Affinage

PHACTR1

Phosphatase and actin regulator 1 · UniProt Q9C0D0

Length
580 aa
Mass
66.3 kDa
Annotated
2026-06-10
56 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PHACTR1 is a G-actin- and protein phosphatase 1 (PP1)-binding protein that couples Rho/actin signaling to substrate-specific dephosphorylation and actomyosin remodeling (PMID:22976292, PMID:32975518). Its four RPEL motifs bind G-actin to retain it in the cytoplasm of resting cells; when Rho-actin signaling lowers free G-actin, importin α-β drives nuclear accumulation, with G-actin, importin, and PP1 competing for overlapping C-terminal/RPEL3 interfaces (PMID:22976292, PMID:38272663). In the nucleus and cytoplasm PHACTR1 acts as a PP1 cofactor: binding remodels the PP1 hydrophobic groove into a composite surface that confers orders-of-magnitude enhanced, sequence-specific reactivity toward cytoskeletal substrates such as IRSp53 and spectrin αII (PMID:32975518). Through this PP1-directed activity and its control of F-actin assembly, PHACTR1 governs stress fiber formation, cell motility and invasion (PMID:22976292), regulates myosin light chain phosphorylation required for macrophage efferocytosis (PMID:33630758), and tunes Slack (KCNT1) Na+-activated K+ channel currents via PP1-dependent dephosphorylation of channel residue S407 (PMID:31914597). In the nervous system PHACTR1 is required for cortical neuron migration, dendritic development, and normal synaptic properties, and de novo missense mutations that selectively impair actin- or PP1-binding cause these neurodevelopmental defects, linking PHACTR1 to infantile epileptic spasms syndrome (PMID:30256902, PMID:38272663). In the vasculature, endothelial PHACTR1 functions as a transcriptional corepressor of PPARγ and partners with MRTF-A and NF-κB p65 to promote disturbed-flow–dependent endothelial inflammation and atherosclerosis (PMID:30293016, PMID:37199156).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2012 High

    Established the core regulatory logic of PHACTR1: how a single protein integrates actin signaling with PP1-dependent cytoskeletal remodeling through competitive G-actin/importin/PP1 binding at RPEL motifs.

    Evidence RPEL mutagenesis, competitive binding and importin assays, localization microscopy, and motility/invasion assays in melanoma cells

    PMID:22976292

    Open questions at the time
    • Did not resolve atomic basis of substrate specificity
    • Physiological substrates beyond actomyosin not defined
  2. 2011 Medium

    Connected PHACTR1 to endothelial biology, showing its expression is VEGF-A165/NRP-1/VEGFR1-dependent and that it controls PP1 activity, F-actin, lamellipodial dynamics, and survival via death-receptor signaling.

    Evidence siRNA knockdown of PHACTR1 and receptors, blocking peptides, PP1 activity assays, tube formation and apoptosis assays in HUVECs

    PMID:21798305 PMID:21939755

    Open questions at the time
    • Mechanism linking PHACTR1 loss to death receptor induction unresolved
    • Single-lab HUVEC system
  3. 2013 Medium

    Placed PHACTR1 in a TGF-β/miR-584 axis driving actin rearrangement and migration in cancer cells, indicating transcriptional/post-transcriptional control of PHACTR1 abundance shapes cytoskeletal output.

    Evidence miR-584 overexpression/knockdown, PHACTR1 siRNA, luciferase reporter, migration and actin staining in breast cancer cells

    PMID:23479725

    Open questions at the time
    • Direct PP1/actin mechanism not dissected in this context
    • In vivo relevance untested
  4. 2017 Medium

    Extended PHACTR1 function to vascular cell fate and neuronal compartmentalization, showing it modulates SMC calcification and localizes to neuronal synapses and developing brain in a stage-dependent manner.

    Evidence Gain/loss-of-function in mESC-derived and human aortic SMCs; subcellular fractionation and immunofluorescence in hippocampal/cortical neurons

    PMID:28720499 PMID:28803787

    Open questions at the time
    • No functional consequence tested for neuronal localization
    • Calcification mechanism downstream of PHACTR1 unclear
  5. 2018 High

    Demonstrated that PHACTR1 is required for cortical neuron migration and synaptic function and that disease mutations act by selectively disrupting actin- or PP1-binding, providing genotype-to-mechanism resolution.

    Evidence Reciprocal Co-IP binding assays of four mutants, in utero electroporation knockdown/rescue, electrophysiology in mouse cortex

    PMID:30256902

    Open questions at the time
    • Synaptic substrate(s) of PHACTR1/PP1 not identified
    • Acute knockdown rather than germline model
  6. 2018 Medium

    Identified endothelial PHACTR1 as a partner of MRTF-A and NF-κB p65 that promotes p65 nuclear translocation and adhesion-molecule/ROS responses to ox-LDL, linking it to pro-inflammatory endothelial activation.

    Evidence Co-IP, PHACTR1/MRTF-A knockdown, p65 immunofluorescence and ROS flow cytometry in HCAECs

    PMID:30293016

    Open questions at the time
    • Direct vs. PP1-dependent role in p65 regulation not separated
    • Single-lab Co-IP
  7. 2019 High

    Showed PHACTR1 channels PP1 activity to ion-channel regulation, dephosphorylating Slack (KCNT1) at S407 to modulate Na+-activated K+ currents.

    Evidence Co-IP, patch-clamp, and mutagenesis of Slack S407 and the PHACTR1 PP1-binding domain

    PMID:31914597

    Open questions at the time
    • In vivo relevance of Slack regulation untested
    • Whether dephosphorylation is direct on S407 not crystallographically shown
  8. 2020 High

    Resolved the structural basis for PHACTR1/PP1 substrate specificity, showing PHACTR1 remodels the PP1 groove into a composite surface that reads sequences C-terminal to the dephosphorylation site.

    Evidence High-resolution crystal structures of holoenzyme-product complexes with IRSp53/spectrin αII, phosphoproteomics, in vitro phosphatase assays, contact-residue mutagenesis

    PMID:32975518

    Open questions at the time
    • Full physiological substrate repertoire incomplete
    • Regulation of holoenzyme assembly in vivo not addressed
  9. 2020 Medium

    Defined a macrophage-autonomous, PP1-independent transcriptional route by which Phactr1 binds CREB to induce KLF4, restraining M1 polarization and foam cell formation and limiting atherosclerosis.

    Evidence Co-IP, Phactr1-/-Apoe-/- mice with bone marrow transplant, KLF4 rescue, polarization and foam cell assays

    PMID:32857129

    Open questions at the time
    • Direct vs. indirect CREB binding not structurally defined
    • Relationship to PHACTR1's actin/PP1 functions unclear
  10. 2021 High

    Linked PHACTR1 to macrophage efferocytosis and plaque stability, showing it maintains MLC phosphorylation needed for apoptotic cell engulfment, with a human risk allele lowering its expression.

    Evidence siRNA in human/mouse macrophages, hematopoietic Phactr1-targeted Ldlr-/- mice, phospho-MLC blotting, efferocytosis and plaque histology

    PMID:33630758

    Open questions at the time
    • Whether MLC is a direct PHACTR1/PP1 substrate or regulated indirectly
    • rs9349379 mechanism on expression not fully resolved
  11. 2021 Medium

    Added a ROCK2-coupled role for Phactr1 in BMSC fate and characterized a disease variant (L519R) that shifts the G-actin/PP1 binding balance toward PP1 and enhanced cytoskeletal activity.

    Evidence Co-IP with ROCK2, ROCK2 inhibitor epistasis, differentiation assays; in vitro G-actin/PP1 binding and localization of L519R

    PMID:33463715 PMID:34709489

    Open questions at the time
    • Mechanistic link between Phactr1 and RhoA/ROCK2 directionality limited
    • Single-mutant binding study
  12. 2023 High

    Identified PHACTR1 as a flow-regulated transcriptional corepressor of PPARγ in endothelium that drives atherosclerosis specifically in disturbed-flow regions.

    Evidence EC-specific and global Phactr1 KO in ApoE-/- mice, RNA-seq, flow-dependent localization, PHACTR1-PPARγ binding, GW9662 epistasis in vivo

    PMID:37199156

    Open questions at the time
    • How nuclear shuttling is sensed from flow not mechanistically tied to RPEL/actin in this study
    • Corepressor complex composition undefined
  13. 2023 Low

    Provided a cancer-cell readout linking PHACTR1 to F-actin–dependent invasion in papillary thyroid carcinoma.

    Evidence Overexpression/knockdown with Transwell assays, F-actin staining, and swinholide A reversal in PTC lines

    PMID:37876444

    Open questions at the time
    • No upstream mechanistic dissection or PP1/actin-binding requirement tested
    • Single pharmacological rescue
  14. 2024 Medium

    Implicated PHACTR1 in mitochondrial morphology, bioenergetics, cell cycle, and iron metabolism, including an unexpected mitochondrial pool acting via AKAP1/Drp1.

    Evidence Multi-omics in HT1080 OE/KD cells with primary-cell validation, mitochondrial fractionation, AKAP1/Drp1 blotting

    PMID:41554990

    Open questions at the time
    • Mechanism of mitochondrial targeting unknown
    • Causal links from omics correlations not fully established
  15. 2024 Low

    Refined the structural model by mapping overlapping G-actin and PP1 (PPP1CA) interfaces to the RPEL3 domain and correlating interface variants with infantile epileptic spasms syndrome.

    Evidence AlphaFold-Multimer modeling with genotype-phenotype analysis of patient missense variants

    PMID:38272663

    Open questions at the time
    • Predictions are computational; binding not measured here
    • Variant functional consequences inferred, not directly assayed

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how PHACTR1's actin/PP1-regulated cytoskeletal function, its CREB/PPARγ transcriptional roles, and its reported mitochondrial activity are mechanistically integrated within a single cell.
  • No unified model linking PP1-dependent and transcriptional functions
  • Physiological substrate map beyond IRSp53/spectrin/MLC/Slack incomplete
  • Mechanism of mitochondrial localization undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0060090 molecular adaptor activity 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005856 cytoskeleton 2 GO:0005739 mitochondrion 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-392499 Metabolism of proteins 2
Partners
ACTBIRSP53KCNT1MRTF-APPARGPPP1CARELAROCK2
Complex memberships
PHACTR1/PP1 (PPP1CA) holoenzyme

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 PHACTR1 contains four G-actin binding RPEL motifs (one N-terminal, three C-terminal) that control its subcellular localization: G-actin binding to the three C-terminal RPEL motifs retains PHACTR1 in the cytoplasm of resting cells, while Rho-actin signaling (serum stimulation) reduces free G-actin and promotes importin α-β-dependent nuclear accumulation of PHACTR1. G-actin and importin α-β bind competitively to nuclear import signals associated with the N- and C-terminal RPEL motifs. G-actin and PP1 also bind competitively to the PHACTR1 C-terminal region; RPEL mutants unable to bind G-actin constitutively accumulate in the nucleus and induce aberrant actomyosin structures in a PP1-binding-dependent manner. In CHL-1 melanoma cells, Phactr1 is required for stress fiber assembly, motility, and invasiveness. Co-immunoprecipitation, site-directed mutagenesis of RPEL motifs, fluorescence microscopy of subcellular localization, importin competition assays, actin binding assays, cell motility/invasion assays Journal of cell science High 22976292
2020 The Phactr1/PP1 holoenzyme has defined substrate specificity: Phactr1 binding remodels PP1's hydrophobic groove to create a composite surface adjacent to the catalytic site. High-resolution crystal structures of Phactr1/PP1 bound to dephosphorylated substrates IRSp53 and spectrin αII showed that substrate sequences C-terminal to the dephosphorylation site make intimate contacts with this composite Phactr1/PP1 surface, which are required for efficient dephosphorylation. Phactr1/PP1 exhibits orders-of-magnitude enhanced reactivity toward its substrates (identified by phosphoproteomics as cytoskeletal components including IRSp53 and spectrin αII) compared to apo-PP1 or other PP1 holoenzymes. Inversion of the phosphate in holoenzyme-product complexes supports the proposed PPP-family catalytic mechanism. X-ray crystallography (high-resolution structures of holoenzyme-product complexes), phosphoproteomics substrate identification, in vitro phosphatase activity assays, mutagenesis of substrate contact residues eLife High 32975518
2018 De novo missense mutations in PHACTR1 (p.Leu500Pro, p.Asn479Ile, p.Ile518Asn) impair actin-binding activity of PHACTR1, while p.Arg521Cys impairs binding to PP1, as shown by immunoprecipitation. Acute knockdown of mouse Phactr1 by in utero electroporation causes defects in cortical neuron migration during corticogenesis, rescued by RNAi-resistant wild-type PHACTR1 but not by the four mutants. The p.Arg521Cys PP1-binding mutant has dominant-negative effects on dendritic development in vivo. Electrophysiological analyses revealed abnormal synaptic properties in Phactr1-deficient excitatory cortical neurons. Co-immunoprecipitation (actin and PP1 binding), in utero electroporation knockdown/rescue in mouse cortex, electrophysiology of cortical neurons Brain : a journal of neurology High 30256902
2021 PHACTR1 prevents dephosphorylation of myosin light chain (MLC), which is necessary for apoptotic cell (AC) engulfment by macrophages. The rs9349379-G/G risk allele is associated with lower PHACTR1 expression in human monocyte-derived macrophages, lower phospho-MLC, and impaired efferocytosis. Silencing PHACTR1 in human and mouse macrophages compromised AC engulfment. Hematopoietic Phactr1-targeted Ldlr-/- mice on Western diet showed impaired lesional efferocytosis, increased plaque necrosis, and thinner fibrous caps. siRNA knockdown of PHACTR1 in human/mouse macrophages, hematopoietic-specific genetic knockout (bone marrow transplant into Ldlr-/- mice), phospho-MLC western blotting, efferocytosis assays, histological analysis of atherosclerotic plaques The Journal of clinical investigation High 33630758
2019 Phactr1 regulates Slack (KCNT1) sodium-activated potassium channels via PP1: co-immunoprecipitation showed Phactr1 links channels to actin. Co-expression of Phactr1 with wild-type Slack channels reduces current amplitude; this effect is absent when the conserved PKC phosphorylation site S407 (which regulates current amplitude) is mutated. A Phactr1 mutant that disrupts PP1 binding but not actin binding fails to alter Slack currents, indicating regulation occurs through PP1 recruitment. Co-immunoprecipitation, patch-clamp electrophysiology, site-directed mutagenesis of Slack S407 and Phactr1 PP1-binding domain FASEB journal High 31914597
2011 PHACTR-1 depletion in HUVECs inhibits tube formation and triggers apoptosis through death receptors DR4, DR5, and FAS; this apoptosis is reversed by death receptor siRNAs or caspase-8 siRNA. PHACTR-1 is an actin- and PP1-binding protein that controls PP1 activity and F-actin remodeling, and its expression is dependent on VEGF-A165. siRNA knockdown of PHACTR-1 and death receptors/caspase-8 in HUVECs, tube formation assay, apoptosis assays Biochimie Medium 21798305
2011 PHACTR-1 expression is regulated downstream of VEGF-A165 via NRP-1 and VEGF-R1 (but not NRP-2 or VEGF-R2). PHACTR-1 depletion decreased PP1 activity, disrupted actin polymerization, and impaired lamellipodial dynamics in HUVECs. Upon VEGF-A165 stimulation, PHACTR-1 promotes formation and maintenance of cellular tubes through NRP-1 and VEGFR1. siRNA knockdown of NRP-1, NRP-2, VEGF-R1, VEGF-R2, and PHACTR-1 in HUVECs; VEGF-A165 receptor blocking peptides; PP1 activity assay; live-cell imaging of lamellipodial dynamics; tube formation assay Cellular signalling Medium 21939755
2013 TGF-β downregulates miR-584 in breast cancer cells, which leads to upregulation of PHACTR1 (a miR-584 target). PHACTR1 upregulation is required for TGF-β-induced actin rearrangement and cell migration; overexpression of miR-584 or knockdown of PHACTR1 causes drastic actin cytoskeleton reorganization and reduces TGF-β-induced cell migration. miRNA overexpression and knockdown, PHACTR1 siRNA knockdown, cell migration assays, actin cytoskeleton staining, luciferase reporter for miR-584/PHACTR1 interaction The Journal of biological chemistry Medium 23479725
2018 PHACTR1 interacts with MRTF-A and NF-κB p65 in human coronary artery endothelial cells (HCAECs) as shown by co-immunoprecipitation. Knockdown of PHACTR1 reduces MRTF-A-dependent nuclear translocation of p65 and attenuates NF-κB activity, reducing ICAM-1, VCAM-1, and VE-cadherin expression and intracellular ROS/p47phox phosphorylation induced by ox-LDL. Knockdown of MRTF-A disrupts the PHACTR1-p65 interaction. Co-immunoprecipitation (PHACTR1-MRTF-A, PHACTR1-p65), siRNA knockdown of PHACTR1 and MRTF-A, immunofluorescence for p65 nuclear translocation, flow cytometry for ROS, western blotting Atherosclerosis Medium 30293016
2023 Endothelial PHACTR1 acts as a transcriptional corepressor of PPARγ: PHACTR1 binds PPARγ through corepressor motifs. PHACTR1 is enriched in endothelial cell nuclei under disturbed flow conditions but shuttles to the cytoplasm under laminar flow. Global or EC-specific Phactr1 knockout in ApoE-/- mice significantly inhibits atherosclerosis in disturbed-flow regions. RNA sequencing identified PPARγ as the top transcription factor regulating differentially expressed genes upon Phactr1 depletion. PPARγ antagonist GW9662 abolishes the protective effects of Phactr1 KO on endothelial activation and atherosclerosis in vivo. EC-specific and global Phactr1 knockout mice (crossed with ApoE-/- on high-fat diet), RNA sequencing, immunostaining for PHACTR1 localization under different flow conditions, co-immunoprecipitation/binding assay for PHACTR1-PPARγ interaction, PPARγ pharmacological antagonism in vivo, siRNA knockdown in HUVECs Arteriosclerosis, thrombosis, and vascular biology High 37199156
2017 PHACTR1 expression in smooth muscle cells modulates vascular calcification: overexpression of Phactr1 in mESC-derived SMCs enhances mineralization and increases osteopontin expression, while downregulation decreases calcification. This was demonstrated in both murine embryonic stem cell-derived SMCs and primary human aortic SMCs. Stable overexpression and knockdown of Phactr1 in mESCs differentiated to SMCs, osteogenic differentiation assay, calcium phosphate deposit quantification, RT-PCR for osteopontin, primary human aortic SMC validation Biochemical and biophysical research communications Medium 28720499
2017 Phactr1 is expressed in developing mouse brain in a developmental stage- and tissue-dependent manner; it localizes to axons, dendrites, and synapses in primary hippocampal neurons and is enriched in synaptosomal and postsynaptic density fractions. In embryonic cortical neurons Phactr1 accumulates in the nucleus, whereas postnatally it distributes diffusely in the cell body. Western blotting with specific antibody, immunohistochemistry, subcellular fractionation (synaptosomal/PSD fractions), immunofluorescence in primary cultured hippocampal neurons Neuroscience research Medium 28803787
2021 Phactr1 interacts with ROCK2 during osteogenic but not adipogenic differentiation of BMSCs (Co-IP). Phactr1 overexpression inhibits osteogenesis (suppresses Runx2 increase) and promotes adipogenesis (increases C/EBPα), while knockdown has opposite effects. ROCK2 inhibition with KD025 reverses Phactr1 effects on both differentiation pathways, placing Phactr1 upstream of RhoA/ROCK2 in BMSC fate determination. Co-immunoprecipitation (Phactr1-ROCK2), lentiviral overexpression and siRNA knockdown of Phactr1, ROCK2 inhibitor KD025, osteogenic/adipogenic differentiation assays (alizarin red, Oil Red O), western blotting for Runx2, C/EBPα, RhoA, ROCK2 Journal of molecular histology Medium 34709489
2020 Phactr1 deficiency in macrophages promotes M1 polarization and foam cell formation. Mechanistically, Phactr1 activates CREB signaling by directly binding to CREB, upregulating CREB phosphorylation and inducing KLF4 expression. KLF4 overexpression partially rescues the excessive inflammation and foam cell formation caused by Phactr1 deficiency. In Phactr1-/-Apoe-/- double-knockout mice, more severe atherosclerotic plaques with elevated proinflammatory cytokines were observed; bone marrow transplant experiments confirmed the protective effect is hematopoietic cell-autonomous. Co-immunoprecipitation (Phactr1-CREB binding), Phactr1-/- Apoe-/- double-knockout mice, bone marrow transplantation, macrophage polarization assays, KLF4 overexpression rescue, western blotting for CREB phosphorylation, foam cell assays Clinical science Medium 32857129
2021 A de novo PHACTR1 missense variant (p.L519R) reduces G-actin binding affinity and increases complex formation with the PP1 catalytic subunit (PPP1CA), as shown by in vitro binding assays. This leads to altered subcellular localization of PHACTR1 and increased ability to induce cytoskeletal rearrangements. In vitro binding assays for G-actin and PP1 affinity, subcellular localization imaging of mutant vs. wild-type PHACTR1 Clinical genetics Medium 33463715
2015 Phactr-1 downregulation in endothelial cells (via inhibition of VEGF-A165/NRP-1/VEGF-R1 signaling with antagonist peptides targeting VEGF exon 7 and 8 cysteine residues) induces expression of MMP regulators (TIMP-1/-2, RECK), inhibits focal adhesion kinases (FAK/PYK2/PAXILLIN) and metabolic stress pathways (AMPK/CREB/eNOS), and upregulates pro-atherogenic/pro-inflammatory factors including CD36, clusterin, cadherin-13, thrombin, PAR-1, ADAM-9/-17, thrombospondin-2, galectin-3, SSAO, and βIG-H3. Antagonist peptide inhibition of VEGF-A165/NRP-1/VEGFR-1, PHACTR1 knockdown in endothelial cells, proteomics/western blotting for downstream pathway components Biochimie Low 26362351
2022 PHACTR1 overexpression in endothelial cells activates NF-κB-dependent ICAM1 and VCAM1 expression and reduces nitric oxide generation by inhibiting Akt/eNOS activation. A proteomic study validated that PHACTR1 interacts with HSPA8 (heat shock protein A8), which is associated with eNOS degradation. RNA sequencing after PHACTR1 OE/KD, NF-κB reporter assays, NO production assays, Akt/eNOS phosphorylation western blotting, co-immunoprecipitation/proteomics for PHACTR1-HSPA8 interaction Frontiers in immunology Low 36091033
2024 BDNF stimulation of primary cortical neurons causes sustained downregulation of PHACTR1 (and PHACTR2/3 but not PHACTR4) mRNA, and this downregulation is blocked by the ERK/MAPK inhibitor U0126, establishing that BDNF regulates PHACTR1 expression through the ERK/MAPK pathway. BDNF stimulation of primary cultured cortical neurons, qRT-PCR for PHACTR family mRNA, pharmacological inhibition with U0126 Drug discoveries & therapeutics Low 39183043
2023 PHACTR1 promotes invasion and migration of papillary thyroid carcinoma cells by inducing F-actin formation; overexpression increases F-actin fluorescence intensity and promotes invasion/migration, while knockdown inhibits these processes. The pro-invasive effect of PHACTR1 overexpression is reversed by the F-actin disruptor swinholide A, confirming dependence on F-actin assembly. PHACTR1 siRNA knockdown and overexpression in PTC cell lines, invasion/migration assays (Transwell), F-actin staining, pharmacological disruption with swinholide A Heliyon Low 37876444
2024 Multi-omics profiling (transcriptomics, proteomics, metabolomics, lipidomics) of HT1080 cells with PHACTR1 overexpression or knockdown reveals that PHACTR1 governs cell cycle progression (altering key regulatory proteins), regulates cellular iron metabolism (including iron-storage proteins), and is detected within mitochondria where it directs mitochondrial morphology and bioenergetics through a signaling axis involving AKAP1 and Drp1. Multi-omics (transcriptomics, proteomics, metabolomics, lipidomics) in PHACTR1 OE/KD HT1080 cells; validation in primary endothelial cells; mitochondrial fractionation/localization; western blotting for AKAP1/Drp1 Communications biology Medium 41554990
2024 AlphaFold-Multimer modeling and analysis of PHACTR1 missense variants in patients indicates that the RPEL3 domain is the site of overlapping binding interfaces for G-actin and PP1 (PPP1CA), suggesting competition between G-actin and PP1 for PHACTR1 binding at this domain. Variants clustering at the PHACTR1-PPP1CA or PHACTR1-G-actin interfaces consistently cause infantile epileptic spasms syndrome. AlphaFold-Multimer structural prediction, genotype-phenotype correlation in patient cohort (whole-exome sequencing), domain-level variant analysis Journal of medical genetics Low 38272663

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection. Nature genetics 168 25420145
2019 Association of the PHACTR1/EDN1 Genetic Locus With Spontaneous Coronary Artery Dissection. Journal of the American College of Cardiology 157 30621952
2016 PHACTR1 Is a Genetic Susceptibility Locus for Fibromuscular Dysplasia Supporting Its Complex Genetic Pattern of Inheritance. PLoS genetics 140 27792790
2011 Neuropilin-1 regulates a new VEGF-induced gene, Phactr-1, which controls tubulogenesis and modulates lamellipodial dynamics in human endothelial cells. Cellular signalling 66 21939755
2013 MicroRNA-584 and the protein phosphatase and actin regulator 1 (PHACTR1), a new signaling route through which transforming growth factor-β Mediates the migration and actin dynamics of breast cancer cells. The Journal of biological chemistry 65 23479725
2012 G-actin regulates the shuttling and PP1 binding of the RPEL protein Phactr1 to control actomyosin assembly. Journal of cell science 55 22976292
2011 Depletion of the novel protein PHACTR-1 from human endothelial cells abolishes tube formation and induces cell death receptor apoptosis. Biochimie 55 21798305
2012 Genome-wide association study in a Lebanese cohort confirms PHACTR1 as a major determinant of coronary artery stenosis. PloS one 47 22745674
2021 Deficiency of macrophage PHACTR1 impairs efferocytosis and promotes atherosclerotic plaque necrosis. The Journal of clinical investigation 44 33630758
2016 Genetic and environmental risk factors for atherosclerosis regulate transcription of phosphatase and actin regulating gene PHACTR1. Atherosclerosis 37 27187934
2018 De novo PHACTR1 mutations in West syndrome and their pathophysiological effects. Brain : a journal of neurology 35 30256902
2015 Disruption of phactr-1 pathway triggers pro-inflammatory and pro-atherogenic factors: New insights in atherosclerosis development. Biochimie 35 26362351
2017 Coronary artery disease associated gene Phactr1 modulates severity of vascular calcification in vitro. Biochemical and biophysical research communications 34 28720499
2020 Molecular basis for substrate specificity of the Phactr1/PP1 phosphatase holoenzyme. eLife 29 32975518
2018 PHACTR1 regulates oxidative stress and inflammation to coronary artery endothelial cells via interaction with NF-κB/p65. Atherosclerosis 23 30293016
2018 PHACTR1 splicing isoforms and eQTLs in atherosclerosis-relevant human cells. BMC medical genetics 18 29884117
2020 Genetic deficiency of Phactr1 promotes atherosclerosis development via facilitating M1 macrophage polarization and foam cell formation. Clinical science (London, England : 1979) 17 32857129
2019 Phosphatase Actin Regulator-1 (PHACTR-1) Knockdown Suppresses Cell Proliferation and Migration and Promotes Cell Apoptosis in the bEnd.3 Mouse Brain Capillary Endothelial Cell Line. Medical science monitor : international medical journal of experimental and clinical research 16 30772888
2022 PHACTR1, a coronary artery disease risk gene, mediates endothelial dysfunction. Frontiers in immunology 15 36091033
2016 PHACTR1 Gene Polymorphism Is Associated with Increased Risk of Developing Premature Coronary Artery Disease in Mexican Population. International journal of environmental research and public health 15 27517945
2015 The rs12526453 Polymorphism in an Intron of the PHACTR1 Gene and Its Association with 5-Year Mortality of Patients with Myocardial Infarction. PloS one 15 26086777
2023 Endothelial PHACTR1 Promotes Endothelial Activation and Atherosclerosis by Repressing PPARγ Activity Under Disturbed Flow in Mice. Arteriosclerosis, thrombosis, and vascular biology 14 37199156
2022 PHACTR-1 (Phosphatase and Actin Regulator 1) Deficiency in Either Endothelial or Smooth Muscle Cells Does Not Predispose Mice to Nonatherosclerotic Arteriopathies in 3 Transgenic Mice. Arteriosclerosis, thrombosis, and vascular biology 14 35387477
2019 PHACTR1 gene polymorphism with the risk of coronary artery disease in Chinese Han population. Postgraduate medical journal 14 30777881
2019 Phactr1 regulates Slack (KCNT1) channels via protein phosphatase 1 (PP1). FASEB journal : official publication of the Federation of American Societies for Experimental Biology 14 31914597
2018 Expression and purification of human phosphatase and actin regulator 1 (PHACTR1) in plant-based systems. Protein expression and purification 13 29894805
2017 Expression analyses of Phactr1 (phosphatase and actin regulator 1) during mouse brain development. Neuroscience research 13 28803787
2017 PHACTR1 and SLC22A3 gene polymorphisms are associated with reduced coronary artery disease risk in the male Chinese Han population. Oncotarget 12 27893421
2023 PHACTR1 modulates vascular compliance but not endothelial function: a translational study. Cardiovascular research 11 35653516
2021 A Study of Associations Between rs9349379 (PHACTR1), rs2891168 (CDKN2B-AS), rs11838776 (COL4A2) and rs4880 (SOD2) Polymorphic Variants and Coronary Artery Disease in Iranian Population. Biochemical genetics 9 34109516
2016 Possible role of intronic polymorphisms in the PHACTR1 gene on the development of cardiovascular disease. Medical hypotheses 9 27876132
2021 Mutation in PHACTR1 associated with multifocal epilepsy with infantile spasms and hypsarrhythmia. Clinical genetics 8 33463715
2020 PHACTR1 is associated with disease progression in Chinese Moyamoya disease. PeerJ 7 32411507
2022 PECAM1, COL4A2, PHACTR1, and LMOD1 Gene Polymorphisms in Patients with Unstable Angina. Journal of clinical medicine 6 35054067
2020 Associations between PHACTR1 gene polymorphisms and pulse pressure in Chinese Han population. Bioscience reports 6 32420588
2018 PHACTR1 genotype predicts coronary artery disease in patients with familial hypercholesterolemia. Journal of clinical lipidology 6 29784573
2024 Genotype and phenotype correlation of PHACTR1-related neurological disorders. Journal of medical genetics 5 38272663
2023 Genetic Variants in PHACTR1 & LPL Mediate Restenosis Risk in Coronary Artery Patients. Vascular health and risk management 5 36814994
2021 Phactr1 negatively regulates bone mass by inhibiting osteogenesis and promoting adipogenesis of BMSCs via RhoA/ROCK2. Journal of molecular histology 4 34709489
2024 PHACTR1 and APOC1 genetic variants are associated with multi-vessel coronary artery disease. Lipids in health and disease 3 39395990
2022 Genome-Wide Transcriptional Profiling Reveals PHACTR1 as a Novel Molecular Target of Resveratrol in Endothelial Homeostasis. Nutrients 3 36364780
2021 The association of polymorphism in PHACTR1 rs9349379 and rs12526453 with coronary artery atherosclerosis or coronary artery calcification. A systematic review. Coronary artery disease 3 33660664
2021 PHACTR1 genetic variability is not critical in small vessel ischemic disease patients and PcomA recruitment in C57BL/6J mice. Scientific reports 3 33727568
2020 Differential expression of PHACTR1 in atheromatous versus normal carotid artery tissue. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 3 31980275
2024 Circular RNA hsa_circ_0002268 (PHACTR1) Is Specific to Gestational Diabetes Mellitus in a Polish Pregnant Population. International journal of molecular sciences 2 39000149
2024 The BDNF-ERK/MAPK axis reduces phosphatase and actin regulator1, 2 and 3 (PHACTR1, 2 and 3) mRNA expressions in cortical neurons. Drug discoveries & therapeutics 2 39183043
2023 PHACTR1 promotes the mobility of papillary thyroid carcinoma cells by inducing F-actin formation. Heliyon 2 37876444
2023 Mechanism of PWAR6 regulating cisplatin drug sensitivity in non-small cell lung cancer through miR-577/PHACTR1. Gene 2 37923092
2019 PHACTR1 haplotypes are associated with carotid plaque presence and affect PHACTR1 mRNA expression in carotid plaque tissue. Gene 2 31200082
2022 Epileptic Encephalopathy with Variants in the PHACTR1 and AFF2 Genes: A Case Report. Cytogenetic and genome research 1 36535243
2021 Association of PHACTR1 intronic variants with the first myocardial infarction and their effect on PHACTR1 mRNA expression in PBMCs. Gene 1 33460763
2026 Multi-omic analysis of human PHACTR1 signaling networks. Communications biology 0 41554990
2025 Coronary Artery Disease Risk Variant rs6903956 Links to Endothelial Dysfunction via PHACTR1 Regulation. bioRxiv : the preprint server for biology 0 40654905
2025 Genetic Basis of Hypsarrhythmia: Expanding the PHACTR1 Spectrum and Pathway to Targeted Therapy. Clinical genetics 0 41054829
2024 Association of PHACTR1 with Coronary Artery Calcium Differs by Sex and Cigarette Smoking. Journal of cardiovascular development and disease 0 39057616
2024 Correction: Dłuski et al. Circular RNA hsa_circ_0002268 (PHACTR1) Is Specific to Gestational Diabetes Mellitus in a Polish Pregnant Population. Int. J. Mol. Sci. 2024, 25, 7040. International journal of molecular sciences 0 39769512

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