Affinage

GOLPH3

Golgi phosphoprotein 3 · UniProt Q9H4A6

Length
298 aa
Mass
33.8 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GOLPH3 is a PtdIns(4)P-binding peripheral Golgi protein that couples Golgi membranes to the actin cytoskeleton and serves as an intra-Golgi sorting adaptor governing secretory trafficking, Golgi architecture, glycoenzyme residence, and oncogenic signaling (PMID:19837035, PMID:19553991). Its Golgi targeting depends on direct, structurally defined binding to PtdIns(4)P generated by Golgi PtdIns 4-kinase, a determinant conserved from the yeast orthologue Vps74 (PMID:19837035, PMID:20026658). Through its PtdIns(4)P-dependent membrane association GOLPH3 directly engages the unconventional myosin MYO18A via the MYO18A PDZ module, building a GOLPH3/MYO18A/F-actin connection that generates tensile force to drive tubule and vesicle budding and to stretch the Golgi into its ribbon morphology (PMID:19837035, PMID:23990465). This force-generating module supports anterograde trafficking, directional cell migration with Golgi reorientation toward the leading edge, and cytokinesis where PtdIns(4)P-dependent GOLPH3 recruitment to the cleavage furrow stabilizes the contractile ring and central spindle (PMID:27708138, PMID:24786584). GOLPH3 additionally functions as a COPI/coatomer adaptor: a conserved N-terminal arginine motif binds coatomer, and GOLPH3 recognizes the cytoplasmic tails of Golgi-resident glycosyltransferases to direct their retrograde intra-Golgi recycling, controlling the residence and stability of mannosyltransferases, EXT1/EXT2 heparan-sulfate enzymes, and glycosphingolipid biosynthetic enzymes (PMID:20026658, PMID:22889169, PMID:23720043, PMID:33749896). It also maintains the cis-Golgi localization of LYSET (TMEM251), stabilizing LYSET-GNPT complexes for mannose-6-phosphate tagging of lysosomal hydrolases (PMID:39587297). GOLPH3 senses and tunes Golgi PtdIns(4)P by directly binding the Sac1 phosphatase, an interaction defined crystallographically that locally terminates PtdIns(4)P signaling and is required for glycoenzyme retention (PMID:22553352, PMID:25113029). In the DNA-damage response, DNA-PK phosphorylates GOLPH3 to amplify MYO18A binding, dispersing the Golgi and promoting cell survival (PMID:24485452). GOLPH3 amplification drives oncogenesis by enhancing growth-factor-induced mTOR signaling and altering glycosphingolipid-dependent plasma-membrane composition to promote proliferation (PMID:19553991, PMID:33749896).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2009 High

    Established the core mechanism by which GOLPH3 functions: how it is targeted to the Golgi and how it physically links the organelle to the cytoskeleton to shape membranes.

    Evidence Proteomic lipid-binding screen, Co-IP, knockdown/overexpression with trafficking and morphology readouts, and EM identifying PtdIns(4)P binding and a GOLPH3/MYO18A/F-actin force-generating complex

    PMID:19837035

    Open questions at the time
    • Did not resolve the structural basis of PtdIns(4)P recognition
    • Quantitative force measurements not provided
  2. 2009 High

    Linked GOLPH3 to oncogenic signaling, showing the trafficking protein also controls cell growth via mTOR and is an amplified oncogene.

    Evidence Gain/loss-of-function in vitro and in vivo, retromer interaction studies, mTOR pathway analysis in cancer cells

    PMID:19553991

    Open questions at the time
    • Molecular bridge between Golgi function and mTOR activation not defined
    • Direct GOLPH3-retromer binding interface not mapped
  3. 2009 High

    Provided the structural and conserved mechanistic basis for PtdIns(4)P binding and revealed GOLPH3's role in retaining Golgi glycoenzymes by recognizing their cytosolic tails.

    Evidence Crystal structure of GOLPH3, PtdIns(4)P-binding assays, site-directed mutagenesis, and in vivo yeast localization/function assays of the Vps74 orthologue

    PMID:20026658

    Open questions at the time
    • Did not define the cytosolic-tail recognition motif at residue resolution
    • Connection to coatomer machinery not yet shown
  4. 2012 High

    Identified the coatomer-binding determinant, mechanistically explaining how GOLPH3-mediated glycosyltransferase retention is coupled to COPI retrograde transport.

    Evidence Binding assays, arginine-motif mutagenesis, pulldown/Co-IP, and in vivo yeast function assays

    PMID:22889169

    Open questions at the time
    • Stoichiometry of GOLPH3-coatomer-cargo assembly unresolved
    • Contribution of Arf1p interaction quantitatively undefined
  5. 2012 High

    Showed GOLPH3 acts as a PtdIns(4)P sensor that recruits the Sac1 phosphatase, revealing a feedback role in controlling Golgi phosphoinositide levels and sphingolipid homeostasis.

    Evidence Quantitative binding assay (Kd), yeast genetics, PtdIns(4)P reporter localization, and lipid analysis

    PMID:22553352

    Open questions at the time
    • Did not provide structure of the Sac1-Vps74 interface
    • Direct demonstration in mammalian cells not included
  6. 2014 High

    Defined the Sac1-Vps74 interface structurally and linked its disruption to loss of intra-Golgi PtdIns(4)P compartmentalization and glycoenzyme residence.

    Evidence Crystal structure of the Sac1 N-terminal domain in complex with Vps74, interface mutagenesis, and PtdIns(4)P reporter assays

    PMID:25113029

    Open questions at the time
    • Human GOLPH3-SACM1L complex not structurally validated
    • Regulation of complex formation in vivo unclear
  7. 2014 High

    Connected GOLPH3 to the DNA-damage response, identifying DNA-PK as the kinase whose phosphorylation amplifies MYO18A binding to disperse the Golgi and promote survival.

    Evidence DNA-damage and kinase assays identifying DNA-PK, Co-IP showing phosphorylation-dependent MYO18A binding, and depletion/overexpression survival readouts

    PMID:24485452

    Open questions at the time
    • Phosphosite-resolved structural effect on MYO18A binding not defined
    • How dispersal mechanistically promotes survival unresolved
  8. 2013 High

    Dissected the MYO18A side of the partnership, showing the PDZ module binds GOLPH3 and modulates MYO18A actin engagement, and that the motor lacks intrinsic ATPase competence.

    Evidence Nucleotide-binding characterization, actin co-sedimentation, EM of decorated F-actin, GOLPH3 pulldowns, and ATPase assays

    PMID:23990465

    Open questions at the time
    • How force is generated despite the motor lacking ATP hydrolysis competence remains unexplained
  9. 2013 High

    Demonstrated that GOLPH3 paralogue GOLPH3L shares PtdIns(4)P-dependent Golgi targeting but cannot engage MYO18A, antagonizing the GOLPH3/MYO18A pathway.

    Evidence PI4P-binding assays, Co-IP for MYO18A, and overexpression/knockdown morphology and trafficking readouts

    PMID:23345592

    Open questions at the time
    • Mechanism by which GOLPH3L antagonizes morphology not defined
    • Whether the two paralogues form heterocomplexes unknown
  10. 2013 High

    Established GOLPH3 as a regulator of intra-Golgi retrograde trafficking and stability of EXT glycosyltransferases, linking it to heparan-sulfate synthesis and Hedgehog signaling.

    Evidence Drosophila loss/overexpression genetics, localization imaging, HSPG functional assay, and mammalian validation

    PMID:23720043

    Open questions at the time
    • Direct EXT cytoplasmic-tail recognition by GOLPH3 not biochemically mapped
  11. 2014 High

    Revealed a cytokinesis function, showing PtdIns(4)P-dependent GOLPH3 recruitment to the cleavage furrow is required for contractile-ring and central-spindle stabilization.

    Evidence Drosophila genetics with PI4P-binding mutants, immunofluorescence, and Co-IP with cytokinesis and trafficking components

    PMID:24786584

    Open questions at the time
    • Whether this requires the MYO18A/F-actin module not directly tested
    • Conservation in mammalian cytokinesis not established here
  12. 2016 High

    Positioned GOLPH3 in directional migration by epistasis, showing the PtdIns(4)P/GOLPH3/MYO18A/F-actin pathway drives Golgi reorientation and leading-edge trafficking.

    Evidence Knockdown/overexpression, live migration assays, organelle reorientation imaging, and lysosome-inhibition epistasis

    PMID:27708138

    Open questions at the time
    • Cargo delivered to the leading edge not identified
    • Upstream polarity cues controlling GOLPH3 unclear
  13. 2017 High

    Identified GTP-Rab1 as a direct regulator controlling GOLPH3 localization at the Golgi and cleavage site, linking a Rab GTPase to GOLPH3-dependent architecture and cytokinesis.

    Evidence Drosophila genetics, GTP-state-specific Rab1 pulldown with GOLPH3, immunofluorescence, TEM, and 3D-SIM

    PMID:28100664

    Open questions at the time
    • Whether Rab1 regulates GOLPH3 in mammalian Golgi unresolved
    • Relationship to COG complex function not mechanistically resolved
  14. 2021 High

    Showed GOLPH3 sorts sequentially-acting glycosphingolipid enzymes for retro-transport as part of cisternal maturation, tying GOLPH3 amplification to altered membrane lipids and proliferation.

    Evidence Binding and vesicle trafficking assays, fractionation, and knockdown/overexpression with glycosphingolipid and signaling analysis

    PMID:33749896

    Open questions at the time
    • Precise tail-recognition rules across enzyme classes not defined
    • Selectivity for branchpoint enzymes mechanistically unexplained
  15. 2024 High

    Extended GOLPH3 client repertoire to LYSET (TMEM251), establishing an essential role in mannose-6-phosphate pathway integrity and lysosomal enzyme maturation.

    Evidence Knockout cell lines, fractionation, Co-IP, and M6P-tagging and lysosomal-enzyme maturation assays

    PMID:39587297

    Open questions at the time
    • Why LYSET is an atypical client and its recognition mode not defined
    • Relative redundancy of GOLPH3 vs GOLPH3L for this client unresolved
  16. 2018 Medium

    Expanded the GOLPH3-mTOR axis by identifying interacting regulators (STK25, CENPH) that tune GOLPH3-dependent mTOR signaling in cancer.

    Evidence Co-IP, GST and His-tag pulldowns, mTOR western blots, glycolysis/proliferation assays, and xenografts

    PMID:28819418 PMID:29996891

    Open questions at the time
    • Direct biochemical mechanism connecting GOLPH3 to mTOR kinase not established
    • Single-lab interactions without reciprocal structural mapping
  17. 2020 Medium

    Implicated GOLPH3 in multiple cancer signaling and trafficking outputs including EGFR glycosylation/ubiquitylation, WNT3A exosome secretion via CKAP4, and selective Golgiphagy via LC3B.

    Evidence Stable RNAi, glycosylation/ubiquitylation assays, IP-MS and Co-IP, fractionation, WNT reporters, and endogenous LC3B Co-IP with TEM

    PMID:32335164 PMID:33238647 PMID:34671013

    Open questions at the time
    • Each output rests on largely single-lab evidence
    • Whether these depend on the canonical PtdIns(4)P/MYO18A or COPI activities not tested
  18. 2005 Medium

    Reported a mitochondrial pool of GOLPH3/MIDAS regulating mitochondrial mass and cardiolipin, raising an early question of dual localization.

    Evidence Stable transfection, siRNA, subcellular fractionation, cardiolipin and mitochondrial mass measurements in HeLa cells

    PMID:16263763

    Open questions at the time
    • Mechanistic basis for mitochondrial mass control not defined
    • Reconciliation with Golgi function unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GOLPH3's force-generating, COPI-adaptor, and lipid-sensing activities are coordinated, and whether its many reported cancer-signaling partners act through or independently of these core Golgi functions, remains unresolved.
  • No integrated structural model linking PtdIns(4)P binding, MYO18A engagement, and cargo-tail recognition
  • Most oncogenic interactors validated only in single labs without mechanistic integration

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0060090 molecular adaptor activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0038024 cargo receptor activity 1
Localization
GO:0005794 Golgi apparatus 4 GO:0005739 mitochondrion 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-162582 Signal Transduction 2 R-HSA-9612973 Autophagy 2 R-HSA-1640170 Cell Cycle 1
Partners
CENPHCKAP4LC3BLYSET (TMEM251)MYO18ARAB1SACM1L (SAC1)STK25
Complex memberships
COPI/coatomerGOLPH3/MYO18A/F-actin complexLYSET-GNPT complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 GOLPH3 binds specifically to phosphatidylinositol-4-phosphate (PtdIns(4)P) at the trans-Golgi membrane, and this binding is required for its Golgi localization. GOLPH3 also directly binds the unconventional myosin MYO18A, connecting the Golgi to F-actin. This GOLPH3/MYO18A/F-actin complex generates a tensile force required for efficient tubule and vesicle formation from the Golgi, and is responsible for stretching the Golgi into its extended ribbon morphology. Proteomic lipid-binding screen, Co-IP, knockdown/overexpression with morphology and trafficking readouts, fluorescence and electron microscopy Cell High 19837035
2009 GOLPH3 localizes to the trans-Golgi network and interacts with components of the retromer complex. GOLPH3 regulates cell size and enhances growth-factor-induced mTOR signaling in human cancer cells, and its amplification drives oncogenesis. Gain- and loss-of-function studies in vitro and in vivo, interaction studies with retromer components, mTOR pathway analysis Nature High 19553991
2009 Yeast Vps74 (GOLPH3 orthologue) requires ongoing PtdIns4P synthesis by the Pik1 PtdIns 4-kinase for Golgi targeting. Vps74/GOLPH3 bind specifically to PtdIns4P; a sulfate ion in a crystal structure of GOLPH3 indicated a phosphoinositide-binding site conserved in Vps74. Mutations in this site abolish phosphoinositide binding in vitro and Vps74 function in vivo. Vps74 retains Golgi-resident mannosyltransferases by recognizing their cytosolic tails. Crystal structure of GOLPH3, PtdIns4P-binding assays, site-directed mutagenesis, in vivo localization/function assays in yeast The Journal of cell biology High 20026658
2014 DNA damage triggers Golgi dispersal through a pathway requiring GOLPH3, MYO18A, and F-actin. DNA-PK phosphorylates GOLPH3 in response to DNA damage, and this phosphorylation increases GOLPH3's interaction with MYO18A, amplifying the tensile force on the Golgi and causing its dispersal throughout the cytoplasm. This Golgi DNA-damage response promotes cell survival after DNA damage. DNA damage assays, kinase assays identifying DNA-PK as the GOLPH3 kinase, Co-IP showing increased GOLPH3-MYO18A interaction after phosphorylation, depletion/overexpression with survival readouts Cell High 24485452
2012 Vps74 (GOLPH3 orthologue) binds directly to the catalytic domain of Sac1 PtdIns4P phosphatase (Kd = 3.8 μM). This interaction allows Vps74 to sense PtdIns4P levels on medial Golgi cisternae and direct Sac1-mediated dephosphorylation, locally terminating PtdIns4P signaling. Loss of Vps74 elevates PtdIns4P on medial Golgi and perturbs complex sphingolipid homeostasis. Binding assay (measured Kd), genetic analysis in yeast, PtdIns4P reporter localization, lipid analysis Molecular biology of the cell High 22553352
2014 The crystal structure of Sac1 N-terminal domain in complex with Vps74 (GOLPH3 orthologue) was solved. The interface involves the N-terminal subdomain of the Sac1 homology domain. Disruption of the Sac1-Vps74 interface broadens intra-Golgi PtdIns4P distribution and causes failure to maintain residence of a medial Golgi mannosyltransferase. Crystal structure determination, interface mutagenesis, in vivo localization assays, PtdIns4P reporter The Journal of cell biology High 25113029
2012 GOLPH3 family proteins (Vps74p) contain a conserved N-terminal arginine-motif that is necessary and sufficient to mediate direct binding to coatomer (COPI). Loss of coatomer binding renders Vps74p non-functional for glycosyltransferase retention. Vps74p oligomerization status and PtdIns4P-binding account for its membrane-binding capacity; an Arf1p-Vps74p interaction also contributes. Binding assays, site-directed mutagenesis of arginine motif, Co-IP/pulldown, in vivo function assays in yeast Traffic (Copenhagen, Denmark) High 22889169
2013 GOLPH3L, a GOLPH3 paralogue, binds PI4P and localizes to the Golgi via PI4P binding, and is required for efficient anterograde trafficking similarly to GOLPH3. However, GOLPH3L is largely unable to bind MYO18A, and perturbation of GOLPH3L produces opposite effects on Golgi morphology compared to GOLPH3/MYO18A, antagonizing the GOLPH3/MYO18A pathway. PI4P-binding assays, Co-IP for MYO18A interaction, overexpression/knockdown with Golgi morphology and trafficking readouts Molecular biology of the cell High 23345592
2013 Human myosin-18A (MYO18A) contains two actin-binding sites: one in the KE-rich region of the N-terminal extension (ATP-independent) and one in the generic motor domain (regulated by nucleotide). The PDZ module of MYO18A mediates direct binding to GOLPH3, and this interaction modulates the actin-binding properties of MYO18A's N-terminal extension. MYO18A motor domain lacks intrinsic ATP hydrolysis competence. Biochemical characterization of nucleotide binding, actin co-sedimentation assays, electron microscopy of decorated F-actin, pulldown assays for GOLPH3 binding, ATPase assay The Journal of biological chemistry High 23990465
2013 Drosophila GOLPH3 (Rotini/Rti) regulates retrograde trafficking of EXT glycosyltransferases (EXT1/EXT2) within the Golgi. Reduction of Rti shifts EXT steady-state distribution toward the trans-Golgi, leading to their degradation; overexpression mislocalizes them toward cis-Golgi/ER. Both loss and overexpression result in incomplete heparan sulfate proteoglycans and perturbed Hedgehog signaling. GOLPH3 similarly modulates EXT1/2 stability in mammalian cells. Drosophila genetics (loss-of-function and overexpression), immunofluorescence localization, HSPG functional assay, mammalian cell validation Development (Cambridge, England) High 23720043
2014 Drosophila GOLPH3 accumulates at the cleavage furrow during cell division and is essential for cytokinesis in spermatocytes and neuroblasts. GOLPH3 is required for contractile ring and central spindle formation, maintaining centralspindlin and Rho1 at the cell equator, and stabilizing Myosin II and Septin rings. The PI(4)P-binding ability of GOLPH3 is essential for its recruitment to the cleavage furrow and for accumulation of PI(4)P- and Rab11-associated secretory organelles at the cleavage site. Drosophila genetics (loss-of-function, PI4P-binding mutants), immunofluorescence, Co-IP with cytokinesis and trafficking components PLoS genetics High 24786584
2016 The PtdIns(4)P/GOLPH3/MYO18A/F-actin pathway is necessary and limiting for directional cell migration. GOLPH3 promotes reorientation of the Golgi toward the leading edge and drives anterograde trafficking to the leading edge. GOLPH3 also promotes reorientation of lysosomes toward the leading edge indirectly, via its effect on the Golgi. Lysosome function itself is dispensable for migration. Knockdown/overexpression, live cell migration assays, organelle reorientation imaging, epistasis analysis with lysosome inhibition Molecular biology of the cell High 27708138
2017 GTP-bound Rab1 directly interacts with GOLPH3 and controls its localization at the Golgi and at the cleavage site during cytokinesis in Drosophila. Loss of Rab1 (omelette/omt) disrupts Golgi architecture and actomyosin ring stabilization. Rab1 colocalizes with COG complex subunit Cog7 and GOLPH3 at Golgi stacks. Drosophila genetics, direct interaction assay (GTP-bound Rab1 pulldown with GOLPH3), immunofluorescence, transmission electron microscopy, 3D-SIM super-resolution microscopy Open biology High 28100664
2021 GOLPH3 sorts a group of sequentially-acting glycosphingolipid biosynthetic enzymes operating at branchpoints into vesicles for intra-Golgi retro-transport, acting as a component of the cisternal maturation mechanism. GOLPH3 controls sub-Golgi localization and lysosomal degradation rate of specific enzymes. Increased GOLPH3 levels (as in tumors) alter glycosphingolipid synthesis and plasma membrane composition, promoting mitogenic signaling and cell proliferation. Binding assays, vesicle trafficking assays, subcellular fractionation, knockdown/overexpression with glycosphingolipid analysis and signaling readouts The EMBO journal High 33749896
2005 MIDAS/GOLPH3 protein expression is enhanced by the absence of mitochondrial DNA (mtDNA). A majority of MIDAS localizes to mitochondria with a small fraction in the Golgi in HeLa cells. Overexpression increases total mitochondrial mass (accompanied by increased cardiolipin), while siRNA-mediated knockdown decreases it, without affecting mtDNA, RNA, or protein amounts. Stable transfection and siRNA knockdown, subcellular fractionation, cardiolipin measurement, mitochondrial mass quantification Journal of cell science Medium 16263763
2012 PI4P and its binding protein GOLPH3 are required for hepatitis C virus (HCV) secretion. Silencing GOLPH3 dramatically reduces HCV virion secretion with concomitant accumulation of intracellular virions, indicating a stall in virion egress. Silencing MYO18A produces the same effect, consistent with GOLPH3 requiring MYO18A to apply tensile force for vesicle budding. siRNA knockdown of GOLPH3 and MYO18A, HCV infectivity and intracellular virion quantification, Golgi morphology analysis The Journal of biological chemistry Medium 22745132
2018 GOLPH3 promotes cell proliferation and activates mTOR signaling via interaction with STK25 (serine/threonine protein kinase 25). STK25 interacts with GOLPH3 (confirmed by Co-IP, GST pull-down, and His-tag pull-down) and negatively regulates GOLPH3-dependent mTOR signaling and aerobic glycolysis. Co-immunoprecipitation, GST pull-down, His-tag pull-down, mTOR pathway western blot, glycolysis assays, xenograft model Journal of experimental & clinical cancer research Medium 29996891
2017 CENPH (centromere protein H) interacts directly with GOLPH3 (confirmed by Co-IP, GST pull-down, His-tag pull-down, and confocal microscopy), and through this interaction attenuates GOLPH3-dependent mTOR signaling (both mTORC1 and mTORC2), reducing rapamycin sensitivity in colorectal cancer cells. Co-immunoprecipitation, GST pull-down, His-tag pull-down, confocal colocalization, mTOR pathway western blot, proliferation assays Journal of Cancer Medium 28819418
2015 GOLPH3 promotes NF-κB pathway activation in hepatocellular carcinoma by promoting K63-linked polyubiquitination of TRAF2, RIP, and NEMO, thereby sustaining NF-κB activation. Overexpression and knockdown, ubiquitination assays (K63-linkage specific), western blot for NF-κB pathway components, in vitro and in vivo tumor models The Journal of pathology Medium 25385148
2013 GOLPH3 regulates glioma cell migration and invasion through modulation of RhoA expression; downregulation of GOLPH3 reduces RhoA levels and inhibits cytoskeletal reorganization, while RhoA overexpression rescues the migration deficit caused by GOLPH3 knockdown. siRNA knockdown, RhoA expression analysis, migration/invasion assays, rescue experiment with RhoA overexpression Biochemical and biophysical research communications Medium 23500462
2014 GOLPH3 promotes glioblastoma cell migration and invasion via the mTOR-YB1 pathway; knockdown of GOLPH3 decreases YB1 levels and mTOR activity, and overexpression-induced migration is blocked by mTOR inhibition (INK128) or YB1 knockdown, placing mTOR and YB1 downstream of GOLPH3 in this pathway. siRNA knockdown, overexpression, mTOR inhibitor epistasis, YB1 knockdown epistasis, migration/invasion assays Molecular carcinogenesis Medium 25156912
2018 GOLPH3 promotes JAK2-STAT3 pathway activation in glioma by acting as a scaffold protein; GOLPH3, JAK2, and STAT3 exist in the same protein complex (demonstrated by Co-IP), and GOLPH3 affects the interaction between JAK2 and STAT3. Co-immunoprecipitation, western blot for p-JAK2 and p-STAT3, overexpression and knockdown, STAT3 knockdown epistasis Journal of neuro-oncology Medium 29713848
2020 GOLPH3 interacts with LC3B (confirmed by endogenous Co-IP in multiple cell lines) and acts as a novel cargo receptor for selective autophagy of the Golgi apparatus (Golgiphagy). Knockdown of GOLPH3 inhibits Golgiphagy. Co-immunoprecipitation (endogenous), immunofluorescence colocalization of Golgi markers with LC3B, transmission electron microscopy, GOLPH3 knockdown Life sciences Medium 32335164
2020 GOLPH3 regulates EGFR glycosylation (sialylation and fucosylation) and ubiquitylation in glioblastoma T98G cells. GOLPH3 knockdown decreases EGFR sialylation and fucosylation, reduces ligand-induced EGFR autophosphorylation, delays ligand-induced EGFR downregulation, causes EGFR accumulation at endo-lysosomal compartments, and abolishes EGF-induced EGFR ubiquitylation. Stable RNAi knockdown, EGFR glycosylation analysis, ubiquitylation assay, surface EGFR quantification, ligand-induced trafficking assays International journal of molecular sciences Medium 33238647
2022 Drosophila GOLPH3 (dGOLPH3) physically interacts with TCTP (Translationally controlled tumor protein) and 14-3-3ζ. dGOLPH3 knockdown reduces wing and eye size, and this phenotype is partially rescued by overexpression of Tctp, 14-3-3ζ, or Rheb. Golgi localization of Rheb in Drosophila cells depends on dGOLPH3. dGOLPH3 depletion reduces phosphorylated S6K (mTORC1 downstream target) and compromises autophagy flux. Co-IP for protein interactions, RNAi-mediated knockdown, genetic rescue assays, Rheb localization imaging, S6K phosphorylation western blot, autophagy flux assay Cell death & disease Medium 36435842
2021 GOLPH3 interacts with cytoskeleton-associated protein 4 (CKAP4), decreases plasma membrane-localized CKAP4, and increases exosome-localized CKAP4, promoting formation of CKAP4-containing exosomes. CKAP4 then binds exosomal WNT3A to enhance its secretion, activating WNT/β-catenin signaling and promoting cancer stem-like phenotype and metastasis. Immunoprecipitation-mass spectrometry, Co-IP, CKAP4 membrane vs. exosome fractionation, WNT3A secretion assay, WNT/β-catenin reporter, in vivo metastasis models Cell death & disease Medium 34671013
2020 GOLPH3 interacts with STIP1 (stress-inducible protein 1) and both are co-localized in pancreatic ductal adenocarcinoma. The GOLPH3-STIP1 interaction activates hTERT and telomerase activity via c-Myc, and upregulates cyclin D1, promoting tumor cell growth. High-throughput BiFC screen, Co-IP, immunohistochemistry colocalization, Q-TRAP telomerase assay, siRNA knockdown, xenograft model Frontiers in oncology Medium 33134174
2024 GOLPH3 and GOLPH3L maintain the cis-Golgi localization of LYSET (TMEM251), an atypical client of GOLPH3/GOLPH3L. Loss of GOLPH3 and GOLPH3L destabilizes LYSET-GNPT complexes, impairs M6P-tagging of lysosomal hydrolases, and causes disturbed maturation and trafficking of lysosomal enzymes, establishing an essential role for GOLPH3/GOLPH3L in mannose 6-phosphate pathway integrity and lysosomal homeostasis. Knockout cell lines, fractionation, Co-IP, M6P-tagging assays, lysosomal enzyme maturation assays The EMBO journal High 39587297
2021 In Drosophila, GOLPH3 interacts with the orthologs of Fragile X mental retardation protein (FMRP) and Ataxin-2 in testes, as identified by affinity purification coupled with mass spectrometry (AP-MS). The GOLPH3 interactome is enriched for proteins involved in vesicle-mediated trafficking, cell proliferation, and cytoskeleton dynamics. Affinity purification coupled with mass spectrometry (AP-MS) in Drosophila testes Cells Low 34571985
2022 In high-glucose conditions, GOLPH3 interacts with Vimentin (demonstrated by GST-pulldown and Co-IP), and this interaction promotes Golgi dispersal. An upstream pathway (NLRP3/VPS35/GOLPH3) regulates this process; NLRP3 promotes VPS35-GOLPH3 interaction, and Golph3 knockout abolishes Vimentin upregulation and Golgi dispersal. GST-pulldown, Co-IP, genetic knockout, Golgi morphology assay Aging Low 36378718
2021 GOLPH3 interacts with and recruits prohibitin-2 (PHB2), a mitophagy receptor, along with LC3-II, to promote autophagy in glioma. PHB2 knockdown abolishes the autophagy-promoting effect of GOLPH3 overexpression, placing PHB2 downstream of GOLPH3 in this pathway. Co-IP, siRNA knockdown epistasis, autophagy assays (LC3-II conversion, chloroquine inhibition), in vivo xenograft American journal of cancer research Low 34094672

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 GOLPH3 bridges phosphatidylinositol-4- phosphate and actomyosin to stretch and shape the Golgi to promote budding. Cell 353 19837035
2009 GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer. Nature 315 19553991
2022 MiDAS 4: A global catalogue of full-length 16S rRNA gene sequences and taxonomy for studies of bacterial communities in wastewater treatment plants. Nature communications 229 35393411
2014 DNA damage triggers Golgi dispersal via DNA-PK and GOLPH3. Cell 203 24485452
2015 MiDAS: the field guide to the microbes of activated sludge. Database : the journal of biological databases and curation 156 26120139
2009 PtdIns4P recognition by Vps74/GOLPH3 links PtdIns 4-kinase signaling to retrograde Golgi trafficking. The Journal of cell biology 144 20026658
2020 MiDAS 3: An ecosystem-specific reference database, taxonomy and knowledge platform for activated sludge and anaerobic digesters reveals species-level microbiome composition of activated sludge. Water research 143 32777640
2012 Overexpression of GOLPH3 promotes proliferation and tumorigenicity in breast cancer via suppression of the FOXO1 transcription factor. Clinical cancer research : an official journal of the American Association for Cancer Research 134 22675169
2012 Role of phosphatidylinositol 4-phosphate (PI4P) and its binding protein GOLPH3 in hepatitis C virus secretion. The Journal of biological chemistry 84 22745132
2021 Golgi maturation-dependent glycoenzyme recycling controls glycosphingolipid biosynthesis and cell growth via GOLPH3. The EMBO journal 83 33749896
2012 Structure-guided design of a high-affinity platelet integrin αIIbβ3 receptor antagonist that disrupts Mg²⁺ binding to the MIDAS. Science translational medicine 81 22422993
2015 GOLPH3 links the Golgi, DNA damage, and cancer. Cancer research 74 25634214
2018 GOLPH3: a Golgi phosphatidylinositol(4)phosphate effector that directs vesicle trafficking and drives cancer. Journal of lipid research 68 30266835
2010 Phylogeography, colonization and population history of the Midas cichlid species complex (Amphilophus spp.) in the Nicaraguan crater lakes. BMC evolutionary biology 67 20977752
2013 GOLPH3L antagonizes GOLPH3 to determine Golgi morphology. Molecular biology of the cell 66 23345592
2020 Oncogenic Roles of GOLPH3 in the Physiopathology of Cancer. International journal of molecular sciences 65 32023813
2013 Transcriptomics of morphological color change in polychromatic Midas cichlids. BMC genomics 64 23497064
2022 Long-Term Effectiveness of Three Anti-CGRP Monoclonal Antibodies in Resistant Chronic Migraine Patients Based on the MIDAS score. CNS drugs 59 35146696
2012 Overexpression of GOLPH3 is associated with poor clinical outcome in gastric cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 58 23132295
2005 MIDAS/GPP34, a nuclear gene product, regulates total mitochondrial mass in response to mitochondrial dysfunction. Journal of cell science 58 16263763
2015 GOLPH3 Mediated Golgi Stress Response in Modulating N2A Cell Death upon Oxygen-Glucose Deprivation and Reoxygenation Injury. Molecular neurobiology 57 25633094
2015 Golgi phosphoprotein 3 (GOLPH3) promotes hepatocellular carcinoma cell aggressiveness by activating the NF-κB pathway. The Journal of pathology 56 25385148
2014 GOLPH3 is essential for contractile ring formation and Rab11 localization to the cleavage site during cytokinesis in Drosophila melanogaster. PLoS genetics 56 24786584
2017 miR34a/GOLPH3 Axis abrogates Urothelial Bladder Cancer Chemoresistance via Reduced Cancer Stemness. Theranostics 55 29187903
2013 Functional characterization of human myosin-18A and its interaction with F-actin and GOLPH3. The Journal of biological chemistry 55 23990465
2017 Rapid and Parallel Adaptive Evolution of the Visual System of Neotropical Midas Cichlid Fishes. Molecular biology and evolution 54 28444297
2016 GOLPH3 drives cell migration by promoting Golgi reorientation and directional trafficking to the leading edge. Molecular biology of the cell 54 27708138
2014 GOLPH3 promotes glioblastoma cell migration and invasion via the mTOR-YB1 pathway in vitro. Molecular carcinogenesis 54 25156912
2012 Local control of phosphatidylinositol 4-phosphate signaling in the Golgi apparatus by Vps74 and Sac1 phosphoinositide phosphatase. Molecular biology of the cell 53 22553352
2012 A conserved N-terminal arginine-motif in GOLPH3-family proteins mediates binding to coatomer. Traffic (Copenhagen, Denmark) 53 22889169
2011 Role of GOLPH3 and GOLPH3L in the proliferation of human rhabdomyosarcoma. Oncology reports 52 21822541
2017 GOLPH3 induces epithelial-mesenchymal transition via Wnt/β-catenin signaling pathway in epithelial ovarian cancer. Cancer medicine 51 28332316
2024 MiDAS 5: Global diversity of bacteria and archaea in anaerobic digesters. Nature communications 49 38918384
2013 GOLPH3 regulates the migration and invasion of glioma cells though RhoA. Biochemical and biophysical research communications 49 23500462
2024 Mosaic integration and knowledge transfer of single-cell multimodal data with MIDAS. Nature biotechnology 46 38263515
2008 Distinct roles of beta1 metal ion-dependent adhesion site (MIDAS), adjacent to MIDAS (ADMIDAS), and ligand-associated metal-binding site (LIMBS) cation-binding sites in ligand recognition by integrin alpha2beta1. The Journal of biological chemistry 45 18820259
2016 GOLPH3 and oncogenesis: What is the molecular link? Tissue & cell 44 27378035
2012 Bifidobacterium reuteri sp. nov., Bifidobacterium callitrichos sp. nov., Bifidobacterium saguini sp. nov., Bifidobacterium stellenboschense sp. nov. and Bifidobacterium biavatii sp. nov. isolated from faeces of common marmoset (Callithrix jacchus) and red-handed tamarin (Saguinus midas). Systematic and applied microbiology 43 22225994
2021 GOLPH3/CKAP4 promotes metastasis and tumorigenicity by enhancing the secretion of exosomal WNT3A in non-small-cell lung cancer. Cell death & disease 40 34671013
2020 GOLPH3 inhibition reverses oxaliplatin resistance of colon cancer cells via suppression of PI3K/AKT/mTOR pathway. Life sciences 40 32818544
2016 miR-186 inhibits cell proliferation of prostate cancer by targeting GOLPH3. American journal of cancer research 40 27648356
2015 The GOLPH3 pathway regulates Golgi shape and function and is activated by DNA damage. Frontiers in neuroscience 40 26500484
2019 Co-delivery of GOLPH3 siRNA and gefitinib by cationic lipid-PLGA nanoparticles improves EGFR-targeted therapy for glioma. Journal of molecular medicine (Berlin, Germany) 38 31673738
2023 GOLPH3 promotes endotoxemia-induced liver and kidney injury through Golgi stress-mediated apoptosis and inflammatory response. Cell death & disease 37 37479687
2017 Rab1 interacts with GOLPH3 and controls Golgi structure and contractile ring constriction during cytokinesis in Drosophila melanogaster. Open biology 37 28100664
2014 Sac1-Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus. The Journal of cell biology 34 25113029
2018 MIDAS: A Modular DNA Assembly System for Synthetic Biology. ACS synthetic biology 33 29620866
2018 STK25-induced inhibition of aerobic glycolysis via GOLPH3-mTOR pathway suppresses cell proliferation in colorectal cancer. Journal of experimental & clinical cancer research : CR 32 29996891
2014 GOLPH3 predicts survival of colorectal cancer patients treated with 5-fluorouracil-based adjuvant chemotherapy. Journal of translational medicine 30 24444035
2014 Mechanisms of GOLPH3 associated with the progression of gastric cancer: a preliminary study. PloS one 30 25286393
2013 The Drosophila GOLPH3 homolog regulates the biosynthesis of heparan sulfate proteoglycans by modulating the retrograde trafficking of exostosins. Development (Cambridge, England) 30 23720043
2018 Golgi phosphoprotein 3 (GOLPH3) promotes hepatocellular carcinoma progression by activating mTOR signaling pathway. BMC cancer 29 29914442
2016 Correlation of GOLPH3 Gene with Wnt Signaling Pathway in Human Colon Cancer Cells. Journal of Cancer 29 27313783
2014 Study of GOLPH3: a potential stress-inducible protein from Golgi apparatus. Molecular neurobiology 28 24395131
2025 Isatuximab, carfilzomib, lenalidomide, and dexamethasone induction in newly diagnosed myeloma: analysis of the MIDAS trial. Blood 27 39841461
2020 Punicalagin inhibits the viability, migration, invasion, and EMT by regulating GOLPH3 in breast cancer cells. Journal of receptor and signal transduction research 27 32024401
2018 ATF-3/miR-590/GOLPH3 signaling pathway regulates proliferation of breast cancer. BMC cancer 27 29534690
2020 Regulation of the Golgi apparatus via GOLPH3-mediated new selective autophagy. Life sciences 26 32335164
2022 An intronic transposon insertion associates with a trans-species color polymorphism in Midas cichlid fishes. Nature communications 25 35027541
2020 A novel protective role for microRNA-3135b in Golgi apparatus fragmentation induced by chemotherapy via GOLPH3/AKT1/mTOR axis in colorectal cancer cells. Scientific reports 25 32601379
2018 GOLPH3 promotes glioma progression via facilitating JAK2-STAT3 pathway activation. Journal of neuro-oncology 25 29713848
2018 Inhibition of glioma growth by a GOLPH3 siRNA-loaded cationic liposomes. Journal of neuro-oncology 25 30105446
2017 MicroRNA-134 suppresses cell proliferation in gastric cancer cells via targeting of GOLPH3. Oncology reports 25 28260021
2010 Genetic, comparative genomic, and expression analyses of the Mc1r locus in the polychromatic Midas cichlid fish (Teleostei, Cichlidae Amphilophus sp.) species group. Journal of molecular evolution 25 20449580
2015 Increased Expression of GOLPH3 is Associated with the Proliferation of Prostate Cancer. Journal of Cancer 24 25874005
2001 A naturally occurring point mutation in the beta3 integrin MIDAS-like domain affects differently alphavbeta3 and alphaIIIbbeta3 receptor function. Thrombosis and haemostasis 22 11776310
2017 CENPH Inhibits Rapamycin Sensitivity by Regulating GOLPH3-dependent mTOR Signaling Pathway in Colorectal Cancer. Journal of Cancer 21 28819418
2016 Cigarette Smoking Condensate Disrupts Endoplasmic Reticulum-Golgi Network Homeostasis Through GOLPH3 Expression in Normal Lung Epithelial Cells. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco 21 27611309
2022 Does MIDAS reduction at 3 months predict the outcome of erenumab treatment? A real-world, open-label trial. The journal of headache and pain 20 36115947
2019 Role of GOLPH3 and TPX2 in Neuroblastoma DNA Damage Response and Cell Resistance to Chemotherapy. International journal of molecular sciences 20 31557970
2019 Crystal structures of Rea1-MIDAS bound to its ribosome assembly factor ligands resembling integrin-ligand-type complexes. Nature communications 19 31296859
2014 High GOLPH3 expression is associated with a more aggressive behavior of epithelial ovarian carcinoma. Virchows Archiv : an international journal of pathology 19 24458516
2020 GOLPH3 Regulates EGFR in T98G Glioblastoma Cells by Modulating Its Glycosylation and Ubiquitylation. International journal of molecular sciences 18 33238647
2022 Molecular parallelism in the evolution of a master sex-determining role for the anti-Mullerian hormone receptor 2 gene (amhr2) in Midas cichlids. Molecular ecology 17 35403749
2022 Metformin antagonizes nickel-refining fumes-induced cell pyroptosis via Nrf2/GOLPH3 pathway in vitro and in vivo. Ecotoxicology and environmental safety 17 36334342
2021 GOLPH3 promotes glioma progression by enhancing PHB2-mediated autophagy. American journal of cancer research 17 34094672
2022 LncRNA NORAD deficiency alleviates kidney injury in mice and decreases the inflammatory response and apoptosis of lipopolysaccharide-stimulated HK-2 cells via the miR-577/GOLPH3 axis. Cytokine 16 35255377
2010 Testing the carotenoid trade-off hypothesis in the polychromatic Midas cichlid, Amphilophus citrinellus. Physiological and biochemical zoology : PBZ 16 20151818
2023 Development of a Golgi-targeted superoxide anion fluorescent probe for elucidating protein GOLPH3 function in myocardial ischemia-reperfusion injury. Analytica chimica acta 15 37032049
2020 GOLPH3 Promotes Angiogenesis of Lung Adenocarcinoma by Regulating the Wnt/β-Catenin Signaling Pathway. OncoTargets and therapy 15 32636646
2019 MiR-3150b-3p inhibits the progression of colorectal cancer cells via targeting GOLPH3. Journal of investigative medicine : the official publication of the American Federation for Clinical Research 15 31678970
2017 Effect of GOLPH3 on cumulus granulosa cell apoptosis and ICSI pregnancy outcomes. Scientific reports 15 28801637
2017 GOLPH3 expression promotes the resistance of HT29 cells to 5‑fluorouracil by activating multiple signaling pathways. Molecular medicine reports 15 29115442
2017 Proteomics Identifies Golgi phosphoprotein 3 (GOLPH3) with A Link Between Golgi Structure, Cancer, DNA Damage and Protection from Cell Death. Molecular & cellular proteomics : MCP 14 28954815
2024 GOLPH3 and GOLPH3L maintain Golgi localization of LYSET and a functional mannose 6-phosphate transport pathway. The EMBO journal 13 39587297
2022 GOLPH3 protein controls organ growth by interacting with TOR signaling proteins in Drosophila. Cell death & disease 13 36435842
2020 GOLPH3 Promotes Cancer Growth by Interacting With STIP1 and Regulating Telomerase Activity in Pancreatic Ductal Adenocarcinoma. Frontiers in oncology 13 33134174
2019 FAP-a and GOLPH3 Are Hallmarks of DCIS Progression to Invasive Breast Cancer. Frontiers in oncology 13 31921678
2017 GOLPH3 promotes cell proliferation and tumorigenicity in esophageal squamous cell carcinoma via mTOR and Wnt/β‑catenin signal activation. Molecular medicine reports 13 28901498
2023 Telomere Fragility and MiDAS: Managing the Gaps at the End of the Road. Genes 12 36833275
2020 Tenacissoside H Induces Apoptosis and Inhibits Migration of Colon Cancer Cells by Downregulating Expression of GOLPH3 Gene. Evidence-based complementary and alternative medicine : eCAM 12 32454851
2017 Tol2 transposon-mediated transgenesis in the Midas cichlid (Amphilophus citrinellus) - towards understanding gene function and regulatory evolution in an ecological model system for rapid phenotypic diversification. BMC developmental biology 12 29169323
1999 Mutation identification DNA analysis system (MIDAS) for detection of known mutations. Electrophoresis 12 10380753
2022 Inhibition of NLRP3 and Golph3 ameliorates diabetes-induced neuroinflammation in vitro and in vivo. Aging 11 36378718
2020 GOLPH3 Regulates Exosome miRNA Secretion in Glioma Cells. Journal of molecular neuroscience : MN 11 32227282
2020 Protosappanin B Exerts Anti-tumor Effects on Colon Cancer Cells via Inhibiting GOLPH3 Expression. Integrative cancer therapies 11 33289438
2017 MIDAS: Mining differentially activated subpaths of KEGG pathways from multi-class RNA-seq data. Methods (San Diego, Calif.) 11 28579402
2023 Long noncoding RNA HOTAIR promotes breast cancer development through the lncRNA HOTAIR/miR-1/GOLPH3 axis. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 10 37099061
2021 Identification of GOLPH3 Partners in Drosophila Unveils Potential Novel Roles in Tumorigenesis and Neural Disorders. Cells 10 34571985
2018 Expression of GOLPH3 in patients with non-small cell lung cancer and xenografts models. Oncology letters 10 29849795

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