PTIP

Summary

Gene Symbol: PTIP
Description: PAX interacting protein 1
Alias: CAGF28, CAGF29, PACIP1, PAXIP1L, PTIP, TNRC2, PAX-interacting protein 1, PAX interacting (with transcription-activation domain) protein 1, PAX transcription activation domain interacting protein 1 like, protein encoded by CAG trinucleotide repeats
Species: human
Products:     PTIP

Top Publications

  1. Lechner M, Levitan I, Dressler G. PTIP, a novel BRCT domain-containing protein interacts with Pax2 and is associated with active chromatin. Nucleic Acids Res. 2000;28:2741-51 pubmed
    ..In this report, we describe the isolation and characterization of a novel gene and its encoded protein, PTIP, which binds to the activation domain of Pax2 and other Pax proteins...
  2. Cho E, Prindle M, Dressler G. BRCT domain-containing protein PTIP is essential for progression through mitosis. Mol Cell Biol. 2003;23:1666-73 pubmed
    The Pax transactivation domain-interacting protein (PTIP) is a large nuclear protein with multiple BRCT domains that was identified on the basis of its interaction with transcription factors of the Pax and Smad families...
  3. Wu J, Prindle M, Dressler G, Yu X. PTIP regulates 53BP1 and SMC1 at the DNA damage sites. J Biol Chem. 2009;284:18078-84 pubmed publisher
    Although PTIP is implicated in the DNA damage response, through interactions with 53BP1, the function of PTIP in the DNA damage response remain elusive...
  4. Manke I, Lowery D, Nguyen A, Yaffe M. BRCT repeats as phosphopeptide-binding modules involved in protein targeting. Science. 2003;302:636-9 pubmed
    ..a library of partially degenerate phosphopeptides, we identified tandem BRCT (BRCA1 carboxyl-terminal) domains in PTIP (Pax transactivation domain-interacting protein) and in BRCA1 as phosphoserine- or phosphothreonine-specific ..
  5. Lee J, Saha P, Yang Q, Lee S, Park J, Suh Y, et al. Targeted inactivation of MLL3 histone H3-Lys-4 methyltransferase activity in the mouse reveals vital roles for MLL3 in adipogenesis. Proc Natl Acad Sci U S A. 2008;105:19229-34 pubmed publisher
    ..These results suggest that ASCOM-MLL3 and ASCOM-MLL4 likely function as crucial but redundant H3K4MT complexes for PPARgamma-dependent adipogenesis. ..
  6. Cho Y, Hong S, Jin Q, Wang L, Lee J, Gavrilova O, et al. Histone methylation regulator PTIP is required for PPARgamma and C/EBPalpha expression and adipogenesis. Cell Metab. 2009;10:27-39 pubmed publisher
    ..Here, we show PTIP, a protein that associates with histone H3K4 methyltransferases, regulates PPARgamma and C/EBPalpha expression in ..
  7. Jowsey P, Doherty A, Rouse J. Human PTIP facilitates ATM-mediated activation of p53 and promotes cellular resistance to ionizing radiation. J Biol Chem. 2004;279:55562-9 pubmed
    Mus musculus Pax2 transactivation domain-interacting protein (Ptip) is an essential gene required for the maintenance of genome stability, although its precise molecular role is unclear...
  8. Wang Y, Zhang J, Hu J, Li G, Lei Y, Zhao J. 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 Res. 2019;36:101391 pubmed publisher
    ..In addition, the iPSC line displayed a normal karyotype. Our model might offer a good platform to further study the pathological mechanisms, to identify early biomarkers, and also for drug testing studies in AD. ..
  9. Oravcová M, Boddy M. Recruitment, loading, and activation of the Smc5-Smc6 SUMO ligase. Curr Genet. 2019;: pubmed publisher
    ..Notably, the cofactors and pathways through which Brc1, Rtt107, and their human orthologue (PTIP) act have appeared largely distinct...

More Information

Publications58

  1. Williams J, Williams R, Dovey C, Guenther G, Tainer J, Russell P. gammaH2A binds Brc1 to maintain genome integrity during S-phase. EMBO J. 2010;29:1136-48 pubmed publisher
    ..pombe Brc1, a 6-BRCT-domain protein that is structurally related to Saccharomyces cerevisiae Rtt107 and mammalian PTIP. Brc1 binds gammaH2A to form spontaneous and DNA damage-induced nuclear foci...
  2. McCoy S, Effgen S, Chiarello L, Jeffries L, Villasante Tezanos A. School-based physical therapy services and student functional performance at school. Dev Med Child Neurol. 2018;60:1140-1148 pubmed publisher
    ..interventions, types, student participation) using the School-Physical Therapy Interventions for Pediatrics (S-PTIP) system. Stepwise linear regressions were used to investigate S-PTIP predictors of SFA outcomes...
  3. Das P, Veazey K, Van H, Kaushik S, Lin K, Lu Y, et al. Histone methylation regulator PTIP is required to maintain normal and leukemic bone marrow niches. Proc Natl Acad Sci U S A. 2018;115:E10137-E10146 pubmed publisher
    ..Here we find that the histone methylation regulator PTIP (Pax interaction with transcription-activation domain protein-1) is required to maintain the integrity of the BM ..
  4. Oravcová M, Gadaleta M, Nie M, Reubens M, Limbo O, Russell P, et al. Brc1 Promotes the Focal Accumulation and SUMO Ligase Activity of Smc5-Smc6 during Replication Stress. Mol Cell Biol. 2019;39: pubmed publisher
    ..Brc1 is a multi-BRCT protein that is structurally related to the budding yeast Rtt107 and human PTIP DNA damage response factors, but functional similarities appear limited...
  5. Gao S, Feng S, Ning S, Liu J, Zhao H, Xu Y, et al. An OB-fold complex controls the repair pathways for DNA double-strand breaks. Nat Commun. 2018;9:3925 pubmed publisher
    53BP1 with its downstream proteins, RIF1, PTIP and REV7, antagonizes BRCA1-dependent homologous recombination (HR) and promotes non-homologous end joining (NHEJ) in an unclear manner...
  6. Ranghini E, Dressler G. Evidence for intermediate mesoderm and kidney progenitor cell specification by Pax2 and PTIP dependent mechanisms. Dev Biol. 2015;399:296-305 pubmed publisher
    ..modifying complex to imprint activating histone methylation marks through interactions with the adaptor protein PTIP. In kidney organ culture, conditional PTIP deletion showed that many Pax2 target genes, which were activated early ..
  7. Mejía Ramírez E, Limbo O, Langerak P, Russell P. Critical Function of γH2A in S-Phase. PLoS Genet. 2015;11:e1005517 pubmed publisher
    ..with Brc1, which is a 6-BRCT-domain protein that is structurally related to budding yeast Rtt107 and mammalian PTIP. Brc1, which localizes at stalled replication forks by binding γH2A, prevents aberrant formation of Replication ..
  8. Preciados M, Yoo C, Roy D. Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases. Int J Mol Sci. 2016;17: pubmed
  9. Zhang A, Peng B, Huang P, Chen J, Gong Z. The p53-binding protein 1-Tudor-interacting repair regulator complex participates in the DNA damage response. J Biol Chem. 2017;292:6461-6467 pubmed publisher
    ..53BP1, including replication timing regulatory factor 1 (RIF1) and Pax transactivation domain-interacting protein (PTIP), in the past few years to elucidate how loss of the 53BP1-dependent repair pathway results in PARPi resistance in ..
  10. McVeigh T, Banka S, Reardon W. Kabuki syndrome: expanding the phenotype to include microphthalmia and anophthalmia. Clin Dysmorphol. 2015;24:135-9 pubmed publisher
    ..Children presenting with microphthalmia/anophthalmia should be examined closely for other signs of Kabuki syndrome, especially at an age where the facial gestalt might be less readily appreciable. ..
  11. Daniel J, Santos M, Wang Z, Zang C, Schwab K, Jankovic M, et al. PTIP promotes chromatin changes critical for immunoglobulin class switch recombination. Science. 2010;329:917-23 pubmed publisher
    ..Here, we showed that activated B cells deficient in the PTIP component of the MLL3 (mixed-lineage leukemia 3)-MLL4 complex display impaired trimethylation of histone 3 at ..
  12. Callen E, Faryabi R, Luckey M, Hao B, Daniel J, Yang W, et al. The DNA damage- and transcription-associated protein paxip1 controls thymocyte development and emigration. Immunity. 2012;37:971-85 pubmed publisher
    ..Here we have shown that PAXIP1 (also known as PTIP), a protein associated with MLL3 and MLL4 methyltransferase and the DNA damage response, regulates RAG-mediated ..
  13. Boersma V, Moatti N, Segura Bayona S, Peuscher M, van der Torre J, Wevers B, et al. MAD2L2 controls DNA repair at telomeres and DNA breaks by inhibiting 5' end resection. Nature. 2015;521:537-540 pubmed publisher
    ..End resection blocks NHEJ while committing to homology-directed repair, and is under the control of 53BP1, RIF1 and PTIP. Consistent with MAD2L2 promoting NHEJ-mediated telomere fusion by inhibiting 5' end resection, knockdown of the ..
  14. Noordermeer S, Adam S, Setiaputra D, Barazas M, Pettitt S, Ling A, et al. The shieldin complex mediates 53BP1-dependent DNA repair. Nature. 2018;560:117-121 pubmed publisher
    ..This function of 53BP1 requires interactions with PTIP3 and RIF14-9, the latter of which recruits REV7 (also known as MAD2L2) to break sites10,..
  15. Froimchuk E, Jang Y, Ge K. Histone H3 lysine 4 methyltransferase KMT2D. Gene. 2017;627:337-342 pubmed publisher
    ..KMT2D associates with WRAD (WDR5, RbBP5, ASH2L, and DPY30), NCOA6, PTIP, PA1, and H3K27 demethylase UTX in one protein complex...
  16. Kumar A, Lualdi M, Loncarek J, Cho Y, Lee J, Ge K, et al. Loss of function of mouse Pax-Interacting Protein 1-associated glutamate rich protein 1a (Pagr1a) leads to reduced Bmp2 expression and defects in chorion and amnion development. Dev Dyn. 2014;243:937-47 pubmed publisher
    ..Loss of mouse Pagr1a function leads to defective extraembryonic development, likely due at least in part to altered BMP signaling, contributing to developmental arrest. ..
  17. Starnes L, Su D, Pikkupeura L, Weinert B, Santos M, Mund A, et al. A PTIP-PA1 subcomplex promotes transcription for IgH class switching independently from the associated MLL3/MLL4 methyltransferase complex. Genes Dev. 2016;30:149-63 pubmed publisher
    ..heavy chain (Igh) locus targets CSR-associated DNA damage and is promoted by the BRCT domain-containing PTIP (Pax transactivation domain-interacting protein)...
  18. Cho Y, Hong T, Hong S, Guo H, Yu H, Kim D, et al. PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complex. J Biol Chem. 2007;282:20395-406 pubmed
    b>PTIP, a protein with tandem BRCT domains, has been implicated in DNA damage response. However, its normal cellular functions remain unclear...
  19. Yu P, Ji L, Lee K, Yu M, He C, Ambati S, et al. Subsets of Visceral Adipose Tissue Nuclei with Distinct Levels of 5-Hydroxymethylcytosine. PLoS ONE. 2016;11:e0154949 pubmed publisher
    ..8-fold from the highest quintile of expressed genes to the lowest. In short, VAT-derived adipocytes appear to be more actively remodeling their chromatin than non-adipocytes. ..
  20. Hueber P, Salgado Diaz M, Chaussy Y, Franc Guimond J, Barrieras D, Houle A. Long-term functional outcomes after penoscrotal hypospadias repair: A retrospective comparative study of proximal TIP, Onlay, and Duckett. J Pediatr Urol. 2016;12:198.e1-6 pubmed publisher
    ..Comparison between surgeries (pTIP vs. Onlay vs...
  21. Wu Q, Tian Y, Zhang J, Tong X, Huang H, Li S, et al. In vivo CRISPR screening unveils histone demethylase UTX as an important epigenetic regulator in lung tumorigenesis. Proc Natl Acad Sci U S A. 2018;115:E3978-E3986 pubmed publisher
    ..From individual knockout of 55 potential TSGs, we identify five genes, including Utx, Ptip, Acp5, Acacb, and Clu, whose knockout significantly promotes lung tumorigenesis...
  22. Fang M, Ren H, Liu J, Cadigan K, Patel S, Dressler G. Drosophila ptip is essential for anterior/posterior patterning in development and interacts with the PcG and trxG pathways. Development. 2009;136:1929-38 pubmed publisher
    ..Mouse PTIP is part of a histone H3K4 methyltransferase complex and contains six BRCT domains and a glutamine-rich region...
  23. Stein A, Goonewardena S, Jones T, Prusick P, Bazzi A, Belyavskaya J, et al. The PTIP-Associated Histone Methyltransferase Complex Prevents Stress-Induced Maladaptive Cardiac Remodeling. PLoS ONE. 2015;10:e0127839 pubmed publisher
    ..To demonstrate the importance of the epigenome in HF, we targeted the PTIP-associated histone methyltransferase complex in adult cardiac myocytes...
  24. Fang R, Barbera A, Xu Y, Rutenberg M, Leonor T, Bi Q, et al. Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic H3K4me2 methylation. Mol Cell. 2010;39:222-33 pubmed publisher
    ..These data provide a possible molecular mechanism linking LSD2 to transcriptional regulation after initiation. ..
  25. Lee J, Wang C, Xu S, Cho Y, Wang L, Feng X, et al. H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation. elife. 2013;2:e01503 pubmed publisher
    ..Together, these findings identify MLL4 as a major mammalian H3K4 mono- and di-methyltransferase essential for enhancer activation during cell differentiation. DOI: http://dx.doi.org/10.7554/eLife.01503.001. ..
  26. Figueroa J, Han S, Garcia Closas M, Baris D, Jacobs E, Kogevinas M, et al. Genome-wide interaction study of smoking and bladder cancer risk. Carcinogenesis. 2014;35:1737-44 pubmed publisher
    ..Our findings provide additional evidence of gene-environment interactions for tobacco and bladder cancer. ..
  27. De Gregoriis G, Ramos J, Fernandes P, Vignal G, Brianese R, Carraro D, et al. DNA repair genes PAXIP1 and TP53BP1 expression is associated with breast cancer prognosis. Cancer Biol Ther. 2017;18:439-449 pubmed publisher
    ..We investigated the expression profile of 7 tBRCT genes (BARD1, BRCA1, LIG4, ECT2, MDC1, PAXIP1/PTIP and TP53BP1) in breast cancer specimens and observed a high correlation between PAXIP1 and TP53BP1 gene expression ..
  28. Guo X, Bai Y, Zhao M, Zhou M, Shen Q, Yun C, et al. Acetylation of 53BP1 dictates the DNA double strand break repair pathway. Nucleic Acids Res. 2017;: pubmed publisher
    ..between 53BP1 and nucleosomes, subsequently blocking the recruitment of 53BP1 and its downstream factors PTIP and RIF1 to DSBs...
  29. Jhuraney A, Woods N, Wright G, Rix L, Kinose F, Kroeger J, et al. PAXIP1 Potentiates the Combination of WEE1 Inhibitor AZD1775 and Platinum Agents in Lung Cancer. Mol Cancer Ther. 2016;15:1669-81 pubmed publisher
    ..We propose that WEE1 and PAXIP1 levels may be used as mechanism-based biomarkers of response when WEE1 inhibitor AZD1775 is combined with DNA-damaging agents. Mol Cancer Ther; 15(7); 1669-81. ©2016 AACR. ..
  30. Wang X, Takenaka K, Takeda S. PTIP promotes DNA double-strand break repair through homologous recombination. Genes Cells. 2010;15:243-54 pubmed publisher
    b>PTIP (Pax2 transactivation domain-interacting protein) is a large nuclear protein containing six BRCT (BRCA1 C-Terminal) domains...
  31. Baas R, van Teeffelen H, Tjalsma S, Timmers H. The mixed lineage leukemia 4 (MLL4) methyltransferase complex is involved in transforming growth factor beta (TGF-?)-activated gene transcription. Transcription. 2017;:1-8 pubmed publisher
    ..p300, PCAF and the Mixed Lineage Leukemia 4 (MLL4) subunit Pax Transactivation domain-Interacting Protein (PTIP) to regulate gene transcription...
  32. Wang J, Aroumougame A, Lobrich M, Li Y, Chen D, Chen J, et al. PTIP associates with Artemis to dictate DNA repair pathway choice. Genes Dev. 2014;28:2693-8 pubmed publisher
    ..Since 53BP1 or its known downstream effectors, PTIP and RIF1 (RAP1-interacting factor 1 homolog), lack enzymatic activities directly implicated in DNA repair, we ..
  33. Issaeva I, Zonis Y, Rozovskaia T, Orlovsky K, Croce C, Nakamura T, et al. Knockdown of ALR (MLL2) reveals ALR target genes and leads to alterations in cell adhesion and growth. Mol Cell Biol. 2007;27:1889-903 pubmed
    ..containing a cohort of proteins shared with other SET1 family complexes and several unique components, such as PTIP and the jumonji family member UTX...
  34. Yan W, Shao Z, Li F, Niu L, Shi Y, Teng M, et al. Structural basis of ?H2AX recognition by human PTIP BRCT5-BRCT6 domains in the DNA damage response pathway. FEBS Lett. 2011;585:3874-9 pubmed publisher
    ..15 Å crystal structure of hPTIP BRCT5/6-?H2AX complex and mutation analysis provide molecular evidence for direct interactions between PTIP and ?H2AX. This interaction proffers a new clue to identify the role of PTIP in DDR pathways.
  35. Margolis R, Abraham M, Gatchell S, Li S, Kidwai A, Breschel T, et al. cDNAs with long CAG trinucleotide repeats from human brain. Hum Genet. 1997;100:114-22 pubmed
    ..These genes are therefore candidates for diseases featuring anticipation, neurodegeneration, or abnormalities of neurodevelopment. ..
  36. Hoffmeister A, Ropolo A, Vasseur S, Mallo G, Bodeker H, Ritz Laser B, et al. The HMG-I/Y-related protein p8 binds to p300 and Pax2 trans-activation domain-interacting protein to regulate the trans-activation activity of the Pax2A and Pax2B transcription factors on the glucagon gene promoter. J Biol Chem. 2002;277:22314-9 pubmed
    ..two-hybrid system, using p8 as bait, allowed us to identify the Pax2 trans-activation domain-interacting protein (PTIP) as another partner of p8...
  37. Reubens M, Rozenzhak S, Russell P. Multi-BRCT Domain Protein Brc1 Links Rhp18/Rad18 and ?H2A To Maintain Genome Stability during S Phase. Mol Cell Biol. 2017;37: pubmed publisher
    ..pombe, the multi-BRCT domain protein Brc1, which is related to budding yeast Rtt107 and mammalian PTIP, plays an important role in maintaining genome integrity and cell viability when cells experience replication ..
  38. Mijic S, Zellweger R, Chappidi N, Berti M, Jacobs K, Mutreja K, et al. Replication fork reversal triggers fork degradation in BRCA2-defective cells. Nat Commun. 2017;8:859 pubmed publisher
    ..Besides MRE11 and PTIP, we show that RAD52 promotes stalled fork degradation and chromosomal breakage in BRCA2-defective cells...
  39. Munoz I, Jowsey P, Toth R, Rouse J. Phospho-epitope binding by the BRCT domains of hPTIP controls multiple aspects of the cellular response to DNA damage. Nucleic Acids Res. 2007;35:5312-22 pubmed
    Human (h)PTIP plays important but poorly understood roles in cellular responses to DNA damage...
  40. Su D, Vanhee S, Soria R, Gyllenbäck E, Starnes L, Højfeldt M, et al. PTIP chromatin regulator controls development and activation of B cell subsets to license humoral immunity in mice. Proc Natl Acad Sci U S A. 2017;114:E9328-E9337 pubmed publisher
    ..mouse models to demonstrate that expression of the multifunctional BRCT (BRCA1 C-terminal) domain-containing PTIP (Pax transactivation domain-interacting protein) chromatin regulator is controlled by B cell activation and ..
  41. Liu Y, Huang Y, Fan J, Zhu G. PITX2 associates with PTIP-containing histone H3 lysine 4 methyltransferase complex. Biochem Biophys Res Commun. 2014;444:634-7 pubmed publisher
    ..methyltransferase (HKMT) mixed-lineage leukemia 4 (MLL4/KMT2D), Pax transactivation domain-interacting protein (PTIP), and other H3K4·HKMT core subunits...
  42. Gohler T, Munoz I, Rouse J, Blow J. PTIP/Swift is required for efficient PCNA ubiquitination in response to DNA damage. DNA Repair (Amst). 2008;7:775-87 pubmed publisher
    ..Under these conditions the TLS polymerase eta was recruited to chromatin and also became monoubiquitinated. PTIP/Swift is an adaptor protein for the ATM/ATR kinases...
  43. Abraham S, Paknikar R, Bhumbra S, Luan D, Garg R, Dressler G, et al. 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. J Biol Chem. 2015;290:7185-94 pubmed publisher
    ..PPM1B can dephosphorylate the Pax2 activation domain and displace the adaptor protein PTIP, thus inhibiting H3K4 methylation and gene activation. Loss of PPM1B prevents Groucho-mediated gene repression...
  44. Lee M, Villa R, Trojer P, Norman J, Yan K, Reinberg D, et al. Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination. Science. 2007;318:447-50 pubmed
    ..Our results suggest a concerted mechanism for transcriptional activation in which cycles of H3K4 methylation by MLL2/3 are linked with the demethylation of H3K27 through UTX. ..
  45. Xiao H, Yu Z, Wu Y, Nan J, Merry D, Sekiguchi J, et al. A polyglutamine expansion disease protein sequesters PTIP to attenuate DNA repair and increase genomic instability. Hum Mol Genet. 2012;21:4225-36 pubmed publisher
    ..receptor (AR), a protein associated with spinal and bulbar muscular atrophy (SBMA), and the nuclear protein PTIP (Pax Transactivation-domain Interacting Protein), a protein with an unusually long Q-rich domain that functions in ..
  46. Patel S, Kim D, Levitan I, Dressler G. The BRCT-domain containing protein PTIP links PAX2 to a histone H3, lysine 4 methyltransferase complex. Dev Cell. 2007;13:580-92 pubmed
    ..PAX2 promotes assembly of an H3K4 methyltransferase complex through the ubiquitously expressed nuclear factor PTIP (pax transcription activation domain interacting protein)...
  47. Gong Z, Cho Y, Kim J, Ge K, Chen J. 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. J Biol Chem. 2009;284:7284-93 pubmed publisher
    ..Pax2 transactivation domain interaction protein (PTIP), a protein that contains six BRCT domains, has been implicated in DNA damage response...