Affinage

GNG13

Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 · UniProt Q9P2W3

Length
67 aa
Mass
7.9 kDa
Annotated
2026-06-10
87 papers in source corpus 3 papers cited in narrative 3 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 3/4 claims corpus-supported (75%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GNG13 (Gγ13) is a G protein gamma subunit that forms functional Gβγ heterodimers and operates at the effector interface of sensory signal transduction in retinal and olfactory neurons (PMID:11675383, PMID:12454992). It associates selectively with Gβ1, Gβ3, and Gβ4 to form stable dimers, and these complexes modulate GIRK1/4 (Kir3.1/3.4) potassium channels, N-type (α1B) calcium channels, and PLCβ activity, demonstrating effector coupling beyond taste reception (PMID:11675383). In the retina, Gγ13 is selectively expressed in rod and ON cone bipolar cells, co-localizing in dendrites with Gαo and co-expressed with Gβ3 and Gβ4, marking it as a component of the ON bipolar cell signaling pathway (PMID:12454992). In olfactory sensory neuron cilia, Gγ13 physically interacts with the GEF Ric-8B and co-localizes with Gαolf and Gβ1, placing it within the odorant signal transduction machinery (PMID:18462949).

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2001 High

    Establishing which Gβ partners Gγ13 binds and whether the resulting dimers couple to effectors defined Gγ13 as a broadly competent signaling subunit rather than a taste-restricted one.

    Evidence In vitro co-translation and stringent co-IP to map Gβ selectivity, plus Xenopus oocyte electrophysiology and cellular PLC assays for effector coupling

    PMID:11675383

    Open questions at the time
    • Endogenous Gβ partner usage in native tissues not resolved
    • No structural model of the Gβγ13 interface
    • Receptor coupling specificity not defined
  2. 2003 High

    Localizing Gγ13 to ON bipolar cell dendrites with Gαo and co-expressed Gβ3/Gβ4 tied the subunit to a specific retinal signal transduction cell type.

    Evidence Immunohistochemistry in GFP-reporter mice, single-cell RT-PCR, and patch-clamp confirmation of ON physiology

    PMID:12454992

    Open questions at the time
    • Functional requirement of Gγ13 for ON bipolar responses not tested by loss-of-function
    • Receptor and downstream effector in this pathway not identified
  3. 2008 Medium

    Identifying a physical interaction with the GEF Ric-8B and co-localization with Gαolf placed Gγ13 within the olfactory cilia signaling apparatus.

    Evidence Co-immunoprecipitation of Ric-8B with Gγ13 and immunofluorescence localization in olfactory sensory neuron cilia

    PMID:18462949

    Open questions at the time
    • Co-IP without reciprocal validation or in vitro reconstitution
    • Functional consequence of the Ric-8B interaction for odorant signaling not demonstrated
    • No mutagenesis mapping the interaction interface

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether Gγ13 is functionally required in vivo for retinal ON-pathway or olfactory signaling, and how its Gβ partner choice is determined in native cells, remains unresolved.
  • No loss-of-function or knockout phenotype in the corpus
  • Native receptor–Gαβγ13–effector chains not reconstituted

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 1 GO:0098772 molecular function regulator activity 1
Localization
GO:0005886 plasma membrane 2 GO:0005929 cilium 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-9709957 Sensory Perception 2
Partners
GNALGNAO1GNB1GNB3GNB4RIC8B
Complex memberships
G protein heterotrimer (Gβγ dimer)

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Gγ13 associates with all five Gβ subunits (Gβ1–5) upon co-translation in vitro, but under stringent co-immunoprecipitation conditions only Gβ1/Gγ13, Gβ3/Gγ13, and Gβ4/Gγ13 form stable dimers. Multiple Gβ/Gγ13 pairings are functional in modulating Kir3.1/3.4 (GIRK1/4) potassium channels, N-type (α1B) calcium channels, PLCβ2 activation, and inhibition of Gαq-stimulated PLCβ1 activity in cellular assays, demonstrating that Gγ13 can participate in signal transduction beyond taste reception. In vitro co-translation, co-immunoprecipitation under high-detergent conditions, Xenopus oocyte electrophysiology (channel modulation), cellular PLC activity assays The Journal of biological chemistry High 11675383
2003 Gγ13 is selectively expressed in rod bipolar cells and ON cone bipolar cells of the retina, where it is co-localized in dendrites with Gαo. Single-cell RT-PCR showed that Gβ3, Gβ4, and Gγ13 are co-expressed in ON bipolar cells but not in OFF bipolar cells, implicating Gγ13 as a selective component of ON bipolar cell signal transduction. Immunohistochemistry in transgenic GFP-reporter mice, single-cell RT-PCR with cDNA probes, patch-clamp recordings to confirm ON physiology The Journal of comparative neurology High 12454992
2008 Ric-8B, a guanine nucleotide exchange factor (GEF), physically interacts with Gγ13 and co-localizes with Gγ13, Gαolf, and Gβ1 in the cilia of olfactory sensory neurons, implicating Gγ13 as a component of odorant signal transduction machinery in the olfactory cilia. Co-immunoprecipitation (Ric-8B with Gγ13), immunofluorescence localization in olfactory sensory neuron cilia Molecular and cellular neurosciences Medium 18462949

Source papers

Stage 0 corpus · 87 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. Proceedings of the National Academy of Sciences of the United States of America 988 8097323
1995 G alpha 12 and G alpha 13 stimulate Rho-dependent stress fiber formation and focal adhesion assembly. The Journal of biological chemistry 409 7559569
1999 Simultaneous disruption of interleukin (IL)-4 and IL-13 defines individual roles in T helper cell type 2-mediated responses. The Journal of experimental medicine 283 10330435
2007 Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T cells that facilitate tumor development. The Journal of experimental medicine 247 17438063
2001 Inherited interleukin-12 deficiency: IL12B genotype and clinical phenotype of 13 patients from six kindreds. American journal of human genetics 217 11753820
2003 Maternal fish oil supplementation in pregnancy reduces interleukin-13 levels in cord blood of infants at high risk of atopy. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 145 12680858
1994 IL-13 induces proliferation, Ig isotype switching, and Ig synthesis by immature human fetal B cells. Journal of immunology (Baltimore, Md. : 1950) 116 7507958
2003 G protein subunit G gamma 13 is coexpressed with G alpha o, G beta 3, and G beta 4 in retinal ON bipolar cells. The Journal of comparative neurology 105 12454992
2000 Gastrointestinal nematode expulsion in IL-4 knockout mice is IL-13 dependent. European journal of immunology 103 10940898
2005 IL-21 effects on human IgE production in response to IL-4 or IL-13. Cellular immunology 102 15919378
2007 Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13. Proceedings of the National Academy of Sciences of the United States of America 91 17307869
2001 Constitutive activation of NF-kappa B and secretion of interleukin-8 induced by the G protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus involve G alpha(13) and RhoA. The Journal of biological chemistry 90 11590141
2004 Distinct transcriptional programs activated by interleukin-10 with or without lipopolysaccharide in dendritic cells: induction of the B cell-activating chemokine, CXC chemokine ligand 13. Journal of immunology (Baltimore, Md. : 1950) 83 15153525
1988 12-O-tetradecanoylphorbol-13-acetate activates phosphatidylethanol and phosphatidylglycerol synthesis by phospholipase D in cell lysates. Biochemical and biophysical research communications 79 3046613
1999 Cytokine-induced apoptosis in epithelial HT-29 cells is independent of nitric oxide formation. Evidence for an interleukin-13-driven phosphatidylinositol 3-kinase-dependent survival mechanism. The Journal of biological chemistry 78 10358077
1997 Activation of phosphatidylinositol 3-kinase by interleukin-13. An inhibitory signal for inducible nitric-oxide synthase expression in epithelial cell line HT-29. The Journal of biological chemistry 70 9139718
2003 Serum Levels of IL-4, IL-10, IL-12, IL-13 and IFN-gamma in Behçet's disease. The Journal of dermatology 69 12928529
2011 Interleukin-13 promotes susceptibility to chlamydial infection of the respiratory and genital tracts. PLoS pathogens 65 21573182
2001 Reduced alloreactive T-cell activation after alcohol intake is due to impaired monocyte accessory cell function and correlates with elevated IL-10, IL-13, and decreased IFNgamma levels. Alcoholism, clinical and experimental research 65 11781510
2006 A new approach to producing functional G alpha subunits yields the activated and deactivated structures of G alpha(12/13) proteins. Biochemistry 63 16388592
2004 Atopy, serum IgE, and interleukin-13 in steroid-responsive nephrotic syndrome. Pediatric nephrology (Berlin, Germany) 57 15064938
2001 Novel B and T cell epitopes of chicken ovomucoid (Gal d 1) induce T cell secretion of IL-6, IL-13, and IFN-gamma. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 53 11422162
1996 Inhibition of proliferation and clonal growth of human breast cancer cells by interleukin 13. Cancer research 52 8758930
1984 Carbon-13 nuclear magnetic resonance study of microtubule protein: evidence for a second colchicine site involved in the inhibition of microtubule assembly. Biochemistry 51 6150726
2007 Inverse association of plasma IL-13 and inflammatory chemokines with lung function impairment in stable COPD: a cross-sectional cohort study. Respiratory research 50 17868461
2008 Ric-8B interacts with G alpha olf and G gamma 13 and co-localizes with G alpha olf, G beta 1 and G gamma 13 in the cilia of olfactory sensory neurons. Molecular and cellular neurosciences 49 18462949
2002 Increased frequency of intracellular interleukin (IL)-13 and IL-10, but not IL-4, expressing CD4+ and CD8+ peripheral T cells of patients with atopic dermatitis. The British journal of dermatology 49 12452862
2012 Neurotransmissions of antidepressant-like effects of kisspeptin-13. Regulatory peptides 48 22999921
1995 Peptide-induced anergy in allergen-specific human Th2 cells results in lack of cytokine production and B cell help for IgE synthesis. Reversal by IL-2, not by IL-4 or IL-13. Journal of immunology (Baltimore, Md. : 1950) 48 7594575
2004 The CXC chemokine receptor encoded by herpesvirus saimiri, ECRF3, shows ligand-regulated signaling through Gi, Gq, and G12/13 proteins but constitutive signaling only through Gi and G12/13 proteins. The Journal of biological chemistry 44 15155729
2015 CD4+CD25+Foxp3+ T regulatory cells, Th1 (CCR5, IL-2, IFN-γ) and Th2 (CCR4, IL-4, Il-13) type chemokine receptors and intracellular cytokines in children with common variable immunodeficiency. International journal of immunopathology and pharmacology 42 26684629
2011 Phagocyte-like NADPH oxidase generates ROS in INS 832/13 cells and rat islets: role of protein prenylation. American journal of physiology. Regulatory, integrative and comparative physiology 41 21228337
2001 IL-13 fusion cytotoxin ameliorates chronic fungal-induced allergic airway disease in mice. Journal of immunology (Baltimore, Md. : 1950) 41 11714828
1996 Characterization of the cloned HEL cell thromboxane A2 receptor: evidence that the affinity state can be altered by G alpha 13 and G alpha q. The Journal of pharmacology and experimental therapeutics 39 8627525
1999 Cyclic AMP-dependent phosphorylation of thromboxane A(2) receptor-associated Galpha(13). The Journal of biological chemistry 38 10488151
2002 Involvement of both extracellular signal-regulated kinase and c-jun N-terminal kinase pathways in the 12-O-tetradecanoylphorbol-13-acetate-induced upregulation of p21(Cip1) in colon cancer cells. Molecular carcinogenesis 36 12203364
2002 Th2 activities induced during virgin T cell priming in the absence of IL-4, IL-13, and B cells. Journal of immunology (Baltimore, Md. : 1950) 36 12218103
2013 The action of kisspeptin-13 on passive avoidance learning in mice. Involvement of transmitters. Behavioural brain research 35 23348107
2019 The effect of apelin-13 on pancreatic islet beta cell mass and myocardial fatty acid and glucose metabolism of experimental type 2 diabetic rats. Peptides 33 30954534
2018 Gβγ signaling to the chemotactic effector P-REX1 and mammalian cell migration is directly regulated by Gαq and Gα13 proteins. The Journal of biological chemistry 31 30446620
1999 Regulatory effects of Th1-type (IFN-gamma, IL-12) and Th2-type cytokines (IL-10, IL-13) on parasite-specific cellular responsiveness in Onchocerca volvulus-infected humans and exposed endemic controls. Immunology 31 10447735
2018 9- and 13-HODE regulate fatty acid binding protein-4 in human macrophages, but does not involve HODE/GPR132 axis in PPAR-γ regulation of FABP4. Therapeutic advances in endocrinology and metabolism 30 29796244
2001 G beta association and effector interaction selectivities of the divergent G gamma subunit G gamma(13). The Journal of biological chemistry 30 11675383
1984 Immune response against the T-independent antigen alpha (1----3) dextran. II. Occurrence of B gamma memory cells in the course of immunization with the native polysaccharide is T cell dependent. European journal of immunology 29 6203758
2015 Interleukin-13 affects the epithelial sodium channel in the intestine by coordinated modulation of STAT6 and p38 MAPK activity. The Journal of physiology 28 26365358
2015 Characterization of an omega-6 linoleate lipoxygenase from Burkholderia thailandensis and its application in the production of 13-hydroxyoctadecadienoic acid. Applied microbiology and biotechnology 26 25586578
2000 Topical delivery of 13-cis-retinoic acid by inhalation up-regulates expression of rodent lung but not liver retinoic acid receptors. Clinical cancer research : an official journal of the American Association for Cancer Research 26 10999756
2018 The Gα12/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity. JCI insight 25 30568036
1993 Brequinar sodium, mycophenolic acid, and cyclosporin A inhibit different stages of IL-4- or IL-13-induced human IgG4 and IgE production in vitro. Annals of the New York Academy of Sciences 23 7509129
2005 Infant home endotoxin is associated with reduced allergen-stimulated lymphocyte proliferation and IL-13 production in childhood. The Journal of allergy and clinical immunology 22 16083802
2013 Drosophila Ric-8 interacts with the Gα12/13 subunit, Concertina, during activation of the Folded gastrulation pathway. Molecular biology of the cell 20 24006487
2011 Downregulation of matrix metalloproteinase-13 by the root extract of Cyathula officinalis Kuan and its constituents in IL-1β-treated chondrocytes. Planta medica 19 21347999
2021 The GABAB receptor mediates neuroprotection by coupling to G13. Science signaling 18 34665640
2021 Inhibition of lysophosphatidic acid receptor 1-3 deteriorates experimental autoimmune encephalomyelitis by inducing oxidative stress. Journal of neuroinflammation 17 34666785
2019 Fibrogenesis in Chronic DSS Colitis is Not Influenced by Neutralisation of Regulatory T Cells, of Major T Helper Cytokines or Absence of IL-13. Scientific reports 17 31296924
2010 Immunoglobulin GM 3 23 5,13,14 phenotype is strongly associated with IgG1 antibody responses to Plasmodium vivax vaccine candidate antigens PvMSP1-19 and PvAMA-1. Malaria journal 17 20696056
2003 Benzylpenicillin differentially conjugates to IFN-gamma, TNF-alpha, IL-1beta, IL-4 and IL-13 but selectively reduces IFN-gamma activity. Clinical and experimental immunology 17 12562387
1998 Subchronic (13-week) oral toxicity study of gamma-cyclodextrin in dogs. Regulatory toxicology and pharmacology : RTP 17 9671570
2019 13C-Metabolic Flux Analysis Reveals the Metabolic Flux Redistribution for Enhanced Production of Poly-γ-Glutamic Acid in dlt Over-Expressed Bacillus licheniformis. Frontiers in microbiology 14 30774627
2010 Mycobacterium tuberculosis Rv1419 encodes a secreted 13 kDa lectin with immunological reactivity during human tuberculosis. European journal of immunology 14 20017196
1989 Differential effects of phorbol 12-myristate 13-acetate on GTP gamma S-induced diacylglycerol formation and arachidonic acid liberation in saponin-permeabilized rabbit platelets. Thrombosis research 14 2499943
2018 Unexpected involvement of IL-13 signalling via a STAT6 independent mechanism during murine IgG2a development following viral vaccination. European journal of immunology 13 29569714
2017 Perinatal Bacterial Exposure Contributes to IL-13 Aeroallergen Response. American journal of respiratory cell and molecular biology 13 28443674
2007 In vitro pharmacological characterisation of a novel cyclic nociceptin/orphanin FQ analogue c[Cys(7,10)]N/OFQ(1-13)NH (2). Naunyn-Schmiedeberg's archives of pharmacology 13 17598088
1991 Negative regulation of interleukin-2 production in primary lymphocytes by 12-O-tetradecanoylphorbol-13-acetate. Lymphokine and cytokine research 13 1715761
2007 Sphingosine-1-phosphate-induced oxygen free radical generation in smooth muscle cell migration requires Galpha12/13 protein-mediated phospholipase C activation. Journal of vascular surgery 12 18155002
2005 Synthesis of (13)C-labeled gamma-hydroxybutyrates for EPR studies with 4-hydroxybutyryl-CoA dehydratase. Bioorganic chemistry 12 15668183
2012 1-Oxoeudesm-11(13)-eno-12,8a-lactone induces G2/M arrest and apoptosis of human glioblastoma cells in vitro. Acta pharmacologica Sinica 11 23160341
2002 Cyclosporin A-mediated killing of Leishmania major by macrophages is independent of reactive nitrogen and endogenous TNF-alpha and is not inhibited by IL-10 and 13. Parasitology research 11 12541065
2022 Concerted regulation of OPG/RANKL/ NF‑κB/MMP-13 trajectories contribute to ameliorative capability of prodigiosin and/or low dose γ-radiation against adjuvant- induced arthritis in rats. International immunopharmacology 10 35944459
2014 Long-term survival (>13 years) in a child with recurrent diffuse pontine gliosarcoma: a case report. Journal of pediatric hematology/oncology 10 24136026
2011 Isoprenylcysteine carboxyl methyltransferase facilitates glucose-induced Rac1 activation, ROS generation and insulin secretion in INS 832/13 β-cells. Islets 10 21346419
2009 Subchronic (13-week) oral toxicity study of dihomo-gamma-linolenic acid (DGLA) oil in rats. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 10 19275928
2008 Studies of the toxicological potential of capsinoids: VII. A 13-week toxicity study of dihydrocapsiate in rats. International journal of toxicology 10 19037801
2014 Probiotic and cultural characteristic of strain Lactobacillus gasseri 4/13 of human origin. Biotechnology, biotechnological equipment 7 26692783
2022 Immunogenicity and protection against Glaesserella parasuis serotype 13 infection after vaccination with recombinant protein LolA in mice. The Journal of veterinary medical science 4 36216558
2018 The effect of splenectomy on the levels of PCV-13-induced memory B- and T cells. International journal of clinical practice 4 29532980
2010 Molecular identification of the novel Gγ-β hybrid hemoglobin: Hb Gγ-β Ulsan (Gγ through 13; β from 19). Blood cells, molecules & diseases 4 21035360
2025 Frog Skin Antimicrobial Peptide 3-13 and Its Analogs Alleviate Atherosclerosis Cholesterol Accumulation in Foam Cells via PPARγ Signaling Pathway. Cells 3 41002435
2024 Clinical features and ALDH5A1 gene findings in 13 Chinese cases with succinic semialdehyde dehydrogenase deficiency. BMC medical genomics 3 38862963
1994 Rapid isolation of G alpha 13 from bovine brain membranes: supportive effect of ethylene glycol. Biochemical and biophysical research communications 3 7980550
2022 Distribution of 22 Single Nucleotide Polymorphisms in 13 Cytokine Genes in Malays, Chinese, and Indians in Peninsular Malaysia. Genetic testing and molecular biomarkers 1 36166739
2012 Theoretical investigation of a novel high density cage compound 4,8,11,14,15-pentanitro-2,6,9,13-tetraoxa-4,8,11,14,15-pentaazaheptacyclo[5.5.1.1(3,11).1(5,9)] pentadecane. Journal of molecular modeling 1 23111684
1979 Diagnostic dilemma of a 13-month-old boy with 'late-onset' combined immunodeficiency. American journal of diseases of children (1960) 1 88898
2023 Impact of hematopoietic stem cell transplantation in glycogen storage disease type Ib: A single-subject research design using 13C-glucose breath test. Molecular genetics and metabolism reports 0 36632325
2011 Determining the activation of rho as an index of receptor coupling to G₁₂/₁₃ proteins. Methods in molecular biology (Clifton, N.J.) 0 21607865
2002 [Effect of interferon inductors on infection induced by hepatitis C virus and activity of mRNA cytokines in cell cultures SW-13 and MT-4]. Voprosy virusologii 0 12508677

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