Affinage

PIR

Pirin · UniProt O00625

Length
290 aa
Mass
32.1 kDa
Annotated
2026-04-28
100 papers in source corpus 28 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PIR encompasses multiple distinct molecular entities studied under the same gene symbol: (1) PIR-B, a murine ITIM-bearing inhibitory receptor that, upon constitutive Lyn/Hck/Fgr-mediated tyrosine phosphorylation, recruits SHP-1 and SHP-2 phosphatases to negatively regulate BCR, FcεRI, TLR9, integrin, and chemokine signaling in B cells, mast cells, macrophages, neutrophils, dendritic cells, and osteoclast precursors, with its activating counterpart PIR-A signaling through FcRγ chain ITAM-dependent pathways (PMID:9547347, PMID:9780174, PMID:12021780, PMID:15723811); (2) Pirin, a nuclear protein whose transcription is driven by NRF2 via an antioxidant response element and which activates E2F1 transcription by directly binding the E2F1 promoter, promoting cell cycle progression (PMID:24390086, PMID:31500513); and (3) the PIR (phosphorylation insulin resistance) domain found in IRS-1 and Grb7/Grb14 adapter proteins, an intrinsically disordered region that engages the insulin receptor kinase domain and whose serine phosphorylation disrupts this interaction to attenuate insulin signaling (PMID:38625937, PMID:14623073). In neurons, PIR-B binds myelin inhibitors (MAG, Nogo, OMgp) and associates with Trk receptors via p75NTR, recruiting SHP-1/SHP-2 to dephosphorylate Trk and suppress axon regeneration (PMID:21364532, PMID:21881600).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Establishing the core inhibitory mechanism of PIR-B: the discovery that PIR-B ITIM tyrosines (especially Y771) recruit SHP-1/SHP-2 to suppress B cell activation resolved how this receptor transduces inhibitory signals, distinguishing it from SHIP-dependent pathways.

    Evidence Tyrosine mutagenesis in PIR-B cytoplasmic domain and SHP-1/SHP-2 double-KO DT40 B cells with functional activation readouts

    PMID:9482905 PMID:9547347

    Open questions at the time
    • Crystal structure of PIR-B ITIM–SHP-1 complex not determined
    • Relative contribution of individual ITIMs beyond Y771 not fully resolved
  2. 1998 High

    Defining the activating counterpart: PIR-A was shown to associate with FcRγ chain via a transmembrane Arg residue, enabling ITAM-dependent calcium mobilization and mast cell activation, establishing the paired receptor paradigm.

    Evidence Chimeric receptor cotransfection in RBL-2H3 and 293T cells, FcRγ KO mice, degranulation and calcium flux assays, Arg mutagenesis

    PMID:10477705 PMID:9730901 PMID:9780174 PMID:9892613

    Open questions at the time
    • Ligand specificity distinguishing PIR-A from PIR-B engagement not clarified
    • Stoichiometry of PIR-A/FcRγ complex unknown
  3. 1999 High

    Identifying the upstream kinase and downstream substrates: Lyn kinase was shown to phosphorylate PIR-B ITIMs, and SHP-1 recruited to PIR-B was shown to dephosphorylate Syk and Btk, explaining how PIR-B intercepts proximal BCR signaling.

    Evidence Dominant-negative SHP-1, co-IP, Lyn-KO mice, kinase/phosphorylation assays

    PMID:10327049 PMID:10611342

    Open questions at the time
    • Whether PIR-B directly dephosphorylates Igα/Igβ or acts only through Syk/Btk not resolved
  4. 1999 High

    Identifying MHC class I as an endogenous PIR-B ligand: reduced PIR-B phosphorylation in MHC-I-deficient mice established that MHC-I molecules provide tonic signals maintaining constitutive PIR-B activation.

    Evidence MHC-I KO mice, phosphorylation Western blot, co-IP

    PMID:10611342

    Open questions at the time
    • Precise MHC-I allele specificity for PIR-B binding not mapped
    • Whether soluble vs membrane-bound MHC-I differentially regulate PIR-B unknown
  5. 2001 High

    Extending PIR-B inhibition to mast cells and revealing SHP-independent ITIM function: PIR-B coligation with FcεRI inhibited IgE-mediated mast cell degranulation, and a third ITIM was found to function independently of SHP-1, SHP-2, and SHIP.

    Evidence PIR-B cytoplasmic mutant transfection in RBL cells, SHP-1-deficient mast cells, serotonin release assay

    PMID:11581305

    Open questions at the time
    • Effector recruited by the third ITIM not identified
    • Relevance of SHP-independent pathway in vivo not tested
  6. 2002 High

    Establishing in vivo physiological consequences: PIR-B KO mice displayed constitutively activated B2 cells, impaired DC maturation, augmented TH2 responses, and increased B1 cells, demonstrating PIR-B as a critical immune checkpoint.

    Evidence PIR-B knockout mice, B cell activation assays, cytokine ELISA, T-dependent antigen immunization

    PMID:12021780

    Open questions at the time
    • Mechanism of DC maturation impairment not fully delineated at the signaling level
    • Role of PIR-B in human immune regulation via LILRB orthologs not directly tested
  7. 2004 High

    Broadening PIR-B's inhibitory reach to innate immunity: PIR-B was shown to suppress neutrophil and macrophage integrin signaling and chemokine responses, with Src kinases Hck/Fgr maintaining tonic PIR-B phosphorylation.

    Evidence Hck/Fgr double-KO and PIR-B KO mice, respiratory burst, chemotaxis, Ca2+ flux, MAPK activation assays

    PMID:15494528 PMID:15723811

    Open questions at the time
    • Direct substrate(s) of SHP-1 downstream of PIR-B in integrin signaling not identified
    • Contribution of individual Src kinases not separated
  8. 2008 High

    Demonstrating cis-interaction with MHC-I and extending to osteoclastogenesis: FRET analysis showed constitutive cis-binding of PIR-B to MHC-I on the same cell, and PIR-B suppressed osteoclast differentiation, linking immune receptor biology to bone homeostasis.

    Evidence FRET, co-IP, in vitro osteoclast differentiation assay, SPR for MHC-I binding, PIR-B KO

    PMID:18787130 PMID:18802077

    Open questions at the time
    • How cis-MHC-I engagement is regulated during activation not determined
    • In vivo bone phenotype of PIR-B KO not characterized
  9. 2009 High

    Connecting PIR-B to TLR9 signaling and autoimmunity: PIR-B on B-1 cells suppressed TLR9-driven Btk phosphorylation and NF-κB activation, preventing natural IgM autoantibody (including rheumatoid factor) production.

    Evidence PIR-B KO × Faslpr double-mutant mice, TLR9 stimulation, Btk/NF-κB biochemistry

    PMID:19687229

    Open questions at the time
    • Whether PIR-B modulates other TLR pathways beyond TLR9 not systematically tested
  10. 2010 High

    Demonstrating PIR-B's role in intestinal immune homeostasis: PIR-B KO mice showed increased susceptibility to DSS colitis, and adoptive transfer of PIR-B-deficient macrophages was sufficient to transfer susceptibility, pinpointing macrophage PIR-B as a disease-relevant checkpoint.

    Evidence PIR-B KO mice, DSS colitis model, macrophage adoptive transfer, MAPK/NF-κB Western blot

    PMID:20398663

    Open questions at the time
    • Specific ligand driving PIR-B activation in gut mucosa not identified
  11. 2011 High

    Revealing a neuronal function: PIR-B was shown to bind myelin inhibitors (MAG, Nogo, OMgp), associate with Trk receptors via p75NTR, and recruit SHP-1/SHP-2 to dephosphorylate Trk, suppressing axon regeneration; in vivo SHP knockdown promoted regeneration after optic nerve crush.

    Evidence Co-IP, in vitro phosphatase assays, SPR for Nogo/MHC-I binding kinetics, p75 mutant mice, in vivo siRNA, optic nerve crush model

    PMID:21364532 PMID:21636572 PMID:21881600

    Open questions at the time
    • Whether PIR-B operates through identical ITIM/SHP mechanism in neurons as in immune cells not fully confirmed
    • Nogo receptor complex hierarchy (NgR1 vs PIR-B) in regeneration not resolved
  12. 2014 Medium

    Identifying NRF2 as the transcriptional driver of human Pirin (PIR): NRF2 was found to bind a conserved ARE downstream of the PIR transcription start site, establishing how Pirin expression is regulated under oxidative stress conditions.

    Evidence Luciferase reporter assays with PIR promoter constructs, ChIP for NRF2 binding

    PMID:24390086

    Open questions at the time
    • Whether other transcription factors co-regulate PIR expression not explored
    • Functional consequence of NRF2-driven PIR upregulation on cell phenotype not directly tested in this study
  13. 2019 Medium

    Establishing Pirin as a transcriptional activator of E2F1: Pirin directly binds the E2F1 promoter and its knockdown causes G1/S arrest and reduced proliferation, linking Pirin to cell cycle control in breast cancer.

    Evidence ChIP, luciferase reporter, siRNA/shRNA knockdown, xenograft model, cell cycle analysis

    PMID:31500513

    Open questions at the time
    • Molecular mechanism by which Pirin activates E2F1 transcription (cofactor interactions, chromatin remodeling) not defined
    • Generalizability beyond breast cancer cell lines not tested
  14. 2000 High

    Characterizing the PIR domain of Grb7/Grb14 adaptor proteins: the PIR domain was shown to bind the activated insulin receptor kinase loop independently of the SH2 domain, and NMR/SAXS revealed it is intrinsically disordered yet functionally active in inhibiting insulin signaling.

    Evidence Two-hybrid, GST pull-down, co-IP, NMR (15N-labeled PIR), SAXS, CD, Xenopus oocyte functional assay

    PMID:10803466 PMID:14623073 PMID:15465854

    Open questions at the time
    • Atomic-resolution structure of PIR domain bound to IR kinase not available
    • In vivo significance of Grb7/14 PIR domain in insulin resistance not directly shown
  15. 2024 High

    Mapping the IRS-1 PIR domain interaction with the insulin receptor: the PIR domain containing Ser307/312/315/323 contacts the N-terminal lobe and hinge of the IR kinase, strengthening IRS-1 binding; serine phosphorylation of these residues disrupts the interaction and reduces AKT signaling, providing a structural basis for insulin resistance.

    Evidence SPR, hydrogen-deuterium exchange MS, phosphomimetic mutagenesis, cell-based insulin signaling assays

    PMID:38625937

    Open questions at the time
    • Which kinase(s) phosphorylate the PIR domain serines in vivo during insulin resistance not identified in this study
    • Whether the IRS-1 PIR domain mechanism is conserved across species not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include: the identity of the SHP-independent effector recruited by the third PIR-B ITIM; whether the distinct PIR-B functions in immune cells versus neurons use identical downstream signaling cascades; and the precise mechanism by which Pirin activates transcription at the E2F1 promoter.
  • Third ITIM effector unidentified
  • No unified signaling model across immune and neuronal PIR-B contexts
  • Pirin's transcriptional cofactors unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0060089 molecular transducer activity 3 GO:0140110 transcription regulator activity 1
Localization
GO:0005886 plasma membrane 7 GO:0005634 nucleus 1
Pathway
R-HSA-168256 Immune System 9 R-HSA-162582 Signal Transduction 5
Partners
BTKE2F1FCERG1LYNNGFRNTRK1SHP-1SHP-2
Complex memberships
PIR-A/FcRγ complexPIR-B/SHP-1 complexPIR-B/Trk/p75NTR complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 PIR-B (paired immunoglobulin-like receptor B) inhibitory signaling requires SHP-1 and SHP-2 phosphatases; mutational analysis identified tyrosine 771 (in VxYxxL motif) as the most critical residue for inhibitory signaling, and PIR-B-mediated inhibition was markedly reduced in SHP-1/SHP-2 double-deficient DT40 B cells but unaffected in SHIP-deficient cells. Mutational analysis of cytoplasmic tyrosines, genetic double-KO DT40 B cells, B cell activation assays The Journal of experimental medicine High 9547347
1998 PIR-B ITIMs, upon tyrosine phosphorylation, recruit SHP-1 protein tyrosine phosphatase (but not SHIP), initiating a SHP-1-dependent inhibitory pathway that negatively regulates B lymphocyte activation. Co-immunoprecipitation, ITIM phosphorylation assays, in vitro binding studies Proceedings of the National Academy of Sciences of the United States of America High 9482905
1999 PIR-B coligation with BCR inhibits BCR-induced tyrosine phosphorylation of Igα/Igβ, Syk, Btk, and PLCγ2; SHP-1 recruited to PIR-B dephosphorylates and inactivates Syk and Btk, which reduces PLCγ2 phosphorylation; Lyn kinase mediates ITIM phosphorylation of PIR-B. Overexpression of catalytically inactive SHP-1 dominant negative, co-IP, kinase assays, calcium flux Oncogene High 10327049
1999 PIR-A associates with the Fc receptor common gamma (FcRγ) chain via a charged Arg residue in its transmembrane region; this association is required for cell surface expression of PIR-A and enables ITAM-dependent activating signaling (calcium mobilization, mast cell activation). Co-transfection, cell surface flow cytometry, FcRγ knockout mice, calcium mobilization assay The Journal of experimental medicine High 9730901 9892613
1998 PIR-A transmembrane domain associates with FcRγ chain via Arg residue; PIR-A cross-linking activates mast cells (calcium mobilization) through ITAM-dependent signaling, while PIR-B delivers inhibitory signals through ITIMs in its cytoplasmic domain suppressing degranulation and Ca2+ mobilization; mutation of 3rd and 4th ITIM tyrosines attenuates PIR-B inhibitory effects. Chimeric receptor expression in RBL-2H3 cells, degranulation assay, cytoplasmic Ca2+ measurement, tyrosine-to-phenylalanine mutagenesis Journal of immunology High 9780174
1999 PIR-B is constitutively tyrosine phosphorylated on macrophages and B lymphocytes and constitutively associated with SHP-1 and Lyn; Lyn kinase is required for PIR-B tyrosine phosphorylation; phosphorylation status is significantly reduced in MHC class I-deficient mice, suggesting MHC class I as an endogenous PIR-B ligand. Co-immunoprecipitation, Lyn-KO mice, MHC-I KO mice, phosphorylation Western blot Proceedings of the National Academy of Sciences of the United States of America High 10611342
1999 PIR-A3 physically interacts with FcεRIγ chain through Arg632 in its transmembrane domain in macrophages; this interaction enables PIR-A to deliver activation signals (nitric oxide production synergized with IFN-γ). Chimeric receptor cotransfection in 293T cells, co-immunoprecipitation, Arg632 mutagenesis, nitric oxide assay Blood High 10477705
2001 PIR-B is preferentially expressed on the mast cell surface where it is constitutively tyrosine phosphorylated and associated with SHP-1; PIR-B coligation with FcεRI inhibits IgE-mediated mast cell activation and serotonin release; a third ITIM was identified that mediates inhibition independent of SHP-1, SHP-2, and SHIP. Co-IP, phosphorylation assays, SHP-1-deficient mast cells, serotonin release assay, RBL cell transfection with PIR-B cytoplasmic mutants The Journal of clinical investigation High 11581305
2002 PIR-B deficiency in mice (PIR-B−/−) leads to impaired dendritic cell maturation, constitutively activated B2 cells, augmented TH2-prone humoral responses (increased IL-4, IgG1, IgE), and increased peritoneal B1 cells, establishing PIR-B as critical for B cell suppression, DC maturation, and TH1/TH2 balance. PIR-B knockout mouse model, B cell activation/proliferation assays, cytokine ELISA, immunization with T-dependent antigens Nature immunology High 12021780
2002 HLA-G interacts with murine PIR-B (a homologue of human ILT4), and this interaction modifies dendritic cell function and prolongs allogeneic graft survival. In vivo graft transplantation model, PIR-B interaction studies with HLA-G European journal of immunology Medium 12207326
2004 Src family kinases Hck and Fgr negatively regulate neutrophil and dendritic cell chemokine signaling by maintaining tonic phosphorylation of PIR-B; in hck−/−fgr−/− cells PIR-B is unphosphorylated and cells are hyperresponsive to chemokines; PIR-B−/− neutrophils and DCs show similarly elevated chemokine responses. Src-family kinase double-KO mice, PIR-B KO mice, Ca2+ flux, MAP kinase activation, actin polymerization, chemotaxis assays Immunity High 15723811
2004 PIR-B negatively regulates neutrophil and macrophage integrin signaling; PIR-B−/− neutrophils show enhanced respiratory burst, granule release, and hyperadhesion on ECM/adhesion molecules; PIR-B−/− macrophages show enhanced phosphorylation of integrin signaling proteins and increased spreading. PIR-B knockout mice, respiratory burst assay, granule release assay, adhesion assay, integrin signaling biochemistry Journal of immunology High 15494528
2005 PIR-B binds MHC class I molecules; PIR-B and CD8αα compete for binding to MHC class I on DCs; PIR-B on DCs blocks CD8 molecule access to MHC-I, thereby reducing CTL triggering; PIR-B-deficient DCs evoke CTLs more efficiently leading to accelerated graft and tumor rejection. Surface plasmon resonance, PIR-B-KO DCs, CTL priming assays, transfectant competition assays Proceedings of the National Academy of Sciences of the United States of America High 18787130
2008 PIR-B and human LILRB inhibitory receptors are expressed on osteoclast precursor cells, constitutively recruit SHP-1 in the presence of RANKL and M-CSF, and suppress osteoclast development in vitro; FRET analysis indicates constitutive binding of PIR-B (and human LILRB1) to MHC class I molecules on the same cell surface (cis) as a regulatory mechanism. Flow cytometry, co-immunoprecipitation, FRET, in vitro osteoclast differentiation assay, PIR-B KO Journal of immunology High 18802077
2009 PIR-B on B-1 cells suppresses TLR9 signaling by dephosphorylating Bruton's tyrosine kinase (Btk), attenuating NF-κB p65RelA activation but not p38 or Erk, and blocking natural IgM autoantibody production including rheumatoid factor. PIR-B KO mice, Fasˡᵖʳ double-mutant, TLR9 stimulation, Btk phosphorylation assays, NF-κB activation assay The Journal of experimental medicine High 19687229
2010 PIR-B negatively regulates macrophage MAPK and NF-κB activation in response to bacterial stimulation; PIR-B−/− mice are more susceptible to DSS-induced colitis; adoptive transfer of PIR-B−/− macrophages into WT mice is sufficient to increase disease susceptibility. PIR-B KO mice, DSS colitis model, macrophage adoptive transfer, cytokine ELISA, MAPK/NF-κB Western blot Gastroenterology High 20398663
2011 PIR-B mediates axon growth inhibition by myelin-derived inhibitors (MAG, Nogo, OMgp); MAG binding to PIR-B leads to PIR-B association with Trk neurotrophin receptors, recruiting SHP-1 and SHP-2 which act as Trk tyrosine phosphatases, reducing basal and neurotrophin-stimulated Trk activity; siRNA knockdown of SHP-1 or SHP-2 in vivo promotes axonal regeneration after optic nerve injury. Co-immunoprecipitation, in vitro phosphatase assays, siRNA knockdown in vivo, optic nerve crush model The EMBO journal High 21364532
2011 p75 neurotrophin receptor interacts with PIR-B upon ligand binding and is required for PIR-B-mediated SHP activation and axon growth inhibition; p75 mutant mice show promotion of axonal regeneration after optic nerve injury. Co-immunoprecipitation, p75 gene mutant mice, optic nerve crush model, SHP activation assay Cell death & disease High 21881600
2011 PIR-B binds Nogo with higher affinity than MHC class I; MHCI binding is restricted to N-terminal PIR-B ectodomains, whereas Nogo binds either N- or C-terminal ectodomains; Nogo and MHCI binding to PIR-B is competitive; endogenous Nogo intensifies PIR-B-mediated suppression of IL-6 release from mast cells. Surface plasmon resonance (kinetic analysis), recombinant PIR-B ectodomain fragments, PIR-B KO mast cells, IL-6 assay The Journal of biological chemistry High 21636572
2014 Basal transcription of the human PIR (Pirin) gene is driven by NRF2 via a highly conserved antioxidant response element (ARE) located 281 bp downstream of the transcription start site; NRF2 was shown to bind this element in vivo. Luciferase reporter assay with PIR promoter constructs, ChIP (NRF2 binding), chromatin immunoprecipitation Molecular and cellular biochemistry Medium 24390086
2019 Pirin (PIR) protein activates E2F1 transcription by directly binding to the E2F1 promoter region; PIR knockdown downregulates E2F1 and its target genes (CDK4, CDK6, cyclin E, cyclin D, DDR1) causing G1/S arrest and reduced proliferation; PIR knockdown also reduces cell migration and invasion in breast cancer cells. Luciferase reporter assay, ChIP, PIR knockdown (siRNA/shRNA), xenograft mouse model, cell cycle analysis Cell cycle Medium 31500513
2020 HPV16 E7 oncoprotein promotes Pirin (PIR) upregulation through the EGFR/PI3K/AKT1/NRF2 signaling pathway, resulting in PIR/NF-κB activation in oral cancer cells. Pathway inhibitor experiments, Western blot, reporter assays for NF-κB activity Cancers Medium 32679705
2024 The PIR domain of IRS-1 (phosphorylation insulin resistance domain, C-terminal to the PTB domain) containing Ser307, Ser312, Ser315, and Ser323 interacts with the N-terminal lobe and hinge region of the IR kinase domain; this interaction strengthens IRS-1 binding to IR and may protect IR from PTP1B-mediated dephosphorylation; phosphorylation of these serines abrogates IRS-1/IR interaction and reduces downstream AKT signaling. Surface plasmon resonance, hydrogen-deuterium exchange mass spectrometry, phosphomimetic mutagenesis, cell-based insulin signaling assays Proceedings of the National Academy of Sciences of the United States of America High 38625937
2000 Grb7 binds activated, tyrosine-phosphorylated insulin receptor through two domains: the SH2 domain and the PIR (phosphotyrosine interacting region) domain; the PIR domain binds the activated tyrosine kinase loop of the insulin receptor; Grb7 is not a substrate of the insulin receptor kinase. Two-hybrid, GST pull-down, co-immunoprecipitation, domain mapping Oncogene Medium 10803466
2003 The PIR domain of Grb14 is an intrinsically unstructured/disordered protein by NMR; despite lacking secondary structure, isolated PIR and PIR-SH2 domains inhibit insulin-induced meiosis reinitiation in Xenopus oocytes, demonstrating functional activity in the absence of folded structure. NMR spectroscopy (15N-labeled PIR), Xenopus oocyte functional assay FEBS letters High 14623073
2004 The PIR domain of Grb14 is natively unfolded in solution (confirmed by SAXS and CD); a short stretch (residues 399-407) may be transiently structured and could mediate binding to the insulin receptor kinase. Small-angle X-ray scattering (SAXS), circular dichroism, computational ensemble modeling Biophysical journal Medium 15465854
2020 C. elegans PIR-1 (ortholog of mammalian PIR-1/DUSP11 RNA phosphatase family) dephosphorylates 5'-triphosphorylated RNAs produced by cellular RNA-dependent RNA polymerases and is required for maturation of Dicer-dependent 26G-RNAs during spermatogenesis and embryogenesis; PIR-1 also regulates the CSR-1 22G-RNA pathway. Genetic KO/depletion, small RNA sequencing, biochemical dephosphorylation assays Molecular cell Medium 33378643

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1986 The protein identification resource (PIR). Nucleic acids research 286 3945547
2011 piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells. Cancer letters 232 22047710
2015 Photorhabdus insect-related (Pir) toxin-like genes in a plasmid of Vibrio parahaemolyticus, the causative agent of acute hepatopancreatic necrosis disease (AHPND) of shrimp. Diseases of aquatic organisms 166 25667334
1998 Requirement of SH2-containing protein tyrosine phosphatases SHP-1 and SHP-2 for paired immunoglobulin-like receptor B (PIR-B)-mediated inhibitory signal. The Journal of experimental medicine 158 9547347
1998 The paired Ig-like receptor PIR-B is an inhibitory receptor that recruits the protein-tyrosine phosphatase SHP-1. Proceedings of the National Academy of Sciences of the United States of America 157 9482905
2006 Pir proteins of Saccharomyces cerevisiae are attached to beta-1,3-glucan by a new protein-carbohydrate linkage. The Journal of biological chemistry 127 16495216
2002 Impaired dendritic cell maturation and increased T(H)2 responses in PIR-B(-/-) mice. Nature immunology 123 12021780
2015 Characterization and PCR Detection Of Binary, Pir-Like Toxins from Vibrio parahaemolyticus Isolates that Cause Acute Hepatopancreatic Necrosis Disease (AHPND) in Shrimp. PloS one 118 26017673
2000 The protein information resource (PIR). Nucleic acids research 116 10592177
1999 Biochemical nature and cellular distribution of the paired immunoglobulin-like receptors, PIR-A and PIR-B. The Journal of experimental medicine 116 9892613
2013 The expression of stem cell protein Piwil2 and piR-932 in breast cancer. Surgical oncology 112 23992744
2002 HLA-G inhibits the functions of murine dendritic cells via the PIR-B immune inhibitory receptor. European journal of immunology 111 12207326
2010 A new cross-linking strategy: protein interaction reporter (PIR) technology for protein-protein interaction studies. Molecular bioSystems 110 20485738
2017 piR-823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF1. Cancer science 109 28618124
1999 Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced activation of Syk and Btk by SHP-1. Oncogene 107 10327049
2008 Inhibitory immunoglobulin-like receptors LILRB and PIR-B negatively regulate osteoclast development. Journal of immunology (Baltimore, Md. : 1950) 104 18802077
2015 piR-55490 inhibits the growth of lung carcinoma by suppressing mTOR signaling. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 101 26408181
1999 Role of NaOH-extractable cell wall proteins Ccw5p, Ccw6p, Ccw7p and Ccw8p (members of the Pir protein family) in stability of the Saccharomyces cerevisiae cell wall. Yeast (Chichester, England) 89 10407261
2005 The Src family kinases Hck and Fgr negatively regulate neutrophil and dendritic cell chemokine signaling via PIR-B. Immunity 85 15723811
1988 The protein identification resource (PIR). Nucleic acids research 85 3353227
2005 The Photorhabdus Pir toxins are similar to a developmentally regulated insect protein but show no juvenile hormone esterase activity. FEMS microbiology letters 81 15796978
2018 Circulating PIWI-Interacting RNAs piR-5937 and piR-28876 Are Promising Diagnostic Biomarkers of Colon Cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 80 29976566
2004 Rat CD8+ FOXP3+ T suppressor cells mediate tolerance to allogeneic heart transplants, inducing PIR-B in APC and rendering the graft invulnerable to rejection. Transplant immunology 79 15589736
1998 Paired immunoglobulin-like receptor (PIR)-A is involved in activating mast cells through its association with Fc receptor gamma chain. The Journal of experimental medicine 78 9730901
2016 piR-651 promotes tumor formation in non-small cell lung carcinoma through the upregulation of cyclin D1 and CDK4. International journal of molecular medicine 77 27431575
1999 Constitutive tyrosine phosphorylation of the inhibitory paired Ig-like receptor PIR-B. Proceedings of the National Academy of Sciences of the United States of America 76 10611342
2011 Myelin suppresses axon regeneration by PIR-B/SHP-mediated inhibition of Trk activity. The EMBO journal 66 21364532
2009 Augmented TLR9-induced Btk activation in PIR-B-deficient B-1 cells provokes excessive autoantibody production and autoimmunity. The Journal of experimental medicine 66 19687229
2010 The pir multigene family of Plasmodium: antigenic variation and beyond. Molecular and biochemical parasitology 65 20045030
2001 Inhibition of IgE-mediated mast cell activation by the paired Ig-like receptor PIR-B. The Journal of clinical investigation 65 11581305
1998 The PIR-International Protein Sequence Database. Nucleic acids research 65 9399794
1999 The PIR-International Protein Sequence Database. Nucleic acids research 64 9847137
2011 piR_015520 belongs to Piwi-associated RNAs regulates expression of the human melatonin receptor 1A gene. PloS one 62 21818375
2004 The inhibitory receptor PIR-B negatively regulates neutrophil and macrophage integrin signaling. Journal of immunology (Baltimore, Md. : 1950) 62 15494528
1998 Inhibitory and stimulatory functions of paired Ig-like receptor (PIR) family in RBL-2H3 cells. Journal of immunology (Baltimore, Md. : 1950) 58 9780174
1993 The PIR-International databases. Nucleic acids research 54 8332528
2010 Paired immunoglobulin-like receptor B (PIR-B) negatively regulates macrophage activation in experimental colitis. Gastroenterology 52 20398663
2004 Arabidopsis NAP and PIR regulate actin-based cell morphogenesis and multiple developmental processes. Plant physiology 52 15516496
1996 The PIR-International Protein Sequence Database. Nucleic acids research 51 8594572
2008 Regulation of cytotoxic T lymphocyte triggering by PIR-B on dendritic cells. Proceedings of the National Academy of Sciences of the United States of America 49 18787130
2019 piR-31470 epigenetically suppresses the expression of glutathione S-transferase pi 1 in prostate cancer via DNA methylation. Cellular signalling 47 31837464
2000 Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2. Oncogene 47 10803466
2004 SAXS study of the PIR domain from the Grb14 molecular adaptor: a natively unfolded protein with a transient structure primer? Biophysical journal 46 15465854
2016 piR-651 and its function in 95-D lung cancer cells. Biomedical reports 45 27123245
2018 Mechanism of piR-DQ590027/MIR17HG regulating the permeability of glioma conditioned normal BBB. Journal of experimental & clinical cancer research : CR 44 30305135
2002 In vitro oligosaccharide synthesis using intact yeast cells that display glycosyltransferases at the cell surface through cell wall-anchored protein Pir. Glycobiology 44 12626410
2011 Low life course socioeconomic status (SES) is associated with negative NEO PI-R personality patterns. International journal of behavioral medicine 43 20012811
2011 The p75 receptor mediates axon growth inhibition through an association with PIR-B. Cell death & disease 43 21881600
2017 A Natural Vibrio parahaemolyticus ΔpirA pirB Mutant Kills Shrimp but Produces neither Pir Toxins nor Acute Hepatopancreatic Necrosis Disease Lesions. Applied and environmental microbiology 42 28576761
2005 A novel recognition system for MHC class I molecules constituted by PIR. Advances in immunology 42 16227090
2020 piR-823 demonstrates tumor oncogenic activity in esophageal squamous cell carcinoma through DNA methylation induction via DNA methyltransferase 3B. Pathology, research and practice 41 32051106
2020 Serum PIWI-Interacting RNAs piR-020619 and piR-020450 Are Promising Novel Biomarkers for Early Detection of Colorectal Cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 40 32066615
2018 The Combination of piR-823 and Eukaryotic Initiation Factor 3 B (EIF3B) Activates Hepatic Stellate Cells via Upregulating TGF-β1 in Liver Fibrogenesis. Medical science monitor : international medical journal of experimental and clinical research 40 30556540
1997 The Protein Information Resource (PIR) and the PIR-International Protein Sequence Database. Nucleic acids research 39 9016497
1998 The pir gene of Erwinia chrysanthemi EC16 regulates hyperinduction of pectate lyase virulence genes in response to plant signals. Proceedings of the National Academy of Sciences of the United States of America 38 9826648
2008 Plasmodium lipid rafts contain proteins implicated in vesicular trafficking and signalling as well as members of the PIR superfamily, potentially implicated in host immune system interactions. Proteomics 36 18563749
2016 Large-Scale and Targeted Quantitative Cross-Linking MS Using Isotope-Labeled Protein Interaction Reporter (PIR) Cross-Linkers. Journal of proteome research 35 28152603
2021 piR-39980 mediates doxorubicin resistance in fibrosarcoma by regulating drug accumulation and DNA repair. Communications biology 34 34799689
2020 piR-39980 promotes cell proliferation, migration and invasion, and inhibits apoptosis via repression of SERPINB1 in human osteosarcoma. Biology of the cell 34 31879982
2023 IL11 signaling mediates piR-2158 suppression of cell stemness and angiogenesis in breast cancer. Theranostics 33 37153732
2020 Circulating SNORD57 rather than piR-54265 is a promising biomarker for colorectal cancer: common pitfalls in the study of somatic piRNAs in cancer. RNA (New York, N.Y.) 33 33376191
2016 Characterization of the Plasmodium Interspersed Repeats (PIR) proteins of Plasmodium chabaudi indicates functional diversity. Scientific reports 33 26996203
2011 Complete sequence of pJIE143, a pir-type plasmid carrying ISEcp1-blaCTX-M-15 from an Escherichia coli ST131 isolate. Antimicrobial agents and chemotherapy 33 21911569
2020 Human Papillomavirus 16 E7 Promotes EGFR/PI3K/AKT1/NRF2 Signaling Pathway Contributing to PIR/NF-κB Activation in Oral Cancer Cells. Cancers 32 32679705
2011 Differential but competitive binding of Nogo protein and class i major histocompatibility complex (MHCI) to the PIR-B ectodomain provides an inhibition of cells. The Journal of biological chemistry 32 21636572
2005 Comparison of cell wall localization among Pir family proteins and functional dissection of the region required for cell wall binding and bud scar recruitment of Pir1p. Eukaryotic cell 32 16278454
1994 The PIR-International Protein Sequence Database. Nucleic acids research 32 7937060
2000 Evidence for the presence of pir-like proteins in Candida albicans. FEMS microbiology letters 31 10802178
2022 Tumour-derived exosomal piR-25783 promotes omental metastasis of ovarian carcinoma by inducing the fibroblast to myofibroblast transition. Oncogene 30 36482201
2021 PIWIL1 interacting RNA piR-017061 inhibits pancreatic cancer growth via regulating EFNA5. Human cell 30 33389678
2024 piR-27222 mediates PM2.5-induced lung cancer by resisting cell PANoptosis through the WTAP/m6A axis. Environment international 29 39106633
2019 Ambient particulate matter attenuates Sirtuin1 and augments SREBP1-PIR axis to induce human pulmonary fibroblast inflammation: molecular mechanism of microenvironment associated with COPD. Aging 29 31299012
2017 Spermatozoa Expression of piR-31704, piR-39888, and piR-40349 and Their Correlation to Sperm Concentration and Fertilization Rate After ICSI. Reproductive sciences (Thousand Oaks, Calif.) 29 28826361
2010 Role of PIR-B in autoimmune glomerulonephritis. Journal of biomedicine & biotechnology 29 20976309
1990 NRL-3D: a sequence-structure database derived from the protein data bank (PDB) and searchable within the PIR environment. Protein sequences & data analysis 29 2259697
2020 Small RNA Profiling of piRNAs in Colorectal Cancer Identifies Consistent Overexpression of piR-24000 That Correlates Clinically with an Aggressive Disease Phenotype. Cancers 28 31940941
2014 Basal PIR expression in HeLa cells is driven by NRF2 via evolutionary conserved antioxidant response element. Molecular and cellular biochemistry 28 24390086
2022 piR-823 inhibits cell apoptosis via modulating mitophagy by binding to PINK1 in colorectal cancer. Cell death & disease 27 35581181
1999 Functional association of FcepsilonRIgamma with arginine(632) of paired immunoglobulin-like receptor (PIR)-A3 in murine macrophages. Blood 27 10477705
1998 Genomic structure of PIR-B, the inhibitory member of the paired immunoglobulin-like receptor genes in mice. Tissue antigens 27 9550322
2000 PIR: a new resource for bioinformatics. Bioinformatics (Oxford, England) 26 10869023
2024 The serine phosphorylations in the IRS-1 PIR domain abrogate IRS-1 and IR interaction. Proceedings of the National Academy of Sciences of the United States of America 24 38625937
2010 Isolation of Pichia pastoris PIR genes and their utilization for cell surface display and recombinant protein secretion. Yeast (Chichester, England) 24 21360733
2022 Serum-derived piR-hsa-164586 of extracellular vesicles as a novel biomarker for early diagnosis of non-small cell lung cancer. Frontiers in oncology 23 36249068
2012 A simple method for construction of pir+ Enterobacterial hosts for maintenance of R6K replicon plasmids. BMC research notes 22 22433797
2003 Characterization of a disulphide-bound Pir-cell wall protein (Pir-CWP) of Yarrowia lipolytica. Yeast (Chichester, England) 22 12673625
2003 The PIR domain of Grb14 is an intrinsically unstructured protein: implication in insulin signaling. FEBS letters 22 14623073
2024 piR-823 tale as emerging cancer-hallmark molecular marker in different cancer types: a step-toward ncRNA-precision. Naunyn-Schmiedeberg's archives of pharmacology 20 39102033
2019 PIR promotes tumorigenesis of breast cancer by upregulating cell cycle activator E2F1. Cell cycle (Georgetown, Tex.) 20 31500513
2024 Small Extracellular Vesicle piR-hsa-30937 Derived from Pancreatic Neuroendocrine Neoplasms Upregulates CD276 in Macrophages to Promote Immune Evasion. Cancer immunology research 19 38572963
2021 piR-hsa-211106 Inhibits the Progression of Lung Adenocarcinoma Through Pyruvate Carboxylase and Enhances Chemotherapy Sensitivity. Frontiers in oncology 19 34249688
2023 FDFT1 repression by piR-39980 prevents oncogenesis by regulating proliferation and apoptosis through hypoxia in tongue squamous cell carcinoma. Life sciences 18 37473805
2020 piR-19166 inhibits migration and metastasis through CTTN/MMPs pathway in prostate carcinoma. Aging 18 32881713
2020 The RNA phosphatase PIR-1 regulates endogenous small RNA pathways in C. elegans. Molecular cell 18 33378643
2019 Nogo-A/Pir-B/TrkB Signaling Pathway Activation Inhibits Neuronal Survival and Axonal Regeneration After Experimental Intracerebral Hemorrhage in Rats. Journal of molecular neuroscience : MN 18 31286407
2018 From the Cover: Roles of mmu_piR_003399 in Microcystin-Leucine Arginine-Induced Reproductive Toxicity in the Spermatogonial Cells and Testis. Toxicological sciences : an official journal of the Society of Toxicology 18 29040791
2018 Multiplex SYBR Green and duplex TaqMan real-time PCR assays for the detection of Photorhabdus Insect-Related (Pir) toxin genes pirA and pirB. Molecular and cellular probes 18 30576786
2014 The contribution of Pir protein family to yeast cell surface display. Applied microbiology and biotechnology 18 24493571
2013 Nevirapine-raltegravir combination, an NRTI and PI/r sparing regimen, as maintenance antiretroviral therapy in virologically suppressed HIV-1-infected patients. Antiviral therapy 18 24145365
2020 PIWI-interacting RNAs piR-13643 and piR-21238 are promising diagnostic biomarkers of papillary thyroid carcinoma. Aging 17 32428871