Affinage

GOLGA4

Golgin subfamily A member 4 · UniProt Q13439

Length
2230 aa
Mass
261.1 kDa
Annotated
2026-04-28
50 papers in source corpus 12 papers cited in narrative 13 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GOLGA4 (golgin-245/p230) is a coiled-coil-rich peripheral membrane protein of the trans-Golgi network (TGN) that functions as a scaffold for selective cargo sorting, cytoskeletal-linked vesicular transport, and autophagosome biogenesis. Its C-terminal GRIP domain is necessary and sufficient for TGN targeting and is recruited by active Arl1 GTPase in a brefeldin A-sensitive, G protein-regulated manner, while overexpression of this domain displaces endogenous GOLGA4 from Golgi membranes (PMID:9013329, PMID:10318758, PMID:16413289). The N-terminal domain directly binds MACF1, and this interaction is specifically required for transport of GPI-anchored proteins from the TGN to the cell periphery along cytoskeletal tracks, as well as for mAtg9 trafficking from the TGN to phagophores during starvation-induced autophagy (PMID:15265687, PMID:25436429). GOLGA4 also associates with CD99 and participates in HLA class I surface expression, and despite high expression in testes, global knockout in mice reveals dispensability for spermatogenesis and male fertility (PMID:18849489, PMID:32736686).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1995 High

    Establishing the molecular identity of GOLGA4 as a coiled-coil Golgi autoantigen resolved the nature of a previously uncharacterized 245 kDa protein recognized by autoimmune sera, opening the gene to functional dissection.

    Evidence cDNA library screening with Sjögren's syndrome autoimmune serum, recombinant protein expression, and immunoprecipitation in HeLa cells

    PMID:8537393

    Open questions at the time
    • Function unknown at this stage
    • No information on membrane attachment mechanism
    • Relationship to other golgins undefined
  2. 1996 High

    Ultrastructural localization of GOLGA4 to the cytosolic face of TGN-derived non-clathrin-coated vesicles, whose recruitment was stimulated by GTPγS/AlF4⁻, established that GOLGA4 cycles between cytosol and TGN membranes under G protein control and marks a distinct TGN vesicle population.

    Evidence Immunogold cryosectioning, streptolysin-O permeabilization with G protein activators, dual immunogold labeling in NRK and HeLa cells

    PMID:8626529 PMID:9013329

    Open questions at the time
    • Identity of the G protein mediating recruitment unknown
    • Cargo carried by p230-positive vesicles undefined
    • Mechanism of membrane binding unresolved
  3. 1999 High

    Mapping the minimal C-terminal GRIP domain (42 amino acids) as necessary and sufficient for Golgi targeting revealed the structural basis of GOLGA4 membrane association and that it competes with endogenous protein for a saturable membrane receptor.

    Evidence Transfection of GFP-tagged deletion mutants in COS cells, alanine scanning mutagenesis, brefeldin A treatment

    PMID:10318758

    Open questions at the time
    • Identity of the GRIP domain receptor on TGN membranes not established
    • No structural information on GRIP-membrane interaction
  4. 2004 High

    Discovery that the N-terminal domain of GOLGA4 directly binds MACF1 and that this interaction is specifically required for GPI-anchored protein transport from TGN to cell periphery—but dispensable for transmembrane cargo—established GOLGA4 as a cargo-selective adaptor linking TGN sorting to cytoskeletal transport.

    Evidence Yeast two-hybrid, reciprocal co-immunoprecipitation, in vitro binding, live-cell transport assay with dominant-negative constructs

    PMID:15265687

    Open questions at the time
    • How GOLGA4 recognizes GPI-anchored cargo specifically is unknown
    • Whether other golgins compensate in vivo unclear
    • No in vivo validation in animal models
  5. 2005 Medium

    Demonstrating that Arl1-GTP directly binds the GRIP domain of GOLGA4 identified the specific small GTPase mediating TGN recruitment, resolving the earlier observation of G protein-dependent membrane association.

    Evidence GST pull-down with recombinant Arl1 and HeLa cell lysates

    PMID:16413289

    Open questions at the time
    • Only pull-down evidence; no mutagenesis of Arl1-binding interface in GOLGA4
    • Contribution of Arl1 versus other factors to in vivo recruitment not quantified
  6. 2008 Medium

    Finding that GOLGA4 associates with CD99 and is required for HLA class I surface expression expanded its functional repertoire beyond GPI-anchored cargo to immune-relevant transmembrane protein trafficking from the TGN.

    Evidence Co-immunoprecipitation, GRIP domain overexpression, flow cytometry of HLA class I

    PMID:18849489

    Open questions at the time
    • Whether GOLGA4 directly binds HLA class I or acts indirectly via CD99 unclear
    • No loss-of-function confirmation (siRNA/KO)
    • Physiological relevance in immune cells not tested
  7. 2014 Medium

    Showing that GOLGA4 and MACF1 are required for mAtg9 trafficking from the TGN to phagophores during starvation revealed an unexpected role for TGN-based golgin-cytoskeletal coupling in autophagosome biogenesis.

    Evidence siRNA knockdown, LC3 puncta and autophagic flux assays, immunofluorescence of mAtg9 trafficking, dominant-negative expression

    PMID:25436429

    Open questions at the time
    • Mechanism by which GOLGA4 selects mAtg9-containing vesicles unknown
    • Single lab finding; independent replication needed
    • Whether GOLGA4 is degraded during autophagy or recycled not determined
  8. 2020 Medium

    Global knockout of Golga4 in mice showing normal spermatogenesis and fertility despite high testicular expression established functional redundancy among golgins and indicated that GOLGA4 is dispensable for at least some in vivo trafficking processes.

    Evidence CRISPR/Cas9 knockout mouse, testicular histology, fertility assays

    PMID:32736686

    Open questions at the time
    • Phenotypic analysis limited to spermatogenesis; other tissues not systematically examined
    • Compensatory upregulation of other golgins not assessed
    • Autophagy and immune phenotypes in KO mice not tested
  9. 2021 Medium

    Identification of oncogenic GOLGA4-RAF1 and GOLGA4-JAK2 fusion genes in melanoma and B-ALL, respectively, demonstrated that the GOLGA4 locus can serve as a fusion partner driving constitutive kinase signaling, with therapeutic implications for targeted kinase inhibitor therapy.

    Evidence RNA sequencing and fusion gene identification in patient tumors; retroviral reconstitution in murine pro-B cells with signaling readout; clinical MEK/JAK inhibitor responses

    PMID:30835257 PMID:34697799

    Open questions at the time
    • Whether GOLGA4 coiled-coil domain contributes to oligomerization-dependent kinase activation not tested
    • Frequency of GOLGA4 fusions in these malignancies unknown
    • Normal GOLGA4 function not disrupted in these studies

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GOLGA4 selects specific cargo (GPI-anchored proteins, mAtg9) at the TGN, the structural basis of its filamentous scaffold assembly, and its non-redundant physiological roles beyond spermatogenesis remain unresolved.
  • No cargo recognition mechanism defined
  • No high-resolution structure of full-length GOLGA4 or GRIP-Arl1 complex
  • Systematic phenotyping of Golga4 KO mice across tissues not performed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005794 Golgi apparatus 7
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-168256 Immune System 1 R-HSA-9612973 Autophagy 1
Partners
ARL1CD99MACF1

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 GOLGA4 (golgin-245/p230) was identified as a 245 kDa Golgi complex autoantigen that is highly enriched in coiled-coil domains and contains a granin family signature decapeptide (ESLALEELEL), identified using autoimmune serum from a Sjögren's syndrome patient to isolate cDNA from a HeLa library. cDNA library screening with autoimmune serum, recombinant protein expression, immunoprecipitation, Western blot The Journal of biological chemistry High 8537393
1996 GOLGA4 (p230) was molecularly cloned and confirmed as a 261 kDa peripheral membrane protein localized to the cytosolic face of the trans-Golgi, containing extensive heptad-repeat coiled-coil domains and a granin motif; its gene was mapped to chromosome 6p12-22. Two alternatively spliced mRNAs differing at the C-terminus were identified. cDNA cloning, sequence analysis, chromosomal mapping, Northern blot The Journal of biological chemistry High 8626529
1996 GOLGA4 (p230) localizes to the trans-Golgi network (TGN) and is recruited to cytoplasmic surfaces of TGN-derived budding vesicles with a thin (~10 nm) non-clathrin coat; this recruitment is stimulated by GTPγS or AlF4- (G protein activators), indicating G protein-regulated cycling between cytosol and TGN membranes. p230-labeled vesicles are distinct from clathrin-coated vesicles and from p200-labeled vesicles, suggesting distinct TGN vesicle populations. Immunogold labeling of cryosections, streptolysin-O permeabilization, G protein activator treatment, dual immunogold labeling Journal of cell science High 9013329
1999 The C-terminal 98 amino acid domain of GOLGA4 (p230) is necessary and sufficient for targeting to the Golgi apparatus. Within this domain, a minimum stretch of 42 amino acids is essential for Golgi targeting. Overexpression of this domain displaces endogenous p230 from Golgi membranes, suggesting competition for the same membrane target. Golgi binding of this domain is brefeldin A-sensitive and G protein-regulated. Transfection of COS cells with deletion mutants and GFP fusions, alanine scanning mutagenesis, brefeldin A treatment, immunofluorescence Journal of cell science High 10318758
2004 The N-terminal domain of GOLGA4 (p230/golgin-245) directly interacts with the C-terminal domain of MACF1 (a microtubule-actin crosslinking protein), as shown by yeast two-hybrid, co-immunoprecipitation, and in vitro binding assay. Expression of the interacting domains of p230 or MACF1 disrupts transport of GPI-anchored proteins (YFP-SP-GPI) from the TGN to the cell periphery, while transmembrane protein (VSVG3-GL-YFP) trafficking is unaffected, indicating that p230–MACF1 interaction specifically mediates GPI-anchored protein transport along cytoskeletal tracts. Yeast two-hybrid, co-immunoprecipitation, in vitro binding assay, double immunofluorescence, dominant-negative overexpression with live-cell transport assay Experimental cell research High 15265687
2008 GOLGA4 (p230/golgin-245) physically associates with CD99 in the TGN and is required for surface expression of HLA class I molecules. Overexpression of the GOLGA4 GRIP domain leads to down-modulation of HLA class I at both the cell surface and intracellularly, placing GOLGA4 in the pathway of HLA class I trafficking from TGN to plasma membrane. Co-immunoprecipitation, overexpression of GRIP domain, immunofluorescence, flow cytometry of HLA class I surface levels Blood Medium 18849489
2014 GOLGA4 (p230/golgin-245) and its binding partner MACF1 are required for autophagosome formation under amino acid starvation: knockdown of p230 or MACF1 reduces autophagic flux and LC3-positive puncta, and impairs mAtg9 recruitment from the TGN to peripheral phagophores. p230 itself is detected in autophagosomes/autolysosomes during autophagosome biogenesis. siRNA knockdown, LC3 puncta assay, autophagic flux measurement, immunofluorescence of mAtg9 trafficking, dominant-negative overexpression Biochemical and biophysical research communications Medium 25436429
2005 Active Arl1 GTPase (Arl1-GTP) directly interacts with the GRIP domain of GOLGA4 (golgin-245) to mediate its recruitment to the TGN. GST-Arl1(GTP) recovers endogenous golgin-245 from HeLa cell cytosol, and GST-GRIP domain of golgin-245 retains endogenous active Arl1. GST pull-down assay with recombinant proteins and HeLa cell lysates Methods in enzymology Medium 16413289
2000 A novel N-terminal splice variant of GOLGA4 (p230) was identified from a human hepatoma cDNA library; the alternative splicing occurs within the first proline-rich domain and is more frequent than the previously reported form. The splice variant localizes to the TGN similarly to canonical p230, suggesting both isoforms function at the TGN. cDNA library screening, RT-PCR, immunofluorescence, immunoblotting with GST fusion protein European journal of cell biology Medium 11139141
2019 A GOLGA4-RAF1 fusion gene was identified in a metastatic melanoma; expression of the fusion was associated with constitutive ERK activation and elevated expression of RAS/RAF downstream effector ETV5, and the tumor showed profound response to MEK inhibitor therapy, indicating the GOLGA4-RAF1 fusion acts as an oncogenic driver through MAPK pathway activation. Molecular characterization of tumor (RNA sequencing, fusion gene identification), ERK/ETV5 expression analysis, clinical MEK inhibitor response The Journal of clinical investigation Medium 30835257
2021 A novel GOLGA4-JAK2 fusion gene was identified in B-cell ALL; expression of GOLGA4-JAK2 in murine pro-B cells promoted cytokine-independent growth and constitutive JAK/STAT signaling, and cells were sensitive to JAK inhibitors, implicating GOLGA4-JAK2 as an oncogenic driver via aberrant JAK2 activation. mRNA sequencing, retroviral expression in murine pro-B cells, cytokine-independent growth assay, JAK/STAT pathway analysis, JAK inhibitor sensitivity British journal of haematology Medium 34697799
2020 GOLGA4 is a Golgi matrix protein highly expressed in mouse testes, but CRISPR/Cas9 global knockout of Golga4 in mice results in normal spermatogenesis, normal sperm morphology, and male fertility, demonstrating that GOLGA4 is dispensable for acrosome biogenesis and spermatogenesis in mice. CRISPR/Cas9 knockout mouse generation, testicular histology, fertility testing Biochemical and biophysical research communications Medium 32736686
2025 Super-resolution microscopy and biochemical analysis revealed that GOLGA4, along with other golgins, localizes precisely to the rim of the Golgi apparatus (not between cisternae) and forms anti-parallel dimers that self-assemble into multi-micron-long filamentous bands in vitro, suggesting golgins physically scaffold the Golgi stack structure. 3D super-resolution microscopy (10-20 nm resolution), biochemical characterization of isolated golgin proteins, in vitro self-assembly assay bioRxivpreprint Medium

Source papers

Stage 0 corpus · 50 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 The P190, P210, and P230 forms of the BCR/ABL oncogene induce a similar chronic myeloid leukemia-like syndrome in mice but have different lymphoid leukemogenic activity. The Journal of experimental medicine 408 10224280
1993 Identification of a novel granulocyte chemotactic protein (GCP-2) from human tumor cells. In vitro and in vivo comparison with natural forms of GRO, IP-10, and IL-8. Journal of immunology (Baltimore, Md. : 1950) 183 8423327
2003 Pharmacological modulation of interleukin-17-induced GCP-2-, GRO-alpha- and interleukin-8 release in human bronchial epithelial cells. European journal of pharmacology 116 12591113
1995 Molecular characterization of Golgin-245, a novel Golgi complex protein containing a granin signature. The Journal of biological chemistry 97 8537393
1983 Immunolocalization of a novel, cytoskeleton-associated polypeptide of Mr 230,000 daltons (p230). The Journal of cell biology 87 6339521
1996 Molecular characterization of trans-Golgi p230. A human peripheral membrane protein encoded by a gene on chromosome 6p12-22 contains extensive coiled-coil alpha-helical domains and a granin motif. The Journal of biological chemistry 82 8626529
1996 p230 is associated with vesicles budding from the trans-Golgi network. Journal of cell science 75 9013329
1983 The p36 substrate of tyrosine-specific protein kinases co-localizes with non-erythrocyte alpha-spectrin antigen, p230, in surface lamina of cultured fibroblasts. The EMBO journal 72 6357780
1995 Establishment and molecular characterization of a novel leukemic cell line with Philadelphia chromosome expressing p230 BCR/ABL fusion protein. Cancer research 71 7606740
2012 Mesenchymal stem cells overexpressing GCP-2 improve heart function through enhanced angiogenic properties in a myocardial infarction model. Cardiovascular research 68 22886775
1999 The Golgi-targeting sequence of the peripheral membrane protein p230. Journal of cell science 65 10318758
2004 Interaction between p230 and MACF1 is associated with transport of a glycosyl phosphatidyl inositol-anchored protein from the Golgi to the cell periphery. Experimental cell research 64 15265687
2007 Arabidopsis GCP2 and GCP3 are part of a soluble gamma-tubulin complex and have nuclear envelope targeting domains. The Plant journal : for cell and molecular biology 60 17714428
2005 Lipid peroxides, superoxide dismutase and circulating IL-8 and GCP-2 in patients with severe obstructive sleep apnea: a pilot study. Sleep & breathing = Schlaf & Atmung 57 15988615
2000 GCP-2-induced internalization of IL-8 receptors: hierarchical relationships between GCP-2 and other ELR(+)-CXC chemokines and mechanisms regulating CXCR2 internalization and recycling. Blood 57 10688807
2003 Genotype frequencies and linkage disequilibrium in the CEPH human diversity panel for variants in folate pathway genes MTHFR, MTHFD, MTRR, RFC1, and GCP2. Birth defects research. Part A, Clinical and molecular teratology 56 14632302
2002 Neutrophilic-chronic myeloid leukemia: low levels of p230 BCR/ABL mRNA and undetectable BCR/ABL protein may predict an indolent course. Cancer 53 12015767
2019 Profound MEK inhibitor response in a cutaneous melanoma harboring a GOLGA4-RAF1 fusion. The Journal of clinical investigation 44 30835257
2008 Regulation of HLA class I surface expression requires CD99 and p230/golgin-245 interaction. Blood 42 18849489
2003 Effects of the glutamate carboxypeptidase II (GCP2 1561C>T) and reduced folate carrier (RFC1 80G>A) allelic variants on folate and total homocysteine levels in kidney transplant patients. Kidney international 42 12753319
2002 BCR/ABL p210, p190 and p230 fusion genes in 250 Mexican patients with chronic myeloid leukaemia (CML). Clinical and laboratory haematology 42 12067277
2000 Analysis of the biologic properties of p230 Bcr-Abl reveals unique and overlapping properties with the oncogenic p185 and p210 Bcr-Abl tyrosine kinases. Blood 41 10779439
2003 The phosphotriesterase gene opdA in Agrobacterium radiobacter P230 is transposable. FEMS microbiology letters 38 12757939
1998 P230 BCR/ABL protein may be associated with an acute leukaemia phenotype. British journal of haematology 38 9886327
2018 The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission. Scientific reports 31 30297725
2011 Amine-reactive OVA multimers for auto-vaccination against cytokines and other mediators: perspectives illustrated for GCP-2 in L. major infection. Journal of leukocyte biology 29 21385949
2008 Neutrophil chemokines GCP-2 and GRO-alpha in patients with inflammatory bowel disease. Journal of digestive diseases 28 18956592
2015 Overexpression and Nucleolar Localization of γ-Tubulin Small Complex Proteins GCP2 and GCP3 in Glioblastoma. Journal of neuropathology and experimental neurology 27 26079448
2014 Trans-Golgi protein p230/golgin-245 is involved in phagophore formation. Biochemical and biophysical research communications 19 25436429
2011 N-substituted glutamyl sulfonamides as inhibitors of glutamate carboxypeptidase II (GCP2). Chemical biology & drug design 16 21219587
2003 Myeloproliferative disease in transgenic mice expressing P230 Bcr/Abl: longer disease latency, thrombocytosis, and mild leukocytosis. Blood 15 12623846
2009 Expression of bovine granulocyte chemotactic protein-2 (GCP-2) in neutrophils and a mammary epithelial cell line (MAC-T) in response to various bacterial cell wall components. Veterinary journal (London, England : 1997) 14 19682932
2024 Preclinical evaluation of a novel CAR-T therapy utilizing a scFv antibody highly specific to MAGE-A4p230-239/HLA-A∗02:01 complex. Molecular therapy : the journal of the American Society of Gene Therapy 12 38243600
2000 Novel variant of p230 trans-Golgi network protein identified by serum from Sjögren's syndrome patient. European journal of cell biology 11 11139141
2005 Interaction of Arl1 GTPase with the GRIP domain of Golgin-245 as assessed by GST (glutathione-S-transferase) pull-down experiments. Methods in enzymology 10 16413289
2020 GOLGA4, A Golgi matrix protein, is dispensable for spermatogenesis and male fertility in mice. Biochemical and biophysical research communications 9 32736686
2020 Minicircle-based GCP-2 ex vivo gene therapy enhanced the reepithelialization and angiogenic capacity. Journal of tissue engineering and regenerative medicine 6 32336047
2005 Antiangiogenic gene therapy of myeloproliferative disease developed in transgenic mice expressing P230 bcr/abl. Gene therapy 6 15616602
2002 Characterization of mouse tGolgin-1 (golgin-245/trans-golgi p230/256 kD golgin) and its upregulation during oligodendrocyte development. DNA and cell biology 6 12162805
2021 Identification of a novel GOLGA4-JAK2 fusion gene in B-cell acute lymphoblastic leukaemia. British journal of haematology 5 34697799
2013 Functional replacement of fission yeast γ-tubulin small complex proteins Alp4 and Alp6 by human GCP2 and GCP3. Journal of cell science 5 23886939
2013 Early Complete Molecular Response to First-Line Nilotinib in Two Patients with Chronic Myeloid Leukemia Carrying the p230 Transcript. Case reports in hematology 5 23956893
2006 Oral administration of imatinib to P230 BCR/ABL-expressing transgenic mice changes clones with high BCR/ABL complementary DNA expression into those with low expression. International journal of hematology 4 17118762
2023 De nove Philadelphia chromosome-positive myelodysplastic syndromes with complex karyotype and p230 BCR::ABL fusion transcript: a case report with a literature review. Hematology (Amsterdam, Netherlands) 2 37288817
2025 Senescent Fibroblasts Drive Melanoma Progression Through GCP-2 Induced CREB Phosphorylation Enhancing Glycolysis. Aging cell 1 41258756
2021 [Clinical Effect of Tyrosine Kinase Inhibitors in the Treatment of P230 Chronic Myeloid Leukemia]. Zhongguo shi yan xue ye xue za zhi 1 34893105
2025 Philadelphia chromosome-positive de novo myelodysplastic syndrome with the p230 BCR::ABL1 fusion gene: a case report. International journal of hematology 0 41148513
2025 Inferior Outcomes of p230-CML with Imatinib: a Report of 2 Cases of p210/p230 Co-Expressed CML Showing Rapid Progression To Leukaemia Cutis along with the Systematic Review. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 0 42040683
2019 Author Correction: The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission. Scientific reports 0 31053746
1997 Isolation and characterization of a 230 kDa protein (p230) specifically expressed in fetal brains: its involvement in neurite outgrowth from rat cerebral cortex neurons grown on monolayer of astrocytes. Journal of biochemistry 0 9498558