Affinage

GOLT1B

Vesicle transport protein GOT1B · UniProt Q9Y3E0

Round 2 corrected
Length
138 aa
Mass
15.4 kDa
Annotated
2026-04-28
105 papers in source corpus 4 papers cited in narrative 4 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GOLT1B is an evolutionarily conserved tetra-spanning membrane protein that cycles between the ER and early Golgi cisternae, where it facilitates both COPII-dependent vesicle budding from the ER and Sed5p/SNARE-dependent vesicle fusion with the Golgi (PMID:10406798, PMID:19383723). In mammalian cells, GOLT1B expression is induced by the unfolded protein response and is required for efficient hepatitis C virus replication in hepatocytes (PMID:35055994). GOLT1B also promotes colorectal cancer metastasis by mediating plasma membrane translocation of DVL2 to activate Wnt/β-catenin signaling and EMT, and by increasing cell-surface PD-L2 levels to foster an immunosuppressive microenvironment (PMID:34059062).

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 1999 High

    The fundamental question of Got1p/GOLT1B's cellular role was resolved: it functions at the Golgi as a facilitator of Sed5p-dependent vesicle fusion, acting after vesicle tethering, with functional redundancy with Sft2p.

    Evidence Synthetic lethality screen between got1 and sft2 mutants combined with in vitro ER-Golgi transport assay and immunofluorescence in yeast

    PMID:10406798

    Open questions at the time
    • Mechanism by which Got1p promotes SNARE-dependent fusion remains undefined
    • Whether Got1p acts directly on SNARE complexes or modulates membrane properties was not resolved
    • Mammalian ortholog function not yet tested
  2. 2009 High

    Beyond Golgi fusion, Got1p was shown to participate in COPII vesicle formation at the ER, resolving its dual role in both vesicle budding and fusion during ER-to-Golgi transport.

    Evidence Multicopy suppressor screen rescuing COPII coat mutants (sec23, sec31), COPII vesicle packaging assay, and live-cell imaging of ER-Golgi cycling in yeast

    PMID:19383723

    Open questions at the time
    • How Got1p influences membrane properties to facilitate vesicle budding is unknown
    • No structural model of Got1p or its membrane-shaping activity exists
    • Direct protein-protein interactions with COPII components not demonstrated
  3. 2021 Medium

    Two studies extended GOLT1B function to mammalian pathophysiology: it is induced by the UPR and required for HCV replication, and it promotes cancer metastasis through plasma membrane delivery of DVL2 (activating Wnt/β-catenin/EMT) and PD-L2 (enabling immune evasion).

    Evidence smFISH, RNAseq, and siRNA knockdown with viral replication readout in hepatocytes (HCV study); overexpression/knockdown in CRC lines, xenograft and PDX models, co-IP for GOLT1B–PD-L2, membrane fractionation for DVL2, and T-cell co-culture apoptosis assay (cancer study)

    PMID:34059062 PMID:35055994

    Open questions at the time
    • GOLT1B–PD-L2 interaction demonstrated by a single co-IP without reciprocal validation or structural mapping
    • DVL2 plasma membrane translocation mechanism (direct cargo vs. indirect effect) not distinguished
    • HCV replication dependence on GOLT1B shown in one study; independent replication pending
    • Whether GOLT1B's role in cancer metastasis generalizes beyond colorectal cancer is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the molecular mechanism by which GOLT1B influences membrane dynamics during vesicle budding and fusion, the structural basis of its tetra-spanning topology, and whether its cargo-delivery functions in cancer are direct or secondary to general ER-Golgi trafficking perturbation.
  • No structural or biophysical characterization of GOLT1B exists
  • No reconstituted system has isolated GOLT1B's contribution to vesicle budding or fusion
  • Selectivity of GOLT1B-dependent cargo transport (DVL2, PD-L2 vs. general secretory cargo) is undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005794 Golgi apparatus 2 GO:0031410 cytoplasmic vesicle 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 3
Partners
DVL2PD-L2

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Yeast Got1p (ortholog of human GOLT1B) is an evolutionarily conserved tetra-spanning membrane protein localized to early Golgi cisternae that facilitates Sed5p-dependent vesicle fusion with the Golgi complex. Synthetic lethality between got1 and sft2 mutants, combined with an in vitro ER-Golgi transport assay, demonstrated that Got1p is required at a step after vesicle tethering to Golgi membranes, and that either Got1p or Sft2p must be present for vesicle fusion with the Golgi in vivo. Genetic synthetic lethality screen, immunofluorescence, subcellular fractionation, in vitro ER-Golgi transport assay The EMBO journal High 10406798
2009 Yeast Got1p was identified as the strongest multicopy suppressor of the thermosensitive yip1-2 allele, and also suppressed temperature-sensitive mutations in SEC23 and SEC31 (COPII coat subunits). Got1p was efficiently packaged into COPII vesicles and cycled rapidly between the ER and Golgi, supporting an unanticipated role in influencing membrane properties to facilitate vesicle formation from the ER. Multicopy suppressor screen, COPII vesicle packaging assay, live-cell imaging of ER-Golgi cycling Journal of cell science High 19383723
2021 Human GOLT1B expression is induced during the unfolded protein response (UPR) in hepatocytes infected with hepatitis C virus (HCV), and GOLT1B is essential for efficient HCV viral replication. GOLT1B was identified as a novel HCV target gene whose expression was elevated by the virus in non-transformed cells and remained high in HCC tumor tissue, linking ER-Golgi trafficking function to viral replication. Single-molecule FISH on frozen tissue sections, laser microdissection followed by RNAseq, UPR induction experiments, siRNA knockdown with viral replication readout Pathogens (Basel, Switzerland) Medium 35055994
2021 GOLT1B, a vesicle transport protein, promotes colorectal cancer (CRC) metastasis by mediating plasma membrane translocation of DVL2 (Dishevelled 2), thereby activating downstream Wnt/β-catenin signaling and inducing epithelial-mesenchymal transition (EMT). Additionally, GOLT1B interacts with PD-L2 and increases its cell surface membrane levels, enabling co-cultured Jurkat T cells to undergo apoptosis and creating an immunosuppressive microenvironment that facilitates cancer cell migration and invasion. CRC cell line overexpression/knockdown, subcutaneous xenograft model, PDX model with siRNA delivery, co-immunoprecipitation (GOLT1B–PD-L2 interaction), membrane fractionation (DVL2 plasma membrane translocation), nuclear β-catenin measurement, T cell co-culture apoptosis assay Cancer cell international Medium 34059062

Source papers

Stage 0 corpus · 105 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2000 Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics. Genome research 392 10810093
2003 Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways. Oncogene 331 12761501
2012 Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature 319 22810586
2011 Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. Immunity 286 21903422
2003 The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome research 285 12975309
2000 Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing. EMBO reports 281 11256614
2018 Mapping the Genetic Landscape of Human Cells. Cell 225 30033366
2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes. Genomics 222 17207965
2021 GOT1 inhibition promotes pancreatic cancer cell death by ferroptosis. Nature communications 212 34381026
2014 Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes. Molecular cell 173 25544563
2001 Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome research 151 11230166
2018 miR-9 regulates ferroptosis by targeting glutamic-oxaloacetic transaminase GOT1 in melanoma. Molecular carcinogenesis 147 30035324
2009 Ubiquitin-mediated proteolysis of HuR by heat shock. The EMBO journal 142 19322201
2022 Exosome-Derived lncRNA NEAT1 Exacerbates Sepsis-Associated Encephalopathy by Promoting Ferroptosis Through Regulating miR-9-5p/TFRC and GOT1 Axis. Molecular neurobiology 108 35038133
2021 Medioresinol as a novel PGC-1α activator prevents pyroptosis of endothelial cells in ischemic stroke through PPARα-GOT1 axis. Pharmacological research 93 33915296
2021 SARS-CoV-2-host proteome interactions for antiviral drug discovery. Molecular systems biology 86 34709727
2017 The STUbL RNF4 regulates protein group SUMOylation by targeting the SUMO conjugation machinery. Nature communications 86 29180619
2017 GOT1-mediated anaplerotic glutamine metabolism regulates chronic acidosis stress in pancreatic cancer cells. Cancer letters 83 28455244
1999 Got1p and Sft2p: membrane proteins involved in traffic to the Golgi complex. The EMBO journal 71 10406798
2023 circFNDC3B Accelerates Vasculature Formation and Metastasis in Oral Squamous Cell Carcinoma. Cancer research 70 36811957
2018 miR-9-5p inhibits pancreatic cancer cell proliferation, invasion and glutamine metabolism by targeting GOT1. Biochemical and biophysical research communications 69 30591220
2017 ZMPSTE24 defends against influenza and other pathogenic viruses. The Journal of experimental medicine 63 28246125
2021 Circ-MBOAT2 knockdown represses tumor progression and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer. Journal of experimental & clinical cancer research : CR 60 33832516
2020 Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D. Nature communications 60 31980649
2014 Human recombinant glutamate oxaloacetate transaminase 1 (GOT1) supplemented with oxaloacetate induces a protective effect after cerebral ischemia. Cell death & disease 56 24407245
2014 Systematic identification of pathological lamin A interactors. Molecular biology of the cell 56 24623722
2020 A novel circular RNA hsa_circRNA_103809/miR-377-3p/GOT1 pathway regulates cisplatin-resistance in non-small cell lung cancer (NSCLC). BMC cancer 46 33276753
2022 Shikonin induces ferroptosis in multiple myeloma via GOT1-mediated ferritinophagy. Frontiers in oncology 45 36387145
2019 Aspulvinone O, a natural inhibitor of GOT1 suppresses pancreatic ductal adenocarcinoma cells growth by interfering glutamine metabolism. Cell communication and signaling : CCS 45 31470862
2020 Tissue of origin dictates GOT1 dependence and confers synthetic lethality to radiotherapy. Cancer & metabolism 36 31908776
1982 Assignment of phosphoglycerate mutase (PGAMA) to human chromosome 10. Regional mapping of GOT1 and PGAMA to subbands 10q26.1 (or q25.3). Annales de genetique 33 6282177
1972 Glutamate oxaloacetate transaminase (got) genetics in the mouse: polymorphism of got-1. Genetics 33 17248564
2023 Exosomes derived from mesenchymal stem cells rescue cartilage injury in osteoarthritis through Ferroptosis by GOT1/CCR2 expression. International immunopharmacology 31 37418985
2015 Expression, purification and preliminary crystallographic studies of human glutamate oxaloacetate transaminase 1 (GOT1). Protein expression and purification 28 26003525
2023 GOT1 regulates CD8+ effector and memory T cell generation. Cell reports 27 36640309
2017 Hedgehog inhibitor sonidegib potentiates 177Lu-octreotate therapy of GOT1 human small intestine neuroendocrine tumors in nude mice. BMC cancer 27 28789624
2011 Genome-wide association study identifies genetic variants in GOT1 determining serum aspartate aminotransferase levels. Journal of human genetics 25 21900944
1982 Chromosome localization of the loci GOT1, PP, NP, SOD1, PEPA and PEPC in the American mink (Mustela vison). TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 25 24270870
2022 Tumor Cell Derived Exosomal GOT1 Suppresses Tumor Cell Ferroptosis to Accelerate Pancreatic Cancer Progression by Activating Nrf2/HO-1 Axis via Upregulating CCR2 Expression. Cells 24 36497150
2020 LncRNA TMPO-AS1 Aggravates the Development of Hepatocellular Carcinoma via miR-429/GOT1 Axis. The American journal of the medical sciences 24 32988599
2021 CircGOT1 promotes cell proliferation, mobility, and glycolysis-mediated cisplatin resistance via inhibiting its host gene GOT1 in esophageal squamous cell cancer. Cell cycle (Georgetown, Tex.) 23 34919012
2017 A heterozygous mutation in GOT1 is associated with familial macro-aspartate aminotransferase. Journal of hepatology 23 28716744
2023 c-Myc protects hepatocellular carcinoma cell from ferroptosis induced by glutamine deprivation via upregulating GOT1 and Nrf2. Molecular biology reports 22 37358765
2017 Inhibition of GOT1 sensitizes colorectal cancer cells to 5-fluorouracil. Cancer chemotherapy and pharmacology 22 28314989
2009 Multicopy suppressor analysis of thermosensitive YIP1 alleles implicates GOT1 in transport from the ER. Journal of cell science 22 19383723
2008 Comparison of [177Lu-DOTA0,Tyr3]-octreotate and [177Lu-DOTA0,Tyr3]-octreotide for receptor-mediated radiation therapy of the xenografted human midgut carcinoid tumor GOT1. Cancer biotherapy & radiopharmaceuticals 22 18298335
2016 The HDM2 (MDM2) Inhibitor NVP-CGM097 Inhibits Tumor Cell Proliferation and Shows Additive Effects with 5-Fluorouracil on the p53-p21-Rb-E2F1 Cascade in the p53wild type Neuroendocrine Tumor Cell Line GOT1. Neuroendocrinology 20 27871087
2021 Structural and functional analysis of disease-associated mutations in GOT1 gene: An in silico study. Computers in biology and medicine 19 34352456
2017 Priming increases the anti-tumor effect and therapeutic window of 177Lu-octreotate in nude mice bearing human small intestine neuroendocrine tumor GOT1. EJNMMI research 18 28097640
2021 Vesicle transporter GOLT1B mediates the cell membrane localization of DVL2 and PD-L2 and promotes colorectal cancer metastasis. Cancer cell international 16 34059062
2016 A new post-intoxication treatment of paraoxon and parathion poisonings using an evolved PON1 variant and recombinant GOT1. Chemico-biological interactions 16 27256520
2004 GOT1 xenografted to nude mice: a unique model for in vivo studies on SSTR-mediated radiation therapy of carcinoid tumors. Annals of the New York Academy of Sciences 16 15153445
2021 Discovery of GOT1 Inhibitors from a Marine-Derived Aspergillus terreus That Act against Pancreatic Ductal Adenocarcinoma. Marine drugs 14 34822459
1999 Genetic homogeneity, high-resolution mapping, and mutation analysis of the urofacial (Ochoa) syndrome and exclusion of the glutamate oxaloacetate transaminase gene (GOT1) in the critical region as the disease gene. American journal of medical genetics 14 10360399
1987 Inheritance and linkage relationships of glutamate oxaloacetate transaminase isoenzymes in apple : 1. The gene GOT-1, a marker for the S incompatibility locus. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 14 24241471
2025 Amino acid metabolism disorder and oxidative stress took part in EGCG alleviating Mn-caused ferroptosis via miR-9-5p/got1 axis. Journal of hazardous materials 13 40007362
2022 Ziprasidone suppresses pancreatic adenocarcinoma cell proliferation by targeting GOT1 to trigger glutamine metabolism reprogramming. Journal of molecular medicine (Berlin, Germany) 13 35212782
1983 Confirmation of a de novo duplication, dup(10)(q24 leads to q26), by GOT1 gene dosage studies. Human genetics 13 6862443
2013 The novel somatostatin receptor 2/dopamine type 2 receptor chimeric compound BIM-23A758 decreases the viability of human GOT1 midgut carcinoid cells. Neuroendocrinology 12 23797089
2024 The role of GOT1 in cancer metabolism. Frontiers in oncology 11 39777342
2023 Substantially elevated serum glutamate and CSF GOT-1 levels associated with cerebral ischemia and poor neurological outcomes in subarachnoid hemorrhage patients. Scientific reports 10 37002262
2024 SIRT1 maintains bone homeostasis by regulating osteoblast glycolysis through GOT1. Cellular and molecular life sciences : CMLS 9 38700532
2018 Time-dependent transcriptional response of GOT1 human small intestine neuroendocrine tumor after 177Lu[Lu]-octreotate therapy. Nuclear medicine and biology 9 29502008
2006 Fusion of ETV6 to GOT1 in a case with myelodysplastic syndrome and t(10;12)(q24;p13). Haematologica 8 16757412
2025 Cold-inducible GOT1 activates the malate-aspartate shuttle in brown adipose tissue to support fuel preference for fatty acids. Cell reports 7 40540398
2020 A maternal GOT1 novel variant associated with early-onset severe preeclampsia identified by whole-exome sequencing. BMC medical genetics 7 32143588
2011 Inhomogeneous activity distribution of 177Lu-DOTA0-Tyr3-octreotate and effects on somatostatin receptor expression in human carcinoid GOT1 tumors in nude mice. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 7 22108870
1981 The possibility of prenatal diagnosis by gene dosage: confirmation of duplication 10q24 to qter from GOT-1 activity in fetal erythrocytes. Prenatal diagnosis 7 6213955
2025 A novel peptide TCL6148 induces ferroptosis via the GOT1/GPX4 pathway to enhance sunitinib sensitivity in renal cell carcinoma. International journal of biological macromolecules 5 40379184
2019 Transcriptional effects of 177Lu-octreotate therapy using a priming treatment schedule on GOT1 tumor in nude mice. EJNMMI research 5 30895393
2009 SNPs in the porcine GOT1 gene improve a QTL for serum aspartate aminotransferase activity on SSC14. Animal genetics 5 19968637
2025 Sirt6 loss activates Got1 and facilitates cleft palate through abnormal activating glycolysis. Cell death & disease 4 40050262
2023 Rod photoreceptor-specific deletion of cytosolic aspartate aminotransferase, GOT1, causes retinal degeneration. Frontiers in ophthalmology 4 38725581
2025 ANXA1 promotes intrahepatic cholangiocarcinoma proliferation and growth by regulating glutamine metabolism through GOT1 stabilization. Journal of experimental & clinical cancer research : CR 3 40390008
2025 Pyridoxal phosphate inhibits alpha-synuclein-induced ferroptosis by activating GOT1 to enhance the methionine salvage pathway in Parkinson's disease. Experimental neurology 3 40752725
2024 Cold-inducible GOT1 activates the malate-aspartate shuttle in brown adipose tissue to support fuel preference for fatty acids. bioRxiv : the preprint server for biology 3 39605634
2023 Co-administration with A1M does not influence apoptotic response of 177Lu-octreotate in GOT1 neuroendocrine tumors. Scientific reports 3 37076494
2025 A Novel circ_0075829/miR-326/GOT1 ceRNA Crosstalk Regulates the Malignant Phenotypes and Drug Sensitivity of Gemcitabine-Resistant Pancreatic Cancer Cells. Journal of biochemical and molecular toxicology 2 39692397
2021 GOLT1B Activation in Hepatitis C Virus-Infected Hepatocytes Links ER Trafficking and Viral Replication. Pathogens (Basel, Switzerland) 2 35055994
1991 Genetic polymorphism of human glutamate oxaloacetate transaminase (GOT1) detected using isoelectric focusing and a sensitive and positive staining method. International journal of legal medicine 2 1716966
1991 Mapping of the silver fox genes: assignments of the genes for ME1, ADK, PP, PEPA, GSR, MPI, and GOT1. Cytogenetics and cell genetics 2 2013231
1983 Prenatal prediction of duplication 10q24 leads to qter by gene dosage of GOT1 on uncultured amniotic cells. Prenatal diagnosis 2 6581480
2025 Integration of Untargeted Metabolomics, Network Pharmacology, Single-Cell RNA Sequencing, and Molecular Dynamics Simulation Reveals GOT1, CYP1A2, and CA2 as Potential Targets of Huang Qin Decoction Preventing Colorectal Cancer Liver Metastasis. Pharmaceuticals (Basel, Switzerland) 1 40732339
2025 Multi-omics revealed GOT1/ALDH3A1 pathway attenuated head and neck squamous cell carcinoma and increased cisplatin sensitivity through ROS induced by mitochondrial dysfunction. Redox report : communications in free radical research 1 41327788
2013 Gene conversion yields novel gene combinations in paralogs of GOT1 in the copepod Tigriopus californicus. BMC evolutionary biology 1 23845062
2026 GOT1 Inhibition Induces Extracellular Matrix Remodeling in Pancreatic Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41527462
2026 Oncolytic virus hijacks GOT1 and pyrimidinosomes to fuel pyrimidine synthesis for replication in tumor cells. Tumour virus research 0 41966328
2026 GOT1 inhibits hepatocellular carcinoma progression by regulating SLC25A5-dependent mitochondrial apoptosis. Oncogene 0 41981252
2026 Redox imbalance dictates dependence on GOT1 versus GOT2 for rod photoreceptor health during aging and stress. bioRxiv : the preprint server for biology 0 41993491
2025 The β-adrenergic receptor-SGK1 signaling pathway in brown adipocytes protects GOT1 from proteasomal degradation. Frontiers in cell and developmental biology 0 40741328
2025 Late apoptotic effects after treatment with 177Lu-octreotate in small-intestine neuroendocrine GOT1 tumor model. International journal of radiation biology 0 40793869
2025 Integrating transcriptomics and machine learning to predict ferroptosis-related genes and analyzing the role of GOT1 in gastric cancer progression. Pathology, research and practice 0 41106221
1995 The use of the isoenzymic marker gene Got-1 in the recognition of incompatibility S alleles in apple. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 0 24173907