Affinage

PHOSPHO1

Phosphoethanolamine/phosphocholine phosphatase · UniProt Q8TCT1

Length
267 aa
Mass
29.7 kDa
Annotated
2026-06-10
35 papers in source corpus 23 papers cited in narrative 23 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

PHOSPHO1 is a Mg2+-dependent phosphatase of the HAD superfamily that initiates skeletal mineralization by hydrolyzing phosphoethanolamine and phosphocholine within matrix vesicles to generate the inorganic phosphate required for hydroxyapatite crystal nucleation (PMID:15175005, PMID:16837257, PMID:17227223). Catalysis depends on the conserved active-site aspartates Asp32 and Asp203, with Asp43 and Asp123 conferring substrate specificity that distinguishes it from phosphoserine phosphatases and from the paralog PHOSPHO2 (PMID:14983068, PMID:16054448). The protein is restricted to mineralizing tissues and packaged into matrix vesicles of growth plate chondrocytes and osteoblasts, where its expression precedes mineral deposition (PMID:15050893, PMID:16837257). Genetic ablation produces growth plate abnormalities, spontaneous fractures, bowed long bones, and osteomalacia, and PHOSPHO1 cooperates non-redundantly with the alkaline phosphatase TNAP: double ablation abolishes skeletal mineralization and causes perinatal lethality, while TNAP overexpression cannot rescue the Phospho1-/- bone defect despite normalizing pyrophosphate (PMID:20684022, PMID:26457330). The Phospho1-/- skeletal phenotype is instead mediated by accumulation of phosphorylated osteopontin, since co-deletion of Spp1 rescues the abnormalities (PMID:24825455). PHOSPHO1-dependent matrix-vesicle mineralization also drives cementum, alveolar bone, enamel, and pathological vascular smooth muscle cell calcification (PMID:22887744, PMID:27016531, PMID:29089903). Beyond mineralization, PHOSPHO1 acts as a negative regulator of brown adipose tissue thermogenesis and systemic glucose homeostasis through its phosphocholine phosphatase activity, with effects mediated by choline availability (PMID:32554489, PMID:33092598). It additionally exhibits PC-PLC and PE-PLC activity generating diacylglycerol and co-localizes with diacylglycerol kinase δ (PMID:39992810). Its expression is suppressed by PTH via the cAMP/PKA pathway (PMID:27444010), and it is potently inhibited by proton pump inhibitors, providing a mechanism for PPI-associated fracture risk and for metabolic benefit (PMID:34213594, PMID:38572109).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2003 Medium

    Establishing the structural basis of PHOSPHO1 catalysis was needed to define its enzyme family and substrate specificity; homology modelling placed it in a novel HAD subgroup with a Mg2+-coordinating aspartate triad.

    Evidence Homology modelling on phosphoserine phosphatase crystal structure

    PMID:14983068

    Open questions at the time
    • No experimental crystal structure
    • Predicted specificity residues required mutagenesis to confirm
  2. 2004 High

    The enzymatic identity of PHOSPHO1 was unknown; in vitro assays defined it as a high-affinity Mg2+-dependent phosphatase toward phosphoethanolamine and phosphocholine producing inorganic phosphate.

    Evidence In vitro enzymatic assay with recombinant human PHOSPHO1 and kinetic parameters

    PMID:15175005

    Open questions at the time
    • Physiological substrate in vivo not yet established
    • Cellular site of activity not addressed
  3. 2004 Medium

    Whether PHOSPHO1 was relevant to mineralization required tissue context; IHC showed exclusive localization to mineralizing skeletal regions and expression only in mineralizing osteoblast lines.

    Evidence Immunohistochemistry of avian skeletal tissue and RT-PCR in osteoblast lines

    PMID:15050893

    Open questions at the time
    • Subcellular compartment not resolved
    • Causal role in mineralization not yet tested
  4. 2005 High

    The predicted catalytic residues needed validation; mutagenesis confirmed Asp32/Asp203 as essential and showed the paralog PHOSPHO2 has distinct substrate specificity, cementing PHOSPHO1's HAD membership.

    Evidence Site-directed mutagenesis and kinetic assays of recombinant PHOSPHO1 and PHOSPHO2

    PMID:16054448

    Open questions at the time
    • No structural confirmation of the catalytic mechanism
    • Does not address in vivo substrate
  5. 2006 High

    Linking PHOSPHO1 to the mineralization machinery required showing where it acts; immunoblotting localized active PHOSPHO1 to matrix vesicles, upregulated with TNAP during chondrocyte differentiation and preceding mineral deposition.

    Evidence Immunoblotting of isolated matrix vesicles, in situ hybridization, qPCR

    PMID:16837257

    Open questions at the time
    • Functional requirement within MVs not yet demonstrated
  6. 2007 High

    Whether PHOSPHO1 activity is functionally required for MV-mediated calcification was open; activity was confined to sonicated MVs and pharmacological inhibition substantially reduced MV mineralization.

    Evidence HTS-derived inhibitors and mineralization assays on isolated Akp2-/- osteoblast MVs

    PMID:17227223

    Open questions at the time
    • Inhibitor specificity not exhaustively controlled
    • Genetic confirmation pending
  7. 2010 High

    Genetic proof and pathway relationship to TNAP were needed; Phospho1 knockout produced skeletal disease, and epistasis with TNAP established cooperative, non-redundant, PPi-independent roles.

    Evidence Knockout and double-knockout mice, histology, MV mineralization, plasma biochemistry

    PMID:19874193 PMID:20684022

    Open questions at the time
    • Molecular mediator of the Phospho1-/- bone defect not yet identified at this stage
  8. 2010 Medium

    Whether PHOSPHO1's role generalized beyond cell culture required developmental and signalling context; inhibition blocked endochondral mineralization in chick limbs and a hedgehog-defective mutant lacked Phospho1/Tnap expression.

    Evidence Micromass and in ovo inhibition, in situ hybridization, talpid3 mutant analysis

    PMID:20053388

    Open questions at the time
    • Direct molecular link between hedgehog signalling and Phospho1 transcription not defined
  9. 2014 High

    The mechanism driving the Phospho1-/- skeletal phenotype was unresolved; double knockout of Spp1 rescued the defects, establishing accumulated phosphorylated osteopontin as the mediator, mechanistically distinct from the PPi pathway of TNAP deficiency.

    Evidence Phospho1/Spp1 double-knockout mice with LC-MS/MS p-OPN quantification and histology

    PMID:24825455

    Open questions at the time
    • How PHOSPHO1 loss leads to p-OPN accumulation mechanistically not fully resolved
  10. 2016 Medium

    The scope of PHOSPHO1 in mineralized tissues and its contribution to MV biogenesis was extended; genetic and phosphate-transporter epistasis showed it acts in MV formation, cementum, and alveolar bone, and PTH suppresses it via cAMP/PKA.

    Evidence Conditional double knockouts with Pit1, AFM of MVs, dental phenotyping, and pharmacological PKA epistasis in osteoblast cultures

    PMID:26773408 PMID:27016531 PMID:27444010

    Open questions at the time
    • Mechanism of MV biogenesis defect unknown
    • Direct transcriptional targets of PKA on Phospho1 not mapped
  11. 2013 High

    Whether PHOSPHO1 contributes to pathological calcification was open; knockout and inhibition of vascular smooth muscle cells showed it is critical for vascular mineralization, cooperating with TNAP.

    Evidence Phospho1-/- VSMC cultures with pharmacological inhibitors and mineralization assays

    PMID:22887744

    Open questions at the time
    • In vivo vascular calcification contribution not addressed in this study
  12. 2020 Medium

    A role outside the skeleton was unknown; knockout mice were cold-tolerant and protected from obesity/insulin resistance, and phosphocholine accumulation or dietary choline rescue established PHOSPHO1 as a choline-mediated negative regulator of BAT thermogenesis and metabolism.

    Evidence Phospho1-/- mice, cold/HFD challenge, exogenous phosphocholine and dietary choline rescue

    PMID:32554489 PMID:33092598

    Open questions at the time
    • Tissue source of metabolically relevant PHOSPHO1 activity not isolated
    • Downstream choline signalling pathway incompletely defined
  13. 2021 Medium

    The pharmacology connecting PHOSPHO1 to clinical drug effects was unclear; proton pump inhibitors directly inhibit PHOSPHO1 with sub-micromolar to micromolar IC50s and suppress osteoblast mineralization, offering a mechanism for PPI-associated fracture risk and metabolic benefit.

    Evidence In vitro IC50 determination, osteoblast mineralization assays, and PHOSPHO1-dependent metabolic rescue in HFD mice

    PMID:34213594 PMID:38572109

    Open questions at the time
    • Off-target contributions of PPIs not fully excluded
    • In vivo bone-versus-metabolism selectivity unclear
  14. 2025 Medium

    Whether PHOSPHO1 has lipid-signalling functions was unexplored; it was shown to possess D609-sensitive PC-PLC and PE-PLC activity generating diacylglycerol and to co-localize with DGKδ, positioning it in a diacylglycerol-generating pathway.

    Evidence In vitro PLC assays, HEK293 overexpression lipidomics, co-sedimentation and co-localization with DGKδ

    PMID:39992810

    Open questions at the time
    • Physiological significance of PLC activity not established in vivo
    • Single lab, first report of this activity
    • DGKδ interaction not validated reciprocally

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single matrix-vesicle phosphatase mechanistically integrates skeletal mineralization, systemic choline/metabolic regulation, and lipid-signalling roles within distinct cellular compartments remains unresolved.
  • No experimental structure of human PHOSPHO1
  • Mechanism linking PHOSPHO1 loss to phosphorylated osteopontin accumulation unresolved
  • Compartment-specific contributions to mineralization versus metabolism not separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 3
Localization
GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-1266738 Developmental Biology 2
Partners
ALPLDGKD

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Human PHOSPHO1 exhibits high specific phosphatase activities toward phosphoethanolamine (PEA) and phosphocholine (PCho), generating inorganic phosphate (Pi). Optimal activity is at pH ~6.7, requires Mg2+, with Km values of 3.0 µM for PEA and 11.4 µM for PCho. In vitro enzymatic assay with recombinant human PHOSPHO1 The Biochemical journal High 15175005
2003 Comparative modelling of human PHOSPHO1 based on phosphoserine phosphatase crystal structure revealed a catalytic Mg2+ coordinated by conserved Asp32, Asp34, and Asp203; Asp43 and Asp123 (not present in PSPs) contribute to substrate specificity, placing PHOSPHO1 in a novel subgroup of the HAD superfamily distinct from phosphoserine phosphatases. Homology modelling based on crystal structure of phosphoserine phosphatase from Methanococcus jannaschii Protein engineering Medium 14983068
2005 Active-site mutagenesis of PHOSPHO1 confirmed that Asp32 and Asp203 are essential catalytic residues; mutation of either abolishes activity, confirming membership in the HAD superfamily. Asp43 and Asp123 are also important for substrate hydrolysis. By contrast, PHOSPHO2 (42% identity) shows high activity toward pyridoxal-5-phosphate rather than PEA/PCho, indicating distinct substrate specificities despite similar active-site architecture. Site-directed mutagenesis of recombinant PHOSPHO1 and PHOSPHO2, in vitro enzymatic assay Biochimica et biophysica acta High 16054448
2004 PHOSPHO1 protein localizes exclusively to mineralizing regions: osteoid of periosteum, forming surfaces of growing osteons, newly formed osteocytes, early hypertrophic chondrocytes of growth plate, and primary spongiosa; absent from soft tissues. PHOSPHO1 gene expression is detected in mineralizing SaOS-2 but not non-mineralizing MG-63 osteoblast-like cells. Immunohistochemistry of avian skeletal tissues with affinity-purified antiserum; RT-PCR in osteoblast cell lines Bone Medium 15050893
2006 PHOSPHO1 is present within matrix vesicles (MVs) isolated from growth plate chondrocytes, as confirmed by immunoblotting. PHOSPHO1 expression in MVs is upregulated alongside TNAP activity when chondrocytes are induced to differentiate with ascorbic acid. PHOSPHO1 mRNA expression during chick embryogenesis precedes mineral deposition, appearing first in the bone collar of the diaphysis. Immunoblotting of isolated MVs; whole-mount in situ hybridization; qPCR; alizarin red/alcian blue staining Bone High 16837257
2007 PHOSPHO1 is functionally present within MVs in an active state (PEA hydrolase activity detected in sonicated but not intact MVs from TNAP-deficient osteoblasts). Pharmacological inhibition of PHOSPHO1 with lansoprazole or SCH202676 reduced MV-mediated mineralization by 56.8% and 70.7%, respectively, establishing a functional role in the initiation of MV-mediated calcification. High-throughput screening of chemical libraries; enzymatic assay on sonicated/intact MVs from Akp2-/- osteoblasts; mineralization assay with isolated MVs Journal of bone and mineral research High 17227223
2010 Genetic ablation of PHOSPHO1 (Phospho1-/- mice) causes growth plate abnormalities, spontaneous fractures, bowed long bones, osteomalacia, and scoliosis. Primary Phospho1-/- chondrocytes and their MVs show reduced mineralizing ability. Plasma PP(i) is elevated in Phospho1-/- mice. Transgenic overexpression of TNAP in Phospho1-/- mice normalizes PP(i) but does NOT correct the bone phenotype, demonstrating PHOSPHO1 has a non-redundant role independent of PP(i) control. Double ablation of PHOSPHO1 and TNAP completely abolishes skeletal mineralization and causes perinatal lethality, establishing their cooperative, non-redundant roles. Knockout mouse generation; histology; primary chondrocyte culture; MV isolation and mineralization assay; biochemical plasma analysis; genetic double-knockout epistasis Journal of bone and mineral research High 20684022
2010 PHOSPHO1 deficiency in MVs secondarily reduces TNAP levels in Phospho1-/- MVs, affecting ATP hydrolysis in those MVs. TNAP is the primary enzyme hydrolyzing both ATP and PP(i) within the MV compartment; lack of NPP1 does not significantly affect MV kinetic parameters for any substrate. Kinetic analysis of phosphosubstrate hydrolysis by isolated MVs from WT, TNAP-/-, NPP1-/-, and PHOSPHO1-/- osteoblasts at physiologic pH Journal of bone and mineral research High 19874193
2010 Pharmacological inhibition of PHOSPHO1 (lansoprazole) in developing chick limb micromass cultures and in ovo completely inhibited mineralization of long bones. PHOSPHO1 and TNAP are co-expressed in a tightly regulated pattern preceding mineralization. The talpid3 chick mutant (defective hedgehog signaling, no endochondral mineralization) lacks Phospho1 and Tnap expression, while flat bones that mineralize normally express both, linking hedgehog signaling to PHOSPHO1-dependent endochondral ossification. In vitro micromass cultures with lansoprazole inhibitor; whole-mount RNA in situ hybridization; talpid3 mutant analysis; alizarin red/alcian blue staining Bone Medium 20053388
2013 PHOSPHO1 is expressed in vascular smooth muscle cells (VSMCs) under calcifying conditions, and Phospho1-/- VSMCs fail to mineralize in vitro. Pharmacological inhibition of PHOSPHO1 with MLS-0263839 reduced VSMC calcification to 41.8% of control; combined PHOSPHO1 + TNAP inhibition reduced it to 20.9% of control, demonstrating PHOSPHO1 plays a critical role in VSMC (vascular) mineralization. Knockout VSMC cultures; pharmacological inhibitors; mineralization assay; gene expression analysis Journal of bone and mineral research High 22887744
2014 Phospho1-/- mice have elevated plasma osteopontin (OPN) and increased proportion of phosphorylated OPN (p-OPN) in the skeleton detected by LC-MS/MS. Ablation of Spp1 (OPN gene) in Phospho1-/- mice rescues scoliosis and improves long bone defects and normalizes chondrocyte differentiation markers, establishing that accumulated phosphorylated OPN mediates the skeletal abnormalities in Phospho1-/- mice (distinct from the PP(i)-mediated mechanism in TNAP-deficient mice). Double-knockout mouse generation; LC-MS/MS for p-OPN quantification; histology; mineralization assay; gene expression analysis Journal of bone and mineral research High 24825455
2016 Combined genetic ablation of Phospho1 and the phosphate transporter Pit1 (Slc20a1, col2a1-Cre) produces more severe skeletal deformities than Phospho1-/- alone. ~80% of [Phospho1-/-; Pit1col2/col2] MVs are devoid of mineral vs. ~50% for Phospho1-/- and ~25% for WT, assessed by atomic force microscopy. PHOSPHO1 function is also involved in MV biogenesis, as both Phospho1-/- and double-KO chondrocytes produce significantly fewer MVs. Conditional double-knockout mouse model; atomic force microscopy of MVs; histology; micro-CT; biomechanical testing Journal of bone and mineral research High 26773408
2016 PTH continuously downregulates Phospho1 and Smpd3 (nSMase2) gene expression in osteoblast cultures and hemi-calvariae. This effect is mimicked by the cAMP agonist forskolin and blocked by the PKA inhibitor PKI(5-24), identifying the cAMP/PKA pathway as the mediator of PTH-driven PHOSPHO1 suppression. BMP-2's stimulatory effect on Phospho1 expression is abolished by PTH. In vitro osteoblast cultures (MC3T3-C14); hemi-calvaria cultures; pharmacological agonist/inhibitor studies; gene expression analysis (qPCR) Calcified tissue international Medium 27444010
2016 PHOSPHO1 (expressed by cementoblasts and alveolar bone osteoblasts) is required for cellular cementum and alveolar bone mineralization. Phospho1-/- mice show increased cementoid (delayed mineralization) in cellular cementum and unmineralized osteoid in alveolar bone with elevated OPN deposition, while acellular cementum is unaffected, demonstrating acellular cementum does not rely on MV-mediated (PHOSPHO1-dependent) initiation of mineralization. Phospho1-/- mouse analysis; histology; immunohistochemistry; in situ hybridization; micro-CT; radiography Journal of dental research Medium 27016531
2015 PHOSPHO1 and TNAP have non-redundant, cooperative roles in osteoblast mineralization. In MC3T3-E1 clone 24 cells (low PHOSPHO1/high TNAP), lentiviral PHOSPHO1 overexpression increases both PHOSPHO1 and TNAP protein and enhances mineralization. Simultaneous pharmacological inhibition of both PHOSPHO1 and TNAP essentially abolishes mineralization (85% reduction), whereas individual inhibitors only partially suppress it. Lentiviral overexpression; pharmacological inhibitors (MLS-0263839 and MLS-0038949); mineralization assays in MC3T3-E1 cell clones and ex vivo metatarsal cultures Biochemistry and biophysics reports Medium 26457330
2008 A novel alternatively spliced PHOSPHO1 transcript (PHOSPHO1-3a) was identified, encoding a 292-amino-acid protein with a 40-amino-acid N-terminal region containing a predicted secretory signal while retaining all three HAD superfamily catalytic domains. Expression confirmed in human and mouse osteoblast-like cells and chondrogenic ATDC5 cells. RT-PCR; sequence analysis; expression in osteoblast and chondrogenic cell lines Biochemical and biophysical research communications Medium 18471996
2017 PHOSPHO1 localizes to ameloblast Tomes' processes and secretory vesicle walls (co-localizing with amelogenin and the exosomal marker HSP70). Phospho1-/- mice display reduced enamel mineralization (2-fold reduction in von Kossa silver grain density), loss of enamel prism 'picket fence' structure, loss of parallel crystal organization, increased prism width, and decreased phosphate incorporation by EDS, establishing PHOSPHO1 as essential for enamel mineralization. Immunohistochemistry; Western blot; scanning electron microscopy; EDS elemental analysis; von Kossa staining; Phospho1-/- mouse model Frontiers in physiology Medium 29089903
2020 PHOSPHO1 knockout mice are cold-tolerant and protected from high-fat diet-induced obesity and insulin resistance. PHOSPHO1 substrate phosphocholine (PC) accumulation (via exogenous PC treatment) is sufficient to induce thermogenic gene expression in BAT and cold tolerance, establishing PHOSPHO1 as a negative regulator of BAT thermogenesis through its phosphocholine phosphatase activity. Phospho1-/- mouse model; cold tolerance testing; high-fat diet challenge; thermogenic gene expression analysis; exogenous phosphocholine treatment Proceedings of the National Academy of Sciences of the United States of America Medium 32554489
2020 Phospho1-/- mice exhibit improved basal glucose homeostasis and resist high-fat diet-induced weight gain and diabetes independently of osteocalcin levels. Decreased serum choline in Phospho1-/- mice is normalized by 2% choline diet feeding, which also normalizes insulin sensitivity and fat mass, establishing that PHOSPHO1's metabolic regulation is mediated via choline availability. Phospho1-/- mouse model; HFD challenge; dietary choline supplementation rescue; serum metabolite measurement; gene expression analysis in osteoblasts BMC biology Medium 33092598
2021 All tested proton pump inhibitors (PPIs) inhibit PHOSPHO1 enzymatic activity in vitro (IC50 range: 0.73 µM for esomeprazole to 19.27 µM for pantoprazole), whereas histamine-2 receptor antagonists do not. Several PPIs inhibit mineralization of bone matrix in primary osteoblast cultures in a concentration-dependent manner, providing a potential mechanism for PPI-associated fracture risk. In vitro PHOSPHO1 enzymatic inhibition assay; primary osteoblast mineralization cultures Calcified tissue international Medium 34213594
2022 In a CKD (renal osteodystrophy) mouse model, cortical bone mineral density is increased alongside upregulated PHOSPHO1 expression. In Phospho1-/- CKD mice, the cortical BMD increase is rescued, establishing that elevated PHOSPHO1 expression directly drives the cortical BMD phenotype in CKD. PTH and phosphate treatment of primary osteoblasts downregulate both PHOSPHO1 and TNAP expression. Dietary adenine CKD model in WT and Phospho1-/- mice; micro-CT; primary osteoblast cultures with PTH/phosphate treatment; gene expression analysis The Journal of endocrinology Medium 35900032
2025 PHOSPHO1 (cytosolic protein) exhibits D609-sensitive phosphatidylcholine-PLC (PC-PLC) and phosphatidylethanolamine-PLC (PE-PLC) activities in vitro, generating diacylglycerol (DG). Overexpression of PHOSPHO1 in HEK293 cells significantly increases cellular levels of saturated/monounsaturated fatty acid-containing DG. PHOSPHO1 co-sediments and co-localizes with diacylglycerol kinase δ (DGKδ), identifying it as a candidate cytosolic PC-/PE-PLC acting upstream of DGKδ. In vitro PLC activity assay; PHOSPHO1 overexpression in HEK293 cells; lipidomic analysis; co-sedimentation; co-localization FEBS letters Medium 39992810
2024 Lansoprazole (LPZ) inhibits adipose PHOSPHO1 (phosphocholine phosphatase) activity and produces metabolic benefits (reduced obesity, insulin resistance, hepatic steatosis, induction of thermogenic gene expression) in a PHOSPHO1-dependent manner in mice. Mechanistically, LPZ may stimulate thermogenesis by inhibiting conversion of 2-AG-LPA to 2-AG, reducing cannabinoid receptor signaling. In vitro PHOSPHO1 inhibition assay; HFD mouse model with LPZ treatment; PHOSPHO1-dependent rescue experiments; gene expression analysis; mitochondrial respiration assay Acta pharmaceutica Sinica. B Medium 38572109

Source papers

Stage 0 corpus · 35 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Loss of skeletal mineralization by the simultaneous ablation of PHOSPHO1 and alkaline phosphatase function: a unified model of the mechanisms of initiation of skeletal calcification. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 179 20684022
2016 DNA methylation of loci within ABCG1 and PHOSPHO1 in blood DNA is associated with future type 2 diabetes risk. Epigenetics 152 27148772
2007 Functional involvement of PHOSPHO1 in matrix vesicle-mediated skeletal mineralization. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 143 17227223
2004 Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities. The Biochemical journal 112 15175005
2010 Kinetic analysis of substrate utilization by native and TNAP-, NPP1-, or PHOSPHO1-deficient matrix vesicles. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 111 19874193
2004 PHOSPHO1-A novel phosphatase specifically expressed at sites of mineralisation in bone and cartilage. Bone 81 15050893
2006 The presence of PHOSPHO1 in matrix vesicles and its developmental expression prior to skeletal mineralization. Bone 69 16837257
2010 Inhibition of PHOSPHO1 activity results in impaired skeletal mineralization during limb development of the chick. Bone 55 20053388
2019 How To Build a Bone: PHOSPHO1, Biomineralization, and Beyond. JBMR plus 53 31372594
2013 Pharmacological inhibition of PHOSPHO1 suppresses vascular smooth muscle cell calcification. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 51 22887744
2016 Skeletal Mineralization Deficits and Impaired Biogenesis and Function of Chondrocyte-Derived Matrix Vesicles in Phospho1(-/-) and Phospho1/Pi t1 Double-Knockout Mice. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 48 26773408
2014 Ablation of osteopontin improves the skeletal phenotype of phospho1(-/-) mice. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 47 24825455
2003 Comparative modelling of human PHOSPHO1 reveals a new group of phosphatases within the haloacid dehalogenase superfamily. Protein engineering 40 14983068
2005 Probing the substrate specificities of human PHOSPHO1 and PHOSPHO2. Biochimica et biophysica acta 32 16054448
2015 The Functional co-operativity of Tissue-Nonspecific Alkaline Phosphatase (TNAP) and PHOSPHO1 during initiation of Skeletal Mineralization. Biochemistry and biophysics reports 28 26457330
2020 Phosphocholine accumulation and PHOSPHO1 depletion promote adipose tissue thermogenesis. Proceedings of the National Academy of Sciences of the United States of America 21 32554489
2016 Role of PHOSPHO1 in Periodontal Development and Function. Journal of dental research 19 27016531
2017 A distinctive patchy osteomalacia characterises Phospho1-deficient mice. Journal of anatomy 18 28737011
2020 PHOSPHO1 is a skeletal regulator of insulin resistance and obesity. BMC biology 17 33092598
2022 Increased PHOSPHO1 expression mediates cortical bone mineral density in renal osteodystrophy. The Journal of endocrinology 16 35900032
2002 Chromosomal localization of the chicken and mammalian orthologues of the orphan phosphatase PHOSPHO1 gene. Animal genetics 15 12464021
2021 Proton Pump Inhibitors Inhibit PHOSPHO1 Activity and Matrix Mineralisation In Vitro. Calcified tissue international 14 34213594
2017 Intravesicular Phosphatase PHOSPHO1 Function in Enamel Mineralization and Prism Formation. Frontiers in physiology 12 29089903
2016 The Expression of PHOSPHO1, nSMase2 and TNAP is Coordinately Regulated by Continuous PTH Exposure in Mineralising Osteoblast Cultures. Calcified tissue international 12 27444010
2022 Perspective on Dentoalveolar Manifestations Resulting From PHOSPHO1 Loss-of-Function: A Form of Pseudohypophosphatasia? Frontiers in dental medicine 8 36185572
2024 Repurposing lansoprazole to alleviate metabolic syndrome via PHOSPHO1 inhibition. Acta pharmaceutica Sinica. B 7 38572109
2008 Identification of a novel splice variant of the haloacid dehalogenase: PHOSPHO1. Biochemical and biophysical research communications 6 18471996
2025 Human PHOSPHO1 exhibits phosphatidylcholine- and phosphatidylethanolamine-phospholipase C activities and interacts with diacylglycerol kinase δ. FEBS letters 5 39992810
2025 Distinct bone metabolic networks identified in Phospho1-/- mice vs. wild type mice using [18F]FDG total-body PET. Frontiers in medicine 4 40470038
2022 PHOSPHO1 Serves as a Key Metabolism-Related Biomarker in the Tumorigenesis of Diffuse Large B-cell Lymphoma. Current medical science 3 35943680
2022 Increased PHOSPHO1 and alkaline phosphatase expression during the anabolic bone response to intermittent parathyroid hormone delivery. Cell biochemistry and function 3 36540015
2013 The use of tissue-nonspecific alkaline phosphatase (TNAP) and PHOSPHO1 inhibitors to affect mineralization by cultured cells. Methods in molecular biology (Clifton, N.J.) 2 23860651
2025 Co-overexpression of the caloric restriction-induced mitochondrial factors PGC-1α and MIPEP upregulates Phospho1 expression in adipocytes. FEBS open bio 1 40574346
2020 PHOSPHO1 Gene DNA Methylations are Associated with a Change in HDL-C Response to Simvastatin Treatment. Current pharmaceutical design 1 32693758
2026 Methylation analysis of PHOSPHO1 and ACACA gene promoters in whole blood samples: insights into metabolic syndrome and associated factors. Journal of diabetes and metabolic disorders 0 41664674

Missed literature

Know a paper Affinage missed for PHOSPHO1? Flag it for the maintainers and the community.

No submissions yet.