Affinage

NAPG

Gamma-soluble NSF attachment protein · UniProt Q99747

Length
312 aa
Mass
34.7 kDa
Annotated
2026-06-10
36 papers in source corpus 3 papers cited in narrative 4 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 2/3 claims corpus-supported (67%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

γ-SNAP (NAPG) is an NSF attachment protein that operates selectively in endosomal membrane trafficking by engaging a restricted set of SNAREs, including syntaxin-7-containing endosomal complexes, and mediating their disassembly in a manner analogous to α-SNAP (PMID:26101353). Functionally, depletion of NAPG partially blocks the exit of EGF receptor and transferrin from EEA1-positive early endosomes, delaying receptor degradation and cargo uptake and establishing a defined role in early endosome cargo progression (PMID:26101353). A separate cellular study links NAPG to inhibition of osteogenic differentiation (PMID:40603950). Beyond these findings, the molecular details of NAPG's recruitment, structure, and broader pathway context have not been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2010 Low

    An initial interaction screen placed NAPG in a candidate protein-protein network by identifying it as a binding partner of the LRP1 cytoplasmic domain, though without functional follow-up for NAPG.

    Evidence Split-ubiquitin yeast two-hybrid screen

    PMID:20205790

    Open questions at the time
    • Single method (yeast two-hybrid) not independently validated for NAPG
    • No demonstration of a functional consequence of the LRP1 interaction
    • NAPG was not the focus of validation in the study
  2. 2015 High

    The question of what compartment NAPG acts in and which SNAREs it engages was answered by showing it interacts with a limited range of endosomal SNAREs (including syntaxin-7 complexes) and mediates their disassembly like α-SNAP, defining it as an endosome-selective SNAP rather than a general trafficking factor.

    Evidence Reciprocal co-IP with mass spectrometry, siRNA knockdown, overexpression, and live-cell endosome imaging

    PMID:26101353

    Open questions at the time
    • Structural basis of selective SNARE engagement not defined
    • Mechanism distinguishing γ-SNAP from α-SNAP specificity unresolved
    • Dependence on NSF demonstrated only in this single study
  3. 2015 Medium

    The physiological output of NAPG-mediated disassembly was established by showing its depletion suppresses EGFR and transferrin exit from EEA1-positive early endosomes, linking SNARE disassembly to cargo progression and receptor degradation kinetics.

    Evidence siRNA knockdown with fluorescence microscopy tracking of EGFR/transferrin and EEA1 co-localization

    PMID:26101353

    Open questions at the time
    • Single-method trafficking readout
    • Partial (not complete) suppression leaves the full requirement for NAPG unclear
    • Downstream effects on signaling not assessed
  4. 2025 Medium

    A new cellular role was identified by showing NAPG inhibits osteogenic differentiation, extending its functional relevance beyond endosomal trafficking.

    Evidence ALP assay, Alizarin Red staining, and Western blot in osteogenic differentiation assays

    PMID:40603950

    Open questions at the time
    • Mechanistic link between endosomal SNARE function and osteogenesis not established
    • Single-lab finding with cellular but not in vivo validation
    • Molecular pathway mediating the differentiation effect unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NAPG achieves its endosome selectivity, how it cooperates with NSF mechanistically, and how its trafficking role connects to its effect on osteogenic differentiation remain unresolved.
  • No structural model of NAPG-SNARE-NSF engagement
  • Mechanism of compartment-restricted SNARE recognition undefined
  • Causal connection between trafficking function and osteogenesis unestablished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005768 endosome 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 2
Partners
LRP1NSFSTX7

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 γ-SNAP (encoded by NAPG) interacts with a limited range of SNAREs, including endosomal SNAREs (e.g., syntaxin-7-containing complexes), and mediates disassembly of these SNARE complexes in a manner analogous to α-SNAP, functioning specifically at endosomes rather than broadly across all trafficking compartments. Immunoprecipitation, mass spectrometry, siRNA-mediated knockdown, overexpression, live-cell imaging of endosome morphology and distribution, functional trafficking assays (EGFR and transferrin trafficking) Journal of cell science High 26101353
2015 Depletion of γ-SNAP (NAPG) by siRNA partially suppresses exit of EGFR and transferrin from EEA1-positive early endosomes, delaying their degradation and uptake, establishing a defined role for NAPG in endosomal trafficking. siRNA knockdown, fluorescence microscopy tracking of EGFR and transferrin trafficking, EEA1 marker co-localization Journal of cell science Medium 26101353
2010 NAPG (γ-SNAP) was identified as a binding partner of the cytoplasmic domain of LRP1 in a split-ubiquitin yeast two-hybrid screen. Split-ubiquitin yeast two-hybrid screen Molecular neurodegeneration Low 20205790
2025 NAPG inhibits osteogenic differentiation, as verified at the protein and cellular levels by ALP assay, Alizarin Red staining (ARS), and Western blot experiments. ALP assay, Alizarin Red staining, Western blot, cellular osteogenic differentiation assay Scientific reports Medium 40603950

Source papers

Stage 0 corpus · 36 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Molecular genetics of bipolar disorder and depression. Psychiatry and clinical neurosciences 214 17239033
2007 Growth of Campylobacter jejuni on nitrate and nitrite: electron transport to NapA and NrfA via NrfH and distinct roles for NrfA and the globin Cgb in protection against nitrosative stress. Molecular microbiology 99 17241202
1999 Essential roles for the products of the napABCD genes, but not napFGH, in periplasmic nitrate reduction by Escherichia coli K-12. The Biochemical journal 80 10548535
2004 The unprecedented nos gene cluster of Wolinella succinogenes encodes a novel respiratory electron transfer pathway to cytochrome c nitrous oxide reductase. FEBS letters 79 15225600
1993 IL-4- and IL-5-secreting lymphocyte populations are preferentially stimulated by parasite-derived antigens in human tissue invasive nematode infections. Journal of immunology (Baltimore, Md. : 1950) 72 8376801
2004 NapGH components of the periplasmic nitrate reductase of Escherichia coli K-12: location, topology and physiological roles in quinol oxidation and redox balancing. The Biochemical journal 64 14674886
1998 Periplasmic nitrate-reducing system of the phototrophic bacterium Rhodobacter sphaeroides DSM 158: transcriptional and mutational analysis of the napKEFDABC gene cluster. The Biochemical journal 46 9560320
2011 The 18p11.22 locus is associated with never smoker non-small cell lung cancer susceptibility in Korean populations. Human genetics 44 21866343
2005 Nitrate reduction by Desulfovibrio desulfuricans: a periplasmic nitrate reductase system that lacks NapB, but includes a unique tetraheme c-type cytochrome, NapM. FEMS microbiology letters 44 15972253
2008 The Tat system proofreads FeS protein substrates and directly initiates the disposal of rejected molecules. The EMBO journal 41 18615097
2008 Characterization of the NapGH quinol dehydrogenase complex involved in Wolinella succinogenes nitrate respiration. Molecular microbiology 39 18631238
2006 The NapF protein of the Escherichia coli periplasmic nitrate reductase system: demonstration of a cytoplasmic location and interaction with the catalytic subunit, NapA. Microbiology (Reading, England) 38 17074894
2010 Extensive proteomic screening identifies the obesity-related NYGGF4 protein as a novel LRP1-interactor, showing reduced expression in early Alzheimer's disease. Molecular neurodegeneration 36 20205790
2007 Role of individual nap gene cluster products in NapC-independent nitrate respiration of Wolinella succinogenes. Microbiology (Reading, England) 34 17975082
1995 Stereoselective binding properties of naproxen glucuronide diastereomers to proteins. Journal of pharmacokinetics and biopharmaceutics 33 8882746
2009 Periplasmic nitrate reduction in Wolinella succinogenes: cytoplasmic NapF facilitates NapA maturation and requires the menaquinol dehydrogenase NapH for membrane attachment. Microbiology (Reading, England) 27 19477904
2009 TatD is a central component of a Tat translocon-initiated quality control system for exported FeS proteins in Escherichia coli. EMBO reports 20 19343049
2019 One-Step Nanosurface Self-Assembly of d-Peptides Renders Bubble-Free Ultrasound Theranostics. Nano letters 19 30868886
2015 γ-SNAP stimulates disassembly of endosomal SNARE complexes and regulates endocytic trafficking pathways. Journal of cell science 18 26101353
2022 Peptide-based direct electrochemical detection of receptor binding domains of SARS-CoV-2 spike protein in pristine samples. Sensors and actuators. B, Chemical 17 36438197
2006 Analysis of variations in the NAPG gene on chromosome 18p11 in bipolar disorder. Psychiatric genetics 17 16395123
2023 Hypobaric hypoxia drives selection of altitude-associated adaptative alleles in the Himalayan population. The Science of the total environment 13 38159773
2018 Genetic polymorphisms in the circumsporozoite protein of Plasmodium malariae show a geographical bias. Malaria journal 13 30012172
2024 Potential Association of Gut Microbial Metabolism and Circulating mRNA Based on Multiomics Sequencing Analysis in Fetal Growth Restriction. Mediators of inflammation 8 38716374
2009 Association study on the NAPG gene and bipolar disorder in the Chinese Han population. Neuroscience letters 8 19429185
2005 Genomic sequence analysis of a potential QTL region for fat trait on pig chromosome 6. Genomics 7 16326071
2007 Identification of the functional periplasmic nitrate reductase (nap) gene cluster from the deep-sea denitrifier Pseudomonas sp. strain MT-1. Bioscience, biotechnology, and biochemistry 6 17690469
2025 Pyrite-driven denitrification by Paracoccus denitrificans: Promoted by enhanced electron transfer and extracellular polymeric substances. Bioresource technology 5 40835143
2024 A detailed analysis of 16S rRNA gene sequencing and conventional PCR-based testing for the diagnosis of bacterial pathogens and discovery of novel bacteria. Antonie van Leeuwenhoek 4 39012584
2021 NAPG mutation in family members with hereditary hemorrhagic telangiectasia in China. BMC pulmonary medicine 4 34112136
2022 Complexes of Sodium Pectate with Nickel for Hydrogen Oxidation and Oxygen Reduction in Proton-Exchange Membrane Fuel Cells. International journal of molecular sciences 3 36430721
2024 Evaluation of circulating plasma proteins in prostate cancer using mendelian randomization. Discover oncology 2 39287922
2023 Carbonized Nickel Complex of Sodium Pectate as Catalyst for Proton-Exchange Membrane Fuel Cells. Membranes 1 37505001
2025 Identification and verification of oxidative stress-related genes in the diagnosis of osteoporosis. Scientific reports 0 40603950
2025 D-peptide engineered hydrogel with dual-enzyme-ALA cascades enables multimodal oxygen modulation for self-sustaining EDT-PDT synergy. Bioactive materials 0 41536918
2009 NAP has no effect on spatial memory after short-term treatment in advanced stage Alzheimer's disease mouse model. Peptides 0 19664667

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