Affinage

Showing ACP5 — TRAP is a alias.

ACP5

Tartrate-resistant acid phosphatase type 5 · UniProt P13686

Length
325 aa
Mass
36.6 kDa
Annotated
2026-06-09
69 papers in source corpus 23 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACP5 (tartrate-resistant acid phosphatase, TRACP/TRAP) is a binuclear metallophosphatase secreted by osteoclasts and macrophages that processes phosphorylated substrates in bone resorption, lysosomal protein maturation, and immune signaling (PMID:14584906, PMID:22158965, PMID:16939395). It is synthesized as a latent proenzyme whose activity is repressed by an exposed loop domain; proteolytic removal of this loop—by cathepsin K in osteoclasts and cathepsin L in macrophages—converts the monomeric 5a isoform into the highly active 5b isoform, which differs in pH optimum, glycosylation, and antigenicity (PMID:14584906, PMID:17511262). Once active, ACP5 dephosphorylates the non-collagenous bone matrix proteins osteopontin and bone sialoprotein, with osteopontin dephosphorylation impairing osteoclast adhesion and migration, and Acp5-deficient mice accumulate osteopontin around the resorption lacuna (PMID:14584906, PMID:11731469). Acting together with the lysosomal acid phosphatase ACP2, ACP5 also removes mannose-6-phosphate from lysosomal proteins, and loss of both enzymes causes accumulation of Man6P-bearing proteins and lysosomal cholesterol (PMID:22158965). In resorbing osteoclasts ACP5 localizes to transcytotic vesicles where it generates reactive oxygen species that further degrade matrix, and in macrophages it co-localizes with engulfed bacteria, contributing to pathogen clearance and to dendritic cell maturation and Th1 polarization (PMID:14584905, PMID:16939395). Loss-of-function ACP5 missense mutations cause spondyloenchondrodysplasia (SPENCD) through protein misfolding that abolishes proteolytic processing into the active 5b form rather than blocking biosynthesis (PMID:32214327). Acp5 transcription is controlled at the promoter by PU.1 and MiTF acting synergistically, repressed by PARP-1 (relieved by RANKL), and activated by IL-6/STAT3, NFATC1 downstream of RANK/Ca2+/calcineurin, RUNX1, and DOT1L-deposited H3K79 methylation (PMID:18021007, PMID:14584903, PMID:33795653, PMID:35690777, PMID:41187901, PMID:41196341). In multiple disease contexts ACP5 acts intracellularly through β-catenin dephosphorylation—stabilizing β-catenin to drive macrophage and preadipocyte proliferation and IGF-1/Akt signaling—and through interactions with β-catenin/SMAD3, p53, CD44, TGFβ2, and VDAC3 to promote tumor invasion, macrophage polarization, and ferroptosis (PMID:32181328, PMID:34418080, PMID:39993028, PMID:41196341, PMID:41692316). A 5b-selective small-molecule inhibitor (5-phenylnicotinic acid) blocks ACP5-dependent cancer cell migration, establishing the enzyme as a druggable target (PMID:26428664).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2001 High

    Established that ACP5 has a physiological substrate in bone by showing it processes osteopontin in vivo, defining its role in non-collagenous matrix protein dephosphorylation.

    Evidence Acp5 and LAP/Acp5 double-knockout mice with immunohistochemistry and bone-extract dephosphorylation assays

    PMID:11731469

    Open questions at the time
    • Did not resolve whether OPN dephosphorylation is required for normal resorption rate
    • Other matrix substrates not surveyed
  2. 2003 High

    Resolved how the latent enzyme becomes active, showing proteolytic loop-domain cleavage by cathepsin K/L relieves active-site repression and generates the active form.

    Evidence In vitro protease cleavage assays and active-site mutagenesis/structural analysis of the loop-Asn91 interaction

    PMID:14584906

    Open questions at the time
    • Physiological activator assignment (cathepsin K vs L) inferred from expression, not direct in vivo proof
    • Kinetics of in vivo processing not quantified
  3. 2003 High

    Demonstrated the functional consequence of phosphatase activity by showing OPN dephosphorylation impairs osteoclast adhesion and migration, linking enzyme chemistry to resorption behavior.

    Evidence In vitro phosphatase assay with OPN, adhesion/migration assays, and lacuna co-localization

    PMID:14584906

    Open questions at the time
    • Causal contribution to net bone resorption in vivo not isolated
  4. 2003 Medium

    Placed ACP5 in transcytotic vesicles and assigned a non-phosphatase ROS-generating activity contributing to matrix degradation and antibacterial defense, broadening its function beyond dephosphorylation.

    Evidence Immunolocalization, ROS assays, and S. aureus clearance in TRACP-deficient mice

    PMID:14584905

    Open questions at the time
    • Molecular mechanism of ROS generation by the iron center not detailed
    • Quantitative contribution of ROS vs phosphatase activity unresolved
  5. 2003 Medium

    Defined transcriptional control of Acp5 during osteoclastogenesis by identifying synergistic PU.1 and MiTF promoter binding sites.

    Evidence Promoter-reporter and overexpression assays in macrophage/osteoclast cell lines

    PMID:14584903

    Open questions at the time
    • Endogenous occupancy not shown by ChIP
    • Interplay with other osteoclast factors not addressed
  6. 2005 Medium

    Showed that osteoblast TRACP activity arises largely from endocytosis of monocyte-secreted enzyme, distinguishing transferred from endogenous latent (cathepsin B-activatable) enzyme.

    Evidence Conditioned-medium depletion, activity assays, cathepsin B activation, and fluoride sensitivity in osteoblast-like cells

    PMID:15878315

    Open questions at the time
    • Receptor mediating osteoblast uptake not identified
    • Functional role of transferred enzyme in osteoblasts unclear
  7. 2006 High

    Extended ACP5 function to adaptive immunity by showing it is required for dendritic cell maturation and Th1 polarization, not for antigen-independent lymphocyte responses.

    Evidence TRACP-/- mice with flow cytometry, DTH, T-cell cytokine and antibody isotype assays

    PMID:16939395

    Open questions at the time
    • Molecular substrate in DCs not identified
    • Mechanistic link between phosphatase activity and maturation not defined
  8. 2007 Medium

    Confirmed isoform conversion biology by showing the secreted 5b form derives from cathepsin K-mediated loop removal from 5a, accounting for their distinct biochemical properties.

    Evidence Gene expression profiling across monocytes/macrophages/osteoclasts and Western blot with loop-specific antiserum

    PMID:17511262

    Open questions at the time
    • Direct in vivo demonstration of cathepsin K cleavage in osteoclasts not provided
  9. 2008 High

    Identified PARP-1 as a sequence-specific transcriptional repressor of Acp5 that is relieved by RANKL, adding negative regulatory control over osteoclast expression.

    Evidence siRNA/inhibitor, EMSA/supershift, and mutant promoter-reporter assays in RAW264.7 cells

    PMID:18021007

    Open questions at the time
    • In vivo relevance of PARP-1 repression not tested
    • Mechanism of RANKL-mediated derepression not detailed
  10. 2008 Medium

    Linked ACP5 trafficking to PLEKHM1-dependent endosomal acidification and exocytosis, and implicated secreted TRACP in osteoclast-osteoblast cross-talk.

    Evidence Patient osteoclast analysis, PLEKHM1 variant co-transfection, endosomal pH measurement, and osteoblast ALP assays with conditioned medium

    PMID:17997709

    Open questions at the time
    • Direct PLEKHM1-ACP5 interaction not shown
    • Mediator of ALP induction in osteoblasts unidentified
  11. 2011 High

    Defined a lysosomal function by showing ACP5 cooperates with ACP2 to remove Man6P from lysosomal proteins, with loss causing Man6P and cholesterol accumulation.

    Evidence Acp2/Acp5 double-knockout mice, 2D Man6P immunoblot, affinity chromatography/MS, and hepatocyte cholesterol assays

    PMID:22158965

    Open questions at the time
    • Full repertoire of Man6P substrates not enumerated
    • Mechanistic link from Man6P removal to cholesterol handling unresolved
  12. 2015 Medium

    Demonstrated druggability and isoform selectivity by identifying a 5b-specific small-molecule inhibitor that blocks ACP5-dependent cancer cell migration.

    Evidence Enzyme kinetics (Kic), structure-based docking, and migration/invasion assays in TRAP-overexpressing MDA-MB-231 cells

    PMID:26428664

    Open questions at the time
    • In vivo efficacy and selectivity not tested
    • Structural basis of 5a vs 5b discrimination not solved
  13. 2017 Medium

    Opened the oncogenic ACP5 axis by showing overexpression drives breast cancer migration/invasion via TGFβ2/TβR signaling and CD44 phosphorylation.

    Evidence Gain/loss-of-function in MDA-MB-231 cells with phosphoproteomics and antibody/chemical pathway blocking

    PMID:28915803

    Open questions at the time
    • Direct enzymatic substrate among CD44/TGFβ components not defined
    • In vivo metastasis not assessed
  14. 2020 High

    Established that SPENCD-causing mutations act through misfolding that prevents processing into the active 5b form, clarifying the molecular basis of disease.

    Evidence Transfection of 8 mutant constructs in HEK-293 with Endo-H, isoform-specific Western blot, and in vitro cleavage assays

    PMID:32214327

    Open questions at the time
    • Connection between enzyme loss and interferon-stimulated gene upregulation not mechanistically resolved here
  15. 2020 Medium

    Placed ACP5 upstream of p53 regulation in lung cancer, showing it promotes p53 Ser392 phosphorylation, degradation, and SMAD3-driven EMT.

    Evidence Overexpression/knockdown in A549 and NCI-H1975 cells, xenografts, and p53 phosphorylation/ubiquitination assays

    PMID:32181328

    Open questions at the time
    • Whether ACP5 acts directly or indirectly on p53 phosphorylation unclear
  16. 2021 Medium

    Positioned ACP5 as an effector of RANK signaling in colorectal cancer downstream of a Ca2+/calcineurin/NFATC1 transcriptional cascade driving migration and invasion.

    Evidence RANK/ACP5 perturbation with calcineurin/NFATC1/PLCγ-IP3R/STIM1 blockade and metastasis assays

    PMID:33795653

    Open questions at the time
    • Direct NFATC1 binding to the Acp5 promoter not shown here
    • Downstream effector of ACP5 in CRC not defined
  17. 2021 Medium

    Defined a proliferative signaling role for the 5a isoform via IGF-1/IRS-1/Akt activation and β-catenin nuclear translocation in preadipocytes.

    Evidence Exogenous TRAP 5a treatment of 3T3-L1 cells with cell-cycle, IGF-1 mRNA, phospho-IRS-1/Akt, and β-catenin assays

    PMID:34418080

    Open questions at the time
    • Receptor/mechanism for extracellular 5a sensing not identified
    • Phosphatase dependence of the effect not isolated
  18. 2022 High

    Demonstrated a CNS role by showing IL-6/STAT3-driven Acp5 induction in prelimbic pyramidal neurons mediates neuropathic pain/depression comorbidity through altered excitability.

    Evidence Cell-type-specific knockdown/overexpression, electrophysiology, behavior, ChIP for STAT3-Acp5 promoter binding, and STAT3-p300 Co-IP

    PMID:35690777

    Open questions at the time
    • Neuronal substrate/effector of ACP5 not identified
    • Mechanism connecting ACP5 to excitability changes unresolved
  19. 2022 Medium

    Placed ACP5 downstream of microglia-derived CCL18/CCR8 signaling as a mediator of glioma growth and invasion.

    Evidence Humanized brain-slice model with iPSC-derived microglia and in vivo glioma models, CCR8 identification, and ACP5 downstream analysis

    PMID:35417708

    Open questions at the time
    • Molecular mechanism by which ACP5 promotes invasion in glioma not defined
    • Direct CCR8-to-ACP5 signaling steps unmapped
  20. 2025 Medium

    Converged multiple disease contexts on a β-catenin dephosphorylation mechanism, showing ACP5 stabilizes β-catenin to drive alveolar macrophage proliferation under cigarette smoke.

    Evidence TRAP-deficient and inhibitor-treated MPI macrophages, phospho-β-catenin immunoblot, proliferation assays, and smoke-exposure mouse model

    PMID:39993028

    Open questions at the time
    • Direct enzymatic action of ACP5 on β-catenin not biochemically proven
    • Kinase/phosphatase competition not resolved
  21. 2025 Medium

    Identified DOT1L/H3K79me1 as an epigenetic activator of Acp5 driving β-catenin and NLRP3-dependent inflammation in diabetic vascular injury.

    Evidence DOT1L overexpression/knockdown in VSMCs, ChIP-Seq for H3K79me1 at the Acp5 promoter, and balloon-injury diabetic rat model

    PMID:41187901

    Open questions at the time
    • Direct vs indirect ACP5 action on β-catenin/NLRP3 not separated
  22. 2025 Medium

    Showed RUNX1-induced ACP5 physically interacts with β-catenin to promote SMAD3 phosphorylation and M2 macrophage polarization supporting NSCLC, establishing an ACP5-β-catenin/SMAD3 axis.

    Evidence RUNX1/ACP5 perturbation in BMDMs with Co-IP, polarization flow cytometry, rescue experiments, and an LLC mouse tumor model

    PMID:41196341

    Open questions at the time
    • Whether the ACP5-β-catenin interaction is enzymatic not established
    • Stoichiometry/site of interaction unmapped
  23. 2026 Medium

    Identified VDAC3 as an ACP5 interactor mediating M1 polarization and macrophage ferroptosis in atherosclerosis, with macrophage-specific knockout reducing plaque burden.

    Evidence LC-MS/MS interactome, ACP5-VDAC3 Co-IP, macrophage-specific Cre/loxP knockout in Apoe-/- mice, and ferroptosis marker assays

    PMID:41692316

    Open questions at the time
    • Whether ACP5 dephosphorylates VDAC3 directly not proven
    • Link from VDAC3 to ferroptosis machinery not mechanistically detailed

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how ACP5's dephosphorylation chemistry mechanistically produces its diverse intracellular signaling outputs (β-catenin, p53, CD44, VDAC3) and whether these involve direct substrate dephosphorylation or indirect effects.
  • No in vitro dephosphorylation of β-catenin, p53, CD44, or VDAC3 demonstrated
  • Mechanism of extracellular/cytosolic ACP5 sensing by target cells unknown
  • Structural basis of substrate selectivity uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 6 GO:0140096 catalytic activity, acting on a protein 3 GO:0016491 oxidoreductase activity 1
Localization
GO:0005576 extracellular region 2 GO:0005764 lysosome 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-1474244 Extracellular matrix organization 2
Partners
ACP2CD44CTNNB1PLEKHM1SMAD3VDAC3

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 TRACP/ACP5 is synthesized as a latent proenzyme; proteolytic cleavage of an exposed loop domain (removing the interaction between loop residue Asp146 and active-site ligand Asn91) activates the enzyme. Cathepsin K and L efficiently cleave the loop domain and activate the latent enzyme; cathepsin K is proposed as the physiological activator in osteoclasts and cathepsin L in macrophages. In vitro protease cleavage assays, active-site mutagenesis/structural analysis of loop-domain interaction Journal of bone and mineral research High 14584906
2003 TRACP/ACP5 dephosphorylates osteopontin (OPN) and bone sialoprotein in the osteoclast resorption lacuna; dephosphorylation of OPN by TRACP impairs OPN-mediated osteoclast adhesion and migration in vitro, supporting a role for TRACP as an osteopontin phosphatase in bone resorption. In vitro phosphatase assay with OPN substrate; cell adhesion and migration assays with dephosphorylated OPN; co-localization of TRACP and OPN in resorption lacunae Journal of bone and mineral research High 14584906
2001 Acp5-deficient mouse osteoclasts accumulate osteopontin adjacent to the resorption lacuna; biochemical analysis of bone extracts from LAP/Acp5 doubly deficient mice shows strongly reduced dephosphorylation of osteopontin, demonstrating that ACP5 is important for processing/dephosphorylation of this non-collagenous bone matrix protein in vivo. Knockout mouse model (Acp5-/- and LAP/Acp5 double-knockout), immunohistochemistry, in vitro dephosphorylation assay with bone extracts Development High 11731469
2011 ACP5 acts in concert with the lysosomal acid phosphatase ACP2 to dephosphorylate mannose 6-phosphate (Man6P) residues on lysosomal proteins after their delivery to lysosomes; loss of both phosphatases causes accumulation of Man6P on lysosomal proteins and unesterified cholesterol in lysosomes of hepatocytes, with the cholesterol-binding protein NPC2 showing altered isoelectric point depending on phosphorylation state. Acp2/Acp5 double-knockout mice, 2D Man6P immunoblot, Man6P affinity chromatography, mass spectrometry, cholesterol accumulation assay in cultured hepatocytes Molecular and cellular biology High 22158965
2003 In resorbing osteoclasts, TRACP/ACP5 localizes to transcytotic vesicles transporting bone matrix degradation products from the resorption lacuna to the basolateral secretory domain. TRACP generates reactive oxygen species (ROS) capable of further destroying organic bone matrix components in these vesicles. In alveolar macrophages, TRACP co-localizes with endocytosed Staphylococcus aureus, and clearance of S. aureus is reduced in TRACP-deficient mice. Subcellular localization by immunolocalization in osteoclasts; ROS generation assay; TRACP-deficient mouse infection model; macrophage overexpression experiments measuring intracellular ROS Journal of bone and mineral research Medium 14584905
2006 Dendritic cells (DCs) from TRACP-knockout mice show impaired LPS-induced upregulation of MHC II and CD80, increased IL-10 production, and defective Th1 responses (reduced IFN-γ, reduced OVA-specific IgG2a, impaired delayed hypersensitivity). T- and B-cell responses not involving antigen presentation were normal, demonstrating that TRACP is specifically required for DC maturation and polarization of naïve T cells toward Th1. TRACP-/- knockout mice, flow cytometry, delayed-type hypersensitivity assay, T-cell proliferation and cytokine assays, antibody isotype measurement Journal of bone and mineral research High 16939395
2008 PARP-1 binds to a specific sequence in the Tracp gene promoter region (-830/-808) and acts as a transcriptional repressor of Tracp expression in pre-osteoclastic cells. RANKL signaling reduces this PARP-1-mediated repression, allowing Tracp upregulation during osteoclastogenesis. siRNA knockdown of PARP-1, PARP-1 inhibitor treatment, EMSA, supershift experiments, promoter-reporter assays with wild-type and mutant constructs in RAW264.7 cells Journal of bone and mineral research High 18021007
2003 The TRACP gene promoter contains functional binding sites for transcription factors PU.1 and MiTF; these factors act synergistically to drive TRACP expression during osteoclast differentiation. Promoter-reporter assays, transcription factor binding site analysis, overexpression experiments in RAW264.7 and RAW/C4 macrophage/osteoclast cell lines Journal of bone and mineral research Medium 14584903
2007 TRACP 5b (the mature osteoclast-secreted isoform) is generated by proteolytic cleavage of the flexible loop domain of TRACP 5a inside osteoclasts or in the resorption lacuna; the resulting 5b isoform lacks the flexible loop and differs from 5a in optimum pH, isoelectric point, glycosylation, and antigenicity. Cathepsin K, strongly expressed in osteoclasts, is the protease responsible. DNA chip gene expression profiling (comparing monocytes, macrophages, osteoclasts), Western blot with loop-region-specific antiserum Rinsho byori / Japanese journal of clinical pathology Medium 17511262
2008 The PLEKHM1 protein is required for endosomal vesicle acidification and TRACP exocytosis in osteoclasts. A PLEKHM1-R714C mutation results in lower intracellular TRACP activity due to increased TRACP secretion rather than reduced expression, and reduces endosomal acidification. TRACP-containing conditioned medium from osteoclasts increases osteoblast alkaline phosphatase activity, implicating secreted TRACP in osteoclast-osteoblast cross-talk. Patient osteoclast functional analysis, co-transfection of PLEKHM1 variants with TRACP vector in HEK293 cells, endosomal pH measurement, RAW264.7 osteoclast-like cell assays, osteoblast alkaline phosphatase assay with conditioned medium Journal of bone and mineral research Medium 17997709
2005 Osteoblast-like cells endocytose TRACP released by monocytes, and this endocytosed TRACP accounts for the bulk of TRACP activity observed in osteoblasts at bone resorption sites. Osteoblast-like cells also express endogenous TRACP mRNA as a latent proform that can be activated by cathepsin B; this endogenous fraction is inhibited by fluoride, distinguishing it from the endocytosed fraction. TRACP depletion from conditioned monocyte medium, TRACP activity assays in osteoblast-like cells, cathepsin B activation assay, cysteine protease inhibitors, RT-PCR for TRACP mRNA Bone Medium 15878315
2017 TRAP/ACP5 overexpression in MDA-MB-231 breast cancer cells promotes cell migration and invasion via TGFβ2/TGFβ receptor signaling and through increased intracellular phosphorylation of CD44; pharmacological or shRNA-mediated inhibition of TRAP reverses these effects. Stable overexpression and shRNA knockdown in MDA-MB-231 cells, migration/invasion assays, global phosphoproteomics and proteomics, antibody-mediated blocking and chemical inhibition of TGFβ2/TβR and CD44 BMC cancer Medium 28915803
2020 ACP5 promotes lung adenocarcinoma cell proliferation, migration, invasion, and EMT by regulating p53 phosphorylation at Ser392, thereby enhancing p53 ubiquitination and degradation; reduced p53 levels increase SMAD3 transcription, which drives EMT. ACP5 overexpression and knockdown in A549 and NCI-H1975 cells, mouse xenograft model, mechanistic studies of p53 phosphorylation/ubiquitination, SMAD3 transcription assays Molecular therapy oncolytics Medium 32181328
2021 RANK signaling in colorectal cancer cells activates PLCγ-mediated IP3R axis and STIM1 to evoke intracellular Ca2+ oscillations, which activate calcineurin to dephosphorylate NFATC1 and induce its nuclear translocation; nuclear NFATC1 then transcriptionally upregulates ACP5, and ACP5 mediates RANK-induced CRC cell migration and invasion. RANK overexpression/knockdown in CRC cells, ACP5 siRNA and overexpression, calcineurin/NFATC1 pathway inhibition, PLCγ-IP3R and STIM1 blockade, in vitro and in vivo metastasis assays Cell death & disease Medium 33795653
2021 TRAP 5a (the monomeric isoform of ACP5) stimulates entry of 3T3-L1 preadipocytes into S-phase in a dose-dependent manner by increasing IGF-1 mRNA, activating IRS-1 and IGF-1 receptor signaling, activating the Akt pathway, and promoting nuclear translocation of β-catenin. TRAP 5a isoform treatment of 3T3-L1 cells, cell cycle analysis (S-phase entry), IGF-1 mRNA quantification, IRS-1 and Akt phosphorylation assays, β-catenin nuclear translocation assay FEBS letters Medium 34418080
2022 In the prelimbic cortex (PrL), ACP5 expression is upregulated in pyramidal neurons following spared nerve injury-induced neuropathic pain/depression comorbidity via the IL-6/STAT3 pathway: IL-6 activates STAT3 phosphorylation, which together with p300-mediated H3 acetylation increases STAT3 binding to the Acp5 promoter and drives Acp5 transcription. Genetic knockdown of Acp5 specifically in PrL pyramidal neurons attenuates decreased neuronal excitability and comorbid behaviors; overexpression in naïve rats recapitulates the phenotype. rs-fMRI, genetic knockdown and overexpression in specific neuron subtypes (pyramidal vs. PV vs. SST neurons), immunohistochemistry, electrophysiology (spike number), ChIP (STAT3 binding to Acp5 promoter), Co-IP (STAT3-p300 interaction), IL-6/STAT3 pathway inhibition Journal of neuroinflammation High 35690777
2022 In glioblastoma cells, CCL18 released by microglia/macrophages signals through its receptor CCR8 to activate ACP5 as a downstream mediator, promoting glioma cell growth and invasion. Humanized brain slice model (iPSC-derived human microglia + human glioma cells in microglia-depleted mouse slices), in vitro, ex vivo, and in vivo glioma models; CCR8 identification as functional CCL18 receptor; ACP5 downstream signaling analysis Cell reports Medium 35417708
2020 All eight reported SPENCD-associated missense mutations in ACP5 drastically reduce enzymatic activity without preventing protein translation; mutant TRACP proteins are not proteolytically processed into the active 5b isoform intracellularly, and most are not secreted into culture medium. Mutation-induced misfolding (rather than failure of biosynthesis) is responsible for loss of phosphatase activity. Transfection of ACP5 mutant constructs into HEK-293 cells, cytochemical and immunocytochemical staining, Western blot with isoform-specific antibodies, Endo-H sensitivity assay, in vitro proteolytic cleavage assay PloS one High 32214327
2025 TRAP/ACP5 stimulates alveolar macrophage proliferation via dephosphorylation of β-catenin: TRAP inhibition or TRAP deficiency increases phosphorylated β-catenin (marking it for ubiquitination and proteasomal degradation), thereby reducing macrophage proliferation. Cigarette smoke increases Acp5-202 transcript expression in lung macrophages, driving TRAP-dependent proliferation. TRAP-deficient MPI macrophages (fetal liver progenitor-derived alveolar-like), TRAP pharmacological inhibitor, cigarette smoke extract treatment, phospho-β-catenin immunoblot, proliferation assay; mouse smoke exposure model with Acp5 transcript quantification American journal of physiology. Lung cellular and molecular physiology Medium 39993028
2025 DOT1L promotes ACP5 expression by depositing H3K79me1 at the Acp5 gene promoter in insulin-stimulated vascular smooth muscle cells (VSMCs); increased ACP5 then inhibits β-catenin phosphorylation and upregulates NLRP3, promoting inflammatory responses after diabetic vascular injury. Lentiviral DOT1L overexpression/knockdown in VSMCs and carotid artery balloon injury model in diabetic rats, ChIP-Seq (H3K79me1 enrichment at Acp5 promoter), Western blot for ACP5/β-catenin/NLRP3, ELISA for cytokines Microvascular research Medium 41187901
2025 RUNX1 promotes M2 polarization of bone-marrow-derived macrophages by upregulating ACP5, which interacts with β-catenin (detected by Co-IP) to promote SMAD3 phosphorylation; silencing ACP5 in RUNX1-overexpressing macrophages blocks M2 polarization and NSCLC cell malignant behavior, and ACP5 overexpression rescues RUNX1-silencing effects. RUNX1 shRNA, ACP5 overexpression/knockdown in BMDMs, Co-immunoprecipitation (ACP5-β-catenin interaction), flow cytometry (macrophage polarization markers), ELISA (cytokines), CCK-8/Transwell assays, in vivo LLC mouse tumor model Inflammation research Medium 41196341
2026 In atherosclerosis, ACP5 interacts with VDAC3 (identified by LC-MS/MS and Co-IP); ACP5 overexpression decreases VDAC3 phosphorylation, promotes M1 macrophage polarization, and promotes macrophage ferroptosis (decreased GSH, increased MDA, Fe2+, lipid peroxides). Macrophage-specific ACP5 knockout in Apoe-/- mice reduces plaque area, M1 macrophage proportion, and 4-HNE expression, while increasing GPX4. LC-MS/MS interactome, Co-immunoprecipitation (ACP5-VDAC3), macrophage-specific Cre/loxP ACP5 knockout in Apoe-/- mice, ACP5 overexpression/knockdown in RAW264.7 and BMDMs, ferroptosis markers (GSH, MDA, Fe2+, GPX4), flow cytometry for macrophage polarization Free radical biology & medicine Medium 41692316
2025 ACP5 knockout in bronchial epithelial cells (BEAS-2B) exposed to diesel exhaust particles results in increased apoptosis and intracellular ROS, and activates the AHR-CYP1A1 inflammatory signaling axis; AHR inhibition prevents inflammation-induced damage, placing ACP5 as a negative regulator of this pathway. CRISPR/Cas9 ACP5 knockout in BEAS-2B cells, DEP exposure, apoptosis and ROS assays, gene expression profiling, AHR inhibitor treatment, in vivo mouse model with conditioned medium from KO cells Scientific reports Medium 40087344
2015 The small molecule 5-phenylnicotinic acid (CD13) inhibits TRAP/ACP5 5b isoform (but not the 5a isoform) with Kic values in the low micromolar range; it inhibits intracellular TRAP activity in TRAP-overexpressing MDA-MB-231 cells and blocks TRAP-dependent cell migration and invasion, demonstrating isoform-selective enzymatic inhibition with functional consequence. Enzyme inhibition kinetics (Kic measurement), structure-based docking, cell-based intracellular TRAP activity assay, migration and invasion assays in TRAP-overexpressing MDA-MB-231 cells Experimental cell research Medium 26428664

Source papers

Stage 0 corpus · 69 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Tartrate-resistant acid phosphatase 5b (TRACP 5b) as a marker of bone resorption. Clinical laboratory 205 17078477
2019 NIH Initiative to Improve Understanding of the Pancreas, Islet, and Autoimmunity in Type 1 Diabetes: The Human Pancreas Analysis Program (HPAP). Diabetes 156 31127054
2001 Overlapping functions of lysosomal acid phosphatase (LAP) and tartrate-resistant acid phosphatase (Acp5) revealed by doubly deficient mice. Development (Cambridge, England) 88 11731469
2016 Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey. Journal of clinical immunology 75 26951490
2008 A new heterozygous mutation (R714C) of the osteopetrosis gene, pleckstrin homolog domain containing family M (with run domain) member 1 (PLEKHM1), impairs vesicular acidification and increases TRACP secretion in osteoclasts. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 61 17997709
2003 TRACP as an osteopontin phosphatase. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 60 14584906
2003 Potential function for the ROS-generating activity of TRACP. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 56 14584905
2011 Mannose 6 dephosphorylation of lysosomal proteins mediated by acid phosphatases Acp2 and Acp5. Molecular and cellular biology 44 22158965
2008 Significance of serum TRACP in rheumatoid arthritis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 38 18410226
2022 Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats. Journal of neuroinflammation 34 35690777
2022 High-grade glioma with pleomorphic and pseudopapillary features (HPAP): a proposed type of circumscribed glioma in adults harboring frequent TP53 mutations and recurrent monosomy 13. Acta neuropathologica 31 35103816
2022 Microglia/macrophage-derived human CCL18 promotes glioma progression via CCR8-ACP5 axis analyzed in humanized slice model. Cell reports 31 35417708
2017 Tartrate-resistant acid phosphatase (TRAP/ACP5) promotes metastasis-related properties via TGFβ2/TβR and CD44 in MDA-MB-231 breast cancer cells. BMC cancer 30 28915803
2015 Severe immune dysregulation with neurological impairment and minor bone changes in a child with spondyloenchondrodysplasia due to two novel mutations in the ACP5 gene. Pediatric rheumatology online journal 28 26346816
2021 RANK promotes colorectal cancer migration and invasion by activating the Ca2+-calcineurin/NFATC1-ACP5 axis. Cell death & disease 26 33795653
2020 Tartrate-Resistant Acid Phosphatase 5/ACP5 Interacts with p53 to Control the Expression of SMAD3 in Lung Adenocarcinoma. Molecular therapy oncolytics 26 32181328
2005 Endogenous expression and endocytosis of tartrate-resistant acid phosphatase (TRACP) by osteoblast-like cells. Bone 23 15878315
2018 ACP5: Its Structure, Distribution, Regulation and Novel Functions. Anti-cancer agents in medicinal chemistry 20 29637867
2014 HpaP modulates type III effector secretion in Ralstonia solanacearum and harbours a substrate specificity switch domain essential for virulence. Molecular plant pathology 20 24405562
2006 TRACP Influences Th1 pathways by affecting dendritic cell function. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20 16939395
2022 Changes in RANKL and TRAcP 5b after discontinuation of denosumab suggest RANKL mediated formation of osteoclasts results in the increased bone resorption. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 19 36543965
2008 Poly(adp-ribose) polymerase-1 regulates Tracp gene promoter activity during RANKL-induced osteoclastogenesis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 18 18021007
2005 Transcriptional profiling on chromosome 19p indicated frequent downregulation of ACP5 expression in hepatocellular carcinoma. International journal of cancer 17 15645427
1993 Assignment of the mouse tartrate-resistant acid phosphatase gene (Acp5) to chromosome 9. Genomics 17 8449511
2021 Androgen receptor (AR) decreases HCC cells migration and invasion via miR-325/ACP5 signaling. Journal of Cancer 16 33753989
2015 The small chemical enzyme inhibitor 5-phenylnicotinic acid/CD13 inhibits cell migration and invasion of tartrate-resistant acid phosphatase/ACP5-overexpressing MDA-MB-231 breast cancer cells. Experimental cell research 16 26428664
2012 ACP5 (Uteroferrin): phylogeny of an ancient and conserved gene expressed in the endometrium of mammals. Biology of reproduction 16 22278982
2018 HpaP, a novel regulatory protein with ATPase and phosphatase activity, contributes to full virulence in Xanthomonas campestris pv. campestris. Environmental microbiology 15 29345052
2010 Potential role of tartrate-resistant acid phosphatase 5b (TRACP 5b) as a surrogate marker of late loosening in patients with total hip arthroplasty: a cohort study. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 15 20063383
2019 A dried blood spot-based method to measure levels of tartrate-resistant acid phosphatase 5b (TRACP-5b), a marker of bone resorption. American journal of human biology : the official journal of the Human Biology Council 14 30897260
2003 Regulation of the murine TRACP gene promoter. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 14 14584903
2023 Spondyloenchondrodysplasia in five new patients: identification of three novel ACP5 variants with variable neurological presentations. Molecular genetics and genomics : MGG 11 37010587
2020 Characterisation of ACP5 missense mutations encoding tartrate-resistant acid phosphatase associated with spondyloenchondrodysplasia. PloS one 11 32214327
2012 A change of osteocalcin (OC) and tartrate resistant acid phosphatase 5b (TRACP-5b) with the menstrual cycle. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 10 22517558
2018 Identification of inhibitors of Tartrate-resistant acid phosphatase (TRAP/ACP5) activity by small-molecule screening. Chemical biology & drug design 9 29500863
2007 Sequence and TLR9 independent increase of TRACP expression by antisense DNA and siRNA molecules. Biochemical and biophysical research communications 8 17570345
2022 HpaP divergently regulates the expression of hrp genes in Xanthomonas oryzae pathovars oryzae and oryzicola. Molecular plant pathology 7 36260328
2021 Tartrate-resistant acid phosphatase type 5/ACP5 promotes cell cycle entry of 3T3-L1 preadipocytes by increasing IGF-1/Akt signaling. FEBS letters 7 34418080
2024 Studies on the in vitro mechanism and in vivo therapeutic effect of the antimicrobial peptide ACP5 against Trichophyton mentagrophytes. Peptides 6 38354953
2022 Novel Mutations in ACP5 and SAMHD1 in a Patient With Pediatric Systemic Lupus Erythematosus. Frontiers in pediatrics 6 35633950
2005 Evaluation of tartrate-resistant acid phosphatase (TRACP) 5b as bone resorption marker in irradiated bone metastases. Anticancer research 6 16334155
1995 Assignment of the uteroferrin gene (ACP5) to swine chromosome 2q12-->q21 by fluorescence in situ hybridization. Cytogenetics and cell genetics 6 7587387
2016 Severe Short Stature in Two Siblings as the Presenting Sign of ACP5 Deficiency. Hormone research in paediatrics 5 26789720
2012 Altered serum levels of the osteoclast-specific TRACP 5b isoform in Chinese children undergoing orthodontic treatment. European journal of orthodontics 5 22467569
2008 Alendronate decreases TRACP 5b activity in osteoarthritic bone. European journal of medical research 5 18226993
2023 Association of ACP5 with the tumor immune microenvironment and its role in cell proliferation and metastasis in pancreatic cancer. American journal of translational research 4 38074824
2022 Molecular characterization and functional analysis of tartrate-resistant acid phosphatase (ACP5) gene in red drum (Sciaenops ocellatus). Fish & shellfish immunology 4 36566835
2020 Kockdown of ACP5 inhibits hepatocellular carcinoma progression. American journal of translational research 4 32509186
2025 The regulatory role of ACP5 in the diesel exhaust particle-induced AHR inflammatory signaling pathway in a human bronchial epithelial cell line. Scientific reports 3 40087344
2025 Expanding clinicopathologic knowledge in high-grade glioma with pleomorphic and pseudopapillary features (HPAP): a report of two cases. Acta neuropathologica communications 3 40355925
2023 Spondyloenchondrodysplasia with immune dysregulation related to ACP5. A report of 4 cases. Archivos argentinos de pediatria 3 37382551
2020 Altered levels of BMD, PRL, BAP and TRACP-5b in male chronic patients with schizophrenia. Scientific reports 3 32788631
2025 TRAPping the effects of tobacco smoking: the regulation and function of Acp5 expression in lung macrophages. American journal of physiology. Lung cellular and molecular physiology 2 39993028
2025 Quercetagetin alleviates ischemic stroke injury by preserving macrophage/microglia homeostasis via inhibiting ACP5. Phytomedicine : international journal of phytotherapy and phytopharmacology 2 40972264
2025 RUNX1 promotes NSCLC progression by ACP5/SMAD3-mediated M2 macrophage polarization. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 2 41196341
2022 Effects of Glimepiride Combined with Recombinant Human Insulin Injection on Serum IGF-1, VEGF and TRACP-5b Oxidative Stress Levels in Patients with Type 2 Diabetes Mellitus. Evidence-based complementary and alternative medicine : eCAM 2 35571731
2010 [Relationship between coronary and abdominal calcification score, serum osteoprotegerin (OPG), and serum tartrate-resistant acid phosphatase (TRACP) -5b in pre-dialysis CKD patients]. Nihon Jinzo Gakkai shi 2 21254698
2008 [Tartrate resistant acid phosphatase--TRACP-5b as a modern bone resorption marker]. Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego 2 18634372
2007 [The mechanism of TRACP 5b maturation]. Rinsho byori. The Japanese journal of clinical pathology 2 17511262
2025 DOT1L-mediated H3K79me1 transcriptional activation of Acp5 aggravates inflammatory responses following diabetic vascular injury. Microvascular research 1 41187901
2021 Autoimmune Hemolytic Anemia Due to Spondyloenchondrodysplasia with Spastic Paraparesis and Intracranial Calcification due to Mutation in ACP5. Journal of pediatric genetics 1 38567175
2016 [Correlation of cytogenetic changes with VEGF and TRacp-5b levels among 60 elderly patients with multiple myeloma]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 27577203
2026 Tartrate-Resistant Acid Phosphatase 5 (TRAP/ACP5) aggravates atherosclerosis by regulating macrophage polarization and promoting ferroptosis. Free radical biology & medicine 0 41692316
2026 BRAF-mutant high-grade glioma with pleomorphic and pseudopapillary features (HPAP): A PLNTY mimic demonstrating tumor progression during longitudinal follow-up. Neuro-oncology advances 0 41798681
2026 Janus kinase inhibitor therapy for the treatment of spondyloenchondrodysplasia with immune dysregulation due to novel ACP5 variants: a multicenter study. Frontiers in immunology 0 41993173
2026 Expanding the Genotypic and Phenotypic Spectrum of SPENCDI: A Novel ACP5 Variant and Literature Review. Genes 0 42074507
2026 The Association Between Longitudinal Changes in TRACP-5b and Bone Metastasis Progression During Osimertinib Therapy. Anticancer research 0 42203350
2025 Identification of TRACP 5b as a local recurrence biomarker in giant cell tumor of bone. Surgical oncology 0 41273883
2006 [Bone and bone related biochemical examinations. Bone and collagen related metabolites. Tartrate-resistant acid phosphatase (TRACP)]. Clinical calcium 0 16751690

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