GIGYF1 is a cytosolic GYF-domain protein that represses translation and couples selected translating mRNAs to decay. Its N-terminal regions bind 4EHP and DDX6, while the GYF domain recognizes proline-rich protein regions. C-terminal eIF3 engagement reduces eIF3–eIF4G1 association, supporting 4EHP-independent repression; adaptor interfaces connect RNA-bound factors and effectors. GIGYF1 also associates with GRB10-containing signaling assemblies.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:20878056 Critical involvement of RQCD1 in the EGFR-Akt pathway in mam... | REMOVE | Summary: Preserve the signaling assembly; omit uninformative generic binding. Reason: RQCD1 pull-downs preserve a positive signaling assembly, without defining direct contact with every member or a specific GIGYF1 activity. Generic binding is uninformative. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20878056 Critical involvement of RQCD1 in the EGFR-Akt pathway in mam... | MODIFY | Summary: Refine the characterized GRB10-recognition mechanism. Reason: Human GRB10/RQCD1 association is positive. Independently, mouse GIGYF1 GYF mutations and GRB10 proline-box deletions establish proline-rich region recognition. The refinement describes that GRB10-facing mechanism; it does not assign the same interface to RQCD1 or claim a human residue assay. Proposed replacements: proline-rich region binding |
| GO:0005515 protein binding | IPI PMID:20878056 Critical involvement of RQCD1 in the EGFR-Akt pathway in mam... | REMOVE | Summary: Retain the RQCD1 interaction without assigning an unsupported activity. Reason: The mapped RQCD1 interaction is positive, but this contact alone does not define a useful GIGYF1 molecular activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28698298 GIGYF1/2 proteins use auxiliary sequences to selectively bin... | MODIFY | Summary: Refine the directly characterized 4EHP-binding interface. Reason: Human GIGYF1 fragments bind 4EHP/EIF4E2 through a structurally resolved, mutationally tested interface. Translation initiation factor binding captures this functional repressor contact. The study distinguishes 4EHP from eIF4E; neither cellular eIF4E1 binding nor its mainly GIGYF2 reporter-rescue endpoint is assigned to GIGYF1. Proposed replacements: translation initiation factor binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: SNRPA’s spliceosomal RNA-recognition role does not establish an RNA-splicing function or a defined spliceosome-recruitment activity for GIGYF1. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: SNRPC’s U1 complex membership describes the partner; the pair alone does not identify GIGYF1 as a spliceosomal constituent or a specific splicing regulator. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: The inspected PRR35 record supplies no established functional class that would justify a more informative GIGYF1 molecular-function assignment. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Refine the positive SNRPB pair using its experimentally tested proline-rich interface. Reason: HuRI preserves the P14678-2 pair and its partially sequence-identified target clone. Independent human BRET experiments in PMID:38225382 test the SNRPB proline-repeat region and GIGYF1 GYF pocket, supporting proline-rich region binding. The later complete ORF sequences do not retroactively establish the exact HuRI clone sequence. No Sm-ring or splicing activity is inferred. Proposed replacements: proline-rich region binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Refine the characterized DDX6-binding interface. Reason: Human GIGYF1 motif–DDX6 pull-down and pocket-mutant assays establish the interface beyond partner class. Retain helicase binding without assigning helicase catalysis; the paper’s GIGYF2 TTP endpoint remains separate. Proposed replacements: DEAD/H-box RNA helicase binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: A PRKAA2/AMPK catalytic-subunit interaction does not establish kinase regulation, energy sensing, or a physiological AMPK-recruitment activity of GIGYF1. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: The source explicitly matches TLE5 isoform Q08117-2. A transcriptional-corepressor partner does not make GIGYF1 a corepressor in that transcriptional mechanism. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: The TROAP pair is positive, with source isoform Q12815-1 under the incoming gene-level accession. Its adhesion-associated characterization does not establish a corresponding GIGYF1 function. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: The TCEA2 transcription-elongation factor partner does not establish GIGYF1 participation in RNA polymerase II elongation or a specific elongation-factor recruitment function. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: The source explicitly matches CCDC57 isoform Q2TAC2-2. The partner’s centrosomal and microtubule roles do not establish those functions for GIGYF1. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: MNS1’s ciliary microtubule-associated role is not evidence that GIGYF1 is a ciliary structural component or a defined ciliary assembly factor. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: NFKBID’s NF-kappa-B-related partner classification does not establish an NF-kappa-B regulatory mechanism for GIGYF1; similarity-derived partner information is not a target experiment. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: KAT5’s histone acetyltransferase activity does not establish a specific GIGYF1 chromatin recruitment or acetyltransferase-regulatory activity. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: Membership of MCRS1 in transcription/chromatin assemblies does not establish GIGYF1 as a member or regulator of those assemblies. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: SMARCD1’s SWI/SNF role does not establish a GIGYF1 chromatin-remodeling function or a defined recruitment mechanism. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: The source maps the STAC3 pair to Q96MF2-2 while the incoming accession is gene-level. STAC3 excitation-contraction function is not transferable to GIGYF1 from this binding pair. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: The source explicitly matches SPAG8 isoform Q99932-2. Sperm/ciliary partner biology does not establish a GIGYF1 motility or ciliary assembly role. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: CRACR2A’s calcium-sensing and store-operated-calcium-entry roles do not establish a corresponding GIGYF1 calcium-regulatory function. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: The source explicitly matches KIFC3 isoform Q9BVG8-5. A motor-protein interaction alone does not establish GIGYF1 as a motor adaptor or identify a transported cargo mechanism. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: SCNM1’s minor-spliceosome classification does not establish GIGYF1 recruitment to that complex or a minor-intron splicing function. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: ENKD1’s microtubule-stabilizing characterization does not establish GIGYF1 microtubule binding or stabilization. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: The source explicitly matches FAM124B isoform Q9H5Z6-2. The inspected partner record does not supply a demonstrated functional class or a GIGYF1 mechanism suitable for a more specific replacement. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: ARMC7’s minor-spliceosome role does not establish a GIGYF1 splicing function or a defined recruitment activity. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: The CBX8 PRC1 chromatin-associated partner does not establish GIGYF1 chromatin recognition or Polycomb repression. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: The NEK6 gene-level pair is positive, but incoming Q9HC98-4 and source Q9HC98-1 are different explicit isoforms. Preserve both identifiers and the unresolved clone-to-isoform crosswalk. Remove the uninformative generic binding term without declaring the pair false or replacing the incoming identifier; no kinase-regulator function follows from the partner class. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: TSHZ2’s probable transcriptional-regulator classification does not establish a defined transcriptional regulatory activity of GIGYF1. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: RBM22’s spliceosomal RNA role does not establish a GIGYF1 splicing mechanism or direct RNA binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: The current official symbol for Q9NX04 is AIRIM. The partner’s 55LCC and ribosome/proteostasis-related functions do not establish GIGYF1 participation in those mechanisms. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: The source explicitly matches ANKRD10 isoform Q9NXR5-2. The inspected partner record does not supply an established molecular function that would justify a specific GIGYF1 binding-function refinement. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Preserve the positive pair; omit uninformative generic protein binding. Reason: SCAF8’s RNA-polymerase-II-associated antitermination role does not establish GIGYF1 transcriptional antitermination or a defined polymerase-recruitment activity. |
| GO:0005515 protein binding | IPI PMID:33053355 4EHP and GIGYF1/2 Mediate Translation-Coupled Messenger RNA ... | REMOVE | Summary: Preserve ZNF598 association without a class-only ligase-binding refinement. Reason: The ZNF598 association and GYF-dependent GIGYF1 rescue remain positive. The inspected experiments do not isolate this contact from other GYF-binding partners. A ubiquitin-ligase partner class alone does not make a useful specific molecular function; generic binding is omitted. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Represent the corroborated DDX6 interaction as DEAD/H-box RNA helicase binding. Reason: BioPlex AP-MS supports association; independent human motif-binding and GIGYF1 rescue studies establish functional DDX6 binding. The source does not resolve the exact target clone or every natural product. Proposed replacements: DEAD/H-box RNA helicase binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Preserve the ZNF598 association but omit uninformative generic protein binding. Reason: The positive BioPlex pair uses ZNF598 Q86UK7-2, distinct from the unsuffixed incoming identifier. Pathway involvement and partner ligase activity do not isolate this contact’s function; generic binding remains uninformative. |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | REMOVE | Summary: Retain the neuronal dynein association without assigning a transport mechanism. Reason: Table S3 records DYNC1H1 as a significant interactor in endogenous GIGYF1_CNCR2 IP-MS from human induced neurons. DYNC1H1 is a dynein motor, but co-enrichment does not establish a GIGYF1 motor-adapter or regulatory activity. Omit uninformative generic binding while retaining the positive association and gene-level product scope. |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | REMOVE | Summary: Preserve the neuronal SMARCC2 association without inferring chromatin regulation. Reason: Table S3 identifies SMARCC2 in GIGYF1_CNCR2 IP-MS. SMARCC2 is a noncatalytic SWI/SNF subunit; the source does not establish that this association recruits or regulates chromatin remodeling through GIGYF1. Its partner class alone is insufficient for a useful molecular-function refinement. Remove generic binding for informativeness, preserving the positive result. |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | REMOVE | Summary: Retain the neuronal STAC3 association as interaction evidence. Reason: Table S3 records a positive GIGYF1_CNCR2–STAC3 association. The endogenous IP-MS experiment does not distinguish direct from indirect association or establish a target-specific STAC3-dependent activity. Its known channel-regulatory role does not transfer to GIGYF1 from copurification. Remove uninformative generic binding without rejecting the observed pair. |
| GO:0005515 protein binding | IPI PMID:38225382 Systematic discovery of protein interaction interfaces using... | MODIFY | Summary: Refine the SNRPB interaction to proline-rich region binding. Reason: Human BRET tests support recognition of SNRPB proline repeats by the GIGYF1 GYF pocket. Exact published ORFs and the separate mouse-Snrpb co-IP are documented in the source companion. No solved interface, Sm-ring activity or splicing function is inferred. Proposed replacements: proline-rich region binding |
| GO:0005515 protein binding | IPI PMID:39251607 Systematic identification of post-transcriptional regulatory... | MODIFY | Summary: Retain DDX6 proximity with independently established helicase binding. Reason: BioID2 detects GIGYF1 proximity to DDX6, while independent human binding and rescue experiments establish the specific interaction. Keep the original proximity assay distinct from direct-binding corroboration. Proposed replacements: DEAD/H-box RNA helicase binding |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the conserved cytosolic compartment. Reason: The actual cytosol IBD reaches the human GIGYF1 leaf through the inspected family tree. Its experimentally annotated GIGYF2 donor and GIGYF1's translation-repression biology support this compartment. The direct-RNA-binding IRD neither removes this localization assertion nor supplies a new nuclear location. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN004461388 SUPPORTS TRANSFER Actual AN0 source and target descent are valid; the current GIGYF2 cytosol source is an HPA IDA record, not a newly inspected human GIGYF1 image. |
| GO:0032991 protein-containing complex | IDA PMID:20878056 Critical involvement of RQCD1 in the EGFR-Akt pathway in mam... | KEEP AS NON CORE | Summary: Retain the experimentally observed signaling complex context. Reason: Human pull-down/co-immunoprecipitation supports the RQCD1/GRB10 assembly as a contextual complex, without establishing fixed stoichiometry or direct contact between every pair. Supporting Evidence: |
| GO:0045947 negative regulation of translational initiation | IBA GO_REF:0000033 | ACCEPT | Summary: Retain conserved repression of translation initiation. Reason: The inspected ancestral assertion reaches GIGYF1, and independent human GIGYF1 experiments support repression involving eIF3 and impaired initiation-complex assembly. The separate ancestral restriction concerns direct RNA-binding repressor activity, not this process. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN004461388 SUPPORTS TRANSFER Actual AN0 is an ancestor of human AN60; the literal GIGYF2 donor matches the original IBD. No target-path loss applies to GO:0045947. |
| GO:0048009 insulin-like growth factor receptor signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain a contextual inherited IGF-receptor signaling role. Reason: The valid Euteleostomi assertion includes GIGYF1. Its mouse source maps GRB10 recognition and reports stimulation-dependent recruitment and enhanced signaling with a GIGYF1 fragment. This supports contextual involvement, without claiming direct receptor binding, kinase activity or universal endogenous stimulation by full-length human GIGYF1. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002683625 SUPPORTS TRANSFER Actual AN50 is an ancestor of target AN60 and mouse donor AN67. Original donor IPI12771153 and its engineered-fragment limitations are retained. |
| GO:1990261 pre-mRNA catabolic process | NAS PMID:33053355 4EHP and GIGYF1/2 Mediate Translation-Coupled Messenger RNA ... | MODIFY | Summary: Describe translation-coupled mRNA decay without an unspliced-precursor claim. Reason: Human GIGYF1 rescue supports turnover of translating mRNAs, including intronless reporters. The evidence does not establish an unspliced-precursor restriction or nuclease activity. Proposed replacements: mRNA catabolic process Supporting Evidence: PMID:33053355 4EHP-GIGYF1/2 complexes trigger co-translational mRNA decay. file:human/GIGYF1/GIGYF1-external-evidence.md |
| GO:0030371 translation repressor activity | IDA PMID:39018414 Repression of mRNA translation initiation by GIGYF1 via disr... | NEW | Summary: Human GIGYF1 represses translation. Reason: Human assays establish repression. The activity is regulatory work, not necessity alone. It asserts neither direct RNA binding nor its absence, and therefore does not conflict with the distinct PAINT restriction. Supporting Evidence: PMID:39018414 GIGYF1, a paralog of GIGYF2, robustly represses cellular mRNA translation |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:39018414 Repression of mRNA translation initiation by GIGYF1 via disr... | NEW | Summary: Selective protein bridging supports adaptor activity. Reason: Human-cell lysate assays show GIGYF1-dependent eIF3 recruitment to RNA. TTP depletion reduces joint GIGYF1/eIF3 recruitment. The GYF mutant retains eIF3 association while reducing TTP binding and target-RNA recruitment. These complementary results support bridging without direct RNA-binding or purified-assembly claims. Supporting Evidence: PMID:39018414 association of eIF3 subunits with Ifnb1 3′UTR is GIGYF1 dependent file:human/GIGYF1/GIGYF1-external-evidence.md |
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Download this section (compressed HTML)Q: Which endogenous transcripts use the GIGYF1 eIF3-associated route, the 4EHP/DDX6 route, or both under the same cellular conditions?
Q: Does full-length human GIGYF1 reproduce the GRB10-dependent signaling effect established with the mouse GYF-containing fragment?
Experiment: Compare matched endogenous GIGYF1 depletion and rescue with full-length recruitment/interface mutants, measuring translation efficiency and RNA decay for the same transcripts.
Hypothesis: Distinct interaction surfaces partition transcript repression from decay while sharing target-recruitment machinery.
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