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Showing RMDN3 — PTPIP51 is a alias.

RMDN3

Regulator of microtubule dynamics protein 3 · UniProt Q96TC7

Length
470 aa
Mass
52.1 kDa
Annotated
2026-06-10
48 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RMDN3 (PTPIP51) is an outer mitochondrial membrane protein that physically tethers mitochondria to the endoplasmic reticulum by binding the ER protein VAPB, establishing mitochondria-associated ER membranes (MERCs/MAMs) that govern interorganelle Ca2+ and lipid exchange (PMID:22131369, PMID:33938112). Mitochondrial targeting requires its N-terminal transmembrane domain (PMID:16820967), while the VAPB interaction is mediated principally by a coiled-coil domain in PTPIP51 acting together with an FFAT-like motif that engages the MSP domain of VAPB (PMID:33938112, PMID:36120587). Through this tether, RMDN3 supports IP3 receptor-mediated transfer of Ca2+ from ER to mitochondria, and its loss or disruption perturbs mitochondrial Ca2+ uptake (PMID:22131369, PMID:36120587). A crystallized TPR domain confers lipid binding and transfer activity: RMDN3 binds and transfers phosphatidic acid, contributes to mitochondrial cardiolipin content (PMID:33938112), and under mitochondrial ROS transfers lipid radicals from mitochondria to the ER, defining a survival function in removing damaging oxidized lipids (PMID:39929810). The strength of tethering is set by post-translational regulation — RMDN3 phosphorylation enhances contact formation under oxidative stress (PMID:39929810), MITOL/MARCH5-mediated ubiquitination at K89 activates its PA-binding activity (PMID:34964862), and RHOA binding to VAPB tunes complex assembly (PMID:41392169). Functionally, the tether constrains autophagosome formation (PMID:28132811), shapes mitochondria-SR contacts and Ca2+-dependent apoptosis in cardiomyocytes (PMID:28345618), and supports synaptic activity and dendritic spine morphology in neurons (PMID:30841933). The tether is a convergence point for ALS/FTD pathology: TDP-43 and FUS disrupt the VAPB-PTPIP51 interaction through GSK-3β activation, and tether disruption is observed in ALS patient motor neurons (PMID:24893131, PMID:27418313, PMID:36051435). Independently of its tethering role, PTPIP51 acts as a 14-3-3-dependent scaffold for Raf-1 in the MAPK cascade, regulated by c-Src phosphorylation at Y176 (PMID:18771726, PMID:22544307).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2006 Medium

    Established that PTPIP51 is a mitochondrial protein whose localization depends on its N-terminal transmembrane domain and which can drive intrinsic apoptosis, anchoring its membrane topology before its tethering role was known.

    Evidence GFP-fusion localization and TM deletion mutants with mitochondrial membrane potential, cytochrome c, caspase-3 and Annexin V readouts

    PMID:16820967

    Open questions at the time
    • Did not connect mitochondrial localization to ER contact sites
    • Apoptosis driven by overexpression; physiological relevance untested
  2. 2011 High

    Identified the direct PTPIP51-VAPB interaction and showed it is required for ER-to-mitochondria Ca2+ transfer, defining PTPIP51 as a MAM tethering partner.

    Evidence Reciprocal Co-IP, siRNA knockdown, mitochondrial Ca2+ uptake assays and MAM fractionation

    PMID:22131369

    Open questions at the time
    • Interaction interface on PTPIP51 not yet mapped
    • Did not establish whether tethering is structural cause or correlate of Ca2+ defect
  3. 2011 Medium

    Showed PTPIP51 is tyrosine-176 phosphorylated by Lyn and c-Src and interacts with c-Kit in AML, defining a kinase-regulated signaling role distinct from tethering.

    Evidence IHC, proximity ligation assay and immunoblot in AML blasts lacking the cognate phosphatase PTP1B

    PMID:21513978

    Open questions at the time
    • In situ interaction assays without biochemical reconstitution
    • Causal contribution to leukemic proliferation not directly tested
  4. 2008 Medium

    Defined PTPIP51 as a 14-3-3-dependent scaffold linking to Raf-1 and activating ERK to control cell morphology and motility, separate from its mitochondrial functions.

    Evidence Migration/adhesion assays, dominant-negative Raf-1/Ras and MEK inhibitor epistasis, Co-IP and deletion mapping of 14-3-3 sites

    PMID:18771726

    Open questions at the time
    • Relationship between scaffold and tether pools of PTPIP51 unclear
    • Endogenous physiological setting not defined
  5. 2012 Medium

    Established that c-Src phosphorylation at Y176 and PTP1B dephosphorylation toggle PTPIP51's association with 14-3-3β and Raf-1, providing a switch controlling the MAPK scaffold.

    Evidence Pharmacological c-Src/PTP1B modulation with proximity ligation assays in keratinocytes

    PMID:22544307

    Open questions at the time
    • No direct phosphosite mutagenesis in functional MAPK output
    • Interactions inferred from in situ proximity, not reconstituted
  6. 2014 High

    Showed the VAPB-PTPIP51 interaction physically tethers ER to mitochondria and that TDP-43 disrupts it via GSK-3β, placing the tether downstream of an ALS/FTD insult and identifying GSK-3β as an upstream negative regulator.

    Evidence Co-IP, EM contact quantification, Ca2+ imaging and GSK-3β kinase assays

    PMID:24893131

    Open questions at the time
    • GSK-3β substrate site on the tether not identified
    • Whether GSK-3β acts on PTPIP51 or VAPB unresolved
  7. 2016 High

    Extended the GSK-3β-dependent tether-disruption mechanism to FUS, showing convergent ALS/FTD pathology on VAPB-PTPIP51 with impaired Ca2+ uptake and ATP production.

    Evidence Co-IP, EM, mitochondrial Ca2+/ATP assays and GSK-3β inhibitor experiments

    PMID:27418313

    Open questions at the time
    • Direct molecular target of GSK-3β still unmapped
    • In vivo relevance in FUS models not addressed
  8. 2017 High

    Demonstrated the tether regulates autophagy through Ca2+ delivery, using a synthetic ER-mitochondria linker to prove causality of contact tightness on autophagosome formation.

    Evidence siRNA, overexpression, synthetic linker rescue and autophagosome quantification with Ca2+ measurements

    PMID:28132811

    Open questions at the time
    • Downstream autophagy machinery linkage not detailed
    • Ca2+ target effectors not identified
  9. 2017 High

    Established a tissue-specific role in cardiomyocytes where PTPIP51 sets mitochondria-SR contact and MCU-dependent Ca2+ uptake, with cardiac knockdown protective against ischemia/reperfusion injury.

    Evidence Adenoviral overexpression, cardiac-specific knockdown, EM, MCU epistasis and infarct size measurement in vivo

    PMID:28345618

    Open questions at the time
    • Whether VAPB is the relevant ER partner in cardiomyocytes untested
    • Upstream regulation in the heart unknown
  10. 2019 High

    Showed the tether operates at neuronal synapses and is activity-dependent, with loss perturbing synaptic function and spine morphology, linking interorganelle contacts to neuronal physiology.

    Evidence Immunofluorescence, proximity ligation assay, activity-evoked Ca2+ imaging and siRNA with synaptic readouts

    PMID:30841933

    Open questions at the time
    • Molecular link between activity and increased contact undefined
    • In vivo synaptic phenotype not established
  11. 2021 High

    Provided the structural basis for lipid handling by crystallizing the TPR domain and demonstrating PTPIP51 binds and transfers phosphatidic acid, contributing to mitochondrial cardiolipin, and mapped VAPB binding to an FFAT-like motif engaging the MSP domain.

    Evidence X-ray crystallography, in vitro phospholipid transfer assays, cardiolipin measurement and motif mutagenesis

    PMID:33938112

    Open questions at the time
    • In-cell directionality and flux of PA transfer not quantified
    • Relationship between lipid transfer and Ca2+ functions unresolved
  12. 2022 High

    Refined the interaction interface by showing the coiled-coil domain, not the FFAT motif alone, is essential for VAPB binding and tethering in full-length proteins, revising the binding model in cells.

    Evidence Co-IP with deletion/mutation constructs, EM contact quantification and IP3R-mediated Ca2+ assays

    PMID:36120587

    Open questions at the time
    • Apparent discordance with FFAT-based in vitro model not fully reconciled
    • Structure of the coiled-coil/VAPB interface unknown
  13. 2022 High

    Identified MITOL/MARCH5 ubiquitination of RMDN3 at K89 as an activating modification for its PA-binding activity, adding post-translational control over lipid-transfer function.

    Evidence APEX2 proximity labeling, Co-IP, K89R mutagenesis and in vitro PA-binding assay

    PMID:34964862

    Open questions at the time
    • Whether ubiquitination affects tethering or only lipid binding unclear
    • In-cell consequences for cardiolipin/PA flux not measured
  14. 2022 Medium

    Confirmed disease relevance by showing reduced VAPB levels and disrupted tethers in human ALS spinal cord motor neurons, translating cell-model findings to patient tissue.

    Evidence Proximity ligation assay in post-mortem human spinal cord and VAPB immunoblotting

    PMID:36051435

    Open questions at the time
    • Correlative tissue analysis, not causal
    • Whether tether loss precedes or follows neurodegeneration unknown
  15. 2022 Medium

    Described a tether-independent PTPIP51-PTEN-CK2 complex that drives EGFR lysosomal degradation and suppresses growth signaling in NSCLC, broadening PTPIP51's signaling repertoire.

    Evidence Co-IP, EGFR ubiquitylation and lysosomal inhibitor assays, downstream signaling immunoblots and xenograft

    PMID:35240162

    Open questions at the time
    • How a mitochondrial protein accesses PTEN/EGFR machinery unclear
    • Single lab; mechanism of CK2 recruitment undefined
  16. 2024 Medium

    Demonstrated therapeutic tractability by rescuing TDP-43-induced tether and synaptic defects with VAPB/PTPIP51 overexpression and with UDCA acting through GSK-3β inhibition.

    Evidence Overexpression rescue, Ca2+ and synaptic assays, UDCA treatment and GSK-3β activity assays

    PMID:38395965

    Open questions at the time
    • In vivo efficacy not established
    • GSK-3β substrate on the tether still unidentified
  17. 2025 High

    Defined a cell-survival function of the tether in oxidative stress: RMDN3 phosphorylation increases MERCs and the TPR domain transfers lipid radicals from mitochondria to ER, preventing toxic accumulation.

    Evidence NanoBiT/MERBiT live-cell MERC assay, in vitro liposome lipid radical transfer, phosphorylation analysis and disruption with cell death readouts

    PMID:39929810

    Open questions at the time
    • Phosphosite(s) and responsible kinase not fully defined
    • Fate of transferred lipid radicals in the ER not traced
  18. 2025 High

    Identified RHOA as an upstream tuner of the tether through binding VAPB and CUL3-regulated turnover, integrating a small-GTPase axis into MERC control.

    Evidence Genome-wide CRISPRi screen, RHOA-VAPB Co-IP, MERCS quantification and disease allele analysis

    PMID:41392169

    Open questions at the time
    • Whether RHOA binds PTPIP51 directly not shown (binds VAPB)
    • Downstream effector linking RHOA to contact formation undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple regulatory inputs (phosphorylation, K89 ubiquitination, RHOA tuning, GSK-3β disruption) are integrated to set tether strength, and how the lipid-transfer versus Ca2+-transfer functions are coordinated, remains unresolved.
  • No unified model coupling lipid and Ca2+ transfer
  • GSK-3β phosphorylation site on the tether unidentified
  • Structure of the full PTPIP51-VAPB tethering interface unsolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0060090 molecular adaptor activity 3 GO:0140104 molecular carrier activity 2
Localization
GO:0005739 mitochondrion 3 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-1430728 Metabolism 2 R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 1
Partners
CGI-99MARCH5PTENPTPN1RAF1RHOASNCAVAPB
Complex memberships
PTPIP51-PTEN-CK2 complexPTPIP51-Raf-1-14-3-3 scaffoldVAPB-PTPIP51 ER-mitochondria tether

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 PTPIP51 (outer mitochondrial membrane protein) directly interacts with the ER-resident protein VAPB, and this interaction is required for normal mitochondrial Ca2+ uptake following release from ER stores. VAPB is a MAM (mitochondria-associated membrane) protein, and loss of either VAPB or PTPIP51 perturbs Ca2+ homeostasis. The ALS-linked VAPBP56S mutant shows altered binding to PTPIP51 and dysregulated Ca2+ uptake. Co-immunoprecipitation, siRNA knockdown, mitochondrial Ca2+ uptake assays, subcellular fractionation (MAM isolation) Human molecular genetics High 22131369
2014 VAPB-PTPIP51 interaction tethers ER to mitochondria. TDP-43 (ALS/FTD-linked) disrupts this interaction and ER-mitochondria associations, perturbing Ca2+ homeostasis. TDP-43 overexpression activates GSK-3β, and GSK-3β regulates the VAPB-PTPIP51 interaction, placing GSK-3β as an upstream negative regulator of the tether. Co-immunoprecipitation, electron microscopy (ER-mitochondria contact quantification), Ca2+ imaging, GSK-3β kinase activity assays, siRNA Nature communications High 24893131
2016 ALS/FTD-associated FUS disrupts the VAPB-PTPIP51 interaction and ER-mitochondria associations, leading to impaired mitochondrial Ca2+ uptake and reduced mitochondrial ATP production. FUS activates GSK-3β, which mediates these disruptions, consistent with a shared GSK-3β-dependent mechanism for ALS/FTD insults on the VAPB-PTPIP51 tether. Co-immunoprecipitation, electron microscopy, mitochondrial Ca2+ and ATP assays, GSK-3β inhibitor experiments EMBO reports High 27418313
2017 The VAPB-PTPIP51 ER-mitochondria tethers regulate autophagy. Overexpression of VAPB or PTPIP51 (tightening contacts) impairs autophagosome formation, while siRNA-mediated knockdown (loosening contacts) stimulates it. An artificial ER-mitochondria linker rescues the effects of VAPB/PTPIP51 siRNA on autophagy, demonstrating that this is a direct consequence of tethering. The mechanism involves Ca2+ delivery from ER to mitochondria. siRNA knockdown, VAPB/PTPIP51 overexpression, synthetic ER-mitochondria linker rescue, autophagosome quantification (fluorescence microscopy), Ca2+ measurements Current biology : CB High 28132811
2017 PTPIP51 regulates mitochondria-sarcoplasmic reticulum (SR) contact in cardiomyocytes. Overexpression of PTPIP51 increases mitochondria-SR contacts and elevates mitochondrial Ca2+ uptake via the mitochondrial Ca2+ uniporter (MCU). Cardiac-specific knockdown of PTPIP51 reduces myocardial infarct size and injury after ischemia/reperfusion. MCU inhibition/knockdown reverses PTPIP51-mediated mitochondrial Ca2+ increase and cardiomyocyte apoptosis. Adenovirus-mediated overexpression, cardiac-specific knockdown, electron microscopy (contact quantification), mitochondrial Ca2+ assays, MCU inhibitor/siRNA epistasis, infarct size measurement Scientific reports High 28345618
2019 VAPB and PTPIP51 localize to neuronal synapses and form contacts there. Stimulating neuronal activity increases ER-mitochondria contacts and the VAPB-PTPIP51 interaction. siRNA loss of VAPB or PTPIP51 perturbs synaptic function and dendritic spine morphology, demonstrating a role for the tether in synaptic activity. Immunofluorescence co-localization, proximity ligation assay, live-cell Ca2+ imaging upon neuronal stimulation, siRNA knockdown with synaptic activity and spine morphology readouts Acta neuropathologica communications High 30841933
2021 Crystal structure of the TPR domain of PTPIP51 reveals an archetypal TPR fold with a lipid-like molecule in the binding pocket. PTPIP51 binds and transfers phospholipids, particularly phosphatidic acid (PA), in vitro. Depletion of PTPIP51 reduces mitochondrial cardiolipin levels. The PTPIP51-VAPB interaction is mediated by an FFAT-like motif in PTPIP51 and the MSP domain of VAPB. X-ray crystallography (TPR domain structure), in vitro phospholipid binding/transfer assays, siRNA knockdown with cardiolipin measurement, mutational analysis of FFAT-like motif and MSP domain EMBO reports High 33938112
2022 The coiled-coil domain of PTPIP51 (not the FFAT motif alone) is essential for VAPB binding in the context of full-length proteins in cells, for formation of ER-mitochondria contacts, and for IP3 receptor-mediated delivery of Ca2+ from ER to mitochondria. Deletion of the FFAT motif had little effect on VAPB binding, while mutation/deletion of the coiled-coil domain markedly reduced binding and abrogated tethering and Ca2+ transfer functions. Immunoprecipitation from transfected cells with deletion/mutation constructs, electron microscopy (ER-mitochondria contact quantification), IP3R-mediated Ca2+ delivery assays Frontiers in cell and developmental biology High 36120587
2022 The mitochondrial E3 ubiquitin ligase MITOL/MARCH5 interacts with and ubiquitinates RMDN3/PTPIP51 at lysine residue 89. Loss of MITOL or K89R substitution in RMDN3 significantly reduces its phosphatidic acid (PA)-binding activity, indicating that MITOL-mediated ubiquitination activates RMDN3 PA-transfer activity at the mitochondria-ER contact site. Proximity-dependent biotin labeling (APEX2), Co-IP, site-directed mutagenesis (K89R), in vitro PA-binding assay Journal of biochemistry High 34964862
2025 Mitochondrial ROS increases MERC (mitochondria-ER contact) formation via RMDN3-VAPB tethering driven by RMDN3 phosphorylation. RMDN3 transfers lipid radicals from mitochondria to the ER via its TPR domain (demonstrated by in vitro liposome assay). Disruption of RMDN3-VAPB tethering causes lipid radical accumulation in mitochondria and cell death, defining a cell survival role for MERCs in lipid radical removal under mitochondrial damage. NanoBiT/MERBiT split-luciferase system for live-cell MERC measurement, in vitro liposome lipid radical transfer assay, RMDN3 phosphorylation analysis, siRNA/genetic disruption with lipid radical and cell death readouts Nature communications High 39929810
2006 PTPIP51 is a mitochondrial protein requiring its N-terminal transmembrane (TM) domain for mitochondrial targeting. Overexpression induces apoptosis via decrease in mitochondrial membrane potential, cytochrome c release, caspase-3 activation, PARP cleavage, and phosphatidylserine externalization. Deletion of the TM domain prevents mitochondrial localization and abrogates apoptosis-inducing function. GFP-fusion subcellular localization, deletion mutant analysis, mitochondrial membrane potential assay (JC-1), cytochrome c release assay, caspase-3 and PARP cleavage, Annexin V staining Apoptosis : an international journal on programmed cell death Medium 16820967
2008 PTPIP51 regulates cell morphology and motility via the Raf-MEK-ERK cascade. It interacts with Raf-1 through 14-3-3 scaffold proteins and activates ERK; this is blocked by MEK inhibitor or dominant-negative Raf-1 but not dominant-negative Ras. Two redundant 14-3-3-binding domains in PTPIP51 were identified by deletion/mutation analysis. Overexpression/siRNA knockdown with migration/adhesion assays, MEK inhibitor and dominant-negative Raf-1/Ras epistasis, Co-IP for Raf-1/14-3-3 interaction, deletion/mutation analysis of 14-3-3-binding domains Cellular signalling Medium 18771726
2012 Tyrosine 176 phosphorylation of PTPIP51 by c-Src regulates its interaction with 14-3-3β and Raf-1. Increased phosphorylation at Y176 causes a sharp drop in PTPIP51-14-3-3β and 14-3-3β-Raf-1 interactions. Phosphorylation status also regulates PTPIP51 interactions with DAGKα and PKA. Pharmacological modulation of c-Src activity and PTP1B phosphatase inhibition in HaCaT keratinocytes, proximity ligation assay (Duolink) for protein interactions, confocal microscopy Cell biochemistry and biophysics Medium 22544307
2012 PTPIP51 interacts with CGI-99 and Nuf2 in vitro and in vivo, and the PTPIP51/CGI-99 and PTPIP51/Nuf-2 complexes localize to the equatorial region during mitosis. PTPIP51 associates with the microtubular cytoskeleton and spindle apparatus. Phosphorylated PTPIP51 accumulates at spindle poles. During M/G1 transition, PTPIP51 interacts strongly with PTP1B, restoring PTPIP51-Raf-1 interaction that is depleted in mitotic cells. Proximity ligation assay (Duolink), confocal microscopy, cell synchronization with nocodazole Biomolecules Medium 24970130
2011 PTPIP51 is phosphorylated at tyrosine 176 by Lyn and c-Src kinases in AML cells. In AML blasts, PTP1B (the cognate phosphatase for PTPIP51) is absent, preventing dephosphorylation. PTPIP51 interacts with c-Kit in AML cells, identifying it as a component of c-Kit signaling. The hyperphosphorylation prevents PTPIP51-Raf-1 interaction, contributing to increased MAPK-driven proliferation. Immunohistochemistry with peptide-specific antibodies, proximity ligation assay, confocal co-localization, immunoblot Leukemia research Medium 21513978
2025 RHOA (small GTPase) binds to the ER protein VAPB and regulates complex formation between VAPB and mitochondrial PTPIP51, thereby tuning MERCS levels. RHOA knockdown or increased degradation via CUL3 overexpression reduces MERCS; RHOA upregulation increases MERCS. Disease alleles of RHOA, CUL3, and VAPB perturb this regulatory mechanism. Genome-wide CRISPRi screen, Co-IP (RHOA-VAPB binding), MERCS quantification upon RHOA/CUL3 manipulation, disease allele analysis Nature communications High 41392169
2022 VAPB protein levels are reduced and VAPB-PTPIP51 tethers are disrupted in post-mortem spinal cord motor neurons from ALS patients, as quantified by proximity ligation assay, confirming that disruption of the tether occurs in human ALS tissue. Proximity ligation assay in post-mortem human spinal cord sections, immunoblotting for VAPB levels Frontiers in cell and developmental biology Medium 36051435
2024 Overexpression of VAPB or PTPIP51 corrects mutant TDP43-induced damage to IP3 receptor delivery of Ca2+ to mitochondria and to synaptic function. UDCA (FDA-approved drug) corrects TDP43-linked damage to the VAPB-PTPIP51 interaction by inhibiting TDP43-mediated GSK3β activation, identifying GSK3β inhibition as the mechanism of UDCA action on this tether. VAPB/PTPIP51 overexpression rescue experiments, Ca2+ imaging, synaptic activity assays, UDCA pharmacological treatment, GSK3β activity assays Acta neuropathologica communications Medium 38395965
2022 PTPIP51 interacts with PTEN to form a PTPIP51-PTEN-CK2 complex, which induces phosphorylation of PTEN at Thr382/383. This leads to ubiquitylation and lysosomal degradation of EGFR, thereby suppressing PI3K/Akt, RAS/RAF/ERK, and JAK/STAT3 downstream signaling in NSCLC cells. Co-immunoprecipitation, PTPIP51 overexpression and knockdown, EGFR ubiquitylation assay, lysosomal inhibitor experiments, downstream signaling (immunoblot), in vivo xenograft Life sciences Medium 35240162
2015 PTPIP51 is required for the differentiation of photoreceptors. Silencing of PTPIP51 in postnatal retinal explants severely impairs final differentiation of photoreceptors (decreased rhodopsin-positive cells), while PTPIP51 misexpression does not alter RPC commitment, indicating a specific role in terminal photoreceptor maturation. Ex vivo electroporation for siRNA knockdown and misexpression in postnatal rat retinal explants, immunostaining for rhodopsin and lineage markers Neuroscience Medium 25999297
2015 PTPIP51 forms a complex with RelA and IκBα. RelA bound to the PTPIP51 promoter represses its mRNA and protein expression. TNFα modulates this PTPIP51/RelA/IκBα complex. Direct PTPIP51-RelA and PTPIP51-IκBα interactions were confirmed in situ. Promoter binding assay, proximity ligation assay (Duolink) for direct protein-protein interactions, immunofluorescence co-localization, PDTC/TNFα pharmacological manipulation Biomolecules Low 25893721
2025 Phosphorylation of α-synuclein at serine 129 increases VAPB-PTPIP51 interactions. α-syn interacts directly with PTPIP51, and this interaction is modulated by the phosphorylation state of α-syn at S129 (confirmed by Co-IP and molecular dynamics simulation). Co-immunoprecipitation, mass spectrometry, molecular dynamics simulation, Co-IP in Thy1-SNCA transgenic mouse brain Acta neuropathologica communications Low 39994794

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 ER-mitochondria associations are regulated by the VAPB-PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43. Nature communications 520 24893131
2011 VAPB interacts with the mitochondrial protein PTPIP51 to regulate calcium homeostasis. Human molecular genetics 475 22131369
2017 The ER-Mitochondria Tethering Complex VAPB-PTPIP51 Regulates Autophagy. Current biology : CB 343 28132811
2016 ALS/FTD-associated FUS activates GSK-3β to disrupt the VAPB-PTPIP51 interaction and ER-mitochondria associations. EMBO reports 224 27418313
2019 The VAPB-PTPIP51 endoplasmic reticulum-mitochondria tethering proteins are present in neuronal synapses and regulate synaptic activity. Acta neuropathologica communications 130 30841933
2021 Phospholipid transfer function of PTPIP51 at mitochondria-associated ER membranes. EMBO reports 104 33938112
2017 PTPIP51 regulates mouse cardiac ischemia/reperfusion through mediating the mitochondria-SR junction. Scientific reports 55 28345618
2006 Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is a novel mitochondria protein with an N-terminal mitochondrial targeting sequence and induces apoptosis. Apoptosis : an international journal on programmed cell death 53 16820967
2025 ER-mitochondria contacts mediate lipid radical transfer via RMDN3/PTPIP51 phosphorylation to reduce mitochondrial oxidative stress. Nature communications 42 39929810
2008 PTPIP51, a novel 14-3-3 binding protein, regulates cell morphology and motility via Raf-ERK pathway. Cellular signalling 34 18771726
2024 Modulation of ER-mitochondria tethering complex VAPB-PTPIP51: Novel therapeutic targets for aging-associated diseases. Ageing research reviews 28 38719161
2004 The novel protein PTPIP51 exhibits tissue- and cell-specific expression. Histochemistry and cell biology 28 15609043
2011 PTPIP51, a positive modulator of the MAPK/Erk pathway, is upregulated in glioblastoma and interacts with 14-3-3β and PTP1B in situ. Histology and histopathology 26 21972092
2022 Disruption of the VAPB-PTPIP51 ER-mitochondria tethering proteins in post-mortem human amyotrophic lateral sclerosis. Frontiers in cell and developmental biology 25 36051435
2022 The PTPIP51 coiled-coil domain is important in VAPB binding, formation of ER-mitochondria contacts and IP3 receptor delivery of Ca2+ to mitochondria. Frontiers in cell and developmental biology 25 36120587
2024 Stimulating VAPB-PTPIP51 ER-mitochondria tethering corrects FTD/ALS mutant TDP43 linked Ca2+ and synaptic defects. Acta neuropathologica communications 19 38395965
2012 PTPIP51 in protein interactions: regulation and in situ interacting partners. Cell biochemistry and biophysics 18 22544307
2024 Mitochondria-associated endoplasmic reticulum membranes tethering protein VAPB-PTPIP51 protects against ischemic stroke through inhibiting the activation of autophagy. CNS neuroscience & therapeutics 17 38584329
2010 PTPIP51-a myeloid lineage specific protein interacts with PTP1B in neutrophil granulocytes. Blood cells, molecules & diseases 16 20627780
2008 The novel protein PTPIP51 is expressed in human keratinocyte carcinomas and their surrounding stroma. Journal of cellular and molecular medicine 16 19012732
2006 Epidermal growth factor-, transforming growth factor-beta-, retinoic acid- and 1,25-dihydroxyvitamin D3-regulated expression of the novel protein PTPIP51 in keratinocytes. Cells, tissues, organs 16 17361080
2011 PTPIP51 is phosphorylated by Lyn and c-Src kinases lacking dephosphorylation by PTP1B in acute myeloid leukemia. Leukemia research 15 21513978
2019 Crosstalks of the PTPIP51 interactome revealed in Her2 amplified breast cancer cells by the novel small molecule LDC3/Dynarrestin. PloS one 14 31075141
2012 Interaction of PTPIP51 with Tubulin, CGI-99 and Nuf2 During Cell Cycle Progression. Biomolecules 14 24970130
2011 PTPIP51 interaction with PTP1B and 14-3-3β in adipose tissue of insulin-resistant mice. International journal of obesity (2005) 14 21266951
2014 The known interactome of PTPIP51 in HaCaT cells—inhibition of kinases and receptors. The international journal of biochemistry & cell biology 13 24501773
2025 Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases. Acta neuropathologica communications 12 40045432
2022 MITOL regulates phosphatidic acid-binding activity of RMDN3/PTPIP51. Journal of biochemistry 12 34964862
2009 Differentiation-dependent PTPIP51 expression in human skeletal muscle cell culture. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 12 19124842
2008 Protein tyrosine phosphatase interacting protein 51 (PTPIP51) mRNA expression and localization and its in vitro interacting partner protein tyrosine phosphatase 1B (PTP1B) in human placenta of the first, second, and third trimester. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 11 18854601
2018 The Importance of the Right Framework: Mitogen-Activated Protein Kinase Pathway and the Scaffolding Protein PTPIP51. International journal of molecular sciences 10 30360441
2016 Orchestrating cellular signaling pathways-the cellular "conductor" protein tyrosine phosphatase interacting protein 51 (PTPIP51). Cell and tissue research 10 27734150
2015 PTPIP51 levels in glioblastoma cells depend on inhibition of the EGF-receptor. Journal of neuro-oncology 10 25862004
2015 PTPIP51—A New RelA-tionship with the NFκB Signaling Pathway. Biomolecules 10 25893721
2013 PTPIP51: a new interaction partner of the insulin receptor and PKA in adipose tissue. Journal of obesity 10 23533724
2007 Expression of PTPIP51 during mouse eye development. Histochemistry and cell biology 10 18084773
2018 Effectiveness of EGFR/HER2-targeted drugs is influenced by the downstream interaction shifts of PTPIP51 in HER2-amplified breast cancer cells. Oncogenesis 8 30139932
2014 Memory and PTPIP51--a new protein in hippocampus and cerebellum. Molecular and cellular neurosciences 8 25496818
2025 Bridging the gap: investigating the role of phosphorylation at the serine 129 site of α-synuclein in VAPB-PTPIP51 interactions. Acta neuropathologica communications 6 39994794
2022 PTPIP51 inhibits non-small-cell lung cancer by promoting PTEN-mediated EGFR degradation. Life sciences 6 35240162
2017 Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling. Biomolecules 6 28754031
2007 Expression of the novel protein PTPIP51 in rat liver: an immunohistochemical study. Histochemistry and cell biology 6 17551746
2015 The protein tyrosine phosphatase interacting protein 51 (PTPIP51) is required for the differentiation of photoreceptors. Neuroscience 3 25999297
2025 Yiqi Huoxue recipe ameliorates diabetic nephropathy by mediating VAPB-PTPIP51 complex to activate autophagy and regulate MAM contact. Frontiers in nutrition 2 41256922
2025 RHOA regulates mitochondria-ER contact sites through modulation of the VAPB/PTPIP51 tether. Nature communications 2 41392169
2021 Paternal mitochondria from an rmd-2, rmd-3, rmd-6 triple mutant are properly positioned in the C. elegans zygote. microPublication biology 2 34296068
2020 PTPIP51 crosslinks the NFκB signaling and the MAPK pathway in SKBR3 cells. Future science OA 1 32518680
2025 RMD-3 and RMD-6 identified as new components of the MSP fibrous body complex in C. elegans spermatocytes. microPublication biology 0 40838123

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