AH receptor-interacting protein (AIP) also known as aryl-hydrocarbon receptor-interacting protein, immunophilin homolog ARA9, or HBV X-associated protein 2 (XAP-2) is a protein that in humans is encoded by the AIPgene.[1][2][3] The protein is a member of FKBP family.
AIP may play a positive role in aryl hydrocarbon receptor-mediated signalling possibly by influencing its receptivity for ligand and/or its nuclear targeting. AIP is the cellular negative regulator of the hepatitis B virus (HBV) X protein.[1]
Role in disease
AIP mutations may be the cause of a familial form of acromegaly, familial isolated pituitary adenoma (FIPA). Somatotropinomas (i.e. GH-producing pituitary adenomas), sometimes associated with prolactinomas, are present in most AIP mutated patients.[4]
↑ 3.03.13.2Carver LA, Bradfield CA (April 1997). "Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo". J. Biol. Chem. 272 (17): 11452–6. doi:10.1074/jbc.272.17.11452. PMID9111057.
↑Petrulis JR, Hord NG, Perdew GH (December 2000). "Subcellular localization of the aryl hydrocarbon receptor is modulated by the immunophilin homolog hepatitis B virus X-associated protein 2". J. Biol. Chem. 275 (48): 37448–53. doi:10.1074/jbc.M006873200. PMID10986286.
↑Ma Q, Whitlock JP (April 1997). "A novel cytoplasmic protein that interacts with the Ah receptor, contains tetratricopeptide repeat motifs, and augments the transcriptional response to 2,3,7,8-tetrachlorodibenzo-p-dioxin". J. Biol. Chem. 272 (14): 8878–84. doi:10.1074/jbc.272.14.8878. PMID9083006.
↑Sumanasekera WK, Tien ES, Turpey R, Vanden Heuvel JP, Perdew GH (February 2003). "Evidence that peroxisome proliferator-activated receptor alpha is complexed with the 90-kDa heat shock protein and the hepatitis virus B X-associated protein 2". J. Biol. Chem. 278 (7): 4467–73. doi:10.1074/jbc.M211261200. PMID12482853.
Chen HS, Perdew GH (1994). "Subunit composition of the heteromeric cytosolic aryl hydrocarbon receptor complex". J. Biol. Chem. 269 (44): 27554–8. PMID7961671.
Ma Q, Whitlock JP (1997). "A novel cytoplasmic protein that interacts with the Ah receptor, contains tetratricopeptide repeat motifs, and augments the transcriptional response to 2,3,7,8-tetrachlorodibenzo-p-dioxin". J. Biol. Chem. 272 (14): 8878–84. doi:10.1074/jbc.272.14.8878. PMID9083006.
Carver LA, LaPres JJ, Jain S, et al. (1999). "Characterization of the Ah receptor-associated protein, ARA9". J. Biol. Chem. 273 (50): 33580–7. doi:10.1074/jbc.273.50.33580. PMID9837941.
Gadelha MR, Une KN, Rohde K, et al. (2000). "Isolated familial somatotropinomas: establishment of linkage to chromosome 11q13.1-11q13.3 and evidence for a potential second locus at chromosome 2p16-12". J. Clin. Endocrinol. Metab. 85 (2): 707–14. doi:10.1210/jc.85.2.707. PMID10690880.
Petrulis JR, Hord NG, Perdew GH (2001). "Subcellular localization of the aryl hydrocarbon receptor is modulated by the immunophilin homolog hepatitis B virus X-associated protein 2". J. Biol. Chem. 275 (48): 37448–53. doi:10.1074/jbc.M006873200. PMID10986286.
Kazlauskas A, Poellinger L, Pongratz I (2001). "The immunophilin-like protein XAP2 regulates ubiquitination and subcellular localization of the dioxin receptor". J. Biol. Chem. 275 (52): 41317–24. doi:10.1074/jbc.M007765200. PMID11013261.
Kazlauskas A, Poellinger L, Pongratz I (2002). "Two distinct regions of the immunophilin-like protein XAP2 regulate dioxin receptor function and interaction with hsp90". J. Biol. Chem. 277 (14): 11795–801. doi:10.1074/jbc.M200053200. PMID11805120.
Patterson CE, Gao J, Rooney AP, Davis EC (2002). "Genomic organization of mouse and human 65 kDa FK506-binding protein genes and evolution of the FKBP multigene family". Genomics. 79 (6): 881–9. doi:10.1006/geno.2002.6777. PMID12036304.
Berg P, Pongratz I (2002). "Two parallel pathways mediate cytoplasmic localization of the dioxin (aryl hydrocarbon) receptor". J. Biol. Chem. 277 (35): 32310–9. doi:10.1074/jbc.M203351200. PMID12065584.
Dull AB, Carlson DB, Petrulis JR, Perdew GH (2002). "Characterization of the phosphorylation status of the hepatitis B virus X-associated protein 2". Arch. Biochem. Biophys. 406 (2): 209–21. doi:10.1016/S0003-9861(02)00444-7. PMID12361709.
Sumanasekera WK, Tien ES, Turpey R, et al. (2003). "Evidence that peroxisome proliferator-activated receptor alpha is complexed with the 90-kDa heat shock protein and the hepatitis virus B X-associated protein 2". J. Biol. Chem. 278 (7): 4467–73. doi:10.1074/jbc.M211261200. PMID12482853.
Zhao Y, Meng XM, Wei YJ, et al. (2004). "Cloning and characterization of a novel cardiac-specific kinase that interacts specifically with cardiac troponin I.". J. Mol. Med. 81 (5): 297–304. doi:10.1007/s00109-003-0427-x. PMID12721663.
Lees MJ, Peet DJ, Whitelaw ML (2003). "Defining the role for XAP2 in stabilization of the dioxin receptor". J. Biol. Chem. 278 (38): 35878–88. doi:10.1074/jbc.M302430200. PMID12837759.
Ramadoss P, Petrulis JR, Hollingshead BD, et al. (2004). "Divergent roles of hepatitis B virus X-associated protein 2 (XAP2) in human versus mouse Ah receptor complexes". Biochemistry. 43 (3): 700–9. doi:10.1021/bi035827v. PMID14730974.