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Showing GOLGA3 — GCP170 is a alias.

GOLGA3

Golgin subfamily A member 3 · UniProt Q08378

Length
1498 aa
Mass
167.4 kDa
Annotated
2026-06-10
19 papers in source corpus 17 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GOLGA3/golgin-160 is a peripheral cytoplasmic-face Golgi protein with a large coiled-coil domain that functions both in cargo-selective post-Golgi trafficking and as a Golgi-localized integrator of apoptotic signaling (PMID:9295333, PMID:15829563). Its N-terminal head domain carries the Golgi targeting information (residues 172–257) and, when truncated, exposes a cryptic nuclear localization signal, so that caspase cleavage of the head can release fragments competent for nuclear translocation (PMID:12130652). This processing is gated by MLK3, which directly phosphorylates the head region and enhances caspase cleavage at Asp139 (PMID:14734651), and by GCP60, which preferentially binds the caspase-generated fragment (residues 140–311) to retain it at the Golgi and block nuclear accumulation in a redox-sensitive manner dependent on GCP60 Cys-463 (PMID:16870622, PMID:17711851). A caspase-resistant golgin-160 dominantly blocks apoptosis induced by death-receptor ligation and ER stress by preventing initiator caspase activation, establishing golgin-160 cleavage as a required step in stimulus-specific apoptotic signaling at the Golgi (PMID:15829563). In constitutive trafficking, golgin-160 binds cargo directly—including the β1-adrenergic receptor via head residues 140–257 and the receptor's third intracellular loop—and promotes their post-Golgi/TGN delivery to the plasma membrane (PMID:17118120, PMID:24566136), with parallel roles in surface delivery of GLUT4/IRAP and the ROMK and other Kir/Kv potassium channels (PMID:17050738, PMID:16543716). Golgin-160 also maintains Golgi structural integrity, its loss causing Golgi fragmentation and impaired extracellular matrix secretion. In vivo, GOLGA3 is essential for male fertility, required for pachytene spermatocyte survival and normal spermiogenesis, with null alleles causing germ cell apoptosis and acrosome and sperm defects (PMID:9892724, PMID:11835574, PMID:23495255).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1997 Medium

    Established the basic identity of GOLGA3 as a peripheral coiled-coil protein on the cytoplasmic face of the Golgi whose membrane association is regulated by phosphorylation.

    Evidence Immunocytochemistry, subcellular fractionation, and immunoelectron microscopy

    PMID:9295333

    Open questions at the time
    • Kinase responsible for phosphorylation not identified
    • No cargo or functional role defined
  2. 1999 Medium

    Showed GOLGA3 is required in vivo, not just a structural Golgi marker, by linking gene disruption to a male germ cell defect.

    Evidence Transgenic mouse gene disruption with linkage and expression analysis

    PMID:9892724

    Open questions at the time
    • Cellular mechanism of the spermatogenesis defect unknown
    • Did not identify the stage of arrest
  3. 2002 Medium

    Mapped the Golgi-targeting region and revealed a cryptic NLS, providing the structural basis for how caspase fragments could be redirected to the nucleus.

    Evidence GFP-tagged deletion constructs and fluorescence microscopy; transgenic rescue defining the germ-cell-essential region

    PMID:11835574 PMID:12130652

    Open questions at the time
    • Nuclear function of fragments not demonstrated
    • Endogenous trigger for fragment release not yet defined
  4. 2003 Medium

    Identified GCP16 as an interaction partner of the Golgi-localization domain, connecting golgin-160 to Golgi-to-surface transport.

    Evidence Yeast two-hybrid using residues 137–237 as bait, co-localization, and transport assays

    PMID:14522980

    Open questions at the time
    • Direct functional consequence of the interaction for golgin-160 unclear
    • Single-lab interaction without reciprocal validation
  5. 2004 High

    Defined MLK3 as a kinase that phosphorylates the golgin-160 head and couples phosphorylation to caspase cleavage, mechanistically linking signaling input to apoptotic processing.

    Evidence In vitro kinase assay with defined substrate region, co-IP, and cleavage analysis

    PMID:14734651

    Open questions at the time
    • Specific phosphorylated residue(s) not pinpointed
    • How phosphorylation enhances caspase accessibility unresolved
  6. 2005 High

    Demonstrated golgin-160 cleavage is functionally required for apoptosis from specific (death-receptor and ER-stress) stimuli, and identified GCP60/PIST partners controlling fragment fate.

    Evidence Caspase-resistant mutant cell lines with caspase activation readouts; yeast two-hybrid and GST pulldown for partner mapping

    PMID:15829563 PMID:15951434

    Open questions at the time
    • Downstream nuclear targets of released fragments unknown
    • Mechanism by which uncleaved golgin-160 blocks initiator caspase activation not resolved
  7. 2006 High

    Expanded golgin-160 cargo specificity to GLUT4/IRAP, ROMK and other K+ channels, and the β1-adrenergic receptor, establishing it as a cargo-selective trafficking adaptor.

    Evidence siRNA/RNAi with rescue, in vitro binding and domain mapping, plasma-membrane fractionation, Xenopus oocyte electrophysiology, immunoEM

    PMID:16543716 PMID:16870622 PMID:17050738 PMID:17118120

    Open questions at the time
    • Shared structural feature recognized across diverse cargos not defined
    • Whether cargo binding and apoptotic functions are mechanistically coupled unknown
  8. 2007 High

    Identified a redox-sensitive switch (GCP60 Cys-463) that controls Golgi retention versus nuclear translocation of golgin-160 fragments, linking oxidative state to fragment fate.

    Evidence Site-directed mutagenesis, in vitro reconstitution with redox manipulation, and cell-based localization

    PMID:17711851

    Open questions at the time
    • Physiological redox conditions that drive the switch in vivo not established
    • Nuclear consequence of fragment delivery still undefined
  9. 2013 Medium

    A null Golga3 allele defined the in vivo germ cell phenotype—late meiotic disruption, germ cell apoptosis, and acrosome/sperm defects—connecting golgin-160 loss to programmed cell death in spermatogenesis.

    Evidence ENU-derived nonsense mutant mice with TUNEL, histology, and IVF

    PMID:23495255

    Open questions at the time
    • Whether apoptosis reflects the Golgi caspase pathway or trafficking failure unclear
    • Cargo dependence of the germ cell phenotype unknown
  10. 2014 Medium

    Localized golgin-160's action on β1AR to the post-Golgi/TGN step via basic residues in the receptor's third intracellular loop.

    Evidence Site-directed mutagenesis, flow cytometry, and pulse-chase trafficking assays

    PMID:24566136

    Open questions at the time
    • Identity of the TGN machinery recruited by golgin-160 unknown
    • Generalizability of the basic-residue motif to other cargos untested
  11. 2019 Low

    Linked golgin-160 to Golgi positioning/size and cell migration in glioma cells, extending its structural role to motility.

    Evidence Lentiviral knockdown with Golgi morphology and Transwell migration/invasion assays

    PMID:30695072

    Open questions at the time
    • Single knockdown approach without direct molecular mechanism
    • No rescue to exclude off-target effects
  12. 2023 Medium

    Confirmed S461 as a phosphosite affecting Golgi localization in cells but showed it is dispensable for fertility in vivo, distinguishing localization-modulating phosphorylation from functional necessity.

    Evidence Dephosphorylation assay, mutagenesis, and CRISPR base-editor knock-in mice with CASA, histology, and TUNEL

    PMID:37090114

    Open questions at the time
    • Kinase for S461 not identified
    • Functional context where S461 phosphorylation matters undefined
  13. 2024 Medium

    Established a non-redundant role in Golgi organization required for ECM protein secretion and glycosaminoglycan synthesis.

    Evidence CRISPR knockout with electron microscopy, ECM secretion, and GAG synthesis assays (preprint)

    Open questions at the time
    • Not yet peer-reviewed
    • Mechanism by which golgin-160 maintains Golgi architecture not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what common molecular feature golgin-160 recognizes across its structurally diverse cargos, and whether its cargo-trafficking and apoptotic-fragment functions are mechanistically integrated.
  • No unifying cargo-recognition determinant identified
  • Nuclear targets of caspase fragments unknown
  • Relationship between germ-cell apoptosis phenotype and the Golgi caspase pathway unestablished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 2
Localization
GO:0005794 Golgi apparatus 2 GO:0005634 nucleus 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
ADRB1GCP16GCP60KCNJ1MLK3PIST

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 GCP170/GOLGA3 is a peripheral membrane protein with a long coiled-coil domain localized to the cytoplasmic face of the Golgi complex. It exists as phosphorylated and unphosphorylated forms, with the unphosphorylated form more tightly associated with the Golgi membrane. It dissociates from Golgi membranes in response to brefeldin A but does not co-localize with β-COP. Immunocytochemistry, subcellular fractionation, immunoelectron microscopy, biochemical extraction The Journal of biological chemistry Medium 9295333
2002 The Golgi targeting information of golgin-160 resides in an 85-amino acid region (residues 172–257) within the N-terminal head domain. Certain truncations of the head domain expose a cryptic nuclear localization signal and nuclear retention information, enabling nuclear accumulation. Caspase cleavage fragments of the head domain could be targeted to the nucleus if released from Golgi membranes. GFP-tagged deletion constructs, fluorescence microscopy, transfection assays The Journal of biological chemistry Medium 12130652
2003 GCP170/GOLGA3 interacts with GCP16, a novel acylated Golgi protein. The interaction was identified using the Golgi localization domain of GCP170 (residues 137–237) as bait in a yeast two-hybrid screen and confirmed by co-localization. Overexpression of wild-type GCP16 inhibits protein transport from the Golgi to the cell surface. Yeast two-hybrid, immunofluorescence co-localization, [3H]palmitic acid labeling, transport assays The Journal of biological chemistry Medium 14522980
2004 Mixed lineage kinase 3 (MLK3) directly phosphorylates golgin-160 in the N-terminal head region (residues 96–259). MLK3 and golgin-160 co-immunoprecipitate and co-localize. Overexpression of MLK3 enhances caspase-dependent cleavage of golgin-160 at Asp139, linking phosphorylation to apoptotic processing. In vitro kinase assay, co-immunoprecipitation, immunofluorescence, overexpression Journal of cell science High 14734651
2005 Golgin-160 interacts with the PDZ-domain protein PIST/GOPC via a leucine-rich repeat within golgin-160 and an internal coiled-coil region of PIST. GCP60 interacts preferentially with the caspase cleavage fragment of golgin-160 (residues 140–311), retaining it at the Golgi and preventing nuclear translocation. A widely expressed isoform, golgin-160B, lacks the leucine repeat and cannot bind PIST. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, immunofluorescence The Journal of biological chemistry High 15951434
2005 Expression of a caspase-resistant mutant of golgin-160 dominantly blocks apoptosis induced by death receptor ligation and ER stress (brefeldin A, DTT, thapsigargin) by preventing initiator caspase activation, but does not affect apoptosis induced by staurosporine or anisomycin, demonstrating that golgin-160 cleavage is required for apoptotic signal transduction at the Golgi in response to specific stimuli. Stable cell lines expressing caspase-resistant golgin-160, cell viability assays, caspase activation assays Molecular biology of the cell High 15829563
2006 GCP60 interacts preferentially with the caspase-generated golgin-160 fragment (residues 140–311) compared to the full-length head domain. This interaction retains the fragment at the Golgi and prevents its nuclear translocation. GCP60 overexpression increases sensitivity to staurosporine-induced apoptosis. Yeast two-hybrid, co-immunoprecipitation, overexpression, fluorescence microscopy The Journal of biological chemistry Medium 16870622
2006 Golgin-160 is required for proper Golgi-based sorting of GLUT4 and IRAP in adipocytes. siRNA-mediated depletion of golgin-160 increased basal plasma membrane GLUT4 by enhancing exocytosis without affecting endocytosis, bypassing normal TGN/Golgi sorting. The C-terminal coiled-coil region (residues 393–1498) inhibited insulin-stimulated GLUT4 translocation when expressed as a dominant interfering fragment. siRNA knockdown, rescue expression, plasma membrane fractionation, glucose uptake assay, dominant-interfering constructs Molecular biology of the cell High 17050738
2006 Golgin-160 interacts with the ROMK potassium channel C-terminus (yeast two-hybrid and co-immunoprecipitation) and facilitates ROMK transport to the cell surface, increasing current amplitude in Xenopus oocytes by raising surface protein density. Golgin-160 also stimulates surface expression of Kir2.1, Kv1.5, and Kv4.3, but not HERG. Yeast two-hybrid, co-immunoprecipitation, Xenopus oocyte electrophysiology, immunofluorescence Cellular physiology and biochemistry Medium 16543716
2006 Golgin-160 promotes cell surface expression of the β1-adrenergic receptor (β1AR). RNAi depletion reduces β1AR surface levels (rescued by RNAi-resistant golgin-160); overexpression increases them. Golgin-160 binds β1AR directly in vitro, with the interaction mapping to residues 140–257 of the golgin-160 head and the third intracellular loop of β1AR. By immunoelectron microscopy, golgin-160 is localized primarily in cis/medial Golgi cisternae. RNAi knockdown, rescue expression, in vitro binding assay, flow cytometry, immunoelectron microscopy Traffic High 17118120
2007 A single cysteine residue in GCP60 (Cys-463) is critical for its interaction with the golgin-160 caspase fragment (residues 140–311). In its reduced form, Cys-463 abolishes the interaction; oxidation (by H2O2 or nitric oxide donor) restores interaction and Golgi retention of the golgin-160 fragment, establishing a redox-regulated mechanism controlling nuclear translocation of golgin-160 fragments. In vitro binding assay, site-directed mutagenesis, redox treatment, co-immunoprecipitation, fluorescence microscopy The Journal of biological chemistry High 17711851
2014 Three basic residues in the third intracellular loop of β1AR are required for golgin-160-dependent trafficking. Mutation of these residues does not affect ER-to-Golgi trafficking but reduces steady-state plasma membrane levels of β1AR, placing golgin-160 action at the post-Golgi (trans-Golgi network) step of β1AR trafficking. Site-directed mutagenesis, flow cytometry, co-immunoprecipitation, pulse-chase trafficking assays International journal of molecular sciences Medium 24566136
1999 Disruption of the Golga3/Mea2 gene in transgenic mice causes a recessive defect in spermatogenesis in homozygous males, with loss of Mea2/Golga3 expression in testis, establishing GOLGA3 as essential for male germ cell development in vivo. Transgenic mouse genetics, FISH mapping, linkage analysis, Southern blot, Northern blot Mammalian genome Medium 9892724
2002 A truncated GOLGA3/Mea2 protein (DeltaMea2, ~2/3 of full-length) localizes to the Golgi of pachytene spermatocytes and round spermatids and can restore spermatogenesis in homozygous Golga3-disrupted mice in a dose-dependent manner, demonstrating that GOLGA3 is required for survival of pachytene spermatocytes. Transgenic rescue experiment, immunofluorescence localization, Northern blot quantification, fertility assay Molecular reproduction and development Medium 11835574
2013 A nonsense mutation in exon 18 of Golga3 (repro27) causes complete absence of GOLGA3 protein and fully penetrant male infertility in mice. Loss of GOLGA3 disrupts late meiosis, causes elevated germ cell apoptosis (TUNEL-positive) beginning at 12 dpp, and produces acrosome formation defects, abnormal sperm head/tail development, and reduced sperm motility. ENU mutagenesis screen, sequencing, immunoblotting, TUNEL assay, histology, IVF Andrology Medium 23495255
2019 Golgin-160 regulates Golgi apparatus positioning and size in glioma cells; knockdown of golgin-160 causes Golgi fragmentation and dispersal, and reduces GDNF-stimulated cell migration and invasion, placing golgin-160 in a pathway linking Golgi organization to cell motility. Lentiviral knockdown, Golgi morphology assay, migration/invasion assays (Transwell) PloS one Low 30695072
2023 S461 is confirmed as a phosphorylation site on GOLGA3 by protein dephosphorylation experiments. The S461L mutation reduces Golgi localization of GOLGA3 in HeLa cells (some protein dispersed to cytoplasm). However, Golga3-S461L knock-in mice have normal fertility and spermatogenesis, demonstrating this phosphorylation site is dispensable for reproductive function in vivo. Site-directed mutagenesis, immunofluorescence, protein dephosphorylation assay, CRISPR base editor knock-in mice, CASA, histology, TUNEL PeerJ Medium 37090114
2024 Golgin-160 knockout causes Golgi fragmentation and vesicle accumulation, and is required for efficient extracellular matrix (ECM) protein secretion and glycosaminoglycan synthesis in cells, establishing a non-redundant role for golgin-160 in Golgi organization supporting ECM secretion. CRISPR knockout, electron microscopy, ECM secretion assays, glycosaminoglycan synthesis assay bioRxivpreprint Medium

Source papers

Stage 0 corpus · 19 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 The NH2-terminal domain of Golgin-160 contains both Golgi and nuclear targeting information. The Journal of biological chemistry 66 12130652
2005 Caspase-resistant Golgin-160 disrupts apoptosis induced by secretory pathway stress and ligation of death receptors. Molecular biology of the cell 54 15829563
2006 Golgin-160 is required for the Golgi membrane sorting of the insulin-responsive glucose transporter GLUT4 in adipocytes. Molecular biology of the cell 53 17050738
2003 Identification and characterization of GCP16, a novel acylated Golgi protein that interacts with GCP170. The Journal of biological chemistry 46 14522980
2006 Golgin-160 promotes cell surface expression of the beta-1 adrenergic receptor. Traffic (Copenhagen, Denmark) 44 17118120
1997 Molecular characterization of GCP170, a 170-kDa protein associated with the cytoplasmic face of the Golgi membrane. The Journal of biological chemistry 43 9295333
2006 GCP60 preferentially interacts with a caspase-generated golgin-160 fragment. The Journal of biological chemistry 40 16870622
2005 Isoform-specific interaction of golgin-160 with the Golgi-associated protein PIST. The Journal of biological chemistry 40 15951434
2004 Phosphorylation of golgin-160 by mixed lineage kinase 3. Journal of cell science 27 14734651
1999 Mea2/Golga3 gene is disrupted in a line of transgenic mice with a reciprocal translocation between Chromosomes 5 and 19 and is responsible for a defective spermatogenesis in homozygotes. Mammalian genome : official journal of the International Mammalian Genome Society 22 9892724
2013 New point mutation in Golga3 causes multiple defects in spermatogenesis. Andrology 21 23495255
2006 Involvement of Golgin-160 in cell surface transport of renal ROMK channel: co-expression of Golgin-160 increases ROMK currents. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 21 16543716
2007 Identification of a redox-sensitive cysteine in GCP60 that regulates its interaction with golgin-160. The Journal of biological chemistry 19 17711851
2002 Golgi matrix protein gene, Golga3/Mea2, rearranged and re-expressed in pachytene spermatocytes restores spermatogenesis in the mouse. Molecular reproduction and development 19 11835574
1997 Cloning and molecular characterization of cDNA encoding a mouse male-enhanced antigen-2 (Mea-2): a putative family of the Golgi autoantigen. DNA sequence : the journal of DNA sequencing and mapping 14 9063644
2019 Golgin-160 and GMAP210 play an important role in U251 cells migration and invasion initiated by GDNF. PloS one 10 30695072
2014 Three basic residues of intracellular loop 3 of the beta-1 adrenergic receptor are required for golgin-160-dependent trafficking. International journal of molecular sciences 8 24566136
2010 Identification of a common autoantigenic epitope of protein disulfide isomerase, golgin-160 and voltage-gated potassium channel in type 1 diabetes. Diabetes research and clinical practice 7 20170975
2023 Mutation of S461, in the GOLGA3 phosphorylation site, does not affect mouse spermatogenesis. PeerJ 2 37090114

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