Protein-coding gene in the species Homo sapiens
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 AIP gene .[ 5] [ 6] [ 7] The protein is a member of the 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.[ 5] Further, it's been known to suppress antiviral signaling and the induction of type I interferon by targeting IRF7, a key player in the antiviral signal pathways.[ 8] AIP consists of an N-terminal FKBP52 like domain and a C-terminal TPR domain. [ 9]
Mutations and role in disease [ edit ]
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.[ 10]
AIP has been shown to interact with the aryl hydrocarbon receptor ,[ 7] [ 11] [ 12] peroxisome proliferator-activated receptor alpha [ 13] and the aryl hydrocarbon receptor nuclear translocator .[ 7] [ 14] Further, it has shown that AIP can interact with IRF7 to exert its novel function of negatively regulating antiviral signal pathways.[ 8]
^ a b c GRCh38: Ensembl release 89: ENSG00000110711 – Ensembl , May 2017
^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024847 – Ensembl , May 2017
^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ a b "Entrez Gene: AIP aryl hydrocarbon receptor interacting protein" .
^ Kuzhandaivelu N, Cong YS, Inouye C, Yang WM, Seto E (December 1996). "XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation" . Nucleic Acids Res . 24 (23): 4741–50. doi :10.1093/nar/24.23.4741 . PMC 146319 . PMID 8972861 .
^ a b c Carver 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 . PMID 9111057 .
^ a b Zhou Q, Lavorgna A, Bowman M, Hiscott J, Harhaj EW (June 2015). "Aryl Hydrocarbon Receptor Interacting Protein Targets IRF7 to Suppress Antiviral Signaling and the Induction of Type I Interferon" . The Journal of Biological Chemistry . 290 (23): 14729–39. doi :10.1074/jbc.M114.633065 . PMC 4505538 . PMID 25911105 .
^ Petrulis JR, Perdew GH (2002). "The role of chaperone proteins in the aryl hydrocarbon receptor core complex". Chemico-Biological Interactions . 141 (1–2): 25–40. Bibcode :2002CBI...141...25P . doi :10.1016/S0009-2797(02)00064-9 . PMID 12213383 .
^ Occhi G, Trivellin G, Ceccato F, et al. (2010). "Prevalence of AIP mutations in a large series of sporadic Italian acromegalic patients and evaluation of CDKN1B status in acromegalic patients with multiple endocrine neoplasia" . Eur. J. Endocrinol . 163 (3): 369–376. doi :10.1530/EJE-10-0327 . PMID 20530095 .
^ 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 . PMID 10986286 .
^ 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 . PMID 9083006 .
^ 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 . PMID 12482853 .
^ Kazlauskas A, Sundström S, Poellinger L, Pongratz I (April 2001). "The hsp90 chaperone complex regulates intracellular localization of the dioxin receptor" . Mol. Cell. Biol . 21 (7): 2594–607. doi :10.1128/MCB.21.7.2594-2607.2001 . PMC 86890 . PMID 11259606 .
Zhou Q, Lavorgna A, et al. (2015). "Aryl Hydrocarbon Receptor Interacting Protein Targets IRF7 to Suppress Antiviral Signaling and the Induction of Type I Interferon" . Journal of Biological Chemistry . 290 (23): 14729–14739. doi :10.1074/jbc.M114.633065 . PMC 4505538 . PMID 25911105 .
Chen HS, Perdew GH (1994). "Subunit composition of the heteromeric cytosolic aryl hydrocarbon receptor complex" . J. Biol. Chem . 269 (44): 27554–8. doi :10.1016/S0021-9258(18)47020-2 . PMID 7961671 .
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 . PMID 9083006 .
Meyer BK, Pray-Grant MG, Vanden Heuvel JP, Perdew GH (1998). "Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity" . Mol. Cell. Biol . 18 (2): 978–88. doi :10.1128/MCB.18.2.978 . PMC 108810 . PMID 9447995 .
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 . PMID 9837941 .
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/jcem.85.2.6386 . PMID 10690880 .
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 . PMID 10986286 .
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 . PMID 11013261 .
Kazlauskas A, Sundström S, Poellinger L, Pongratz I (2001). "The hsp90 chaperone complex regulates intracellular localization of the dioxin receptor" . Mol. Cell. Biol . 21 (7): 2594–607. doi :10.1128/MCB.21.7.2594-2607.2001 . PMC 86890 . PMID 11259606 .
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 . PMID 11805120 .
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 . PMID 12036304 .
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 . PMID 12065584 .
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 . PMID 12361709 .
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences" . Proc. Natl. Acad. Sci. U.S.A . 99 (26): 16899–903. Bibcode :2002PNAS...9916899M . doi :10.1073/pnas.242603899 . PMC 139241 . PMID 12477932 .
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 . PMID 12482853 .
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 . PMID 12721663 . S2CID 13468188 .
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 . PMID 12837759 .
Yano M, Terada K, Mori M (2003). "AIP is a mitochondrial import mediator that binds to both import receptor Tom20 and preproteins" . J. Cell Biol . 163 (1): 45–56. doi :10.1083/jcb.200305051 . PMC 2173431 . PMID 14557246 .
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 . PMID 14730974 .
Occhi G, Trivellin G, Ceccato F, et al. (2010). "Prevalence of AIP mutations in a large series of sporadic Italian acromegalic patients and evaluation of CDKN1B status in acromegalic patients with multiple endocrine neoplasia" . Eur. J. Endocrinol . 163 (3): 369–376. doi :10.1530/EJE-10-0327 . PMID 20530095 .