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Gene Review

AIP  -  aryl hydrocarbon receptor interacting protein

Homo sapiens

Synonyms: AH receptor-interacting protein, ARA9, Aryl-hydrocarbon receptor-interacting protein, FKBP16, FKBP37, ...
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Disease relevance of AIP


Psychiatry related information on AIP


High impact information on AIP


Chemical compound and disease context of AIP


Biological context of AIP


Anatomical context of AIP

  • These mutations resulted in the loss of AhR binding to endogenous XAP2 in COS-1 cells and reduced binding of exogenously expressed XAP2 [18].
  • In vitro experiments using proteins generated in reticulocyte lysates confirmed this interaction and indicated that ARA9 can be co-immunoprecipitated with the AHR using antisera raised specifically for either the AHR or the 90-kDa heat shock protein [19].
  • Multiple somatotopic representations of the face, lips, and fingers were localized and mapped in primary motor cortex (MI), ventral premotor cortex (PMv), polysensory zone (PZ), primary (SI) and secondary (SII) somatosensory cortex, parietal ventral area (PV) and 7b, as well as anterior and ventral intraparietal areas (AIP and VIP) [20].
  • From Northern blot analyses, XAP2 is ubiquitously expressed in both liver-derived and non-liver-derived cell lines as well as in normal non-liver tissues [16].
  • Surprisingly, however, we found that AIP still could induce H2O2-independent apoptosis more slowly than H2O2-dependent one in HL-60 cells even in the presence of antioxidants [21].

Associations of AIP with chemical compounds

  • In contrast, hAhR-YFP localized predominantly in the cytoplasm, and coexpression of XAP2 did not affect this localization, and did not block nuclear accumulation in the presence of leptomycin B [22].
  • Furthermore, all of these serine mutants were able to sequester murine AhR-YFP into the cytoplasm as well as wild-type XAP2 [17].
  • These results indicate that AIP induces apoptosis in cells by two distinct mechanisms; one rapid and mediated by H2O2, the other delayed and mediated by deprivation of L-lysine, both of which utilize caspase-9/cytochrome c system [21].
  • In this study, we confirmed that recombinant AIP generated enough H2O2 in culture medium to induce rapid apoptosis in cells and this apoptosis was clearly inhibited by co-cultivation with antioxidants such as catalase and N-acetyl-cysteine [21].
  • In addition, since non-natriferic concentrations of cortisol did not induce similar proteins, AIP synthesis appears to be mineralocorticoid-specific [23].

Physical interactions of AIP

  • Additionally the XAP2 binding-deficient AhR mutants showed overall higher transcriptional activity when compared with the non-mutant receptor [18].
  • The ALG-2/AIP-complex, a modulator at the interface between cell proliferation and cell death? A hypothesis [24].

Regulatory relationships of AIP

  • XAP2 expression caused an overall repression of constitutive and ligand-induced AhR transcriptional activity [18].
  • We have identified the mechanism of XAP-2-induced cytoplasmic localization of the receptor and studied the potential cross-talk between CRM-1 and XAP-2 [25].

Other interactions of AIP


Analytical, diagnostic and therapeutic context of AIP

  • Using the yeast two-hybrid method, we have isolated a clone that encodes a novel X-associated cellular protein: XAP2 [16].
  • In a proteomics screening to identify novel survivin-binding partners, we found that the aryl hydrocarbon receptor-interacting protein (AIP) directly associates with survivin in vitro and in co-immunoprecipitation experiments in vivo [28].
  • Three segments of the AIP gene that contain the reported mutation sites for Q14X, IVS3-1G>A, and R304X were amplified by PCR and sequenced [29].
  • Our event related fMRI study was designed to address specifically the question, how CIP and AIP interact in the process of adjustment of hand orientation towards objects [30].
  • RESULTS: Patients who were admitted for pleurisy, cancer of the kidney and renal pelvis, or conduction disorders and complications of cardiac devices had the highest rates of developing AIP during hospitalization, with AIP rates at 2.24%, 1.14%, and 0.83% respectively [31].


  1. Mutation analysis of aryl hydrocarbon receptor interacting protein (AIP) gene in colorectal, breast, and prostate cancers. Georgitsi, M., Karhu, A., Winqvist, R., Visakorpi, T., Waltering, K., Vahteristo, P., Launonen, V., Aaltonen, L.A. Br. J. Cancer (2007) [Pubmed]
  2. Epstein-Barr virus encoded nuclear protein EBNA-3 binds XAP-2, a protein associated with Hepatitis B virus X antigen. Kashuba, E., Kashuba, V., Pokrovskaja, K., Klein, G., Szekely, L. Oncogene (2000) [Pubmed]
  3. Role of procalcitonin and granulocyte colony stimulating factor in the early prediction of infected necrosis in severe acute pancreatitis. Müller, C.A., Uhl, W., Printzen, G., Gloor, B., Bischofberger, H., Tcholakov, O., Büchler, M.W. Gut (2000) [Pubmed]
  4. Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations. Georgitsi, M., Raitila, A., Karhu, A., Tuppurainen, K., Mäkinen, M.J., Vierimaa, O., Paschke, R., Saeger, W., van der Luijt, R.B., Sane, T., Robledo, M., De Menis, E., Weil, R.J., Wasik, A., Zielinski, G., Lucewicz, O., Lubinski, J., Launonen, V., Vahteristo, P., Aaltonen, L.A. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  5. Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. Daly, A.F., Vanbellinghen, J.F., Khoo, S.K., Jaffrain-Rea, M.L., Naves, L.A., Guitelman, M.A., Murat, A., Emy, P., Gimenez-Roqueplo, A.P., Tamburrano, G., Raverot, G., Barlier, A., De Herder, W., Penfornis, A., Ciccarelli, E., Estour, B., Lecomte, P., Gatta, B., Chabre, O., Sabaté, M.I., Bertagna, X., Garcia Basavilbaso, N., Stalldecker, G., Colao, A., Ferolla, P., Wémeau, J.L., Caron, P., Sadoul, J.L., Oneto, A., Archambeaud, F., Calender, A., Sinilnikova, O., Montañana, C.F., Cavagnini, F., Hana, V., Solano, A., Delettieres, D., Luccio-Camelo, D.C., Basso, A., Rohmer, V., Brue, T., Bours, V., Teh, B.T., Beckers, A. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  6. Large genomic deletions in AIP in pituitary adenoma predisposition. Georgitsi, M., Heliövaara, E., Paschke, R., Kumar, A.V., Tischkowitz, M., Vierimaa, O., Salmela, P., Sane, T., De Menis, E., Cannavò, S., Gündogdu, S., Lucassen, A., Izatt, L., Aylwin, S., Bano, G., Hodgson, S., Koch, C.A., Karhu, A., Aaltonen, L.A. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  7. The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas. Leontiou, C.A., Gueorguiev, M., van der Spuy, J., Quinton, R., Lolli, F., Hassan, S., Chahal, H.S., Igreja, S.C., Jordan, S., Rowe, J., Stolbrink, M., Christian, H.C., Wray, J., Bishop-Bailey, D., Berney, D.M., Wass, J.A., Popovic, V., Ribeiro-Oliveira, A., Gadelha, M.R., Monson, J.P., Akker, S.A., Davis, J.R., Clayton, R.N., Yoshimoto, K., Iwata, T., Matsuno, A., Eguchi, K., Musat, M., Flanagan, D., Peters, G., Bolger, G.B., Chapple, J.P., Frohman, L.A., Grossman, A.B., Korbonits, M. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  8. Clinical and hormonal aspects of pancreatic diabetes. Bank, S., Marks, I.N., Vinik, A.I. Am. J. Gastroenterol. (1975) [Pubmed]
  9. AIP is a mitochondrial import mediator that binds to both import receptor Tom20 and preproteins. Yano, M., Terada, K., Mori, M. J. Cell Biol. (2003) [Pubmed]
  10. The hsp90 chaperone complex regulates intracellular localization of the dioxin receptor. Kazlauskas, A., Sundström, S., Poellinger, L., Pongratz, I. Mol. Cell. Biol. (2001) [Pubmed]
  11. Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity. Meyer, B.K., Pray-Grant, M.G., Vanden Heuvel, J.P., Perdew, G.H. Mol. Cell. Biol. (1998) [Pubmed]
  12. Pyrimidinones: inducers of NK cell activity and antitumor immunity. Lotzová, E., Savary, C.A. Comp. Immunol. Microbiol. Infect. Dis. (1986) [Pubmed]
  13. Mutations in the aryl hydrocarbon receptor interacting protein gene are not highly prevalent among subjects with sporadic pituitary adenomas. Barlier, A., Vanbellinghen, J.F., Daly, A.F., Silvy, M., Jaffrain-Rea, M.L., Trouillas, J., Tamagno, G., Cazabat, L., Bours, V., Brue, T., Enjalbert, A., Beckers, A. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  14. Characterization of the Ah receptor-associated protein, ARA9. Carver, L.A., LaPres, J.J., Jain, S., Dunham, E.E., Bradfield, C.A. J. Biol. Chem. (1998) [Pubmed]
  15. The transactivation domain of the Ah receptor is a key determinant of cellular localization and ligand-independent nucleocytoplasmic shuttling properties. Ramadoss, P., Perdew, G.H. Biochemistry (2005) [Pubmed]
  16. XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation. Kuzhandaivelu, N., Cong, Y.S., Inouye, C., Yang, W.M., Seto, E. Nucleic Acids Res. (1996) [Pubmed]
  17. Characterization of the phosphorylation status of the hepatitis B virus X-associated protein 2. Dull, A.B., Carlson, D.B., Petrulis, J.R., Perdew, G.H. Arch. Biochem. Biophys. (2002) [Pubmed]
  18. The aryl hydrocarbon (Ah) receptor transcriptional regulator hepatitis B virus X-associated protein 2 antagonizes p23 binding to Ah receptor-Hsp90 complexes and is dispensable for receptor function. Hollingshead, B.D., Petrulis, J.R., Perdew, G.H. J. Biol. Chem. (2004) [Pubmed]
  19. Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo. Carver, L.A., Bradfield, C.A. J. Biol. Chem. (1997) [Pubmed]
  20. Dodecapus: An MR-compatible system for somatosensory stimulation. Huang, R.S., Sereno, M.I. Neuroimage (2007) [Pubmed]
  21. Apoptosis-inducing protein, AIP, from parasite-infected fish induces apoptosis in mammalian cells by two different molecular mechanisms. Murakawa, M., Jung, S.K., Iijima, K., Yonehara, S. Cell Death Differ. (2001) [Pubmed]
  22. Divergent roles of hepatitis B virus X-associated protein 2 (XAP2) in human versus mouse Ah receptor complexes. Ramadoss, P., Petrulis, J.R., Hollingshead, B.D., Kusnadi, A., Perdew, G.H. Biochemistry (2004) [Pubmed]
  23. Aldosterone-induced proteins in toad urinary bladders. Identification and characterization using two-dimensional polyacrylamide gel electrophoresis. Geheb, M., Huber, G., Hercker, E., Cox, M. J. Biol. Chem. (1981) [Pubmed]
  24. The ALG-2/AIP-complex, a modulator at the interface between cell proliferation and cell death? A hypothesis. Krebs, J., Klemenz, R. Biochim. Biophys. Acta (2000) [Pubmed]
  25. Two parallel pathways mediate cytoplasmic localization of the dioxin (aryl hydrocarbon) receptor. Berg, P., Pongratz, I. J. Biol. Chem. (2002) [Pubmed]
  26. Regulation of transactivation function of the aryl hydrocarbon receptor by the Epstein-Barr virus-encoded EBNA-3 protein. Kashuba, E.V., Gradin, K., Isaguliants, M., Szekely, L., Poellinger, L., Klein, G., Kazlauskas, A. J. Biol. Chem. (2006) [Pubmed]
  27. Role of AIP and its homologue the blindness-associated protein AIPL1 in regulating client protein nuclear translocation. van der Spuy, J., Cheetham, M.E. Biochem. Soc. Trans. (2004) [Pubmed]
  28. Regulation of survivin stability by the aryl hydrocarbon receptor-interacting protein. Kang, B.H., Altieri, D.C. J. Biol. Chem. (2006) [Pubmed]
  29. Aryl hydrocarbon receptor interacting protein variants in sporadic pituitary adenomas. Yu, R., Bonert, V., Saporta, I., Raffel, L.J., Melmed, S. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  30. Functional properties and interaction of the anterior and posterior intraparietal areas in humans. Shikata, E., Hamzei, F., Glauche, V., Koch, M., Weiller, C., Binkofski, F., Büchel, C. Eur. J. Neurosci. (2003) [Pubmed]
  31. Accidental iatrogenic pneumothorax in hospitalized patients. Zhan, C., Smith, M., Stryer, D. Medical care. (2006) [Pubmed]
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