Affinage

AP3S1

AP-3 complex subunit sigma-1 · UniProt Q92572

Round 2 corrected Audit flag: rerun needed
Length
193 aa
Mass
21.7 kDa
Annotated
2026-04-28
47 papers in source corpus 9 papers cited in narrative 9 extracted findings

Mechanistic narrative

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Mechanism profile

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Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 AP3S1 (CLAPS3) was identified as a novel gene encoding a peptide homologous to clathrin-adaptor small chains (sigma subunits) in rat, mouse, and yeast, with a 193-amino-acid open reading frame and ubiquitous expression across human tissues; it was mapped to chromosome 12p13.2→p13.1 by FISH. cDNA library cloning, Northern blot analysis, FISH chromosomal mapping Cytogenetics and cell genetics Medium 8697810
1997 AP3S1 encodes sigma3A, one of two sigma3 isoforms (sigma3A and sigma3B) that are components of the AP-3 heterotetrameric complex (also containing p47A/mu3, delta, and beta3 subunits). The complex localizes to the TGN region and peripheral structures including transferrin receptor-positive endosomes, and recognizes the tyrosine-based sorting signal YQRL via its medium chain (p47A), implicating AP3S1/sigma3A in tyrosine-based sorting. Northern blot, Western blot, co-immunoprecipitation, immunofluorescence microscopy, tyrosine-signal binding assay The EMBO journal High 9118953
1997 Sigma3 (AP3S1) is confirmed as a subunit of the AP-3 adaptor-like complex. Immunofluorescence with anti-delta antibodies shows AP-3 associates with the Golgi region and peripheral post-TGN structures. The delta subunit is homologous to the Drosophila garnet gene product, linking AP-3 (and thus AP3S1) to lysosome/pigment granule trafficking pathways. EST database search, cDNA cloning, antibody generation against recombinant subunits, co-immunoprecipitation, immunofluorescence microscopy The Journal of cell biology High 9151686
1998 The AP-3 complex (containing AP3S1/sigma3) associates with clathrin through direct interaction of the beta3 appendage domain with the amino-terminal domain of clathrin heavy chain, via a conserved clathrin-binding consensus motif. AP-3 and clathrin colocalize in cells by immunofluorescence and immunoelectron microscopy, indicating AP3S1-containing AP-3 functions as part of a clathrin coat. In vitro binding assay, immunofluorescence microscopy, immunoelectron microscopy Science High 9545220
2003 The AP-3 complex (which includes AP3S1/sigma3) selectively mediates targeting of the zinc transporter ZnT3 to synaptic vesicles. ZnT3's cytosolic tail interacted with AP-3 in cell-free assays, and ZnT3 synaptic vesicle content was reduced in AP-3-deficient (mocha) neurons, while synaptophysin (routed via AP-2) was unaffected, demonstrating that AP-3 generates a molecularly distinct synaptic vesicle subpopulation. Cell-free binding assay (AP-3 tail interaction), pharmacological disruption of vesicle biogenesis, immunoisolation of vesicle subpopulations, analysis of AP-3-deficient (mocha) mouse neurons Molecular biology of the cell High 14657250
2005 AP-3 (containing AP3S1/sigma3) functions independently of AP-1 in sorting tyrosinase from tubular early endosomes to melanosomes. Both AP-3 and AP-1 recognize the tyrosinase dileucine-based melanosome sorting signal and localize to clathrin-coated buds on endosomes. In AP-3-deficient melanocytes, tyrosinase accumulates in multivesicular endosomes, with compensatory increase in AP-1-dependent sorting, demonstrating partially redundant endosome-to-melanosome pathways. Immunofluorescence and immunoelectron microscopy in AP-3-deficient melanocytes, dileucine-signal recognition assay, analysis of mocha (AP-3-null) melanocytes Molecular biology of the cell High 16162817
2010 Partial knockdown of Ap3s1 (and Ap1s1) in zebrafish sensitized developing melanocytes to hypopigmentation under low-copper environmental conditions, demonstrating that AP3S1-dependent intracellular trafficking is required for copper loading into cuproproteins (such as tyrosinase) in melanocytes. Yeast chemical-genetic profiles confirmed that defects in trafficking pathways cause sensitivity to copper depletion. Morpholino-based knockdown in zebrafish, phenotypic analysis of melanocyte pigmentation, yeast chemical-genetic screening Disease models & mechanisms Medium 20713646
2024 AP3S1 knockdown in ovarian cancer cells reduced tumor cell migration and invasion through modulation of the TGF-β/SMAD signaling pathway, suggesting AP3S1 has a regulatory role in tumor cell motility linked to this pathway. siRNA knockdown in ovarian cancer cell lines, migration and invasion assays, TGF-β/SMAD pathway analysis European journal of medical research Low 38609993
2024 AP3S1 protein was identified as a novel interactor with multiple HPAI H7N9 viral proteins (hemagglutinin, matrix 1, neuraminidase, nucleoprotein, PB1, PB2) by co-immunoprecipitation, suggesting AP3S1-dependent intracellular trafficking participates in the life cycle of highly pathogenic avian influenza H7N9 in human cells. siRNA knockdown screen, co-immunoprecipitation of AP3S1 with viral proteins Heliyon Low 38560106

Source papers

Stage 0 corpus · 47 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
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
1997 AP-3: an adaptor-like protein complex with ubiquitous expression. The EMBO journal 332 9118953
1998 Association of the AP-3 adaptor complex with clathrin. Science (New York, N.Y.) 319 9545220
1997 Characterization of the adaptor-related protein complex, AP-3. The Journal of cell biology 318 9151686
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nature biotechnology 266 15146197
2005 Functions of adaptor protein (AP)-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes. Molecular biology of the cell 213 16162817
2015 A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning. eLife 198 26673895
2019 A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. Nature immunology 159 30833792
2009 Ubiquitin-mediated proteolysis of HuR by heat shock. The EMBO journal 142 19322201
2022 A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets. Nature biotechnology 140 36217030
2019 Systematic bromodomain protein screens identify homologous recombination and R-loop suppression pathways involved in genome integrity. Genes & development 110 31753913
2010 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Molecular medicine (Cambridge, Mass.) 108 20379614
2003 The zinc transporter ZnT3 interacts with AP-3 and it is preferentially targeted to a distinct synaptic vesicle subpopulation. Molecular biology of the cell 100 14657250
2014 Proteomic analysis of the epidermal growth factor receptor (EGFR) interactome and post-translational modifications associated with receptor endocytosis in response to EGF and stress. Molecular & cellular proteomics : MCP 99 24797263
2020 Targeting TRIM37-driven centrosome dysfunction in 17q23-amplified breast cancer. Nature 93 32908313
2018 Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function. EMBO reports 92 29467282
2012 Charting the landscape of tandem BRCT domain-mediated protein interactions. Science signaling 92 22990118
2003 Genomic evidence for the absence of a functional cholesteryl ester transfer protein gene in mice and rats. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 64 12798933
2010 Combined zebrafish-yeast chemical-genetic screens reveal gene-copper-nutrition interactions that modulate melanocyte pigmentation. Disease models & mechanisms 37 20713646
1999 A physical, transcript, and deletion map of chromosome region 12p12.3 flanked by ETV6 and CDKN1B: hypermethylation of the LRP6 CpG island in two leukemia patients with hemizygous del(12p). Genomics 28 10036184
2013 Common fusion transcripts identified in colorectal cancer cell lines by high-throughput RNA sequencing. Translational oncology 27 24151535
1996 Cloning, expression pattern and mapping to 12p 13.2 --> p13.1 of CLAPS3, a gene encoding a novel clathrin-adaptor small chain. Cytogenetics and cell genetics 12 8697810
2022 Integrative Genomic Analyses of 1,145 Patient Samples Reveal New Biomarkers in Esophageal Squamous Cell Carcinoma. Frontiers in molecular biosciences 11 35127817
2006 Downregulation of genes encoding for subunits of adaptor complex-3 in cervical carcinomas. Biochemistry. Biokhimiia 9 17125464
2022 The integrative network of circRNA, miRNA and mRNA of epicardial adipose tissue in patients with atrial fibrillation. American journal of translational research 8 36247236
1999 Fine physical and transcript mapping of a 1.8 Mb region spanning the locus for childhood acute lymphoblastic leukemia on chromosome 12p12. 3. Gene 8 10580149
2025 Molecular patterns and mechanisms of tumorigenesis in HPV-associated and HPV-independent sinonasal squamous cell carcinoma. Nature communications 7 40500270
2024 Host proteins interact with viral elements and affect the life cycle of highly pathogenic avian influenza A virus H7N9. Heliyon 5 38560106
2017 Genetic diagnosis of a Chinese multiple endocrine neoplasia type 2A family through whole genome sequencing. Journal of biosciences 5 28569245
2023 Resveratrol ameliorates intestinal lipid metabolism through the PPAR signaling pathway in high-fat diet-fed red tilapia (Oreochromis niloticus). Fish & shellfish immunology 4 38128680
2016 High-Content Analysis of the Golgi Complex by Correlative Screening Microscopy. Methods in molecular biology (Clifton, N.J.) 3 27632005
2024 Functional analysis and validation of oncodrive gene AP3S1 in ovarian cancer through filtering of mutation data from whole-exome sequencing. European journal of medical research 2 38609993
2024 Molecular patterns and mechanisms of tumorigenesis in HPV-associated and HPV-independent sinonasal squamous cell carcinoma. bioRxiv : the preprint server for biology 2 38979305
2026 Autophagy-Mitophagy Pathway-Linked Genetic Variants Associate with Systemic Inflammation and Interact with Dietary Factors in Asian and European Cohorts. International journal of molecular sciences 0 41977248