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Gene Review

PTPN13  -  protein tyrosine phosphatase, non-receptor...

Homo sapiens

Synonyms: FAP-1, Fas-associated protein-tyrosine phosphatase 1, PNP1, PTP-BAS, PTP-BL, ...
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Disease relevance of PTPN13


High impact information on PTPN13

  • A protein tyrosine phosphatase, FAP-1, capable of interacting with the cytosolic domain of Fas, was identified [6].
  • The variant TTR is not present in the serum of 100 normal individuals, in four cases of primary and six cases of secondary amyloidosis, nor in 26 non-inheriting members of families with FAP1 [7].
  • Amyloid fibrils isolated from type I FAP (FAP1) of Portuguese, Swedish, and Japanese origins consist of a variant transthyretin (TTR) that contains a methionine-for-valine substitution at position 30 or a mixture of normal TTR and this variant form [7].
  • Forced expression of FAP-1 reduces cell surface Fas levels and increases the intracellular pool of Fas within the cytoskeleton network [8].
  • FasL, Fas, FADD, RIP, caspase-8, caspase-3, Bid, FLIP(S+L), FLASH and FAP-1, proteins known to act within the Fas-apoptosis cascade, showed no changes in their expression levels in cells treated with butyrate compared with untreated cells [9].

Chemical compound and disease context of PTPN13

  • Crystal structure of the PTPL1/FAP-1 human tyrosine phosphatase mutated in colorectal cancer: evidence for a second phosphotyrosine substrate recognition pocket [4].
  • Conserved serine-rich motifs identified in the repeat units of P120 and P140 were also found in the repeat units of the human granulocytotropic ehrlichiosis agent 130-kDa protein and of the fimbria-associated adhesin protein Fap1 of Streptococcus parasanguis [10].

Biological context of PTPN13


Anatomical context of PTPN13


Associations of PTPN13 with chemical compounds

  • We use the second PDZ domain (PDZ2) of the human protein tyrosine phosphatase (hPTP1E) as a model to study the energetics of peptide binding to a class I PDZ domain [15].
  • In particular, we demonstrate that a conserved C-terminal cysteine of PRK2 is indispensable for the interaction with PTP-BL [16].
  • Interestingly, a positively charged pocket is located near the PTPL1 catalytic site, reminiscent of the second phosphotyrosine binding site in PTP1B, which is required to dephosphorylate peptides containing two adjacent phosphotyrosine residues (as occurs for example in the activated insulin receptor) [4].
  • Both the carboxyl group and side chain of the valine residue at the C terminus of Fas are essential, and the leucine and serine residues in the 2nd and 3rd positions, respectively, from the C terminus are important for the interactions with PDZ 2 and PDZ 4 of PTPL1 [17].
  • In addition, hPTP1E contains five imperfect repeats possessing significant homology to the GLGF repeats of the junction-associated guanylate kinases such as the Drosophila discs-large tumor suppressor gene (dlg-1) [18].

Physical interactions of PTPN13


Enzymatic interactions of PTPN13


Regulatory relationships of PTPN13


Other interactions of PTPN13

  • These results provide the first evidence that PTPL1/FAP-1 has a key role in the apoptotic process in human breast cancer cells independent of Fas but associated with an early inhibition of the insulin receptor substrate-1/phosphatidylinositol 3-kinase pathway [2].
  • Taken together, PTP-BL, RIL and TRIP6 may function as components of multi-protein complexes at actin-based sub-cellular structures [19].
  • RNA expression analysis revealed overlapping patterns of expression for TRIP6, RIL and PTP-BL, most notably in tissues of epithelial origin [19].
  • Head-to-head juxtaposition of Fas-associated phosphatase-1 (FAP-1) and c-Jun NH2-terminal kinase 3 (JNK3) genes: genomic structure and seven polymorphisms of the FAP-1 gene [26].
  • Both Fas ligand and Fas-associated phosphatase-1 (FAP-1) were expressed only in COLO320DM [27].

Analytical, diagnostic and therapeutic context of PTPN13


  1. PTPN13, a fas-associated protein tyrosine phosphatase, is located on the long arm of chromosome 4 at band q21.3. Inazawa, J., Ariyama, T., Abe, T., Druck, T., Ohta, M., Huebner, K., Yanagisawa, J., Reed, J.C., Sato, T. Genomics (1996) [Pubmed]
  2. Protein-tyrosine phosphatase PTPL1/FAP-1 triggers apoptosis in human breast cancer cells. Bompard, G., Puech, C., Prébois, C., Vignon, F., Freiss, G. J. Biol. Chem. (2002) [Pubmed]
  3. Opposite roles of FAP-1 and dynamin in the regulation of Fas (CD95) translocation to the cell surface and susceptibility to Fas ligand-mediated apoptosis. Ivanov, V.N., Ronai, Z., Hei, T.K. J. Biol. Chem. (2006) [Pubmed]
  4. Crystal structure of the PTPL1/FAP-1 human tyrosine phosphatase mutated in colorectal cancer: evidence for a second phosphotyrosine substrate recognition pocket. Villa, F., Deak, M., Bloomberg, G.B., Alessi, D.R., van Aalten, D.M. J. Biol. Chem. (2005) [Pubmed]
  5. FAP-1 in pancreatic cancer cells: functional and mechanistic studies on its inhibitory role in CD95-mediated apoptosis. Ungefroren, H., Kruse, M.L., Trauzold, A., Roeschmann, S., Roeder, C., Arlt, A., Henne-Bruns, D., Kalthoff, H. J. Cell. Sci. (2001) [Pubmed]
  6. FAP-1: a protein tyrosine phosphatase that associates with Fas. Sato, T., Irie, S., Kitada, S., Reed, J.C. Science (1995) [Pubmed]
  7. Diagnostic radioimmunoassay for familial amyloidotic polyneuropathy before clinical onset. Nakazato, M., Kurihara, T., Matsukura, S., Kangawa, K., Matsuo, H. J. Clin. Invest. (1986) [Pubmed]
  8. FAP-1 association with Fas (Apo-1) inhibits Fas expression on the cell surface. Ivanov, V.N., Lopez Bergami, P., Maulit, G., Sato, T.A., Sassoon, D., Ronai, Z. Mol. Cell. Biol. (2003) [Pubmed]
  9. Inhibition of histone deacetylase activity enhances Fas receptor-mediated apoptosis in leukemic lymphoblasts. Bernhard, D., Skvortsov, S., Tinhofer, I., Hübl, H., Greil, R., Csordas, A., Kofler, R. Cell Death Differ. (2001) [Pubmed]
  10. Glycosylation of homologous immunodominant proteins of Ehrlichia chaffeensis and Ehrlichia canis. McBride, J.W., Yu, X.J., Walker, D.H. Infect. Immun. (2000) [Pubmed]
  11. Association of protein-tyrosine phosphatase PTP-BAS with the transcription-factor-inhibitory protein IkappaBalpha through interaction between the PDZ1 domain and ankyrin repeats. Maekawa, K., Imagawa, N., Naito, A., Harada, S., Yoshie, O., Takagi, S. Biochem. J. (1999) [Pubmed]
  12. Identification of IkappaBalpha as a substrate of Fas-associated phosphatase-1. Nakai, Y., Irie, S., Sato, T.A. Eur. J. Biochem. (2000) [Pubmed]
  13. Interaction of the protein tyrosine phosphatase PTPL1 with the PtdIns(3,4)P2-binding adaptor protein TAPP1. Kimber, W.A., Deak, M., Prescott, A.R., Alessi, D.R. Biochem. J. (2003) [Pubmed]
  14. Extinction of insulin-like growth factor-I mitogenic signaling by antiestrogen-stimulated Fas-associated protein tyrosine phosphatase-1 in human breast cancer cells. Freiss, G., Puech, C., Vignon, F. Mol. Endocrinol. (1998) [Pubmed]
  15. Energetics of Peptide Recognition by the Second PDZ Domain of Human Protein Tyrosine Phosphatase 1E. Milev, S., Bjelić, S., Georgiev, O., Jelesarov, I. Biochemistry (2007) [Pubmed]
  16. The protein kinase C-related kinase PRK2 interacts with the protein tyrosine phosphatase PTP-BL via a novel PDZ domain binding motif. Gross, C., Heumann, R., Erdmann, K.S. FEBS Lett. (2001) [Pubmed]
  17. Characterization of the interactions between PDZ domains of the protein-tyrosine phosphatase PTPL1 and the carboxyl-terminal tail of Fas. Saras, J., Engström, U., Góñez, L.J., Heldin, C.H. J. Biol. Chem. (1997) [Pubmed]
  18. A novel protein-tyrosine phosphatase with homology to both the cytoskeletal proteins of the band 4.1 family and junction-associated guanylate kinases. Banville, D., Ahmad, S., Stocco, R., Shen, S.H. J. Biol. Chem. (1994) [Pubmed]
  19. The zyxin-related protein TRIP6 interacts with PDZ motifs in the adaptor protein RIL and the protein tyrosine phosphatase PTP-BL. Cuppen, E., van Ham, M., Wansink, D.G., de Leeuw, A., Wieringa, B., Hendriks, W. Eur. J. Cell Biol. (2000) [Pubmed]
  20. Solution structure of the PDZ2 domain from cytosolic human phosphatase hPTP1E complexed with a peptide reveals contribution of the beta2-beta3 loop to PDZ domain-ligand interactions. Kozlov, G., Banville, D., Gehring, K., Ekiel, I. J. Mol. Biol. (2002) [Pubmed]
  21. FAS associated phosphatase (FAP-1) blocks apoptosis of astrocytomas through dephosphorylation of FAS. Foehr, E.D., Lorente, G., Vincent, V., Nikolich, K., Urfer, R. J. Neurooncol. (2005) [Pubmed]
  22. The putative tumor suppressor gene PTPN13/PTPL1 induces apoptosis through insulin receptor substrate-1 dephosphorylation. Dromard, M., Bompard, G., Glondu-Lassis, M., Puech, C., Chalbos, D., Freiss, G. Cancer Res. (2007) [Pubmed]
  23. PTPL1 is a direct transcriptional target of EWS-FLI1 and modulates Ewing's Sarcoma tumorigenesis. Abaan, O.D., Levenson, A., Khan, O., Furth, P.A., Uren, A., Toretsky, J.A. Oncogene (2005) [Pubmed]
  24. Immunohistochemical Localization of Fas-associated phosphatase-1 (FAP-1) in Alzheimer disease hippocampus. Savaskan, E., Ravid, R., Meier, F., Müller-Spahn, F., Jockers, R. Appl. Immunohistochem. Mol. Morphol. (2005) [Pubmed]
  25. Identification of two Fas-associated phosphatase-1 (FAP-1) promoters in human cancer cells. Irie, S., Li, Y., Kanki, H., Ohyama, T., Deaven, L.L., Somlo, S., Sato, T.A. DNA Seq. (2001) [Pubmed]
  26. Head-to-head juxtaposition of Fas-associated phosphatase-1 (FAP-1) and c-Jun NH2-terminal kinase 3 (JNK3) genes: genomic structure and seven polymorphisms of the FAP-1 gene. Yoshida, S., Harada, H., Nagai, H., Fukino, K., Teramoto, A., Emi, M. J. Hum. Genet. (2002) [Pubmed]
  27. Anti-Fas antibody-induced apoptosis in human colorectal carcinoma cell lines: role of the p53 gene. Hayashi, H., Tatebe, S., Osaki, M., Goto, A., Sato, K., Ito, H. Apoptosis (1998) [Pubmed]
  28. ZRP-1, a zyxin-related protein, interacts with the second PDZ domain of the cytosolic protein tyrosine phosphatase hPTP1E. Murthy, K.K., Clark, K., Fortin, Y., Shen, S.H., Banville, D. J. Biol. Chem. (1999) [Pubmed]
  29. The gene (PTPN13) encoding the protein tyrosine phosphatase PTP-BL/PTP-BAS is located in mouse chromosome region 5E/F and human chromosome region 4q21. van den Maagdenberg, A.M., Olde Weghuis, D., Rijss, J., Merkx, G.F., Wieringa, B., Geurts van Kessel, A., Hendriks, W.J. Cytogenet. Cell Genet. (1996) [Pubmed]
  30. Expression and potential role of Fas-associated phosphatase-1 in ovarian cancer. Meinhold-Heerlein, I., Stenner-Liewen, F., Liewen, H., Kitada, S., Krajewska, M., Krajewski, S., Zapata, J.M., Monks, A., Scudiero, D.A., Bauknecht, T., Reed, J.C. Am. J. Pathol. (2001) [Pubmed]
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