Affinage

PTBP2

Polypyrimidine tract-binding protein 2 · UniProt Q9UKA9

Length
531 aa
Mass
57.5 kDa
Annotated
2026-06-10
49 papers in source corpus 30 papers cited in narrative 30 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

PTBP2 (nPTB/brPTB) is a neuronal pyrimidine-tract RNA-binding protein that acts as a sequence-specific splicing repressor, binding pyrimidine-rich elements upstream of or within alternative exons to enforce embryonic and tissue-specific splicing programs (PMID:22802532). Across the developing nervous system it temporarily suppresses adult-specific protein isoforms governing neurite growth, pre- and post-synaptic assembly, and synaptic transmission, so that its loss causes precocious adult isoform expression, failed neuronal maturation, and cell death (PMID:24448406); mechanistically this includes repression of PSD-95 (Dlg4) exon 18, which generates an NMD-targeted transcript until PTBP2 is downregulated (PMID:22246437), and control of axonogenesis-associated splicing such as the Shtn1 isoform switch that tunes actin polymerization and axon formation (PMID:30733148). PTBP2 operates in a developmental relay with its paralog PTBP1, which represses PTBP2 exon 10 to produce an NMD substrate; the two proteins bind RNA similarly genome-wide yet differ in repression activity, a difference attributable not to differential binding but to protein domains—RRM1, RRM2, and the unstructured N-terminal and linker regions—and to cofactor recruitment (PMID:17679092, PMID:27926877, PMID:27288314, PMID:38336291). Its splicing output is modulated by associated regulators including Matrin3 and hnRNPM, which dissociate upon phosphorylation by the kinase KIS, coupling PTBP2 activity to synaptic spine maturation (PMID:38597390). Beyond the nucleus, cytosolic PTBP2 binds the 3' UTR of Hnrnpr mRNA and drives its axonal localization and eIF5A2-dependent local translation to support axon growth (PMID:37438340). PTBP2 also functions outside the nervous system: it is required for spermatogenesis, where it regulates a splicing network controlling germ-Sertoli communication and F-actin organization (PMID:28636946, PMID:26391954), and it promotes immunoglobulin class-switch recombination by interacting with AID and enhancing its binding to switch-region DNA (PMID:21186367). In disease, ASO-mediated disruption of PTBP2 binding to SYNGAP1 mRNA redirects splicing to increase SYNGAP1 expression in patient-derived neurons, defining a therapeutic strategy for SYNGAP1 haploinsufficiency (PMID:37149717).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2007 High

    Established that PTBP2 protein levels are themselves regulated, both by miR-133 acting on its 3' UTR during muscle differentiation and by PTBP1-driven nonproductive splicing of its own exon 10, explaining how PTBP2 abundance is dynamically controlled.

    Evidence Luciferase 3' UTR reporters with MRE mutagenesis and miR-133 gain/loss in C2C12 cells; quantitative proteomics and double siRNA knockdown with splicing readouts in HeLa cells

    PMID:17210790 PMID:17679092

    Open questions at the time
    • Did not address PTBP2's own splicing target spectrum in neurons
    • Functional redundancy with PTBP1 quantified only on a subset of exons
  2. 2008 Medium

    Resolved why PTBP2 protein is far less abundant than PTBP1 despite high identity, showing its expression is throttled by suboptimal codon content and confirming PTBP2 is a bona fide splicing repressor.

    Evidence Transfection of native vs codon-optimized nPTB constructs with translation and splicing repression assays

    PMID:18335065

    Open questions at the time
    • Physiological selective advantage of codon-limited expression not tested in vivo
    • Single-lab observation
  3. 2012 High

    Defined PTBP2's genome-wide binding mode and developmental function, showing it binds pyrimidine-rich sequences to repress adult exons and is required for neuronal progenitor polarity, proper neurogenesis timing, and PSD-95 expression for synapse maturation.

    Evidence HITS-CLIP in mouse neocortex, splicing microarrays and Ptbp2-null mice; RT-PCR splicing and re-expression with electrophysiology

    PMID:22246437 PMID:22802532

    Open questions at the time
    • Cofactors mediating exon-specific repression not identified
    • Distinction from PTBP1 binding not yet resolved
  4. 2014 High

    Showed PTBP2 maintains an embryonic splicing program that suppresses adult isoforms until terminal neuronal maturation, with its depletion causing precocious maturation failure and death—establishing PTBP2 as a developmental timing switch.

    Evidence Ptbp2 conditional knockout mouse with transcriptome-wide RNA-seq and neuron viability/maturation assays

    PMID:24448406

    Open questions at the time
    • Specific isoform switches driving maturation failure not individually dissected here
    • Upstream signals controlling PTBP2 downregulation timing unknown
  5. 2016 High

    Determined the basis for differential PTBP1 vs PTBP2 activity, showing similar genome-wide RNA binding but distinct repression strengths attributable to specific RRM and linker segments and cofactor interactions, and that both repress cryptic exons via CU microsatellites.

    Evidence PTBP1/PTBP2 chimeric protein splicing assays and Raver1 binding; Ptbp1 knockin/Ptbp2 knockout mice with CLIP-seq; RNA-seq motif analysis after knockdown

    PMID:27288314 PMID:27681424 PMID:27926877

    Open questions at the time
    • Identity of cofactors conferring exon-specific differential sensitivity not fully defined
    • Cryptic exon repression study single-lab without reconstitution
  6. 2019 High

    Linked PTBP2 splicing control to axon formation specifically, identifying Shtn1 isoform regulation as a mechanism by which PTBP2 prevents premature axonogenesis-associated splicing.

    Evidence Conditional knockout mouse, primary cortical neuron transcriptomics, in vitro axon assays, Shtn1 actin-binding/polymerization characterization

    PMID:30733148

    Open questions at the time
    • Relative contribution of Shtn1 vs other targets to axon phenotype not quantified
    • Mechanism timing of PTBP2 loss during axonogenesis not detailed
  7. 2023 High

    Revealed a cytosolic, splicing-independent function for PTBP2 in axon growth, binding Hnrnpr mRNA to drive its axonal localization and eIF5A2-dependent local translation.

    Evidence Subcellular fractionation, live imaging, CLIP, ribosome association and eIF5A2 interaction assays, conditional cytosolic Ptbp2 depletion in motoneurons

    PMID:37438340

    Open questions at the time
    • What partitions PTBP2 between nucleus and cytoplasm not established
    • Full set of cytosolic mRNA cargos beyond Hnrnpr unknown
  8. 2023 High

    Demonstrated therapeutic targetability of PTBP2-mediated splicing, showing ASO disruption of PTBP2 binding to SYNGAP1 mRNA redirects splicing and raises SYNGAP1 expression in patient-derived neurons.

    Evidence CLIP-seq in human brain and iPSC-neurons, ASO perturbation, RT-PCR/western and SYNGAP1-haploinsufficient patient iPSC-neuron experiments

    PMID:37149717

    Open questions at the time
    • In vivo efficacy and durability of ASO approach not tested
    • Off-target effects on other PTBP2 splicing events not characterized
  9. 2024 High

    Connected post-translational regulation to PTBP2 function, showing KIS kinase phosphorylates PTBP2 to dissociate Matrin3 and hnRNPM and impair complex RNA binding, with opposing roles in synaptic spine maturation.

    Evidence In vitro kinase assay, Co-IP of PTBP2-Matrin3-hnRNPM before/after phosphorylation, genome-wide exon usage and spine morphology assays

    PMID:38597390

    Open questions at the time
    • Specific phosphosites required for dissociation not pinpointed by mutagenesis here
    • Single-lab finding
  10. 2017 High

    Extended PTBP2's role to spermatogenesis, showing it regulates a splicing network controlling germ-Sertoli communication and F-actin organization and is essential for germ cell survival and spermatid differentiation.

    Evidence Germ cell-specific and global Ptbp2 knockout mice, RNA-seq, histology, F-actin staining, flow cytometry

    PMID:26391954 PMID:28636946

    Open questions at the time
    • Tissue-specific determinants of which exons are PTBP2-sensitive in testis vs brain unknown
    • Direct targets driving the F-actin phenotype not individually validated
  11. 2014 Medium

    Identified PTBP2's mechanistic basis for differential RNA binding through structural characterization of its C-terminal RRMs and showed activity can be modulated by sequestration in complexes such as SFPQ.

    Evidence Crystal and NMR structures of nPTB RRMs 3-4; Co-IP of SFPQ/PTBP2 and MALAT1 RNA pulldown with CRC proliferation/migration phenotypes

    PMID:24688880 PMID:25025966

    Open questions at the time
    • Structure of full-length PTBP2 RNA complex not solved
    • SFPQ/MALAT1 axis demonstrated in cancer cells only, single lab
  12. 2025 Medium

    Documented mRNA-stabilizing functions of PTBP2 in cancer cells, binding 3' UTRs of BNIP3 and Polk to support autophagy and limit DNA damage, broadening its role beyond splicing repression.

    Evidence RIP-seq, Ptbp2 KO CML cell lines and patient samples, rescue experiments, LC3-II/autophagy and comet/γH2AX DNA damage readouts, xenografts

    PMID:40113750 PMID:41667423

    Open questions at the time
    • Mechanism of 3' UTR-mediated stabilization not resolved
    • Generalizability beyond CML cells untested, single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PTBP2 is partitioned and switched between its nuclear splicing-repressor role, cytosolic mRNA-localization/stabilization roles, and non-canonical transcriptional and immune functions, and which cofactors and modifications dictate each, remains unresolved.
  • No unified model linking phosphorylation/acetylation state to subcellular function
  • Determinants of nuclear vs cytoplasmic localization unknown
  • Functional consequences of individual PTMs not established by mutagenesis

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0140110 transcription regulator activity 4 GO:0060089 molecular transducer activity 2 GO:0045182 translation regulator activity 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-112316 Neuronal System 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-168256 Immune System 1
Partners
AIDEIF5A2HNRNPH1HNRNPMMATRIN3PTBP1SFPQSMN
Complex memberships
PTBP2-Matrin3-hnRNPM complexSFPQ/PTBP2 complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 PTBP2 (nPTB) expression during myoblast differentiation is post-transcriptionally repressed by the muscle-restricted microRNA miR-133, which targets two miR-133-responsive elements in the PTBP2 3' UTR; this reduction in PTBP2 leads to increased inclusion of PTB-repressed exons during myotube differentiation. Luciferase reporter assay with 3' UTR constructs, transfection of synthetic miR-133, LNA oligonucleotide block of miR-133/miR-1/206, western blot, RT-PCR of target exons in C2C12 cells Genes & development High 17210790
2007 PTB represses PTBP2 (nPTB) exon 10 splicing, causing nonproductive mRNA subject to nonsense-mediated decay; upon PTB knockdown, nPTB is upregulated via increased exon 10 inclusion, demonstrating cross-regulation between PTB and PTBP2 through nonproductive alternative splicing. PTBP2 and PTB have a large degree of functional overlap in splicing repression. Quantitative proteomics of HeLa cells after PTB knockdown, siRNA double knockdown of PTB and nPTB, RT-PCR of alternative splicing events Molecular cell High 17679092
2012 PTBP1 and PTBP2 repress splicing of PSD-95 (Dlg4) exon 18; this repression leads to premature translation termination and nonsense-mediated mRNA decay of Psd-95 transcripts during early neural development. Sequential downregulation of first PTBP1 and then PTBP2 during embryonic development allows exon 18 inclusion and PSD-95 protein expression required for synapse maturation. RT-PCR splicing assays, re-expression of PTBP1/PTBP2 in differentiated neurons, electrophysiology and synaptic marker analysis in mouse embryonic brain Nature neuroscience High 22246437
2012 Ptbp2 binds pyrimidine-rich sequences upstream of and/or within alternative exons to inhibit adult-specific alternative splicing in neuronal progenitors; Ptbp2-null mice show aberrant neuronal progenitor polarity, premature neurogenesis, and reduced progenitor pools, identifying a role for Ptbp2 in neurogenesis through repression of exons encoding proteins associated with cell fate, proliferation, and the actin cytoskeleton. HITS-CLIP in developing mouse neocortex, splicing-sensitive microarrays, Ptbp2 knockout mouse (two independent strains), histological analysis Genes & development High 22802532
2014 PTBP2 controls a program of embryonic alternative splicing that temporarily represses adult protein isoforms (affecting neurite growth, pre- and post-synaptic assembly, synaptic transmission) until final neuronal maturation; depletion of PTBP2 causes precocious expression of adult isoforms in embryonic cortex, leading to failure of neuronal maturation and death. Ptbp2 conditional knockout mouse, transcriptome-wide RNA-seq and splicing analysis, cultured neuron viability and maturation assays eLife High 24448406
2010 PTBP2 physically interacts with the cytidine deaminase AID (identified by proteomic screen using in vivo biotinylation of AID) and promotes binding of AID to transcribed switch-region DNA; shRNA-mediated knockdown of PTBP2 in B cells decreases AID binding to switch regions and considerably impairs immunoglobulin class-switch recombination. In vivo biotinylation proteomic screen, co-immunoprecipitation, shRNA knockdown of PTBP2 in B cells, ChIP for AID at switch regions, CSR assay Nature immunology High 21186367
2016 PTBP1 exhibits greater splicing repression activity than PTBP2 per unit protein on target exons; chimera analysis identified that multiple segments of PTBP1 (RRM1, the linker between RRM2-RRM3, and RRM2) contribute to higher repression activity. RRM2 of PTBP1 increases repression potentially via stronger binding to the cofactor Raver1. In vivo coexpression splicing assay, in vitro splicing assay, PTBP1/PTBP2 chimeric protein constructs, Raver1 binding assays RNA (New York, N.Y.) High 27288314
2016 PTBP1 and PTBP2 repress nonconserved cryptic exons using CU microsatellites as binding elements, establishing them as members of a family of cryptic exon repressors. This activity is distinct from TDP-43, which uses UG microsatellites. RNA-seq analysis after PTBP1/PTBP2 knockdown, identification of cryptic exon inclusion events, motif analysis Cell reports Medium 27681424
2016 A PTBP1 knockin allele can rescue forebrain-specific but not pan-neuronal Ptbp2 knockout, demonstrating both redundant and distinct functional roles. Despite similar RNA binding across the transcriptome (shown by CLIP), many developmentally regulated exons show different sensitivities to PTBP1 vs. PTBP2, indicating differential activity does not derive from differential RNA binding but likely from cofactor interactions. Ptbp1 knockin mouse bred to Ptbp2 knockout, CLIP-seq comparing RNA binding, splicing-sensitive assays across brain regions Cell reports High 27926877
2019 PTBP2 governs axonogenesis-associated alternative splicing in cortical neurons; its cortical depletion prematurely induces axonogenesis-associated splicing and specifically impairs axon formation in vitro and in vivo. PTBP2-controlled splicing of Shtn1 determines SHTN1's capacity to regulate actin interaction, polymerization, and axon growth; precocious Shtn1 isoform switching contributes to disorganized axon formation in Ptbp2-/- neurons. Transcriptome profiling of primary cortical neurons, PTBP2 conditional knockout mouse, in vitro axon formation assays, Shtn1 isoform functional characterization including actin binding/polymerization assays Neuron High 30733148
2017 Ptbp2 controls a network of alternatively spliced genes involved in cell adhesion, migration, and polarity in spermatogenic cells; Ptbp2 ablation in germ cells results in disorganization of F-actin cytoskeleton in Sertoli cells, demonstrating that PTBP2-regulated alternative splicing is required for germ-Sertoli cell communication during spermatogenesis. Germ cell-specific Ptbp2 conditional knockout mouse, RNA-seq, splicing analysis, histology, F-actin staining Cell reports High 28636946
2015 Ptbp2 is essential for spermatogenesis; Ptbp2 ablation results in germ cell loss due to increased apoptosis of meiotic spermatocytes and postmeiotic arrest of spermatid differentiation, and Ptbp2 is required for alternative splicing regulation in the testis in a tissue-specific manner (not all Ptbp2-sensitive exons in brain are also sensitive in testis). Ptbp2 knockout mouse, dual fluorescence flow cytometry of germ cells, histology, RT-PCR of alternative splicing events in brain vs. testis Molecular and cellular biology High 26391954
2009 Knockdown of PTBP2 (alone or combined with PTBP1) in glioma cell lines slows cell proliferation, inhibits cell migration, and increases cell adhesion to fibronectin and vitronectin. shRNA knockdown of PTBP1 and/or PTBP2 in U251 and LN229 glioma cell lines, proliferation assays, migration assays, adhesion assays Brain : a journal of neurology Medium 19506066
2015 PTBP1 and PTBP2 bind to an exonic splicing suppressor in SRSF3 exon 4 and inhibit its inclusion, resulting in overexpression of full-length functional SRSF3 in oral squamous cell carcinoma cells; SRSF3, in turn, promotes PTBP2 expression, establishing a feed-forward loop. RT-PCR splicing assays, overexpression and knockdown of PTBP1/PTBP2, luciferase/minigene assays, RNA binding analysis in OSCC cells Scientific reports Medium 26416554
2014 MALAT1 lncRNA binds to SFPQ, thereby releasing PTBP2 from the SFPQ/PTBP2 complex; the increased free PTBP2 promotes colorectal cancer cell proliferation and migration. Co-immunoprecipitation of SFPQ/PTBP2 complex, RNA pulldown for MALAT1-SFPQ interaction, overexpression/knockdown in CRC cells and nude mouse xenografts British journal of cancer Medium 25025966
2018 Mass spectrometry analysis identified distinct phosphorylation modifications in PTBP2 located in the unstructured N-terminal, Linker 1, and Linker 2 regions (not present in PTBP1), and acetylation modifications including lysine residues in the nuclear localization sequence of PTBP2. Mass spectrometry analysis of post-translational modifications on PTBP1 and PTBP2 under splicing reaction conditions Biochemistry Medium 29851470
2022 hnRNPH1 recruits PTBP2 (and SRSF3) to modulate alternative splicing in germ cells; conditional knockout of Hnrnph1 in spermatogenic cells causes abnormal splicing events affecting meiosis and germ-Sertoli communication genes. Co-immunoprecipitation of hnRNPH1-PTBP2 complex, conditional Hnrnph1 knockout mouse, RNA-seq splicing analysis, histology Nature communications Medium 35739118
2023 PTBP2 has a cytosolic role in axon growth in motoneurons: cytoplasmic Ptbp2 binds the 3' UTR of Hnrnpr mRNA and promotes its axonal localization and local translation via association with ribosomes in a manner dependent on translation factor eIF5A2; depletion of cytosolic Ptbp2 reduces axonal Hnrnpr mRNA localization and hnRNP R synthesis, causing defective axon growth. Subcellular fractionation and live imaging for cytosolic/axonal Ptbp2 localization, CLIP for Ptbp2-Hnrnpr mRNA interaction, ribosome association assays, eIF5A2 interaction, conditional depletion of cytosolic Ptbp2 with axon growth phenotype readout Nature communications High 37438340
2023 PTBP2 binding to SYNGAP1 mRNA promotes alternative splicing and nonsense-mediated decay of SYNGAP1; antisense oligonucleotides that disrupt PTBP2 binding sites redirect splicing and increase SYNGAP1 mRNA and protein expression in human iPSC-derived neurons and in SYNGAP1 haploinsufficient patient-derived neurons. CLIP-seq in human brain tissue and iPSC-neurons to map PTBP2 binding sites, ASO-mediated disruption of PTBP2 binding, RT-PCR and western blot for SYNGAP1 isoforms/expression, patient-derived iPSC-neuron experiments Nature communications High 37149717
2024 KIS kinase phosphorylates PTBP2, causing its dissociation from co-regulators Matrin3 and hnRNPM and hindering the RNA-binding capability of the complex; KIS and PTBP2 have opposing functional interactions in synaptic spine emergence and maturation. In vitro kinase assay showing KIS phosphorylates PTBP2, co-immunoprecipitation of PTBP2-Matrin3-hnRNPM complex before/after phosphorylation, genome-wide exon usage profiling in neurons, spine morphology assays eLife High 38597390
2024 Unstructured linker regions (Linker 1 and Linker 2) and the N-terminal region of PTBP2 play a role in its differential splicing activity compared to PTBP1; phosphorylation in these unstructured regions alters their physical properties as shown by molecular dynamics, and hybrid PTBP1-PTBP2 constructs with PTBP1 linker regions show altered splicing repression activity. Hybrid PTBP1-PTBP2 chimeric protein constructs assayed in splicing assays, molecular dynamics simulation of phosphorylated unstructured regions, evolutionary conservation bioinformatics analysis The Journal of biological chemistry Medium 38336291
2025 PTBP2 binds to the 3' UTR of BNIP3 mRNA and stabilizes its expression; Ptbp2 knockout in CML cells decreases BNIP3 levels and impairs autophagy (measured by LC3-II in bafilomycin-treated cells), and re-expression of BNIP3 in Ptbp2-KO cells restores the autophagy phenotype. RIP-seq identifying PTBP2-BNIP3 3'UTR interaction, Ptbp2 knockout CML cell lines, LC3-II western blot as autophagy readout, BNIP3 rescue experiment, subcutaneous xenograft and tail vein engraftment in NOD/SCID mice Cell death & disease Medium 40113750
2026 PTBP2 binds to the 3' UTR of DNA polymerase kappa (Polk) mRNA, stabilizing its expression; Ptbp2 knockout reduces Polk levels and increases DNA damage (comet assay, γH2AX foci) upon hydroxyurea treatment, which is rescued by Polk re-expression. POLK interacts with MRE11 of the MRN complex to regulate ATM-CHK2 signaling. RIP-seq (3' UTR binding), Ptbp2 KO CML cell lines and patient samples, comet assay and γH2AX foci, Polk rescue experiment, co-immunoprecipitation of POLK-MRE11, sister chromatid exchange and BrdU incorporation assays Cell death discovery Medium 41667423
2014 Crystal and solution structures of the C-terminal domain of nPTB (nPTB34, containing RRMs 3 and 4) reveal that RRMs 3 and 4 interact with each other to form a stable unit with RNA-binding surfaces on opposite sides facing away from each other, similar to PTB34; amino acid differences are located on exposed β-sheet surfaces and loops, likely modulating RNA interactions. X-ray crystallography and NMR solution structure determination of nPTB RRMs 3-4 PeerJ High 24688880
2022 Under in vitro splicing conditions, PTBP2 interacts with a distinct set of proteins compared to PTBP1; PTBP2 does not interact with many mRNA processing/splicing regulators that PTBP1 does, and both proteins interact with chromatin remodeling and transcription regulators. The study identified potential 'writer' and 'eraser' enzymes for PTM modifications on PTBP2. In vitro splicing reactions with HeLa nuclear extract, mass spectrometry of co-precipitated proteins for PTBP1 vs. PTBP2 PloS one Medium 35113929
2023 PTBP2 binding to SYNGAP1 mRNA promotes alternative splicing and nonsense-mediated decay of SYNGAP1. PTBP2 prevents IRF9 alternative splicing and upregulates STAT1 to stimulate CCL5 secretion and IFN-stimulated gene factor-dependent type I interferon secretion in neuroblastoma cells, inducing monocyte/macrophage chemotaxis and sustaining proinflammatory monocyte phenotype. PTBP2 overexpression/knockdown in neuroblastoma cells, RT-PCR for IRF9 splicing, western blot for STAT1, ELISA for CCL5/IFN, monocyte chemotaxis and polarization assays Research (Washington, D.C.) Medium 37040518
2021 The lncRNA Rbakdn binds to Ptbp2 protein and stabilizes it against ubiquitin-mediated degradation; Rbakdn knockdown leads to decreased Ptbp2 levels through the ubiquitination degradation pathway. RNA immunoprecipitation (Ribotrap + co-IP), Rbakdn knockdown in vitro and intratesticular injection in mice, ubiquitination assay for Ptbp2 degradation Frontiers in genetics Medium 34707642
2023 PTBP2 binds to the lncRNA Tesra in testicular germ cells and is required for Tesra-mediated transcriptional activation of Prss42/Tessp-2; knockdown of PTBP2 significantly decreases Prss42/Tessp-2 promoter activity in an in vitro reporter system. Ribotrap assay followed by LC-MS/MS to identify Tesra-binding proteins, RNA immunoprecipitation confirming PTBP2-Tesra association, Tet-on reporter system for Prss42/Tessp-2 promoter activity, PTBP2 knockdown Gene Medium 37858745
2008 Human nPTB (PTBP2) expression is severely limited by its extremely suboptimal codon content (high proportion of A/U at third codon position), resulting in ~1–3% the expression level of PTB despite similar mRNA levels and 74% amino acid identity; codon optimization restores expression to PTB-equivalent levels and confirms PTBP2 acts as a splicing repressor. Transfection of native vs. codon-optimized nPTB constructs, western blot, in vivo and in vitro translation assays, splicing repression assays PloS one Medium 18335065
2024 Smn (survival motoneuron protein) is an interactor of Ptbp2 in cytosolic compartments of motoneurons; Smn depletion reduces Ptbp2 levels specifically in axons (not somata), and re-expression of Ptbp2 in axons rescues defects in axon elongation and growth cone maturation in Smn-deficient motoneurons. Co-immunoprecipitation of Smn-Ptbp2 in motoneuron cytosolic fractions, subcellular fractionation and immunofluorescence for axonal Ptbp2 levels in Smn-KD motoneurons, lentiviral re-expression of Ptbp2 in axons, axon growth and growth cone assays Frontiers in molecular neuroscience Medium 39246602

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/PTBP2 complex. British journal of cancer 327 25025966
2007 MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development. Genes & development 305 17210790
2007 Crossregulation and functional redundancy between the splicing regulator PTB and its paralogs nPTB and ROD1. Molecular cell 266 17679092
2012 PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2. Nature neuroscience 206 22246437
2012 Neuronal regulation of pre-mRNA splicing by polypyrimidine tract binding proteins, PTBP1 and PTBP2. Critical reviews in biochemistry and molecular biology 168 22655688
2012 Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain. Genes & development 164 22802532
2014 The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation. eLife 137 24448406
2009 Splicing factors PTBP1 and PTBP2 promote proliferation and migration of glioma cell lines. Brain : a journal of neurology 127 19506066
2016 PTBP1 and PTBP2 Serve Both Specific and Redundant Functions in Neuronal Pre-mRNA Splicing. Cell reports 105 27926877
2010 The splicing regulator PTBP2 interacts with the cytidine deaminase AID and promotes binding of AID to switch-region DNA. Nature immunology 89 21186367
2019 Axonogenesis Is Coordinated by Neuron-Specific Alternative Splicing Programming and Splicing Regulator PTBP2. Neuron 81 30733148
2018 PTB/nPTB: master regulators of neuronal fate in mammals. Biophysics reports 67 30310857
2015 PTBP1 and PTBP2 impaired autoregulation of SRSF3 in cancer cells. Scientific reports 67 26416554
2022 hnRNPH1 recruits PTBP2 and SRSF3 to modulate alternative splicing in germ cells. Nature communications 62 35739118
2016 PTBP1 and PTBP2 Repress Nonconserved Cryptic Exons. Cell reports 62 27681424
2017 Ptbp2 Controls an Alternative Splicing Network Required for Cell Communication during Spermatogenesis. Cell reports 57 28636946
2001 Comparative expression analysis of the genes encoding polypyrimidine tract binding protein (PTB) and its neural homologue (brPTB) in prenatal and postnatal mouse brain. Mechanisms of development 56 11231079
2023 PTBP2-Mediated Alternative Splicing of IRF9 Controls Tumor-Associated Monocyte/Macrophage Chemotaxis and Repolarization in Neuroblastoma Progression. Research (Washington, D.C.) 53 37040518
2015 RNA Binding Protein Ptbp2 Is Essential for Male Germ Cell Development. Molecular and cellular biology 50 26391954
2021 SON drives oncogenic RNA splicing in glioblastoma by regulating PTBP1/PTBP2 switching and RBFOX2 activity. Nature communications 38 34548489
2010 HuB/C/D, nPTB, REST4, and miR-124 regulators of neuronal cell identity are also utilized in the lens. Molecular vision 31 21139978
2023 Mapping PTBP2 binding in human brain identifies SYNGAP1 as a target for therapeutic splice switching. Nature communications 28 37149717
2018 Post-Translational Modifications in Polypyrimidine Tract Binding Proteins PTBP1 and PTBP2. Biochemistry 27 29851470
2016 Multiple determinants of splicing repression activity in the polypyrimidine tract binding proteins, PTBP1 and PTBP2. RNA (New York, N.Y.) 27 27288314
2008 Expression of human nPTB is limited by extreme suboptimal codon content. PloS one 22 18335065
2004 Evolutionary conservation of a 2-kb intronic sequence flanking a tissue-specific alternative exon in the PTBP2 gene. Genomics 22 14667811
2022 Polypyrimidine tract binding proteins PTBP1 and PTBP2 interact with distinct proteins under splicing conditions. PloS one 18 35113929
2023 Cytosolic Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr. Nature communications 15 37438340
2014 Solution and crystal structures of a C-terminal fragment of the neuronal isoform of the polypyrimidine tract binding protein (nPTB). PeerJ 12 24688880
2011 Evidence that "brain-specific" FOX-1, FOX-2, and nPTB alternatively spliced isoforms are produced in the lens. Current eye research 12 21714144
2021 A Novel Meiosis-Related lncRNA, Rbakdn, Contributes to Spermatogenesis by Stabilizing Ptbp2. Frontiers in genetics 11 34707642
2012 Expression analysis of the polypyrimidine tract binding protein (PTBP1) and its paralogs PTBP2 and PTBP3 during Xenopus tropicalis embryogenesis. The International journal of developmental biology 11 23124965
2023 PTBP2 attenuation facilitates fibroblast to neuron conversion by promoting alternative splicing of neuronal genes. Stem cell reports 10 37832540
2022 PTBP2 - a gene with relevance for both Anorexia nervosa and body weight regulation. Translational psychiatry 9 35680849
2005 Identification and analysis of the human neural polypyrimidine tract binding protein (nPTB) gene promoter region. Gene 9 16002244
2019 PTBP2 exon 10 inclusion is associated with the progression of CML and it is BCR-ABL1 dependent. The international journal of biochemistry & cell biology 8 30726713
2017 Association between RNA-binding protein Ptbp2 and germ cell injury in an experimentally-induced unilateral cryptorchidism murine model. PloS one 7 29045475
2025 PTBP2 promotes cell survival and autophagy in chronic myeloid leukemia by stabilizing BNIP3. Cell death & disease 4 40113750
2025 Polypyrimidine tract binding proteins PTBP1 and PTBP2 associate with distinct proteins and have distinct post-translational modifications in neuronal nuclear extract. PloS one 4 40465779
2024 Unstructured linker regions play a role in the differential splicing activities of paralogous RNA binding proteins PTBP1 and PTBP2. The Journal of biological chemistry 2 38336291
2024 KIS counteracts PTBP2 and regulates alternative exon usage in neurons. eLife 2 38597390
2023 PTBP2 binds to a testis-specific long noncoding RNA, Tesra, and activates transcription of the Prss42/Tessp-2 gene. Gene 2 37858745
2026 Ptbp2 Alleviates Neuroinflammation and Blood-brain Barrier Disruption via Modulating Microglial Polarization in Ischemic Stroke. Molecular neurobiology 1 41615539
2024 Ptbp2 re-expression rescues axon growth defects in Smn-deficient motoneurons. Frontiers in molecular neuroscience 1 39246602
2024 Construction of an Aspergillus oryzae △nptB△pyrG Host for Homologous Expression of Lipase and Catalytic Property Characterization of Recombinant Lipase. Applied biochemistry and biotechnology 1 39325292
2026 Isoform-Specific Splicing of ANK2 by PTBP2 Orchestrates Retinal Pigment Epithelial-to-Neuron Fate Conversion. Journal of neurochemistry 0 41555757
2026 DNA polymerase kappa stabilized by Ptbp2 interacts with MRE11 and promotes genomic instability in leukemia. Cell death discovery 0 41667423
2026 Transcription factor SOX4 promotes proliferation, invasion and lymphatic metastasis of laryngeal squamous cell carcinoma via PTBP2 activation. Frontiers in oncology 0 42255218
2025 Analysis and identification of PTBP2 as an oncogene in hepatocellular carcinoma. Discover oncology 0 40220253

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