK1/RACK1-goa.tsv GO:0045879 negative regulation of smoothened signaling pathway biological_process ECO:0000314 IDA PMID:32467643
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: file:human/RACK1/RACK1-goa.tsv GO:0051434 BH3 domain binding molecular_function ECO:0000314 IDA PMID:20541605
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. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0045296 cadherin binding molecular_function ECO:0007005 HDA PMID:25468996
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: file:human/RACK1/RACK1-goa.tsv GO:0030332 cyclin binding molecular_function ECO:0000353 IPI PMID:15159402 UniProtKB:P78396
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: file:human/RACK1/RACK1-goa.tsv GO:0043022 ribosome binding molecular_function ECO:0000314 IDA PMID:28132843
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(...	KEEP AS NON CORE	Summary: Interaction with LARP4 (Q71RC2); a bare protein-binding annotation. Reason: Real interaction (translation-associated) but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:21098120 UniProtKB:Q71RC2
GO:0005515 protein binding	IPI PMID:20010870 Copine-III interacts with ErbB2 and promotes tumor cell migr...	KEEP AS NON CORE	Summary: Interaction with CPNE3 (O75131); a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20010870 UniProtKB:O75131
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. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0071363 cellular response to growth factor stimulus biological_process ECO:0000314 IDA PMID:20010870
GO:0005515 protein binding	IPI PMID:19674157 Receptor for activated C-kinase 1 regulates the cellular loc...	KEEP AS NON CORE	Summary: Interaction with ABCB4 (P21439) regulating its localization; a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19674157 UniProtKB:P21439
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...	KEEP AS NON CORE	Summary: Interaction with IRE1/ERN1 (O75460) within the IRE1-RACK1-PP2A complex; a bare protein-binding annotation. Reason: Real interaction but uninformative MF; informative aspects captured by the kinase-inhibitor and complex annotations. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20103773 UniProtKB:O75460
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: file:human/RACK1/RACK1-goa.tsv GO:0035591 signaling adaptor activity molecular_function ECO:0000315 IMP PMID:20103773
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: file:human/RACK1/RACK1-goa.tsv GO:0071333 cellular response to glucose stimulus biological_process ECO:0000314 IDA PMID:20103773
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: file:human/RACK1/RACK1-goa.tsv GO:1990630 IRE1-RACK1-PP2A complex cellular_component ECO:0000314 IDA PMID:20103773
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. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:1900102 negative regulation of endoplasmic reticulum unfolded protein response biological_process ECO:0000304 TAS PMID:22013210
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: file:human/RACK1/RACK1-goa.tsv GO:0010629 negative regulation of gene expression biological_process ECO:0000315 IMP PMID:19451233
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. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0003723 RNA binding molecular_function ECO:0007005 HDA PMID:22658674
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). Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0003723 RNA binding molecular_function ECO:0007005 HDA PMID:22681889
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. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005739 mitochondrion cellular_component ECO:0000315 IMP PMID:19767770
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. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005829 cytosol cellular_component ECO:0000315 IMP PMID:19767770
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: file:human/RACK1/RACK1-goa.tsv GO:0070062 extracellular exosome cellular_component ECO:0007005 HDA PMID:19056867
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: file:human/RACK1/RACK1-goa.tsv GO:0043065 positive regulation of apoptotic process biological_process ECO:0000315 IMP PMID:19767770
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: file:human/RACK1/RACK1-goa.tsv GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction biological_process ECO:0000315 IMP PMID:19767770
GO:0005515 protein binding	IPI PMID:14500341 Alternative splicing of the human proto-oncogene c-H-ras ren...	KEEP AS NON CORE	Summary: Interaction with HRAS (P01112); a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:14500341 UniProtKB:P01112
GO:0005515 protein binding	IPI PMID:18816594 mrtl-A translation/localization regulatory protein encoded w...	KEEP AS NON CORE	Summary: Interaction with a partner (Q14899); a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18816594 UniProtKB:Q14899
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. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005634 nucleus cellular_component ECO:0000314 IDA PMID:17108144
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: file:human/RACK1/RACK1-goa.tsv GO:0001891 phagocytic cup cellular_component ECO:0000314 IDA PMID: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: file:human/RACK1/RACK1-goa.tsv GO:0001934 positive regulation of protein phosphorylation biological_process ECO:0000314 IDA PMID:11312657
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: file:human/RACK1/RACK1-goa.tsv GO:0001934 positive regulation of protein phosphorylation biological_process ECO:0000314 IDA PMID:17108144
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...	KEEP AS NON CORE	Summary: Interaction with SRC captured by IPI; a bare protein-binding annotation (informative aspect captured by tyrosine-kinase-inhibitor MF). Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:11279199 UniProtKB:P00523
GO:0005515 protein binding	IPI PMID:11312657 Rack1 binds HIV-1 Nef and can act as a Nef-protein kinase C ...	KEEP AS NON CORE	Summary: Interaction with HIV-1 Nef (P03404); a bare protein-binding annotation. Reason: Real (viral) interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:11312657 UniProtKB:P03404
GO:0005515 protein binding	IPI PMID:17108144 Receptor for activated C kinase 1 (RACK1) and Src regulate t...	KEEP AS NON CORE	Summary: Interaction with the androgen receptor (P10275); a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:17108144 UniProtKB:P10275
GO:0005515 protein binding	IPI PMID:19785988 RACK1 associates with CLEC-2 and promotes its ubiquitin-prot...	KEEP AS NON CORE	Summary: Interaction with CLEC1B/CLEC-2 (Q9P126) promoting its degradation; a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19785988 UniProtKB:Q9P126
GO:0005515 protein binding	IPI PMID:20541605 RACK1 promotes Bax oligomerization and dissociates the inter...	KEEP AS NON CORE	Summary: Interaction with BAX/BCL2L1 (Q07812/Q07817); bare protein-binding annotations (informative aspect captured by BH3-domain binding). Reason: Real interactions but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20541605 UniProtKB:Q07812
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-goa.tsv GO:0005634 nucleus cellular_component ECO:0000314 IDA PMID:10849009
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-goa.tsv GO:0005737 cytoplasm cellular_component ECO:0000314 IDA PMID:10849009
GO:0005737 cytoplasm	IDA PMID:19785988 RACK1 associates with CLEC-2 and promotes its ubiquitin-prot...	ACCEPT	Summary: Direct cytoplasmic localization. Reason: Core compartment. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005737 cytoplasm cellular_component ECO:0000314 IDA PMID:19785988
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. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0030971 receptor tyrosine kinase binding molecular_function ECO:0000314 IDA PMID:9584165
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: file:human/RACK1/RACK1-goa.tsv GO:0042169 SH2 domain binding molecular_function ECO:0000314 IDA PMID:11279199
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: file:human/RACK1/RACK1-goa.tsv GO:0042169 SH2 domain binding molecular_function ECO:0000314 IDA PMID:9584165
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: file:human/RACK1/RACK1-goa.tsv GO:0043065 positive regulation of apoptotic process biological_process ECO:0000314 IDA PMID:20541605
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: file:human/RACK1/RACK1-goa.tsv GO:0043547 positive regulation of GTPase activity biological_process ECO:0000314 IDA PMID:20499158
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-goa.tsv GO:0048471 perinuclear region of cytoplasm cellular_component ECO:0000314 IDA PMID:11279199
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. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0030496 midbody cellular_component ECO:0000314 IDA PMID:15166316
GO:0005515 protein binding	IPI PMID:18954305 Structural basis and specificity of human otubain 1-mediated...	KEEP AS NON CORE	Summary: Interaction with OTUB1 (Q96FW1); a bare protein-binding annotation. Reason: Real interaction but uninformative MF; not core. Supporting Evidence: file:human/RACK1/RACK1-goa.tsv GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18954305 UniProtKB:Q96FW1
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: file:human/RACK1/RACK1-goa.tsv GO:0019903 protein phosphatase binding molecular_function ECO:0000353 IPI PMID:11278757 UniProtKB:P28827
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: file:human/RACK1/RACK1-goa.tsv GO:0005102 signaling receptor binding molecular_function ECO:0000303 NAS PMID:12809483

Core Functions

Integral structural component of the small (40S) ribosomal subunit that binds the ribosome and contributes to translational control/repression.

Molecular Function:

ribosome binding

In Complex:

cytosolic small ribosomal subunit

Supporting Evidence:

file:human/RACK1/RACK1-uniprot.txt
Component of the 40S ribosomal subunit involved in translational repression
PMID:23636399
Structures of the human and Drosophila 80S ribosome

Ribosomal scaffold for ribosome-associated quality control of stalled/collided ribosomes, promoting regulatory ubiquitylation of a subset of 40S ribosomal proteins (with ZNF598) to resolve terminal stalls.

Molecular Function:

ribosome binding

Directly Involved In:

rescue of stalled cytosolic ribosome

In Complex:

cytosolic small ribosomal subunit

Supporting Evidence:

PMID:28132843
the 40S ribosomal protein RACK1 help to resolve poly(A)-induced stalled ribosomes
PMID:28132843
RACK1 regulates RPS2, RPS3, and RPS20 ubiquitylation

Signaling scaffold/molecular adaptor whose WD40 propeller assembles and regulates diverse signaling complexes, including binding/stabilizing activated protein kinase C and inhibiting Src-family tyrosine kinases.

Molecular Function:

molecular adaptor activity

Cellular Locations:

cytosol

Supporting Evidence:

file:human/RACK1/RACK1-uniprot.txt
Scaffolding protein involved in the recruitment, assembly and/or regulation of a variety of signaling molecules.
file:human/RACK1/RACK1-uniprot.txt
Inhibits the activity of SRC kinases including SRC, LCK and YES1.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms.

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity.

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB Subcellular Location vocabulary mapping.

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara.

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10849009

The PKC targeting protein RACK1 interacts with the Epstein-Barr virus activator protein BZLF1.

PMID:11046044

Receptor for activated C-kinase (RACK-1), a WD motif-containing protein, specifically associates with the human type I IFN receptor.

PMID:11278757

The PTPmu protein-tyrosine phosphatase binds and recruits the scaffolding protein RACK1 to cell-cell contacts.

PMID:11279199

The interaction of Src and RACK1 is enhanced by activation of protein kinase C and tyrosine phosphorylation of RACK1.

RACK1 directly binds the SH2 domain of SRC and binds protein kinase C; perinuclear cytoplasmic localization.

PMID:11312657

Rack1 binds HIV-1 Nef and can act as a Nef-protein kinase C adaptor.

PMID:12809483

ST7 is a novel low-density lipoprotein receptor-related protein (LRP) with a cytoplasmic tail that interacts with proteins related to signal transduction pathways.

PMID:12958311

The scaffolding protein RACK1 interacts with androgen receptor and promotes cross-talk through a protein kinase C signaling pathway.

PMID:14500341

Alternative splicing of the human proto-oncogene c-H-ras renders a new Ras family protein that trafficks to cytoplasm and nucleus.

PMID:15159402

Identification of interaction partners and substrates of the cyclin A1-CDK2 complex.

PMID:15166316

Dissection of the mammalian midbody proteome reveals conserved cytokinesis mechanisms.

PMID:17108144

Receptor for activated C kinase 1 (RACK1) and Src regulate the tyrosine phosphorylation and function of the androgen receptor.

PMID:17956333

Interaction of integrin beta1 with cytokeratin 1 in neuroblastoma NMB7 cells.

PMID:18057008

Cell surface levels of organellar Na+/H+ exchanger isoform 6 are regulated by interaction with RACK1.

PMID:18194455

Acetylcholinesterase-R increases germ cell apoptosis but enhances sperm motility.

PMID:18420585

RACK1 and CIS mediate the degradation of BimEL in cancer cells.

PMID:18816594

mrtl-A translation/localization regulatory protein encoded within the human c-myc locus and distributed throughout the endoplasmic and nucleoplasmic reticular network.

PMID:18954305

Structural basis and specificity of human otubain 1-mediated deubiquitination.

PMID:19056867

Large-scale proteomics and phosphoproteomics of urinary exosomes.

PMID:19451233

Stxbp4 regulates DeltaNp63 stability by suppression of RACK1-dependent degradation.

PMID:19674157

Receptor for activated C-kinase 1 regulates the cellular localization and function of ABCB4.

PMID:19767770

A novel pro-apoptotic function of RACK1: suppression of Src activity in the intrinsic and Akt pathways.

PMID:19785988

RACK1 associates with CLEC-2 and promotes its ubiquitin-proteasome degradation.

PMID:20010870

Copine-III interacts with ErbB2 and promotes tumor cell migration.

PMID:20080539

The Polycomb group protein EED couples TNF receptor 1 to neutral sphingomyelinase.

PMID:20103773

A crucial role for RACK1 in the regulation of glucose-stimulated IRE1alpha activation in pancreatic beta cells.

RACK1 acts as a signaling adaptor recruiting PP2A to inhibit the IRE1 kinase, negatively regulating the ER unfolded protein response.

PMID:20499158

RACK1 promotes breast carcinoma migration/metastasis via activation of the RhoA/Rho kinase pathway.

PMID:20541605

RACK1 promotes Bax oligomerization and dissociates the interaction of Bax and Bcl-XL.

RACK1 binds the BH3 domain of BAX, promotes BAX oligomerization and disrupts the BAX-Bcl-XL interaction to promote apoptosis.

PMID:20573744

A stimulatory role for the La-related protein 4B in translation.

PMID:20819076

Interaction with receptor for activated C-kinase 1 (RACK1) sensitizes the phosphodiesterase PDE4D5 towards hydrolysis of cAMP and activation by protein kinase C.

PMID:20871634

Regulation of receptor for activated C kinase 1 protein by the von Hippel-Lindau tumor suppressor in IGF-I-induced renal carcinoma cell invasiveness.

PMID:21098120

La-related protein 4 binds poly(A), interacts with the poly(A)-binding protein MLLE domain via a variant PAM2w motif, and can promote mRNA stability.

PMID:21146485

Identification of cyclophilin-40-interacting proteins reveals potential cellular function of cyclophilin-40.

PMID:21347310

The RACK1 signaling scaffold protein selectively interacts with Yersinia pseudotuberculosis virulence function.

PMID:21525958

The ribosomal protein RACK1 is required for microRNA function in both C. elegans and humans.

PMID:21750715

The inhibitor of growth protein 5 (ING5) depends on INCA1 as a co-factor for its antiproliferative effects.

PMID:21988832

Toward an understanding of the protein interaction network of the human liver.

PMID:22013210

The unfolded protein response: integrating stress signals through the stress sensor IRE1α.

PMID:22210188

Interaction of protein inhibitor of activated STAT 2 (PIAS2) with receptor of activated C kinase 1, RACK1.

PMID:22658674

Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.

PMID:22681889

The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.

PMID:23636399

Structures of the human and Drosophila 80S ribosome.

RACK1 is an integral component of the 40S ribosomal subunit in the human 80S ribosome structure.

PMID:23651062

RACK1 (receptor for activated C-kinase 1) interacts with FBW2 (F-box and WD-repeat domain-containing 2) to up-regulate GCM1 (glial cell missing 1) stability and placental cell migration and invasion.

PMID:23866081

Lyn, a Src family kinase, regulates activation of epidermal growth factor receptors in lung adenocarcinoma cells.

PMID:24006492

Endosomal acidification by Na+/H+ exchanger NHE5 regulates TrkA cell-surface targeting and NGF-induced PI3K signaling.

PMID:24947010

DJ-1 interacts with RACK1 and protects neurons from oxidative-stress-induced apoptosis.

PMID:25468996

E-cadherin interactome complexity and robustness resolved by quantitative proteomics.

PMID:25901680

Structure of the human 80S ribosome.

Cryo-EM structure of the human 80S ribosome including RACK1 as part of the cytosolic small (40S) ribosomal subunit.

PMID:25910212

Widespread macromolecular interaction perturbations in human genetic disorders.

PMID:28132843

ZNF598 and RACK1 Regulate Mammalian Ribosome-Associated Quality Control Function by Mediating Regulatory 40S Ribosomal Ubiquitylation.

The 40S ribosomal protein RACK1 and the ZNF598 ubiquitin ligase help resolve poly(A)-induced stalled ribosomes by mediating regulatory 40S ribosomal ubiquitylation; RACK1 regulates RPS2, RPS3 and RPS20 ubiquitylation.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:29743600

Trafficking, localization and degradation of the Na(+),HCO(3)(-) co-transporter NBCn1 in kidney and breast epithelial cells.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:32467643

Dual functions of Rack1 in regulating Hedgehog pathway.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

PMID:37712706

The matrix protein of respiratory syncytial virus suppresses interferon signaling via RACK1 association.

PMID:38190388

A novel Trichinella spiralis serine proteinase disrupted gut epithelial barrier and mediated larval invasion through binding to RACK1 and activating MAPK/ERK1/2 pathway.

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

PMID:9584165

RACK1, a receptor for activated C kinase and a homolog of the beta subunit of G proteins, inhibits activity of src tyrosine kinases and growth of NIH 3T3 cells.

RACK1 inhibits the activity of Src tyrosine kinases and inhibits growth of NIH 3T3 cells.

Reactome:R-HSA-5626962

RACK1 localized in cytosol (Reactome).

Reactome:R-HSA-5626981

RACK1 localized in cytosol (Reactome).

Reactome:R-HSA-5626982

RACK1 localized in cytosol (Reactome).

Suggested Experiments

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.

📚 Additional Documentation

Notes

(RACK1-notes.md)

RACK1 (GNB2L1 / P63244) review notes

Identity / core

RACK1 = "Receptor for Activated C Kinase 1"; a seven-bladed WD40 beta-propeller protein.
It is now classified as an integral component of the small (40S) ribosomal subunit
("Small ribosomal subunit protein RACK1", RACK1/RPS27A-family naming per Ban et al. 2014
nomenclature, PMID:24524803). It sits on the head of the 40S near the mRNA exit channel.

UniProt FUNCTION: "Component of the 40S ribosomal subunit involved in translational
repression (PubMed:23636399). Involved in the initiation of the ribosome quality control
(RQC), a pathway that takes place when a ribosome has stalled during translation, by
promoting ubiquitination of a subset of 40S ribosomal subunits (PubMed:28132843)."
[file:human/RACK1/RACK1-uniprot.txt]

Ribosome / RQC core function (best-supported, the curation focus)

Structural: integral 40S component, seen in 80S cryo-EM [PMID:23636399 "Structures of the
human and Drosophila 80S ribosome"; PMID:25901680 "Structure of the human 80S ribosome"].
RQC: RACK1 is required to resolve poly(A)-induced stalled ribosomes by regulating 40S
ribosomal ubiquitylation [PMID:28132843 "the 40S ribosomal protein RACK1 help to resolve
poly(A)-induced stalled ribosomes"; "RACK1 regulates RPS2, RPS3, and RPS20 ubiquitylation"].
Loss of RACK1 (or ZNF598) causes defective resolution of stalled ribosomes and readthrough
of poly(A) stall sequences. RACK1 thus acts upstream/alongside the ZNF598 E3 ligase as the
ribosomal scaffold for collision-sensing and regulatory 40S ubiquitylation.
IBA transfers from yeast Asc1: rescue of stalled cytosolic ribosome (GO:0072344), negative
regulation of translational frameshifting (GO:2001125), ribosome binding (GO:0043022),
negative regulation of translation (GO:0017148). These are well supported by the yeast Asc1
literature and human RQC work => core/QC.

Moonlighting / signaling roles (well-documented but many are scaffold-context-specific)

RACK1 is a classic signaling scaffold. UniProt lists dozens of partners. These reflect a
genuine adaptor/scaffold activity but most individual BP annotations are context-specific
(single-study, single pathway). Per batch curation rules I keep the genuine scaffold MF
(molecular adaptor / PKC binding) but mark individual pathway BP transfers as non-core or
over-annotation when supported only by a single moonlighting study, and demote the dozens of
bare "protein binding" (GO:0005515) IPI interactome hits to non-core (they record real
interactions but are uninformative as MF).

Notable: binds/stabilizes active PKC (GO:0005080 protein kinase C binding, IDA PMID:11279199);
inhibits SRC-family kinases (GO:0030292 protein tyrosine kinase inhibitor activity IDA
PMID:9584165); promotes HIF1A and CLEC1B ubiquitin-dependent degradation; scaffold for many
GPCR/channel trafficking events. These are bona fide but peripheral to the ribosomal core.

Localization

Overwhelmingly cytoplasmic/ribosome-associated (cytosol, 40S subunit). Reported nuclear,
plasma membrane, perinuclear, dendrite, mitochondrion, exosome localizations are context- or
moonlighting-specific; cytosol/small ribosomal subunit are the core compartments. Mitochondrion
(IMP PMID:19767770) and extracellular exosome (HDA) are over-annotations relative to core.

Curation decisions summary

Core MF: structural constituent of ribosome (40S) + ribosome binding; RQC scaffold.
Core BP: rescue of stalled cytosolic ribosome (RQC); cytoplasmic translation / translational
repression kept non-core (broad).
Signaling scaffold MF (molecular adaptor activity, PKC binding) kept but non-core.
Bare protein binding IPI (interactome): KEEP_AS_NON_CORE (real interactions, uninformative MF).
Single-study moonlighting BP/CC: KEEP_AS_NON_CORE or MARK_AS_OVER_ANNOTATED.

Pn Notes

(RACK1-pn-notes.md)

RACK1 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: P63244
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-07c
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/RACK1/RACK1-ai-review.yaml
AIGR review HTML: present - genes/human/RACK1/RACK1-ai-review.html
Gene notes: present - genes/human/RACK1/RACK1-notes.md
GOA TSV: present - genes/human/RACK1/RACK1-goa.tsv
UniProt record: present - genes/human/RACK1/RACK1-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/RACK1.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/RACK1.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

Description: 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.
Existing/core annotation action counts: ACCEPT: 25; KEEP_AS_NON_CORE: 110; MARK_AS_OVER_ANNOTATED: 4

PN Consistency Summary

Consistency: Partial. Review/notes and PN agree strongly on the 40S structural + RQC scaffold core (integral 40S protein, collision sensing, ZNF598-dependent RPS2/3/20 ubiquitylation, GO:0072344, GO:0016567, GO:0043022). Two PN rows are absent from the review/notes: (a) ribosome biogenesis / pre-40S placement, and (b) the ATG5/autophagy regulator role (PN Notes cite the RACK1-ATG5 paper). GOA confirms NO biogenesis, pre-40S, GO:0042254, GO:0030688, GO:0016236 or ATG terms. So PN asserts two roles the review neither covers nor refutes.
PN story / NEW pressure: GO:0042254 ribosome biogenesis and GO:0030688 preribosome SSU precursor (both verified real) are genuinely new and NOT in review/GOA. RACK1 is incorporated late into pre-40S particles, so a biogenesis/pre-40S association is biologically plausible — but the review's stance is that RACK1's ribosomal role is structural/translational/RQC, not assembly. This is a candidate ADD that needs literature support before projection (the review did not assess it). GO:0072344 already captured (IMP+IBA). GO:0006515 broader/redundant with GO:0072344.
Evidence alignment: PN row3 cites the RACK1-ATG5 autophagy paper (title only, no PMID); this paper is absent from the review references entirely. PN biogenesis rows cite nothing. Review RQC evidence (PMID:28132843, 23636399, 25901680) does not overlap PN's cited material. Divergence: autophagy + biogenesis literature uncited in review.
Verdict: Core RQC/40S consistent; PN biogenesis (GO:0042254/GO:0030688) and ATG5-autophagy stories are NOT in the review — candidate ADDs requiring verification, currently over-reaching as auto-projections.

Full Consistency Review

UniProt: P63244 · batch: proteostasis-batch-2026-06-07c · review status: COMPLETE (very large, ~80 annotations; core = 40S/RQC scaffold)
PN placement: 3 rows — Translation|Cytosolic translation|Ribosome biogenesis factor|pre-40S complex; …|Ribosome-associated QC|Ribosomal rescue; Autophagy-Lysosome Pathway|…|Modulation of ATG5-ATG12-ATG16 complex activity. PN-node mapping: biogenesis-group→mapped GO:0042254 ribosome biogenesis (new_to_goa); pre-40S-type→mapped GO:0030688 preribosome SSU precursor (new_to_goa); rescue-type→GO:0072344 (already_in_goa); RQC-group→GO:0006515 (new); ALP leaf/group no_mapping. Projected: GO:0042254, GO:0030688, GO:0006515 (all new), GO:0072344 (in GOA).
Consistency: Partial. Review/notes and PN agree strongly on the 40S structural + RQC scaffold core (integral 40S protein, collision sensing, ZNF598-dependent RPS2/3/20 ubiquitylation, GO:0072344, GO:0016567, GO:0043022). Two PN rows are absent from the review/notes: (a) ribosome biogenesis / pre-40S placement, and (b) the ATG5/autophagy regulator role (PN Notes cite the RACK1-ATG5 paper). GOA confirms NO biogenesis, pre-40S, GO:0042254, GO:0030688, GO:0016236 or ATG terms. So PN asserts two roles the review neither covers nor refutes.
PN story / NEW pressure: GO:0042254 ribosome biogenesis and GO:0030688 preribosome SSU precursor (both verified real) are genuinely new and NOT in review/GOA. RACK1 is incorporated late into pre-40S particles, so a biogenesis/pre-40S association is biologically plausible — but the review's stance is that RACK1's ribosomal role is structural/translational/RQC, not assembly. This is a candidate ADD that needs literature support before projection (the review did not assess it). GO:0072344 already captured (IMP+IBA). GO:0006515 broader/redundant with GO:0072344.
Mapping strategy: RACK1 is a ribosomal scaffold/collision sensor, not a biogenesis factor by the review's framing; projecting GO:0042254/GO:0030688 from the pre-40S node risks the TRAPP-like/biogenesis over-propagation the dossier itself warns about. Recommend these stay gene-curated, not auto-projected, until verified. RQC-group→GO:0006515 broader than the exact GO:0072344 already present.
Evidence alignment: PN row3 cites the RACK1-ATG5 autophagy paper (title only, no PMID); this paper is absent from the review references entirely. PN biogenesis rows cite nothing. Review RQC evidence (PMID:28132843, 23636399, 25901680) does not overlap PN's cited material. Divergence: autophagy + biogenesis literature uncited in review.
Verdict: Core RQC/40S consistent; PN biogenesis (GO:0042254/GO:0030688) and ATG5-autophagy stories are NOT in the review — candidate ADDs requiring verification, currently over-reaching as auto-projections.
Recommended edits: [YAML] Consider adding a note/annotation on the RACK1-ATG5 autophagy-regulator role (PN-cited) and the pre-40S/biogenesis association if literature supports — both are absent from the current review. [MAP] Do NOT auto-project GO:0042254/GO:0030688 to RACK1 from the biogenesis/pre-40S node without gene-level evidence (RACK1 framed as structural/RQC scaffold, not an assembly factor); GO:0006515 broader than the exact GO:0072344 already present. [REF] RACK1-ATG5 paper (resolve to a PMID) missing from review references.

PN Dossier Context

review_batch: proteostasis-batch-2026-06-07c
review_yaml: genes/human/RACK1/RACK1-ai-review.yaml
PN workbook rows: 3

PN row 1: Translation | Cytosolic translation | Ribosome biogenesis factor | pre-40S complex

UniProt: P63244
In branches: TR, ALP
PN-node mapping records (path + ancestors):
- [type] Translation|Cytosolic translation|Ribosome biogenesis factor|pre-40S complex
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0030688 preribosome, small subunit precursor]
  rationale: This PN type denotes pre-40S particles. The GO preribosome small-subunit precursor term is the direct complex target.
- [group] Translation|Cytosolic translation|Ribosome biogenesis factor
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0042254 ribosome biogenesis]
  rationale: This PN group collects factors assigned through cytosolic ribosome biogenesis, including SSU-processosome and pre-60S maturation machinery. The full PN path resolves the earlier over-annotation problem: these genes are not being placed by core translational elongation or decoding, but by assembly and maturation of ribosomal subunits. GO ribosome biogenesis is therefore the appropriate propagation target.
- [class] Translation|Cytosolic translation
  status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
  rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
- [branch] Translation
  status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
  rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.

PN row 2: Translation | Cytosolic translation | Ribosome-associated QC | Ribosomal rescue

UniProt: P63244
In branches: TR, ALP
PN-node mapping records (path + ancestors):
- [type] Translation|Cytosolic translation|Ribosome-associated QC|Ribosomal rescue
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0072344 rescue of stalled cytosolic ribosome]
  rationale: This PN RQC type denotes rescue of stalled cytosolic ribosomes. The matching GO process term is the direct target.
- [group] Translation|Cytosolic translation|Ribosome-associated QC
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0006515 protein quality control for misfolded or incompletely synthesized proteins]
  rationale: The PN ribosome-associated quality-control group covers surveillance and disposal of stalled or defective nascent-chain translation products. GO lacks a dedicated ribosome-associated QC term in the local cache, so the broader protein-quality-control process is the best supported target.
- [class] Translation|Cytosolic translation
  status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
  rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
- [branch] Translation
  status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
  rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.

PN row 3: Autophagy-Lysosome Pathway | Autophagophore initiation and elongation | ATG8 homolog processing, upstream | Preparation of ATG8 homologs for lipidation | Modulation of ATG5-ATG12-ATG16 complex activity

UniProt: P63244
In branches: TR, ALP
Notes: RACK1 interacts with ATG5. Importantly, classical autophagy inducers (starvation or mammalian target of rapamycin blockage) stimulated RACK1-ATG5 interaction. Knockdown of RACK1 or prevention of its binding to ATG5 using mutagenesis blocked autophagy activation. RACK1 may recruit other proteins to the phagophore membrane.
PN references (titles):
- RACK1 Is an Interaction Partner of ATG5 and a Novel Regulator of Autophagy - ScienceDirect
PN-node mapping records (path + ancestors):
- [subtype] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|ATG8 homolog processing, upstream|Preparation of ATG8 homologs for lipidation|Modulation of ATG5-ATG12-ATG16 complex activity
  status=no_mapping scope= GO=[]
  rationale: This PN leaf is a regulator bucket rather than a shared gene function or shared process participation class. The current gene set is too heterogeneous for a single defensible GO target.
- [type] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|ATG8 homolog processing, upstream|Preparation of ATG8 homologs for lipidation
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a contextual PN role. The label is useful for curator triage, but by itself does not support a universal GO assertion for all member genes beyond curated ancestor or child mappings.
- [group] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|ATG8 homolog processing, upstream
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation
  status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
  rationale: This class is a real macroautophagy context, but its descendants include core factors, component buckets, upstream modulators, localization roles, and residual categories. Projecting generic macroautophagy from this ancestor creates TRAPP-like overpropagation, so candidate GO annotations must come from narrower curated nodes.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (4)

GO:0042254 ribosome biogenesis | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Translation|Cytosolic translation|Ribosome biogenesis factor
GO:0030688 preribosome, small subunit precursor | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Translation|Cytosolic translation|Ribosome biogenesis factor|pre-40S complex
GO:0006515 protein quality control for misfolded or incompletely synthesized proteins | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Translation|Cytosolic translation|Ribosome-associated QC
GO:0072344 rescue of stalled cytosolic ribosome | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Translation|Cytosolic translation|Ribosome-associated QC|Ribosomal rescue

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: P63244
gene_symbol: RACK1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
existing_annotations:
- term:
    id: GO:0005080
    label: protein kinase C binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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).
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Binds to and stabilizes activated protein kinase C (PKC), increasing PKC-mediated phosphorylation.
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:28132843
      supporting_text: the 40S ribosomal protein RACK1 help to resolve poly(A)-induced stalled ribosomes
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: RACK1 binds the ribosome; as an integral 40S component this is well supported structurally and functionally.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Component of the 40S ribosomal subunit involved in translational repression
- term:
    id: GO:2001125
    label: negative regulation of translational frameshifting
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic transfer from yeast Asc1, which suppresses translational frameshifting/readthrough at stalls; consistent with RACK1's role in preventing readthrough of stall sequences.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:28132843
      supporting_text: subsequent readthrough of poly(A)-containing stall sequences
- term:
    id: GO:0001891
    label: phagocytic cup
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Localization to phagocytic cups reported during Yersinia infection; a specialized infection context rather than a core compartment.
    action: KEEP_AS_NON_CORE
    reason: Supported by IDA in an infection setting (PMID:21347310) but peripheral to the core cytosolic/ribosomal localization.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Cell projection, phagocytic cup
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: A nuclear pool of RACK1 is reported in some contexts (e.g. with HIF1A/AR signaling), but the predominant localization is cytosolic/ribosomal.
    action: KEEP_AS_NON_CORE
    reason: Context-dependent nuclear localization is documented (IDA PMID:10849009, PMID:17108144) but is non-core relative to the cytosolic ribosomal pool.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Nucleus {ECO:0000269|PubMed:10849009}
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Cytoplasmic localization, consistent with RACK1's predominant cytosolic/ribosome-associated pool.
    action: ACCEPT
    reason: Core compartment; corroborated by extensive experimental evidence (multiple EXP/IDA annotations) and UniProt.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cell membrane'
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: RACK1 is recruited to the plasma membrane as a peripheral membrane protein in some signaling/trafficking contexts.
    action: KEEP_AS_NON_CORE
    reason: Documented peripheral membrane localization (e.g. via KRT1/ITGB1, PMID:17956333) but secondary to the cytosolic ribosomal pool.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Cell membrane {ECO:0000269|PubMed:11312657
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Dendritic/neuronal-projection localization inferred from the mouse ortholog; reflects neuronal expression, not a core compartment.
    action: KEEP_AS_NON_CORE
    reason: Based on ISS/By similarity to mouse P68040; plausible in neurons but peripheral to the core role.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Cell projection, dendrite
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based electronic annotation of ribosome binding, redundant with and consistent with the experimentally supported ribosome-binding annotations.
    action: ACCEPT
    reason: Correct core molecular function for an integral 40S protein; agrees with IDA/IBA ribosome-binding evidence.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Component of the 40S ribosomal subunit involved in translational repression
- term:
    id: GO:0043204
    label: perikaryon
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Perikaryon localization inferred from the mouse ortholog; a neuronal-expression context.
    action: KEEP_AS_NON_CORE
    reason: By similarity to mouse P68040; non-core neuronal localization.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Perikaryon {ECO:0000250|UniProtKB:P68040}
- term:
    id: GO:0045182
    label: translation regulator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based annotation that RACK1 has translation-regulator activity, consistent with its role in translational repression/control on the 40S subunit.
    action: KEEP_AS_NON_CORE
    reason: Broad but accurate MF; the more specific core functions are ribosome binding and the structural/RQC roles.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Component of the 40S ribosomal subunit involved in translational repression
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Perinuclear localization that shifts to the cell periphery upon PKC activation; a signaling-context distribution within the cytoplasm.
    action: KEEP_AS_NON_CORE
    reason: Documented (IDA PMID:11279199) but a sub-cytoplasmic distribution peripheral to core function.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Cytoplasm, perinuclear region
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10849009
  qualifier: enables
  review:
    summary: Interaction with Epstein-Barr virus BZLF1 captured by IntAct; a real but uninformative bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Records a genuine (viral) interaction but "protein binding" is uninformative as a molecular function; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:10849009 UniProtKB:P03206
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11046044
  qualifier: enables
  review:
    summary: IntAct interaction with IFNAR2 (P48551); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:11046044 UniProtKB:P48551
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12809483
  qualifier: enables
  review:
    summary: IntAct interaction with LRP12 (Q9Y561); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:12809483 UniProtKB:Q9Y561
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18194455
  qualifier: enables
  review:
    summary: IntAct interaction with ACHE (P22303); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18194455 UniProtKB:P22303
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18420585
  qualifier: enables
  review:
    summary: IntAct interactions (BCL2L11, DYNLL1 and ortholog) captured in a single screen; bare protein-binding annotations.
    action: KEEP_AS_NON_CORE
    reason: Real interactions but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18420585 UniProtKB:O43521
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20080539
  qualifier: enables
  review:
    summary: IntAct interaction with EED (O75530); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20080539 UniProtKB:O75530
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20871634
  qualifier: enables
  review:
    summary: IntAct interaction with VHL (P40337); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20871634 UniProtKB:P40337
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21146485
  qualifier: enables
  review:
    summary: IntAct interaction with PPID (Q08752); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:21146485 UniProtKB:Q08752
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21525958
  qualifier: enables
  review:
    summary: IntAct interaction with AGO2 (Q9UKV8); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction (RACK1 associates with the miRNA machinery) but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:21525958 UniProtKB:Q9UKV8
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21750715
  qualifier: enables
  review:
    summary: IntAct interaction with INCA1 (Q0VD86); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:21750715 UniProtKB:Q0VD86
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21988832
  qualifier: enables
  review:
    summary: Liver interactome interaction with LARP4B (Q92615); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction (RACK1 binds LARP4/LARP4B translation factors) but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:21988832 UniProtKB:Q92615
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22210188
  qualifier: enables
  review:
    summary: IntAct interaction with PIAS2 (O75928); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:22210188 UniProtKB:O75928
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23651062
  qualifier: enables
  review:
    summary: IntAct interaction with FBXW2 (Q9UKT8); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:23651062 UniProtKB:Q9UKT8
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23866081
  qualifier: enables
  review:
    summary: IntAct interactions with LYN (P07948) and PAG1 (Q9NWQ8); bare protein-binding annotations.
    action: KEEP_AS_NON_CORE
    reason: Real interactions but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:23866081 UniProtKB:P07948
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24947010
  qualifier: enables
  review:
    summary: IntAct interaction with PARK7/DJ-1 (Q99497); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction (DJ-1 binds RACK1 in oxidative-stress protection) but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:24947010 UniProtKB:Q99497
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25910212
  qualifier: enables
  review:
    summary: IntAct interaction with ACTN2 (P35609); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25910212 UniProtKB:P35609
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: IntAct interactions with HELZ (P42694) and LARP4B (Q92615); bare protein-binding annotations.
    action: KEEP_AS_NON_CORE
    reason: Real interactions but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:28514442 UniProtKB:P42694
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Large IntAct interactome study capturing many RACK1 partners (USP10, CNOT2, CRMP1, etc.); bare protein-binding annotations.
    action: KEEP_AS_NON_CORE
    reason: Real high-throughput interactions but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:Q14694
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex interactome capturing HELZ/LARP4B interactions; bare protein-binding annotations.
    action: KEEP_AS_NON_CORE
    reason: Real interactions but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:P42694
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: IntAct interactome capturing HELZ, BYSL, USP10, LARP4B; bare protein-binding annotations.
    action: KEEP_AS_NON_CORE
    reason: Real interactions but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:35271311 UniProtKB:P42694
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:38190388
  qualifier: enables
  review:
    summary: IntAct interaction with a partner (O96871); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:38190388 UniProtKB:O96871
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Multimodal cell-maps interactome capturing HELZ/LARP4B; bare protein-binding annotations.
    action: KEEP_AS_NON_CORE
    reason: Real interactions but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:40205054 UniProtKB:P42694
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:24947010
  qualifier: enables
  review:
    summary: RACK1 self-associates to form homodimers/homooligomers via its WD40 propeller.
    action: KEEP_AS_NON_CORE
    reason: Self-association is documented (PMID:15140893, PMID:20529362) and regulates ribosome binding, but is a structural property rather than the core function.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Monomer; also forms homodimers and homooligomers
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: Self-association captured in an interactome study; same homodimerization property as above.
    action: KEEP_AS_NON_CORE
    reason: Documented homodimerization; structural rather than core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Monomer; also forms homodimers and homooligomers
- term:
    id: GO:0008200
    label: ion channel inhibitor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Inferred from the mouse ortholog; reflects RACK1 inhibition of channels such as TRPM6/PKD2L1 via scaffolding, not an intrinsic channel-blocking activity.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Inhibits TRPM6 channel activity.
- term:
    id: GO:0015935
    label: small ribosomal subunit
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: part_of
  review:
    summary: RACK1 is part of the small (40S) ribosomal subunit.
    action: ACCEPT
    reason: Core cellular component; RACK1 is an integral 40S component (cryo-EM PMID:23636399).
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Component of the small (40S) ribosomal subunit
- term:
    id: GO:0043005
    label: neuron projection
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Neuronal-projection localization inferred from the mouse ortholog.
    action: KEEP_AS_NON_CORE
    reason: Neuronal-expression context; non-core compartment.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Cell projection, dendrite
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Neuronal cell body localization inferred from the mouse ortholog.
    action: KEEP_AS_NON_CORE
    reason: Neuronal-expression context; non-core compartment.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Perikaryon {ECO:0000250|UniProtKB:P68040}
- term:
    id: GO:0044297
    label: cell body
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Cell body localization inferred from the mouse ortholog.
    action: KEEP_AS_NON_CORE
    reason: Neuronal-expression context; non-core compartment.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Perikaryon {ECO:0000250|UniProtKB:P68040}
- term:
    id: GO:1903751
    label: negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Anti-apoptotic role under oxidative stress, inferred from the mouse ortholog and supported by the DJ-1/RACK1 IGI annotation.
    action: KEEP_AS_NON_CORE
    reason: A specific stress-signaling moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide
- term:
    id: GO:0002181
    label: cytoplasmic translation
  evidence_type: NAS
  original_reference_id: PMID:25901680
  qualifier: involved_in
  review:
    summary: As a 40S ribosomal protein RACK1 participates in cytoplasmic translation; a broad process term.
    action: KEEP_AS_NON_CORE
    reason: True but broad; RACK1's specific contributions are translational repression and RQC. Kept non-core per the broad-translation guideline.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Component of the 40S ribosomal subunit involved in translational repression
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: NAS
  original_reference_id: PMID:25901680
  qualifier: located_in
  review:
    summary: Cytoplasmic localization (ComplexPortal/ribosome curation).
    action: ACCEPT
    reason: Core compartment.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Component of the 40S ribosomal subunit involved in translational repression
- term:
    id: GO:0022627
    label: cytosolic small ribosomal subunit
  evidence_type: NAS
  original_reference_id: PMID:25901680
  qualifier: part_of
  review:
    summary: RACK1 is part of the cytosolic small ribosomal subunit (human 80S cryo-EM structure).
    action: ACCEPT
    reason: Core cellular component; precise and well supported.
    supported_by:
    - reference_id: PMID:25901680
      supporting_text: Structure of the human 80S ribosome
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence nucleoplasm signal; a minor pool relative to the dominant cytosolic localization.
    action: KEEP_AS_NON_CORE
    reason: Context-dependent nuclear pool; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005654 nucleoplasm cellular_component ECO:0000314 IDA GO_REF:0000052
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence cytosol signal, the dominant localization.
    action: ACCEPT
    reason: Core compartment, directly observed.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000314 IDA GO_REF:0000052
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:11279199
  qualifier: located_in
  review:
    summary: Experimental cytoplasmic localization.
    action: ACCEPT
    reason: Core compartment, direct experimental evidence.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component ECO:0000269 EXP PMID:11279199
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:12958311
  qualifier: located_in
  review:
    summary: Experimental cytoplasmic localization.
    action: ACCEPT
    reason: Core compartment, direct experimental evidence.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component ECO:0000269 EXP PMID:12958311
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:20499158
  qualifier: located_in
  review:
    summary: Experimental cytoplasmic localization.
    action: ACCEPT
    reason: Core compartment, direct experimental evidence.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component ECO:0000269 EXP PMID:20499158
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:20573744
  qualifier: located_in
  review:
    summary: Experimental cytoplasmic localization.
    action: ACCEPT
    reason: Core compartment, direct experimental evidence.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component ECO:0000269 EXP PMID:20573744
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:23636399
  qualifier: located_in
  review:
    summary: Cytoplasmic localization consistent with ribosome-associated pool (80S cryo-EM study).
    action: ACCEPT
    reason: Core compartment.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component ECO:0000269 EXP PMID:23636399
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:37712706
  qualifier: located_in
  review:
    summary: Experimental cytoplasmic localization (RSV matrix protein study).
    action: ACCEPT
    reason: Core compartment.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component ECO:0000269 EXP PMID:37712706
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: EXP
  original_reference_id: PMID:11312657
  qualifier: located_in
  review:
    summary: Plasma membrane localization in a signaling context (HIV-1 Nef/PKC adaptor).
    action: KEEP_AS_NON_CORE
    reason: Peripheral membrane localization in a specific context; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005886 plasma membrane cellular_component ECO:0000269 EXP PMID:11312657
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: EXP
  original_reference_id: PMID:17956333
  qualifier: located_in
  review:
    summary: Plasma membrane recruitment via KRT1/ITGB1.
    action: KEEP_AS_NON_CORE
    reason: Context-specific peripheral membrane localization; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005886 plasma membrane cellular_component ECO:0000269 EXP PMID:17956333
- term:
    id: GO:0043204
    label: perikaryon
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Perikaryon localization by similarity to mouse ortholog.
    action: KEEP_AS_NON_CORE
    reason: Neuronal-expression context; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Perikaryon {ECO:0000250|UniProtKB:P68040}
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5626962
  qualifier: located_in
  review:
    summary: Reactome cytosol localization.
    action: ACCEPT
    reason: Core compartment.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-5626962
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5626981
  qualifier: located_in
  review:
    summary: Reactome cytosol localization.
    action: ACCEPT
    reason: Core compartment.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-5626981
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5626982
  qualifier: located_in
  review:
    summary: Reactome cytosol localization.
    action: ACCEPT
    reason: Core compartment.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-5626982
- term:
    id: GO:0030291
    label: protein serine/threonine kinase inhibitor activity
  evidence_type: IMP
  original_reference_id: PMID:20103773
  qualifier: enables
  review:
    summary: RACK1 inhibits the IRE1 kinase within an IRE1-RACK1-PP2A complex, attenuating the ER unfolded protein response.
    action: KEEP_AS_NON_CORE
    reason: A specific signaling-scaffold/inhibitory role (recruits PP2A to dephosphorylate IRE1); genuine but non-core moonlighting.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0030291 protein serine/threonine kinase inhibitor activity molecular_function ECO:0000315 IMP PMID:20103773
- term:
    id: GO:0008047
    label: enzyme activator activity
  evidence_type: IDA
  original_reference_id: PMID:20819076
  qualifier: enables
  review:
    summary: RACK1 acts as an activator/adaptor in a GPCR/adenylate-cyclase signaling context.
    action: KEEP_AS_NON_CORE
    reason: Reflects scaffold/adaptor activity in a specific pathway; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0008047 enzyme activator activity molecular_function ECO:0000314 IDA PMID:20819076
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IPI
  original_reference_id: PMID:20819076
  qualifier: enables
  review:
    summary: Enzyme binding (Q08499/PDE4D) captured by IPI; relatively uninformative MF.
    action: KEEP_AS_NON_CORE
    reason: Records a real enzyme interaction but is a generic MF; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0019899 enzyme binding molecular_function ECO:0000353 IPI PMID:20819076 UniProtKB:Q08499
- term:
    id: GO:0106070
    label: regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:20819076
  qualifier: involved_in
  review:
    summary: RACK1 regulates a GPCR/adenylate-cyclase signaling pathway.
    action: KEEP_AS_NON_CORE
    reason: A specific signaling moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway
- term:
    id: GO:1903751
    label: negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide
  evidence_type: IGI
  original_reference_id: PMID:24947010
  qualifier: involved_in
  review:
    summary: Genetic interaction with DJ-1/PARK7 protecting neurons from oxidative-stress-induced apoptosis.
    action: KEEP_AS_NON_CORE
    reason: A specific oxidative-stress moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IPI
  original_reference_id: PMID:24947010
  qualifier: enables
  review:
    summary: RACK1 self-association (homodimerization).
    action: KEEP_AS_NON_CORE
    reason: Structural self-association property; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Monomer; also forms homodimers and homooligomers
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18057008
  qualifier: enables
  review:
    summary: Interaction with SLC9A6 regulating its distribution; a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18057008 UniProtKB:Q8IVB4
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24006492
  qualifier: enables
  review:
    summary: Interaction with SLC9A5/NHE5 regulating its trafficking; a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:24006492 UniProtKB:Q14940
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29743600
  qualifier: enables
  review:
    summary: Interaction with SLC4A7/NBCn1; a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:29743600 UniProtKB:Q9R1N3-2
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:29743600
  qualifier: located_in
  review:
    summary: Direct cytoplasmic localization.
    action: ACCEPT
    reason: Core compartment.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component ECO:0000314 IDA PMID:29743600
- term:
    id: GO:0045879
    label: negative regulation of smoothened signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:32467643
  qualifier: involved_in
  review:
    summary: RACK1 negatively regulates Hedgehog/Smoothened signaling (FlyBase-curated).
    action: KEEP_AS_NON_CORE
    reason: A specific developmental-signaling moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0045879 negative regulation of smoothened signaling pathway biological_process ECO:0000314 IDA PMID:32467643
- term:
    id: GO:0031334
    label: positive regulation of protein-containing complex assembly
  evidence_type: IDA
  original_reference_id: PMID:20541605
  qualifier: involved_in
  review:
    summary: RACK1 promotes BAX oligomerization (a pro-apoptotic complex-assembly event).
    action: KEEP_AS_NON_CORE
    reason: A specific apoptosis-scaffolding moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Promotes apoptosis by increasing oligomerization of BAX
- term:
    id: GO:0032091
    label: negative regulation of protein binding
  evidence_type: IDA
  original_reference_id: PMID:20541605
  qualifier: involved_in
  review:
    summary: RACK1 disrupts the BAX-BCL2L1 (Bcl-XL) interaction, promoting apoptosis.
    action: KEEP_AS_NON_CORE
    reason: A specific apoptosis-related moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: disrupting the interaction of BAX with the anti-apoptotic factor BCL2L
- term:
    id: GO:0051434
    label: BH3 domain binding
  evidence_type: IDA
  original_reference_id: PMID:20541605
  qualifier: enables
  review:
    summary: RACK1 binds the BH3 domain of BAX, mediating its pro-apoptotic oligomerization.
    action: KEEP_AS_NON_CORE
    reason: A specific, informative interaction MF in apoptosis; genuine but non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0051434 BH3 domain binding molecular_function ECO:0000314 IDA PMID:20541605
- term:
    id: GO:0045296
    label: cadherin binding
  evidence_type: HDA
  original_reference_id: PMID:25468996
  qualifier: enables
  review:
    summary: High-throughput proteomics placing RACK1 in the E-cadherin interactome.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interaction; non-core MF.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0045296 cadherin binding molecular_function ECO:0007005 HDA PMID:25468996
- term:
    id: GO:0030332
    label: cyclin binding
  evidence_type: IPI
  original_reference_id: PMID:15159402
  qualifier: enables
  review:
    summary: Interaction with a cyclin (P78396); a specific interaction MF.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction relevant to cell-cycle moonlighting; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0030332 cyclin binding molecular_function ECO:0000353 IPI PMID:15159402 UniProtKB:P78396
- term:
    id: GO:0016567
    label: protein ubiquitination
  evidence_type: IMP
  original_reference_id: PMID:28132843
  qualifier: involved_in
  review:
    summary: RACK1 promotes regulatory ubiquitination of a subset of 40S ribosomal proteins (RPS2, RPS3, RPS20) during RQC.
    action: ACCEPT
    reason: Core RQC function. RACK1 regulates 40S ubiquitylation that initiates ribosome quality control.
    supported_by:
    - reference_id: PMID:28132843
      supporting_text: RACK1 regulates RPS2, RPS3, and RPS20 ubiquitylation
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IDA
  original_reference_id: PMID:28132843
  qualifier: enables
  review:
    summary: Direct demonstration of RACK1 ribosome binding in the RQC study.
    action: ACCEPT
    reason: Core MF; RACK1 is ribosome-bound and acts on stalled ribosomes.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0043022 ribosome binding molecular_function ECO:0000314 IDA PMID:28132843
- term:
    id: GO:0072344
    label: rescue of stalled cytosolic ribosome
  evidence_type: IMP
  original_reference_id: PMID:28132843
  qualifier: involved_in
  review:
    summary: Loss-of-function shows RACK1 is required to resolve poly(A)-induced stalled ribosomes (RQC).
    action: ACCEPT
    reason: Core function, directly demonstrated by IMP.
    supported_by:
    - reference_id: PMID:28132843
      supporting_text: the 40S ribosomal protein RACK1 help to resolve poly(A)-induced stalled ribosomes
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21098120
  qualifier: enables
  review:
    summary: Interaction with LARP4 (Q71RC2); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction (translation-associated) but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:21098120 UniProtKB:Q71RC2
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20010870
  qualifier: enables
  review:
    summary: Interaction with CPNE3 (O75131); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20010870 UniProtKB:O75131
- term:
    id: GO:0071363
    label: cellular response to growth factor stimulus
  evidence_type: IDA
  original_reference_id: PMID:20010870
  qualifier: involved_in
  review:
    summary: RACK1/CPNE3 role downstream of ErbB2 growth-factor signaling in migration.
    action: KEEP_AS_NON_CORE
    reason: A specific growth-factor-signaling moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0071363 cellular response to growth factor stimulus biological_process ECO:0000314 IDA PMID:20010870
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19674157
  qualifier: enables
  review:
    summary: Interaction with ABCB4 (P21439) regulating its localization; a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19674157 UniProtKB:P21439
- term:
    id: GO:0042998
    label: positive regulation of Golgi to plasma membrane protein transport
  evidence_type: IMP
  original_reference_id: PMID:19674157
  qualifier: involved_in
  review:
    summary: RACK1 promotes transport of ABCB4 from Golgi to the apical membrane.
    action: KEEP_AS_NON_CORE
    reason: A specific trafficking moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Involved in the transport of ABCB4 from the Golgi to the apical bile canalicular membrane
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20103773
  qualifier: enables
  review:
    summary: Interaction with IRE1/ERN1 (O75460) within the IRE1-RACK1-PP2A complex; a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; informative aspects captured by the kinase-inhibitor and complex annotations.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20103773 UniProtKB:O75460
- term:
    id: GO:0035591
    label: signaling adaptor activity
  evidence_type: IMP
  original_reference_id: PMID:20103773
  qualifier: enables
  review:
    summary: RACK1 acts as a signaling adaptor recruiting PP2A to IRE1; a genuine scaffold/adaptor molecular function.
    action: KEEP_AS_NON_CORE
    reason: Captures RACK1's bona fide adaptor function, though in a specific UPR context; a representative scaffold MF kept as non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0035591 signaling adaptor activity molecular_function ECO:0000315 IMP PMID:20103773
- term:
    id: GO:0071333
    label: cellular response to glucose stimulus
  evidence_type: IDA
  original_reference_id: PMID:20103773
  qualifier: involved_in
  review:
    summary: RACK1/IRE1 role in the response to glucose, linked to UPR regulation.
    action: KEEP_AS_NON_CORE
    reason: A specific stimulus-response moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0071333 cellular response to glucose stimulus biological_process ECO:0000314 IDA PMID:20103773
- term:
    id: GO:1990630
    label: IRE1-RACK1-PP2A complex
  evidence_type: IDA
  original_reference_id: PMID:20103773
  qualifier: part_of
  review:
    summary: RACK1 is part of a defined IRE1-RACK1-PP2A complex that attenuates the UPR.
    action: KEEP_AS_NON_CORE
    reason: A genuine specific complex but a moonlighting (UPR) context; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:1990630 IRE1-RACK1-PP2A complex cellular_component ECO:0000314 IDA PMID:20103773
- term:
    id: GO:1900102
    label: negative regulation of endoplasmic reticulum unfolded protein response
  evidence_type: TAS
  original_reference_id: PMID:22013210
  qualifier: involved_in
  review:
    summary: RACK1 negatively regulates the ER UPR (via IRE1 dephosphorylation).
    action: KEEP_AS_NON_CORE
    reason: A specific UPR moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:1900102 negative regulation of endoplasmic reticulum unfolded protein response biological_process ECO:0000304 TAS PMID:22013210
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:19451233
  qualifier: involved_in
  review:
    summary: RACK1 negatively regulates gene expression in a specific context.
    action: KEEP_AS_NON_CORE
    reason: Broad/specific-context moonlighting BP; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0010629 negative regulation of gene expression biological_process ECO:0000315 IMP PMID:19451233
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22658674
  qualifier: enables
  review:
    summary: RACK1 captured in high-throughput mRNA-interactome (RNA-binding proteome) screens, consistent with its position on the 40S subunit near mRNA.
    action: KEEP_AS_NON_CORE
    reason: Plausible given ribosomal context but from high-throughput crosslinking; non-core MF.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0003723 RNA binding molecular_function ECO:0007005 HDA PMID:22658674
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22681889
  qualifier: enables
  review:
    summary: RACK1 in a second RNA-interactome capture screen.
    action: KEEP_AS_NON_CORE
    reason: High-throughput RNA-binding; non-core MF (ribosome-associated).
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0003723 RNA binding molecular_function ECO:0007005 HDA PMID:22681889
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IMP
  original_reference_id: PMID:19767770
  qualifier: located_in
  review:
    summary: A mitochondrial localization reported in a single study; inconsistent with the dominant cytosolic/ribosomal pool.
    action: MARK_AS_OVER_ANNOTATED
    reason: Single-study, conflicting localization not corroborated by structural/proteomic consensus; likely over-annotation.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005739 mitochondrion cellular_component ECO:0000315 IMP PMID:19767770
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IMP
  original_reference_id: PMID:19767770
  qualifier: located_in
  review:
    summary: Cytosolic localization (same study).
    action: ACCEPT
    reason: Core compartment.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000315 IMP PMID:19767770
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  qualifier: located_in
  review:
    summary: Detection in extracellular exosome proteomics; abundant cytosolic/ribosomal proteins are commonly detected in such fractions.
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput exosome proteomics; likely a contaminant of abundant ribosomal protein, not a functional exosomal localization.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0070062 extracellular exosome cellular_component ECO:0007005 HDA PMID:19056867
- term:
    id: GO:0060090
    label: molecular adaptor activity
  evidence_type: TAS
  original_reference_id: PMID:20819076
  qualifier: enables
  review:
    summary: RACK1 functions as a molecular adaptor/scaffold; this is its defining non-ribosomal molecular function.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Scaffolding protein involved in the recruitment, assembly and/or regulation of a variety of signaling molecules.
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:19767770
  qualifier: involved_in
  review:
    summary: RACK1 promotes apoptosis in some contexts.
    action: KEEP_AS_NON_CORE
    reason: A specific apoptosis moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0043065 positive regulation of apoptotic process biological_process ECO:0000315 IMP PMID:19767770
- term:
    id: GO:0051898
    label: negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: IMP
  original_reference_id: PMID:19767770
  qualifier: involved_in
  review:
    summary: RACK1 negatively regulates PI3K/AKT signaling (e.g. by recruiting PP2A to AKT1).
    action: KEEP_AS_NON_CORE
    reason: A specific signaling moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction biological_process ECO:0000315 IMP PMID:19767770
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14500341
  qualifier: enables
  review:
    summary: Interaction with HRAS (P01112); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:14500341 UniProtKB:P01112
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18816594
  qualifier: enables
  review:
    summary: Interaction with a partner (Q14899); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18816594 UniProtKB:Q14899
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17108144
  qualifier: located_in
  review:
    summary: Nuclear localization with the androgen receptor in a signaling context.
    action: KEEP_AS_NON_CORE
    reason: Context-dependent nuclear pool; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005634 nucleus cellular_component ECO:0000314 IDA PMID:17108144
- term:
    id: GO:0001891
    label: phagocytic cup
  evidence_type: IDA
  original_reference_id: PMID:21347310
  qualifier: located_in
  review:
    summary: Direct localization to phagocytic cups during Yersinia infection.
    action: KEEP_AS_NON_CORE
    reason: Infection-context localization; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0001891 phagocytic cup cellular_component ECO:0000314 IDA PMID:21347310
- term:
    id: GO:0001934
    label: positive regulation of protein phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:11312657
  qualifier: involved_in
  review:
    summary: RACK1 enhances PKC-mediated phosphorylation of substrates (here HIV-1 Nef).
    action: KEEP_AS_NON_CORE
    reason: Reflects the PKC-scaffold role in a specific context; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0001934 positive regulation of protein phosphorylation biological_process ECO:0000314 IDA PMID:11312657
- term:
    id: GO:0001934
    label: positive regulation of protein phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:17108144
  qualifier: involved_in
  review:
    summary: RACK1 promotes SRC-mediated phosphorylation of the androgen receptor.
    action: KEEP_AS_NON_CORE
    reason: A specific signaling-scaffold role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0001934 positive regulation of protein phosphorylation biological_process ECO:0000314 IDA PMID:17108144
- term:
    id: GO:0005080
    label: protein kinase C binding
  evidence_type: IDA
  original_reference_id: PMID:11279199
  qualifier: enables
  review:
    summary: Direct binding to protein kinase C; the canonical RACK1 scaffold molecular function.
    action: KEEP_AS_NON_CORE
    reason: Well-established direct MF and namesake activity, but secondary to the ribosomal/RQC core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Binds to and stabilizes activated protein kinase C (PKC), increasing PKC-mediated phosphorylation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11279199
  qualifier: enables
  review:
    summary: Interaction with SRC captured by IPI; a bare protein-binding annotation (informative aspect captured by tyrosine-kinase-inhibitor MF).
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:11279199 UniProtKB:P00523
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11312657
  qualifier: enables
  review:
    summary: Interaction with HIV-1 Nef (P03404); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real (viral) interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:11312657 UniProtKB:P03404
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17108144
  qualifier: enables
  review:
    summary: Interaction with the androgen receptor (P10275); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:17108144 UniProtKB:P10275
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19785988
  qualifier: enables
  review:
    summary: Interaction with CLEC1B/CLEC-2 (Q9P126) promoting its degradation; a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19785988 UniProtKB:Q9P126
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20541605
  qualifier: enables
  review:
    summary: Interaction with BAX/BCL2L1 (Q07812/Q07817); bare protein-binding annotations (informative aspect captured by BH3-domain binding).
    action: KEEP_AS_NON_CORE
    reason: Real interactions but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20541605 UniProtKB:Q07812
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:10849009
  qualifier: located_in
  review:
    summary: Direct nuclear localization (EBV BZLF1 study).
    action: KEEP_AS_NON_CORE
    reason: Context-dependent nuclear pool; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005634 nucleus cellular_component ECO:0000314 IDA PMID:10849009
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:10849009
  qualifier: located_in
  review:
    summary: Direct cytoplasmic localization.
    action: ACCEPT
    reason: Core compartment.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component ECO:0000314 IDA PMID:10849009
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:19785988
  qualifier: located_in
  review:
    summary: Direct cytoplasmic localization.
    action: ACCEPT
    reason: Core compartment.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component ECO:0000314 IDA PMID:19785988
- term:
    id: GO:0008200
    label: ion channel inhibitor activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: Ion channel inhibitor activity inferred by similarity; same indirect scaffold effect as the IEA annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: Indirect (scaffold-mediated) channel modulation overstated as a direct MF.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Inhibits TRPM6 channel activity.
- term:
    id: GO:0015935
    label: small ribosomal subunit
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: part_of
  review:
    summary: RACK1 is part of the small ribosomal subunit (by similarity).
    action: ACCEPT
    reason: Core cellular component.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Component of the small (40S) ribosomal subunit
- term:
    id: GO:0017148
    label: negative regulation of translation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: RACK1 is involved in translational repression on the 40S subunit.
    action: KEEP_AS_NON_CORE
    reason: Concordant with UniProt (translational repression); a genuine but broad translation-control role kept non-core relative to the RQC-specific core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Component of the 40S ribosomal subunit involved in translational repression
- term:
    id: GO:0030178
    label: negative regulation of Wnt signaling pathway
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: RACK1 inhibits Wnt signaling and regulates cell polarity/gastrulation (inferred from Xenopus ortholog).
    action: KEEP_AS_NON_CORE
    reason: A developmental-signaling moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: inhibits Wnt signaling, and regulates cellular polarization and oriented cell division during gastrulation
- term:
    id: GO:0030292
    label: protein tyrosine kinase inhibitor activity
  evidence_type: IDA
  original_reference_id: PMID:9584165
  qualifier: enables
  review:
    summary: RACK1 inhibits Src-family tyrosine kinases (SRC, LCK, YES1); a direct, informative molecular function.
    action: KEEP_AS_NON_CORE
    reason: Well-supported direct MF (RACK1 inhibits Src activity and cell growth), but a signaling moonlighting function rather than the ribosomal core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Inhibits the activity of SRC kinases including SRC, LCK and YES1.
- term:
    id: GO:0030308
    label: negative regulation of cell growth
  evidence_type: IDA
  original_reference_id: PMID:9584165
  qualifier: involved_in
  review:
    summary: RACK1 inhibits cell growth (prolongs G0/G1) via Src inhibition.
    action: KEEP_AS_NON_CORE
    reason: A growth-control moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Inhibits cell growth by prolonging the G0/G1 phase of the cell cycle.
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: IDA
  original_reference_id: PMID:20499158
  qualifier: involved_in
  review:
    summary: RACK1 promotes cell migration (via RhoA activation) in breast carcinoma.
    action: KEEP_AS_NON_CORE
    reason: A migration/metastasis moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Promotes migration of breast carcinoma cells by binding to and activating RHOA
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Dendritic localization by similarity.
    action: KEEP_AS_NON_CORE
    reason: Neuronal-context localization; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Cell projection, dendrite
- term:
    id: GO:0030971
    label: receptor tyrosine kinase binding
  evidence_type: IDA
  original_reference_id: PMID:9584165
  qualifier: enables
  review:
    summary: RACK1 binds receptor tyrosine kinases (e.g. via its interactions with IGF1R/SRC pathway components).
    action: KEEP_AS_NON_CORE
    reason: A specific interaction MF in growth-factor signaling; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0030971 receptor tyrosine kinase binding molecular_function ECO:0000314 IDA PMID:9584165
- term:
    id: GO:0032436
    label: positive regulation of proteasomal ubiquitin-dependent protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:19785988
  qualifier: involved_in
  review:
    summary: RACK1 promotes ubiquitin-proteasome degradation of clients such as CLEC1B and HIF1A.
    action: KEEP_AS_NON_CORE
    reason: A specific client-degradation moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Promotes the ubiquitination and proteasome-mediated degradation of proteins such as CLEC1B and HIF1A.
- term:
    id: GO:0032880
    label: regulation of protein localization
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: RACK1 regulates localization of partner proteins (inferred from ortholog).
    action: KEEP_AS_NON_CORE
    reason: A broad scaffold-trafficking role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Required for VANGL2 membrane localization
- term:
    id: GO:0042169
    label: SH2 domain binding
  evidence_type: IDA
  original_reference_id: PMID:11279199
  qualifier: enables
  review:
    summary: RACK1 binds the SH2 domain of SRC; an informative interaction MF underlying Src regulation.
    action: KEEP_AS_NON_CORE
    reason: A specific, real interaction MF in Src signaling; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0042169 SH2 domain binding molecular_function ECO:0000314 IDA PMID:11279199
- term:
    id: GO:0042169
    label: SH2 domain binding
  evidence_type: IDA
  original_reference_id: PMID:9584165
  qualifier: enables
  review:
    summary: RACK1 binds the SH2 domain of Src-family kinases.
    action: KEEP_AS_NON_CORE
    reason: Specific interaction MF in Src signaling; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0042169 SH2 domain binding molecular_function ECO:0000314 IDA PMID:9584165
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: IDA
  original_reference_id: PMID:20541605
  qualifier: involved_in
  review:
    summary: RACK1 promotes apoptosis via BAX oligomerization.
    action: KEEP_AS_NON_CORE
    reason: An apoptosis moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0043065 positive regulation of apoptotic process biological_process ECO:0000314 IDA PMID:20541605
- term:
    id: GO:0043547
    label: positive regulation of GTPase activity
  evidence_type: IDA
  original_reference_id: PMID:20499158
  qualifier: involved_in
  review:
    summary: RACK1 activates RHOA GTPase to promote migration.
    action: KEEP_AS_NON_CORE
    reason: A specific signaling moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0043547 positive regulation of GTPase activity biological_process ECO:0000314 IDA PMID:20499158
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:11279199
  qualifier: located_in
  review:
    summary: Perinuclear localization that redistributes on PKC activation.
    action: KEEP_AS_NON_CORE
    reason: A sub-cytoplasmic distribution; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0048471 perinuclear region of cytoplasm cellular_component ECO:0000314 IDA PMID:11279199
- term:
    id: GO:0050765
    label: negative regulation of phagocytosis
  evidence_type: IMP
  original_reference_id: PMID:21347310
  qualifier: involved_in
  review:
    summary: RACK1 binding to Yersinia YopK inhibits phagocytosis (infection context).
    action: KEEP_AS_NON_CORE
    reason: An infection-related moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: which leads to inhibition of phagocytosis and survival of bacteria
- term:
    id: GO:0051302
    label: regulation of cell division
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Regulation of cell division inferred from ortholog (oriented cell division during gastrulation).
    action: KEEP_AS_NON_CORE
    reason: A developmental moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: regulates cellular polarization and oriented cell division during gastrulation
- term:
    id: GO:0051726
    label: regulation of cell cycle
  evidence_type: IDA
  original_reference_id: PMID:9584165
  qualifier: involved_in
  review:
    summary: RACK1 regulates the cell cycle (G0/G1 prolongation via Src inhibition).
    action: KEEP_AS_NON_CORE
    reason: A growth/cell-cycle moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Inhibits cell growth by prolonging the G0/G1 phase of the cell cycle.
- term:
    id: GO:2000114
    label: regulation of establishment of cell polarity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Regulation of cell polarity inferred from ortholog.
    action: KEEP_AS_NON_CORE
    reason: A developmental moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: regulates cellular polarization and oriented cell division during gastrulation
- term:
    id: GO:2000543
    label: positive regulation of gastrulation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: RACK1 promotes gastrulation (inferred from Xenopus ortholog).
    action: KEEP_AS_NON_CORE
    reason: A developmental moonlighting role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: regulates cellular polarization and oriented cell division during gastrulation
- term:
    id: GO:0030496
    label: midbody
  evidence_type: IDA
  original_reference_id: PMID:15166316
  qualifier: located_in
  review:
    summary: Detection in the midbody proteome during cytokinesis.
    action: KEEP_AS_NON_CORE
    reason: A cytokinesis-localization observed in proteomics; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0030496 midbody cellular_component ECO:0000314 IDA PMID:15166316
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18954305
  qualifier: enables
  review:
    summary: Interaction with OTUB1 (Q96FW1); a bare protein-binding annotation.
    action: KEEP_AS_NON_CORE
    reason: Real interaction but uninformative MF; not core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18954305 UniProtKB:Q96FW1
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Neuronal cell body localization by similarity.
    action: KEEP_AS_NON_CORE
    reason: Neuronal-context localization; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-uniprot.txt
      supporting_text: Perikaryon {ECO:0000250|UniProtKB:P68040}
- term:
    id: GO:0019903
    label: protein phosphatase binding
  evidence_type: IPI
  original_reference_id: PMID:11278757
  qualifier: enables
  review:
    summary: RACK1 binds a protein phosphatase (P28827), consistent with its adaptor role recruiting phosphatases (e.g. PP2A).
    action: KEEP_AS_NON_CORE
    reason: A specific interaction MF supporting the scaffold role; non-core.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0019903 protein phosphatase binding molecular_function ECO:0000353 IPI PMID:11278757 UniProtKB:P28827
- term:
    id: GO:0005102
    label: signaling receptor binding
  evidence_type: NAS
  original_reference_id: PMID:12809483
  qualifier: enables
  review:
    summary: RACK1 binds signaling receptors (asserted, NAS); a generic interaction MF.
    action: KEEP_AS_NON_CORE
    reason: Reflects scaffold interactions with receptors; non-core and relatively generic.
    supported_by:
    - reference_id: file:human/RACK1/RACK1-goa.tsv
      supporting_text: GO:0005102 signaling receptor binding molecular_function ECO:0000303 NAS PMID:12809483
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms.
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity.
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB Subcellular Location vocabulary mapping.
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara.
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10849009
  title: The PKC targeting protein RACK1 interacts with the Epstein-Barr virus activator protein BZLF1.
  findings: []
- id: PMID:11046044
  title: Receptor for activated C-kinase (RACK-1), a WD motif-containing protein, specifically associates with the human type I IFN receptor.
  findings: []
- id: PMID:11278757
  title: 'The PTPmu protein-tyrosine phosphatase binds and recruits the scaffolding protein RACK1 to cell-cell contacts.'
  findings: []
- id: PMID:11279199
  title: The interaction of Src and RACK1 is enhanced by activation of protein kinase C and tyrosine phosphorylation of RACK1.
  findings:
  - statement: RACK1 directly binds the SH2 domain of SRC and binds protein kinase C; perinuclear cytoplasmic localization.
    reference_section_type: RESULTS
- id: PMID:11312657
  title: Rack1 binds HIV-1 Nef and can act as a Nef-protein kinase C adaptor.
  findings: []
- id: PMID:12809483
  title: ST7 is a novel low-density lipoprotein receptor-related protein (LRP) with a cytoplasmic tail that interacts with proteins related to signal transduction pathways.
  findings: []
- id: PMID:12958311
  title: The scaffolding protein RACK1 interacts with androgen receptor and promotes cross-talk through a protein kinase C signaling pathway.
  findings: []
- id: PMID:14500341
  title: Alternative splicing of the human proto-oncogene c-H-ras renders a new Ras family protein that trafficks to cytoplasm and nucleus.
  findings: []
- id: PMID:15159402
  title: 'Identification of interaction partners and substrates of the cyclin A1-CDK2 complex.'
  findings: []
- id: PMID:15166316
  title: Dissection of the mammalian midbody proteome reveals conserved cytokinesis mechanisms.
  findings: []
- id: PMID:17108144
  title: Receptor for activated C kinase 1 (RACK1) and Src regulate the tyrosine phosphorylation and function of the androgen receptor.
  findings: []
- id: PMID:17956333
  title: Interaction of integrin beta1 with cytokeratin 1 in neuroblastoma NMB7 cells.
  findings: []
- id: PMID:18057008
  title: Cell surface levels of organellar Na+/H+ exchanger isoform 6 are regulated by interaction with RACK1.
  findings: []
- id: PMID:18194455
  title: 'Acetylcholinesterase-R increases germ cell apoptosis but enhances sperm motility.'
  findings: []
- id: PMID:18420585
  title: RACK1 and CIS mediate the degradation of BimEL in cancer cells.
  findings: []
- id: PMID:18816594
  title: 'mrtl-A translation/localization regulatory protein encoded within the human c-myc locus and distributed throughout the endoplasmic and nucleoplasmic reticular network.'
  findings: []
- id: PMID:18954305
  title: Structural basis and specificity of human otubain 1-mediated deubiquitination.
  findings: []
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
- id: PMID:19451233
  title: 'Stxbp4 regulates DeltaNp63 stability by suppression of RACK1-dependent degradation.'
  findings: []
- id: PMID:19674157
  title: Receptor for activated C-kinase 1 regulates the cellular localization and function of ABCB4.
  findings: []
- id: PMID:19767770
  title: 'A novel pro-apoptotic function of RACK1: suppression of Src activity in the intrinsic and Akt pathways.'
  findings: []
- id: PMID:19785988
  title: RACK1 associates with CLEC-2 and promotes its ubiquitin-proteasome degradation.
  findings: []
- id: PMID:20010870
  title: Copine-III interacts with ErbB2 and promotes tumor cell migration.
  findings: []
- id: PMID:20080539
  title: The Polycomb group protein EED couples TNF receptor 1 to neutral sphingomyelinase.
  findings: []
- id: PMID:20103773
  title: 'A crucial role for RACK1 in the regulation of glucose-stimulated IRE1alpha activation in pancreatic beta cells.'
  findings:
  - statement: RACK1 acts as a signaling adaptor recruiting PP2A to inhibit the IRE1 kinase, negatively regulating the ER unfolded protein response.
    reference_section_type: RESULTS
- id: PMID:20499158
  title: RACK1 promotes breast carcinoma migration/metastasis via activation of the RhoA/Rho kinase pathway.
  findings: []
- id: PMID:20541605
  title: RACK1 promotes Bax oligomerization and dissociates the interaction of Bax and Bcl-XL.
  findings:
  - statement: RACK1 binds the BH3 domain of BAX, promotes BAX oligomerization and disrupts the BAX-Bcl-XL interaction to promote apoptosis.
    reference_section_type: RESULTS
- id: PMID:20573744
  title: A stimulatory role for the La-related protein 4B in translation.
  findings: []
- id: PMID:20819076
  title: 'Interaction with receptor for activated C-kinase 1 (RACK1) sensitizes the phosphodiesterase PDE4D5 towards hydrolysis of cAMP and activation by protein kinase C.'
  findings: []
- id: PMID:20871634
  title: Regulation of receptor for activated C kinase 1 protein by the von Hippel-Lindau tumor suppressor in IGF-I-induced renal carcinoma cell invasiveness.
  findings: []
- id: PMID:21098120
  title: La-related protein 4 binds poly(A), interacts with the poly(A)-binding protein MLLE domain via a variant PAM2w motif, and can promote mRNA stability.
  findings: []
- id: PMID:21146485
  title: Identification of cyclophilin-40-interacting proteins reveals potential cellular function of cyclophilin-40.
  findings: []
- id: PMID:21347310
  title: The RACK1 signaling scaffold protein selectively interacts with Yersinia pseudotuberculosis virulence function.
  findings: []
- id: PMID:21525958
  title: The ribosomal protein RACK1 is required for microRNA function in both C. elegans and humans.
  findings: []
- id: PMID:21750715
  title: 'The inhibitor of growth protein 5 (ING5) depends on INCA1 as a co-factor for its antiproliferative effects.'
  findings: []
- id: PMID:21988832
  title: Toward an understanding of the protein interaction network of the human liver.
  findings: []
- id: PMID:22013210
  title: 'The unfolded protein response: integrating stress signals through the stress sensor IRE1α.'
  findings: []
- id: PMID:22210188
  title: 'Interaction of protein inhibitor of activated STAT 2 (PIAS2) with receptor of activated C kinase 1, RACK1.'
  findings: []
- id: PMID:22658674
  title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
  findings: []
- id: PMID:22681889
  title: The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
  findings: []
- id: PMID:23636399
  title: Structures of the human and Drosophila 80S ribosome.
  findings:
  - statement: RACK1 is an integral component of the 40S ribosomal subunit in the human 80S ribosome structure.
    reference_section_type: RESULTS
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication title matches PubMed ("Structures of the human and Drosophila 80S ribosome"); cryo-EM structure places RACK1 as an integral 40S subunit component, establishing the core ribosome-binding/structural-subunit function (GO:0043022, GO:0022627).
- id: PMID:23651062
  title: RACK1 (receptor for activated C-kinase 1) interacts with FBW2 (F-box and WD-repeat domain-containing 2) to up-regulate GCM1 (glial cell missing 1) stability and placental cell migration and invasion.
  findings: []
- id: PMID:23866081
  title: Lyn, a Src family kinase, regulates activation of epidermal growth factor receptors in lung adenocarcinoma cells.
  findings: []
- id: PMID:24006492
  title: Endosomal acidification by Na+/H+ exchanger NHE5 regulates TrkA cell-surface targeting and NGF-induced PI3K signaling.
  findings: []
- id: PMID:24947010
  title: DJ-1 interacts with RACK1 and protects neurons from oxidative-stress-induced apoptosis.
  findings: []
- id: PMID:25468996
  title: E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
  findings: []
- id: PMID:25901680
  title: Structure of the human 80S ribosome.
  findings:
  - statement: Cryo-EM structure of the human 80S ribosome including RACK1 as part of the cytosolic small (40S) ribosomal subunit.
    reference_section_type: RESULTS
- id: PMID:25910212
  title: Widespread macromolecular interaction perturbations in human genetic disorders.
  findings: []
- id: PMID:28132843
  title: ZNF598 and RACK1 Regulate Mammalian Ribosome-Associated Quality Control Function by Mediating Regulatory 40S Ribosomal Ubiquitylation.
  findings:
  - statement: The 40S ribosomal protein RACK1 and the ZNF598 ubiquitin ligase help resolve poly(A)-induced stalled ribosomes by mediating regulatory 40S ribosomal ubiquitylation; RACK1 regulates RPS2, RPS3 and RPS20 ubiquitylation.
    reference_section_type: RESULTS
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication title matches PubMed; Results show RACK1 (with ZNF598) is required for regulatory 40S ubiquitylation that resolves stalled/collided ribosomes, establishing RACK1's ribosome-associated quality control (RQC) scaffold role.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings: []
- id: PMID:29743600
  title: 'Trafficking, localization and degradation of the Na(+),HCO(3)(-) co-transporter NBCn1 in kidney and breast epithelial cells.'
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32467643
  title: 'Dual functions of Rack1 in regulating Hedgehog pathway.'
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:37712706
  title: The matrix protein of respiratory syncytial virus suppresses interferon signaling via RACK1 association.
  findings: []
- id: PMID:38190388
  title: 'A novel Trichinella spiralis serine proteinase disrupted gut epithelial barrier and mediated larval invasion through binding to RACK1 and activating MAPK/ERK1/2 pathway.'
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:9584165
  title: RACK1, a receptor for activated C kinase and a homolog of the beta subunit of G proteins, inhibits activity of src tyrosine kinases and growth of NIH 3T3 cells.
  findings:
  - statement: RACK1 inhibits the activity of Src tyrosine kinases and inhibits growth of NIH 3T3 cells.
    reference_section_type: RESULTS
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: GOA-anchored (this PMID supports GO:0030292 protein tyrosine kinase inhibitor activity in RACK1-goa.tsv); seminal paper establishing RACK1's Src-family kinase inhibition / signaling-scaffold core function.
- id: Reactome:R-HSA-5626962
  title: RACK1 localized in cytosol (Reactome).
  findings: []
- id: Reactome:R-HSA-5626981
  title: RACK1 localized in cytosol (Reactome).
  findings: []
- id: Reactome:R-HSA-5626982
  title: RACK1 localized in cytosol (Reactome).
  findings: []
core_functions:
- description: Integral structural component of the small (40S) ribosomal subunit that binds the ribosome and contributes to translational control/repression.
  molecular_function:
    id: GO:0043022
    label: ribosome binding
  in_complex:
    id: GO:0022627
    label: cytosolic small ribosomal subunit
  supported_by:
  - reference_id: file:human/RACK1/RACK1-uniprot.txt
    supporting_text: Component of the 40S ribosomal subunit involved in translational repression
  - reference_id: PMID:23636399
    supporting_text: Structures of the human and Drosophila 80S ribosome
- description: Ribosomal scaffold for ribosome-associated quality control of stalled/collided ribosomes, promoting regulatory ubiquitylation of a subset of 40S ribosomal proteins (with ZNF598) to resolve terminal stalls.
  molecular_function:
    id: GO:0043022
    label: ribosome binding
  in_complex:
    id: GO:0022627
    label: cytosolic small ribosomal subunit
  supported_by:
  - reference_id: PMID:28132843
    supporting_text: the 40S ribosomal protein RACK1 help to resolve poly(A)-induced stalled ribosomes
  - reference_id: PMID:28132843
    supporting_text: RACK1 regulates RPS2, RPS3, and RPS20 ubiquitylation
  directly_involved_in:
  - id: GO:0072344
    label: rescue of stalled cytosolic ribosome
- description: Signaling scaffold/molecular adaptor whose WD40 propeller assembles and regulates diverse signaling complexes, including binding/stabilizing activated protein kinase C and inhibiting Src-family tyrosine kinases.
  molecular_function:
    id: GO:0060090
    label: molecular adaptor activity
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/RACK1/RACK1-uniprot.txt
    supporting_text: Scaffolding protein involved in the recruitment, assembly and/or regulation of a variety of signaling molecules.
  - reference_id: file:human/RACK1/RACK1-uniprot.txt
    supporting_text: Inhibits the activity of SRC kinases including SRC, LCK and YES1.
proposed_new_terms: []
suggested_questions:
- question: 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?
- question: 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?
suggested_experiments:
- description: 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.
- description: 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.
- description: Cryo-EM of collided disomes reconstituted with RACK1, ZNF598 and EDF1 to define the structural basis of RACK1-dependent recruitment of the ubiquitylation machinery.

RACK1

Gene Description

Existing Annotations Review

Core Functions

Integral structural component of the small (40S) ribosomal subunit that binds the ribosome and contributes to translational control/repression.

Ribosomal scaffold for ribosome-associated quality control of stalled/collided ribosomes, promoting regulatory ubiquitylation of a subset of 40S ribosomal proteins (with ZNF598) to resolve terminal stalls.

Signaling scaffold/molecular adaptor whose WD40 propeller assembles and regulates diverse signaling complexes, including binding/stabilizing activated protein kinase C and inhibiting Src-family tyrosine kinases.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

RACK1 (GNB2L1 / P63244) review notes

Identity / core

Ribosome / RQC core function (best-supported, the curation focus)

Moonlighting / signaling roles (well-documented but many are scaffold-context-specific)

Localization

Curation decisions summary

Pn Notes

RACK1 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: Translation | Cytosolic translation | Ribosome biogenesis factor | pre-40S complex

PN row 2: Translation | Cytosolic translation | Ribosome-associated QC | Ribosomal rescue

PN row 3: Autophagy-Lysosome Pathway | Autophagophore initiation and elongation | ATG8 homolog processing, upstream | Preparation of ATG8 homologs for lipidation | Modulation of ATG5-ATG12-ATG16 complex activity

Projected GO annotations (4)

Note

📄 View Raw YAML