Affinage

PCP4

Calmodulin regulator protein PCP4 · UniProt P48539

Length
62 aa
Mass
6.8 kDa
Annotated
2026-06-10
52 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PCP4/PEP-19 is a small, intrinsically disordered neuronal IQ-motif polypeptide that functions as a stimulus-selective modulator of calmodulin (CaM)-dependent signaling (PMID:3464961, PMID:8663125, PMID:19106096). It binds both apo- and Ca2+-CaM through its IQ motif in a calcium-independent manner and antagonizes CaM-dependent enzymes such as neuronal nitric oxide synthase and CaM kinase II, selectively dampening CaMKII activation under depolarization but not all calcium-mobilizing stimuli (PMID:8663125, PMID:10751438). Structural and kinetic studies establish the basis for this regulation: an adjacent acidic sequence with intrinsic Ca2+-binding activity packs against the C-domain of CaM and electrostatically steers Ca2+ to its binding loops, reshaping Ca2+ association kinetics and cooperativity, and this acidic sequence is independently required for PCP4 to modulate cellular Ca2+ signaling beyond simple CaM binding (PMID:19106096, PMID:20973509, PMID:23204517, PMID:27876793, PMID:30744532). PCP4 activity is tuned by post-translational control—protein kinase C phosphorylates the IQ-motif serine to weaken CaM binding, and calpain degrades PCP4 during Ca2+ overload, with CaM binding being required for its neuroprotective function (PMID:16740252, PMID:18502590). Through this CaM/CaMKII axis, PCP4 is a determinant of cerebellar synaptic plasticity, with null mice showing potentiation instead of depression at parallel fiber–Purkinje cell synapses and locomotor learning deficits, and is required for dendritic spine maintenance (PMID:21576365, PMID:39852553). The same Ca2+/CaM/CaMKII pathway governs cardiac His-Purkinje excitability and arrhythmia susceptibility, neuronal differentiation, and—via gene dosage in Down syndrome models—ependymal and airway ciliary beating through a Ca2+/CaM/PDE1/cAMP mechanism (PMID:21491429, PMID:25295538, PMID:28069794, PMID:32178446). In a nuclear role, PCP4 regulates transcription of neuronal differentiation factors NeuroD1 and Ascl1 (PMID:32641824).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1986 High

    Establishing PCP4 as a discrete brain-specific small protein with sequence homology to calcium-binding proteins framed the central question of whether it participates in Ca2+ signaling.

    Evidence HPLC purification and amino acid sequencing of cerebellar polypeptide

    PMID:3464961

    Open questions at the time
    • Sequence homology alone did not demonstrate Ca2+ or CaM binding
    • No functional partner identified at this stage
  2. 1996 High

    Identifying calcium-independent CaM binding via an IQ motif and antagonism of nNOS defined PCP4 as a CaM regulator distinct from related IQ-motif proteins.

    Evidence In vitro CaM binding, nNOS activity assay, PKC phosphorylation assay, peptide SAR

    PMID:8663125

    Open questions at the time
    • In vitro nNOS inhibition not validated in intact cells
    • 1996 finding of no PKC substrate activity later revised
  3. 2000 High

    Showing stimulus-selective inhibition of CaMKII in intact cells established that PCP4 discriminates between calcium signaling modes rather than acting as a global CaM sink.

    Evidence Stable PC12 transfection, in situ CaMKII activity under K+ vs ATP stimulation; separate study of apoptosis protection

    PMID:10751438 PMID:11117479

    Open questions at the time
    • Molecular basis of stimulus selectivity unresolved here
    • Apoptosis protection mechanism not linked to a defined effector
  4. 2006 High

    Demonstrating PKC phosphorylation of the IQ-motif serine reduces CaM binding without conformational change revealed a post-translational switch governing PCP4 activity.

    Evidence Kinase screen, PKCgamma phosphorylation, fluorescence anisotropy binding, NMR of camstatin/phospho-camstatin

    PMID:16740252

    Open questions at the time
    • Physiological context and stimulus driving phosphorylation not defined
    • Reconciliation with earlier report of no PKC substrate activity not addressed
  5. 2008 High

    Structural disorder studies and identification of calpain-mediated degradation connected PCP4's conformational flexibility and turnover to its neuroprotective role under Ca2+ overload.

    Evidence NMR of full-length PEP-19 with kinetic binding; calpain inhibitor studies, CaM-binding-deficient mutant rescue, ischemia model

    PMID:18502590 PMID:19106096

    Open questions at the time
    • Downstream effectors of neuroprotection beyond CaM binding not mapped
    • Calpain cleavage sites not defined
  6. 2010 High

    NMR dynamics resolved how PCP4 binding to the CaM C-domain redistributes Ca2+ binding preference and cooperativity, providing the mechanism for altered Ca2+ kinetics.

    Evidence Solution NMR, chemical shift perturbation, relaxation dispersion on apo and Ca2+ C-CaM

    PMID:20973509

    Open questions at the time
    • Effect on full-length CaM and N-domain not characterized here
    • Consequence for downstream enzyme regulation not directly measured
  7. 2011 High

    Pcp4-null and overexpression mouse models causally linked PCP4 to cerebellar plasticity polarity (LTD vs LTP), motor learning, and CaMKII-driven neuronal differentiation.

    Evidence Genetic knockout electrophysiology and rotarod; TgPCP4 and Ts1Cje models with neuronal markers and CaMKII-delta Western blot

    PMID:21491429 PMID:21576365

    Open questions at the time
    • Circuit-level basis of plasticity reversal not fully resolved
    • Differentiation phenotype from one lab
  8. 2012 High

    Mutagenesis showed the acidic sequence has intrinsic Ca2+-binding activity required for cellular Ca2+ modulation beyond IQ-motif CaM binding, separating two functional modules.

    Evidence Acidic-sequence mutants, Ca2+ imaging in HeLa cells, ATP dose-response

    PMID:23204517

    Open questions at the time
    • Acidic-sequence target in cells (channel/release machinery) not identified
  9. 2014 High

    Tissue-specific studies extended the CaM/CaMKII axis to cardiac Purkinje excitability, cardiomyocyte hypertrophy, aldosterone synthesis, and CaMKK/Akt survival signaling.

    Evidence Pcp4-null cardiac electrophysiology and Ca2+ imaging; cardiomyocyte hypertrophy assays; H295R adrenocortical CYP11B2 reporter; breast cancer knockdown with CaMKK/Akt readouts

    PMID:24403568 PMID:25048017 PMID:25153723 PMID:25295538

    Open questions at the time
    • Whether all tissues use an identical CaM-binding mechanism not directly compared
    • Non-neuronal mechanistic details partly single-lab
  10. 2016 High

    The PEP-19/apo-C-CaM NMR structure provided the atomic basis for electrostatic steering of Ca2+, and synaptosome MS plus breast cancer studies broadened the functional and spatial map.

    Evidence NMR structure with electrostatic surface analysis; MALDI MS imaging of synaptosomes; siRNA EMT phenotyping in MCF-7/T47D

    PMID:27384474 PMID:27760390 PMID:27876793

    Open questions at the time
    • Structure of complex with full Ca2+-CaM or with target enzymes not determined
    • EMT role from single lab
  11. 2020 High

    Gene-dosage rescue defined a Pcp4–Ca2+/CaM–PDE1–cAMP ciliopathy pathway and identified a nuclear, transcriptional role over NeuroD1/Ascl1, expanding PCP4 beyond cytoplasmic CaM regulation.

    Evidence Ts1Rhr:Pcp4 genetic rescue with TRPV4/PDE1/CaM pharmacology and cAMP/cilia readouts; neuroblastoma knockdown with promoter luciferase and nuclear immunostaining

    PMID:28069794 PMID:30744532 PMID:32178446 PMID:32641824

    Open questions at the time
    • Mechanism of PCP4 nuclear import and direct transcriptional partners unknown
    • Link between cytoplasmic CaM role and nuclear transcription not reconciled
  12. 2023 Medium

    Disease-model studies tied PCP4 to amyloid processing, dendritic spine maintenance in TDP-43 proteinopathy, and prostate cancer suppression via CAMKK2 stabilization, broadening its pathological relevance.

    Evidence PCP4 overexpression in AD models with ADAM10/AbetaPP readouts; neuronal knockdown/rescue spine density in TDP-43 mutant; gain/loss-of-function prostate models with CAMKK2/AMPK/AR axis

    PMID:37302034 PMID:39852553 PMID:40746562

    Open questions at the time
    • Each disease link rests on a single lab
    • Direct PCP4 binding to the implicated effectors (ADAM10, CAMKK2) versus indirect regulation not fully distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PCP4 switches between its cytoplasmic CaM-modulatory function and its nuclear transcriptional role, and what defines its substrate/target selectivity across diverse tissues, remains unresolved.
  • No mechanism for nuclear translocation defined
  • No structural model of PCP4 with target enzymes beyond CaM
  • Tissue-specific selectivity determinants unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3
Partners
CALM1CAMK2ACAMK2DCAMKK2CAPN1PRKCG

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 PEP-19 (PCP4) is a 61 amino acid, 7.6 kDa brain-specific polypeptide whose primary amino acid sequence shares homology with calcium-binding proteins including the beta chain of S100 and intestinal calcium binding protein, and is the primary translation product of cerebellar poly(A)+ mRNA. HPLC purification, amino acid sequencing, molecular characterization Proceedings of the National Academy of Sciences of the United States of America High 3464961
1996 PEP-19 binds calmodulin in a calcium-independent manner (apparent Kd ~1.2 µM) via an IQ motif, acts as an antagonist of calmodulin-dependent neuronal nitric oxide synthase activity in vitro, and is not a substrate for protein kinase C, distinguishing it from neuromodulin and neurogranin despite sharing the IQ motif. In vitro calmodulin binding assay, neuronal nitric oxide synthase activity assay, protein kinase C phosphorylation assay, peptide structure-activity relationship (camstatins) The Journal of biological chemistry High 8663125
2000 PEP-19 expression in transfected PC12 cells selectively inhibits CaM kinase II activation upon depolarization by high K+ but not upon ATP-induced calcium influx, demonstrating stimulus-selective regulation of calmodulin-dependent signaling in intact cells without altering calmodulin expression or cellular calcium permeability. Stable transfection of PC12 cells, CaM kinase II activity assay in situ, depolarization and ATP stimulation paradigms The Journal of neuroscience : the official journal of the Society for Neuroscience High 10751438
2000 Expression of PEP-19 in PC12 cells inhibits apoptosis induced by UV irradiation and staurosporine, as evidenced by reduced LDH release, decreased DNA ladder formation, reduced chromatin condensation, and decreased caspase activation. Stable transfection of PC12 cells, LDH release assay, DNA ladder assay, chromatin condensation assay, caspase activation assay Neuroreport Medium 11117479
2006 The serine residue within the IQ motif of PEP-19 is selectively phosphorylated by four isoforms of protein kinase C (including PKCgamma), and phosphorylation inhibits PEP-19 binding to calmodulin without changing its overall conformation, suggesting phosphorylation reduces hydrophobic interactions with calmodulin. Kinase screen against 42 kinases using truncated camstatin peptide, PKCgamma phosphorylation of full-length PEP-19, fluorescent anisotropy binding assay, NMR solution structures of camstatin and phospho-camstatin Brain research High 16740252
2008 PEP-19 is an intrinsically disordered protein with residual structure localized to its acidic/IQ motif; it binds apo-calmodulin 50-fold more slowly than Ca2+-calmodulin, and intrinsic disorder allows it to bind either apo- or Ca2+-CaM via different structural modes via conformational selection. NMR spectroscopy of full-length PEP-19, kinetic binding assays The Journal of biological chemistry High 19106096
2008 PEP-19 is a substrate for calpain; endogenous PEP-19 levels are significantly reduced following glutamate exposure in neurons (preceding cell death), and this reduction is blocked by calpain inhibitors. Calmodulin-binding-deficient mutant PEP-19 fails to protect cells from Ca2+-overload-induced death, demonstrating that calmodulin binding is required for neuroprotection. Calpain inhibitor treatment, immunoprecipitation of wild-type vs. mutant PEP-19 with calmodulin, cell death assays in HEK293T and primary cortical neurons, transient global ischemia model in gerbils Neuroscience High 18502590
2010 PEP-19 binding to the C-domain of calmodulin causes greater structural change in apo C-CaM than in Ca2+-C-CaM, promotes preferential binding of the first Ca2+ to site IV, decreases Ca2+ binding cooperativity, and causes allosteric redistribution of conformational exchange residues around Ca2+ binding site IV in apo C-CaM. NMR spectroscopy (solution), chemical shift perturbation, relaxation dispersion measurements Biochemistry High 20973509
2011 Pep-19/Pcp4-null mice display altered cerebellar synaptic plasticity: parallel fiber-Purkinje cell synapses exhibit long-term potentiation instead of long-term depression, and the mice show marked deficits in locomotor learning on an accelerating rotarod. Genetic knockout (null mice), electrophysiological recording of LTD/LTP at cerebellar synapses, accelerating rotarod behavioral test Molecular and cellular biology High 21576365
2011 Three copies of the Pcp4 gene (as in Down syndrome models TgPCP4 and Ts1Cje) induce premature neuronal differentiation during embryogenesis and are associated with increased CaMKII-delta activation, demonstrating that Pcp4 overexpression drives neuronal differentiation via a Pcp4-Ca2+-CaM-CaMKII pathway. Transgenic mouse model (TgPCP4), Ts1Cje DS mouse model, immunofluorescence for neuronal markers (βIII-tubulin, Map2c, calbindin, calretinin), Western blot for CaMKII activation The Journal of comparative neurology Medium 21491429
2012 The acidic sequence of PEP-19 has intrinsic Ca2+ binding activity and is required (beyond IQ-motif CaM binding) to sensitize HeLa cells to ATP-induced Ca2+ release, increasing the percentage of responding cells and the frequency of Ca2+ oscillations; mutations in the acidic sequence abolish this cellular effect. Mutagenesis of acidic sequence, Ca2+ imaging in HeLa cells transfected with wild-type or mutant PEP-19, ATP dose-response experiments The Journal of biological chemistry High 23204517
2013 PCP4 overexpression in adult TgPCP4 mice increases cerebellar CaMK2alpha activity and cerebellar LTD, and produces learning impairments, while at postnatal day 14 it induces earlier neuronal maturation. Transgenic mouse model (TgPCP4), CaMK2alpha activity measurement, electrophysiological LTD recording, behavioral learning assays Neurobiology of disease Medium 24291518
2014 PCP4, expressed exclusively in the cardiac His-Purkinje network, regulates CaMKII activation, intracellular calcium handling, and cardiac electrophysiology; Pcp4-null mice show CaMKII activation, abnormal electrophysiology, dysregulated calcium handling, proarrhythmic behavior in isolated Purkinje cells, and profound autonomic dysregulation in vivo. Transcriptional profiling of genetically labeled cardiomyocytes, Pcp4-null mouse electrophysiology, calcium imaging in isolated Purkinje cells, in vivo arrhythmia monitoring The Journal of clinical investigation High 25295538
2014 PCP4 knockdown in H295R adrenocortical carcinoma cells significantly decreases CYP11B2 mRNA levels and aldosterone production; PCP4 vector transfection significantly increases CYP11B2 luciferase reporter activity in the presence of angiotensin-II, demonstrating PCP4 regulates aldosterone synthesis. siRNA knockdown of PCP4, ELISA of aldosterone, CYP11B2 luciferase reporter assay, quantitative RT-PCR Journal of molecular endocrinology Medium 24403568
2016 The NMR solution structure of PEP-19 complexed with the C-domain of apo calmodulin reveals that the acidic sequence of PEP-19 associates between helices E and F of CaM via hydrophobic interactions, with acidic side chains extending toward the solvent to form a negatively charged surface near Ca2+ binding loop III, consistent with electrostatic steering of Ca2+ to site III of CaM. NMR solution structure determination of PEP-19/C-domain CaM complex, electrostatic surface potential analysis Nature communications High 27876793
2016 PCP4/PEP19 knockdown in MCF-7 and T47D breast cancer cells reduces filopodia-like structures and vinculin expression, increases E-cadherin expression, and decreases migration, invasion, and cell adhesion, indicating PCP4/PEP19 promotes epithelial-mesenchymal transition-related processes. siRNA knockdown, morphological analysis, vinculin and E-cadherin immunostaining, migration/invasion/adhesion assays Oncotarget Medium 27384474
2017 Pcp4 gene dosage controls ependymal cilia beating in mouse brain; restoring Pcp4 to two copies in the Ts1Rhr Down syndrome model rescues both ventricular enlargement and ependymal cilia beating deficiency, demonstrating a Pcp4-dependent ciliopathy mechanism. Genetic rescue (Ts1Rhr:Pcp4+/+/- mice), cilia beat frequency/amplitude measurements, ventricular volume measurement Human molecular genetics High 28069794
2019 Overexpression of PCP4/PEP-19 in human myometrial smooth muscle cells reduces agonist-induced intracellular Ca2+ levels; the acidic-sequence mutant form fails to do so, confirming that the acidic sequence (not just IQ-motif CaM binding) is required for Ca2+ modulation in myometrial cells. Stable expression of wild-type and mutant PCP4/PEP-19 in myometrial cells, intracellular Ca2+ imaging Reproductive sciences Medium 30744532
2020 Pcp4 gene dose-dependent elevation of intracellular Ca2+ in airway ciliary cells activates TRPV4, leading to Ca2+/calmodulin-dependent PDE1 activation that degrades cAMP and impairs ciliary beat frequency in Ts1Rhr mice; genetic restoration of Pcp4 to two copies normalizes Ca2+ levels, cAMP, and ciliary function. Genetic rescue (Ts1Rhr:Pcp4+/+/-), intracellular Ca2+ measurement in ciliary cells, cAMP quantification, PDE1 inhibitor (8MmIBMX) and calmodulin inhibitor (calmidazolium) pharmacology, ciliary beat frequency/amplitude measurement International journal of molecular sciences High 32178446
2020 PCP4/PEP19 knockdown in human neuroblastoma M17 cells increases neurite outgrowth and upregulates NeuroD1 while downregulating Ascl1 at the transcriptional level (confirmed by luciferase reporter assay); PCP4/PEP19 was found to localize to nuclei of neuroblastoma cells, suggesting a nuclear role in suppressing neuronal differentiation. siRNA knockdown, neurite outgrowth quantification, luciferase reporter assay for NeuroD1 and Ascl1 promoters, immunohistochemistry for nuclear localization Laboratory investigation; a journal of technical methods and pathology Medium 32641824
2023 PCP4 overexpression promotes AβPP processing and Aβ production by upregulating endogenous AβPP expression and downregulating ADAM10 at the transcriptional level; AAV-mediated PCP4 overexpression in APP23/PS45 transgenic mice increases Aβ deposition, plaque formation, and worsens learning and memory. PCP4 overexpression in human AβPP stable cell lines and neural cells, AAV-PCP4 injection in transgenic AD mice, Western blot, RT-PCR, immunohistochemistry, behavioral test Journal of Alzheimer's disease : JAD Medium 37302034
2025 PCP4 is required for maintaining dendritic spine density in neurons; PCP4 knockdown reduces spine density and PCP4 expression can rescue spine loss in neurons expressing a disease-causing TDP-43 mutant. Neuronal knockdown of PCP4, spine density measurement, rescue experiment in TDP-43 mutant neurons Brain : a journal of neurology Medium 39852553
2025 PCP4 inhibits prostate cancer progression by stabilizing CAMKK2 protein and regulating the Ca2+/CAMKK2/AMPK/AR signaling axis; PCP4 is transcriptionally suppressed by the androgen receptor. Gain- and loss-of-function in prostate cancer cell lines, mouse models, molecular/biochemical experiments for CAMKK2 protein stability, phosphorylation of AMPK and AKT, AR reporter Frontiers in immunology Medium 40746562
2014 PCP4/PEP19 knockdown in breast cancer cells (MCF-7 and SK-BR-3) induces apoptosis and slightly decreases Akt phosphorylation; CaMKK2 knockdown in SK-BR-3 but not MCF-7 cells similarly decreases phospho-Akt and increases apoptosis, while CaMKK1 knockdown has differential effects, placing PCP4 upstream of CaMKK/Akt survival signaling. siRNA knockdown of PCP4, CaMKK1, CaMKK2; apoptosis assays; phospho-Akt Western blot Oncotarget Medium 25153723
2014 PEP-19 overexpression suppresses angiotensin II-induced cardiomyocyte hypertrophy by inhibiting CaMKII and calcineurin activation, reducing ANP and BNP expression, and partially ameliorating phospho-phospholamban (Thr-17) elevation and sarcoplasmic reticulum Ca2+ release. PEP-19 transfection in cardiomyocytes, CaMKII and calcineurin activity assays, gene expression (ANP, BNP), phospholamban phosphorylation, Ca2+ imaging Journal of pharmacological sciences Medium 25048017
2016 PEP-19/pcp4 is present at the synapse (confirmed by mass spectrometric analysis of synaptosomes) and its level in the dorsal striatum is higher in the late spatial learning phase compared to the early learning phase, extending its synaptic plasticity role to forebrain spatial learning. MALDI MS imaging of brain sections, top-down tandem MS identification, mass spectrometric synaptosome fractionation Biochimica et biophysica acta. Proteins and proteomics Medium 27760390

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1986 Isolation, sequence, and developmental profile of a brain-specific polypeptide, PEP-19. Proceedings of the National Academy of Sciences of the United States of America 106 3464961
2006 Decreased striatal levels of PEP-19 following MPTP lesion in the mouse. Journal of proteome research 96 16457591
1996 Camstatins are peptide antagonists of calmodulin based upon a conserved structural motif in PEP-19, neurogranin, and neuromodulin. The Journal of biological chemistry 84 8663125
1988 An immunochemical analysis of the distribution of a brain-specific polypeptide, PEP-19. Journal of neurochemistry 75 3183658
1987 The polypeptide PEP-19 is a marker for Purkinje neurons in cerebellar cortex and cartwheel neurons in the dorsal cochlear nucleus. Archives italiennes de biologie 73 3449006
2000 Small proteins that modulate calmodulin-dependent signal transduction: effects of PEP-19, neuromodulin, and neurogranin on enzyme activation and cellular homeostasis. Molecular neurobiology 67 11414283
2004 Decreased expression of NEFH and PCP4/PEP19 in the prefrontal cortex of alcoholics. Neuroscience research 66 15236863
2011 Impaired locomotor learning and altered cerebellar synaptic plasticity in pep-19/PCP4-null mice. Molecular and cellular biology 64 21576365
1998 PEP-19 immunohistochemistry defines the basal ganglia and associated structures in the adult human brain, and is dramatically reduced in Huntington's disease. Neuroscience 64 9697113
2014 Distinct physiological and developmental properties of hippocampal CA2 subfield revealed by using anti-Purkinje cell protein 4 (PCP4) immunostaining. The Journal of comparative neurology 59 24166578
2014 PCP4 regulates Purkinje cell excitability and cardiac rhythmicity. The Journal of clinical investigation 50 25295538
2000 Calmodulin-binding peptide PEP-19 modulates activation of calmodulin kinase II In situ. The Journal of neuroscience : the official journal of the Society for Neuroscience 48 10751438
2000 Expression of PEP-19 inhibits apoptosis in PC12 cells. Neuroreport 48 11117479
2008 PEP-19, an intrinsically disordered regulator of calmodulin signaling. The Journal of biological chemistry 43 19106096
2011 PCP4 (PEP19) overexpression induces premature neuronal differentiation associated with Ca(2+) /calmodulin-dependent kinase II-δ activation in mouse models of Down syndrome. The Journal of comparative neurology 37 21491429
2020 miR-122 Exerts Inhibitory Effects on Osteoblast Proliferation/Differentiation in Osteoporosis by Activating the PCP4-Mediated JNK Pathway. Molecular therapy. Nucleic acids 34 32199130
2017 Brain ventriculomegaly in Down syndrome mice is caused by Pcp4 dose-dependent cilia dysfunction. Human molecular genetics 31 28069794
2003 PEP-19 overexpression in human uterine leiomyoma. Molecular human reproduction 31 14561813
2008 Degradation of PEP-19, a calmodulin-binding protein, by calpain is implicated in neuronal cell death induced by intracellular Ca2+ overload. Neuroscience 29 18502590
1993 High-resolution mapping of D16led-1, Gart, Gas-4, Cbr, Pcp-4, and Erg on distal mouse chromosome 16. Genomics 28 8406490
1996 Organization of ventrolateral periolivary cells of the cat superior olive as revealed by PEP-19 immunocytochemistry and Nissl stain. The Journal of comparative neurology 27 8725296
2014 PCP4: a regulator of aldosterone synthesis in human adrenocortical tissues. Journal of molecular endocrinology 26 24403568
2014 Distribution of PCP4 protein in the forebrain of adult mice. Acta histochemica 24 24954028
2014 Anti-apoptotic effects of PCP4/PEP19 in human breast cancer cell lines: a novel oncotarget. Oncotarget 23 25153723
2004 Pcp4l1, a novel gene encoding a Pcp4-like polypeptide, is expressed in specific domains of the developing brain. Gene expression patterns : GEP 21 15053978
2016 PEP-19 modulates calcium binding to calmodulin by electrostatic steering. Nature communications 20 27876793
2007 Expression of Pcp4 gene during osteogenic differentiation of bone marrow mesenchymal stem cells in vitro. Molecular and cellular biochemistry 20 18008138
2016 PCP4/PEP19 promotes migration, invasion and adhesion in human breast cancer MCF-7 and T47D cells. Oncotarget 19 27384474
1996 Molecular genetic characterization and comparative mapping of the human PCP4 gene. Somatic cell and molecular genetics 19 8914602
1998 PEP-19 immunoreactivity in the cochlear nucleus and superior olive of the cat. Neuroscience 18 9460761
2013 Developmental molecular and functional cerebellar alterations induced by PCP4/PEP19 overexpression: implications for Down syndrome. Neurobiology of disease 17 24291518
1989 Developmental expression of polypeptide PEP-19 in cerebellar cell suspensions transplanted into the cerebellum of pcd mutant mice. Experimental brain research 17 2792250
2003 PCP4 is highly expressed in ectoderm and particularly in neuroectoderm derivatives during mouse embryogenesis. Gene expression patterns : GEP 16 12609609
2010 Intrinsically disordered PEP-19 confers unique dynamic properties to apo and calcium calmodulin. Biochemistry 15 20973509
1996 Cloning of the cDNA for a human homolog of the rat PEP-19 gene and mapping to chromosome 21q22.2-q22.3. Human genetics 15 8931698
1993 Structure and regulation of the gene encoding the neuron-specific protein PEP-19. Brain research. Molecular brain research 13 8361346
2012 The calmodulin regulator protein, PEP-19, sensitizes ATP-induced Ca2+ release. The Journal of biological chemistry 12 23204517
2007 Cloning of a rat-specific long PCP4/PEP19 isoform. International journal of molecular medicine 10 17273800
2006 The influence of phosphorylation on the activity and structure of the neuronal IQ motif protein, PEP-19. Brain research 10 16740252
2020 PCP4/PEP19 downregulates neurite outgrowth via transcriptional regulation of Ascl1 and NeuroD1 expression in human neuroblastoma M17 cells. Laboratory investigation; a journal of technical methods and pathology 9 32641824
2011 RNA-binding activity of the rat calmodulin-binding PEP-19 protein and of the long PEP-19 isoform. International journal of molecular medicine 9 22020791
2023 Molecular Mechanism of Long Noncoding RNA SNHG14 in Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells through the NEDD4L/FOXA2/PCP4 Axis. Stem cells international 8 36644009
2023 PCP4 Promotes Alzheimer's Disease Pathogenesis by Affecting Amyloid-β Protein Precursor Processing. Journal of Alzheimer's disease : JAD 6 37302034
2020 Airway Ciliary Beating Affected by the Pcp4 Dose-Dependent [Ca2+]i Increase in Down Syndrome Mice, Ts1Rhr. International journal of molecular sciences 6 32178446
2016 MS imaging and mass spectrometric synaptosome profiling identify PEP-19/pcp4 as a synaptic molecule involved in spatial learning in mice. Biochimica et biophysica acta. Proteins and proteomics 6 27760390
2014 Overexpression of PEP-19 suppresses angiotensin II-induced cardiomyocyte hypertrophy. Journal of pharmacological sciences 6 25048017
2018 Upregulation of PCP4 in human aldosterone-producing adenomas fosters human adrenocortical tumor cell growth via AKT and AMPK pathway. International journal of clinical and experimental pathology 5 31938214
2025 Deep learning analyses of splicing variants identify the link of PCP4 with amyotrophic lateral sclerosis. Brain : a journal of neurology 4 39852553
2013 Differential distribution of the Ca (2+) regulator Pcp4 in the branchial arches is regulated by Hoxa2. PloS one 2 23671666
2025 Number of subfields of the rat dorsal subiculum defined by NOS and PCP4 immunoreactivity changes according to different levels of observation. Neuroscience 1 39755232
2025 PCP4 inhibits the progression of prostate cancer through Ca2+/CAMKK2/AMPK/AR pathway. Frontiers in immunology 0 40746562
2019 Expression, Regulation, and Function of the Calmodulin Accessory Protein PCP4/PEP-19 in Myometrium. Reproductive sciences (Thousand Oaks, Calif.) 0 30744532

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