Affinage

AP5M1

AP-5 complex subunit mu-1 · UniProt Q9H0R1

Length
490 aa
Mass
54.8 kDa
Annotated
2026-06-09
100 papers in source corpus 5 papers cited in narrative 5 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AP5M1 (MUDENG/MuD) is a 490-amino-acid adaptin-domain-containing protein that regulates the intrinsic apoptotic program, with context-dependent pro-death and anti-apoptotic activities documented across multiple cancer cell types (PMID:18395520, PMID:27136675). Ectopic overexpression drives cell death in Jurkat and HeLa cells, and in cervical cancer cells this killing operates strictly through the mitochondrial pathway: AP5M1 upregulates BAX and loses all apoptotic activity in BAX-knockout or BAX-knockdown cells (PMID:18395520, PMID:31427081). During TRAIL-induced apoptosis, AP5M1 is itself a caspase-3 substrate, cleaved at D276 and D290 within its adaptin domain to generate a fragment with reduced cell-killing activity, indicating that an intact adaptin domain is required for its pro-death function (PMID:23665015). In astroglioma cells AP5M1 acts as an anti-apoptotic factor at the Bid/Bcl-2 junction downstream of TRAIL: its depletion enhances cleavage of caspase-3, caspase-9, and Bid, drives conversion of Bcl-2 to a truncated 25-kDa pro-apoptotic fragment, and this TRAIL-sensitizing effect is abrogated by co-depletion of Bid (PMID:27136675). AP5M1 localizes predominantly to the endoplasmic reticulum and partly to mitochondria (PMID:27136675). Beyond its role in apoptotic signaling, no clathrin- or adaptor-complex trafficking function has been characterized for AP5M1 in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2008 Medium

    Established AP5M1/MUDENG as a discrete protein and first linked it to cell death, defining the founding question of how an adaptin-domain protein influences viability.

    Evidence Full-length ORF cloning and ectopic overexpression in Jurkat and HeLa cells with viability assays

    PMID:18395520

    Open questions at the time
    • Overexpression phenotype only; no endogenous loss-of-function
    • No pathway placement beyond domain homology
    • Trafficking role of the adaptin domain untested
  2. 2013 High

    Identified AP5M1 as a caspase-3 substrate cleaved at D276/D290, showing that adaptin-domain integrity is required for its pro-death activity and placing the protein downstream of caspase activation.

    Evidence In vitro recombinant caspase-3 cleavage assay with mutagenesis-validated sites, confirmed in Jurkat and BJAB cells under TRAIL

    PMID:23665015

    Open questions at the time
    • Functional consequence of the cleavage fragment in vivo not resolved
    • Does not explain how intact protein engages the death machinery
  3. 2013 Low

    Provided reagent and expression validation across cell lines and tissues, confirming endogenous protein presence and the middle domain as antigenic.

    Evidence Monoclonal antibody (M3H9) generation, ELISA, immunoblot, and IHC on astroglioma, astrocytes, and mouse ovary/uterus

    PMID:23909422

    Open questions at the time
    • Antibody characterization only; establishes no mechanism
    • Physiological role in the reproductive tissues not addressed
  4. 2016 High

    Reframed AP5M1 as anti-apoptotic in astroglioma and placed its function at the Bid/Bcl-2 junction, resolving where in the TRAIL pathway it acts.

    Evidence Stable overexpression and shRNA knockdown with TRAIL stimulation, caspase/Bid/Bcl-2 immunoblotting, Bid co-depletion epistasis, and subcellular fractionation

    PMID:27136675

    Open questions at the time
    • Direct binding partners at the Bid/Bcl-2 node not identified
    • Mechanism reconciling pro-death overexpression and anti-apoptotic depletion phenotypes unresolved
    • Molecular basis of ER/mitochondrial localization unknown
  5. 2019 Medium

    Demonstrated that AP5M1's apoptotic activity in cervical cancer is entirely BAX-dependent, anchoring it to the mitochondrial apoptotic pathway.

    Evidence Overexpression with BAX knockout and siRNA knockdown, apoptosis assays, and patient-tissue mRNA correlation

    PMID:31427081

    Open questions at the time
    • Whether AP5M1 acts directly or indirectly on BAX not determined
    • Reconciliation with anti-apoptotic role in astroglioma not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether AP5M1 retains any clathrin- or adaptor-complex trafficking function predicted by its mu2-homologous adaptin domain, and how this relates to its apoptotic role, remains unresolved.
  • No identified membrane cargo or coat partners
  • No structural model of the adaptin domain in context
  • Direct molecular partners at apoptotic nodes unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005739 mitochondrion 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-5357801 Programmed Cell Death 3

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 MUDENG (AP5M1) encodes a 490 amino acid protein containing an adaptin domain homologous to the mu2 subunit of adaptor protein complexes related to clathrin-mediated endocytosis; ectopic overexpression of MUDENG induced cell death in Jurkat T cells and HeLa cells, establishing it as a pro-death protein. Cloning of full-length ORF, ectopic overexpression in cell lines (Jurkat, HeLa), cell viability assays Biochemical and biophysical research communications Medium 18395520
2013 MUDENG (AP5M1) is cleaved by caspase-3 at residues D276 and D290 within its adaptin domain during TRAIL-induced apoptosis; in vitro cleavage assay with recombinant active caspase-3 confirmed these cleavage sites, and cleaved MUDENG showed reduced cell-killing activity, indicating that intact adaptin domain integrity is required for MUDENG's pro-death function. In vitro caspase cleavage assay using recombinant active caspase proteins, site identification by mutagenesis of cleavage sites, cell viability assays in Jurkat and BJAB cells Biochemical and biophysical research communications High 23665015
2016 MUDENG (AP5M1/MuD) functions as an anti-apoptotic protein in human astroglioma cells: MuD protein levels decrease ~33% following TRAIL stimulation (via caspase-3-mediated cleavage), stable overexpression of MuD enhanced cell survival upon TRAIL treatment (77% vs 46%), and MuD depletion increased susceptibility to TRAIL by enhancing cleavage of caspase-3, caspase-9, and Bid. MuD depletion also caused Bcl-2 conversion to a truncated pro-apoptotic 25-kDa fragment, and the TRAIL-sensitizing effect of MuD depletion was abrogated by Bid co-depletion, placing MuD function at the Bid/Bcl-2 junction. MuD localizes predominantly in the endoplasmic reticulum and partly in mitochondria. Stable transfection (overexpression and shRNA knockdown), TRAIL stimulation, caspase activation assays, Bid and Bcl-2 immunoblotting, subcellular fractionation/localization, genetic epistasis via Bid co-knockdown Oncogenesis High 27136675
2019 AP5M1 (MUDENG) induces apoptosis in cervical cancer cells in a BAX-dependent manner: AP5M1 overexpression upregulated BAX protein levels, and AP5M1 completely lost apoptotic activity in BAX-knockout or BAX-knockdown cervical cancer cells, demonstrating functional dependence on BAX for the mitochondrial apoptotic pathway. Overexpression in cervical cancer cell lines, BAX knockout and knockdown (siRNA), cell viability/apoptosis assays, mRNA correlation analysis in patient tissues Biochemical and biophysical research communications Medium 31427081
2013 A monoclonal antibody (M3H9) against residues 244–326 in the middle domain of human MUDENG (AP5M1) was generated, confirming protein expression in astroglioma cell lines, primary astrocytes, and formalin-fixed mouse ovary and uterus tissues, and validating the middle domain as an antigenic region. Monoclonal antibody generation, ELISA, immunoblot, immunohistochemistry on formalin-fixed paraffin-embedded tissues Monoclonal antibodies in immunodiagnosis and immunotherapy Low 23909422

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 The NuMA-related Mud protein binds Pins and regulates spindle orientation in Drosophila neuroblasts. Nature cell biology 267 16648843
2006 The Drosophila NuMA Homolog Mud regulates spindle orientation in asymmetric cell division. Developmental cell 251 16740476
2006 Drosophila Pins-binding protein Mud regulates spindle-polarity coupling and centrosome organization. Nature cell biology 215 16648846
2010 The Fz-Dsh planar cell polarity pathway induces oriented cell division via Mud/NuMA in Drosophila and zebrafish. Developmental cell 111 21074723
1992 Rapid mapping in Salmonella typhimurium with Mud-P22 prophages. Journal of bacteriology 110 1311301
2005 Diversity and vertical distribution of cultured and uncultured Deltaproteobacteria in an intertidal mud flat of the Wadden Sea. Environmental microbiology 104 15683401
1988 Packaging specific segments of the Salmonella chromosome with locked-in Mud-P22 prophages. Genetics 94 2835289
1985 Directed formation of deletions and duplications using Mud(Ap, lac). Genetics 77 3156064
2011 An ana2/ctp/mud complex regulates spindle orientation in Drosophila neuroblasts. Developmental cell 56 21920316
2019 Characterization of the innate immunity in the mud crab Scylla paramamosain. Fish & shellfish immunology 54 31362092
2011 Canoe binds RanGTP to promote Pins(TPR)/Mud-mediated spindle orientation. The Journal of cell biology 53 22024168
2013 The complete mitochondrial genome sequence and gene organization of the mud crab (Scylla paramamosain) with phylogenetic consideration. Gene 47 23384716
2020 Mud in the blood: the role of protein-mineral complexes and extracellular vesicles in biomineralisation and calcification. Journal of structural biology 46 32711043
2012 Evolution and phylogeny of the mud shrimps (Crustacea: Decapoda) revealed from complete mitochondrial genomes. BMC genomics 43 23153176
2011 Cloning and characterisation of the SpToll gene from green mud crab, Scylla paramamosain. Developmental and comparative immunology 43 21945833
2011 Rab5 GTPase controls chromosome alignment through Lamin disassembly and relocation of the NuMA-like protein Mud to the poles during mitosis. Proceedings of the National Academy of Sciences of the United States of America 43 21987826
2020 Exosome-mediated apoptosis pathway during WSSV infection in crustacean mud crab. PLoS pathogens 42 32433716
2015 Ecdysone receptor in the mud crab Scylla paramamosain: a possible role in promoting ovarian development. The Journal of endocrinology 40 25563354
2017 Cloning, Expression, and the Effects of Processing on Sarcoplasmic-Calcium-Binding Protein: An Important Allergen in Mud Crab. Journal of agricultural and food chemistry 36 28692255
2015 Warts phosphorylates mud to promote pins-mediated mitotic spindle orientation in Drosophila, independent of Yorkie. Current biology : CB 35 26592339
1993 The Salmonella typhimurium nadC gene: sequence determination by use of Mud-P22 and purification of quinolinate phosphoribosyltransferase. Journal of bacteriology 32 8419294
2021 Molting Alters the Microbiome, Immune Response, and Digestive Enzyme Activity in Mud Crab (Scylla paramamosain). mSystems 31 34636669
2020 Mapping and IgE-binding capacity analysis of heat/digested stable epitopes of mud crab allergens. Food chemistry 31 33279350
2007 Nonomuraea maheshkhaliensis sp. nov., a novel actinomycete isolated from mangrove rhizosphere mud. The Journal of general and applied microbiology 30 17726296
2019 Cloning, Expression, and Epitope Identification of Myosin Light Chain 1: An Allergen in Mud Crab. Journal of agricultural and food chemistry 27 31469568
2016 The retinoid X receptor from mud crab: new insights into its roles in ovarian development and related signaling pathway. Scientific reports 27 27009370
2014 Isoform-specific functions of Mud/NuMA mediate binucleation of Drosophila male accessory gland cells. BMC developmental biology 27 25527079
2012 Inscuteable regulates the Pins-Mud spindle orientation pathway. PloS one 27 22253744
2011 Molecular characterization of hepcidin gene from mud loach (Misgurnus mizolepis; Cypriniformes). Fish & shellfish immunology 27 21959039
2013 Characterization of the circulating hemocytes in mud crab (Scylla olivacea) revealed phenoloxidase activity. Developmental and comparative immunology 26 24316230
2013 Expression of Hsp70 in the mud crab, Scylla paramamosain in response to bacterial, osmotic, and thermal stress. Cell stress & chaperones 25 23325574
2013 Characterization of microRNAs in mud crab Scylla paramamosain under Vibrio parahaemolyticus infection. PloS one 25 24023678
2015 A review of maturation diets for mud crab genus Scylla broodstock: Present research, problems and future perspective. Saudi journal of biological sciences 23 26981008
2012 SUMO-1 of mud crab (Scylla paramamosain) in gametogenesis. Gene 23 22579467
2021 Characterization of the foxl2 gene involved in the vtg expression in mud crab (Scylla paramamosain). Gene 22 34224832
2019 A janus kinase from Scylla paramamosain activates JAK/STAT signaling pathway to restrain mud crab reovirus. Fish & shellfish immunology 21 30936049
2013 Characterization and expression of SpHsp60 in hemocytes after challenge to bacterial, osmotic and thermal stress from the mud crab Scylla paramamosain. Fish & shellfish immunology 20 23891593
2009 CNS evolution: new insight from the mud. Current biology : CB 20 19674543
2019 Molecular characterization, expression and antimicrobial activities of a c-type lysozyme from the mud crab, Scylla paramamosain. Developmental and comparative immunology 19 30986432
2019 C-Type allatostatin and its putative receptor from the mud crab serve an inhibitory role in ovarian development. The Journal of experimental biology 19 31558587
2016 A bone morphogenetic protein ligand and receptors in mud crab: A potential role in the ovarian development. Molecular and cellular endocrinology 19 27345242
2022 A truncated peptide Spgillcin177-189 derived from mud crab Scylla paramamosain exerting multiple antibacterial activities. Frontiers in cellular and infection microbiology 18 36061863
2020 Profiling prokaryotic community in pit mud of Chinese strong-aroma type liquor by using oligotrophic culturing. International journal of food microbiology 18 33202299
2019 Comparative profiling of ovarian and testicular piRNAs in the mud crab Scylla paramamosain. Genomics 18 30807818
2013 A novel peroxinectin involved in antiviral and antibacterial immunity of mud crab, Scylla paramamosain. Molecular biology reports 18 24132569
2008 A novel protein, MUDENG, induces cell death in cytotoxic T cells. Biochemical and biophysical research communications 18 18395520
2022 Metabolite-Based Mutualistic Interaction between Two Novel Clostridial Species from Pit Mud Enhances Butyrate and Caproate Production. Applied and environmental microbiology 17 35695571
2018 A clip domain serine protease regulates the expression of proPO and hemolymph clotting in mud crab, Scylla paramamosain. Fish & shellfish immunology 17 29747010
2017 Clinical and anti-aging effect of mud-bathing therapy for patients with fibromyalgia. Molecular and cellular biochemistry 17 29214470
2017 Sequential activities of Dynein, Mud and Asp in centrosome-spindle coupling maintain centrosome number upon mitosis. Journal of cell science 16 28864767
2016 Vitellogenin2: spermatozoon specificity and immunoprotection in mud crabs. Reproduction (Cambridge, England) 16 27458256
2022 Property of mud and its application in cosmetic and medical fields: a review. Environmental geochemistry and health 15 35254605
2020 Enhanced Immune Protection of Mud Crab Scylla paramamosain in Response to the Secondary Challenge by Vibrio parahaemolyticus. Frontiers in immunology 15 33193336
2019 Influence of red mud on mechanical and durability performance of self-compacting concrete. Journal of hazardous materials 15 31238214
2022 ATP catabolism and bacterial succession in postmortem tissues of mud crab (Scylla paramamosain) and their roles in freshness. Food research international (Ottawa, Ont.) 14 35400413
2022 Chemotaxis of Clostridium Strains Isolated from Pit Mud and Its Application in Baijiu Fermentation. Foods (Basel, Switzerland) 14 36429231
2021 Estuarine microbial diversity and nitrogen cycling increase along sand-mud gradients independent of salinity and distance. Environmental microbiology 14 33973326
2018 Identification and comparative analysis of the ovary and testis microRNAome of mud crab Scylla paramamosain. Molecular reproduction and development 14 29693769
2017 Serotonin induces ecdysteroidogenesis and methyl farnesoate synthesis in the mud crab, Scylla serrata. Biochemical and biophysical research communications 14 28690150
2013 Identification, characterization, and functional analysis of Tube and Pelle homologs in the mud crab Scylla paramamosain. PloS one 14 24116143
2022 Identification and functional analysis of the doublesex gene in the mud crab Scylla paramamosain. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 13 35017065
2019 Reducing Allergenicity to Arginine Kinase from Mud Crab Using Site-Directed Mutagenesis and Peptide Aptamers. Journal of agricultural and food chemistry 13 30966750
2018 Engineered biochar composite fabricated from red mud and lipid waste and synthesis of biodiesel using the composite. Journal of hazardous materials 13 30530021
2016 Characterization of MUDENG, a novel anti-apoptotic protein. Oncogenesis 13 27136675
2016 Biological properties of mud extracts derived from various spa resorts. Environmental geochemistry and health 13 27443881
2015 Characterization and expression analysis of the prophenoloxidase activating factor from the mud crab Scylla paramamosain. Genetics and molecular research : GMR 13 26345816
2025 Vitellogenin receptor mediates heat adaptability of oocyte development in mud crabs and zebrafish. Nature communications 12 40253379
2020 miR-9 and miR-263 Regulate the Key Genes of the ERK Pathway in the Ovary of Mud Crab Scylla paramamosain. Marine biotechnology (New York, N.Y.) 12 32651722
2019 Bio-mining of Lanthanides from Red Mud by Green Microalgae. Molecules (Basel, Switzerland) 12 30959876
2018 Morphological, biochemical and histological analysis of mud crab ovary and hepatopancreas at different stages of development. Animal reproduction science 12 29910008
2017 Improvement of enzyme activity and soluble expression of an alkaline protease isolated from oil-polluted mud flat metagenome by random mutagenesis. Enzyme and microbial technology 12 28859816
2013 A monoclonal antibody against human MUDENG protein. Monoclonal antibodies in immunodiagnosis and immunotherapy 12 23909422
2025 Structure and metabolic function of spatiotemporal pit mud microbiome. Environmental microbiome 11 39833926
2019 Role of neuroparsin 1 in vitellogenesis in the mud crab, Scylla paramamosain. General and comparative endocrinology 11 31430448
2018 miR-34 regulates reproduction by inhibiting the expression of MIH, CHH, EcR, and FAMeT genes in mud crab Scylla paramamosain. Molecular reproduction and development 11 30286264
2021 Large lipid transfer proteins in hepatopancreas of the mud crab Scylla paramamosain. Comparative biochemistry and physiology. Part D, Genomics & proteomics 10 33667756
2020 Characterization of gonad differentially expressed SoxB2 genes in mud crab Scylla paramamosain. Gene 10 32109560
2019 A signal transducers and activators of transcription (STAT) gene from Scylla paramamosain is involved in resistance against mud crab reovirus. Fish & shellfish immunology 10 31539571
2018 Does the bone morphogenetic protein 7 inhibit oocyte maturation by autocrine/paracrine in mud crab? General and comparative endocrinology 10 29746856
2016 Bacillus vini sp. nov. isolated from alcohol fermentation pit mud. Archives of microbiology 10 27055557
2014 Balamuthia mandrillaris therapeutic mud bath in Jamaica. Epidemiology and infection 10 25335452
2013 MUDENG is cleaved by caspase-3 during TRAIL-induced cell death. Biochemical and biophysical research communications 10 23665015
2010 Molecular cloning, expression, and characterization of cathepsin L from mud loach (Misgurnus mizolepis). Applied biochemistry and biotechnology 10 20401701
2019 Characterization and expression analysis of seven putative JHBPs in the mud crab Scylla paramamosain: Putative relationship with methyl farnesoate. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 9 31816410
2011 Induction of mud crab (Scylla paramamosain) tropomyosin and arginine kinase specific hypersensitivity in BALB/c mice. Journal of the science of food and agriculture 9 21780134
2022 Characterization of phosphofructokinase (PFK) from mud crab Scylla paramamosain and its role in mud crab dicistrovirus-1 proliferation. Fish & shellfish immunology 8 35367375
2022 Chestnut Wood Mud as a Source of Ellagic Acid for Dermo-Cosmetic Applications. Antioxidants (Basel, Switzerland) 8 36139755
2022 The mud-dwelling clam Meretrix petechialis secretes endogenously synthesized erythromycin. Proceedings of the National Academy of Sciences of the United States of America 8 36442100
2021 Immunomodulatory role of short neuropeptide F in the mud crab Scylla paramamosain. Developmental and comparative immunology 8 34536467
2021 A Dicer2 from Scylla paramamosain activates JAK/STAT signaling pathway to restrain mud crab reovirus. Developmental and comparative immunology 8 34626689
2020 B-type allatostatin modulates immune response in hepatopancreas of the mud crab Scylla paramamosain. Developmental and comparative immunology 8 32376281
2020 An effector caspase Sp-caspase first identified in mud crab Scylla paramamosain exhibiting immune response and cell apoptosis. Fish & shellfish immunology 8 32446967
2020 The MUDENG Augmentation: A Genesis in Anti-Cancer Therapy? International journal of molecular sciences 8 32759789
2020 Bacillus alkalicellulosilyticus sp. nov., isolated from extremely alkaline bauxite residue (red mud) site. Archives of microbiology 8 33047173
2024 Diversity, Methane Oxidation Activity, and Metabolic Potential of Microbial Communities in Terrestrial Mud Volcanos of the Taman Peninsula. Microorganisms 7 39065117
2023 Genome assembly of the Korean intertidal mud-creeper Batillaria attramentaria. Scientific data 7 37507420
2022 Chemical and microbial characterization of sugarcane mill mud for soil applications. PloS one 7 35972931
2021 B-type allatostatin regulates immune response of hemocytes in mud crab Scylla paramamosain. Developmental and comparative immunology 7 33631272
2020 DNA Methylation Inhibits the Expression of CFSH in Mud Crab. Frontiers in endocrinology 7 32328029
2019 BAX is an essential key mediator of AP5M1-induced apoptosis in cervical carcinoma cells. Biochemical and biophysical research communications 7 31427081

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