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Gene Review

PPFIBP1  -  PTPRF interacting protein, binding protein...

Homo sapiens

Synonyms: KIAA1230, L2, Liprin-beta-1, PTPRF-interacting protein-binding protein 1, Protein tyrosine phosphatase receptor type f polypeptide-interacting protein-binding protein 1, ...
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Disease relevance of PPFIBP1

  • CONCLUSIONS: In the current study the authors identified genomic regions and new candidate genes (RPS6, CDK4, and PPFIBP1) that were associated with tumor progression and prognosis in patients with high-grade chondrosarcomas [1].
  • A peptide derived from the human papillomavirus L2 protein is recognized by a myelin basic protein (MBP)-specific T cell clone from a multiple sclerosis patient and by MBP-specific autoantibodies purified from multiple sclerosis brain tissue [2].
  • The translation of 15-lipoxygenase (LOX) mRNA in erythroid precursor cells and of the L2 mRNA of human papilloma virus type 16 (HPV-16) in squamous epithelial cells is silenced when either of these cells is immature and is activated in maturing cells by unknown mechanisms [3].
  • Three new members of this family have now been cloned and characterized, two proteins from Legionella pneumophila (L1 H-NOX and L2 H-NOX) and one from Nostoc punctiforme (Np H-NOX) [4].
  • McCoy cells infected with Chlamydia trachomatis serovars E or L2 revealed, by indirect immunofluorescence microscopy, collocation of microtubules and Chlamydia-containing vesicles during the process of migration from the host cell surface to a perinuclear location [5].

High impact information on PPFIBP1

  • During 6 months of treatment, the bone mineral density of the L2 to L4 vertebrae increased 3%; this value exceeded the coefficient of variation of this measurement [6].
  • NO dissociation kinetics for L1 H-NOX and L2 H-NOX have been determined and support a model in which NO dissociates from the distal side of the heme in both 5- and 6-coordinate complexes [4].
  • S100A4-liprin beta1 interaction resulted in the inhibition of liprin beta1 phosphorylation by both kinases in vitro [7].
  • We mapped the S100A4 binding site at the C terminus of the liprin beta1 molecule between amino acid residues 938 and 1005 [7].
  • Immunofluorescence staining demonstrated the co-localization of S100A4 and liprin beta1 in the cytoplasm and particularly at the protrusion sites of the plasma membrane [7].

Chemical compound and disease context of PPFIBP1

  • Chlamydia trachomatis serovar L2 induces protein tyrosine phosphorylation during uptake by HeLa cells [8].
  • Using synthetic peptides we have shown that positively charged sequences present at the C terminus of the L1 protein and the N and C termini of the L2 protein of human papillomavirus type 16 (HPV-16) bind to both DNA and heparan sulfate receptors [9].

Biological context of PPFIBP1

  • Chromosome segment-specific cDNA array analysis of 29 expressed sequences within the whole interval between D12S1617 and sts-N38796 indicated overexpression of four ESTs, two corresponding to DEC2 and PPFIBP1, and two to ESTs with unknown function [10].
  • The complete absence of the L1 domain reduced the enhancements of both of these activities but not the maximal effector-stimulated PDK activity through acetylation of L2 [11].
  • These results indicate that aspects of both the nonproductive and productive phases of the viral life cycle occur normally in the absence of functional L2 [12].
  • In addition, the polyadenylation factor CStF-64 was also found to interact specifically with the region in L2 located 174 nucleotides downstream of the early polyadenylation signal [13].
  • mRNA instability elements in the human papillomavirus type 16 L2 coding region [14].

Anatomical context of PPFIBP1

  • We have now used cell lines deficient for promyelocytic leukemia (PML) protein, the main structural component of ND10, to study the role of this nuclear protein for L2 incorporation into virus-like particles (VLPs) [15].
  • In immunoblotting with anti-phosphotyrosine antibodies of C. trachomatis L2-infected HeLa cells, but not with uninfected cells, two rows of spots were observed with a molecular mass of 69 and 71 kDa and pI from 5.0 to 5 [16].
  • The functional relationship between L1 and L2 lysosome subpopulations has been studied in cultured thyroid cells reassociated into follicles [17].
  • Treatment of prelabelled thyroid cells with chloroquine and leupeptin induced the accumulation of immunoprecipitable 125I-thyroglobulin into a lysosome fraction corresponding to the L2 subpopulation [17].
  • CONCLUSIONS: Keratoconus corneas have elevated levels of cathepsins V/L2, -B, and -G, which can stimulate hydrogen peroxide production, which, in turn, can upregulate catalase, an antioxidant enzyme [18].

Associations of PPFIBP1 with chemical compounds

  • In the current study, we demonstrate that saturated (palmitic and myristic; 50 mum) fatty acids (FA) inhibit activity of the promoter of the major (L2) transcript of the GH receptor gene; unsaturated (oleic and linoleic) FA (200 mum) do not alter activity of the promoter [19].
  • We have previously shown that C. trachomatis L2 induces tyrosine phosphorylation of eukaryotic proteins upon their entry by phagocytosis [16].
  • Furthermore, we demonstrate that a specific, highly conserved, histidine residue in the C-terminal region of L2 is essential for the function of the translational apparatus [20].
  • Near 1 microM Ca(2+), tight binding of PDP1 but not PDP1c to gel-anchored L2 required Mg(2+) [21].
  • The overall polypeptide composition of L, L1 and L2 analysed by polyacrylamide-gel electrophoresis was very similar, except for thyroglobulin which was more abundant in L2 than in either L or L1 [17].

Other interactions of PPFIBP1

  • These findings indicate two target regions within the 3.5-Mb segment in 12p11-12, one proximal including PPFIBP1, and one distal including KRAS2 [10].

Analytical, diagnostic and therapeutic context of PPFIBP1

  • We showed by the immunoprecipitation analysis that S100A4 interacts specifically with liprin beta1 in vivo [7].
  • The L2 sequence was introduced by PCR (by replacing 13 codons) into sequences coding for L1 surface loops D-E (chideltaC-L2), E-F (chideltaA-L2), and an internal loop C-D (chideltaH-L2); into the h4 helix (chideltaF-L2); and between h4 and beta-J structural regions (chideltaE-L2) [22].
  • The presence of inhibitory sequences in the L1 and L2 mRNAs may aid the virus in avoiding the host immunosurveillance and in establishing persistent infections [14].
  • Isothermal titration calorimetry and (45)Ca(2+) binding studies failed to detect binding of Ca(2+) (<100 microM) to L2 or PDP1c, alone, but readily detected binding to L2 and PDP1c [21].
  • Estradiol or levormeloxifene inhibited loss of lumbar spine bone mineral density (BMD) following ovariectomy compared with untreated monkeys (ovx -5.0%; sham -0.4%; est +0.2%; L1 -3.6%, L2 -2.0%, L3 -2.5%) [23].


  1. Array-comparative genomic hybridization of central chondrosarcoma: identification of ribosomal protein S6 and cyclin-dependent kinase 4 as candidate target genes for genomic aberrations. Rozeman, L.B., Szuhai, K., Schrage, Y.M., Rosenberg, C., Tanke, H.J., Taminiau, A.H., Cleton-Jansen, A.M., Bovée, J.V., Hogendoorn, P.C. Cancer (2006) [Pubmed]
  2. In vivo survival of viral antigen-specific T cells that induce experimental autoimmune encephalomyelitis. Ufret-Vincenty, R.L., Quigley, L., Tresser, N., Pak, S.H., Gado, A., Hausmann, S., Wucherpfennig, K.W., Brocke, S. J. Exp. Med. (1998) [Pubmed]
  3. c-Src-mediated phosphorylation of hnRNP K drives translational activation of specifically silenced mRNAs. Ostareck-Lederer, A., Ostareck, D.H., Cans, C., Neubauer, G., Bomsztyk, K., Superti-Furga, G., Hentze, M.W. Mol. Cell. Biol. (2002) [Pubmed]
  4. Nitric oxide binding to prokaryotic homologs of the soluble guanylate cyclase beta1 H-NOX domain. Boon, E.M., Davis, J.H., Tran, R., Karow, D.S., Huang, S.H., Pan, D., Miazgowicz, M.M., Mathies, R.A., Marletta, M.A. J. Biol. Chem. (2006) [Pubmed]
  5. Chlamydia trachomatis utilizes the host cell microtubule network during early events of infection. Clausen, J.D., Christiansen, G., Holst, H.U., Birkelund, S. Mol. Microbiol. (1997) [Pubmed]
  6. Treating a patient with the Werner syndrome and osteoporosis using recombinant human insulin-like growth factor. Rubin, C.D., Reed, B., Sakhaee, K., Pak, C.Y. Ann. Intern. Med. (1994) [Pubmed]
  7. Liprin beta 1, a member of the family of LAR transmembrane tyrosine phosphatase-interacting proteins, is a new target for the metastasis-associated protein S100A4 (Mts1). Kriajevska, M., Fischer-Larsen, M., Moertz, E., Vorm, O., Tulchinsky, E., Grigorian, M., Ambartsumian, N., Lukanidin, E. J. Biol. Chem. (2002) [Pubmed]
  8. Chlamydia trachomatis serovar L2 induces protein tyrosine phosphorylation during uptake by HeLa cells. Birkelund, S., Johnsen, H., Christiansen, G. Infect. Immun. (1994) [Pubmed]
  9. Positively charged sequences of human papillomavirus type 16 capsid proteins are sufficient to mediate gene transfer into target cells via the heparan sulfate receptor. Bousarghin, L., Touzé, A., Combita-Rojas, A.L., Coursaget, P. J. Gen. Virol. (2003) [Pubmed]
  10. Detailed genomic mapping and expression analyses of 12p amplifications in pancreatic carcinomas reveal a 3.5-Mb target region for amplification. Heidenblad, M., Jonson, T., Mahlamäki, E.H., Gorunova, L., Karhu, R., Johansson, B., Höglund, M. Genes Chromosomes Cancer (2002) [Pubmed]
  11. Requirements for the adaptor protein role of dihydrolipoyl acetyltransferase in the up-regulated function of the pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase. Yang, D., Gong, X., Yakhnin, A., Roche, T.E. J. Biol. Chem. (1998) [Pubmed]
  12. The minor capsid protein L2 contributes to two steps in the human papillomavirus type 31 life cycle. Holmgren, S.C., Patterson, N.A., Ozbun, M.A., Lambert, P.F. J. Virol. (2005) [Pubmed]
  13. A downstream polyadenylation element in human papillomavirus type 16 L2 encodes multiple GGG motifs and interacts with hnRNP H. Oberg, D., Fay, J., Lambkin, H., Schwartz, S. J. Virol. (2005) [Pubmed]
  14. mRNA instability elements in the human papillomavirus type 16 L2 coding region. Sokolowski, M., Tan, W., Jellne, M., Schwartz, S. J. Virol. (1998) [Pubmed]
  15. Nuclear localization but not PML protein is required for incorporation of the papillomavirus minor capsid protein L2 into virus-like particles. Becker, K.A., Florin, L., Sapp, C., Maul, G.G., Sapp, M. J. Virol. (2004) [Pubmed]
  16. Characterization of Chlamydia trachomatis l2-induced tyrosine-phosphorylated HeLa cell proteins by two-dimensional gel electrophoresis. Birkelund, S., Bini, L., Pallini, V., Sanchez-Campillo, M., Liberatori, S., Clausen, J.D., Ostergaard, S., Holm, A., Christiansen, G. Electrophoresis (1997) [Pubmed]
  17. Identification of two subpopulations of thyroid lysosomes: relation to the thyroglobulin proteolytic pathway. Selmi, S., Rousset, B. Biochem. J. (1988) [Pubmed]
  18. Increased levels of catalase and cathepsin V/L2 but decreased TIMP-1 in keratoconus corneas: evidence that oxidative stress plays a role in this disorder. Kenney, M.C., Chwa, M., Atilano, S.R., Tran, A., Carballo, M., Saghizadeh, M., Vasiliou, V., Adachi, W., Brown, D.J. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  19. Inhibition of Growth Hormone Receptor Gene Expression by Saturated Fatty Acids: Role of Kruppel-Like Zinc Finger Factor, ZBP-89. Thimmarayappa, J., Sun, J., Schultz, L.E., Dejkhamron, P., Lu, C., Giallongo, A., Merchant, J.L., Menon, R.K. Mol. Endocrinol. (2006) [Pubmed]
  20. Functional implications of ribosomal protein L2 in protein biosynthesis as shown by in vivo replacement studies. Uhlein, M., Weglöhner, W., Urlaub, H., Wittmann-Liebold, B. Biochem. J. (1998) [Pubmed]
  21. Formation of a complex of the catalytic subunit of pyruvate dehydrogenase phosphatase isoform 1 (PDP1c) and the L2 domain forms a Ca2+ binding site and captures PDP1c as a monomer. Turkan, A., Hiromasa, Y., Roche, T.E. Biochemistry (2004) [Pubmed]
  22. Chimeric human papillomavirus type 16 (HPV-16) L1 particles presenting the common neutralizing epitope for the L2 minor capsid protein of HPV-6 and HPV-16. Varsani, A., Williamson, A.L., de Villiers, D., Becker, I., Christensen, N.D., Rybicki, E.P. J. Virol. (2003) [Pubmed]
  23. Levormeloxifene prevents increased bone turnover and vertebral bone loss following ovariectomy in cynomolgus monkeys. Hotchkiss, C.E., Stavisky, R., Nowak, J., Brommage, R., Lees, C.J., Kaplan, J. Bone (2001) [Pubmed]
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