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Gene Review

NACA  -  nascent polypeptide-associated complex...

Homo sapiens

Synonyms: HSD48, NACA1, skNAC
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Disease relevance of NACA


Psychiatry related information on NACA


High impact information on NACA

  • NACA was recently defined as a coactivator of c-jun-mediated transcription factors in osteoblasts, and RBM3 as a protein from the heterogeneous nuclear ribonucleoprotein family [6].
  • The alpha-NAC protein was specifically expressed in differentiated osteoblasts at the centers of ossification [7].
  • Kinetics studies with purified c-Jun homodimer and recombinant alpha-NAC proteins allowed determination of the mechanism of coactivation by alpha-NAC: the coactivator stabilized the AP-1 complex formed by the c-Jun homodimer on its DNA recognition sequence through an eightfold reduction in the dissociation constant (kd) of the complex [7].
  • Interestingly, the expression of alpha-NAC was first detected at 14.5 to 15 days postconception, concomitantly with the onset of ossification during embryogenesis [7].
  • The use of deletion mutants in pull-down assays revealed that alpha-NAC interacted with amino acids 1 to 89 of the c-Jun protein and that the coactivator could interact with both the unphosphorylated and the serine 73-phosphorylated form of c-Jun [7].

Biological context of NACA

  • In this study, we investigate the role of NACA in human hematopoiesis [8].
  • Using a phosphorothioate-modified oligodeoxynucleotide antisense directed specifically against alpha NAC mRNA, protein expression was inhibited and increased CD8(+) cell proliferation and CD25 expression were observed irrespective of the culture conditions [9].
  • The decrease in alpha-NAC as a transcriptional coactivator could contribute to the characteristic decline of the c-Jun-mediated transcriptional machinery and could function as the complementary mechanism in c-Jun-mediated apoptosis [4].
  • Mapping of the human gene for the alpha-NAC/1.9.2 (NACA/1.9.2) transcriptional coactivator to Chromosome 12q23-24.1 [10].
  • By using nitrocellulose-blotted murine lung and skin extracts, purified recombinant human as well as murine alpha-NAC and murine alpha-NAC-derived synthetic peptides, the IgE, IgG1, and IgG2a antibody responses were measured, and their epitope specificity was mapped [11].

Anatomical context of NACA

  • Now we used SMART cDNA synthesis and subsequent "virtual Northern" blot to analyze differential expression of NACA and ANX2 genes in various hematologic cell lines and compared the data to those obtained by standard Northern analyses [12].
  • NACA is a positive regulator of human erythroid-cell differentiation [8].
  • Protein distribution analyses indicate that NACA is expressed in undifferentiated TF-1 cells and in human-cord-blood-derived CD34(+) progenitor cells [8].
  • This is the first description of the function of the alpha NAC protein in human CD8(+) T cells [9].
  • Interestingly, one such coactivator specifically expressed in bone cells during development, alpha NAC (Nascent-polypeptide-associated complex And Coactivator alpha), is converted into a DNA-binding activator by differential splicing in differentiated myotubes [13].

Associations of NACA with chemical compounds

  • Decreased alpha-NAC may result in the mistargeting, mistranslation, and proteolysis of proteins by affecting overall NAC function [4].

Other interactions of NACA

  • We conclude that aberrant regulation of NACA or ANX2 does not play a relevant role in JMML pathogenesis [12].
  • The significant decrease in alpha-NAC mRNA was shown by semiquantitative reverse transcription-polymerase chain reaction, and in parallel, the significant decrease of alpha-NAC protein, which was even more pronounced when related to either actin or neuron-specific enolase levels, was also observed in both disorders [4].
  • Expression analysis of alpha-NAC and ANX2 in juvenile myelomonocytic leukemia using SMART polymerase chain reaction and "virtual Northern" hybridization [12].
  • A recent genome survey indicates that Archaea do not harbor well conserved equivalents of the co-chaperones trigger factor, Hip, Hop, BAG-1, and NAC, although the data suggest that Archaea have proteins related to Hop and to the NAC alpha subunit whose functions remain to be elucidated [14].

Analytical, diagnostic and therapeutic context of NACA

  • After validating the technique, we used virtual Northern blots to analyze expression of NACA and ANX2 in progenitor cultures of nine children with JMML and five healthy individuals [12].
  • N-terminal-deleted c-Jun protein failed to interact with alpha-NAC in mammalian two-hybrid assays, while mutant c-Jun proteins lacking the leucine zipper or the basic domain retained interaction with alpha-NAC in vivo [7].


  1. NACA as a potential cellular target of hepatitis B virus preS1 protein. Li, D., Wang, X.Z., Ding, J., Yu, J.P. Dig. Dis. Sci. (2005) [Pubmed]
  2. Comparison of bystander trauma care for moderate versus severe injury. Thierbach, A.R., Pelinka, L.E., Reuter, S., Mauritz, W. Resuscitation. (2004) [Pubmed]
  3. Activation of the JNK-AP-1 signal transduction pathway is associated with pathogenesis and progression of human osteosarcomas. Papachristou, D.J., Batistatou, A., Sykiotis, G.P., Varakis, I., Papavassiliou, A.G. Bone (2003) [Pubmed]
  4. Human brain nascent polypeptide-associated complex alpha subunit is decreased in patients with Alzheimer' s disease and Down syndrome. Kim, S.H., Shim, K.S., Lubec, G. J. Investig. Med. (2002) [Pubmed]
  5. Mental health needs assessment of off-reservation American Indian people in northern Arizona. Chester, B., Mahalish, P., Davis, J. American Indian and Alaska native mental health research : journal of the National Center. (1999) [Pubmed]
  6. Capture of cytokine-responsive genes (NACA and RBM3) using a gene trap approach. Baghdoyan, S., Dubreuil, P., Eberlé, F., Gomez, S. Blood (2000) [Pubmed]
  7. Bone-specific expression of the alpha chain of the nascent polypeptide-associated complex, a coactivator potentiating c-Jun-mediated transcription. Moreau, A., Yotov, W.V., Glorieux, F.H., St-Arnaud, R. Mol. Cell. Biol. (1998) [Pubmed]
  8. NACA is a positive regulator of human erythroid-cell differentiation. Lopez, S., Stuhl, L., Fichelson, S., Dubart-Kupperschmitt, A., St Arnaud, R., Galindo, J.R., Murati, A., Berda, N., Dubreuil, P., Gomez, S. J. Cell. Sci. (2005) [Pubmed]
  9. Investigation of alpha nascent polypeptide-associated complex functions in a human CD8(+) T cell ex vivo expansion model using antisense oligonucleotides. Al-Shanti, N., Steward, C.G., Garland, R.J., Rowbottom, A.W. Immunology (2004) [Pubmed]
  10. Mapping of the human gene for the alpha-NAC/1.9.2 (NACA/1.9.2) transcriptional coactivator to Chromosome 12q23-24.1. Yotov, W.V., St-Arnaud, R. Mamm. Genome (1996) [Pubmed]
  11. Induction of autoallergy with an environmental allergen mimicking a self protein in a murine model of experimental allergic asthma. Bünder, R., Mittermann, I., Herz, U., Focke, M., Wegmann, M., Valenta, R., Renz, H. J. Allergy Clin. Immunol. (2004) [Pubmed]
  12. Expression analysis of alpha-NAC and ANX2 in juvenile myelomonocytic leukemia using SMART polymerase chain reaction and "virtual Northern" hybridization. Hämmerle, K., Shayan, P., Niemeyer, C.M., Flotho, C. Cancer Genet. Cytogenet. (2003) [Pubmed]
  13. Transcriptional regulation during mesenchymal cell differentiation: the role of coactivators. St-Arnaud, R. Crit. Rev. Eukaryot. Gene Expr. (1998) [Pubmed]
  14. Molecular biology of stress genes in methanogens: potential for bioreactor technology. Conway de Macario, E., Macario, A.J. Adv. Biochem. Eng. Biotechnol. (2003) [Pubmed]
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