Affinage

PAXIP1

PAX-interacting protein 1 · UniProt Q6ZW49

Length
1069 aa
Mass
121.3 kDa
Annotated
2026-06-10
61 papers in source corpus 32 papers cited in narrative 31 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

PAXIP1 (PTIP) is a multi-BRCT-domain nuclear scaffold that couples sequence-specific DNA-binding factors to histone H3K4 methylation machinery and functions in parallel in the DNA damage response (PMID:10908331, PMID:17500065, PMID:19124460). As an integral component of a Set1-like MLL3/MLL4 (KMT2C/KMT2D) H3K4 methyltransferase complex containing ASH2L, RBBP5, WDR5, hDPY-30, NCOA6, UTX, and the PTIP-binding protein PA1/PAGR1, it carries H3K4-specific HMT activity (PMID:17500065). Through its BRCT modules PTIP bridges DNA-binding transcription factors—PAX2, PITX2, and DACH1—to this complex, assembling it at target elements to deposit H3K4 methylation and activate (or, in the DACH1 context, repress) developmentally and metabolically regulated genes (PMID:10908331, PMID:17925232, PMID:24486544, PMID:33998601). This activity underlies its requirement for H3K4me3, pluripotency-gene expression, and lineage differentiation in embryonic stem cells, for adipogenic induction of PPARγ and C/EBPα, and for H3K4me3 and germline transcription that license immunoglobulin class switch recombination and Tcra V(D)J recombination (PMID:19583951, PMID:19544464, PMID:20671152, PMID:23159437); a PTIP-PA1 subcomplex can mediate transcription and class switch recombination independently of MLL3/MLL4 (PMID:26744420). PTIP also organizes 3D chromatin, maintaining long-range enhancer-promoter contacts at the Igh locus and, together with its PAGR1 partner, promoting global cohesin association with chromatin to support cohesin-dependent enhancer-promoter looping and tumor suppression downstream of STAG2 (PMID:21282469, PMID:37070193, PMID:37702151, PMID:39652422, PMID:39345539). In the DNA damage response, PTIP is recruited to break sites through direct BRCT5/6 recognition of phospho-γH2AX downstream of the γH2AX→MDC1→RNF8 axis, acts upstream of 53BP1 and ATM-dependent SMC1 phosphorylation, and promotes NHEJ via the Artemis nuclease while also facilitating homologous recombination and PCNA-ubiquitination-dependent translesion synthesis (PMID:18353733, PMID:19124460, PMID:19414588, PMID:20088963, PMID:22064073, PMID:25512557). PTIP is essential for mitotic progression and chromosome segregation, localizing to the mitotic centrosome via its C-terminal BRCT domains (PMID:12588986, PMID:36153541).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2000 High

    Established PAXIP1's founding identity as a five-BRCT nuclear protein that directly binds the PAX2 activation domain, defining it as a transcription-factor-associated chromatin protein.

    Evidence Yeast two-hybrid, in vitro binding, co-IP and nuclear co-localization in cultured cells

    PMID:10908331

    Open questions at the time
    • Did not identify the chromatin-modifying activity downstream of PAX2 binding
    • Functional consequence of the interaction unresolved
  2. 2003 High

    Demonstrated PTIP is genetically essential for mitotic progression and genome integrity, the first in vivo evidence of a core proliferative role.

    Evidence Constitutive null mouse embryos with mitotic, DNA-damage, and proliferation readouts

    PMID:12588986

    Open questions at the time
    • Molecular basis linking PTIP loss to DNA damage and mitotic failure not defined
    • Could not separate transcriptional from DNA-repair contributions
  3. 2004 High

    Connected PTIP to the ATM-dependent DNA damage response by showing IR-induced, ATM-requiring association with 53BP1 and a requirement for p53-Ser15 phosphorylation.

    Evidence Co-IP, deletion mapping, siRNA, phospho-Western, survival assays in human cells

    PMID:15456759

    Open questions at the time
    • Direct recruitment mechanism to damage sites unknown
    • Whether PTIP acts upstream or downstream of 53BP1 unresolved
  4. 2007 High

    Defined PTIP as an integral subunit of a Set1-like MLL3/MLL4 H3K4 methyltransferase complex and identified PA1 as its direct partner, establishing the molecular basis of its transcriptional activity.

    Evidence Complex co-purification with mass spectrometry, in vitro HMT assay, direct binding assays

    PMID:17500065 PMID:17925232

    Open questions at the time
    • Whether all functions require the full MLL3/MLL4 complex unresolved
    • Range of recruiting DNA-binding factors not yet enumerated
  5. 2008 High

    Extended PTIP's repair role to replication stress, showing it is required for PCNA ubiquitination and recruitment of translesion polymerase eta and Rad51.

    Evidence Xenopus egg extract immunodepletion plus mammalian RNAi with chromatin fractionation

    PMID:18353733

    Open questions at the time
    • Direct versus indirect contribution to PCNA ubiquitination not separated
    • Mechanism connecting PTIP to the ubiquitination machinery undefined
  6. 2009 High

    Ordered PTIP within the DNA damage signaling cascade — recruited via γH2AX→MDC1→RNF8, acting downstream of RNF8 and upstream of 53BP1 — and established its requirement for ATM-dependent SMC1 phosphorylation and for HR.

    Evidence siRNA epistasis, foci imaging, phospho-Western, DT40 gene disruption and HR substrate assays

    PMID:19124460 PMID:19414588 PMID:20088963

    Open questions at the time
    • Direct phospho-mark recognized by PTIP not yet structurally defined
    • How PTIP regulates 53BP1 localization mechanistically unresolved
  7. 2009 High

    Generalized PTIP's MLL-complex function to developmental and lineage transcription programs, showing it maintains H3K4 methylation required for pluripotency, adipogenesis, and homeotic patterning.

    Evidence Conditional/constitutive knockouts in mouse ES cells and MEFs and Drosophila null alleles with ChIP and rescue

    PMID:19429789 PMID:19544464 PMID:19583951

    Open questions at the time
    • Locus selectivity of PTIP-dependent H3K4 methylation not fully explained
    • Direct versus indirect transcriptional targets not all defined
  8. 2010 High

    Showed PTIP licenses immunoglobulin class switch recombination by driving H3K4me3 and germline transcription at switch regions while separately contributing at DSBs.

    Evidence B-cell conditional knockout with ChIP-seq, RNA-seq, and CSR assays

    PMID:20671152

    Open questions at the time
    • Relative contribution of transcription versus DSB function to CSR not quantified
    • Mechanism of switch-region targeting unresolved
  9. 2011 High

    Revealed PTIP organizes 3D chromatin, being required for enhancer-promoter looping at the Igh locus, linking H3K4 methylation to higher-order genome architecture.

    Evidence Conditional knockout with ChIP and chromosome conformation capture

    PMID:21282469

    Open questions at the time
    • Whether looping defect is cause or consequence of lost H3K4 methylation unresolved
    • Generality beyond the Igh locus not yet tested
  10. 2011 High

    Provided the structural basis for damage-site recruitment by solving the PTIP BRCT5/6–γH2AX complex, demonstrating direct phospho-Ser139 recognition.

    Evidence 2.15 Å X-ray crystallography with mutagenesis and binding assays

    PMID:22064073

    Open questions at the time
    • Does not address how recruitment is coordinated with the RNF8 pathway
    • Affinity contributions of other BRCT pairs not defined
  11. 2012 High

    Demonstrated PTIP couples H3K4me3-dependent germline transcription to programmed DSB resolution during V(D)J recombination and to thymocyte egress, broadening its lymphocyte developmental role.

    Evidence Thymocyte conditional knockout with ChIP, LMPCR DSB detection, and trafficking assays

    PMID:23159437

    Open questions at the time
    • Direct mechanistic link between H3K4me3 and RAG cleavage not fully resolved
    • Whether S1pr1 regulation is direct unresolved
  12. 2012 Medium

    Linked PTIP to disease by showing poly-glutamine-expanded androgen receptor sequesters PTIP from damage foci, sensitizing cells and worsening SBMA muscle pathology.

    Evidence Co-IP, foci imaging, DNA damage assays, and PTIP-heterozygous SBMA mouse model

    PMID:22736030

    Open questions at the time
    • Single-lab finding without independent replication
    • Whether sequestration fully accounts for the phenotype unresolved
  13. 2014 High

    Identified Artemis as a PTIP-binding effector downstream of the 53BP1-PTIP axis that promotes NHEJ by blocking end resection, explaining PTIP's role in repair pathway choice and PARP-inhibitor response.

    Evidence Co-IP, double-knockout epistasis, end-resection and PARP-inhibitor sensitivity assays

    PMID:25512557

    Open questions at the time
    • Structural basis of the PTIP-Artemis interaction undefined
    • How Artemis recruitment is regulated temporally unresolved
  14. 2014 Medium

    Showed PTIP-MLL4 activity is recruited by the homeodomain factor PITX2, extending the TF-bridging paradigm to additional developmental regulators.

    Evidence Co-IP, in vitro HMT assay, ChIP, and domain mapping

    PMID:24486544

    Open questions at the time
    • Single-lab finding
    • In vivo significance of PITX2-PTIP cooperation not tested
  15. 2015 Medium

    Established a phosphorylation-controlled activation/repression switch in which PPM1B dephosphorylates the PAX2 activation domain to displace PTIP and recruit Groucho repressors.

    Evidence Co-IP, phosphatase assays, ChIP, reporter assays, and siRNA

    PMID:25631048

    Open questions at the time
    • Single-lab finding
    • Genome-wide scope of the switch not defined
  16. 2016 High

    Dissected PTIP function by showing a PTIP-PA1 BRCT subcomplex mediates transcription and class switch recombination independently of MLL3/MLL4 and of damage-site localization.

    Evidence Quantitative proteomics, domain mutagenesis, B-cell knockout, and CSR assays

    PMID:26744420

    Open questions at the time
    • Identity of additional PA1-subcomplex effectors unresolved
    • Mechanism of MLL-independent transcriptional activation undefined
  17. 2016 Medium

    Connected PTIP BRCT domains to cell-cycle and apoptotic control through interaction with WEE1 kinase and modulation of CDK1 phosphorylation and chemosensitivity.

    Evidence Co-IP interaction network, pharmacologic screen, ectopic expression, caspase-3 assays

    PMID:27196765

    Open questions at the time
    • Single-lab finding with correlative functional readout
    • Whether WEE1 regulation is direct unresolved
  18. 2021 Medium

    Revealed PTIP can be used for transcriptional repression, recruited by DACH1 to reduce promoter H3K4me3, demonstrating context-dependent outcomes of PTIP-H3K4me3 activity.

    Evidence Co-IP, ChIP for H3K4me3, RNA-seq, conditional knockout, and siRNA in podocytes

    PMID:33998601

    Open questions at the time
    • Single-lab finding
    • Mechanism by which DACH1-PTIP reduces rather than deposits H3K4me3 unresolved
  19. 2022 Medium

    Extended PTIP enhancer function to macrophage metabolism, showing it cooperates with p300 to establish an H3K27ac-marked CD38 enhancer governing NAD+ metabolism and inflammation.

    Evidence Macrophage conditional knockout, ChIP-seq, metabolic profiling, cytokine assays

    PMID:35354042

    Open questions at the time
    • Single-lab finding
    • Direct versus indirect role at the CD38 enhancer not separated
  20. 2022 Medium

    Demonstrated PTIP is required for proper chromosome segregation and localizes to the mitotic centrosome via its C-terminal BRCT domains, providing a molecular handle on its mitotic role.

    Evidence siRNA, live-cell imaging, immunofluorescence, and BRCT domain mapping in HeLa cells

    PMID:36153541

    Open questions at the time
    • Single-lab finding
    • Centrosomal binding partners undefined
  21. 2023 High

    Established that PAXIP1, with PAGR1, promotes global cohesin chromatin association and cohesin-dependent enhancer-promoter contacts, linking it to STAG2-cohesin biology and a tumor-suppressive axis.

    Evidence CRISPR screens, ChIP-seq for cohesin, Hi-C, ATAC-seq, co-IP, FDF-motif mutagenesis, and in vivo lung tumor epistasis

    PMID:37070193 PMID:37702151 PMID:39345539 PMID:39652422

    Open questions at the time
    • Mechanism by which PAXIP1/PAGR1 loads or stabilizes cohesin undefined
    • Whether cohesin role is separable from H3K4 methylation function unresolved
  22. 2024 Medium

    Identified UFMylation of PTIP under replication stress as a regulator of nascent-DNA degradation at stalled forks in BRCA1-deficient cells, adding a post-translational layer to its fork-protection role.

    Evidence Denaturing co-IP, DNA fiber assays, and PARP-inhibitor sensitivity with siRNA

    PMID:38657865

    Open questions at the time
    • Single-lab finding
    • UFMylation site and how it alters PTIP activity undefined
  23. 2024 Medium

    Showed PTIP drives an intermediate post-irradiation H3K4me3 increase that epigenetically induces PRDM1 to promote cell-cycle arrest, tying its MLL-complex function to the damage response output.

    Evidence Hematopoietic conditional knockout, ChIP for H3K4me3, expression and cell-cycle assays after IR

    PMID:39097652

    Open questions at the time
    • Single-lab finding
    • Directness of PRDM1 regulation not fully established
  24. 2025 Medium

    Reported a non-canonical mitochondrial pool of PTIP that triggers cytochrome c release and apoptosis, dependent on its N-terminal glutamine-rich region and specific BRCT residues.

    Evidence Subcellular fractionation, immunofluorescence, cytochrome c release and apoptosis assays, domain mutagenesis

    PMID:41608385

    Open questions at the time
    • Single-lab finding without independent replication
    • Trigger and transport machinery for nuclear-to-mitochondrial relocation undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PTIP partitions among its distinct roles — MLL-dependent transcription, MLL-independent PA1 transcription, cohesin loading, DNA repair, and mitochondrial apoptosis — and how each is selectively engaged at given loci or conditions remains unresolved.
  • No unifying model assigning PTIP molecules to specific functions
  • Regulation of context-specific recruitment (TF identity, post-translational modification, subcomplex composition) undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0140110 transcription regulator activity 4 GO:0042393 histone binding 1
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 2 GO:0005739 mitochondrion 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 3 R-HSA-4839726 Chromatin organization 3 R-HSA-1640170 Cell Cycle 2
Partners
53BP1ARTEMISDACH1PAGR1PAX2PITX2STAG2WEE1
Complex memberships
MLL3/MLL4 (KMT2C/KMT2D) Set1-like H3K4 methyltransferase complexPTIP-PA1/PAGR1 subcomplexcohesin (STAG2)

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 PTIP (PAXIP1) was identified as a novel protein that directly binds to the activation domain of PAX2 (and other Pax proteins) in vitro, in yeast two-hybrid assays, and in tissue culture cells. The octapeptide repression domain of Pax2 inhibits this binding. PTIP contains five BRCT domains and co-localizes with Pax2 in the nucleus at actively expressed chromatin and the nuclear matrix fraction. Yeast two-hybrid, in vitro binding, co-immunoprecipitation in tissue culture, nuclear fractionation, co-localization Nucleic acids research High 10908331
2003 PTIP is essential for progression through mitosis. PTIP-null mouse embryos show reduced mitosis, widespread cell death, DNA damage preceding nuclear condensation, and defective phospho-histone H3 expression. Neither embryonic fibroblasts nor embryonic stem cells from PTIP mutants proliferate in culture. Trophoblast cells are more sensitive to DNA-damaging agents. Constitutive null allele generation in mice, immunostaining for mitotic markers (phospho-H3), DNA damage markers, cell culture proliferation assays Molecular and cellular biology High 12588986
2004 Human PTIP (hPTIP) contains 1069 amino acids and six BRCT domains. It shows increased association with 53BP1 in response to ionizing radiation (IR), and this IR-induced association requires ATM. PTIP is required for ATM-mediated phosphorylation of p53 at Ser15 and for IR-induced up-regulation of p21. PTIP depletion increases cellular sensitivity to IR. Co-immunoprecipitation, deletion analysis, siRNA knockdown, Western blot for p53-Ser15 phosphorylation and p21, cell survival assays The Journal of biological chemistry High 15456759
2007 Endogenous PTIP and a novel protein PA1 are components of a Set1-like histone H3K4 methyltransferase (HMT) complex containing ASH2L, RBBP5, WDR5, hDPY-30, NCOA6, MLL3, MLL4, and UTX. The PTIP complex carries HMT activity specifically methylating H3K4. PA1 binds PTIP directly and requires PTIP for interaction with the rest of the complex. hDPY-30 binds ASH2L directly. Co-purification, mass spectrometry, co-immunoprecipitation, in vitro HMT assay, direct binding assays The Journal of biological chemistry High 17500065
2007 PTIP bridges the DNA-binding protein PAX2 to the ALR/MLL3/MLL4 H3K4 methyltransferase complex. PAX2 promotes assembly of this complex and H3K4 methylation at a PAX2-binding DNA element through PTIP. Without PTIP, PAX2 binds DNA but fails to assemble the ALR complex. PTIP-null and conditional mutants show reduced H3K4 methylation levels. Co-purification, conditional and constitutive knockout mice, chromatin immunoprecipitation (ChIP), H3K4 methylation assays Developmental cell High 17925232
2008 PTIP/Swift is required for efficient PCNA ubiquitination and recruitment of TLS polymerase eta to chromatin in response to DNA damage. Immunodepletion of PTIP/Swift from Xenopus egg extracts prevented PCNA ubiquitination and polymerase eta recruitment during replicative stress. PTIP depletion in mammalian cells by RNAi reduced PCNA ubiquitination and decreased recruitment of polymerase eta and Rad51 to chromatin. Xenopus egg extract immunodepletion, siRNA knockdown in mammalian cells, chromatin fractionation assays DNA repair High 18353733
2009 Recruitment of PTIP to damaged chromatin depends on the DNA damage signaling pathway γH2AX→MDC1→RNF8, which in turn facilitates sustained localization of PA1 to DNA break sites. The N-terminal PA1-binding domain and C-terminal focus-localization domain of PTIP are critical for its DNA damage repair function, which is likely independent of the MLL complexes. Co-immunoprecipitation, siRNA knockdown, immunofluorescence for DNA damage foci, domain deletion analysis, cell viability after ionizing radiation The Journal of biological chemistry High 19124460
2009 PTIP is required for PPARγ and C/EBPα expression during adipogenesis. PTIP deletion in mouse embryonic fibroblasts markedly decreases PPARγ expression and impairs H3K4 trimethylation and RNA Pol II occupancy at PPARγ and C/EBPα promoters. Rescue of the adipogenesis defect in PTIP-/- MEFs requires co-expression of both PPARγ and C/EBPα. Conditional knockout mice, ChIP for H3K4me3 and RNA Pol II, rescue experiments with PPARγ/C/EBPα co-expression, adipogenesis assays Cell metabolism High 19583951
2009 RNF8 controls DNA damage-induced nuclear foci formation of PTIP, which in turn regulates 53BP1 localization to DNA damage sites. PTIP is also required for ATM-dependent SMC1 phosphorylation at damage sites. PTIP acts downstream of RNF8 and upstream of 53BP1 in the DNA damage response pathway. siRNA knockdown, immunofluorescence for nuclear foci, Western blot for SMC1 phosphorylation, epistasis analysis The Journal of biological chemistry High 19414588
2009 Drosophila PTIP ortholog is essential for anterior/posterior patterning and segmentation. Loss of Drosophila ptip decreases global H3K4 methylation and increases H3K27 methylation. Drosophila PTIP is required to activate homeotic gene expression in response to derepression of Polycomb group genes, and binds to promoter sequences coincident with increased H3K4 trimethylation. Genetic null alleles in Drosophila, global histone methylation analysis, cell culture reporter assays, ChIP at homeotic gene promoters Development (Cambridge, England) High 19429789
2009 PTIP is required to maintain H3K4 methylation in embryonic stem cells. PTIP deletion in ES cells leads to spontaneous differentiation to trophectoderm, loss of pluripotency, reduced Oct4 expression, reduced H3K4 methylation, and impaired differentiation along all three germ layers in embryoid bodies. Conditional PTIP knockout in ES cells using Cre recombinase, flow cytometry, immunostaining, ChIP for H3K4 methylation Stem cells (Dayton, Ohio) Medium 19544464
2010 PTIP promotes DNA double-strand break repair through homologous recombination (HR). PTIP-deficient chicken DT40 cells show increased spontaneous DNA lesions, sensitivity to IR and camptothecin, and reduced HR efficiency as measured by artificial recombination substrates. PTIP-depleted HeLa cells also show reduced HR efficiency. Gene disruption in DT40 cells, HR efficiency assay with recombination substrates, sensitivity assays (IR, camptothecin), siRNA in HeLa cells Genes to cells : devoted to molecular & cellular mechanisms High 20088963
2010 PTIP promotes H3K4me3 and transcription initiation at downstream switch regions of the immunoglobulin heavy-chain (Igh) locus in activated B cells. PTIP-deficient B cells show impaired H3K4me3 and transcription at Igh switch regions, leading to defective class switch recombination (CSR). PTIP accumulation at DSBs also contributes to CSR and genome stability independently of Igh switch transcription. Conditional B-cell-specific PTIP knockout, ChIP-seq, RNA-seq, class switch recombination assays, flow cytometry Science (New York, N.Y.) High 20671152
2011 PTIP is required for long-range chromatin interactions between the 3' regulatory region enhancer and germline transcript promoters at the immunoglobulin heavy chain locus. Loss of PTIP in mature B cells inhibits CSR by suppressing H3K4 methylation at germline transcript promoters, reduces Pax5 binding, and abolishes chromatin looping detected by chromosome conformation capture. CD19-Cre conditional PTIP knockout, ChIP, chromosome conformation capture (3C), class switch recombination assays Molecular and cellular biology High 21282469
2011 The tandem BRCT5-BRCT6 domain of human PTIP directly recognizes the γH2AX tail, and this interaction depends on phosphorylation of H2AX Ser139. Crystal structure at 2.15 Å resolution of the hPTIP BRCT5/6-γH2AX complex was determined, and mutation analysis confirmed the molecular basis for the interaction. X-ray crystallography (2.15 Å resolution), mutagenesis, binding assays FEBS letters High 22064073
2012 PAXIP1/PTIP regulates RAG-mediated cleavage and repair during V(D)J recombination in DP thymocytes. Loss of PAXIP1 diminishes Jα H3K4me3 and germline transcription, suppresses DSB formation at 3' Jα segments, and results in accumulation of unresolved Tcra breaks. PAXIP1 is also essential for S1PR1-mediated mature thymocyte egress from the thymus through transcriptional activation of S1pr1. Conditional knockout in thymocytes, ChIP for H3K4me3, DSB detection assays (LMPCR), flow cytometry, gene expression analysis Immunity High 23159437
2012 The mutant androgen receptor (AR) with poly-glutamine expansion (associated with SBMA) specifically interacts with PTIP and sequesters PTIP away from radiation-induced nuclear foci. This results in increased sensitivity to DNA-damaging agents and chromosomal instabilities. In a mouse model of SBMA, DNA damage is detected in muscle cells and muscular atrophy is accelerated when one copy of PTIP is removed. Co-immunoprecipitation, immunofluorescence for nuclear foci, DNA damage assays, mouse genetic model (PTIP heterozygosity in SBMA model) Human molecular genetics Medium 22736030
2014 PTIP binds to Artemis nuclease as a PTIP-binding protein. Loss of Artemis restores PARP inhibitor resistance in BRCA1-deficient cells, demonstrating Artemis is a major downstream effector of the 53BP1-PTIP pathway that prevents end resection and promotes NHEJ, directly competing with homologous recombination repair. Co-immunoprecipitation, genetic epistasis (double knockout cell lines), PARP inhibitor sensitivity assays, end resection assays Genes & development High 25512557
2014 PITX2 associates with the PTIP-containing MLL4/KMT2D histone H3K4 methyltransferase complex. This association is dependent on PITX2's homeodomain. The PITX2 protein complex possesses H3K4 HMT activity, and ChIP shows co-occupancy of PITX2 and PTIP on PITX2 transcriptional target promoters. Co-immunoprecipitation, in vitro HMT assay, chromatin immunoprecipitation (ChIP), domain deletion analysis Biochemical and biophysical research communications Medium 24486544
2015 The phosphatase PPM1B can dephosphorylate the Pax2 activation domain and displace PTIP, thereby inhibiting H3K4 methylation and gene activation. PPM1B is an essential component of the Groucho4 repressor complex recruited by Pax2. Loss of PPM1B prevents Groucho-mediated gene repression, demonstrating that phosphorylation state of Pax2 controls the switch between PTIP-mediated activation and PPM1B/Groucho-mediated repression. Co-immunoprecipitation, phosphatase assays, ChIP, reporter gene assays, siRNA knockdown The Journal of biological chemistry Medium 25631048
2016 A PTIP-PA1 subcomplex functions independently from the MLL3/MLL4 complex to mediate transcription and class switch recombination. Using quantitative proteomics in primary lymphocytes, a tandem BRCT domain of PTIP was identified as sufficient for CSR, with PA1 as its main functional partner. PTIP promotes CSR separately from its association with the MLL3/MLL4 complex and from its localization to sites of DNA damage. Quantitative proteomics, domain mapping by mutagenesis, B-cell conditional knockout, class switch recombination assays Genes & development High 26744420
2016 PAXIP1 BRCT domains interact with WEE1 kinase and regulate WEE1-mediated phosphorylation of CDK1. Ectopic expression of PAXIP1 promotes enhanced caspase-3-mediated apoptosis in cells treated with WEE1 inhibitor AZD1775 and cisplatin. Co-immunoprecipitation (BRCT-mediated interaction network), pharmacologic screen, ectopic expression, caspase-3 activity assays Molecular cancer therapeutics Medium 27196765
2021 DACH1 interacts with PTIP and is recruited by DACH1 to its promoter-binding sites. DACH1-PTIP recruitment represses transcription and reduces promoter H3K4Me3 levels. DACH1 knockdown in podocytes combined with hyperglycemia triggers target gene upregulation and increased promoter H3K4Me3, revealing that DACH1 uses PTIP-H3K4Me3 activity for transcriptional repression at DACH1 target loci. Co-immunoprecipitation, ChIP for H3K4me3, RNA sequencing, conditional knockout mice, siRNA knockdown The Journal of clinical investigation Medium 33998601
2022 PTIP governs NAD+ metabolism in macrophages by regulating CD38 expression. PTIP cooperates with acetyltransferase p300 to establish an active intronic enhancer of CD38 with enriched H3K27ac. PTIP deletion impairs proinflammatory response, promotes metabolic switch from glycolysis to oxidative phosphorylation, and alters NAD+ metabolism via downregulating CD38. Conditional knockout in macrophages, ChIP for H3K27ac, metabolic profiling (NAD+ measurement), cytokine assays, enhancer identification by ChIP-seq Cell reports Medium 35354042
2022 PTIP is essential for proper chromosome segregation during mitosis in HeLa cells. PTIP inactivation results in prolonged mitotic time, inefficient chromosome alignment, and increased cell death during mitotic exit. PTIP localizes to the mitotic centrosome via its C-terminal BRCT domains. siRNA knockdown, live-cell imaging, immunofluorescence for centrosome localization, BRCT domain deletion analysis Cell division Medium 36153541
2023 PAXIP1 and STAG2 converge to maintain 3D genome architecture and facilitiate promoter-enhancer contacts for glucocorticoid receptor (GR)-dependent transcription. PAXIP1 is required for stability of cohesin on chromatin, cohesin localization to GR-occupied sites, and maintenance of enhancer-promoter interactions. PAXIP1 and STAG2 depletion alter the GR transcriptome without altering the GR cistrome. CRISPR genome-wide screen, ChIP-seq for cohesin, ATAC-seq, Hi-C, co-immunoprecipitation, conditional knockdown Nucleic acids research High 37070193
2023 PAXIP1 (with binding partner PAGR1) promotes global chromatin association of cohesin independently of DNA replication, transcription, or DNA repair. Depletion of PAXIP1 severely aggravates cohesion defects in ESCO2 mutant cells leading to mitotic cell death. Cohesin regulation by PAXIP1 requires PAGR1 and a conserved FDF motif in PAGR1. PAXIP1 co-localizes with cohesin on active gene promoters and enhancers. CRISPR synthetic lethality screens, ChIP-seq for cohesin, co-immunoprecipitation, domain mutagenesis (FDF motif), cohesion assays, live-cell imaging Nucleic acids research High 37702151
2024 PTIP undergoes UFMylation in response to replication stress (detected by denaturing co-immunoprecipitation). This post-translational modification promotes end resection and degradation of nascent DNA at stalled replication forks in BRCA1-deficient cells. PTIP-depleted and UFL1-depleted BRCA1 knockdown cells are less sensitive to PARP inhibitors. Denaturing co-immunoprecipitation, DNA fiber assays for fork degradation, cell viability assay with PARP inhibitors, siRNA knockdown The Journal of biological chemistry Medium 38657865
2024 PTIP is required for H3K4me3 upregulation in an intermediate phase after ionizing radiation and promotes cell cycle arrest by epigenetically inducing PRDM1. PTIP is a component of the MLL histone methyltransferase complex required for this radiation-induced H3K4me3 increase and downstream PRDM1 expression. Conditional knockout in hematopoietic cells, ChIP for H3K4me3, gene expression analysis, cell cycle assays after IR Scientific reports Medium 39097652
2024 PAXIP1 and PAGR1 are epistatic to STAG2 in oncogenic KRAS-driven lung tumorigenesis in vivo. Gene expression and chromatin accessibility profiles in STAG2- and PAXIP1-deficient neoplastic cells are similar, functionally linking STAG2-cohesin to the PAXIP1/PAGR1 heterodimeric complex as a tumor-suppressive axis. Somatic CRISPR-Cas9 in autochthonous mouse lung cancer model, tumor barcoding, RNA-seq, ATAC-seq, genetic epistasis in vivo The Journal of experimental medicine High 39345539 39652422
2025 A fraction of PTIP is actively transported from the nucleus to mitochondria, causing mitochondrial aggregation, cytochrome c release into the cytoplasm, and cellular apoptosis. Deletion of an N-terminal glutamine-rich region, mutation of a conserved threonine within BRCT3, and truncation of the C-terminal BRCT5 domain each significantly reduced apoptosis. Subcellular fractionation, immunofluorescence for mitochondrial localization, cytochrome c release assay, domain deletion/mutagenesis, apoptosis assays Journal of cellular signaling Medium 41608385

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complex. The Journal of biological chemistry 442 17500065
2007 The BRCT-domain containing protein PTIP links PAX2 to a histone H3, lysine 4 methyltransferase complex. Developmental cell 198 17925232
2010 PTIP promotes chromatin changes critical for immunoglobulin class switch recombination. Science (New York, N.Y.) 129 20671152
2009 Histone methylation regulator PTIP is required for PPARgamma and C/EBPalpha expression and adipogenesis. Cell metabolism 114 19583951
2014 PTIP associates with Artemis to dictate DNA repair pathway choice. Genes & development 97 25512557
2000 PTIP, a novel BRCT domain-containing protein interacts with Pax2 and is associated with active chromatin. Nucleic acids research 71 10908331
2003 BRCT domain-containing protein PTIP is essential for progression through mitosis. Molecular and cellular biology 69 12588986
2009 Accumulation of Pax2 transactivation domain interaction protein (PTIP) at sites of DNA breaks via RNF8-dependent pathway is required for cell survival after DNA damage. The Journal of biological chemistry 68 19124460
2004 Human PTIP facilitates ATM-mediated activation of p53 and promotes cellular resistance to ionizing radiation. The Journal of biological chemistry 67 15456759
2019 Long non-coding RNA PAXIP1-AS1 facilitates cell invasion and angiogenesis of glioma by recruiting transcription factor ETS1 to upregulate KIF14 expression. Journal of experimental & clinical cancer research : CR 64 31823805
2024 Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer. Annals of oncology : official journal of the European Society for Medical Oncology 55 38244928
2011 Role of PTIP in class switch recombination and long-range chromatin interactions at the immunoglobulin heavy chain locus. Molecular and cellular biology 55 21282469
2012 The DNA damage- and transcription-associated protein paxip1 controls thymocyte development and emigration. Immunity 42 23159437
2010 PTIP promotes DNA double-strand break repair through homologous recombination. Genes to cells : devoted to molecular & cellular mechanisms 41 20088963
2009 Control of histone methylation and genome stability by PTIP. EMBO reports 41 19229280
2009 PTIP regulates 53BP1 and SMC1 at the DNA damage sites. The Journal of biological chemistry 41 19414588
2019 Long non-coding RNAs influence the transcriptome in pulmonary arterial hypertension: the role of PAXIP1-AS1. The Journal of pathology 40 30450722
2021 DACH1 protects podocytes from experimental diabetic injury and modulates PTIP-H3K4Me3 activity. The Journal of clinical investigation 37 33998601
2008 PTIP/Swift is required for efficient PCNA ubiquitination in response to DNA damage. DNA repair 32 18353733
2016 A PTIP-PA1 subcomplex promotes transcription for IgH class switching independently from the associated MLL3/MLL4 methyltransferase complex. Genes & development 31 26744420
2019 lncRNA Gm10451 regulates PTIP to facilitate iPSCs-derived β-like cell differentiation by targeting miR-338-3p as a ceRNA. Biomaterials 29 31220795
2011 Structural basis of γH2AX recognition by human PTIP BRCT5-BRCT6 domains in the DNA damage response pathway. FEBS letters 28 22064073
2015 The Groucho-associated phosphatase PPM1B displaces Pax transactivation domain interacting protein (PTIP) to switch the transcription factor Pax2 from a transcriptional activator to a repressor. The Journal of biological chemistry 27 25631048
2009 Drosophila ptip is essential for anterior/posterior patterning in development and interacts with the PcG and trxG pathways. Development (Cambridge, England) 27 19429789
2009 The role of PTIP in maintaining embryonic stem cell pluripotency. Stem cells (Dayton, Ohio) 27 19544464
2016 PAXIP1 Potentiates the Combination of WEE1 Inhibitor AZD1775 and Platinum Agents in Lung Cancer. Molecular cancer therapeutics 23 27196765
2015 Evidence for intermediate mesoderm and kidney progenitor cell specification by Pax2 and PTIP dependent mechanisms. Developmental biology 23 25617721
2023 The HOXD9-mediated PAXIP1-AS1 regulates gastric cancer progression through PABPC1/PAK1 modulation. Cell death & disease 22 37225681
2020 Regeneration after acute kidney injury requires PTIP-mediated epigenetic modifications. JCI insight 21 31917689
2021 H3K27ac-induced lncRNA PAXIP1-AS1 promotes cell proliferation, migration, EMT and apoptosis in ovarian cancer by targeting miR-6744-5p/PCBP2 axis. Journal of ovarian research 20 34108034
2024 PTIP UFMylation promotes replication fork degradation in BRCA1-deficient cells. The Journal of biological chemistry 19 38657865
2023 PAXIP1 and STAG2 converge to maintain 3D genome architecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription. Nucleic acids research 18 37070193
2022 PTIP governs NAD+ metabolism by regulating CD38 expression to drive macrophage inflammation. Cell reports 17 35354042
2018 Histone methylation regulator PTIP is required to maintain normal and leukemic bone marrow niches. Proceedings of the National Academy of Sciences of the United States of America 17 30297393
2021 LncRNA PAXIP1-AS1 fosters the pathogenesis of pulmonary arterial hypertension via ETS1/WIPF1/RhoA axis. Journal of cellular and molecular medicine 16 34245091
2012 A polyglutamine expansion disease protein sequesters PTIP to attenuate DNA repair and increase genomic instability. Human molecular genetics 16 22736030
2023 CRISPR screens in sister chromatid cohesion defective cells reveal PAXIP1-PAGR1 as regulator of chromatin association of cohesin. Nucleic acids research 15 37702151
2015 The PTIP-Associated Histone Methyltransferase Complex Prevents Stress-Induced Maladaptive Cardiac Remodeling. PloS one 15 26001054
2017 PTIP chromatin regulator controls development and activation of B cell subsets to license humoral immunity in mice. Proceedings of the National Academy of Sciences of the United States of America 14 29078319
2012 Arrested spermatogenesis and evidence for DNA damage in PTIP mutant testes. Developmental biology 14 23063797
2008 An allelic series uncovers novel roles of the BRCT domain-containing protein PTIP in mouse embryonic vascular development. Molecular and cellular biology 12 18710940
2024 Ptip safeguards the epigenetic control of skeletal stem cell quiescence and potency in skeletogenesis. Science bulletin 10 38493069
2014 PITX2 associates with PTIP-containing histone H3 lysine 4 methyltransferase complex. Biochemical and biophysical research communications 8 24486544
2024 PTIP epigenetically regulates DNA damage-induced cell cycle arrest by upregulating PRDM1. Scientific reports 5 39097652
2017 PTIP promotes recurrence and metastasis of hepatocellular carcinoma by regulating epithelial-mesenchymal transition. Oncotarget 5 28938547
2025 Allele-Specific Regulation of PAXIP1-AS1 by SMC3/CEBPB at rs112651172 in Psychiatric Disorders Drives Synaptic and Behavioral Dysfunctions in Mice. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 4 40911142
2022 PTIP-Associated Protein 1: More Than a Component of the MLL3/4 Complex. Frontiers in genetics 4 35754824
2021 PTIP Inhibits Cell Invasion in Esophageal Squamous Cell Carcinoma via Modulation of EphA2 Expression. Frontiers in oncology 4 33833989
2019 Establishment of TUSMi008-A, an induced pluripotent stem cell (iPSC) line from a 76-year old Alzheimer's disease (AD) patient with PAXIP1 gene mutation. Stem cell research 4 30831521
2021 PTIP Deficiency in B Lymphocytes Reduces Subcutaneous Fat Deposition in Mice. Biochemistry. Biokhimiia 3 33993864
2024 A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis. The Journal of experimental medicine 2 39652422
2023 Ptip is essential for tooth development via regulating Wnt pathway. Oral diseases 2 36648392
2023 PTIP Deficiency in B Lymphocytes Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice. Discovery medicine 2 37272101
2022 An essential role for PTIP in mediating Hox gene regulation along PcG and trxG pathways. The FEBS journal 2 35655387
2022 The genomic stability regulator PTIP is required for proper chromosome segregation in mitosis. Cell division 2 36153541
2025 Ptip and the Trr-COMPASS-like Complex Regulate Cardiac Progenitor Cell Division in the Drosophila Embryonic Heart Tube. International journal of molecular sciences 1 40869273
2025 PAX-Interacting Protein 1 (PTIP) Promotes Apoptosis. Journal of cellular signaling 1 41608385
2024 A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis. bioRxiv : the preprint server for biology 1 39345539
2026 PTIP inhibits proliferation, migration, and angiogenesis of retinal microvascular endothelial cells in a high-glucose environment. In vitro cellular & developmental biology. Animal 0 41514145
2026 Chromatin regulator PTIP: A critical safeguard against B cell apoptosis and exhaustion in TLR-4-driven inflammation. Life sciences 0 41812975
2025 A Newly Characterized, Two BRCT Domain-Containing Isoform of PAX-Interacting Protein (PTIP) Generated via Frame Shift and Alternative Pre-mRNA Splicing. Journal of cellular signaling 0 41623573

Missed literature

Know a paper Affinage missed for PAXIP1? Flag it for the maintainers and the community.

No submissions yet.