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.