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Gene Review

PIR  -  pirin (iron-binding nuclear protein)

Homo sapiens

Synonyms: Pirin
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Disease relevance of PIR

  • The sets of sequences examined were taken from the 1989 PIR database and consisted of 1,792 "super-family" proteins selected to have little sequence identity, 623 E. coli sequences, and 398 human sequences [1].
  • The long-term treatments eliminated >80% (COM) or >60% (PIR) of adult female worms (P<.001), and the COM regimen effected a sustained depletion of Wolbachia organisms [2].
  • Sixteen of 24 residents in the village of Arso PIR II taking supervised weekly chloroquine prophylaxis (5 mg base/kg) had asexual parasitemia with P. vivax at least once during eight weeks of surveillance [3].
  • Similarly, in Wor, a village near Arso PIR, the gametocyte rate for P. falciparum diminished from 83% to 25% in transmigrants from Java between their eleventh and twenty-fifth month of residence in Irian Jaya, a period during which the falciparum malaria rate remained stable between 30% and 50% [4].
  • RESULTS: The survival of osteosarcoma patients treated with PIR was significantly better than that with DOX (p = 0.023) based on 2-year follow-up [5].

High impact information on PIR

  • Monoclonal and polyclonal antibodies produced against a recombinant PIR protein identified cell surface glycoproteins of approximately 85 and approximately 120 kD on B cells, granulocytes, and macrophages [6].
  • A disulfide-linked homodimer associated with the cell surface PIR molecules was identified as the Fc receptor common gamma (FcRgammac) chain [6].
  • Dendritic cells, monocytes/macrophages, and mast cells expressed the PIR molecules in varying levels, but T cells and NK cells did not [6].
  • In contrast, the PIR-B protein has an uncharged transmembrane region and a long cytoplasmic tail containing four potential immunoreceptor tyrosine-based inhibitory motifs [7].
  • Mapping studies indicated that ZIP interacted through its ZZ zinc finger domain with the phosphorylated insulin receptor interacting region (PIR) of Grb14 [8].

Chemical compound and disease context of PIR


Biological context of PIR

  • Pirin is a recently identified eukaryotic protein implicated in transcriptional activation and apoptosis [10].
  • These findings suggest an enzymatic role for Pirin, most likely in biological redox reactions involving oxygen, and provide compelling evidence that Pirin requires the participation of the metal ion for its interaction with Bcl-3 to co-regulate the NF-kappaB transcription pathway and the interaction with NFI in DNA replication [11].
  • The PIR of Grb14, which also interacts with the catalytic domain of the insulin receptor (IR) and inhibits its activity, was preferentially phosphorylated by PKCzeta [8].
  • In the two-hybrid system, two domains of rGrb14 can mediate the interaction with insulin receptors: the Src homology 2 (SH2) domain and a region between the PH and SH2 domains that we named PIR (for phosphorylated insulin receptor-interacting region) [12].
  • The RESID Database can be used to predict atomic masses for peptides, and is being enhanced to provide molecular structures for graphical presentation on the PIR Web site using widely available molecular viewing programs [13].

Associations of PIR with chemical compounds

  • Molecular surface comparisons of YhhW and Pirin with structurally similar proteins suggested quercetin as a potential ligand [10].
  • The five highly conserved motifs can be used to discriminate the known 5-methylcytosine forming methyltransferases from all other methyltransferases of known sequence, and from all other identified proteins in the PIR, GenBank and EMBL databases [14].
  • The N-terminal amino acid sequence of the first 20 amino acids, which was registered at the PIR Data Submission as the N-terminal partial sequence of Gly m 2, was determined according the Edman degradation method [15].
  • A clinical trial of standard chloroquine therapy for uncomplicated malaria at Arso PIR V in northeastern Indonesian Papua was conducted during 1995 [16].
  • To this end, I evaluated the conservation of the 5-residue motif in all the apolipoprotein sequences known (PIR data bank no. 42) and tested the thyroid hormone binding properties of two animal apolipoproteins that were available (bovine apo A-I and rabbit apo E) [17].

Other interactions of PIR

  • In the same subjects, the effects of PD and PIR on the GH response to GHRH (1.0 microg/kg i.v. at 0 minutes) have also been studied [18].
  • The PIR-Inter-national databases and search tools are accessible on the PIR web site at and at the MIPS web site at [19].
  • Between the PH (pleckstrin homology) and SH2 (Src homology 2) domains is a new binding domain implicated in the interaction with receptor tyrosine kinases called PIR (phosphorylated insulin receptor interaction region) [20].
  • In rigorous jackknife tests, unknown sequences from Pfam-A and PIR-PSD were compared with the probes for each family [21].
  • We show here that pirA (sll1773) encoding an ortholog of Pirin together with an adjacent gene, pirB (ssl3389), was upregulated under high salinity and some other stress conditions in a cyanobacterium Synechocystis sp. PCC 6803 [22].

Analytical, diagnostic and therapeutic context of PIR


  1. The evolution of proteins from random amino acid sequences: II. Evidence from the statistical distributions of the lengths of modern protein sequences. White, S.H. J. Mol. Evol. (1994) [Pubmed]
  2. Antibiotic chemotherapy of onchocerciasis: in a bovine model, killing of adult parasites requires a sustained depletion of endosymbiotic bacteria (Wolbachia species). Gilbert, J., Nfon, C.K., Makepeace, B.L., Njongmeta, L.M., Hastings, I.M., Pfarr, K.M., Renz, A., Tanya, V.N., Trees, A.J. J. Infect. Dis. (2005) [Pubmed]
  3. Resistance to chloroquine by Plasmodium vivax in Irian Jaya, Indonesia. Baird, J.K., Basri, H., Purnomo, n.u.l.l., Bangs, M.J., Subianto, B., Patchen, L.C., Hoffman, S.L. Am. J. Trop. Med. Hyg. (1991) [Pubmed]
  4. Evidence for specific suppression of gametocytemia by Plasmodium falciparum in residents of hyperendemic Irian Jaya. Baird, J.K., Jones, T.R., Purnomo, n.u.l.l., Masbar, S., Ratiwayanto, S., Leksana, B. Am. J. Trop. Med. Hyg. (1991) [Pubmed]
  5. Pirarubicin-based versus doxorubicin-based osteosarcoma chemotherapy. Shinozaki, T., Watanabe, H., Yanagawa, T., Shirakura, K., Takagishi, K. The Annals of pharmacotherapy. (2002) [Pubmed]
  6. Biochemical nature and cellular distribution of the paired immunoglobulin-like receptors, PIR-A and PIR-B. Kubagawa, H., Chen, C.C., Ho, L.H., Shimada, T.S., Gartland, L., Mashburn, C., Uehara, T., Ravetch, J.V., Cooper, M.D. J. Exp. Med. (1999) [Pubmed]
  7. A novel pair of immunoglobulin-like receptors expressed by B cells and myeloid cells. Kubagawa, H., Burrows, P.D., Cooper, M.D. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  8. The adapter protein ZIP binds Grb14 and regulates its inhibitory action on insulin signaling by recruiting protein kinase Czeta. Cariou, B., Perdereau, D., Cailliau, K., Browaeys-Poly, E., Béréziat, V., Vasseur-Cognet, M., Girard, J., Burnol, A.F. Mol. Cell. Biol. (2002) [Pubmed]
  9. The Eurevie Study: contrasting effect of piretanide and thiazides in mild to moderate hypertension. Charansonney, O.L., Lièvre, M., Laville, M., Lion, L., Derobert, E., Visèle, N., Decourt, S., de Rusunan, M.P., Luciani, J., Vasmant, D., Boissel, J.P., Grünfeld, J.P. Thérapie. (1997) [Pubmed]
  10. Structural and biochemical analysis reveal pirins to possess quercetinase activity. Adams, M., Jia, Z. J. Biol. Chem. (2005) [Pubmed]
  11. Crystal structure of human pirin: an iron-binding nuclear protein and transcription cofactor. Pang, H., Bartlam, M., Zeng, Q., Miyatake, H., Hisano, T., Miki, K., Wong, L.L., Gao, G.F., Rao, Z. J. Biol. Chem. (2004) [Pubmed]
  12. Identification of the rat adapter Grb14 as an inhibitor of insulin actions. Kasus-Jacobi, A., Perdereau, D., Auzan, C., Clauser, E., Van Obberghen, E., Mauvais-Jarvis, F., Girard, J., Burnol, A.F. J. Biol. Chem. (1998) [Pubmed]
  13. The RESID Database of protein structure modifications. Garavelli, J.S. Nucleic Acids Res. (1999) [Pubmed]
  14. Predictive motifs derived from cytosine methyltransferases. Pósfai, J., Bhagwat, A.S., Pósfai, G., Roberts, R.J. Nucleic Acids Res. (1989) [Pubmed]
  15. Purification and characterization of a soybean hull allergen responsible for the Barcelona asthma outbreaks. II. Purification and sequencing of the Gly m 2 allergen. Codina, R., Lockey, R.F., Fernández-Caldas, E., Rama, R. Clin. Exp. Allergy (1997) [Pubmed]
  16. Very high risk of therapeutic failure with chloroquine for uncomplicated Plasmodium falciparum and P. vivax malaria in Indonesian Papua. Sumawinata, I.W., Bernadeta, n.u.l.l., Leksana, B., Sutamihardja, A., Purnomo, n.u.l.l., Subianto, B., Sekartuti, n.u.l.l., Fryauff, D.J., Baird, J.K. Am. J. Trop. Med. Hyg. (2003) [Pubmed]
  17. A thyroid hormone binding motif is evolutionarily conserved in apolipoproteins. Benvenga, S. Thyroid (1997) [Pubmed]
  18. Acetylcholine does not play a major role in mediating the endocrine responses to ghrelin, a natural ligand of the GH secretagogue receptor, in humans. Broglio, F., Gottero, C., Benso, A., Prodam, F., Casanueva, F.F., Dieguez, C., van der Lely, A.J., Deghenghi, R., Arvat, E., Ghigo, E. Clin. Endocrinol. (Oxf) (2003) [Pubmed]
  19. Protein Information Resource: a community resource for expert annotation of protein data. Barker, W.C., Garavelli, J.S., Hou, Z., Huang, H., Ledley, R.S., McGarvey, P.B., Mewes, H.W., Orcutt, B.C., Pfeiffer, F., Tsugita, A., Vinayaka, C.R., Xiao, C., Yeh, L.S., Wu, C. Nucleic Acids Res. (2001) [Pubmed]
  20. SAXS study of the PIR domain from the Grb14 molecular adaptor: a natively unfolded protein with a transient structure primer? Moncoq, K., Broutin, I., Craescu, C.T., Vachette, P., Ducruix, A., Durand, D. Biophys. J. (2004) [Pubmed]
  21. A sequence alignment-independent method for protein classification. Vries, J.K., Munshi, R., Tobi, D., Klein-Seetharaman, J., Benos, P.V., Bahar, I. Appl. Bioinformatics (2004) [Pubmed]
  22. A cyanobacterial gene encoding an ortholog of Pirin is induced under stress conditions. Hihara, Y., Muramatsu, M., Nakamura, K., Sonoike, K. FEBS Lett. (2004) [Pubmed]
  23. Purification, crystallization and preliminary X-ray analysis of human pirin. Zeng, Q., Li, X., Bartlam, M., Wang, G., Pang, H., Rao, Z. Acta Crystallogr. D Biol. Crystallogr. (2003) [Pubmed]
  24. The PIR-International Protein Sequence Database. Barker, W.C., Garavelli, J.S., McGarvey, P.B., Marzec, C.R., Orcutt, B.C., Srinivasarao, G.Y., Yeh, L.S., Ledley, R.S., Mewes, H.W., Pfeiffer, F., Tsugita, A., Wu, C. Nucleic Acids Res. (1999) [Pubmed]
  25. Amoxicillin dose-effect relationship with Streptococcus pneumoniae in a mouse pneumonia model and roles of in vitro penicillin susceptibilities, autolysis, and tolerance properties of the strains. Azoulay-Dupuis, E., Moine, P., Bedos, J.P., Rieux, V., Vallee, E. Antimicrob. Agents Chemother. (1996) [Pubmed]
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