The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

APEH  -  acylaminoacyl-peptide hydrolase

Homo sapiens

Synonyms: AARE, ACPH, APH, Acyl-peptide hydrolase, Acylamino-acid-releasing enzyme, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of APEH


Psychiatry related information on APEH

  • Best sensitivity and response time were obtained with sensors prepared with 250 U of OPH and measuring at 37 degrees C in 1.0 mM HEPES buffer, pH 9.3, containing 100 mM NaCl [5].

High impact information on APEH

  • The constitutional heterozygosity for the DNF15S2 locus and for one allele of the c-erbA beta and the c-raf-1 proto-oncogenes was lost in nonpapillary RCCs, whereas both alleles were retained in each papillary RCC analyzed [6].
  • An 87% identity has been found between the reported cDNA sequence that encodes acylpeptide hydrolase (EC [Mitta, M., Asada, K., Uchimura, Y., Kimizuka, F., Kato, I., Sakiyama, F. & Tsunasawa, S. (1989) J. Biochem. 106, 548-551] and a cDNA transcribed from a locus (DNF15S2) on the short arm of human chromosome 3, reported by Naylor et al [7].
  • [Naylor, S.L., Marshall, A., Hensel, C., Martinez, P.F., Holley, B. & Sakaguchi, A.Y. (1989) Genomics 4, 355-361]; the DNF15S2 locus suffers deletions in small cell lung carcinoma associated with a reduction or loss of acylase activity (EC [7].
  • Therefore, the locus which plays a role in non-small-cell tumorigenesis probably lies closer to DNF15S2 than to ERBA beta and is almost certainly not the latter [8].
  • This sequence is the first described that can regulate a basal promoter in response to starvation for several individual amino acids and therefore can be called an amino acid response element (AARE) [9].

Chemical compound and disease context of APEH


Biological context of APEH

  • More recently we have identified a putative CpG island in the vicinity of D3F15S2, suggesting that DNA sequences in or around this site may have coding potential (Boldog, F., Erlandsson, R., Klein, G. & Sümegi, J. (1989). Cancer Genet. Cytogenet., 42, 295-306) [2].
  • A gene that corresponds to the most frequently lost RFLP site (D3F15S2) is expressed in a variety of human tissues, and at a particularly high level in the kidney [14].
  • The screening of a human placenta cDNA library with DNA probes derived from D3F15S2 has led to the isolation of several cDNA clones [2].
  • Of the 23 tumors informative for D3F15S2, one showed LOH [15].
  • One SCLC cell line, H748, has an interstitial deletion of chromosome 3p and shows allele loss for the DNF15S2 locus detected by the probe lambda H3 [3].

Anatomical context of APEH

  • Identification of oxidized protein hydrolase of human erythrocytes as acylpeptide hydrolase [16].
  • We did not detect changes in the level of binding of this factor to the AARE by using nuclear extracts from HeLa cells grown under starved conditions, suggesting that activation of this factor(s) results from posttranslational modification or complexing with other proteins that do not affect its DNA-binding properties [17].
  • Both the nucleus of the basal optic root (nBOR) and nucleus lentiformis mesencephali of the AOS were shown to project to the area ventralis of Tsai (AVT), which in turn was shown to project to the Hp/APH [18].
  • Furthermore, AS NSRE-2 can confer endoplasmic reticulum stress responsiveness to the CHOP AARE [19].
  • None of the informative thyroid tumors studied had allelic loss detected with probes for chromosome 2q (D2S44), 3p (D3F15S2, D3S32), 3q (D3S46), 4p (D4S125), 6p (D6S40), 8q (D8S39), 9q (D9S7), 12p (D12S14), 13q (D13S52), 17p (D17S30), or 18q (D18S10) [20].

Associations of APEH with chemical compounds


Other interactions of APEH

  • This was confirmed in one case with loss of a THRB allele where both proximal (D3F15S2) and distal (RAF1) markers retained heterozygosity [15].
  • In 18 matched carcinoma specimens, LOH (deletion) was observed at D3S32 in 0 of 7, at D3F15S2 in 9 of 12 (75%), and at THRB in 3 of 9 cases (33%) [23].
  • This group is unrelated to the classical trypsin and subtilisin families, and includes dipeptidyl peptidase IV, acylaminoacyl peptidase and oligopeptidase B, in addition to the prototype prolyl oligopeptidase [24].

Analytical, diagnostic and therapeutic context of APEH

  • We have determined the allelotypes of 215 established lung cancer cell lines by PCR analysis at six loci on the short arm of chromosome 3 (3p): D3S3 (3p12-p13), D3S30 (3p13), D3S2 (3p14-p21.1), D3S32 (3p21), D3F15S2 (3p21), and THRB (3p24) [4].
  • Six peptide fragments of OPH obtained by digestion of DFP-labeled OPH with lysyl endopeptidase were isolated by use of reverse-phase high-performance liquid chromatography, and the sequence of more than eight amino acids from the N-terminal position of each peptide was determined [16].
  • From site-directed mutagenesis, it was concluded that one of these sites functions as an amino acid response element (AARE) to regulate transcription [25].
  • Electrophoretic mobility shift assay and transient transfection experiments show that several transcription factors that belong to the C/EBP or ATF families bind the AARE sequence and activate transcription [26].
  • A method is described for the identification of the aminoglycoside-phosphorylating (APH) enzymes APH(2'') and APH(3') by the high performance liquid chromatographic (HPLC) identification of their products of reaction with kanamycin and ATP [27].


  1. YAC-assisted cloning of transcribed sequences from the human chromosome 3p21 region. Pengue, G., Calabrò, V., Cannada-Bartoli, P., De Luca, P., Esposito, T., Taillon-Miller, P., LaForgia, S., Druck, T., Huebner, K., D'Urso, M. Hum. Mol. Genet. (1993) [Pubmed]
  2. A gene near the D3F15S2 site on 3p is expressed in normal human kidney but not or only at a severely reduced level in 11 of 15 primary renal cell carcinomas (RCC). Erlandsson, R., Bergerheim, U.S., Boldog, F., Marcsek, Z., Kunimi, K., Lin, B.Y., Ingvarsson, S., Castresana, J.S., Lee, W.H., Lee, E. Oncogene (1990) [Pubmed]
  3. The DNF15S2 locus at 3p21 is transcribed in normal lung and small cell lung cancer. Naylor, S.L., Marshall, A., Hensel, C., Martinez, P.F., Holley, B., Sakaguchi, A.Y. Genomics (1989) [Pubmed]
  4. Frequent involvement of chromosome 3p alterations in lung carcinogenesis: allelotypes of 215 established cell lines at six chromosome 3p loci. Buchhagen, D.L. J. Cell. Biochem. Suppl. (1996) [Pubmed]
  5. Disposable potentiometric enzyme sensor for direct determination of organophosphorus insecticides. Gäberlein, S., Knoll, M., Spener, F., Zaborosch, C. The Analyst. (2000) [Pubmed]
  6. Differentiation between papillary and nonpapillary renal cell carcinomas by DNA analysis. Kovacs, G., Wilkens, L., Papp, T., de Riese, W. J. Natl. Cancer Inst. (1989) [Pubmed]
  7. Genetic relationship between acylpeptide hydrolase and acylase, two hydrolytic enzymes with similar binding but different catalytic specificities. Jones, W.M., Scaloni, A., Bossa, F., Popowicz, A.M., Schneewind, O., Manning, J.M. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  8. Loss of heterozygosity in a gene coding for a thyroid hormone receptor in lung cancers. Leduc, F., Brauch, H., Hajj, C., Dobrovic, A., Kaye, F., Gazdar, A., Harbour, J.W., Pettengill, O.S., Sorenson, G.D., van den Berg, A. Am. J. Hum. Genet. (1989) [Pubmed]
  9. Amino acids control mammalian gene transcription: activating transcription factor 2 is essential for the amino acid responsiveness of the CHOP promoter. Bruhat, A., Jousse, C., Carraro, V., Reimold, A.M., Ferrara, M., Fafournoux, P. Mol. Cell. Biol. (2000) [Pubmed]
  10. Acyl peptide hydrolase, a serine proteinase isolated from conditioned medium of neuroblastoma cells, degrades the amyloid-beta peptide. Yamin, R., Bagchi, S., Hildebrant, R., Scaloni, A., Widom, R.L., Abraham, C.R. J. Neurochem. (2007) [Pubmed]
  11. Chimeric vector construction for higher-plant transformation. Balázs, E., Bouzoubaa, S., Guilley, H., Jonard, G., Paszkowski, J., Richards, K. Gene (1985) [Pubmed]
  12. Whole cell-enzyme hybrid amperometric biosensor for direct determination of organophosphorous nerve agents with p-nitrophenyl substituent. Lei, Y., Mulchandani, P., Chen, W., Wang, J., Mulchandani, A. Biotechnol. Bioeng. (2004) [Pubmed]
  13. Mechanism of aminoglycoside resistance among beta-lactam-resistant Escherichia coli in the United States. Gaynes, R.P., Cooksey, R., Thornsberry, C., Swenson, J.M., Hughes, J.M. Diagn. Microbiol. Infect. Dis. (1987) [Pubmed]
  14. The gene from the short arm of chromosome 3, at D3F15S2, frequently deleted in renal cell carcinoma, encodes acylpeptide hydrolase. Erlandsson, R., Boldog, F., Persson, B., Zabarovsky, E.R., Allikmets, R.L., Sümegi, J., Klein, G., Jörnvall, H. Oncogene (1991) [Pubmed]
  15. Submicroscopic deletions of 3p sequences in pleomorphic adenomas with t(3;8)(p21;q12). Sahlin, P., Mark, J., Stenman, G. Genes Chromosomes Cancer (1994) [Pubmed]
  16. Identification of oxidized protein hydrolase of human erythrocytes as acylpeptide hydrolase. Fujino, T., Watanabe, K., Beppu, M., Kikugawa, K., Yasuda, H. Biochim. Biophys. Acta (2000) [Pubmed]
  17. Cis- and trans-acting elements involved in amino acid regulation of asparagine synthetase gene expression. Guerrini, L., Gong, S.S., Mangasarian, K., Basilico, C. Mol. Cell. Biol. (1993) [Pubmed]
  18. Optic flow input to the hippocampal formation from the accessory optic system. Wylie, D.R., Glover, R.G., Aitchison, J.D. J. Neurosci. (1999) [Pubmed]
  19. Differences in the molecular mechanisms involved in the transcriptional activation of the CHOP and asparagine synthetase genes in response to amino acid deprivation or activation of the unfolded protein response. Bruhat, A., Averous, J., Carraro, V., Zhong, C., Reimold, A.M., Kilberg, M.S., Fafournoux, P. J. Biol. Chem. (2002) [Pubmed]
  20. Allelotype of human thyroid tumors: loss of chromosome 11q13 sequences in follicular neoplasms. Matsuo, K., Tang, S.H., Fagin, J.A. Mol. Endocrinol. (1991) [Pubmed]
  21. Layer-by-layer self-assembled chitosan/poly(thiophene-3-acetic acid) and organophosphorus hydrolase multilayers. Constantine, C.A., Mello, S.V., Dupont, A., Cao, X., Santos, D., Oliveira, O.N., Strixino, F.T., Pereira, E.C., Cheng, T.C., Defrank, J.J., Leblanc, R.M. J. Am. Chem. Soc. (2003) [Pubmed]
  22. Homocysteine regulates expression of Herp by DNA methylation involving the AARE and CREB binding sites. Lenz, B., Bleich, S., Beutler, S., Schlierf, B., Schwager, K., Reulbach, U., Kornhuber, J., B??nsch, D. Exp. Cell Res. (2006) [Pubmed]
  23. Polymerase chain reaction-based restriction fragment length polymorphism analysis of the short arm of chromosome 3 in primary head and neck squamous carcinoma. el-Naggar, A.K., Lee, M.S., Wang, G., Luna, M.A., Goepfert, H., Batsakis, J.G. Cancer (1993) [Pubmed]
  24. The prolyl oligopeptidase family. Polgár, L. Cell. Mol. Life Sci. (2002) [Pubmed]
  25. Transcriptional control of the human sodium-coupled neutral amino acid transporter system A gene by amino acid availability is mediated by an intronic element. Palii, S.S., Chen, H., Kilberg, M.S. J. Biol. Chem. (2004) [Pubmed]
  26. Induction of CHOP expression by amino acid limitation requires both ATF4 expression and ATF2 phosphorylation. Averous, J., Bruhat, A., Jousse, C., Carraro, V., Thiel, G., Fafournoux, P. J. Biol. Chem. (2004) [Pubmed]
  27. The identification of the aminoglycoside-phosphorylating enzymes APH(2'') and APH(3') from the characterization of their reaction products by high performance liquid chromatography. Lovering, A.M., White, L.O., Reeves, D.S. J. Antimicrob. Chemother. (1986) [Pubmed]
WikiGenes - Universities