Affinage

AP3S1

AP-3 complex subunit sigma-1 · UniProt Q92572

Length
193 aa
Mass
21.7 kDa
Annotated
2026-06-09
17 papers in source corpus 4 papers cited in narrative 4 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 3/3 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AP3S1 (CLAPS3) encodes a small clathrin-adaptor chain that functions as a subunit of the AP-3 adaptor complex in intracellular vesicular trafficking, and is expressed ubiquitously across human tissues (PMID:8697810). Its trafficking role is required for copper homeostasis: partial knockdown in zebrafish sensitized developing melanocytes to hypopigmentation under low-copper conditions, placing AP3S1 in the intracellular trafficking pathway essential for copper loading into cuproproteins (PMID:20713646). Beyond these established roles, mechanistic detail is limited in the available corpus: AP3S1 has been reported as a host interactor of multiple HPAI H7N9 viral proteins (PMID:38560106) and its knockdown reduces ovarian cancer cell migration and invasion in a manner linked to TGF-β/SMAD signaling (PMID:38609993), but neither the structural basis of cargo recognition nor the biochemical mechanism of these activities has been characterized.

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 1996 Medium

    Establishing the molecular identity of AP3S1 answered whether the gene encodes a defined trafficking component, identifying it as a small clathrin-adaptor chain conserved across species and broadly expressed.

    Evidence cDNA cloning from a human fetal-brain library with Northern blot and FISH mapping

    PMID:8697810

    Open questions at the time
    • No functional assay of adaptor activity or cargo specificity
    • Assembly into the AP-3 complex not demonstrated biochemically here
    • Subcellular localization not resolved
  2. 2010 Medium

    Linking AP3S1 to copper homeostasis answered whether its trafficking function has a defined physiological consequence, showing it is required for copper loading into cuproproteins during melanocyte development.

    Evidence Morpholino partial knockdown in zebrafish with pigmentation readout, corroborated by yeast chemical-genetic profiling

    PMID:20713646

    Open questions at the time
    • Specific cargo or transporter trafficked by AP-3 in copper delivery not identified
    • Partial knockdown leaves residual function unaddressed
    • Mechanism not validated in human cells
  3. 2024 Low

    A host-factor screen addressed whether AP3S1 participates in viral infection, identifying it as an interactor of multiple HPAI H7N9 proteins.

    Evidence siRNA knockdown screen followed by co-immunoprecipitation of AP3S1 with H7N9 viral proteins

    PMID:38560106

    Open questions at the time
    • Single Co-IP without reciprocal pulldown or functional rescue
    • Direct versus indirect interaction not distinguished
    • Consequence for viral replication not quantified
  4. 2024 Low

    A cancer cell study addressed whether AP3S1 influences tumor cell behavior, linking its knockdown to reduced migration and invasion via TGF-β/SMAD signaling.

    Evidence siRNA knockdown in ovarian cancer cell lines with migration/invasion assays and pathway analysis

    PMID:38609993

    Open questions at the time
    • Pathway placement relies on bioinformatics without direct biochemical validation
    • Mechanistic link between AP-3 trafficking and TGF-β/SMAD undefined
    • Single cell-line model and single knockdown approach

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AP3S1 within the AP-3 complex selects cargo and how its trafficking function mechanistically connects to copper delivery, viral life cycle, and TGF-β/SMAD signaling remains unresolved.
  • No structural model of cargo recognition
  • No direct biochemical link between AP-3 trafficking and the reported viral or signaling phenotypes
  • Endogenous human cargo not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 2
Complex memberships
AP-3 adaptor complex

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 AP3S1 (CLAPS3) encodes a novel clathrin-adaptor small chain of 193 amino acids (22 kDa) with homology to clathrin-adaptor small chains in rat, mouse, and yeast, and is expressed ubiquitously across human tissues as a 1.35-kb transcript. cDNA cloning from human fetal-brain library, Northern blot analysis, FISH chromosomal mapping Cytogenetics and cell genetics Medium 8697810
2010 Partial knockdown of Ap3s1 (an intracellular trafficking component, AP-3 complex subunit) in zebrafish sensitized developing melanocytes to hypopigmentation under low-copper conditions, placing AP3S1 in the intracellular trafficking pathway essential for copper loading into cuproproteins. Morpholino-based partial knockdown in zebrafish combined with yeast chemical-genetic profiling; phenotypic readout of melanocyte pigmentation under copper-depleted conditions Disease models & mechanisms Medium 20713646
2024 AP3S1 protein interacts with multiple HPAI H7N9 viral proteins (hemagglutinin, matrix 1, neuraminidase, nucleoprotein, PB1, PB2) as demonstrated by co-immunoprecipitation, identifying AP3S1 as a novel host interactor involved in modulating the viral life cycle. siRNA knockdown screen followed by co-immunoprecipitation of AP3S1 with HPAI H7N9 viral proteins Heliyon Low 38560106
2024 AP3S1 knockdown in ovarian cancer cells reduced tumor cell migration and invasion, with mechanistic placement in the TGF-β/SMAD signaling pathway. siRNA knockdown in ovarian cancer cell lines with migration/invasion assays; pathway analysis implicating TGF-β/SMAD European journal of medical research Low 38609993

Source papers

Stage 0 corpus · 17 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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 67 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
2022 Integrative Genomic Analyses of 1,145 Patient Samples Reveal New Biomarkers in Esophageal Squamous Cell Carcinoma. Frontiers in molecular biosciences 12 35127817
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 The integrative network of circRNA, miRNA and mRNA of epicardial adipose tissue in patients with atrial fibrillation. American journal of translational research 9 36247236
2006 Downregulation of genes encoding for subunits of adaptor complex-3 in cervical carcinomas. Biochemistry. Biokhimiia 9 17125464
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
2023 Resveratrol ameliorates intestinal lipid metabolism through the PPAR signaling pathway in high-fat diet-fed red tilapia (Oreochromis niloticus). Fish & shellfish immunology 6 38128680
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
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

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