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Gene Review

ANP32A  -  acidic (leucine-rich) nuclear...

Homo sapiens

Synonyms: Acidic leucine-rich nuclear phosphoprotein 32 family member A, Acidic nuclear phosphoprotein pp32, C15orf1, HPPCn, I1PP2A, ...
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Disease relevance of ANP32A

  • We had previously described the leucine-rich acidic nuclear protein (LANP) as a candidate mediator of toxicity in the polyglutamine disease, spinocerebellar ataxia type 1 (SCA1) [1].
  • Adenovirus E4orf6 targets pp32/LANP to control the fate of ARE-containing mRNAs by perturbing the CRM1-dependent mechanism [2].
  • Enhanced sensitivity to cytochrome c-induced apoptosis mediated by PHAPI in breast cancer cells [3].
  • Taken together, our results suggest that nucleolin, PHAP II, and PHAP I appear to be functional as potential receptors in the HIV binding process by virtue of their capacity to interact with the V3 loop of gp120 [4].
  • The current investigation was designed to compare the beneficial effects of LANP and vessel dilator in persons with congestive heart failure (CHF) [5].
  • The addition of recombinant pp32/putative human HLA class II-associated protein (pp32/PHAPI), described as a putative tumor suppressor in prostate cancer, successfully restored defective cytochrome c-induced caspase activation in vitro [6].

High impact information on ANP32A

  • LANP is expressed predominantly in Purkinje cells, the primary site of pathology in SCA1 [7].
  • GrnA-induced cytotoxicity and cleavage of PHAP II, a previously identified GrnA substrate, are unimpaired in Jurkat cells that overexpress bcl-2 [8].
  • C-fos mRNA was exported together with E4orf6, E1B-55kD, pp32/LANP, and HuR proteins [2].
  • Using this approach, we have also assessed the ability of putative apoptosome regulatory proteins, such as Smac/DIABLO and PHAPI, to regulate the activity of native apoptosomes [9].
  • Mapmodulin inhibits the initial rate of MAP2 binding to microtubules, a property that may allow mapmodulin to displace MAPs from the path of organelles translocating along microtubules [10].

Biological context of ANP32A


Anatomical context of ANP32A

  • LANP thus could play a key role in neuronal development and/or neurodegeneration by its interactions with microtubule associated proteins [1].
  • Here we report on two putative HLA class II associated proteins (PHAPI and PHAPII) which have been purified from the cytosolic fraction of the human lymphoblastoid B-cell line H2LCL using an affinity matrix composed of the synthetic biotinylated cytoplasmic region of the DR2 alpha chain immobilized on avidin agarose [16].
  • PHAP II begins to be degraded within minutes of initiation of cytotoxic T lymphocyte attack [17].
  • In support of this possibility, mapmodulin stimulates the microtubule- and dynein-dependent localization of Golgi complexes in semi-intact CHO cells [10].
  • Overexpression of GFP-I1PP2A/lanp in PC12 cells leads to markedly reduced neurite length on laminin 5 after induction with nerve growth factor [18].

Associations of ANP32A with chemical compounds

  • The sequence obtained for PHAPI revealed a novel primary structure with a leucine/isoleucine rich N-terminal region [16].
  • Herein we describe the characteristic features of the Anp32 family represented by the cerebellar leucine-rich repeat protein (Lanp) and the cerebellar developmental-regulated protein 1 (Cpd1) [19].
  • The phosphatase binds to the cytoplasmic membrane-proximal conserved GFFKR motif of the alpha integrin subunit, whereas I1PP2A/lanp requires a longer sequence for binding [18].
  • Filler treatment with small amounts of MAPM shifted the alpha-relaxations to higher temperatures; they were shifted back to lower temperatures when the filler was treated with large amounts of silane [20].
  • 3-Acryloxypropyltrimethoxysilane (MAPM) and 4-aminobutyltriethoxysilane (ABTE) were used as silanating coupling agents [20].

Other interactions of ANP32A

  • Further experiments revealed that silencing of ANP32A and ANP32B inhibited AAV replication, while overexpression of all of the components of the TAF-I/Set complex increased de novo AAV DNA synthesis in permissive cells [21].
  • Both PHAPI and PHAPII have an extended highly acidic C-terminal region [16].
  • We have purified and characterized a 31-kDa protein named mapmodulin that binds to the microtubule-associated proteins (MAPs) MAP2, MAP4, and tau [10].
  • PHAP II, a substrate of granzyme A, is degraded within minutes of CTL attack [22].

Analytical, diagnostic and therapeutic context of ANP32A

  • Immunofluorescence studies demonstrate that both LANP and ataxin-1 colocalize in nuclear matrix-associated subnuclear structures [7].
  • Using affinity chromatography with recombinant mutant inactive granzyme A, we previously isolated two granzyme A-binding proteins, PHAP (putative HLA-associated protein) I and II [22].
  • Aided performance was represented by the Profile of Hearing Aid Performance (PHAP, Cox & Gilmore, 1990) [23].
  • These requirements were met by exposure of cell cultures to: (1) PHAE, the erythroagglutinating component of PHAP, or (2) to either non-erythroagglutinating mitogens, PHAL, Con A, OKT3 or SEA, or to antigens of typhus group rickettsiae or salmonellae, provided that the RBC membrane was desialyted [24].


  1. Mapmodulin/leucine-rich acidic nuclear protein binds the light chain of microtubule-associated protein 1B and modulates neuritogenesis. Opal, P., Garcia, J.J., Propst, F., Matilla, A., Orr, H.T., Zoghbi, H.Y. J. Biol. Chem. (2003) [Pubmed]
  2. Adenovirus E4orf6 targets pp32/LANP to control the fate of ARE-containing mRNAs by perturbing the CRM1-dependent mechanism. Higashino, F., Aoyagi, M., Takahashi, A., Ishino, M., Taoka, M., Isobe, T., Kobayashi, M., Totsuka, Y., Kohgo, T., Shindoh, M. J. Cell Biol. (2005) [Pubmed]
  3. Enhanced sensitivity to cytochrome c-induced apoptosis mediated by PHAPI in breast cancer cells. Schafer, Z.T., Parrish, A.B., Wright, K.M., Margolis, S.S., Marks, J.R., Deshmukh, M., Kornbluth, S. Cancer Res. (2006) [Pubmed]
  4. Identification of V3 loop-binding proteins as potential receptors implicated in the binding of HIV particles to CD4(+) cells. Callebaut, C., Blanco, J., Benkirane, N., Krust, B., Jacotot, E., Guichard, G., Seddiki, N., Svab, J., Dam, E., Muller, S., Briand, J.P., Hovanessian, A.G. J. Biol. Chem. (1998) [Pubmed]
  5. Comparison of vessel dilator and long-acting natriuretic peptide in the treatment of congestive heart failure. Vesely, D.L., Dietz, J.R., Parks, J.R., Antwi, E.A., Overton, R.M., McCormick, M.T., Cintron, G., Schocken, D.D. Am. Heart J. (1999) [Pubmed]
  6. pp32/PHAPI determines the apoptosis response of non-small-cell lung cancer. Hoffarth, S., Zitzer, A., Wiewrodt, R., Hähnel, P.S., Beyer, V., Kreft, A., Biesterfeld, S., Schuler, M. Cell Death Differ. (2008) [Pubmed]
  7. The cerebellar leucine-rich acidic nuclear protein interacts with ataxin-1. Matilla, A., Koshy, B.T., Cummings, C.J., Isobe, T., Orr, H.T., Zoghbi, H.Y. Nature (1997) [Pubmed]
  8. Granzyme A loading induces rapid cytolysis and a novel form of DNA damage independently of caspase activation. Beresford, P.J., Xia, Z., Greenberg, A.H., Lieberman, J. Immunity (1999) [Pubmed]
  9. Analysis of the composition, assembly kinetics and activity of native Apaf-1 apoptosomes. Hill, M.M., Adrain, C., Duriez, P.J., Creagh, E.M., Martin, S.J. EMBO J. (2004) [Pubmed]
  10. Mapmodulin: a possible modulator of the interaction of microtubule-associated proteins with microtubules. Ulitzur, N., Humbert, M., Pfeffer, S.R. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  11. Anp32e (Cpd1) and related protein phosphatase 2 inhibitors. Santa-Coloma, T.A. Cerebellum (2003) [Pubmed]
  12. Phosphorylated retinoblastoma protein complexes with pp32 and inhibits pp32-mediated apoptosis. Adegbola, O., Pasternack, G.R. J. Biol. Chem. (2005) [Pubmed]
  13. Molecular identification of I1PP2A, a novel potent heat-stable inhibitor protein of protein phosphatase 2A. Li, M., Makkinje, A., Damuni, Z. Biochemistry (1996) [Pubmed]
  14. Localization of the gene encoding the putative human HLA class II associated protein (PHAPI) to chromosome 15q22.3-q23 by fluorescence in situ hybridization. Fink, T.M., Vaesen, M., Kratzin, H.D., Lichter, P., Zimmer, M. Genomics (1995) [Pubmed]
  15. Mediation of the antiproliferative effect of cyclosporine on human lymphocytes by blockade of interleukin 2 biosynthesis. Kermani-Arab, V., Salehmoghaddam, S., Danovitch, G., Hirji, K., Rezai, A. Transplantation (1985) [Pubmed]
  16. Purification and characterization of two putative HLA class II associated proteins: PHAPI and PHAPII. Vaesen, M., Barnikol-Watanabe, S., Götz, H., Awni, L.A., Cole, T., Zimmermann, B., Kratzin, H.D., Hilschmann, N. Biol. Chem. Hoppe-Seyler (1994) [Pubmed]
  17. Recombinant human granzyme A binds to two putative HLA-associated proteins and cleaves one of them. Beresford, P.J., Kam, C.M., Powers, J.C., Lieberman, J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  18. Integrin alpha3beta1 interacts with I1PP2A/lanp and phosphatase PP1. Mutz, D., Weise, C., Mechai, N., Hofmann, W., Horstkorte, R., Br??ning, G., Danker, K. J. Neurosci. Res. (2006) [Pubmed]
  19. The Anp32 family of proteins containing leucine-rich repeats. Matilla, A., Radrizzani, M. Cerebellum (2005) [Pubmed]
  20. The effects of different additives on the dielectric relaxation and the dynamic mechanical properties of urethane dimethacrylate. Mohsen, N.M., Craig, R.G., Filisko, F.E. Journal of oral rehabilitation. (2000) [Pubmed]
  21. Regulation of adeno-associated virus DNA replication by the cellular TAF-I/set complex. Pegoraro, G., Marcello, A., Myers, M.P., Giacca, M. J. Virol. (2006) [Pubmed]
  22. A role for heat shock protein 27 in CTL-mediated cell death. Beresford, P.J., Jaju, M., Friedman, R.S., Yoon, M.J., Lieberman, J. J. Immunol. (1998) [Pubmed]
  23. Estimation of client-assessed hearing aid performance based upon unaided variables. Crowley, H.J., Nabelek, I.V. Journal of speech and hearing research. (1996) [Pubmed]
  24. Activation and enhanced contact of human T-lymphocytes with autologous red blood cells are required for their stable adherence at 37 degrees. Khavkin, T., Kuchler, M., Carl, M., Murphy, J.R., Baqar, S., Triemer, R.E., Liao, M.J., Testa, D. Virchows Arch., B, Cell Pathol. (1993) [Pubmed]
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