Affinage

YIPF2

Protein YIPF2 · UniProt Q9BWQ6

Length
316 aa
Mass
35.2 kDa
Annotated
2026-06-11
26 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

YIPF2 is a multi-transmembrane Golgi-resident protein that controls membrane dynamics in the endomembrane system and the surface delivery of specific cargo proteins (PMID:27999994, PMID:31189879). It is anchored at the trans-Golgi region by five closely stacked transmembrane domains, with a cytosolic N-terminus and a lumenal C-terminus, and its depletion produces specific Golgi morphological changes (PMID:27999994); together with YIPF1 and YIPF6 it forms a complex in the medial-/trans-Golgi, with YIPF6 required to maintain YIPF1 and YIPF2 protein levels, and loss of YIPF2 delays Golgi reassembly and reduces glycan synthesis (PMID:28286305). Mechanistically, YIPF2 acts as a Rab-GDF (GDI-displacement factor) that recruits and activates Rab5 and Rab22a GTPases to endomembranes, thereby governing the endocytic recycling and ER-Golgi maturation/glycosylation of CD147; reduced YIPF2 increases CD147 surface delivery and MMP secretion (PMID:31189879). YIPF2 also binds TNFRSF10B (DR5) and RAB8, blocking the TNFRSF10B-RAB8 interaction to prevent RAB8-mediated internalization and thus sustaining surface receptor levels and chemotherapy-induced apoptosis (PMID:32303681), and it likewise regulates CD147 translocation in oligodendrocytes to modulate MCT1-CD147 coupling (PMID:39078594). Beyond trafficking, an intact YIPF2-containing Golgi supports homologous recombination repair, and YIPF2 loss impairs HR and triggers DNA damage response and senescence (PMID:39238039).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2016 Medium

    Established where YIPF2 resides and how it is oriented in the membrane, providing the structural basis for a role in endomembrane dynamics.

    Evidence Immunofluorescence, RNAi depletion, and membrane topology analysis showing trans-Golgi localization, five transmembrane domains, and Golgi morphology defects

    PMID:27999994

    Open questions at the time
    • Molecular partners and biochemical activity not defined
    • Mechanism linking depletion to Golgi morphology change unresolved
  2. 2017 Medium

    Showed YIPF2 operates within a YIPF1/YIPF2/YIPF6 complex and is functionally required for Golgi reassembly and glycan synthesis, framing it as a structural/regulatory component rather than an isolated protein.

    Evidence Co-immunoprecipitation, RNAi knockdown, brefeldin A washout reassembly assay, and glycan synthesis measurement in HT-29 cells

    PMID:28286305

    Open questions at the time
    • Stoichiometry and architecture of the complex not resolved
    • Direct biochemical activity underlying reassembly defect not identified
  3. 2019 High

    Defined YIPF2's molecular activity as a Rab-GDF that activates Rab5 and Rab22a, connecting it mechanistically to endocytic recycling and ER-Golgi maturation of CD147.

    Evidence MAPPIT PPI screen, GST-RBD Rab activation pull-down, biotin chase trafficking assays, flow cytometry, zymography, and RNAi in HCC cells

    PMID:31189879

    Open questions at the time
    • Structural basis of GDI displacement not determined
    • Whether additional Rab substrates exist beyond Rab5/Rab22a unknown
  4. 2020 Medium

    Extended YIPF2 cargo regulation to TNFRSF10B by showing it antagonizes RAB8-mediated receptor internalization to sustain surface levels and apoptotic signaling.

    Evidence Reciprocal co-IP, surface flow cytometry, RNAi knockdown, and apoptosis assays in NSCLC cells

    PMID:32303681

    Open questions at the time
    • Direct vs indirect nature of YIPF2-RAB8 antagonism unclear
    • Whether this uses the same Rab-GDF activity as CD147 regulation not established
  5. 2024 Medium

    Revealed an unexpected role for YIPF2 in genome maintenance, linking an intact Golgi to homologous recombination repair.

    Evidence Whole-genome RNAi screen with HR repair assay, DNA damage response, and senescence readouts

    PMID:39238039

    Open questions at the time
    • Mechanistic link between Golgi/YIPF2 and HR machinery undefined
    • No molecular intermediary identified
  6. 2024 Medium

    Showed YIPF2 control of CD147 surface trafficking is physiologically relevant in oligodendrocytes, affecting MCT1-CD147 coupling in a disease model.

    Evidence Western blot, co-IP, proteomics, in vitro oligodendrocyte assays, and in vivo diabetic encephalopathy mouse model

    PMID:39078594

    Open questions at the time
    • Whether the Rab-GDF activity drives this effect not directly tested
    • Generalizability beyond the hIAPP/diabetic context unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single trans-Golgi Rab-GDF coordinates cargo-specific surface trafficking, Golgi reassembly, and genome stability through one or distinct molecular activities remains unresolved.
  • No structure of YIPF2 or its Rab/cargo complexes
  • Unclear whether trafficking and DNA-repair roles share a common mechanism

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005794 Golgi apparatus 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-9609507 Protein localization 2
Partners
CD147RAB22ARAB5ARAB8ATNFRSF10BYIPF1YIPF6
Complex memberships
YIPF1/YIPF2/YIPF6 complex

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 YIPF2 localizes primarily to the trans-Golgi region of the Golgi complex. It has a membrane topology with a long soluble N-terminal region oriented toward the cytosol, followed by 5 closely stacked transmembrane domains, and a C-terminus oriented toward the Golgi lumen. RNAi-mediated depletion of YIPF2 causes specific morphological changes to the Golgi apparatus, suggesting a role in regulating membrane dynamics in the endomembrane system. Immunofluorescence microscopy, RNA interference, membrane topology analysis Histochemistry and cell biology Medium 27999994
2017 YIPF1, YIPF2, and YIPF6 localize to the medial-/trans-Golgi and trans-Golgi network. YIPF6 forms stable complexes with YIPF1 and YIPF2, and knockdown of YIPF6 reduces YIPF1 and YIPF2 protein levels. Knockdown of YIPF1 and YIPF2 (but not YIPF6) markedly delays reassembly of the Golgi apparatus after brefeldin A washout, and also reduces intracellular glycan synthesis in HT-29 cells. Immunofluorescence staining, co-immunoprecipitation/complex formation analysis, RNAi knockdown, brefeldin A treatment/washout assay, glycan synthesis measurement Experimental cell research Medium 28286305
2019 YIPF2 is an ER-Golgi-resident transmembrane protein that acts as a Rab-GDF (GDI-displacement factor). It recruits and activates Rab5 and Rab22a GTPases to endomembrane structures. YIPF2 modulates endocytic recycling of CD147 through distinctive regulation of Rab5 and Rab22a, and mediates mature processing of CD147 via the ER-Golgi trafficking route, including its glycosylation. Decreased YIPF2 expression leads to increased CD147 cell-surface delivery and enhanced MMP secretion, promoting HCC malignant phenotypes. MAPPIT protein-protein interaction screen, confocal imaging, flow cytometry, biotin-labeled chase assays, GST-RBD pull-down (Rab GTPase activation), gelatin zymography, RNAi knockdown with phenotypic readouts Cell death & disease High 31189879
2020 YIPF2 physically interacts with TNFRSF10B (DR5/TRAIL-R2) and RAB8. YIPF2 promotes recycling of TNFRSF10B to the plasma membrane and inhibits the physical interaction between TNFRSF10B and RAB8, thereby suppressing RAB8-mediated removal of TNFRSF10B from the plasma membrane to the cytoplasm. This maintains high cell-surface levels of TNFRSF10B and promotes chemotherapeutic agent-mediated apoptosis in NSCLC cells. Co-immunoprecipitation, flow cytometry (surface level measurement), RNAi knockdown, cell apoptosis assays Cell death & disease Medium 32303681
2024 YIPF2 plays a critical role in maintaining genome stability. Depletion of YIPF2 hinders homologous recombination (HR) repair, triggering DNA damage response and cellular senescence. Overexpression of YIPF2 facilitates cellular recovery from chemotherapy-induced DNA damage or replicative senescence-associated DNA damage. Only an intact Golgi apparatus containing YIPF2 provides a protective effect on genome integrity. Whole-genome RNAi screen, HR repair assay, DNA damage response assays, overexpression/knockdown with senescence readouts Cell & bioscience Medium 39238039
2024 YIPF2 modulates the transfer of CD147 to the cell membrane in oligodendrocytes. hIAPP interferes with binding of MCT1 to CD147, and YIPF2 inhibition increases CD147 translocation to the membrane, optimizing MCT1-CD147 binding and ameliorating hIAPP-induced acidosis and demyelination in a diabetic encephalopathy model. Western blotting, co-immunoprecipitation, proteomic differential analysis of CD147-co-immunoprecipitated proteins, in vitro oligodendrocyte assays, in vivo DE mouse model with cognitive readouts Neuroscience bulletin Medium 39078594

Source papers

Stage 0 corpus · 26 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood 491 21670465
2009 Dual and opposing roles of primary cilia in medulloblastoma development. Nature medicine 336 19701203
2009 Structural basis for subversion of cellular control mechanisms by the adenoviral E1A oncoprotein. Proceedings of the National Academy of Sciences of the United States of America 111 19651603
2004 Muscle-specific RING finger-2 (MURF-2) is important for microtubule, intermediate filament and sarcomeric M-line maintenance in striated muscle development. Journal of cell science 81 15199100
2013 A conserved apomixis-specific polymorphism is correlated with exclusive exonuclease expression in premeiotic ovules of apomictic boechera species. Plant physiology 52 24163323
2018 MKRN2 inhibits migration and invasion of non-small-cell lung cancer by negatively regulating the PI3K/Akt pathway. Journal of experimental & clinical cancer research : CR 47 30103781
2015 MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet. Cardiovascular diabetology 42 26242235
2001 Phylogenetic conservation of the makorin-2 gene, encoding a multiple zinc-finger protein, antisense to the RAF1 proto-oncogene. Genomics 40 11597136
2019 YIPF2 is a novel Rab-GDF that enhances HCC malignant phenotypes by facilitating CD147 endocytic recycle. Cell death & disease 26 31189879
2016 Functional characterisation of the YIPF protein family in mammalian cells. Histochemistry and cell biology 22 27999994
2020 YIPF2 promotes chemotherapeutic agent-mediated apoptosis via enhancing TNFRSF10B recycling to plasma membrane in non-small cell lung cancer cells. Cell death & disease 19 32303681
2000 Human glial cell-line-derived neurotrophic factor: a structure-function analysis. Biochemical and biophysical research communications 19 10679267
2023 Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis. Nature communications 17 37925548
2017 YIPF1, YIPF2, and YIPF6 are medial-/trans-Golgi and trans-Golgi network-localized Yip domain family proteins, which play a role in the Golgi reassembly and glycan synthesis. Experimental cell research 13 28286305
2022 Cell-based analysis reveals that sex-determining gene signals in Ostrinia are pivotally changed by male-killing Wolbachia. PNAS nexus 10 36712932
2023 LINC00294/miR-620/MKRN2 axis provides biomarkers and negatively regulates malignant progression in colorectal carcinoma. Human & experimental toxicology 8 37218161
1997 Molecular cloning and brain localization of HZF-2 alpha, a new member of the Rev-erb subfamily of orphan nuclear receptors. Journal of neurobiology 8 9058325
2024 The serum small non-coding RNA (SncRNA) landscape as a molecular biomarker of age associated muscle dysregulation and insulin resistance in older adults. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 7 38294260
2013 C-terminal in Sp1-like artificial zinc-finger proteins plays crucial roles in determining their DNA binding affinity. BMC biotechnology 4 24289163
2024 Inhibition of YIPF2 Improves the Vulnerability of Oligodendrocytes to Human Islet Amyloid Polypeptide. Neuroscience bulletin 3 39078594
2014 A subtraction tolerization method of immunization allowed for Wilms' tumor protein-1 (WT1) identification in melanoma and discovery of an antitumor peptide sequence. Journal of immunological methods 3 25205401
2025 A dataset on NFKB1/NFKB2 knockout Jurkat cells and primary CD4+ T cells generated by CRISPR/Cas9 mediated gene disruption. Data in brief 2 40027254
2024 YIPF2 regulates genome integrity. Cell & bioscience 2 39238039
2023 Molecular characterization of Satsuma mandarin (Citrus unshiu Marc.) VASCULAR PLANT ONE-ZINC FINGER2 (CuVOZ2) interacting with CuFT1 and CuFT3. Plant biotechnology (Tokyo, Japan) 2 38213920
2024 Venous thromboembolism and severe COVID-19: a Mendelian randomization trial and transcriptomic analysis. Frontiers in immunology 1 38742101
2026 Integrative transcriptomic analysis identifies synovium-derived biomarkers for OA-related synovitis and builds a validated diagnostic nomogram. Medicine 0 41760060

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